Search Results (37,345)

Surgical resection remains a cornerstone in the multidisciplinary management of central nervous system (CNS) tumors, particularly diffuse gliomas. Traditionally, the role of surgery has been evaluated primarily through quantitative metrics such as extent of resection and its association with survival outcomes. However, despite maximal and radiologically complete resections, recurrence remains nearly universal in malignant CNS tumors, suggesting that surgical cytoreduction alone does not fully account for post-surgical disease dynamics. Emerging biological and molecular evidence indicates that surgery represents not merely a technical intervention, but a biologically active event that profoundly reshapes tumor evolution and treatment response. In this review, we propose a conceptual framework that redefines surgery as a key biological driver in CNS tumor progression. We synthesize evidence demonstrating that surgical trauma induces inflammation, hypoxia, vascular remodeling, immune modulation, and extracellular matrix reorganization, collectively reprogramming the residual tumor microenvironment. These changes create selective pressures that favor the survival and expansion of adaptive tumor cell subpopulations, including invasive and stem-like phenotypes. From an evolutionary perspective, surgical resection functions as an acute selective bottleneck acting on heterogeneous tumor ecosystems, contributing to clonal selection and molecular divergence at recurrence. We further examine the dissociation between surgical (anatomical) margins and molecular (biological) margins, highlighting how biologically active tumor cells infiltrate beyond radiologically defined boundaries. This discrepancy provides a biological explanation for marginal and distant recurrences and challenges anatomy-based paradigms of surgical completeness. Importantly, we discuss how surgery-induced biological changes influence postoperative radiotherapy and systemic therapies, affecting radiosensitivity, target delineation, and therapeutic vulnerability. Finally, we outline future directions toward surgery-integrated precision neuro-oncology, emphasizing the potential of spatial profiling, liquid biopsy, advanced imaging, and artificial intelligence to capture perioperative tumor evolution. By reframing surgery as a biological inflection point rather than a neutral prelude to adjuvant treatment, this review advocates for a dynamic, biology-driven continuum of care aimed at anticipating tumor adaptation and improving long-term disease control in CNS tumors. Full article

Background/Objectives: Obstructive sleep apnea (OSA) is a prevalent disorder in adults, characterized by recurrent upper airway obstruction during sleep, resulting in intermittent hypoxia, sympathetic activation, and sleep fragmentation. It is linked to significant cardiovascular, metabolic, neurocognitive, and psychosocial morbidity. There is increasing evidence that continuous positive airway pressure (CPAP) adherence remains suboptimal in many patients, and in those patients, surgery is often indicated. Methods: This protocol report presents an updated and protocol-driven surgical approach grounded in clinical evidence and experience, highlighting the role of drug-induced sleep endoscopy (DISE) and personalized multi-level interventions for adult patients with OSA. The integration of anatomical phenotyping and DISE-directed planning enables precise surgical targeting. The protocol emphasizes patient selection, individualized treatment based on obstruction patterns, and perioperative optimization. This surgical algorithm improves the success rates and long-term outcomes in patients who are intolerant of CPAP therapy. Results: A DISE-guided and multi-level surgical approach includes uvulopalatoplasty, septoplasty, tongue base reduction, palatoplasty, and maxillomandibular advancement (MMA). Preoperative assessments include BMI and the STOP-BANG and Epworth Sleepiness scales, while postoperative care emphasizes follow-up polysomnography and adjunctive therapies only when necessary. Regional experiences in Saudi Arabia and Canada underscore the importance of standardized evidence-based surgical care. Conclusions: The purpose of this article is to establish a clear protocol for managing patients diagnosed with OSA, drawing on a review of the existing literature and the insights of experienced surgeons in the field of sleep apnea, and to update current protocols with modern evidence. Full article

