Search Results (3,505)

Robot-assisted radical prostatectomy (RARP) is the definitive surgical treatment for localized prostate cancer (PCa). Some patients with post-RARP biological recurrence (BCR) eventually develop distant metastases and subsequent PCa-related mortality. The objective of this study was to clarify the predictive factors for the risk of metastatic disease after BCR in patients with PCa who underwent RARP. This multicenter retrospective cohort study was conducted in nine Japanese institutions and enrolled 491 men with BCR, detected between 2011 and 2024. During the median 59-month follow-up period, 44 patients (9.0%) had radiological confirmation of distant metastasis. Patients with developed metastases after BCR exhibited higher biopsy Gleason grade and pathological T stage, increased lymphovascular invasion (LVI) in the surgical specimen, and a shorter interval from RARP to BCR. In univariate analysis, LVI and a time to BCR after RARP of ≤14.9 months were significant predictors of distant metastasis. In the multivariate analysis, LVI constituted a significant independent predictor of distant metastasis (p = 0.011). The 3-year metastasis-free survival (MFS) rates were 85.5% and 94.1% in patients with and without LVI, respectively. The MFS was significantly prolonged in patients with negative LVI compared to those with positive LVI (p = 0.007). In Japanese males with BCR after RARP, LVI was identified as an independent predictor of metastatic progression. Full article

Respiratory diseases remain one of the most significant health challenges in modern swine production, leading to substantial economic losses, compromised animal welfare, and increased antimicrobial use. In recent years, advances in artificial intelligence (AI), particularly machine learning and deep learning, have enabled the development of non-invasive, continuous monitoring systems based on pig vocalizations. Among these, audio-based technologies have emerged as especially promising tools for early detection and monitoring of respiratory disorders under real farm conditions. This review provides a comprehensive synthesis of AI-driven audio classification approaches applied to pig farming, with focus on respiratory health and welfare monitoring. First, the biological and acoustic foundations of pig vocalizations and their relevance to health and welfare assessment are outlined. The review then systematically examines sound acquisition technologies, feature engineering strategies, machine learning and deep learning models, and evaluation methodologies reported in the literature. Commercially available systems and recent advances in real-time, edge, and on-farm deployment are also discussed. Finally, key challenges related to data scarcity, generalization, environmental noise, and practical deployment are identified, and emerging opportunities for future research including multimodal sensing, standardized datasets, and explainable AI are highlighted. This review aims to provide researchers, engineers, and industry stakeholders with a consolidated reference to guide the development and adoption of robust AI-based acoustic monitoring systems for respiratory health management in swine. Full article

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by dopaminergic neuronal loss and abnormal α-synuclein aggregation. Circulating microRNAs (miRNAs) have emerged as promising biomarkers and potential modulators of PD-related molecular pathways. In this study, we investigated the expression levels of four candidate miRNAs—miR-15a-5p, miR-16-5p, miR-139-5p, and miR-34a-3p—in patients with PD compared with healthy controls. A total of 47 PD patients and 45 age- and sex-matched controls were enrolled. Plasma miRNA levels were quantified using standardized RNA extraction, cDNA synthesis, and qPCR protocols. We observed marked upregulation of miR-15a-5p and robust downregulation of both miR-139-5p and miR-34a-3p in PD patients, whereas miR-16-5p showed no significant difference between groups. Target gene prediction and functional enrichment analysis identified 432 unique genes, with enrichment in biological processes related to protein ubiquitination and catabolic pathways, and signaling cascades such as mTOR, PI3K-Akt, MAPK, and Hippo pathways, all of which are implicated in neurodegeneration. Elevated miR-15a-5p may contribute to pro-apoptotic mechanisms, while reduced miR-139-5p and miR-34a-3p expression may reflect impaired mitochondrial function, diminished neuroprotection, or compensatory regulatory responses. Together, these dysregulated circulating miRNAs provide novel insight into PD pathophysiology and highlight their potential as accessible, non-invasive biomarkers. Further longitudinal studies in larger and more diverse cohorts are warranted to validate their diagnostic and prognostic value and to explore their utility as therapeutic targets. Full article

