Search Results (39,243)

Background: Sclerosing adenosis (SA) is a benign, proliferative breast lesion that frequently mimics malignancy on multimodality imaging. The appropriate clinical management of SA diagnosed via core needle biopsy (CNB) remains a highly debated topic in breast oncology. This study aimed to evaluate the clinical, imaging, and histopathological characteristics of CNB-diagnosed SA-spectrum lesions and to determine the rate of, and factors associated with, pathological upgrade at the time of surgical excision in a symptomatic cohort. Methods: This retrospective, single-center study evaluated 34 symptomatic female patients who received a CNB diagnosis of SA. Patients were assessed using targeted ultrasound (US, n = 34), digital mammography (n = 19), and/or dynamic contrast-enhanced breast MRI (n = 17). Based on CNB findings, lesions were classified as isolated SA, complex/accompanied SA, or atypical SA. Patients subsequently underwent either definitive surgical excision or long-term imaging surveillance. Upgrades were defined as the presence of a high-risk B3 lesion not identified on CNB (Level 1) or overt malignancy, such as ductal carcinoma in situ or invasive carcinoma (Level 2), at final surgical pathology. Results: Twenty-one patients (61.8%) underwent surgical excision, while thirteen (38.2%) were managed with radiological follow-up (median surveillance 16 months, range 7–84). Within the surgical cohort, 9 of 21 patients (42.9%; 95% CI: 24.5–63.5%) demonstrated an upgrade: 6 (28.6%; 95% CI: 13.8–50.0%) to a B3-level lesion and 3 (14.3%; 95% CI: 5.0–34.6%) to malignancy. Notably, two of the three malignant upgrades originated from lesions initially classified as isolated SA without atypia on CNB. Due to the limited sample size, no single clinical or imaging variable (BI-RADS category, lesion size, or age) reached statistical significance as an independent predictor of upgrade (all p > 0.10). All patients managed with imaging surveillance remained radiologically stable. Conclusions: In stark contrast to the 1–2% upgrade rates traditionally reported in asymptomatic screening populations, symptomatic SA-spectrum lesions selected for surgical excision following CNB exhibited a substantially higher overall upgrade rate (42.9%) and malignant upgrade rate (14.3%) in our cohort, albeit with wide confidence intervals reflecting the modest surgical subgroup size. The occurrence of malignant upgrades from presumed isolated SA underscores the limitations of CNB sampling and highlights the necessity of multimodality imaging–pathology concordance. Because this estimate derives exclusively from patients already selected for surgery on the basis of clinical and imaging suspicion, it reflects the upgrade risk of this pre-selected, imaging-discordant subgroup and should not be extrapolated to the baseline risk of all CNB-diagnosed SA. Accordingly, these findings caution against extending non-operative management without further scrutiny to symptomatic SA cases showing a similar degree of imaging–pathology discordance: in such cohorts, surgical excision or large-volume vacuum-assisted excision may still merit consideration despite the absence of atypia on CNB, although this observation is drawn from a small, non-randomly selected surgical subgroup and should be interpreted with corresponding caution. Full article

Background: This scoping review maps and synthesizes the scientific evidence on the epidemiological profile and determinants of sick leave and work-related accidents in Brazil, with an emphasis on studies using data from the Brazilian Federal Medical Expert Service of the Ministry of Social Security. Methods: Following the PRISMA-ScR guidelines and the JBI Manual for Evidence Synthesis, eight databases (SciELO, PubMed/MEDLINE, Scopus, Web of Science, LILACS, CINAHL, PsycINFO, Embase) were searched for quantitative observational studies published between 2000 and 2025. Out of the 218 studies identified, 18 met the eligibility criteria. Results: Cross-sectional designs (66.7%) and ecological/time-series designs (22.2%) predominated. The findings identified musculoskeletal disorders as the leading cause of work absence; mental disorders were the third leading cause, exhibiting an upward trend; and a significant influence of institutional factors, especially the Social Security Technical Epidemiological Nexus, on the observed patterns. Determinants operate at the individual, occupational/organizational, and institutional levels. Conclusions: Empirical research on work disability in Brazil remains fragmented, providing limited capacity for causal inference. The findings support five priority areas: sectoral risk management, workplace mental health, territorial strategies for musculoskeletal disorders, sick leave trajectory policies, and data governance, all of which necessitate longitudinal and quasi-experimental studies to evaluate interventions and the impact of institutional changes. Full article

