Search Results (10,581)

Personalized learning in higher education aims to enhance student motivation, engagement, and academic outcomes. Learner personas as representations of students offer a promising approach to personalizing learning in technology-enhanced environments, particularly in combination with learning analytics (LA). This study explores how LA can be used to identify activity patterns based on data from the E-Learning Activities Recommender System (ELARS). The activity data of STEM students (N = 90) were analyzed using K-Means clustering. The analyses were based on timing, the percentage of task completion, and their combination to identify distinct engagement patterns. Based on these, six clusters (learner personas) were identified: consistent performers, overachievers, last-minute underperformers, low-engagement students, late moderate achievers, and early proactive performers. For each persona, GenAI prompts and personalized interventions based on motivational and instructional frameworks were proposed. These will inform further development of the ELARS system, with the goal of enabling personalization, promoting self-regulated learning, and encouraging students to integrate GenAI tools into their learning. The study shows how the combination of clustering techniques for learner persona development with GenAI prompt engineering and adaptive interventions has the potential to drive the design of personalized learning environments. Full article

Exosomal microRNAs (ex-miRs), encapsulated in extracellular vesicles (EVs), play a vital role in facilitating paracrine communication among granulosa cells (GCs), cumulus cells (CCs), and the oocyte inside follicular fluid (FF). These small non-coding RNAs are crucial for regulating folliculogenesis, oocyte maturation, and early embryonic development via modulating intracellular signaling networks. Dysregulation o has been associated with reproductive disorders such as polycystic ovarian syndrome (PCOS), diminished ovarian reserve (DOR), and inadequate ovarian response (POR), impacting oocyte quality and fertility outcomes. This narrative review consolidates molecular data from current human and animal studies regarding ex-miR expression patterns, functional targets, and pathway involvement within the context of assisted reproductive technologies (ARTs). A literature-based analysis was undertaken, focusing on signaling pathways, pathogenic processes, and clinical implications. Specifically, ex-miRs—such as miR-21, miR-34c, miR-143-3p, miR-155-5p, miR-339-5p, and miR-424-5p—were identified as regulators of critical pathways including phosphoinositide 3-kinase (PI3K)–AKT, ERK1/2, TGF-β/SMAD, and Rb–E2F1. These ex-miRs regulate apoptosis, glycolysis, mitochondrial function, and cell cycle expansion to influence oocyte competence. Pathological patterns in PCOS and POR are associated with altered ex-miR expression that disrupts metabolic and developmental signaling. Research utilizing animal models confirmed that modifications in EV-associated miRNA influence in vitro maturation (IVM) efficiency and blastocyst quality. Ex-miRs serve as intriguing non-invasive biomarkers and potential therapeutic targets for ARTs. Their mechanical involvement in oocyte and follicular physiology positions them for integration into forthcoming precision-based infertility therapies. For its implementation in reproductive medicine, EV profiling requires standardization and further functional validation in clinical environments. Full article

Background: Colorectal cancer (CRC) remains a major cause of cancer-related mortality worldwide, underscoring the need for more efficient and resource-conscious screening strategies. Methods: We screened 51,437 individuals (50–74 y) in South-West Oltenia, Romania, with FIT values of ≥20 µg Hb/g. Of the 2825 FIT-positive individuals, 1550 completed colonoscopy, and we recorded their age, sex, residence, education, comorbidities, medications, and FIT values. After imputing < 8% missing data via multiple imputation, we reduced dimensionality with an autoencoder (ReLU, dropout 0.5, L2, 100 epochs, batch 32) and applied K-Means clustering (k = 5). The following are examples of actionable clusters: Cluster 0 (“High-FIT malignant”): FIT > 200 µg/g, age > 65, diabetes; Cluster 2 (“Low-risk mixed”): FIT 100–199 µg/g, age < 60, no comorbidities; Cluster 3 (“Intermediate-risk older”): FIT 150–200 µg/g, ≥3 comorbidities, rural. Cluster labels were then predicted by a feed-forward neural network (64–32 neurons, dropout 0.6) and validated via 5-fold cross-validation plus a temporal hold-out. Results: Five distinct patient clusters were identified, enabling the development of a composite risk score. Notably, Cluster 0, characterized by elevated FIT levels, exhibited a malignancy rate of 50.91%, while the overall CRC diagnostic rate among colonoscoped patients was approximately 13.87%. This stratification model enhances the diagnostic yield by prioritizing high-risk patients for urgent colonoscopy and sparing low-risk individuals from unnecessary invasive procedures. Conclusions: The AI-driven composite risk score offers a refined framework for CRC risk stratification and optimized resource allocation. Its implementation can lead to earlier detection of advanced lesions, thereby improving patient outcomes. Further external validation on independent cohorts and regions is essential to confirm its broad utility, with potential future integration of additional biomarkers (e.g., genetic or omics-based indicators) to further enhance predictive accuracy. Full article

