Search Results (1,452)

Prostate cancer (PCa) is the second most frequently diagnosed solid malignancy in men and a major cause of cancer-related mortality worldwide. While localized disease is associated with excellent long-term survival, advanced and castration-resistant PCa continues to represent a major therapeutic challenge. Current management ranges from active surveillance for indolent tumors to multimodal systemic approaches for metastatic disease. In this context, natural compounds are attracting increasing interest as adjunctive or novel therapeutic agents. Among these, silymarin, a Silybum marianum-derived flavonolignan complex, has shown promising antineoplastic activity in preclinical PCa models. In vitro, silymarin compounds consistently inhibit PCa cell proliferation by inducing G1 and G2/M cell cycle arrest, upregulating cyclin-dependent kinase inhibitors, and activating caspase-dependent apoptotic pathways. They also modulate key oncogenic signaling pathways involved in cell survival, proliferation, invasion, and metastasis. In vivo xenograft and transgenic models further show reduced tumor growth, angiogenesis, and metastatic spread with limited systemic toxicity. Emerging clinical evidence, including systematic reviews and meta-analyses, suggests translational potential; however, robust randomized trials are needed to define optimal formulations, dosing strategies, and therapeutic efficacy in PCa patients. This review provides a comprehensive overview of the molecular mechanisms, preclinical efficacy, and emerging clinical evidence supporting silymarin as a candidate for future PCa research. Full article

Upper tract urothelial carcinoma (UTUC) presents distinct diagnostic and therapeutic challenges because of its rarity, anatomic constraints, frequent understaging at biopsy, and risk of systemic recurrence after radical nephroureterectomy. Current perioperative management is driven primarily by clinicopathologic risk factors, which may be insufficient to identify occult molecular residual disease (MRD) or to determine which patients are most likely to benefit from systemic therapy. This narrative review summarizes available evidence on circulating tumor DNA (ctDNA) in UTUC and related urothelial carcinoma settings, classifies the level of evidence supporting each application, and proposes a research framework for prospective evaluation. The strongest UTUC-specific evidence supports ctDNA as a prognostic biomarker associated with recurrence risk, whereas predictive validity for selecting chemotherapy, immune checkpoint inhibitors, antibody-drug conjugates, targeted therapy, or surveillance intensity remains unproven. Evidence from muscle-invasive bladder cancer, including ctDNA-correlative and ctDNA-guided perioperative trials, provides biologic rationale but should not be directly translated into routine UTUC care without disease-specific validation. We outline key implementation questions, including target population, assay selection, timing, false-positive and false-negative results, lead-time bias, and integration of plasma ctDNA with utDNA. Prospective UTUC-specific trials are needed to determine whether ctDNA-guided perioperative strategies improve survival, reduce unnecessary toxicity, and are cost-effective. Full article

Environmental health services play a critical role in communicable disease outbreaks by addressing environmental determinants of disease transmission. However, the scope, impact, and challenges of Environmental Health Practitioner (EHP)-led interventions remain insufficiently documented. Aim and objectives: This systematic review objectively assessed the role, impacts, and challenges of municipal environmental health services in outbreak response, with a focus on South Africa, to inform the standardisation and strengthening of disease surveillance and prevention. Methods: The PICO framework guided the development of search terms and research questions. PubMed, Scopus, Google Scholar, and Web of Science were searched for English-language, full-text studies published between 2010 and 2024. Studies not meeting these inclusion criteria were excluded. Screening and reporting followed PRISMA guidelines, and data were synthesised using a standardised extraction tool. Results: A total of 58 studies were included. The key EHP functions identified were water quality monitoring, vector control, food safety, waste management, and outbreak response. While South Africa demonstrated comparatively advanced systems, persistent implementation challenges remain, including the integration of environmental monitoring with disease surveillance. The findings emphasised the need for integrating environmental monitoring with disease surveillance systems and integrating WASH and climate-responsive strategies. Conclusions and recommendation: The review recommends strengthening guidelines and advancing evidence-based practice. Enhancing EHP roles within surveillance frameworks is essential for improving outbreak preparedness and public health resilience. Full article

