Search Results (18,969)

Soil degradation poses a serious threat to the sustainability of global agricultural development, endangering the foundation and environment of human survival. Therefore, elucidating the effects of different agricultural production patterns on the quality and health of paddy soils is of great significance. To investigate the impact of the integrated rice-red swamp crayfish farming on paddy soil health, this paper systematically analyzed the differences in 19 soil physicochemical indicators and bacterial and eukaryotic microbial communities between the traditional rice monoculture (TRM) and integrated rice-red swamp crayfish (Procambarus clarkii) farming (IRPF), and it features a comprehensive quantitative assessment of paddy soil health status through Principal Component Analysis based on a minimum dataset. The experimental results showed that IRPF significantly increased the soil aggregate mean weight diameter, total phosphorus, available potassium, cation exchange capacity, pH, available zinc, and available silicon contents. Meanwhile, IRPF exerted marked effects on the beta diversity and composition of both bacterial and eukaryotic microbial communities, markedly enhancing the relative abundances of Bacillariophyta and Chlorophyta in the paddy soil. The integrated analysis of 19 soil physicochemical indicators along with bacterial and eukaryotic microbial community parameters revealed that the Soil Health Index under IRPF was obviously higher than that under the rice monoculture. In conclusion, the integrated rice-red swamp crayfish farming system markedly impacted the soil fertility, effectively improved soil aggregate structure and enhanced the overall paddy soil health status, representing a promising and sustainable agricultural production pattern within a single production cycle. Full article

Mitophagy serves as an essential quality control mechanism that maintains mitochondrial homeostasis through selective autophagic clearance of damaged organelles. Vascular dementia (VD) has been increasingly associated with mitophagy dysregulation in recent studies. However, the precise molecular mechanisms underlying mitophagy’s involvement in VD pathogenesis remain poorly characterized. To elucidate the role of mitophagy in VD, we systematically examined the expression of key mitophagy pathways in hippocampal neurons of bilateral common carotid artery occlusion (BCCAO) rats and in oxygen–glucose deprivation (OGD)-treated HT22 cells. Intriguingly, under autophagy-deficient conditions, both BNIP3 and BNIP3L were markedly downregulated, whereas FUNDC1 expression increased; PINK1/Parkin levels remained unaltered. To further dissect the functional contributions of BNIP3 and BNIP3L, we administered the mitochondrial fission inhibitor Mdivi-1 to BCCAO model rats. Histopathological analysis revealed pronounced neuronal damage and apoptosis in the hippocampal region, which was further exacerbated upon Mdivi-1 treatment. In vitro, BNIP3 silencing significantly compromised cell viability, elevated reactive oxygen species (ROS) accumulation, disrupted mitochondrial membrane potential (ΔΨm), suppressed mitophagy, and increased apoptotic rates. Conversely, BNIP3 overexpression reversed these detrimental effects. Notably, treatment with the autophagy inhibitor 3-methyladenine (3-MA) diminished LC3B-Tomm20 colocalization and intensified apoptosis, reinforcing the critical role of BNIP3-mediated mitophagy in neuronal survival. Similarly, BNIP3L overexpression enhanced cell viability, attenuated ROS production, restored ΔΨm, and mitigated apoptosis, while 3-MA treatment again impaired mitophagic flux and worsened cell death. Collectively, these findings underscore the critical and distinct roles of BNIP3 and BNIP3L in maintaining mitochondrial homeostasis and neuronal survival under ischemic conditions. Full article

Background: The Magnetic Resonance Imaging (MRI)-based tumor segmentation remains a challenging problem in medical imaging due to tumor heterogeneity, unpredictable morphological features, and the high complexity of calculations needed to implement it in clinical practice, putting it out of the scope of real-time applications. Although neural networks have significantly improved segmentation performance, they still struggle to capture morphological tumor features while maintaining computational efficiency. This work introduces Hybrid Adaptive Attention U-Net (HAAU-Net) framework, combining context-aware morphologically stable features and spatial channel attention to achieve high-quality tumor segmentation with less computational cost. Methods: The proposed HAAU-Net framework integrates multi-scale Adaptive Attention Blocks (AAB), Context-Aware Morphological Feature Module (CAMFM) and Spatial-Channel Hybrid Attention Mechanism (SCHAM). CAMFM is used to maintain the stability of morphological features by hierarchical aggregation and dynamic normalization of features. SCHAM enhances feature representation by modelling channels and spatial regions where the strongest feature are determined to use in segmentation. On the BRaTS 2022/2023 data, the proposed HAAU-Net is evaluated using four modalities including T1, T1GD, T2 and T2-FLAIR sequences. Results: The proposed model able to obtain 96.8% segmentation accuracy with a Dice coefficient of 0.89 on the entire tumor region, outperforming the alternative U-Net (0.83) and conventional CNN methods of segmentation (0.81). The proposed HAAU-Net architecture cuts the computational complexity of the standard deep learning models by 43% and still achieve real-time inference (28 FPS on a regular GPU). The hybrid model used to predict survival has a C-Index of 0.91 which is higher than the traditional SVM-based methods (0.72).Conclusions: Spatial-channel attention, combined with morphologically stable features, can be combined to allow clinically significant interpretability in attention maps. The proposed framework significantly improves segmentation performance while maintaining computational effeciency. This broad system has a serious potential of AI- enabled clinical decision support system and early prognostic diagnosis in neuro-oncology with practical deployment capability. Full article