A complex study was performed of the disturbances in geophysics parameters that were observed during a short-term period of earthquake preparation. On 4 March 2024, an $M6.1$ earthquake (N 42.93, E 76.966) occurred with the epicenter 12.2 km apart from the complex of geophysical monitoring. Preparation of the earthquake we detected in real time, 8 days prior to the main shock, when a characteristic cove-like decrease appeared in the gamma-ray flux measured 100 m below the surface of the ground, which observation indicated an approaching earthquake with high probability. Besides the gamma-ray flux, anomalies connected with the earthquake preparation were studied in the variation of the Earth’s natural pulsed electromagnetic field (ENPEMF) at very low frequencies (VLF) $f=7.5$ kHz and $f=10.0$ kHz and at ultra-low frequency (ULF) in the range of 0.001–20 Hz, as well as in the shift of Doppler frequency (DFS) of the ionospheric signal. A drop detected in DFS agrees well with the decrease in gamma radiation background. A sequence of disturbance appearance was revealed, first in the variations of ENPEMF in the VLF band and of the subsurface gamma-ray flux, both of which reflect the activation dynamic of tectonic processes in the lithosphere, and next in the variation of DFS. Two types of earthquake-connected effects may be responsible for the transmission of the perturbation from the lithosphere into the ionosphere: the ionizing gamma-ray flux and the ULF/VLF emission, as direct radiation from the nearby earthquake source. In the article, we emphasize the role of medium ionization in the propagation of seismogenic effects as a channel for realizing the lithosphere–ionosphere coupling. Full article

While the effects of elevated CO₂ (eCO₂) on crops have been extensively studied, cultivar-specific responses and impacts under higher CO₂ concentrations (>800 μmol/mol) remain unclear. Here, we addressed these two aspects to reveal the effects of eCO₂ (approximately 900 μmol/mol) on the yield and quality of three wheat cultivars, Chinese spring (CS), Chuanmai 44 and Neimai 9. The results indicated the net photosynthetic rate (Pn) and water use efficiency (WUEi) of the three cultivars significantly increased under 900 μmol/mol CO₂ concentration. Elevated CO₂ increased the hundred-grain weight (HGW) of Chuanmai 44 (+32.51%, p < 0.05) and Neimai 9 (+8.47% p < 0.05), but had little effect on HGW of CS. CO₂ elevation significantly increased the N content in the grain of CS (+7.27%, p < 0.05). Elevated CO₂ enhanced amino acid biosynthesis in CS but suppressed it in Chuanmai 44 and Neimai 9. No significant changes in grain mineral concentrations occurred in CS and Chuanmai 44 under eCO₂ conditions. Neimai 9 demonstrated significant decreases in K and Mg, with non-significant reductions in other elements. The effects of eCO₂ on grain yield and quality were closely linked to cultivars. This study will provide insights for understanding effects of CO₂ concentration and cultivar interactions on crop growth and selecting wheat cultivar to cope with future climate change. Full article

