To evaluate the efficacy and safety of rivaroxaban and low molecular weight heparin (LMWH) for the prevention of postoperative venous thrombosis (VTE) following primary unilateral total hip arthroplasty (THA) and total knee arthroplasty (TKA). A total of 11,686 patients who received rivaroxaban and LMWH (6,110 cases of THA and 5,576 cases of TKA) between January 2014 and November 2017 in 26 large teaching hospitals were enrolled. The patients were divided into two groups according to the postoperative use of anticoagulant drugs, including 4,591 cases in the rivaroxaban group (2,288 cases of THA and 2,303 cases of TKA) and 7,095 cases in the LMWH group (3,822 cases of THA and 3,273 cases of TKA). The incidence of deep vein thrombosis (DVT) in the lower extremities, and pulmonary embolism (PE), were analyzed as indicators of efficacy. The incidences of postoperative bleeding events, total blood loss (TBL), and transfusion rate, were considered as safety indicators. The overall incidence of DVT was 0.40% (47/11,686) in patients undergoing primary THA/TKA. The incidence of DVT in the rivaroxaban group was 0.74% (34/4591); this was significantly higher than that in the LMWH group (0.18%; 13/7095) (OR 4.07, 95% CI 2.14-7.71;p < 0.001). In the THA subgroup, the incidence of DVT in the rivaroxaban group was 0.52% (12/2288 cases); this was significantly higher than that in the LMWH group 0.10% (0.10%; 4/3822) (p = 0.002). In the TKA subgroup, the incidence of DVT was 0.96% (22/2303 cases) in the rivaroxaban group and 0.27% (9/3273 cases) in the LMWH group (p < 0.001). Only one patient treated with LMWH after TKA was diagnosed with symptomatic PE in this study. There was no significance difference in terms of safety between rivaroxaban and LMWH (p > 0.05) in terms of the incidence of bleeding events and TBL. However, in the TKA subgroup, TBL was significantly higher in the rivaroxaban group than in the LMWH group (915 ± 514 ml vs. 872 ± 487 ml, p = 0.030). With regards to transfusion rate, patients in the rivaroxaban group had a significantly higher need for blood transfusion than those in the LMWH group (OR 3.30,95% CI 2.88-3.78;p < 0.001). Subgroup analysis revealed that the transfusion rates in the THA and TKA sub-groups were both higher in the rivaroxaban group (14.8%, 14.2%) than those in the LMWH group (6.5%, 3.0%) (p < 0.001). For patients following primary unilateral THA/TKA, LMWH is superior to rivaroxaban in terms of the prevention of symptomatic in-hospital DVT' and the control of TBL and transfusion rates. However, the efficacy of these drugs for controlling bleeding events was similar when compared between the two groups.
Sex hormones and hormonal contraceptives influence the regulation of sleep-wake behavior. However, there are very few large-scale studies to date that have comprehensively evaluated how hormonal contraceptives influence women's sleep health. The purpose of this systematic review was to synthesize the existing research on hormonal contraceptive use and sleep in women ages 18-50. The systematic review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement checklist. Nineteen studies were included in this review. Data were extracted and evaluated for risk of bias and heterogeneity. The included studies demonstrated high heterogeneity in terms of objective and/or subjective sleep-related measures and non-sleep primary study outcomes and demonstrated significant risks of bias, underscoring the need for methodological consistency in assessing women's sleep health. Several clinical considerations may be gleaned from this existing research in terms of the behavioral assessment and treatment of sleep difficulties in women using hormonal contraceptives. Additional investigation is needed to identify standardized research and clinical methodology guidelines for assessing and treating women's sleep health.