Liver cancer, also known as hepatocellular carcinoma (HCC), remains a major global health concern, with high mortality driven by late-stage diagnosis, limited treatment efficacy, and frequent therapeutic resistance. Matrix metalloproteinases (MMPs), a large family of zinc-dependent endopeptidases, are central to the biological processes that drive liver tumor initiation and progression. By degrading and reorganizing extracellular matrix components, MMPs facilitate tumor expansion, tissue invasion, and metastatic dissemination. In addition, these enzymes regulate the availability of growth factors, cytokines, and chemokines, thereby influencing angiogenesis, inflammation, immune cell recruitment, and the development of an immunosuppressive tumor microenvironment. Aberrant expression or activity of multiple MMP family members is consistently associated with aggressive clinicopathologic features, including vascular invasion, increased metastatic potential, and reduced patient survival, highlighting their promise as prognostic markers and actionable therapeutic targets. Past attempts to modulate MMP activity were hindered by broad inhibition profiles and dose-limiting toxicities, underscoring the need for improved specificity and delivery strategies. Recent advances in molecular design, biologics engineering, and nanotechnology have revitalized interest in MMP targeting by enabling more selective, context-dependent modulation of proteolytic activity. Preclinical studies demonstrate that carefully tuned MMP inhibition can limit tumor invasion, enhance anti-angiogenic responses, and potentially improve the efficacy of existing systemic therapies, including immuno-oncology agents. This review synthesizes current knowledge on the multifaceted roles of MMPs in HCC pathobiology and evaluates emerging therapeutic strategies that may finally unlock the clinical potential of targeting these proteases. Full article

The progression of neoplastic diseases is driven by a complex interplay of biological processes, including uncontrolled proliferation, enhanced invasion, metastasis, and profound metabolic reprogramming. Among the hallmarks of cancer, as revised by Hanahan and Weinberg, the reprogramming of energy metabolism has emerged as a critical feature that enables cancer cells to meet their heightened bioenergetic and biosynthetic demands. One significant aspect of this metabolic adaptation is the accumulation of lipid droplets (LDs) dynamic, cytoplasmic organelles primarily involved in lipid storage and metabolic regulation. LDs serve as reservoirs of neutral lipids and play a multifaceted role in cancer cell physiology. Their accumulation is increasingly recognized as a marker of tumor aggressiveness and poor prognosis. By storing lipids, LDs provide a readily accessible source of energy and essential building blocks for membrane synthesis, supporting rapid cell division and growth. Moreover, LDs contribute to cellular homeostasis by modulating oxidative stress, maintaining redox balance, and regulating autophagy, particularly under nutrient-deprived or hypoxic conditions commonly found in the tumor microenvironment. Importantly, LDs have been implicated in the development of resistance to cancer therapies. They protect cancer cells from the cytotoxic effects of chemotherapeutic agents by buffering endoplasmic reticulum (ER) stress, inhibiting apoptosis, and facilitating survival pathways. The presence of LDs has been shown to correlate with increased resistance to a variety of chemotherapeutic drugs, although the precise molecular mechanisms underlying this phenomenon remain incompletely understood. Emerging evidence suggests that chemotherapy itself can induce changes in LD accumulation, further complicating treatment outcomes. Given their central role in cancer metabolism and therapy resistance, LDs represent a promising target for therapeutic intervention. Strategies aimed at disrupting lipid metabolism or inhibiting LD biogenesis have shown potential in sensitizing cancer cells to chemotherapy and overcoming drug resistance. In this review, we comprehensively examine the current understanding of LD biology in cancer, highlight studies that elucidate the link between LDs and drug resistance, and discuss emerging approaches to target lipid metabolic pathways to enhance therapeutic efficacy across diverse cancer types. Full article

Canine ehrlichiosis, caused by Ehrlichia canis, represents a relevant challenge in veterinary medicine, particularly in resource-limited settings where access to laboratory-based diagnostics may be constrained. This pilot and exploratory study aimed to evaluate the feasibility of a portable electronic olfactometer as a non-invasive screening approach, based on the analysis of volatile organic compounds (VOCs) present in breath, saliva, and hair samples from dogs. Signals were acquired using an array of eight metal-oxide (MOX) gas sensors (MQ and TGS series). After preprocessing, principal component analysis (PCA) was applied for dimensionality reduction, and the resulting features were analyzed using supervised machine-learning classifiers, including AdaBoost, support vector machines (SVM), k-nearest neighbors (k-NN), and Random Forests (RF). A total of 38 dogs (19 PCR-confirmed infected cases and 19 controls) were analyzed, generating 114 samples evenly distributed across the three biological matrices. Among the evaluated models, SVM showed the most consistent performance, particularly for saliva samples, achieving an accuracy, sensitivity, and precision of 94.7% (AUC = 0.964). In contrast, breath and hair samples showed lower discriminative performance. Given the limited sample size and the exploratory nature of the study, these results should be interpreted as preliminary; nevertheless, they suggest that electronic olfactometry may represent a complementary, low-cost, non-invasive screening tool for future research on canine ehrlichiosis, rather than a standalone diagnostic method. Full article