Modern changes in natural and anthropogenic conditions in mountain ecosystems highlight the growing need to assess the status of medicinal plant populations and factors influencing their resilience. This study presents findings from a comprehensive investigation of three previously undocumented wild populations of Chelidonium majus L., discovered in the gorges of Kaindy, Shet-Merke, and Kolsai in the eastern part of the Kungey Alatau range. The research included analysis of phytocenotic conditions, population age structure, morphometric and morpho-anatomical traits of plants, along with physicochemical properties of soils. It was found that C. majus is associated with meadow-type moisture regimes and occurs spottily, mainly in moist microhabitats within open and semi-shaded plant communities. Population sizes ranged from 264 to 296 individuals, with average densities between 5.1 and 16.3 individuals per m². All studied populations exhibited complete ontogenetic spectra, dominated by generative stages (56.1–67.2%), indicating preserved reproductive potential despite limited recruitment at early developmental phases. Morpho-anatomical analysis revealed high phenotypic plasticity: under drier, poorer soil conditions, xeromorphic features developed, whereas mesomorphic structures prevailed in more favorable habitats. Soil analysis indicated that Shet-Merke population enjoys optimal growth and regeneration conditions. These results suggest that current C. majus populations in the region remain relatively stable, though strongly dependent on edaphic–hydrological and phytocenotic factors—underscoring the necessity of integrated monitoring to ensure conservation of medicinal plant resources. Full article

Background: Although survival in coronary artery disease (CAD) has improved with modern therapies, quality of life (QoL) remains an important clinical concern. Our study aimed to evaluate QoL, life satisfaction, and disease acceptance in CAD patients and to identify their clinical and lifestyle determinants. Methods: This single-center, prospective study included patients undergoing percutaneous coronary intervention for myocardial infarction (MI) or chronic coronary syndrome (CCS). QoL was assessed using validated questionnaires (WHOQOL-BREF, SWLS, AIS). Comparative analyses between the MI and CCS groups were performed, and the determinants of the outcomes were evaluated using regression models. Results: The study included 220 patients (110 MI and 110 CCS) with a median age of 64 years (IQR 54–70); 30% were women. The WHOQOL-BREF-assessed QoL was comparable between MI and CCS patients, whereas MI patients reported higher life satisfaction (SWLS 24 vs. 20, p = 0.003). Smoking was the strongest determinant of poorer QoL, associated with lower SWLS (β = −2.75; p < 0.001) and WHOQOL-BREF (β = −4.46; p = 0.014). Alcohol consumption (β = −6.22; p = 0.008), hypertension (β = −7.10; p < 0.001), and chronic obstructive pulmonary disease (β = −9.84; p < 0.001) were also independently associated with lower WHOQOL-BREF scores. Subgroup analyses showed heterogeneity between MI and CCS patients. Conclusions: QoL in CAD patients might be influenced more by lifestyle factors and multimorbidity than by CAD phenotype. Smoking, alcohol, and cardiopulmonary comorbidities might have the most consistent adverse associations with QoL. These findings highlight the potential importance of integrating lifestyle and comorbidity management to improve QoL and patient-reported outcomes in CAD care. Full article

Background: Acinetobacter baumannii (A. baumannii) is a formidable nosocomial pathogen and is classified by the World Health Organization (WHO) as a critical-priority pathogen, owing to its rapid evolution into extensively drug-resistant (XDR) and pan-drug-resistant (PDR) strains. Colistin remains one of the last-resort therapeutic options, although resistance rates are increasing in endemic regions such as Greece. In this study, we investigated the molecular basis of colistin resistance and characterized the clonal backgrounds of clinical XDR/PDR A. baumannii isolates collected between January and June 2022 from two tertiary-care hospitals in Thessaloniki, Northern Greece. Methods: We analyzed forty non-duplicate XDR/PDR clinical isolates. Antimicrobial susceptibility was determined using the VITEK 2 system, broth microdilution, and gradient diffusion methods. The lipid A biosynthesis genes (lpxA, lpxC, lpxD) and the pmrCAB operon were amplified by PCR and sequenced for all isolates. A representative subset of strains (n = 10/40) underwent multilocus sequence typing (MLST) according to the Pasteur MLST scheme. Results: All isolates proved colistin-resistant (MIC ≥ 4 µg/mL), and 95% were classified as PDR. Sequence analysis revealed multiple nonsynonymous mutations in the pmrCAB operon, with the PmrB A226V substitution predominating and extensive amino-acid changes observed in PmrC. In contrast, lpx genes exhibited limited protein-level variation, limited to lineage-associated polymorphisms (LpxC N287D, LpxD E117K). A novel six-nucleotide insertion in pmrB was identified in one isolate. MLST demonstrated a predominance of ST2 (International Clone 2), with single representatives of ST115 (IC2) and ST1 (IC1). Conclusions: In this cohort from Northern Greece, chromosomal mutations in the pmrCAB operon, within a predominantly ST2/IC2 background, were strongly associated with colistin resistance. These findings underscore the urgent need for continued molecular surveillance and targeted infection-control measures to limit further spread of PDR A. baumannii. Full article