The aim of this study was to compare the healing after 24 months between initial endodontic treatment and retreatment using fractal analysis and the periapical index (PAI) scores. Eighty-three mandibular teeth with 5 mm lesions from 76 patients were selected, and then the teeth were divided into two groups: the primary endodontic treatment group and the retreatment group. Panoramic X-rays evaluated before and after 2 years of treatment were determined in both treatment groups. Differences between groups were evaluated by fractal analysis. Post-treatment fractal dimensions were not statistically significant in either group compared to pre-treatment values (p > 0.05). In the primary endodontic treatment group, the mean pre-treatment fractal dimension value was 1.48 ± 0.11 (mean ± SD), while it was determined as 1.52 ± 0.12(mean ± SD) at 24 months of follow-up. In the retreatment group, the mean pre-treatment fractal dimension value was 1.45 ± 0.16 (mean ± SD), while it was determined as 1.50 ± 0.15(mean ± SD) at 24 months of follow-up. There was no statistically significant difference between the groups in terms of fractal dimension differences. Statistically significant decreases were observed in PAI values within the group (p < 0.001), and no significant difference was observed between the groups in terms of time-dependent decreases (p > 0.05). In the primary endodontic treatment group, the PAI score was 4.83 ± 0.38 (mean ± SD) before treatment, while it was determined as 1.71 ± 1.33(mean ± SD) at 24 months of follow-up. In the retreatment group, the pre-treatment significance level was 4.76 ± 0.43(mean ± SD), while at 24 months of follow-up it was determined to be 1.80 ± 1.21(mean ± SD). Fractal analysis may provide complementary quantitative information regarding periapical bone changes; however, FD measurements obtained from panoramic radiographs should be interpreted cautiously because of the inherent limitations of this imaging modality. Integrating fractal analysis with traditional scoring systems allows for a comprehensive assessment of long-term bone formation in both primary endodontic treatment and retreatment. Consequently, both primary endodontic treatment and retreatment showed similar patterns in periapical bone healing over 24 months, and no significant difference was found between the two groups in fractal dimension values or PAI scores. The absence of statistically significant FD changes should not be interpreted as definitive evidence of absent trabecular remodeling.
Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment with significant improvements in survival rates. With the increase in ICI use in the clinical setting, several case reports and series have described neurological adverse events associated with it. We conducted this systematic review and meta-analysis to estimate the incidence of neurological adverse events among ICI clinical trials. We searched PubMed, Embase, Scopus, and the Cochrane Central Register of Controlled Trials (CENTRAL) on November 25, 2025, using ICI and clinical trial as keywords along with their related MeSH terms. The inclusion criteria involved clinical trials investigating the efficacy or safety of any ICI as the only systemic therapy among never treated patients with cancer. To eliminate the impact of other systemic therapies, trials that used ICIs as an adjuvant to another systemic treatment or included patients previously treated with any systemic therapies were excluded. The incidence and its 95% confidence interval (95%CI) were used as the effect measures in the analysis. Subgroup analyses were conducted based on the type of cancer and number of ICIs used in the trial. We included a total of 8,826 patients with cancer from 31 clinical trials. The pooled incidence of neurological adverse events was 1.78 × 10-3% (95%CI 1.06 × 10-3%-2.78 × 10-3%). There was no difference (p = 0.481) in the incidence of neurological side effects between trials that used one ICI (1.83 × 10-3%; 95%CI 0.81 × 10-3%-3.22 × 10-3%) compared to those that used two ICIs (0.90 × 10-3%; 95%CI 0.01 × 10-3%-2.64 × 10-3%). There was also no significant difference (p > 0.622) in the incidence among patients with hepatocellular carcinoma (HCC) (1.20 × 10-3%; 95%CI 0.01 × 10-3%-3.67 × 10-3%), non-small cell lung carcinoma (NSCLC) (1.83 × 10-3%; 95%CI 0.01 × 10-3%-6.0 × 10-3%), and melanoma (1.16 × 10-3%; 95%CI 0.22 × 10-3%-2.71 × 10-3%). The most common neurological adverse events were peripheral neuropathy (1.34 × 10-3%; 95%CI 0.61 × 10-3%-2.3 × 10-3%), myositis (0.78 × 10-3%; 95%CI 0.29 × 10-3%-1.49 × 10-3%), aseptic meningitis (0.71 × 10-3%; 95%CI 0.25 × 10-3%-1.40 × 10-3%), autoimmune demyelinating polyneuropathy (0.66 × 10-3%; 95%CI 0.21 × 10-3%-1.32 × 10-3%), epilepsy (0.66 × 10-3%; 95%CI 0.21 × 10-3%-1.32 × 10-3%), and myasthenia gravis (0.66 × 10-3%; 95%CI 0.21 × 10-3%-1.32 × 10-3%). Taken all together, the incidence of ICI-related neurological adverse events among patients with cancer is low and estimated at 1 in 5000 patients. Individual data analysis of ICI clinical trials is needed to examine the factors associated with ICI-related neurological adverse events.