Cervical cancer remains a significant global health burden, disproportionately affecting women in low- and middle-income countries despite being preventable. Since 2018, rapid advances in molecular profiling, immunotherapy, refinement of minimally invasive surgery, and targeted therapeutics have transformed diagnostic and therapeutic paradigms. This narrative review synthesizes clinical and translational progress across the continuum of care from 2018 to 2025. We summarize the evolving landscape of precision screening—including HPV genotyping, DNA methylation assays, liquid biopsy, and AI-assisted cytology—and discuss their implications for global elimination goals. Surgical management has shifted toward evidence-based de-escalation with data from SHAPE, ConCerv, and ongoing RACC informing fertility preservation and minimally invasive approaches. For locally advanced disease, KEYNOTE-A18 establishes pembrolizumab plus chemoradiation as a new curative standard, while INTERLACE underscores the benefit of induction chemotherapy. In the metastatic setting, survival outcomes have improved with the integration of checkpoint inhibitors (KEYNOTE-826, BEATcc, EMPOWER-Cervical 1), vascular-targeted therapies, and antibody–drug conjugates, including tisotumab vedotin and emerging HER2 and TROP-2–directed agents. We further highlight emerging biomarkers—PD-L1, TMB, MSI status, HPV integration patterns, APOBEC signatures, methylation classifiers, ctHPV-DNA—and their evolving role in treatment selection and surveillance. Future directions include neoadjuvant checkpoint inhibition, PARP-IO combinations, HER3-directed ADCs, DDR-targeted radiosensitizers, HPV-specific cellular therapies, and AI-integrated precision medicine. Collectively, these advances are reshaping cervical cancer care toward biologically individualized, globally implementable strategies capable of accelerating WHO elimination targets. Full article

Foundries represent complex exposure scenarios where metals, particulate matter, and combustion by-products coexist, posing potential cumulative biological effects. Urinary metabolic profiles from 64 foundry workers and 78 residents living in surrounding areas were investigated using multivariate statistical modeling. Differences in urinary metabolite patterns were observed between the two groups, including lower levels of several amino acids (e.g., valine, alanine, tyrosine, and tryptophan) and tricarboxylic acid intermediates (e.g., citrate and succinate), together with higher levels of selected branched-chain amino acid catabolites (e.g., 3-hydroxyisobutyrate and erythro-2,3-dihydroxybutyrate) in workers. Variations in gut microbiota-related metabolites, such as phenylacetylglycine and p-cresol sulphate, were also detected. Based on these metabolic patterns, potential molecular mechanisms related to energy metabolism, oxidative stress and host–microbiome interaction are discussed as interpretative hypotheses. The comparison between workers and residents was interpreted, taking into account differences in demographic and lifestyle characteristics between groups. Overall, the results indicate that occupational exposure in foundries is associated with measurable differences in urinary metabolic profiles, demonstrating that the applied NMR-based metabolomic strategy is capable of capturing early biological effects and supporting its potential as a non-invasive and holistic biomonitoring tool for evaluating the health impact of complex occupational exposures. Full article

Background: Colorectal cancer (CRC) is currently the third most common cancer worldwide, with high heterogeneity and poor prognosis. Gene expression-based molecular subtypes can effectively dissect tumor heterogeneity, but their clinical translation remains challenging. This study aims to conduct radiogenomic analysis regarding molecular subtypes and establish prognostic signatures for survival prediction of colorectal cancer. Methods: In this retrospective study involving 2948 CRC patients from 8 cohorts, we utilized a supervised deep learning framework to extract quantitative feature representations of molecular subtypes. Through correlation analysis, we selected key gene expression features related to these subtypes to establish a prognostic signature. A similar pipeline was applied to derive a non-invasive radiomic prognostic signature. Finally, we validated the prognostic value of both signatures in multiple cohorts and explored their biological interpretation. Results: We successfully established a molecular subtype-associated gene signature and a non-invasive radiogenomic signature. The gene signature classified patients into high-risk and low-risk groups with significantly different prognoses. The low-risk group had a better prognosis and showed a greater potential benefit from immunotherapy. Similarly, the radiogenomic signature exhibited characteristics related to molecular subtypes and comparable performance in prognostic prediction. Multivariate analysis confirmed the independent prognostic value of both signatures. In summary, this retrospective study demonstrates that our framework translates molecular subtypes into cost-effective biomarkers for risk stratification and treatment guidance. Full article