Soil salinization severely threatens agricultural sustainability in saline–alkali regions, and high-throughput, efficient screening of salt-tolerant rice varieties is critical to mitigating this threat. Traditional evaluation methods are constrained by low throughput, limited spatiotemporal resolution, and the lack of standardized indicators. To address these gaps, this study established a multi-scale spectral phenotyping framework integrating ground-based hyperspectral, UAV-borne multispectral, and Sentinel-2 satellite remote sensing data for high-throughput screening of salt-tolerant rice. Field experiments were conducted with 12 rice lines at five key growth stages in Ningxia, China, with synchronous ground spectral measurements and UAV image acquisition on the same day for each stage. Five feature selection methods were employed to screen salt stress-sensitive hyperspectral bands, with classification accuracy validated via a Support Vector Machine (SVM) model. The results showed that: (1) rice spectral characteristics varied dynamically across growth stages, and first-order differential transformation effectively amplified subtle spectral variations in stress-sensitive regions; (2) the Minimum Redundancy–Maximum Relevance (mRMR) method outperformed other methods, achieving 100% classification accuracy at key growth stages, with sensitive bands dominated by red edge bands (58.33%); (3) the constructed Salt Stress Index (SIR) showed strong correlations with classical vegetation indices and rice yield, and could clearly distinguish salt-tolerant and salt-sensitive rice varieties, with stable performance against field environmental noise; and (4) band matching between UAV and Sentinel-2 data enabled multi-scale data fusion and regional-scale salt stress monitoring. This framework realizes the transformation from qualitative spectral description to quantitative salt tolerance evaluation, providing standardized technical support for salt-tolerant rice breeding and precision management of saline–alkali lands. Full article

Advanced-stage ovarian cancer remains a major clinical challenge because of its aggressive behavior and the frequent development of chemoresistance. The nuclear factor erythroid-derived 2–like 2 (NRF2) signaling pathway regulates cellular redox homeostasis. However, its role in ovarian cancer stem-like cells remains unclear. Therefore, we aimed to investigate the effects of NRF2 overexpression on acetaldehyde dehydrogenase (ALDH)⁺ KURAMOCHI ovarian cancer cells in vitro and in vivo. In particular, we investigated the effects of NRF2 on tumor-associated behaviors, chemoresistance, and signaling pathways. Lentivirus-mediated NRF2 overexpression activated extracellular signal-regulated kinase and AKT signaling. Moreover, it modulated tumor-associated phenotypes, including proliferation, migration, and invasion. NRF2-overexpressing cells exhibited significantly enhanced migratory and invasive capacities, increased resistance to paclitaxel and carboplatin, and reduced apoptosis. Furthermore, the expression of anti-apoptotic proteins was upregulated, and caspase-3 activation was attenuated. In xenograft models, NRF2 overexpression promoted tumor growth and increased the expression of antioxidant and angiogenic factors, including heme oxygenase-1 and vascular endothelial growth factor A. Collectively, these findings demonstrate that NRF2 regulates ovarian cancer aggressiveness and chemoresistance by coordinating stress response signaling, survival pathways, and tumor progression. Therefore, targeting NRF2-mediated signaling represents a promising therapeutic strategy for overcoming drug resistance and improving outcomes in patients with ovarian cancer. Full article