Timely identification of canopy decline in commercial strawberry production is challenging because visual scouting often misses subtle or spatially heterogeneous symptoms. We developed a plant-level UAV-based monitoring framework that integrates repeated multispectral imagery, canopy-derived metrics, unsupervised clustering, and Random Survival Forest (RSF) time-to-event modeling. The framework was applied across three commercial strawberry fields in Oxnard, California using nine UAV surveys collected from December 2022 to June 2023, yielding 159,220 plant-level monitoring units. NDRE- and Redness Index-based classifications quantified proportional and absolute canopy dieback within standardized hexagonal units and supported survival-based modeling of canopy decline progression. Across withheld test plants from all survey dates, overall concordance indices ranged from 0.88 to 0.95 across fields, indicating strong ability to rank plants by time-to-decline risk under heterogeneous field conditions. Spatial risk maps revealed localized high-risk clusters that expanded over time in fields with greater canopy deterioration, while fields with minimal visible decline exhibited diffuse but stable risk distributions. Post-hoc comparison with operational fumigation rates (280, 336, and 392 kg Pic-Clor 60/ha) showed no consistent association with predicted canopy decline risk. These results demonstrate that framing repeated UAV observations as a time-to-event process enables fine-scale spatiotemporal modeling of canopy decline dynamics and supports risk stratification for targeted field monitoring in commercial strawberry systems. Full article

The management of Culex pipiens (Diptera: Culicidae), key vectors of arboviruses like West Nile virus, necessitates sustainable alternatives to chemical insecticides. This study screened indigenous entomopathogenic fungi (EPF) from forest soils in Achaia, Greece, for their larvicidal efficacy against Cx. pipiens biotype molestus. Fifteen fungal isolates were obtained via insect baiting and identified as Beauveria and Metarhizium species. A comprehensive bioassay at 1 × 10⁸ conidia mL⁻¹ revealed significant variation in pathogenicity after 72 h. Two isolates, Beauveria bassiana (BB) (Hypocreales: Cordycipitaceae) and Metarhizium anisopliae (K3(1)) (Hypocreales: Clavicipitaceae), exhibited the highest virulence among the tested isolates, each causing 60% mortality with a rapid median lethal time (LT₅₀) of ~18.5 h. Survival analysis, Cox modeling, and non-linear kinetic modeling (Gompertz/Richards) classified three distinct virulence clusters: high/rapid, moderate/consistent, and low/delayed. A pathogenicity network analysis and a composite virulence index further validated BB and K3(1) as the most effective candidates. These results demonstrate the high isolate specificity of fungal efficacy and underscore the importance of screening local fungal diversity. The identified high-virulence isolates represent promising, environmentally sound candidates for the development of targeted biopesticides. Future research should focus on formulation for aquatic environments and integration into resistance-resilient integrated vector management programs. Full article