The work presents and examines a fiber anchoring system of NSM CFRP strips proposed for strengthening RC beams. The study included 11 beams: 3 unstrengthened beams, 3 beams strengthened with NSM CFRP strip without anchorage, and 5 beams strengthened with NSM CFRP strips with additional anchorage in two variants (the fiber anchor wrapped around the CFRP strip end and fan-folded on the beam surface; the fiber anchor connected with a 20 cm overlap to the strip). All beams were loaded until failure with two concentrated forces (four-point loading test). The measurements were carried out using digital image correlation (DIC). The obtained ultimate load values reached an average of 43.5 kN for unstrengthened beams, while for strengthened beams, they ranged between 56.6 kN and 60.2 kN. The strengthening efficiency was comparable for all beams regardless of the anchorage used and ranged from 29% to 37%. All strengthened beams failed due to strip debonding. The obtained results did not allow confirmation of the effectiveness of the proposed anchoring system. Detailed analysis showed that the lack of anchoring effectiveness was related to the debonding initiating factor, i.e., vertical crack opening displacement, which has not been described in proper detail by the researchers. Full article

Alterations in aggressive-variant prostate cancer-associated tumor suppressor genes (AVPC-TSG: TP53, RB1, PTEN) are related with androgen insensitivity and aggressive disease. However, their prognostic and predictive role in metastatic hormone-sensitive prostate cancer (mHSPC) is unclear. This single-center retrospective study assesses the value of AVPC-TSG alterations in refining prognosis and predicting the response to androgen receptor pathway inhibitors (ARPIs) in mHSPC. We included 158 patients with genomic tumor sequencing undergoing treatment for mHSPC between 2013 and 2023. We compared patients with AVPC-TSGalt tumors (≥1 alteration in TP53, RB1, or PTEN/PI3K/AKT pathway genes) to those with AVPC-TSGwt tumors (i.e., without alterations in AVPC-TSG). Cox analyses were performed for progression-free survival (PFS) and overall survival (OS). AVPC-TSGwt status was associated with improved PFS and OS in both univariate and multivariate (MV) analyses (MV PFS: HR 0.58, 95%CI: 0.38–0.89, p = 0.012; MV OS: HR 0.48, 95%CI: 0.26–0.91, p = 0.025). AVPC-TSGalt mHSPC patients seemed to derive no PFS benefit from ARPI addition (PFS: HR 1.13, 95%CI: 0.58–2.19, p = 0.721), while AVPC-TSGwt mHSPC patients did (PFS: HR 0.51, 95%CI: 0.28–0.93 p = 0.029). Integrating AVPC-TSG status with CHAARTED volume criteria, we identified three distinct subgroups: “good risk” (AVPC-TSGwt low volume), “intermediate risk” (either AVPC-TSGalt low volume or AVPC-TSGwt high volume), and “poor risk” (AVPC-TSGalt high volume) with median PFS of 46.8, 28.2, and 15.7 months, respectively. Only the “intermediate risk” subgroup seemed to derive PFS benefit from ARPI addition (HR 0.36, 95%CI: 0.19–0.70, p = 0.002). AVPC-TSG status assessment refines prognosis and may predict PFS benefits of ARPIs in mHSPC. AVPC-TSGalt mHSPC patients should be considered for clinical trials as they may not benefit from current standard approaches. Full article