Background/Objectives: Multidrug-resistant (MDR) Acinetobacter baumannii (Ab) has emerged as a significant bacterial pathogen responsible for nosocomial infections. The most common clinical manifestations of Ab infection include ventilator-associated pneumonia and catheter-related bloodstream/urinary infections. Given the extensive MDR phenotype of Ab, preventive vaccination strategies are crucial for protecting susceptible populations. Methods: We utilized immunoinformatics to identify candidate peptides containing both putative B- and T-cell epitopes from proteins associated with Ab pathogenesis. Subsequently, we designed novel Acinetobacter Multi-Epitope Vaccines (AMEVs), each comprising an Ab thioredoxin A (TrxA) leader protein, five to seven of the identified peptide antigens, and a C-terminal His(6x)-tag to facilitate protein purification. Results: Subcutaneous vaccination of C57BL/6 mice with AMEV1 or AMEV2, formulated with TiterMax adjuvant, conferred 60% and 80% protection, respectively, against intraperitoneal Ab challenge. AMEV vaccination induced a robust antibody response to each corresponding whole protein and most of its component peptides. We then constructed an improved vaccine, AMEV5, which included the Ab TrxA protein and seven confirmed B-cell epitope peptides. Subcutaneous immunization of BALB/c mice (n = 10 per group) with rAMEV5 emulsified in Adda03 adjuvant activated antigen-specific IL-5-secreting T cells and antibody-producing B cells. Evaluation of vaccine efficacy demonstrated that AMEV2- and AMEV5-immunized mice were protected from a lethal intraperitoneal Ab challenge, with survival rates of 70% and 90%, respectively. Conclusions: These study results provide insights into the application of reverse vaccinology to combat the rise of MDR Acinetobacter infection. Full article

Background: A non-dipping blood pressure pattern, defined as an insufficient nocturnal decline in systolic blood pressure, is associated with increased cardiovascular risk and target organ damage. While metabolic abnormalities contribute to circadian blood pressure dysregulation, the independent roles of systemic inflammation and atherogenic burden in individuals without overt metabolic disease remain insufficiently characterized. We aimed to evaluate the associations of systemic inflammatory response index (SIRI) and atherogenic index of plasma (AIP) with nocturnal blood pressure pattern. Methods: This retrospective cross-sectional study included 469 adults who underwent 24 h ambulatory blood pressure monitoring (ABPM) at a single tertiary cardiology outpatient clinic. Participants were classified as dippers (≥10% nocturnal systolic BP decline) or non-dippers (<10%). Hierarchical logistic regression models were constructed sequentially: Model 1 (age, sex), Model 2 (Model 1 + AIP, fasting glucose), and Model 3 (Model 2 + SIRI). Discriminative performance was assessed using receiver operating characteristic (ROC) analysis. Results: Non-dipping was present in 62.5% of participants. LDL cholesterol, AIP, and SIRI were higher in non-dippers, whereas CRP was higher in dippers. In hierarchical regression, AIP was independently associated with non-dipping in Model 2 (OR = 3.672, p = 0.003). After addition of SIRI, SIRI remained independently associated (OR = 1.913, p < 0.001), and model explanatory power increased (Nagelkerke R² = 0.104). AIP, fasting glucose (inverse association), and age also remained significant. Individual discrimination was modest for SIRI (AUC = 0.572) and AIP (AUC = 0.576), while the multivariable model achieved an area under the curve (AUC) of 0.660. Non-dipping prevalence increased across SIRI quartiles (p for trend = 0.009). Conclusions: Both inflammatory and atherogenic burden were associated with a non-dipping blood pressure pattern in individuals without overt metabolic disease. Although the discriminative capacity was modest, combined inflammatory–metabolic assessment may provide additional biological insight into circadian blood pressure dysregulation. Full article

Background and Objectives: Peripheral neuropathy (PNP) is a frequent and debilitating complication among patients with diabetes mellitus (DM) and other metabolic conditions, substantially affecting morbidity, functional status, and quality of life. Identifying predictors of PNP is essential for optimizing early diagnostic strategies and improving long-term management outcomes. The aim of this study was to determine the predictive factors of PNP in a cohort of patients with DM. Materials and Methods: A cross-sectional study including 117 patients diagnosed with DM assessed for PNP was conducted. All patients were evaluated clinically and biologically. PNP was clinically assessed using the Toronto Clinical Scoring System (TCSS) score and sudomotor function by Sudoscan. Results: The patients included were mostly males with type 2 DM and metabolic syndrome phenotypes. Moreover, the patients with PNP were much older than those without PNP (65 [57–69] vs. 59.50 [46–68] years, p = 0.008), with a longer duration of DM (10 [6–15.50] vs. 5.5 (2–14] years, p = 0.019), and associated autonomic diabetic neuropathy (χ² = 24.382, p < 0.001). Furthermore, TCSS and Sudoscan were correlated with a history of PNP, especially Sudoscan, which showed a very good discriminative ability for diabetic neuropathy diagnosis (AUC = 0.816). In a multivariable logistic regression including age, DM duration, and HbA1c, age was independently associated with PNP, with each additional year increasing the odds of neuropathy by approximately 6% (OR = 1.06, 95% CI 0.02–1.09, p = 0.002). When age was excluded, DM duration showed a borderline association with PNP (OR = 1.055, CI95% 0.997–1.117), suggesting potential overlap between these variables. Adding sudomotor assessment to the initial model improved the model performance (AUC 0.70–0.72). Conclusions: Age emerged as the main independent predictor of diabetic neuropathy, highlighting the role of cumulative metabolic exposure in the development of neural damage. Moreover, sudomotor assessment may have a complementary role in PNP assessment. Full article

