To evaluate finerenone-associated adverse events (AEs) and to investigate the association between finerenone use and renal injury via data mining of the Food and Drug Administration Adverse Event Reporting System (FAERS). To minimize statistical bias, the data extraction period was set from database inception (2004) to provide a stable background for disproportionality analysis. Four disproportionality algorithms (ROR, PRR, BCPNN, and MGPS) and stricter case-screening methods were employed to improve analytical precision. Additionally, a clinical priority evaluation was conducted to rank clinical risks and surveillance levels for these AEs. Supplementary analysis was performed to assess the relationship between finerenone and renal injury, as well as associated risk factors. A total of 1316 finerenone-related reports were identified. 30 AEs were detected as significantly positive signals, with most being related to renal function (15 PTs, 50%), blood pressure (5 PTs, 16.67%), and blood potassium (4 PTs, 13.33%). Among them, blood glucose increased, blood creatine increased, and flank pain were new potential AEs. Acute kidney injury, hyperkalemia, renal impairment, glomerular filtration rate decreased, blood creatinineincreased, blood potassium increased, and hyponatremia exhibited moderate clinical priority levels and warrant further study. Signals reflecting renal injury were detected in patients regardless of baseline nephropathy. Male sex, taking more than 3 drugs, and using amlodipine may be risk factors for finerenone-related nephrotoxicity. These results highlight new finerenone-related AEs, provide ranked guidance for pharmacovigilance through clinical priority evaluation, and clarify factors that influence renal injury, providing guidance for individualized treatment and improved drug safety.
The goal of this study was to identify symptoms that occur in children post-SARS-CoV-2 infection, their trajectory over the first-year post-enrollment, and relationship to age. Longitudinal comparison of infected and uninfected cohorts. Participants (0-21 years) with laboratory-confirmed SARS-CoV-2 infection were enrolled as infected. The uninfected cohort was individuals without laboratory evidence of SARS-CoV-2 infection. Primary outcome was presence or absence of symptoms. 852 participants (705 infected, 147 uninfected) completed baseline visits. Of those, 558 infected subjects completed a 12-month post-enrollment visit. Twenty symptoms were identified as more common in infected participants compared to uninfected, at either baseline or 12-months, with symptoms varying by age. Some symptoms in the infected were more frequent at baseline (e.g. fever, weight loss), whereas many symptoms persisted through 12-months. Several symptoms were more frequent at 12-months (e.g. dysmenorrhea, persistent headache). Presence of symptoms at 12-months was not significantly associated with the wave of circulating virus at original infection. Interim analysis at one-year post-enrollment identifies 20 symptoms that infected participants were more likely to report post SARS-CoV-2 infection compared to uninfected, at either visit. Type of symptoms varies by age. Ongoing longitudinal data up to 3-years post-enrollment will increase understanding of long-term symptoms of SARS-CoV-2 infection in children and their trajectory. NCT04830852. Although most children recover fully from SARS-CoV-2 infection, some children experience a variety of prolonged symptoms following infection. Many studies attempting to characterize these symptoms and trajectory are not prospective nor longitudinal and lack comparison to uninfected controls. This longitudinal analysis identifies and characterizes post-COVID symptoms in children and adolescents and their trajectory through the first-year post enrollment compared to an uninfected cohort. 20 post-infection symptoms were identified as occurring more frequently in the infected as compared to uninfected cohort. Age played a critical role in the type and frequency of symptoms after SARS-CoV-2 infection. Gastrointestinal symptoms were prominent.
Chitin is the second most abundant polysaccharide in nature, and its degradation by marine microorganisms plays a critical role in the global carbon and nitrogen cycles. This study investigated the marine bacterium Microbulbifer harenosus CGMCC 1.13584T to elucidate its chitin metabolic pathway through genomic and transcriptomic analyses. When cultured with chitin as the carbon source, the strain exhibited an extended lag phase and enhanced extracellular chitinase activity. Genome sequencing revealed the presence of genes involved in both hydrolytic and oxidative chitin degradation pathways. Transcriptomic analysis showed that genes associated with the hydrolytic pathway were significantly upregulated upon chitin induction. In contrast, within the oxidative degradation pathway, only early-stage response genes (such as those encoding LPMOs) were markedly upregulated, while genes involved in subsequent metabolic steps (converting GlcNAc1A to KDG-6-P) did not show significant upregulation. Furthermore, a gene encoding a GH10 domain-containing protein was found to be substantially upregulated during growth on chitin. These findings indicate that Microbulbifer harenosus CGMCC 1.13584T utilizes a coordinated chitin degradation mechanism, where the hydrolytic pathway dominates carbon flux during active growth, while the oxidative pathway (via LPMOs) likely provides critical initial structural disruption.