Background/Objectives: Vaccine development pipelines are forward-looking indicators of public health preparedness, reflecting the capacity to address unmet medical needs and emerging threats. This descriptive analysis aims to characterise the 2025 clinical-stage pipeline of infectious disease vaccines and prophylactic monoclonal antibody candidates developed by Vaccines Europe member companies, and to describe how pipeline characteristics address evolving public health priorities. Methods: A descriptive analysis was conducted using publicly available data compiled in the Vaccines Europe Pipeline Review 2025, with validation by participating companies. Candidates in clinical development or regulatory review were classified using a standardised framework by pathogen/disease, target population, public health priority, and technologies. Results: The Vaccines Europe member company pipeline comprises 91 candidates across clinical development phases, 19% of which are in Phase III and 7% undergoing regulatory review. This pipeline is predominantly targeting respiratory pathogens (75%), with a strong life-course focus (85% evaluated in adults and/or older adults), and sustained activity in bacterial pathogens relevant to antimicrobial resistance. Notably, 41% of candidates were classified as addressing diseases, disease combinations, or indications for which no licenced preventive product exists. This category includes candidates targeting diseases without a preventive solution, as well as novel combination vaccines and therapeutic approaches in areas where individual components or preventive vaccines are already available. This captures vaccines candidates in different stages of development, not necessarily first-in-disease innovation. The pipeline shows broad technological diversity (12 technologies), dominated by RNA approaches and multivalent candidates, with growing focus on climate-sensitive, zoonotic, and pandemic-prone pathogens. Conclusions: Within the pipeline of Vaccines Europe member companies, this analysis describes development activity oriented toward broader prevention, platform-based approaches, and preparedness-relevant targets. As a structured and recurring annual assessment, the Vaccines Europe Pipeline Review supports horizon scanning and evidence-based dialogue between industry and vaccine ecosystem stakeholders. In order to maximise the impact of vaccine development pipelines to public health, predictable investment, streamlined trial and regulatory pathways, strong surveillance, and real-world data systems, coordinated decision-making is required to enable timely and equitable access, and complementary incentive and procurement reforms. Full article

Heritable thoracic aortic diseases (HTAD) are inherited conditions that increase the risk of thoracic aortic aneurysms, dissections, and premature aortic rupture. Advances in human genetics and experimental models have transformed our understanding of these disorders from a phenotype-based classification system to a mechanism-based view involving extracellular matrix (ECM) architecture, transforming growth factor-β (TGFβ) signaling, and vascular smooth muscle cell contractility. Marfan syndrome, Loeys–Dietz syndrome, and nonsyndromic HTAD demonstrate how genetic mutations can disrupt the components that stabilize the aortic wall. These pathogenic mechanisms influence matrix organization, intracellular signaling, and the contractile machinery within the mechanically stressed proximal aorta. In this review, we summarize current mechanistic insights into the major forms of HTAD and discuss how new molecular and cellular concepts could influence surveillance, genetic counseling, and genotype-guided therapeutic strategies. Full article

Background/Objectives: Sacral giant cell tumor of bone (GCTB) is a rare, mostly benign but locally aggressive neoplasm that carries significant diagnostic and treatment challenges due to its anatomic complexity, proximity to sacral nerve roots as well as the blood vessels, and potential impact on bowel, bladder, sexual, and lumbopelvic function and stability. This narrative review aimed to synthesize current evidence on the epidemiology, clinical presentation, diagnostic evaluation, classification, management strategies, outcomes, and surveillance of sacral GCTB. Methods: A focused literature search of PubMed/MEDLINE and Google Scholar was conducted for studies published between January 2000 and January 2026, with additional manual review of reference lists. Given the rarity of the tumor and the observed heterogeneity in study designs, treatment strategies, and outcomes, the evidence was synthesized narratively. Results: Sacral GCTB mainly affects young adults with an indolent nature, often presenting late with progressive low back or buttock pain, radiculopathy, or neurological deficits. Magnetic resonance imaging is the preferred modality for determining local extent, whereas histopathologic biopsy and molecular testing remain essential for definitive diagnosis. Conventional grading systems, such as Enneking and Campanacci, have limited value in sacral disease, as anatomical extent and anticipated neurological morbidity are more relevant for treatment planning. Surgery remains the cornerstone for resectable disease, yet management plans should balance local tumor control against preservation of sacral nerve roots and mechanical stability. Denosumab, selective arterial embolization, and radiotherapy may play important roles in selected unresectable or high-morbidity cases. Local recurrence remains a major concern, and long-term surveillance is recommended because tumor relapse, treatment-related morbidity, and distant metastasis may occur late. Conclusions: Current evidence supports a multidisciplinary, individualized approach to sacral GCTB, guided by tumor extent, expected neurological morbidity, and patient-centered functional outcomes. Prospective multicenter studies are needed to refine treatment algorithms and improve risk stratification. Full article