The emergence of antimicrobial resistance (AMR) in Clostridium difficile (C. difficile), particularly to last-line antibiotics such as linezolid, represents a critical challenge in clinical settings. This study investigates the genomic epidemiology of linezolid-resistant C. difficile, focusing on the distribution and mutational patterns of the chloramphenicol–florfenicol resistance (cfr) gene and its association with multidrug resistance. We analyzed 514 clinical isolates (354 from NCBI Pathogen Detection, 160 from EnteroBase), revealing distinct prevalence patterns among cfr subtypes: cfr(C) was dominant (156/354 NCBI strains; 101/160 EnteroBase strains), whereas cfr(B) frequently harbored missense mutations (p.R247K, p.V294I, and less commonly p.A334T). The cfr(E) subtype was exclusively identified in ribotype 027 (RT027) strains. Notably, cfr(C) exhibited a strong association with RT017, correlating with a conserved 99 bp genomic deletion. Phylogenetic analysis linked cfr-carriage to predominant sequence types (ST1 in NCBI strains, ST37 in EnteroBase isolates). Furthermore, the co-occurrence of cfr with additional AMR genes conferred resistance to macrolides (erythromycin, azithromycin) and tetracyclines, indicating a convergent evolution toward multidrug resistance. These findings underscore the interplay between cfr mutations, hypervirulent ribotypes, and AMR dissemination, necessitating enhanced surveillance to mitigate the spread of resistant C. difficile lineages. Full article

Background/Objectives: The genus Vitis comprises approximately 70 species with high genetic diversity, among which Vitis vinifera is the most economically significant. Despite numerous studies on the genetic characterizations of V. vinifera, selecting optimal chloroplast DNA barcoding regions for intraspecific differentiation remains unresolved. Most studies have focused on nuclear markers (SSRs, SNPs) or widely used chloroplast loci (e.g., matk, rbcl), which have shown limited resolution at the subspecies level. In this study, the complete chloroplast genomes of 34 V. vinifera accessions from different varieties and hybrids (vinifera, sylvestris, caucasica, and labrusca) were analyzed to identify the key genomic regions for DNA barcoding. Methods: Using bioinformatics tools, we assessed the genome structure, nucleotide variability, microsatellites, codon usage bias, and phylogenetic relationships among the investigated varieties. Results: The chloroplast genomes displayed a quadripartite structure, with lengths ranging from 160,906 to 160,929 bp and a guanine–cytosine (GC) content of ~37.4%. Phylogenetic analysis revealed an unusual position for VV-5 vini and VVVL-3 lab, suggesting potential taxonomic misclassification or hybridization effects. A single locus showed low discrimination power, but the concatenation of five loci (ccsA-trnN-GUU, rpl16, rpl2-rps19, rpoC2, and trnM-CAU) exhibited significantly improved resolution (44.11% K2P), surpassing traditional markers. Conclusions: This study addresses the gap in the literature regarding the use of concatenated chloroplast loci for subspecies research; the results validate these markers across a broader range of Vitis accessions and integrate nuclear and mitochondrial data to achieve a more comprehensive understanding of the evolutionary history and genetic diversity of V. vinifera. Full article

Bone-associated pathologies are major contributors to chronic pathology statistics. Current gold standard treatments present limitations such as the ability to act as scaffolds whilst effectively delivering medications to promote cellular proliferation. Recent advancements in biomaterials have suggested whey protein isolate (WPI) hydrogel as a potential candidate to act as a scaffold with the capacity for drug delivery for bone regeneration. In this study, we investigate whey protein isolate hydrogels enhanced with the phytocannabinoid cannabidiol (CBD). The use of CBD in WPI hydrogels for bone regeneration is original. The results suggest that CBD was successfully incorporated into the hydrogels bound potentially through hydrophobic interactions formed between hydrophobic patches of the protein and the hydrophobic cannabinoid. The incorporation of CBD into the WPI hydrogels improved the mechanical strength of the hydrogels. The Young’s modulus was improved from 2700 kPa ± 117 kPa to 7100 kPa ± 97 kPa when compared to the WPI control, without plant-derived cannabinoids, to the WPI with the maximum CBD concentration. Furthermore, statistically significant differences for both Young’s modulus and compressive strength were observable between the WPI control and CBD hydrogel variables. The release of CBD from the WPI hydrogels was confirmed with the results suggesting a maximum release of 20 μM over the 5-day period. Furthermore, the hydrogels supported the proliferation and synthesis of collagen and calcium, as well as the alkaline phosphatase activity of MC3T3-E1 pre-osteoblasts, which demonstrates the potential of WPI/CBD hydrogels as a biomaterial for osseous tissue regeneration. Full article