Congenital melanocytic nevi (CMN) are pigmented skin lesions present at birth with a variable risk of developing into melanoma over time. The mitogen-activated protein kinase signaling (MAPK) pathway plays a critical role in the development and progression of CMN, making it a key target for therapeutic interventions. Precision medicine aims to optimize therapeutic efficacy while minimizing adverse effects by tailoring treatments to individuals’ genetic and molecular profiles. This literature review examines the potential of precision medicine in managing CMN, with a specific focus on MEK inhibition within the MAPK pathway, summarizing current preclinical and clinical evidence, mechanisms of action, and therapeutic integration with surgical management strategies. Although early results are promising, the need for personalized treatment strategies, informed by genetic testing and biomarker profiling, is emphasized to improve the management of CMN and reduce the risk of malignant transformation. Further research is necessary to establish the long-term safety and effectiveness of MEK inhibition in CMN therapy, which could offer a more targeted and individualized approach to care. Full article

Perioperative treatment for colorectal cancer (CRC) is undergoing a paradigm shift from uniform cytotoxic regimens toward strategies guided by tumor location, microsatellite instability (MSI)/mismatch repair (MMR) status, and recurrence risk. Four clinically relevant subgroups now shape decision-making: microsatellite stable (MSS)/proficient MMR (pMMR) colon cancer, microsatellite instability-high (MSI-H)/deficient MMR (dMMR) colon cancer, MSS/pMMR rectal cancer, and MSI-H/dMMR rectal cancer. In MSS/pMMR colon cancer, adjuvant therapy is being refined through risk-adapted treatment duration and selective use of neoadjuvant chemotherapy. In MSS/pMMR rectal cancer, total neoadjuvant therapy, selective omission of pelvic radiotherapy, and watch-and-wait strategies are redefining treatment sequencing and organ preservation. In MSI-H/dMMR colon cancer, immune checkpoint inhibitor (ICI) therapy has shown marked activity in both adjuvant and neoadjuvant settings. In MSI-H/dMMR rectal cancer, neoadjuvant ICI therapy is being explored as a non-operative organ preservation strategy. In parallel, circulating tumor DNA (ctDNA)-based minimal residual disease (MRD) assessment is emerging as a tool for postoperative escalation, de-escalation, and surveillance. Across these settings, the maturity of the evidence varies widely, ranging from established phase III standards to guideline-endorsed but still single-arm approaches and investigational strategies that require prospective validation before routine adoption. This review summarizes the current evidence and remaining challenges in biology-, site-, and risk-adapted perioperative management of CRC. Full article

The internal audit function provides consulting services and recommendations for management on performance quality, business environment security, or risk management. Internal auditors are expected to monitor the senior managers’ behaviors and support them in operational and strategic decision making. They should recognize and reduce the possibility of an employee’s opportunistic behavior, improve internal control, and prevent financial fraud. Therefore, they should be highly qualified, and their competencies are to be constantly updated. Hence, they are encouraged to learn and participate in certification processes organized by various institutions, e.g., the Institute of Internal Auditors (IIA). Although there are many strategies of learning in the certification process, this study focuses on learning-by-testing approach. This method emphasizes the use of testing to acquire the internal audit knowledge needed to successfully pass the professional certified exams. Beyond that, the authors present the use of large language models (LLMs) in internal auditing. However, the research goal is to how the large language models (LLMs) can be used to answer questions included in the Certified Internal Auditor (CIA) exam directed by the Institute of Internal Auditors (IIA). In the research section, fourteen LLMs were evaluated using English and Polish-language CIA test sets comprising 184 and 183 multiple-choice questions, respectively, with accuracy as the primary performance metric. The best-performing individual model achieved approximately 91% accuracy, while the Friedman test identified statistically significant overall differences among the models for both datasets. The findings indicate that a multi-agent system can achieve better performance than an individual LLM. The learning-by-testing method can be supported not only by the use of professional association materials but also by the opportunity learners have to enrich their knowledge through the use of LLMs in the learning process. Full article