Currently, the increased incidence of invasive fungal infections globally is posing a significant challenge to public health. Due to drug resistance issues, the clinical efficacy of existing antifungal drugs is seriously insufficient, while new drug development progresses slowly. Consequently, there is an urgent need to discover and develop novel antifungal therapeutics. Natural products have the characteristics of wide sources and few adverse reactions and are one of the sources for developing antifungal drugs. Numerous studies have shown that many compounds isolated from plants and traditional Chinese medicine have antifungal activity and diverse antifungal mechanisms. Thymol, a monoterpene phenol compound from thyme (Lamiaceae), has multiple biological functions such as antibacterial, antioxidant, and anti-inflammatory. Recent research has found that thymol has strong antifungal activity, and its molecular mechanisms involve cell membrane rupture, interference with cell wall synthesis, disruption of mitochondrial function and energy metabolism, inhibition of biofilm, inhibition of virulence factor expression, inhibition of key enzymes, and induction of cell apoptosis. This review aimed to summarize the antifungal activity of thymol and the underlying molecular mechanisms, safety, and potential clinical applications. Emerging technologies in thymol delivery systems and future research directions are also discussed. The comprehensive analysis aims to provide a detailed understanding of fungal infections and the role of thymol in antifungal treatment, offering insights for further research and clinical practice. Full article

In struggling against invasive species ravaging riverscape ecosystems, gaps in dispersal pathway knowledge and fragmented approaches across scales have long stalled effective riparian management worldwide. To reduce these limitations and enhance invasion management strategies, selecting appropriate alien species as models for in-depth pathway analysis is essential. Alternanthera philoxeroides (Mart.) Griseb. (alligator weed) emerges as an exemplary model species, boasting an invasion record of around 120 years spanning five continents worldwide, supported by genetic evidence of repeated introductions. In addition, the clonal reproduction of A. philoxeroides supports swift establishment, while its amphibious versatility allows occupation of varied riparian environments, with spread driven by natural water-mediated dispersal (hydrochory) and human-related vectors at multiple scales. Thus, leveraging A. philoxeroides, this review proposes a comprehensive multi-scale framework, which integrates monitoring with remote sensing, environmental DNA, Internet of Things, and crowdsourcing for real-time detection. Also, the framework can further integrate, e.g., MaxEnt (Maximum Entropy Model) for climatic suitability and mechanistic simulations of hydrodynamics and human-mediated dispersal to forecast invasion risks. Furthermore, decision-support systems developed from the framework can optimize controls like herbicides and biocontrol, managing uncertainties adaptively. At the global scale, the dispersal paradigm can employ AI-driven knowledge graphs for genetic attribution, multilayer networks, and causal inference to trace pathways and identify disruptions. Based on the premise that our multi-scale framework can bridge invasion ecology with riverscape management using A. philoxeroides as a model, we contend that the implementation of the proposed framework tackles core challenges, such as sampling biases, shifting environmental dynamics, eco–evolutionary interactions using stratified sampling, and adaptive online algorithms. This methodology is purposed to offer scalable tools for other aquatic invasives, evolving management from reactive measures to proactive, network-based approaches that effectively interrupt dispersal routes. Full article

Delphastus Casey (Coleoptera: Coccinellidae: Serangiini) comprises small predatory ladybird beetles that feed on immature whiteflies. Several Delphastus species are utilized as biological control agents. However, Delphastus pallidus (LeConte) has been understudied for the past several decades. Recent landscape surveys in South Florida revealed a marked increase in D. pallidus populations associated with multiple whitefly species. We evaluated whitefly species preferences of D. pallidus using choice and no-choice assays conducted in incubators and insectaries. Seven whitefly species were confirmed as prey and ranked in order of preference: Bemisia tabaci Gennadius > Aleurothrixus trachoides (=Aleurotrachelus trachoides) (Back) > Singhiella simplex (Singh) > Paraleyrodes bondari Peracchi > Aleurodicus rugioperculatus Martin > Asiothrixus antidesmae (Takahashi) > Aleurodicus dugesii Cockerell. Findings indicate that D. pallidus feeds on a taxonomically and morphologically diverse set of whiteflies, including both waxy and non-waxy species, which likely facilitates establishment and dispersal in ornamental and agricultural landscapes. This study is the first to document D. pallidus as a potentially native U.S. predatory beetle that attacks at least seven whitefly species. Knowledge of its prey preferences will inform mass-rearing strategies and potential deployment for whitefly biocontrol. Full article