In this report, we describe systemic granulomatous mycobacteriosis in an orbiculate batfish from an aquarium in South Korea. Gross examination of the deceased fish showed multifocal nodular lesions in multiple internal organs including the gills, spleen, and kidney. Histopathological analysis demonstrated severe chronic systemic granulomatous inflammation, and Ziehl–Neelsen staining highlighted abundant intralesional acid-fast bacilli. Molecular analysis based on partial sequencing of the 16S ribosomal RNA (rRNA) and heat shock protein 65 (hsp65) genes showed that the detected organism was most closely related to Mycobacterium marinum. Because the molecular analysis was performed using partial sequences obtained from formalin-fixed, paraffin-embedded tissues, definitive species-level identification was not possible. This case represents systemic granulomatous mycobacteriosis associated with a Mycobacterium marinum-like organism in orbiculate batfish in an aquarium in South Korea and emphasizes the need for continuous disease surveillance and improved diagnostic awareness of non-tuberculous mycobacterial infections in ornamental and public aquarium fish. Full article

Recently, a strain of Streptococcus agalactiae serotype Ia sequence type 7 clonal complex 1 (SaIa ST7 CC1) has emerged in Latin American tilapia aquaculture as an international threat. This study evaluated outbreaks of acute streptococcosis occurring between 2021 and 2025 on commercial Nile tilapia (Oreochromis niloticus) farms in six Latin American countries, aiming to integrate molecular, clinical, pathological, and environmental data. In total, 360 moribund or recently dead fish at various production stages (larvae/fry, pre-grow-out, and grow-out) were examined, and 25 S. agalactiae isolates were serotyped and subjected to real-time PCR analysis, multilocus sequence typing (MLST), virulence and antimicrobial resistance gene profiling, and antimicrobial susceptibility testing. All isolates belonged to SaIa and shared the same ST7 CC1 MLST profile, forming a highly homogeneous cluster with reference SaIa ST7 CC1 strains previously isolated from tilapia farms in Asia. These results are consistent with the regional spread of a single clonal line. At the larval and fry stages, SaIa ST7 CC1 was associated with hyperacute septicemia, gastrointestinal hemorrhage, and frequent intestinal intussusception, whereas in pre-grow-out and grow-out fish, neurological signs were more prominent, followed by ocular signs, systemic hemorrhages, and coelomic lesions. Histopathological examination showed profuse colonization of the brain, spleen, liver, and intestine by Gram-positive cocci, accompanied by marked acute circulatory and inflammatory lesions and few chronic granulomatous responses, consistent with a rapidly progressing, highly aggressive infectious process. All outbreaks occurred during extended periods of warm water (>32 °C), with large day–night thermal gradients and reduced dissolved oxygen, suggesting that thermal stress may exacerbate disease expression in affected systems. All SaIa ST7 CC1 strains exhibited phenotypic susceptibility to florfenicol and amoxicillin, whereas 84% (21/25) and 100% (25/25) exhibited intermediate susceptibility to oxytetracycline and enrofloxacin, respectively. In total, 5 of the 21 isolates (23.8%) with intermediate susceptibility to oxytetracycline carried tetracycline resistance genes (tetM, tetO). These findings identify SaIa ST7 CC1 as a clinically significant emerging threat associated with thermally facilitated and geographically expanding streptococcosis in tilapia production in Latin America. Immediate priorities include screening imported broodstock using MLST or whole-genome sequencing (WGS), harmonized regional molecular surveillance, climate-adaptive farm management practices, prudent antimicrobial use, and serotype-matched vaccination and breeding strategies that improve both disease and heat resilience. Full article