Background/Objectives: The advent of immune checkpoint inhibitors (ICIs) and targeted therapies has revolutionized advanced melanoma treatment but introduced unique immune-related adverse events (irAEs). Hematological irAEs (Hem-irAEs) are rare but carry disproportionately high morbidity and mortality. This review systematically synthesizes current literature to comprehensively understand the incidence, pathophysiology, clinical presentation, and management of Hem-irAEs in modern melanoma therapy. Methods: A comprehensive Web of Science literature search (January 2015 to January 2026) identified studies reporting hematological adverse events associated with melanoma immunotherapy and targeted therapies. After screening 2274 records, 130 relevant studies were included for quantitative data extraction, focusing on incidence rates and toxicity grading. Results: Hem-irAEs occur infrequently (under 4% overall incidence for ICIs) but possess staggering mortality rates between 12% and 15.5%. The most common manifestations are immune thrombocytopenia (ITP), autoimmune hemolytic anemia, and neutropenia. Combination regimens significantly amplify toxicity frequency and severity. Diagnosis requires meticulous baseline monitoring and bone marrow biopsies to differentiate peripheral destruction from central marrow failure. First-line management mandates ICI discontinuation and high-dose corticosteroids, utilizing targeted second-line immunosuppressants for refractory syndromes. Conclusions: Hem-irAEs embody a profound clinical paradox: while mild toxicities often herald a robust anti-tumor response, severe hematological events drastically increase non-cancer mortality, negating these oncological benefits. Navigating this “double-edged sword” demands a paradigm shift toward proactive risk stratification. Integrating predictive biomarkers including baseline autoantibodies, Human Leukocyte Antigens (HLA) profiling, and systemic inflammatory indices is crucial to identify vulnerable populations before treatment. Optimizing outcomes requires highly personalized vigilance to balance the life-saving efficacy of immunotherapy against the catastrophic threat of hematopoietic failure. Full article

High-risk human papillomavirus (HR-HPV) infection is the principal etiological factor in cervical cancer, with genotype distribution and cytological associations varying across populations. This retrospective study aimed to characterize the prevalence and genotype distribution of HR-HPV among 1747 Bulgarian women, including a subgroup of 1134 women with paired HPV polymerase chain reaction (PCR) and liquid-based cytology (LBC) results. The study population comprised women undergoing routine cervical screening (76.0%, n = 1328) and women tested because of clinical indications, including gynecological symptoms (24.0%, n = 419). The overall HR-HPV prevalence was 31.4% (549/1747) and was significantly higher among women tested for clinical indications than among those undergoing routine screening. HPV16 was the most frequently detected genotype, followed by multiple HR-HPV infections and other genotypes, including HPV31, HPV51, HPV66, HPV18, HPV45, HPV56, HPV68, and HPV33. Cytological abnormalities were identified in 24.7% (280/1134) of women with paired HPV and cytology results. HR-HPV positivity was strongly associated with abnormal cytology; however, 27.3% (233/854) of women with negative cytology were also HR-HPV positive. Integrating HPV genotyping with cytology may improve risk stratification and support more targeted clinical management. Despite the increasing use of LBC and HPV co-testing, comparative data describing HR-HPV genotype distribution and its relationship with cytological findings in screening and symptomatic populations remain limited. These findings provide epidemiological evidence on HR-HPV infection patterns in Bulgarian women and establish a foundation for future studies evaluating genotype-specific risks, disease progression, and population-based surveillance strategies. Full article