L-asparaginase is an amidohydrolase enzyme that catalyses the hydrolysis of L-asparagine into L-aspartic acid and ammonia. This enzyme has significant biotechnological applications, functioning as an antineoplastic agent in the pharmaceutical industry and as a tool for reducing acrylamide formation in the food industry. This study aimed to identify a filamentous fungus strain capable of synthesizing a new L-asparaginase and to perform its biochemical characterisation. Among the fungal isolates screened using plate assays and submerged fermentation, Cunninghamella echinulata strain PA3S12MM was identified as a promising L-asparaginase producer. The highest enzymatic induction was achieved using 5% (w/v) glucose as the carbon source and 0.4% (w/v) chicken feather as an agro-industrial nitrogen source, under incubation for 120 h. The enzyme exhibited an apparent Km app of 0.011 mmol L⁻¹ and a Vmax app of 126.5 mmol L⁻¹ min⁻¹ for the hydrolysis of L-asparagine. Partial purification revealed that the enzyme displayed optimal activity at pH 7.0 and a temperature of 85 °C. In terms of substrate specificity, the enzyme demonstrated 100% relative activity toward L-asparagine and 32.9% toward L-glutamine. Enzymatic activity was enhanced by β-mercaptoethanol but inhibited by Mn²⁺, L-cysteine, and dithiothreitol (DTT). These findings suggest that C. echinulata PA3S12MM is a promising candidate for large-scale biotechnological production of a new fungal L-asparaginase, with biochemical indicators of potential for applications in both pharmaceutical and food industries.
Shared decision making (SDM) is an approach in which healthcare providers and patients collaboratively consider the best available evidence when making treatment decisions; patients are also supported in evaluating available options and forming informed preferences. However, evidence regarding treatment decision making contexts involving SDM for patients with liver disease remains limited. Therefore, this scoping review analyzes the contextual environments in which SDM is implemented during the treatment of patients with liver disease and examines the characteristics of patient participation in the SDM process. This study focused on treatment decision making contexts (context) involving SDM (concept) among patients with liver disease (population). Following the Arksey and O'Malley scoping review method, structured searches of articles published until March 2025 were conducted in four electronic databases: PubMed, Cumulative Index to Nursing and Allied Health Literature, Embase, and Web of Science. The search terms used were "shared decision making" and "liver disease." Eight studies were ultimately included in the review. SDM was applied in treatment contexts, including medication initiation, surgical decision making, and the selection of therapeutic approaches such as hepatic resection and radiofrequency ablation. Five (62.5%) out of the eight studies included surgery as an option, and four (50.0%) focused on patients with liver cancer. When the patients with liver disease participated in the SDM process, they were presented with treatment options, provided information about these options, and asked to express their preferences. However, only one study evaluated decision making outcomes. Cancer-related and surgical decision making contexts were the most frequent targets for SDM in this review. However, patient decision aids (PDAs) are currently unavailable for any liver disease. Additionally, only one study included a process for re-evaluating prior decisions. Future research and clinical practice should incorporate mechanisms for re-evaluating prior decisions and support the development of PDAs for liver disease.
The aim of this study was to evaluate the biomechanical behavior of subperiosteal implant systems manufactured from titanium and yttria-stabilized tetragonal zirconia polycrystal (Y-TZP) materials under different implant thicknesses and screw diameters using three-dimensional finite element analysis (FEA). Eight FEA models were generated from maxillary geometry obtained using computed tomography (CT). Two implant materials (Titanium and Y-TZP), two implant thicknesses (1.0 mm and 1.5 mm), and two screw diameters (1.5 mm and 2.0 mm) were evaluated. Three loading conditions were simulated: bilateral vertical loading of 150 N on premolars and first molar, unilateral oblique loading of 100 N at 30°, and bilateral vertical loading of 150 N on the incisors. Total displacement values, maximum and minimum principal stresses in the bone; Von Mises stresses in the bone, subperiosteal implant, abutment, and metal framework were analyzed. Increasing implant thickness reduced stress levels in the bone while increasing stresses within the subperiosteal implant and metal framework. Larger screw diameters decreased stress in the bone and implant but increased stress concentration in the metallic substructure. The higher elastic modulus of Y-TZP reduced stress transmission to the bone; however, higher stresses were observed within the implant body and framework. Implant thickness, screw diameter, and material stiffness influenced the biomechanical behavior of subperiosteal implants. Both materials produced bone stress values below thresholds associated with bone resorption. Y-TZP demonstrated favorable stress distribution in terms of reduced bone stress due to its material properties. In vitro, in vivo, and clinical studies are required to validate its long-term biomechanical performance and clinical applicability in subperiosteal implant systems.