Background: Persistent endodontic infections involving Enterococcus faecalis and Candida albicans are a major cause of root canal treatment failure. Although conventional irrigants, such as sodium hypochlorite and chlorhexidine (CHX), exhibit strong immediate antimicrobial activity, microbes may survive and recover from the initial antimicrobial effect, hence limiting their effectiveness, especially in complex root canal anatomies and in the apical terminus of the tooth. Antibacterial dressing techniques were not proven satisfactory due to depletion of the antibacterial component or difficulty in spreading it evenly along the entire root canal. This study aimed to develop and evaluate the antimicrobial efficacy and release characteristics of a novel sustained-release device (SRD), delivering CHX via gutta-percha points coated with a sustained-release formulation used as a temporary intracanal medicament. Methods: Gutta-percha points were coated with two sustained-release CHX varnishes (CHX1 and CHX2) or a placebo and assessed in vitro. Antimicrobial activity against E. faecalis and C. albicans was evaluated using agar diffusion assays over time. Release kinetics were analyzed using Rhodamine-labeled SRD in a 3D-printed acrylic molar tooth model via fluorescence microscopy. Additionally, biofilm-infected acrylic molar teeth were treated with a placebo, a single 2% CHX irrigation, or SRD-coated gutta-percha points placed as an intracanal dressing prior to obturation. Microbial viability was quantified by colony-forming unit (CFU/mL) analysis from root canals and gutta-percha points. Statistical analysis was performed using one-way ANOVA followed by Tukey’s post hoc multiple comparison test (p < 0.05). Results: SRD-coated gutta-percha points demonstrated sustained antimicrobial activity for up to 21 days against E. faecalis and 19 days against C. albicans. Fluorescence analysis, in an acrylic tooth model, confirmed continuous release for up to 15 days, with pronounced diffusion in the isthmus and palatal canals. In biofilm-infected acrylic teeth models, SRD treatment resulted in a significant reduction of 2–3 log₁₀ CFU/mL compared to placebo groups (p < 0.001) and prevented microbial rebound over the 14-day observation period. In contrast, a single application of 2% CHX solution showed only transient reduction followed by regrowth. Conclusions: Sustained-release CHX delivery via polymer-coated gutta-percha points provided prolonged antimicrobial activity against bacterial and fungal biofilms compared to conventional single-dose CHX application in this in vitro model. These findings support the potential use of coated gutta-percha points as a removable intracanal drug delivery platform prior to final obturation, although further studies incorporating direct-release quantification and in vivo validation are required before clinical translation. Full article

Streptococcus pneumoniae resists host defenses through multiple surface factors, yet their specific contribution to protection against antimicrobial peptides remains incompletely understood. We examined the role of pneumococcal surface protein A (PspA) and the polysaccharide capsule in protection against the human defensin HNP-1. PspA conferred increased resistance to HNP-1-induced killing, shown by a decreased killing in the presence of purified recombinant PspA and an increased sensitivity when PspA was deficient from the surface of strains of two different genetic backgrounds or when anti-PspA antibody was present. The capsule also conferred protection against HNP-1, which was serotype-dependent, with type 2 protecting better than type 4, and free polysaccharides acted as decoys by sequestering HNP-1. Removal of surface PspA from capsule-deficient mutants revealed additive contributions of both factors to survival. Molecular docking analysis suggests a potential electrostatic interaction between PspA and HNP-1. These findings highlight the independent and complementary roles of PspA and the capsule in pneumococcal resistance to HNP-1 and provide novel insights that may inform future vaccine design and antimicrobial strategies. Full article

Background and Objectives: The benefits of prophylactic supraclavicular lymph node dissection for esophageal squamous cell carcinoma (ESCC) remain controversial. This study investigated whether prophylactic supraclavicular (cervical) lymphadenectomy improves the long-term outcomes of patients with upper or middle thoracic esophageal squamous cell carcinoma. Materials and Methods: This retrospective, single-center study included 290 patients who underwent thoracoscopic esophagectomy between January 2010 and December 2017. Patients treated with two-field lymphadenectomy (2FL) were compared with those who underwent prophylactic three-field lymphadenectomy (p3FL) after propensity score matching based on age, tumor location, clinical T and N stage, and preoperative treatment. The primary outcome was overall survival (OS), and secondary outcomes included postoperative complications and recurrence patterns. In a secondary analysis, the long-term outcomes were assessed in patients with solitary postoperative cervical (supraclavicular) lymph node recurrence in the 2FL group. Results: In the overall cohort, statistically significant differences were observed between the groups with respect to age, tumor location (p = 0.0002), cT and cN stages (p < 0.0001 and p < 0.0001), preoperative treatment (p = 0.02). No significant differences were observed between groups regarding age, organ for reconstruction, or postoperative complications. After propensity score matching, no significant differences were observed between the 2FL and p3FL groups in terms of overall survival or postoperative complications. Six patients (4.4%) in the p3FL group had pathologically confirmed supraclavicular lymph node metastasis, whereas four patients (2.6%) in the 2FL group developed solitary postoperative cervical lymph node recurrence. Patients with isolated cervical recurrence achieved favorable long-term survival following additional treatment. Conclusions: Prophylactic cervical lymphadenectomy did not improve the survival of patients with upper or middle thoracic esophageal squamous cell carcinoma. Given the low incidence of isolated cervical lymph node recurrence and the favorable outcomes achievable with additional treatment, routine prophylactic supraclavicular dissection appears unnecessary when two-field lymphadenectomy is feasible. Full article