The growing demand for eggs from alternative housing systems is driven by perceived nutritional and welfare benefits. However, the trade-off between enhanced bioactive composition and exposure to environmental contaminants remains insufficiently explored. This study evaluated the physical traits, bioactive compounds, and heavy metal content of 480 commercially available table eggs from four housing systems: organic, free-range, barn, and enriched cages. Organic eggs exhibited the highest albumen quality, expressed by Haugh units (92.03 vs. 70.86 in cages) and lysozyme activity (144,877 U/mL vs. 119,830 U/mL in cages), alongside the highest concentrations of fat-soluble vitamins (e.g., vitamin A at 1600 μg/100 g and vitamin E at 3267 μg/100 g) and n-3 polyunsaturated fatty acids, including docosahexaenoic acid (DHA: 0.673% vs. 0.360% in cages). Conversely, organic eggs presented the weakest eggshells (breaking strength of 34.19 N vs. 47.05 N in cages) and a less favourable lipid profile regarding atherogenicity (AI: 0.411) and thrombogenicity (TI: 3.455) indices. Crucially, organic eggs contained significantly higher levels of lead (0.361 mg/kg) compared to indoor systems (0.041 mg/kg in barn and 0.102 mg/kg in cages), highlighting their susceptibility to environmental pollution. Cage and barn eggs were associated with higher chemical safety and shell strength but demonstrated a lower overall bioactive value. Ultimately, the choice of table eggs may involve a trade-off between the health-promoting benefits of extensive systems and the potential risks of heavy metal contamination, emphasising the need for integrated food safety management. Full article

Background: Obesity is a chronic, multifactorial disease that demands personalized and sustainable management approaches. Digital health technologies, such as artificial intelligence, wearable devices, mobile health apps, and virtual reality (VR), may support obesity care by providing enhanced behavioral monitoring, personalized feedback, and patient engagement. Objective: This critical narrative review discusses the current evidence on artificial intelligence, wearable technologies, and VR in the context of precision nutrition and obesity management and their possible clinical applications and limitations. Method: A critical narrative review was conducted using peer-reviewed literature published between 2019 and 2026 and identified through PubMed and Google Scholar. Search terms included combinations of “precision nutrition,” “personalized nutrition,” “obesity,” “weight management,” “metabolic health,” “digital health,” “artificial intelligence,” “machine learning,” “mobile health,” “wearable devices,” and “omics” using Boolean operators. Evidence from randomized controlled trials, systematic reviews, meta-analyses, and key conceptual studies was critically synthesized due to substantial heterogeneity in interventions and outcomes. Result: Wearables and mobile applications can enable continuous self-monitoring of physical activity, dietary intake, sleep, and physiological measures. Artificial intelligence may improve dietary personalization, risk prediction, glycemic control, and adaptive feedback. VR offers an immersive way to tackle behavioral and cognitive mechanisms related to overeating such as cravings, food cue reactivity, and inhibitory control. However, the evidence is heterogeneous, with many studies limited by short follow-up periods, small samples, variable adherence, and insufficient clinical validation. Conclusions: Artificial intelligence, wearable technologies, and VR are promising tools for precision obesity management, but their long-term clinical effectiveness remains uncertain. Future research should prioritize adequately powered trials, longer follow-up, standardized outcomes, transparent algorithms, ethical data governance, and integration with multidisciplinary nutrition and obesity care. Full article

Climate change is reshaping species distributions worldwide, making reliable prediction of invasive species increasingly important for ecological risk assessment and pest management. However, species distribution models (SDMs) calibrated with regional occurrence records may underestimate potential suitable habitats because of niche truncation. Here, we evaluated the effects of occurrence data extent on SDM predictions using the globally invasive agricultural pest Spodoptera frugiperda (J. E. Smith, 1797) (Lepidoptera: Noctuidae). Global occurrence records (1763 records) and China-specific occurrence records (946 records) were combined with climatic, topographic, and vegetation variables to construct ensemble SDMs using the Biomod2 platform under current and future climate scenarios (SSP1-2.6, SSP2-4.5, and SSP5-8.5). Model performance, environmental variable contributions, habitat suitability patterns, and centroid shifts were compared between the two datasets. The global model showed excellent predictive performance (True Skill Statistic (TSS) = 0.851, Receiver Operating Characteristic (ROC) = 0.977) with balanced contributions from multiple environmental variables, whereas the China model achieved only acceptable performance (TSS = 0.690, ROC = 0.905) and relied predominantly on Bio06. Both models consistently identified southern China and the Huang-Huai Plain as the core highly suitable regions. Future projections revealed under higher emission scenarios (SSP5-8.5), particularly toward northern and western China. Centroid analyses further indicated consistent northwestward shifts under higher emission scenarios (SSP5-8.5), whereas low-emission scenarios produced less directional and more variable centroid movements. These results demonstrate that the spatial extent of occurrence records exerts a greater influence on SDM predictions than differences among modeling algorithms. Although models of China may underestimate invasion risk because invasive populations have not reached ecological equilibrium, the spatial stability of highly suitable habitats and centroid migration direction provide robust indicators for cross-model comparisons. This study provides methodological guidance for occurrence data selection and improves invasion risk assessment and management of S. frugiperda under climate change. Full article