Do-not-attempt-resuscitation (DNAR) orders are commonly issued for patients of advanced age in the setting of severe illness with an anticipated risk of mortality. However, DNAR orders are also observed among extremely elderly patients who are not critically ill at admission. The characteristics and outcomes of such patients remain poorly understood. This study aimed to characterize these patients and to examine the association between DNAR status and discharge outcomes. We retrospectively analyzed non-critically ill (National Early Warning Score [NEWS] of 4 or less) hospitalized patients aged 85 years or older admitted to a university hospital in Japan between 2022 and 2024 using electronic medical record data. Patients with and without DNAR orders were compared in terms of age, sex, activities of daily living (ADL), disease severity (NEWS), primary diagnoses, comorbidities, laboratory data, and discharge outcomes using univariable analyses. A Fine‒Gray competing-risk model examined the association between DNAR orders and transfer to post-acute care facilities, with discharge to home and death as competing events. Among the 1,230 eligible patients, 72 (5.9%) had DNAR orders. Patients with DNAR orders were older, had lower ADL, and had higher NEWS at admission. Primary diagnoses and comorbidities showed no consistent pattern between the two groups. Laboratory findings at admission showed lower hemoglobin and albumin levels and higher C-reactive protein levels in the DNAR group. Patients with DNAR orders were less likely to be discharged home, more likely to be transferred to post-acute care facilities or die in hospital, and had longer hospital stays. DNAR orders were associated with a higher probability of transfer to post-acute facilities (subdistribution hazard ratio 2.11; 95% confidence interval 1.21-3.69). Among non-critically ill extremely elderly hospitalized patients, those with DNAR orders were older, had lower ADL, and had higher disease severity. The presence of DNAR orders was associated with unfavorable discharge outcomes independent of age, ADL, and disease severity.
Osteoarthritis (OA) is a degenerative joint disease closely linked to iron dysregulation. While the role of iron in OA is recognized, the precise mechanism of cell death remains unclear. This study aimed to elucidate how chronic low-dose iron exposure influences chondrocyte survival, iron metabolism, and ferroptosis susceptibility. The 32-day exposure effects of low-dose (20 µM) ferric ammonium citrate (FAC) treatment on the immortalized human chondrocyte cell line (C-20/A4) in terms of survival and susceptibility to ferroptosis were investigated. Cell viability, morphology, and expression of key iron regulatory genes (IRGs) and ferroptosis-related stress genes were assessed. At day-32 of FAC treatment, chondrocyte proliferation and glutathione peroxidase 4 (GPX4) expression increased relative to controls (p < 0.0001). Inhibition of GPX4 with RSL3 in FAC-treated cells resulted in significantly increased cell death (p < 0.001), indicating a possible protective role of GPX4. Iron chelation with deferoxamine conferred protection against ferroptosis. Dynamic changes in IRGs and cell cycle regulators, consistent with an adaptive strategy to resist iron overload and support survival, were observed. In-silico analysis of OA cartilage transcriptomic data identified 170 differentially expressed genes. Functional enrichment showed upregulation of ubiquitin-dependent catabolic processes and downregulation of mitotic pathways, supporting altered stress responses and cell cycle disruptions in iron-exposed chondrocytes. Chronic low-dose iron exposure induced an adaptive upregulation of GPX4, enhancing chondrocyte resistance to cell death by ferroptosis by maintaining lipid peroxide reduction. Therapeutic modulation of GPX4 and iron homeostasis may offer novel strategies for OA management where cartilage iron imbalance is implicated.
Anterior disc displacement with reduction (ADDwR) is a common temporomandibular joint disorder in adolescents. Conventional anterior repositioning splints (ARS) often lack anatomical adaptation, which may limit their therapeutic precision and patient comfort. This study aimed to compare the efficacy of a digitally designed anatomical repositioning splint (D-ARS) with that of a conventional ARS in adolescent ADDwR patients. In this randomized controlled trial, 82 adolescents (aged 12-16 years) with ADDwR were randomly allocated to receive either a D-ARS (n = 41) or an ARS (n = 41). At the 6‑month follow‑up, clinical outcomes were evaluated through three modalities: disc recapture was assessed by magnetic resonance imaging (MRI), condylar volume changes were measured using cone‑beam computed tomography (CBCT), and patient‑reported wearing comfort was quantified with the Oral Impacts on Daily Performance (OIDP) questionnaire. Statistical analyses included chi-square tests, t-tests, and non-parametric tests as appropriate. The D-ARS group achieved a significantly higher disc recapture rate than the ARS group (94.44% vs. 79.63%, p = 0.022). Both groups showed significant increases in condylar volume [D-ARS: +202.17 mm³ (95% CI: 177.72-226.63), ARS: +208.9 mm³ (95% CI: 178.8-241.25), both p < 0.001], with no intergroup difference (p = 0.5615). Patient-reported comfort was superior in the D-ARS group, with lower OIDP scores (14.43% vs. 35.63%, p < 0.001). At the 6-month follow-up, the D-ARS group exhibited significantly better disc recapture success and patient-reported wearing comfort than the ARS group, while no significant difference was observed between the two groups in terms of condylar growth promotion. Chinese Clinical Trial Registry (ChiCTR2400080947, registered on February 19, 2024). Available from: http://www.chictr.org.cn/.