Background: Cardiovascular complications stemming from diabetes pose a grave threat to patients’ survival. Both type 1 diabetes (T1D) and type 2 diabetes (T2D) significantly increase the risk of heart failure, yet no reports have clarified whether there are differences in the pathway alterations involved in these two conditions. Investigating the heterogeneity of the cardiac remodeling between these two types of diabetes is conducive to reducing the incidence of cardiovascular events in diabetic patients in clinical practice. Methods: T1D and T2D models were established in adult mice, and the hearts were collected for RNA sequencing. Differential expression analysis (DEA) was performed. Integrating functional enrichment analyses, we probed into gene and pathway heterogeneity. Subsequently, we compared single-cell RNA sequencing (scRNA-seq) data of hearts from T1D and T2D mice, focusing on three cell populations (endothelial cells, macrophages, and fibroblasts) to identify gene and pathway differences. Finally, we evaluated shared genes and common signaling pathway changes across these three cell populations in both diabetes types. Results: We have successfully established T1D and T2D models in mice. Compared with shared genes, the two types of diabetes had more consistent pathway changes. Further scRNA-seq analysis identified endothelial cells, macrophages, and fibroblasts as significantly associated with the diabetic phenotype. In shared pathway, endothelial cells were significantly enriched in pathways related to endothelial proliferation and angiogenesis; macrophages were enriched in immune response pathways; and fibroblasts were enriched in pathways involving fibrosis, cell proliferation, and apoptosis. In endothelial cells, inflammatory response and fatty acid metabolism pathways were predominantly enriched in T1D, while energy metabolism pathways were dominant in T2D. In macrophages, antiviral immune pathways were specifically enriched in T1D, whereas macrophages in T2D were additionally implicated in the regulation of cardiomyocyte function. In fibroblasts, immune-related pathways were characteristically enriched in T1D, while cell respiration and energy supply pathways were prominent in T2D. Common functional enrichment pathways across the three cell types in both diabetes types mainly involved innate immune responses and cardiac morphogenesis, with the proportion of shared pathways being significantly higher than that of shared genes. Conclusions: This study, by combining RNA sequencing and scRNA-seq, revealed that cardiac pathologies induced by T1D and T2D exhibit a higher degree of consistent pathway changes compared to shared gene changes. Interventions targeting these common pathways may hold greater value in preventing and treating diabetic cardiomyopathy. Full article

Background/Objectives: Insulin resistance (IR) is increasingly recognized as a factor associated with metabolic syndrome and various cancers. The metabolic score for insulin resistance (METS-IR) has emerged as a reliable surrogate marker for assessing IR. This study evaluated the association between the METS-IR and the gastric cancer (GC) incidence using data from a nationwide South Korean cohort. Methods: Data were obtained from the National Health Insurance Service (NHIS) cohort. A total of 318,336 participants aged ≥40 years who underwent a nationwide health screening between 2009 and 2010 were included and followed until GC diagnosis, death, or 31 December 2019. The METS-IR was calculated and categorized into quartiles. Hazard ratios (HRs) for GC incidence were estimated using Cox proportional hazards models. The analyses were adjusted for confounders, including age, sex, socioeconomic status, lifestyle factors, and comorbidities. Results: Participants in the highest METS-IR quartile (Q4) exhibited a significantly higher crude incidence of GC (2.26 per 1000 person-years) than those in the lowest quartile (Q1: 1.97 per 1000 person-years). Adjusted HRs showed a modest but statistically significant increase in GC risk in Q4 (HR: 1.10; 95% confidence interval: 1.02–1.19; p = 0.01) compared to Q1. Kaplan–Meier analysis revealed that participants with higher METS-IR levels had significantly shorter GC-free survival times than those in the lower quartiles. Restricted cubic spline analysis revealed a nonlinear relationship between the METS-IR and GC risk, with higher METS-IR levels associated with an increased risk. Conclusions: An elevated METS-IR was associated with an increased GC risk, suggesting its potential utility in stratifying GC risk. The METS-IR may help identify high-risk individuals and support GC prevention. Full article