Carpal tunnel syndrome (CTS) is the most common peripheral nerve entrapment disorder, with a lifetime prevalence estimated at approximately 10%. This narrative review explores the historical evolution, current management strategies, and emerging trends in CTS diagnosis and treatment. Early recognition of CTS led to the development of conservative interventions, including splinting, corticosteroid injections, and physical therapy, aimed at alleviating median nerve compression and associated symptoms. The advent of open carpal tunnel release established surgery as the definitive treatment for moderate-to-severe CTS, with subsequent refinements—such as mini-open and endoscopic techniques—focused on minimizing tissue trauma and expediting recovery. Comparative studies demonstrate similar long-term efficacy between surgical modalities, though endoscopic approaches often provide faster short-term recovery. Advances in diagnostic imaging, including high-resolution ultrasound, have improved early detection and dynamic assessment of median nerve compression. Emerging therapies, such as regenerative biologics, neuromobilization, and minimally invasive surgical innovations, offer promising adjuncts to current care. Despite substantial progress, further research is needed to clarify optimal patient selection, refine minimally invasive techniques, and explore regenerative interventions. This review underscores the importance of individualized, evidence-based, and patient-centered approaches to CTS management, integrating both established and emerging strategies to optimize functional outcomes and quality of life. Full article

Chromium (Cr) toxicity poses a significant challenge to agricultural productivity, human health, and food security. Biochar (BC) is a versatile amendment employed to alleviate Cr toxicity. Chromium stress impairs growth by inducing membrane damage and cellular oxidation, as well as inhibiting chlorophyll synthesis, photosynthetic efficiency, water uptake, and nutrient absorption. This review consolidates information on the mechanisms through which BC mitigates Cr stress. Biochar facilitates Cr immobilization by reduction, adsorption, precipitation, and complexation processes. It enhances growth by improving photosynthetic efficiency, water and nutrient uptake, osmolyte synthesis, and hormonal balance. Additionally, biochar promotes resilient bacterial communities that reduce Cr and enhance nutrient cycling. The effectiveness of BC is not universal and largely depends on its feedstock properties and pyrolysis temperature. This review provides insights into soil quality, plant function, and human health, which contribute to providing a comprehensive assessment of the capacity of BC to mitigate Cr toxicity. This review highlights that BC application can reduce Cr entry into the food chain, thus decreasing its health risk. This review also identifies knowledge gaps and outlines future research directions to increase the efficiency of BC in mitigating Cr toxicity. This review also offers insights into the development of eco-friendly measures to remediate Cr-polluted soils. Full article

Urinary bladder neoplasms are clinically relevant in dogs and cats and are also common in humans, all of which may share exposure to environmental factors that influence disease risk. In Veterinary Medicine, however, their etiological determinants remain poorly defined. Urinary bladder neoplasia range from non-invasive lesions limited to the mucosa to invasive forms that infiltrate the muscular layer, which are more aggressive and metastatic. In dogs, invasive urothelial carcinoma (UC) represents the most frequently diagnosed type, while in cats, it is less common but displays similar biological behavior. Hematuria and dysuria are the predominant clinical signs, and although urinary bladder cancer accounts for only a small proportion of canine neoplasms, it is associated with considerable morbidity and mortality. Several risk factors have been identified, including breed, sex, age, obesity, diet, neuter status, and environmental exposures. Female dogs, especially Terrier breeds, are more susceptible, whereas in cats, males and short-haired animals are more often affected. Contact with insecticides, herbicides, and antiparasitic products is a recognized risk factor in dogs, although this association has not been consistently demonstrated in cats. Neutering and obesity appear to increase risk in dogs, and dietary patterns may offer protection, with regular vegetable consumption linked to a reduced incidence. Understanding these determinants is essential to improve early detection, guide preventive measures, and strengthen comparative oncology research. Full article