To compare and analyze the efficacy and safety of an overall strategy of immunotherapy combined with chemoradiotherapy in patients with limited-stage small cell lung cancer (LS-SCLC)-including induction immunotherapy plus chemotherapy followed by radiotherapy, with or without consolidation and second-line immunotherapy (ICT+RT)-versus conventional chemoradiotherapy alone (CRT), thereby providing evidence-based support for optimizing the clinical use of immunotherapy in LS-SCLC. A total of 375 patients with LS-SCLC treated between June 2018 and June 2024 were retrospectively included, including 37 patients in the ICT+RT group and 338 in the CRT group. After balancing baseline characteristics such as age, sex, and ECOG performance status using 1:2 propensity score matching (PSM), progression-free survival (PFS) and overall survival (OS) were used as the primary endpoints to compare the efficacy and safety of the two treatment strategies. Notably, substantial treatment heterogeneity existed within the ICT+RT group, including variable induction immunochemotherapy for 2-6 cycles, consolidation immunotherapy after radiotherapy in 32.4% of patients, and second-line immunotherapy after disease progression in 54.1% of patients. After PSM, 35 patients in the ICT+RT group and 70 in the CRT group were successfully matched, and baseline characteristics were well balanced between the two groups (all SMDs < 0.1). No significant difference in median PFS was observed between the ICT+RT and CRT groups (13.6 vs. 10.8 months; P = 0.430). However, given the small sample size of the ICT+RT group, statistical power was limited, and a potential PFS benefit could not be excluded. OS was significantly prolonged in the ICT+RT group (median OS not reached vs. 24.3 months; P = 0.009), and the 3-year OS rate was significantly higher than that in the CRT group (56.6%vs. 33.2%). Multivariable analysis showed that the overall strategy of immunotherapy combined with chemoradiotherapy was an independent protective factor for OS (HR = 0.38, 95% CI 0.18-0.81; P = 0.012). In terms of safety, the incidences of grade ≥3 anemia (8.11%vs. 1.18%) and thrombocytopenia (13.51%vs. 2.96%) were significantly higher in the ICT+RT group than in the CRT group (both P < 0.05), whereas the incidences of other adverse events were comparable. For patients with LS-SCLC, an overall strategy of immunotherapy combined with chemoradiotherapy (including induction ± consolidation ± second-line immunotherapy) may significantly improve OS; however, this benefit reflects the cumulative effect of multistage immunotherapy exposure and cannot be attributed solely to induction immunochemotherapy followed by radiotherapy. This strategy did not improve PFS and was associated with an increased risk of hematologic toxicity, indicating that closer blood count monitoring is warranted in clinical practice. Given the marked sample size imbalance in the ICT+RT group (n = 37) and the substantial intragroup treatment heterogeneity, these findings require validation in large-scale prospective studies.
Coptidis Rhizoma (CR) is a typical cold-attribute herb with potential anti-anxiety properties. Bile is of cold nature and can also interfere with the central nervous system. Bile-processed CR (BCR) exhibits synergistically enhanced anti-anxiety performance. However, the underlying mechanism and material basis for this synergism are not clear. To decipher the enhanced anti-anxiety mechanism and material basis of BCR from the perspective of cross-organ regulation. A rat model of anxiety with sthenic heat syndrome was established to systematically evaluate the enhanced anti-anxiety efficacy of BCR in terms of anxiety behaviour, liver metabolism, and histopathology. Subsequently, the gut microbiome sequencing and untargeted metabolomics of the brain, liver, and serum were performed to explore the mechanism of BCR and CR in regulating the gut-liver-brain axis. In vivo and in vitro molecular biology experiments were performed to further clarify the mechanisms underlying the differential efficacy of BCR and CR. Finally, supramolecular self-assembly simulation and tissue distribution in target organs were carried out to predict the material basis for the enhanced efficacy of BCR. BCR performed better than CR in improving the anxiety behaviour and liver metabolism and in alleviating cerebral injury in the rat model of anxiety. The results of gut microbiome and metabolomic analyses indicated that BCR was superior to CR in reshaping the gut microbiota composition and correcting the metabolic disorders in the brain, liver, and serum. Mechanistically, multiomic analysis revealed that BCR and CR (especially BCR) could block the TLR4/NF-κB pathway in the colon, attenuate hepatic inflammation, improve the integrity of the intestinal mucosa and blood-brain barrier, and inhibit the NLRP3/Caspase-1/IL-1β pathway in the brain, thereby blocking the transmission of inflammation along the gut-liver-brain axis and exerting anti-anxiety effects. BCR and CR (particularly BCR) could suppress the overactivation of ammonia-induced MAPK/NF-κB/iNOS pathway and overexpression of glutamine synthetase in the brain, consequently maintaining the normal morphology and glutamate uptake function (GLAST and GLT-1 activities) of astrocytes, alleviating neuronal apoptosis caused by glutamate excitotoxicity (GluN2B), and ultimately blocking the transmission of neurotoxicity along the gut-liver-brain axis to relieve anxiety. The alkaloid-bile acid supramolecules assembled during the decoction of BCR enabled more alkaloids and bile acids to be distributed in the brain and liver, providing material support for the enhanced effect of BCR. BCR was superior to CR in blocking the transmission of inflammation and neurotoxic substances along the gut-liver-brain axis and, hence, exerted stronger efficacy in alleviating neuroinflammation and improving neuronal survival in the rat model of anxiety. The alkaloid-bile acid supramolecules may provide the material foundation. This study fully considers the characteristic of traditional Chinese medicine being able to exert therapeutic effects through multiple pathways, providing novel avenues for research on the processing mechanism.