Why do pandemics keep emerging despite decades of surveillance and response? Paleopathology, the study of disease traces in ancient remains, has been revolutionized by ancient DNA (aDNA) analysis and next-generation sequencing (NGS). Reconstructing pathogen genomes from archaeological material enables the identification of extinct lineages, the refinement of disease chronologies, and the characterization of long-term host-pathogen co-evolution. This provides context for public health challenges, including the emergence of pandemics and antimicrobial resistance (AMR). Infectious diseases are increasingly understood as complex phenomena arising from biological, ecological, and sociopolitical forces. Integrating paleopathology, aDNA, and paleomicrobiology supports a deep-time syndemic framework, revealing how recurring biosocial drivers have structured infectious disease risk throughout history. Ancient resistome studies demonstrate that AMR predates modern antibiotic use, reframing resistance as an intrinsic ecological feature rather than solely a modern phenomenon. Coronavirus disease 2019 (COVID-19) reaffirmed how infection intersects with chronic disease, health system fragility, and social inequities. This review highlights how integrating evolutionary perspectives into One Health shifts surveillance from a reactive approach to upstream risk mitigation and spillover prevention. Full article

Background/Objectives: The global health landscape is currently confronted with dual challenges from both infectious diseases and chronic conditions. Medical–preventive integration has emerged as a pivotal strategy to address these issues, aiming to create a comprehensive, closed-loop framework that spans disease prevention, treatment, rehabilitation, and healthcare, ultimately improving population health outcomes. In the Chinese context, existing policies remain fragmented, scattered across various healthcare-related regulations, and lack systematic and comprehensive analysis. This policy fragmentation may impede the creation of synergistic effects essential for the effective implementation of integrated healthcare strategies. Methods: This study adopted a mixed-methods approach to analyze 85 national policies: a three-stage coding process identified 1088 policy nodes, and a three-dimensional framework (policy instruments (X) × full-cycle health service (Y) × integration stages (Z)) was applied to uncover systemic imbalances. Social network analysis and Latent Dirichlet Allocation (LDA) topic modeling were utilized to map interagency collaboration patterns and thematic shifts, which were visualized using Gephi and Sankey. Results: The analysis revealed that policy instruments are predominantly supply-side (45.04%) and environmental-side (40.35%), with demand-side instruments (14.61%) being notably underutilized, particularly in health financing. Rehabilitation services, representing just 8.27% of the policy focus, were identified as a significant gap in the comprehensive health service cycle. While 44.58% of the instruments facilitated collaboration of medical and preventive services, integration of medical–preventive management stagnated at 25.28%, reflecting institutional inertia that impedes the redistribution of cross-sector resources. Agency collaboration evolved from a siloed approach (2015–2018) to a networked structure (2019–2021) and transitioned to centralized governance post-2022. Thematic shifts in policy discourse moved from a “Healthy China” focus toward pandemic-driven disease surveillance, culminating in the recent development of smart health ecosystems. Conclusions: China’s policies for medical–preventive integration demonstrate notable structural imbalances, particularly in the economic instruments related to health financing and the private-sector participation in healthcare. These imbalances may impede the effective allocation of healthcare resources and hinder the seamless transition toward integrated care. Future policy efforts should focus on optimizing the structure of policy instruments, addressing gaps in the full lifecycle of health services, advancing integration reforms, and promoting the transformation of the healthcare system through enhanced collaborative governance among key stakeholders. Full article