Residual cardiovascular risk persists despite intensive statin therapy in patients with established atherosclerotic cardiovascular disease (CVD). Omega-3 fatty acids, particularly high-dose eicosapentaenoic acid (EPA), have been proposed as adjunctive therapy, yet trial results conflict, likely due to formulation differences. We conducted a formulation-focused meta-analysis to determine whether high-dose EPA-dominant supplementation reduces cardiovascular events and to quantify the impact of mixed EPA/docosahexaenoic acid (DHA) regimens on efficacy. Following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 guidelines, we searched MEDLINE, Embase, CENTRAL, and trial registries through May 2025 for randomized controlled trials, including placebo-controlled and open-label designs, of high-dose EPA-dominant omega-3 (≥ 1.8 g/day; ≥ 50% EPA) in adults with established CVD or other high-risk settings. Six trials (n = 42,738; 31-85% male) were eligible. Random-effects models generated pooled risk ratios (RRs), with I2 assessing heterogeneity; sensitivity analyses excluded mixed EPA/DHA formulations. Imaging surrogate outcomes were summarized narratively when study modalities were not directly comparable. EPA-based therapy significantly reduced hospitalizations for unstable angina (RR 0.75, 95% CI 0.66-0.87; I2 = 0%). Overall effects on recurrent myocardial infarction and revascularization were not statistically significant, but both became significant after exclusion of STRENGTH, the only mixed EPA/DHA cardiovascular outcomes trial. No significant effect was observed for ischemic stroke, cardiovascular death, or high-sensitivity C-reactive protein (hs-CRP). CHERRY and EVAPORATE both suggested attenuation of plaque progression, but these imaging studies were not pooled because intravascular ultrasound and coronary computed tomography angiography-derived measures were not directly comparable. High-dose EPA-dominant therapy was associated with fewer unstable angina hospitalizations, and formulation appeared to modify clinical benefit. Among blinded, placebo-controlled, cardiovascular outcomes trials, 4 g/day icosapent ethyl is the only formulation independently associated with reduced cardiovascular events. Larger formulation-specific trials are needed to clarify the roles of purified EPA, mixed EPA/DHA regimens, and patient selection. PROSPERO identifier number: CRD420251063069.
The PE_PGRS gene family in Mycobacterium tuberculosis exhibits extensive sequence variability across genotypes, which is consistent with antigenic divergence. Here we investigate how Mtb-despite lacking horizontal gene transfer-balances genomic stability with adaptive plasticity. Comparative analysis of 88 bacterial genomes reveals that PE_PGRS genes exhibit features facilitating mutability, including a significantly elevated CGGC tetramer density (mean 4.97 per 100 nt; range 1.7-7.4) compared with the genome-wide average (1.62 per 100 nt; p = 0.011) and depleted in out-of-frame stop codons, potentially conferring robustness to 1-nt and 2-nt frameshifts. Computational predictions suggest that CGGC motifs may promote secondary DNA structures, potentially destabilizing replication and contributing to replication errors, while the scarcity of out-of-frame stop codons allows continued translation beyond frameshifts, leading to changes in protein sequence and length. This dual organization may contribute to the observed adaptability of M. tuberculosis and could highlight a broader principle by which some pathogens evolve under strong constraints on horizontal gene transfer. We propose that CGGC-rich regions may function as programmed mutational hotspots across a wide range of microorganisms.