Large language models (LLMs) have demonstrated strong performance in answering knowledge-based questions in healthcare education. Specialty examinations offer a standardized and objective framework to assess these capabilities. However, to date, no study has evaluated LLM performance on the Turkish Pharmacy Specialty Examination (EUS), a nationally standardized exam applied for the purpose of admitting candidates to pharmacy specialization programs. Therefore, this study aimed to comparatively evaluate LLM performance on EUS questions in terms of accuracy, self-reported confidence, and readability. This study conducted a comparative evaluation of three LLMs-ChatGPT-5.1, DeepSeek-R1, and Gemini 2.5 Flash-using publicly available 84 multiple-choice questions from the EUS between 2017 and 2025. Each question was submitted to each model in a separate, newly initiated session using a standardized prompt. Model performance was assessed based on answer accuracy, self-reported confidence (1-5 scale), and readability of generated responses, using the Flesch reading ease (FRE), gunning fog index (GFI), and simple measure of Gobbledygook (SMOG) indices. All statistical analyses were performed using non-parametric repeated-measures methods, including Cochran's Q test for paired categorical comparisons and the Friedman test with Durbin-Conover post-hoc analyses for readability scores, with two-tailed significance set at p < 0.05. Overall, the evaluated LLMs exhibited high performance. Gemini 2.5 Flash achieved the highest overall accuracy rate (92.9%), followed by ChatGPT-5.1 (90.5%) and DeepSeek-R1 (89.3%), with no statistically significant difference among the models (p = 0.584). Self-reported confidence was predominantly maximal (5/5), with ChatGPT-5.1, DeepSeek-R1, and Gemini 2.5 Flash assigning maximum confidence to 87.5, 55.6, and 66.7% of incorrect responses, respectively. Significant differences in readability were observed among the evaluated LLMs. ChatGPT-5.1 generated texts with lower GFI and SMOG scores compared with DeepSeek-R1 and Gemini 2.5 Flash (p < 0.05), indicating lower linguistic complexity. No statistically significant differences were identified among models for FRE. LLMs demonstrated high and comparable accuracy when answering domain-specific pharmacy examination questions; however, occasional overconfidence in incorrect responses highlights the need for careful oversight. Differences in linguistic complexity underscore the importance of selecting models optimized for readability in educational settings. Overall, these findings suggest that LLMs may have potential as supplementary tools in pharmacy education within examination-based contexts, provided that expert guidance and critical appraisal are maintained to ensure reliability and clarity.
This study aims to develop biodegradable chitosan-based films containing Chlorella vulgaris biomass and tannic acid, and to further enhance the optimized matrix through the incorporation of juniper seed (Juniperus excelsa) extract (EX). The effects of EX incorporation were evaluated relative to both the baseline chitosan film and the optimized extract-free matrix film in terms of functional, antioxidant, antibacterial, thermal, and structural properties. Distinct from conventional chitosan-based films, the present work applies a mixture-design optimization strategy to a chemically complex algae-chitosan system, enabling systematic evaluation of multicomponent interactions rather than one-factor-at-a-time modifications. The film formulation was optimized using a D-optimal mixture design, with algae (ALG) (15-45%), chitosan (CH) (30-55%), glycerol (GLY) (20-45%), and tannic acid (TA) (0-15%) as independent variables and tensile strength (TS), elongation-at-break (EAB), elastic modulus (EM) and water vapor permeability (WVP) as the response parameters. The validated film (V) containing 29.7% ALG, 43.3% CH, 25% GLY, and 2% TA, showed TS of 5.72 ± 0.36 MPa, EAB of 20.07 ± 1.58%, EM of 25.96 ± 2.51 MPa, and WVP of 0.24 ± 0.02 g.mm/m2.h.kPa. The optimized film was then supplemented with EX at 5%, 10%, and 15% (v/v), yielding VEX5, VEX10, and VEX15 films, respectively. Spectroscopic and thermal analyses revealed enhanced intermolecular interactions among chitosan, microalgal components, tannic acid, and juniper seed extract polyphenols, including hydrogen bonding and π-π associations, leading to a more cohesive polymer network and improved thermal stability compared to the baseline chitosan film, as evidenced by shifts in degradation-related thermal events. Scanning Electron Microscopy (SEM) observations showed a progression from smooth surfaces in the control chitosan film to increasingly compact morphologies in extract-loaded samples, with VEX15 exhibiting the most uniform structure. Antibacterial assays of film-forming solutions against Staphylococcus aureus, Escherichia coli, and Salmonella Typhimurium revealed increasing inhibition zones with higher EX content, indicating a synergistic effect with algal and polyphenolic components. Overall, the algae-chitosan-glycerol-tannic acid film system enriched with J. excelsa extract offers improved structural stability, antioxidant potential, environmentally responsive degradability, and functional performance, highlighting its potential for sustainable packaging.