Objective: This study aimed to evaluate the prognostic significance of lymphocyte-associated inflammatory markers and the HALP score in patients with Hodgkin’s lymphoma. Methods: This was a retrospective study that included patients who were diagnosed with Hodgkin’s lymphoma and followed up between 2004 and 2024. The inflammatory markers (NLR, PLR, MLR, SII, SIRI, and PIV) and HALP score were calculated from the patients’ biochemical and hematological parameters, and the relationship between these parameters and stage, spleen and liver involvement, relapse, mortality, overall survival, and progression-free survival was analyzed. Results: A total of 117 patients were included, and multivariate analysis indicated that progression-free survival was statistically and significantly associated with treatment type (p = 0.0285), PLR (p = 0.0188), and PIV (p = 0.0297). In terms of overall survival, age (p = 0.0011), treatment type (p = 0.0108), and SIRI (p = 0.0108) remained as statistically significant predictors. Although the HALP score showed a significant association with PFS in the univariate analysis (p = 0.0104), this association did not persist in the multivariate model. In addition, no statistically significant relationship between the HALP score and OS was observed in either the univariate or multivariate analysis. Conclusions: The SIRI is a prognostic marker in Hodgkin’s lymphoma and may be useful for predicting overall survival. Full article

The remarkable evolution of oncological therapies has dramatically improved cancer survival rates but has simultaneously introduced a significant burden of cardiovascular complications. Cardio-oncology has emerged as a critical multidisciplinary field focused on mitigating the “collateral damage” of life-saving anticancer treatments, ranging from traditional chemotherapeutics to novel immunotherapies. This review provides a comprehensive analysis of the pathophysiological mechanisms, clinical phenotypes, and evolving management strategies for cancer therapy-related cardiac dysfunction (CTRCD). An extensive synthesis of the current literature was conducted, focusing on the molecular pathways of cardiotoxicity, including Topoisomerase IIβ inhibition by anthracyclines, HER2 signaling disruption by targeted agents, and immune-mediated myocarditis triggered by checkpoint inhibitors (ICIs). Cardiotoxicity is increasingly recognized as a spectrum of phenotypes. Heart failure with reduced ejection fraction (HFrEF) remains a primary concern with cytotoxic agents, while heart failure with preserved ejection fraction (HFpEF) is emerging as a critical complication of radiation therapy and tyrosine kinase inhibitors (TKIs). The integration of advanced diagnostic tools—specifically Global Longitudinal Strain (GLS) and Cardiac Magnetic Resonance (CMR) mapping—has shifted the clinical focus toward subclinical detection. Furthermore, pivotal clinical trials such as PRADA and SUCCOUR have validated early pharmacological prophylaxis and strain-guided interventions. Emerging challenges, including the management of CAR-T cell-induced cytokine release syndrome and the specific cardiovascular needs of pediatric and geriatric populations, are also explored. The future of cardio-oncology lies in precision medicine, leveraging genomic profiling and artificial intelligence to identify high-risk individuals. A proactive, multidisciplinary approach is essential to ensure that the success of modern oncology is not compromised by irreversible cardiovascular morbidity. Full article

Background/Objectives: Pancreatic cancer-associated cachexia (CAC) is a complex, multifactorial and multi-organ metabolic syndrome affecting approximately 80% of patients with pancreatic ductal adenocarcinoma (PDAC). Recent epidemiological data show that cachexia is a primary cause of mortality in PDAC, directly accounting for approximately 30% of cancer-related deaths and significantly limiting the tolerability of cancer therapy and is associated with adverse effects of treatment. It is defined by systemic weight loss, skeletal muscle atrophy (sarcopenia), and adipose tissue depletion, often driven by systemic inflammation and metabolic dysregulation. Methods: The literature was searched in PubMed and Scopus using combinations of keywords. The search covers the literature between 2016 and 2026, but papers before this period were also included because of their historical importance. Studies with higher evidential value, such as prospective studies, randomized controlled trials, and meta-analyses, were prioritized and emphasized in our analysis. Results: CAC in PC arises from a systemic inflammatory response driven by tumor–host interactions and the release of pro-inflammatory mediators, such as growth differentiation factor 15 (GDF-15) and parathyroid hormone-related protein (PTHrP), which promotes anorexia and weight loss. The most commonly used diagnostic criteria include unintentional weight loss of more than 5% of body mass within 6 months, a body mass index (BMI) below 20 kg/m², or weight loss greater than 2% in the presence of sarcopenia. Emerging evidence supports the use of AI-based body composition analysis and novel biomarkers, including GDF-15 levels, to improve the detection and monitoring of cachexia. This review highlights that, despite the absence of pharmacological agents specifically approved for CAC in the United States and Europe, current guidelines recommend multimodal supportive care, including low-dose olanzapine, nutritional support, and exercise-based interventions. Furthermore, we identify recent phase 2 trials targeting the GDF-15 pathway, such as the GDF-15 inhibitor ponsegromab, which have demonstrated significant improvements in body weight and physical activity, suggesting a potential breakthrough in targeted therapies for CAC. Conclusions: CAC in PDAC represents a critical unmet medical need in oncology. It manifests as a lethal systemic pathology that demands early identification and targeted personalized pharmacological and nutritional interventions. Early diagnosis and targeted intervention represent promising strategies for improving survival and quality of life in this high-risk patient population. Full article