Calcium oxalate (CaOx) crystals in plants can form naturally within their idioblasts but may also be induced by other factors, such as environmental pollution. Here, we report qualitative and semiquantitative results obtained using scanning electron microscopy (SEM) and energy-dispersive X-ray (EDX) from two experiments in which tomato seedlings were moderately irrigated with Sulfamethoxazole (SMX) and Amoxicillin (AMX) solutions (0.25 mM). Abundant prismatic CaOx co-crystals appeared on the leaf surface induced by these two antibiotics compared to the distilled water (DW) control. Applying a non-thermal plasma (NTP) treatment for 20 min (T20) to the SMX initial solution led to a dramatic suppression of these crystals, with a shift toward spherical structures. Furthermore, the investigation into the composition of both crystal types, indicated different percentual levels of O, C, Ca, K, Mg, S, and Mn as main constituent minerals involved in crystal formation. However, crystal morphology was affected by each applied experimental condition, while detecting their constituent elements depended on their mineral homogeneity at the micro- or macro-field scales. Although both antibiotics induced crystal formation and T20 phenotypically reduced the abundance of the acicular–prismatic crystals by removing the effects of SMX, their mode of action has not yet been clarified. Full article

Retained placenta (RP) is a significant postpartum complication in dairy cows. Although abnormal estradiol (E₂) levels are implicated, the underlying cellular mechanisms remain poorly defined. Through RNA-seq analysis of postpartum blood from cows with or without RP, we identified Serum and Glucocorticoid-regulated Kinase 1 (SGK1) as a differentially expressed gene candidate. Analysis of fetal cotyledonary tissues revealed that SGK1 expression was significantly elevated in these tissues, concomitant with markers of suppressed apoptosis, increased levels of tight junction proteins, and an inhibited epithelial–mesenchymal transition (EMT) phenotype. To explore a potential mechanistic link between E₂ and these cellular alterations, we investigated the E₂-SGK1 axis in bovine endometrial epithelial cells in vitro. E₂ treatment upregulated SGK1 expression, reduced apoptosis, increased tight junction protein levels, and suppressed EMT. Conversely, SGK1 knockdown induced apoptosis, disrupted tight junctions, and impaired EMT. Notably, E₂ could not rescue the apoptosis and EMT alterations in SGK1-knockdown cells, indicating that SGK1 is a critical mediator of these E₂ effects in this cellular model. Based on these initial correlative findings in tissues, combined with the subsequent mechanistic experiments in cells, we propose a novel model whereby dysregulation of the E₂- SGK1 axis could contribute to RP pathogenesis by stabilizing the placental interface. Our findings provide the first experimental evidence linking SGK1 to RP and establish a foundation for future in vivo validation. Full article