In the context of the aging of the global population, the prevalence of knee joint disorders continues to rise. Concurrently, the integration of robotic systems and intelligent implants represents an inevitable trend in orthopedic surgery. A comprehensive evaluation of the safety and effectiveness of robot-assisted total knee arthroplasty (RA-TKA) is therefore urgently needed to inform clinical decision-making. To explore the advantages of 9 RA-TKAs across 8 outcomes. A systematic literature search was conducted in the PubMed, Web of Science, Embase, Cochrane Library, CBM, CNKI, Wanfang, and VIP databases from inception to December 1, 2025. The risk of bias and methodological quality were assessed via Review Manager (version 5.4). Network meta-analysis was performed via RStudio (version 4.4.1). A total of 36 studies involving 2841 patients were included. In direct comparisons, conventional TKA (C-TKA) yielded shorter operative times than MAKO, HURWA, SkyWalker, ROSA, and Brainlab Knee did. CORI also had a shorter operative time than Brainlab Knee did. Compared with the C-TKA, MAKO, HURWA, SkyWalker and TiRobot groups, the ROSA group presented higher KSS-knee scores. In addition, C-TKA, HURWA, and CORI presented higher KSS-knee scores than did SkyWalker. For the KSS-function scores, the C-TKA and ROSA scores were higher than the HURWA score. C-TKA demonstrated a greater postoperative ROM than HURWA did. For HKA angle deviation, C-TKA resulted in greater deviation than MAKO, HURWA, SkyWalker, TiRobot, and EPMEDBOT did. In the comprehensive best probability ranking, C-TKA (93%) ranked highest in terms of operative time. SkyWalker (87%) ranked highest in terms of blood loss. SkyWalker (91%) ranked highest in terms of the KSS-knee scores. HURWA (87%) ranked highest in terms of the KSS function scores. MAKO (85%) ranked highest for HSS. The YUANHUA (76%) ranked highest for the WOMAC. The CORI (69%) ranked highest for ROM. SkyWalker (87%) ranked highest for HKA angle deviation. Overall, RA-TKA demonstrated superior safety and effectiveness compared with C-TKA, with different robotic systems exhibiting distinct advantages across outcome measures. Nevertheless, C-TKA retains a significant advantage in reducing the operative time, highlighting an important area for further optimization of robotic-assisted TKA.
Peptic ulcer disease (PUD) remains a significant public health concern globally, particularly in regions with high prevalence of risk factors such as Helicobacter pylori infection and Non-Steroidal Anti-Inflammatory Drug (NSAID) use. This study aimed to investigate the prevalence of PUD and its associated risk factors among hospitalized patients in a tertiary hospital in southwest Iran. A mixed-methods design was employed, including a comprehensive literature review, checklist development and validation via a modified Delphi process, a cross-sectional prevalence study, and a hospital-based case-control study. Data were collected from 43,324 patient records (2019-2023) at Abadan University Teaching Hospital. Risk factors were assessed using a validated 21-item checklist, and multivariate logistic regression was used to identify independent predictors of PUD. Among all admissions, 6,874 cases of PUD were identified, indicating a point prevalence of 15.9% (95% CI: 15.6-16.2). NSAID use (75.3%), H. pylori infection (70.1%), smoking (46.9%), and corticosteroid use (30.2%) were highly prevalent among PUD patients. Significant independent risk factors included age ≥ 60 years (AOR: 1.65), NSAID use (AOR: 2.58), H. pylori positivity (AOR: 2.41), smoking (AOR: 1.45), and ulcer size ≥ 5 mm (AOR: 2.19). Despite the high rate of NSAID use, only 26.4% received gastroprotective therapy. The findings underscore the high burden of PUD in hospitalized patients in southwest Iran, with modifiable risk factors such as NSAID use, H. pylori infection, and smoking playing a critical role. Targeted interventions, including Proton Pump Inhibitor (PPI) co-prescription, H. pylori eradication, and lifestyle modifications, are essential to reduce PUD incidence and its complications.
Acetabular fractures are uncommon, but serious injuries. Demographic changes may have a significant impact on planning healthcare structures to improve treatment outcomes. Aim of this nationwide, registry-based retrospective controlled study was to identify incidence trends, demographic characteristics, and care structures of patients with acetabular fractures in Germany. We analyzed inpatient data from the Institute for the Hospital Remuneration System (InEK). Based on 52 095 patients with primary diagnosis of an acetabular fracture between 2019 and 2024, we calculated incidence rates for different age-groups and put a spotlight on geriatric acetabular fractures (> 65 years of age). Incidence rates in patients under 65 years remained stable, whereas patients over 65 years showed a significant age-dependent increase with an exponential rise in men aged 80 + with the highest incidence being 122.4/100 000 inhabitants annually. We recorded high levels of co-morbidity and nursing care dependency for elderly patients after acetabular fracture. Although 43% of patients were treated in hospitals > 500 beds, acetabular fractures were managed across all hospital sizes. There is a rapidly increasing incidence of geriatric acetabular fractures, predominantly driven by elderly male patients over 80 years. Patients over 65 years are associated with high rates of co-morbidities and nursing care levels.