Existing literature indicates that bullying victimization elevates the risk of depression among adolescents; however, longitudinal evidence on the associations between specific types of victimization (physical, verbal, relational, and cyberbullying) and depression remains limited, particularly with regard to gender differences. This study examined the predictive effects of these four forms of victimization on depression at a six-month follow-up and further explored the moderating role of gender. We collected two-wave longitudinal data from 457 Grade 10 students (230 boys, 227 girls; Mage = 15.93, SD = 1.94) at a high school in Gansu Province, China, in June 2024 (T1) and December 2024 (T2). Participants completed a series of self-report questionnaires, including measures of demographic characteristics, the Revised Bullying Victimization Questionnaire (BVQ-R), and the depression subscale of the Depression Anxiety Stress Scales (DASS-21). Hierarchical multiple regression analyses were conducted to examine both main and interaction effects, and simple slope analyses were performed to probe significant interactions. After adjusting for demographic covariates, all four forms of T1 bullying victimization significantly predicted higher levels of depressive symptoms at T2 in the main-effects models. In the interaction models, none of the victimization × gender interaction terms reached statistical significance. These findings suggest that multiple forms of bullying victimization are prospectively associated with subsequent depressive symptoms and that these associations do not appear to vary by gender in this sample.
The stability of the bottom structure and the scientific management of ore drawing are critical to the successful application of the block caving method. In view of the engineering conditions of the Lower Orebody of the Cukaru Peki Copper-Gold Mine operated by Serbia Zijin Copper Doo Bor characterized by great burial depth, high in-situ stress, and large-scale mechanized ore extraction. This study systematically optimizes the layout form and key geometric parameters of the bottom structure through a comprehensive approach combining engineering analogy, theoretical analysis, numerical simulation, and orthogonal experimental design. The results indicate that, in terms of the layout at the extraction level, the branching herringbone configuration is the optimal scheme. It not only ensures sufficient overlap of draw zones and stability of the sill pillar, but also better accommodates the efficient operation of electric load-haul-dump (LHD) machines. Regarding key parameter determination, coupled analyses of vertical and planar geometric relationships demonstrate that the optimal vertical distance between the extraction level and the undercut level is 20 m. The spacing of drawpoint crosscuts and drifts is determined to be 32 m and 18 m, respectively. The optimized dimensions of the ore pass are identified as 5.0 m for the lower opening width and 14 m for the upper opening width, which significantly reduce the incidence of drawpoint hang-ups. For the undercutting scheme, an advancing undercut method combined with an inclined narrow-section layout is recommended, with an undercut height of 6 m. Furthermore, numerical simulations reveal the influence of the advanced undercut distance on stress redistribution. It is recommended that a reasonable distance of 30-36 m be maintained between ore pass operations and the advancing undercut front to effectively mitigate structural damage caused by high stress concentrations in the bottom structure. The parameter system established in this study provides a scientific basis for the safe and efficient exploitation of the Cukaru Peki deposit operated by Serbia Zijin Copper Doo Bor and offers important engineering guidance for bottom structure design in similar deep block caving mines.