Background: Artificial intelligence (AI) is transitioning from experimental pilots to core public health functions such as disease surveillance, resource planning, and analysis of social and structural determinants of health. Yet, health data collection and stewardship remain fragmented across the globe; some jurisdictions still rely on paper-based systems, while others operate noninteroperable digital systems that can exacerbate inequities. Treating health data as a global good therefore requires governance that enables innovation while protecting rights, safety, and trust. This study aims to develop a conceptual meso-level capability framework that translates responsible AI principles into organizational practices for public health agencies. Methods: We developed the framework using a targeted narrative synthesis of contemporary governance guidance and documented early implementation experiences, purposively selected to represent major strands of current practice and debate. A structured expert panel consultation (n = 9) was subsequently conducted to assess the face validity and content validity of the proposed framework domains. Results: We propose the Public Health Responsible AI Capability (PH-RAIC) framework, which adapts principles of transparency, accountability, fairness, ethics, and safety to institutional realities faced by public health agencies. PH-RAIC identifies four interdependent capability domains: (1) strategic governance and alignment; (2) data and infrastructure stewardship; (3) participatory design, equity, and public engagement; and (4) lifecycle oversight, learning, and decommissioning. All four domains achieved Content Validity Index (CVI) values ≥ 0.85 in the expert panel consultation. The framework is presented as a conceptual, meso-level model that has undergone preliminary expert validation but requires further empirical testing in real-world agency settings. Conclusions: PH-RAIC links these domains to example practices, diagnostic questions, and illustrative measurement indicators to help agencies navigate efficiency–equity trade-offs and strengthen legitimacy and accountability in AI-enabled public health systems. It offers a validated conceptual basis for future empirical testing and operational readiness tools. Full article

Avian influenza (AI) remains a serious threat to poultry and public health worldwide due to its zoonotic nature and pandemic potential. This paper develops and analyzes a coupled system of nonlinear ordinary differential equations and an SEIR-SEIR model that describes the transmission dynamics of avian influenza in both human and bird populations. The model incorporates multiple transmission routes (bird-to-bird, bird-to-human, human-to-human), exposed/latent compartments in both hosts, disease-induced mortality, and demographic processes. From a mathematical perspective, we present a rigorous analysis of this eight-dimensional dynamical system. We prove positivity and boundedness of solutions in ${\mathbb{R}}_{+}^8$, characterize the equilibrium points, and derive the basic reproduction numbers $R_0^b$ and $R_0^h$ using the next-generation matrix method. Local asymptotic stability of the disease-free equilibrium is established via the Routh–Hurwitz criterion. A composite Lyapunov function is constructed to prove global asymptotic stability when both reproduction numbers are less than unity—a result that exploits the cascade structure of the system and provides a template for analyzing similar multi-host models. Sensitivity analysis using normalized forward sensitivity indices identifies critical parameters. In addition, we use neural network models to validate both models and provide error analysis. These results emphasize the crucial role of controlling cross-species transmission and improving recovery efforts, which have significant implications for the design of effective intervention and surveillance programs in the context of the One Health framework. Full article

Intensive pig farming presents substantial challenges for individual health monitoring due to high stocking densities, complex occlusion scenarios, and the need for continuous real-time surveillance. Existing monitoring approaches rely heavily on manual inspection, which is labor-intensive and prone to delayed detection of abnormal behaviors and disease symptoms. This study proposes an embedded intelligent monitoring system integrating a pan-tilt gimbal platform with an improved multi-object tracking and anomaly detection framework for automated pig health surveillance. The system employs a modified Periodfill_DeepSORT algorithm that incorporates a ReID network with appearance features and motion prediction trajectories to maintain identity consistency under occlusion and re-entry scenarios. For anomaly detection, a lightweight YOLOv8-based network was trained on 772 abnormal samples across three behavioral categories: movement abnormalities, postural abnormalities, and disease-related abnormalities. Experimental results demonstrate that the Periodfill_DeepSORT algorithm achieves a Multiple Object Tracking Accuracy (MOTA) of 95.34%, a Multiple Object Tracking Precision (MOTP) of 94.77%, and an IDF1 score of 96.88%, with only 12 identity switches across 2000 frames involving 12 targets—27 fewer than the standard DeepSORT algorithm. In occlusion scenarios, MOTA improved from 61.1% to 78.3%. The anomaly detection network achieves an overall detection accuracy of 94.5%, representing an 8.8 percentage point improvement over the baseline model, with recognition accuracies of 96.2% for movement abnormalities, 94.1% for postural abnormalities, and 92.8% for disease-related abnormalities. The system operates at 90 frames per second on embedded hardware with a power consumption of 3.2 watts and a startup time of approximately 1 s, with gimbal angle errors maintained within 3°. These results demonstrate the system’s effectiveness and practical feasibility for real-time intelligent health monitoring in intensive livestock farming environments. Full article