The effects of temperature, time, and solvent concentration on the yield of bioactive compounds (BCs) with cytotoxic activity against three cell lines (Hep2c, RD, and L2OB) from Erica carnea L., as well as their influence on kinetic and thermodynamic parameters (enthalpy, entropy, and free energy), were investigated. The extract obtained at 30% ethanol, 50 °C, and 80 min showed the highest cytotoxic activity with IC₅₀ values of 14.29, 13.93, and 22.23 µg/mL, respectively. The kinetics of BC extraction with cytotoxic activity was better described by the unsteady-state diffusion model compared to the Ponomarev model. The activation energy obtained was in the range of Ea = (4.92–26.57) kJ/mol. The thermodynamic parameters under transition theory at 50 °C were ∆S* = (−220.22)–(−285.15) J/Kmol, ∆H* = (2.24–23.88) kJ/mol, and ∆G* = (94.34–96.30) kJ/mol, indicating that the extraction of BCs with cytotoxic activity against the three cell lines is an irreversible and endothermic process. In addition to cytotoxic activity, the extracts demonstrated strong antioxidant activity (e.g., DPPH IC₅₀ = 16.55 µg/mL) and antibacterial activity against multiple bacterial strains. Five antioxidant assays were applied, along with tests against eight bacterial strains for antibacterial activity. These findings suggest that Erica carnea L. is a promising natural source of multifunctional bioactive compounds with therapeutic potential. Full article

Background:Early defibrillation improves outcomes in cardiac arrest, but the optimal defibrillation strategy and energy requirements remain debated. This study investigated whether arterial blood gas (ABG) parameters could predict optimal defibrillation energy requirements for achieving the highest first-shock success rates in an animal model. Our study focused on clinical scenarios where ABG measurements are readily available, such as ventricular tachycardia and ventricular fibrillation storms requiring multiple shock deliveries. Materials and Methods: In the experimental setting, ventricular fibrillation was induced by 50 Hz direct current (DC), and the defibrillation threshold (DFT) was determined using a stepwise defibrillation protocol. ABG parameters were measured before each defibrillation attempt, recording partial arterial pressure of carbon dioxide (PaCO₂) and oxygen (PaO₂), pH, hematocrit (Hct), sodium (Na⁺), potassium (K⁺), and bicarbonate (HCO₃⁻) levels. The relationships between ABG parameters and the DFT were analyzed for 15 subjects using classical data analysis techniques and machine learning (ML) algorithms. Multiple ML models were trained and tested to predict the higher energy needed for successful defibrillation based on the ABG parameters. Results: Statistically significant differences were found in Hct and Na⁺ levels between the two DFT categories, above 130 Joules (J) and below 40 J (p < 0.01). The DFT negatively correlated with PaO₂ and positively correlated with Hct and Na⁺. However, other ABG parameters did not show significant correlations with DFT. Using ML, we predicted cases requiring higher defibrillation E. Our best-performing model, the Extra Trees Classifier, achieved 83% overall accuracy, with 100% and 67% precision rates for higher and lower DFT categories, respectively. We validated the model using bootstrap resampling and 10-fold cross-validation, confirming consistent performance. We identified Hct, PaCO₂, and PaO₂ as significant contributors to model prediction based on the feature importance value. Conclusions: Modern data analysis techniques applied to ABG parameters may guide personalized defibrillation energy selection, particularly in controlled clinical environments such as catheterization laboratories and intensive care units where ABG measurements are readily available. Full article