Agriculture is increasingly challenged by climate change-driven stresses, including rising temperatures, erratic rainfall, soil degradation, with increased frequency of pests and disease outbreaks. This disrupts crop productivity and threatens global food security, underscoring the urgent need for sustainable, adaptive strategies, which are environment-friendly. Microorganisms, integral to soil health, nutrient cycling, and plant stress physiology, offer promising nature-based solutions for climate resilient agriculture. Yet their potential remains underutilized due to technical, ecological, and socio-economic barriers that hinder widespread adoption. This review addresses these research gaps and practical challenges, while outlining future perspectives for scaling up microbe-based technologies through integration with omics and AI tools. The major points addressed in this review are (1) Major advances in microbial applications that directly support crop resilience and ecosystem sustainability. It examines recent progress made towards enhancing the effectiveness of biofertilizers (including mycorrhizal fungi), biopesticides and developing novel products, detailing how these innovations enhance nutrient acquisition, regulate phytohormonal balance, improve water-use efficiency, mitigate abiotic stresses such as drought, salinity, heat and pH, and minimize losses incurred due to pathogen and pests; (2) Mechanistic insights into microbial mediation of nutrient cycling, soil aggregation, and stress alleviation in terms of plant-microbe or soil-plant microbiome networking; (3) The role of emerging biotechnological tools, including metagenomics, microbiome engineering, and synthetic biology, that enable the design of more effective and context-specific microbial interventions that can be integrated with artificial intelligence (AI) and machine learning (ML) tools for precise application (4) Emphasis on both the benefits and constraints of microbial inoculants is documented as well as novel strategies for their effective use as sustainable solutions for climate ready agriculture. Ultimately, microbial innovations are positioned as pivotal in building climate-resilient agroecosystems capable of sustaining productivity and reducing environmental footprints.
To clinically and radiographically compare two osseodensification techniques in terms of implant stability and osseointegration in a split-mouth design. 7 patients with an edentulous maxillary anterior area who need implant placement were divided into 2 groups. Group A included 7 implants and was prepared using the Densah Bur technique (DB-Group), while Group B included 7 implants and was prepared using the Magnetic Mallet technique (MM-Group). Surgery was performed, followed by clinical and radiographic follow-up to evaluate implant stability in both groups. A linear mixed model (LMM) statistical analysis was utilized to handle the clustering effect of the data. The mixed model revealed a stable data analysis owing to the significant intercept for all of the dependent variables (P < 0.001). Densah Burs technique demonstrated lower postoperative pain, faster wound healing, higher implant stability, and greater preservation of labial bone thickness, while both methods showed similar long-term bone density and crestal width outcomes. Within the confines of this study, the rotary-based Densah Bur osseodensification technique was associated with higher implant stability and labial plate thickness, alongside comparable bone density. These findings suggest potentially more predictable osteotomy compaction and autografting in the maxillary anterior esthetic zone implant osteotomy preparation. Trial was retrospectively registered at pactr.samrc.ac.za [PACTR202412717492416-(2024-12-31)].
Animals rely on sensory perception to initiate and execute a wide range of behaviors. In social interactions, house mice primarily depend on olfactory and auditory cues, whereas the contribution of visual input remains less well understood. To address this gap, we systematically examined the impact of lighting on social interactions using a same-sex resident-intruder assay in male and female mice. Behaviors were categorized into self-behavior, social investigation, allogrooming, aggression (males), and mounting (females), and were analyzed in terms of total duration, frequency, latency, temporal dynamics, behavioral transitions, and variability. Across sexes, we found no significant differences in overall behavioral composition or variability between light and dark conditions. Although some behavioral transitions differed between conditions, none remained significant after multiple-comparison correction. Nevertheless, temporal analyses revealed subtle lighting-dependent patterns, with certain behaviors exhibiting time-dependent changes that reached statistical significance only under specific illumination conditions. These findings suggest that under the conditions tested, visual cues were not found to substantially alter the overall repertoire of social behaviors, but may modulate their temporal organization. Together, our results indicate that vision may function as a modulatory cue that influences when specific behaviors are expressed, highlighting the importance of temporal dynamics in behavioral analysis.
Medical education is transforming due to new technologies such as artificial intelligence (AI). Although AI is being considered for medical education, its integration into the curriculum remains limited. Furthermore, few studies evaluate how these tools affect students' diagnostic accuracy during clinical rotations. This study aims to evaluate available evidence regarding AI tools in medical students, identifying their effects on clinical education and clinical decision-making, as well as their implications for medical practice during clinical rotations. For this purpose, a scoping review was conducted in December 2025. The literature search was performed across key databases using MeSH and DeCS terms. Studies published between 2015 and 2025 were included.After screening, 26 articles were included. Most studies suggest a positive effect of AI on students' clinical education and clinical decision-making, particularly in solving clinical cases and interpreting images. AI appears to support students in reaching performance levels closer to experienced physicians, which could influence medical care quality. Seven articles reported a neutral effect, warning that incorrect or unclear AI responses might cause confusion. In conclusion, this review suggests that AI may have a positive effect on medical students, especially those with less clinical experience, potentially bringing them on par with more experienced professionals. The need for structured AI integration into the curriculum is underscored, as it has the potential to improve academic performance and provide enriched learning environments. However, ensuring adequate training and regulation for its efficient use is key to addressing the associated ethical and legal implications in healthcare settings.