Kidney transplant recipients (KTRs) face a significantly elevated risk of persistent high-risk human papillomavirus (HR-HPV) infection and subsequent anal squamous cell carcinoma (ASCC) due to chronic immunosuppressive therapy impairing immunosurveillance. Despite the markedly increased risk of ASCC in this vulnerable cohort, standardized screening protocols and optimal clinical management guidelines are not exhaustive. Chronically compromised immunosurveillance permits prolonged HR-HPV carriage and viral genome integration, driving oncogenesis via the E6 and E7 oncoproteins. While calcineurin inhibitors exert pro-oncogenic effects, transitioning to mTOR inhibitors offers distinct antiproliferative and antiviral advantages. Early detection relies on risk-stratified screening utilizing digital anorectal examination, anal cytology, and high-resolution anoscopy. For managing anal intraepithelial neoplasia, traditional topical agents and minimally invasive ablative procedures are widely used, although high recurrence rates present a major clinical challenge. This review analyzes HPV pathogenesis and clinical management in KTRs, evaluating the impact of immunosuppressive regimens and exploring innovative diagnostic and therapeutic strategies. To address viral persistence without compromising the allograft, integrating novel non-invasive, target-specific nutraceuticals may represent an interesting complementary approach. Ultimately, mitigating post-transplant ASCC requires a multidisciplinary strategy that couples early localized screening with tailored systemic immunosuppression. Full article

Artificial Intelligence-driven detection mechanisms present both opportunities and challenges in modern systems, particularly within smart cities that rely on complex operational technologies. In the context of Saudi urban infrastructure, rapidly evolving and multidimensional cyber threats require advanced, energy-efficient security solutions. This research proposes an Artificial Intelligence-based Threat Detection Mechanism designed to proactively identify and mitigate cyber threats while maximizing energy efficiency and minimizing cost and system complexity. Purpose: The proposed theoretical framework focuses on securing sustainable smart cities by integrating Artificial Intelligence-based anomaly detection with quantum-enhanced algorithms to address high-dimensional and emerging cyber threats across interconnected urban systems. The Artificial Intelligence-based Threat Detection Mechanism enables early and proactive threat detection across sustainable smart city networks, including connections to external and global infrastructures, ensuring continuous monitoring, resilience, and service continuity. Methods: The methodology emphasizes the development of energy-efficient Artificial Intelligence models and quantum protocols, incorporating intelligent risk assessment, adaptive calibration, and automated response mechanisms. In addition, the framework introduces distributed security hubs to enhance cybersecurity robustness and scalability. Anticipated Results and Conclusions: Anticipated outcomes include improved security management policies, automated threat detection and response, and adaptive protection against evolving cyber risks. The proposed framework provides a scalable and cost-effective solution aligned with sustainability objectives. Ultimately, this research contributes a proactive and intelligent framework for securing smart city ecosystems, supporting long-term development goals and aligning with Saudi Vision 2030. Full article

Objectives: This study aimed to assess the impact of the COVID-19 pandemic on the epidemiology, microbiology, clinical presentation, management, and outcomes of infective endocarditis (IE). Methods: A retrospective cohort study was conducted, including 100 adult patients with definite IE diagnosed between January 2020 and December 2025 at a Romanian tertiary care centre. Patients were stratified by year of admission into pandemic (2020–2022) and post-pandemic (2023–2025) groups. Results: Among the 100 patients (47 in the pandemic period and 53 in the post-pandemic period), the time from symptom onset to diagnosis was significantly shorter in the post-pandemic period (median of 24 days versus 40 days; p < 0.01). We observed changes in the microbiological profile. The proportion of staphylococcal IE was lower, while the proportions of enterococcal and streptococcal IE were slightly higher in the post-pandemic period. In-hospital mortality decreased significantly from 51.1% to 24.5% (p = 0.006). Embolic events were more frequent in the post-pandemic period (62.3% vs. 39.1%; p = 0.022). Vegetation size was associated with embolic risk (OR: 1.05 per mm; p < 0.01). Pandemic-period admission (aOR 3.11; p = 0.020) and sepsis (aOR 11.30; p = 0.006) were independently associated with higher in-hospital mortality. Conclusions: The COVID-19 pandemic was associated with delayed presentation and worse outcomes in IE. Post-pandemic improvements likely reflect healthcare system adaptation and earlier diagnosis. Microbiological aetiology remains a key determinant of prognosis. Full article