Background/Objectives: Active surveillance (AS) is recommended for men with low-risk prostate cancer to minimize overtreatment while monitoring for disease progression. However, current surveillance strategies rely heavily on repeat biopsies, which are invasive and associated with morbidity. MyProstateScore 2.0—Active Surveillance (MPS2-AS) is a urine-based biomarker test developed to predict progression to Grade Group ≥ 2 (GG ≥ 2) and Grade Group ≥ 3 (GG ≥ 3) prostate cancers in men on AS. The objective of this study was to analytically validate the reproducibility and robustness of MPS2-AS analyte detection and risk score calculation across key laboratory variables. Methods: Analytical precision was evaluated using pooled urine specimens processed using the MPS2-AS laboratory workflow. Eight pooled urine samples were tested in a within-laboratory design across five days, with two runs per day, and two replicates per run. Additional reproducibility studies assessed variability across three QuantStudio™ 12K Flex Real-Time PCR Systems and three OpenArray™ chip lots. Ten RNA biomarkers were quantified by RT-PCR and used to calculate the MPS2-AS GG1-2 and GG1-3 risk scores. Variance components were estimated using hierarchical ANOVA. Results: The MPS2-AS analyte measurements demonstrated high precision across within-laboratory testing, with standard deviations ranging from 0.00 to 0.60 and coefficients of variation (%CV) from 0.00 to 4.01%. The reproducibility across qPCR instruments and OpenArray chip lots showed similar robustness, with analyte %CVs of ≤4.57% and ≤4.10%, respectively. These stable analyte measurements translated to reproducible model outputs, with %CV ≤ 10.69% for the GG1-2 risk score and ≤7.20% for the GG1-3 risk score across all tested conditions. No systematic bias was observed between runs, days, instruments, or reagent lots. Conclusions: MPS2-AS demonstrates strong analytical precision and reproducibility for quantifying urinary biomarkers and generating GG1-2 and GG1-3 risk scores. These results support the reliability of MPS2-AS for clinical laboratory implementation and its use as a non-invasive tool to inform biopsy decisions in men with Grade Group 1 prostate cancer undergoing active surveillance. Full article

Nipah virus (NiV) is an animal-borne RNA virus of the genus Henipavirus that poses a significant global health threat. This threat is driven by the virus’s high mortality rate, its capacity to cause epidemics, and the lack of licensed therapeutic interventions or vaccines. Since its initial identification during the 1998–1999 outbreak in Malaysia and Singapore, recurrent episodes have occurred primarily in Bangladesh and India, with mortality rates frequently exceeding 70%. Fruit bats of the genus Pteropus serve as the biological host for the virus. Transmission to humans occurs via contact with infected wildlife, consumption of contaminated products, such as freshly harvested date palm sap, or direct person-to-person exposure. Other modes of transmission, such as transplacentally or via breast milk, are still under investigation. The clinical presentation of NiV infection varies widely, from mild flu-like symptoms to life-threatening respiratory disease and acute encephalitis. It frequently attacks the nervous system, which can lead to coma, permanent neurological damage, or relapsing encephalitis. The virus enters host cells via ephrin-B2/B3 receptors, enabling systemic dissemination and infiltration of the central nervous system. Diagnosis relies primarily on RT-PCR and serological assays, and virus isolation requires high-containment laboratories. Management remains largely supportive, as no approved antiviral therapy exists. Experimental agents, such as remdesivir, favipiravir, and monoclonal antibodies such as m102.4, have shown promise in preclinical studies. Multiple vaccine platforms—including subunit, viral vector, mRNA, and nanoparticle-based approaches—are under development, though none is yet licensed for human use. Strengthened surveillance, infection control measures, and continued research are essential to mitigate the threat posed by this emerging pathogen. This review summarizes current knowledge on NiV, including its virology, epidemiology, pathogenesis, transmission, and recent progress in therapeutic and vaccine development. Full article