Flooding, as a major abiotic stress, significantly impacts the growth and survival of poplar plantations in the floodplains of the middle and lower reaches of the Yangtze River. Elucidating the molecular mechanisms underlying flooding responses in poplar is crucial for enhancing plantation productivity. In this study, two important eastern cottonwood cultivars, Populus deltoides ‘Jianghan 1’ (HBI) and P. deltoides Bartr. CL (CL), were investigated. By integrating long-term growth surveys and transcriptome sequencing, we analyzed their phenotypic traits and molecular responses to flooding stress. After 7 years of seasonal flooding, HBI exhibited a survival rate of 73.91%, along with superior height (23.1 m) and diameter at breast height (DBH, 26.3 cm), compared with CL, indicating HBI as a flooding-tolerant cultivar. Transcriptome analysis identified 1098 shared differentially expressed genes (DEGs) in the leaves of flooded HBI and CL, which were mainly enriched in stress signal perception, oxidative stress regulation, energy metabolism and circadian rhythm. Cultivar-specific DEG analysis revealed that CL mainly activated pathways related to oxidative stress and damage repair pathways, whereas HBI-specific genes were significantly enriched in hormone signal transduction, growth regulation, flavonoid synthesis and photosynthesis. Based on this distinct enrichment pattern in the tolerant cultivar HBI, we propose that it possesses adaptive advantages under flooding stress. Specifically, HBI likely coordinates multiple physiological processes by activating ethylene and other hormone-related genes, thereby regulating hypoxia adaptation, reoxygenation-induced oxidative stress, photosynthetic recovery, and flavonoid-mediated antioxidant defense. This coordinated regulation collectively sustains growth vigor and enhances survival under seasonal inundation. Our findings demonstrate clear transcriptomic divergence underlying flooding tolerance among poplar cultivars, laying a theoretical foundation for the selection of flooding-tolerant varieties and the sustainable development of forestry in flood-prone regions. Furthermore, these results broaden the current knowledge of flooding stress biology in woody plants. Full article

Heart failure (HF) is associated with substantial morbidity and mortality. Metabolic abnormalities are increasingly recognized as integral to HF pathophysiology and may provide incremental value for phenotyping and prediction of outcomes. However, a comprehensive synthesis of metabolic alterations and their prognostic implications remains limited. This scoping review aimed to map metabolic changes in HF, describe analytical methods, and evaluate their diagnostic and prognostic relevance for clinical risk assessment. Methods: We systematically searched PubMed, Scopus, Web of Science, Cochrane Central, and grey literature from January 2010 to December 2024 to identify studies evaluating metabolic profiling in patients with HF. Two independent reviewers screened studies using predefined inclusion criteria and data were extracted using a customized charting form. Discrepancies were resolved by consensus or a third reviewer. We reported and synthesized findings narratively in accordance with scoping review methodology. Results: Seventy-two studies (66 observational and 6 randomized) were included, encompassing HF phenotypes including HF with reduced ejection fraction (HFrEF), HF with mildly reduced ejection fraction (HFmrEF), and HF with preserved ejection fraction (HFpEF). The analytical approaches included mass spectrometry and nuclear magnetic resonance (¹H-NMR) platforms. The main metabolite classes that demonstrated prognostic significance were amino acids, acylcarnitines, and lipids, and gut-derived metabolites, which were associated with mortality, HF hospitalization, or disease progression. Several studies reported incremental prognostic value beyond conventional biomarker; however, most were exploratory, with modest sample sizes, limited external validation, and heterogeneous methodologies. Conclusions: Metabolomic profiling identifies biologically relevant alterations predicted worse clinical outcomes in HF and may complement existing risk assessment strategies. Nevertheless, standardized workflows and large prospective validation studies are required before clinical implementation can be considered. Full article

GWASs have successfully identified numerous genetic variants linked to complex traits, but traditional univariate approaches often fail to capture shared genetic architecture across multiple phenotypes. As the scale of genomic data continues to increase, the demand for more efficient multi-phenotype analysis methods has become particularly critical. In addition, the issue of population structure must also be properly addressed to ensure robust and unbiased results. Multivariate methods for multi-phenotype analysis, such as GAMMA, address this by combining linear mixed models with multivariate distance matrix regression to account for population structure; however, since these methods utilize computationally intensive models, developing efficient implementations is essential for practical analysis. Although GAMMA is a well-designed and effective tool, its original implementation relies on multiple programming environments and requires frequent data exchanges between components. These factors increase computational burden and complicate installation and execution for users unfamiliar with programming, making practical applications, particularly for high-dimensional datasets, challenging. Here, we present GAMMA-RAY, a high-performance C++ implementation that streamlines the computational pipeline, leverages parallel processing, and employs efficient matrix operations to achieve substantial reductions in runtime and memory usage. GAMMA-RAY provides both a user-friendly web-based interface for non-programmers and a standalone version for secure local execution. We further applied GAMMA-RAY to a yeast dataset and identified putative trans-eQTLs, in which several variants overlapped with previously reported cis- and trans-eQTLs. In addition, functional enrichment analysis revealed that the associated trans-eGenes are enriched, a conclusion consistently supported by biological annotation resources and underscoring the biological significance of these results. Full article