Introduction: Pediatric clavicle fractures are among the most common fractures in this age group. Current research supports the efficacy of nonoperative treatment for these injuries in pediatric patients. Our study seeks to examine the current trends in the management of these fractures and determine whether they align with the existing evidence-based guidelines. Methods: A retrospective analysis of pediatric patients with clavicle fractures between 1 January 2014 and 31 December 2024 was analyzed. A retrospective query was performed using the TriNetX Research Network. Patients were dichotomized into two groups based on open reduction internal fixation and nonoperative or closed treatment codes over this period, performing subgroup analyses by sex, race, and age. Results: We evaluated 78,251 patients between 10 and 18 years with clavicle fractures from 2014 to 2024, of whom 3546 underwent open reduction and internal fixation (ORIF). ORIF utilization increased from 1.62% in 2014 to 5.89% in 2024, representing a 263.6% increase from the 2014 baseline. Males consistently underwent ORIF more often than females. Adolescents (15–18 years) had substantially higher and faster-rising ORIF rates than younger patients (10–14 years), increasing from 3.4% to 12.4% versus 0.8% to 2.5% between 2014 and 2024 (APC 7.5% vs. 0%, p = 0.001). White patients had higher ORIF rates than African American patients, although some disparities narrowed over time. Conclusions: Despite limited supporting evidence, current trends demonstrate a substantial increase in the surgical management of pediatric clavicle fractures, with operative treatment rising by 263.6% by 2024. This increase in ORIF procedures may expose patients to potentially avoidable risks, including infection, anesthesia-related complications, implant-related issues, and prolonged recovery, without clearly established benefits in many cases. Full article

Background: Incretin-based therapies (IBTs), including glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonists (GIP/GLP-1 RAs), have transformed the management of obesity and type 2 diabetes mellitus (T2DM). Although these agents provide substantial metabolic and cardiometabolic benefits, their effects on skeletal muscle, particularly in older adults at increased risk of sarcopenia and functional decline, remain incompletely understood. Methods: This narrative review synthesizes evidence from randomized controlled trials (RCTs) and observational studies evaluating the effects of semaglutide and tirzepatide on skeletal muscle mass (SMM), muscle quality, strength, and physical performance. Current evidence on nutritional and exercise strategies aimed at preserving skeletal muscle during IBT was also reviewed. Results: Both semaglutide and tirzepatide induce substantial weight loss accompanied by reductions in lean body mass (LBM). However, current evidence indicates that LBM loss is generally proportional to the magnitude of weight loss and should not be interpreted as a direct surrogate for skeletal muscle loss or drug-induced myotoxicity. Tirzepatide appears to improve skeletal muscle composition by reducing muscle fat infiltration (MFI), whereas semaglutide shows more heterogeneous effects on muscle strength and physical performance, particularly in older or frail individuals. Emerging evidence highlights the importance of muscle quality, nutritional adequacy, and resistance exercise as key determinants of muscle preservation, although functional outcomes and data in older adults remain limited. Conclusions: The effects of incretin-based therapies (IBTs) on skeletal muscle are multifactorial and influenced by age, baseline muscle reserve, nutritional status, and physical activity. Preserving skeletal muscle health should be considered an integral component of obesity management through individualized nutritional care, adequate protein intake, resistance exercise, and regular functional assessment. Future research should prioritize the standardized evaluation of muscle quality and function and determine whether targeted nutritional interventions can improve the quality of weight loss and support healthy aging during IBT. Full article