Cancer cells resort to metabolic reprogramming to sustain proliferation. Lung cancer has one of the highest mortality rates of all types of cancer. An important factor in its high mortality rate is its tumors’ ability to undergo significant metabolic reprogramming. Phytochemicals can counteract this altered metabolism and exhibit anticancer properties. Coleus hadiensis, a plant used in traditional medicine, has shown such potential. This study evaluated the in vitro cytotoxic activity of its methanolic extract and its effects on the metabolism of HTB-177 lung cancer cells. Qualitative and quantitative phytochemical analysis of this extract was performed to characterize its main constituents. Lung cancer cells were treated with different extract concentrations to evaluate their response to the extract. Cytotoxicity was determined using an MTT assay, and metabolites were analyzed through ¹H-NMR spectroscopy combined with multivariate statistical analysis. Transcriptomic profiling was also conducted to assess gene expression changes in metabolic pathways. Three main phenolic compounds were identified in the extract. The HPLC profile revealed peaks corresponding to gallic acid (GA), ferulic acid (FA), and rosmarinic acid (RA). The extract exhibited cytotoxic activity with an IC₅₀ of 192.85 µg/mL. Metabolic alterations were observed mainly in glycolysis, the Krebs cycle, and lipid metabolism—key pathways for tumor growth. Transcriptomic data revealed altered metabolism-related genes. The upregulation of ME1 correlated with the observed increase in pyruvate levels, while the downregulation of ALDH7A1 and ASRGL1 was linked to altered amino acid catabolism. Furthermore, transcriptomic data revealed the upregulation of the pro-apoptotic gene HRK. These results indicate that the methanolic extract of C. hadiensis possesses cytotoxic activity against lung cancer cells by modulating central metabolic routes and gene expression linked to cancer cell survival and proliferation. Full article

Background/Objectives: Active surveillance (AS) is a viable option for patients with low-risk/low-burden prostate cancer (PCa). Approximately 40–50% of patients will develop disease progression and conversion to active treatment. Therefore, better risk stratification may aid patients and urologists to improve decision making. Herein, the proliferation marker Ki-67 was examined for its prognostic potential in AS patients. Methods: Fifty-nine patients were included. Median follow-up time was 58 months (range, 10–162 months). Tumor-bearing biopsies were evaluated using immunohistochemistry (IHC) staining for Ki-67 and evaluated using digital imaging analysis to determine the percentage of Ki-67-positive PCa cells per biopsy. Results: Thirty-three of 59 patients (55.9%) developed progression. Thirty-one of 59 patients (52.5%) showed Ki-67-positive biopsies (median 0.8%; range, 0–11.9%). The median of Ki-67-positive cells was 1.5% (range, 0–11.9%) in patients with and 0% (range, 0–6.3%) in patients without progression. Comparing patients with Ki-67-positive and Ki-67-negative biopsies showed a worse progression free survival (PFS) in patients with Ki-67-positive biopsies after a period of 15 months, however, without reaching statistical significance (p = 0.071). A 5% threshold for Ki-67 positivity led to a significant difference in PFS. Further exploratory analysis revealed that patients with Ki-67-positive biopsies and aged ≥65 years or with >1 tumor-bearing biopsy show a significantly worse outcome (p = 0.038 and p = 0.037, respectively). Conclusions: Our results suggest that patients with Ki-67-positive biopsies remaining in AS for >1 year have an increased risk for PCa progression and conversion to treatment. Studies to further confirm Ki-67 as a marker for risk stratification, especially with a positivity cut-off of 5%, are warranted in larger cohorts of AS patients. Full article