Background: Several targeted drugs have been recently approved for the treatment of PIK3CA-mutated hormone receptor-positive (HR+)/HER2-negative (HER2−) breast cancer (BC). This study aimed at a comprehensive evaluation of the spectrum of PIK3CA alterations in Russian BC patients. Methods: The tumor material from 1872 patients with ER+/HER2− BC was tested by a combination of PCR-based methods. Results: Mutations were detected in 693/1872 (37%) cases, including 46 BC with two PIK3CA lesions. The three most common substitutions (E542K, E545K, and H1047R) were identified in 542/693 (78%) PIK3CA-mutated cases, while as many as 5.5–12% of identified mutations were not potentially detectable by common commercial kits. The study included patients of Slavic and non-Slavic ethnicities residing in regions with different climate conditions, however, these factors did not influence the distribution of PIK3CA mutations. The presence of PIK3CA variants was associated with older patient age at diagnosis (p = 0.0002), smaller tumor size (p = 0.005), lower grade (p = 0.005), Ki67 <20% (p = 0.0001) and progesterone receptor-positive status (p = 0.002) at the initial disease diagnosis, and fewer distant metastases at the time of the detection of BC spread (p = 0.0001). In a subgroup of 413 BC patients who received adjuvant tamoxifen or aromatase inhibitors, PIK3CA mutations were not associated with resistance to either type of treatment. Conclusions: The results of this study highlight the need to extend the PIK3CA testing beyond the hotspot regions of this gene. Although PIK3CA alterations contribute to the pathogenesis of HR+/HER2− BC and represent a target for several novel drugs, they are not intrinsically associated with unfavorable clinical characteristics of this subtype of cancer disease. Full article

: NiMn₂O₄ thermosensitive ceramics using Bi₂O₃ as a low-temperature ablating aid were prepared by laser melting deposition. Analyzing the structural, morphological, and electrical properties of the ceramics revealed important roles of Bi₂O₃. The room-temperature resistance decreased gradually with the increasing of the Bi₂O₃ content, the thermal constant of the ceramics varied from 2870.1 to 3853.2 K, and the activation energy varied from 0.2473 to 0.3320 eV. Furthermore, the alleviation of the aging issue was attributed to the grain growth and the densification of the ceramics due to the addition of Bi₂O₃ and the corresponding cationic redistribution. As a result, an optimized resistance drifting (∆R/R = 5.72%) of the ceramic was obtained with the addition of Bi₂O₃. Full article

Over the past two decades, metabolic syndrome (MetS) and infections caused by multidrug-resistant (MDR) pathogens have emerged as converging global health challenges. Traditionally investigated as separate entities, accumulating evidence increasingly supports a bidirectional relationship between them, mediated by chronic inflammation, immune dysregulation, gut microbiota alterations, and antibiotic-driven expansion of the resistome. This narrative review examines the complex immunometabolic interplay linking MetS and MDR infections, focusing on molecular mechanisms, clinical implications, and prospective research directions. A systematic literature search was conducted using major databases, including PubMed and Scopus, targeting studies from the last 15 years that explore the interface between metabolic dysfunction and antimicrobial resistance. Particular attention is given to key immunometabolic pathways such as the IRS–PI3K–AKT–mTOR axis; the contribution of visceral adiposity and Toll-like receptor (TLR)-mediated inflammation; and the role of gut dysbiosis in augmenting both susceptibility to infections and metabolic derangements. Evidence is presented supporting the hypothesis that MetS increases host vulnerability to MDR pathogens, while chronic MDR infections may reciprocally induce systemic metabolic reprogramming. Viral infections with established metabolic sequelae (e.g., HIV, hepatitis C virus [HCV], and cytomegalovirus [CMV]) are also considered to broaden the conceptual framework. Although current data remain largely associative and fragmented, the emerging MetS–MDR syndemic model poses substantial challenges for translational research, antimicrobial stewardship, and personalized therapeutic strategies. Recognizing this reciprocal relationship is pivotal for refining infection risk stratification, optimizing treatment, and informing public health policies. Further investigations are warranted to elucidate the magnitude and directionality of this association and to identify predictive immunometabolic biomarkers that may guide targeted interventions in high-risk populations. Full article