To compare perioperative outcomes between the 48-h short-stay pathway and traditional inpatient management for patients undergoing robot-assisted partial nephrectomy (RAPN), and to evaluate the feasibility, safety, recovery efficiency, and economic benefits of the 48-h short-stay pathway. This retrospective study included 175 patients who underwent RAPN between February 2022 and June 2024. Patients were assigned to a 48-h short-stay group (n = 60) or a traditional inpatient group (n = 115). A 1:1 propensity score matching (PSM) was conducted to balance baseline characteristics, including age, sex, BMI, comorbidities, tumor features, surgeon identity, and surgical year. Perioperative outcomes, recovery indicators, complications, and medical costs were compared. After PSM, 53 matched pairs were analyzed. The short-stay group showed significantly shorter operative time, less intraoperative blood loss, shorter warm ischemia time, earlier mobilization, earlier oral intake, faster bowel function recovery, and shorter bed rest (all P < 0.05). The short-stay group had 71.7% of patients discharged on postoperative day (POD) 1 and 100% within 48 h, while the traditional group had 22.6% on POD1, 33.96% on POD2, and 43.4% on POD ≥ 3 (P < 0.001). Both total and postoperative hospital stays were significantly shorter in the short-stay group (2.00 vs. 6.00 days, P < 0.001), with lower hospitalization costs (P < 0.001). Postoperative creatinine was lower in the short-stay group (P = 0.023), while creatinine change was comparable (P = 0.063). Complication rates, emergency department visits, and 30-day readmission rates were similar between groups (all P > 0.05). The short-stay group had a significantly lower drain placement rate (P = 0.002) without increased adverse events. The 48-h short-stay pathway for selected patients undergoing RAPN is feasible and safe. It accelerates postoperative recovery, shortens hospital stay, reduces medical costs, and optimizes healthcare resource utilization, without compromising safety or oncological early outcomes.
Health-related quality of life (HRQoL) is a vital indicator of evaluating care outcomes and prognosis, yet little is understood about its developmental trajectories in older patients with chronic pain. This study aimed to identify latent HRQoL trajectories and their predictors, and to develop explainable machine learning models for predicting HRQoL deterioration. This prospective cohort study assessed 608 older patients with chronic pain at admission and at 1, 3, and 6 months post-admission, collecting data on HRQoL, general characteristics, pain level, activities of daily living (ADL), depression, and perceived social support. Growth mixture modeling was applied to identify trajectories of physical and mental HRQoL. Predictors were selected using LASSO regression and SVM-RFE. Nine explainable machine learning models were developed for both components, and SHAP interpreted the outputs. An HRQoL decision-support dashboard was developed to facilitate potential clinical application. Three physical HRQoL trajectories were identified: Stable High, Decline and Low Stability, alongside two mental HRQoL trajectories: Improvement and Decline. Key predictors included education level, pain duration, pain level, ADL, depression, and perceived social support, with ADL and pain level being the most influential for physical and mental HRQoL, respectively. This dual-trajectory study identified five distinct HRQoL patterns in older patients with chronic pain, elucidating key predictors via explainable machine learning. The proposed HRQoL decision-support dashboard may provide an interpretable tool to support understanding of predictive relationships and assist healthcare professionals in HRQoL assessment. Not applicable.
Pediatric sepsis is a leading cause of global morbidity and mortality, yet high-resolution, granular subnational assessments remain scarce. Chile and Mexico are the only countries in Latin America that possess robust vital registration systems and open access databases with marginal levels of missing cases. This offers a unique opportunity to quantify the subnational burden of pediatric sepsis, identify healthcare system constrictions, and guide targeted public health interventions. This retrospective longitudinal study analyzed official hospital discharge and non-fetal death records of pediatrics (< 10 years old) from Chile and Mexico between 2014 and 2024. Age-standardized incidence (ASIR) and mortality (ASMR) rates, standardized ratios, and the mortality-to-incidence ratio (MIR), were calculated to assess mortality relative to subnational hospital output. A novel dynamic risk stratification matrix was developed to classify ICD-10 sepsis-related causes into four risk/severity quadrants based on year-specific ASIR and MIR indicators. A total of 656,234 discharges and 2,035 deaths in Chile, and 964,452 discharges and 77,252 deaths in Mexico were analyzed. Subnational trends were highly heterogeneous. Chile exhibited a predominantly low pediatric MIR (median < 1%) with isolated hotspots with significant structural deviations to the North. High-severity sepsis causes in Chile were relatively rare. Conversely, Mexico displayed an alarmingly high MIR (median 7.2%), with systemic persistency in States such as Chiapas and Nuevo León. Strikingly, high-severity causes in Mexico (e.g., unspecified septicaemia, bacterial meningitis) were highly frequent, accounting for 88-97% of pediatric sepsis deaths. Furthermore, systemic instances of code-specific MIR > 1.0 in Mexico suggest significant health system fragmentation and decoupling of hospital discharge from vital statistic registries. Pediatric sepsis in Latin America encompasses distinct realities, ranging from localized critical care gaps to high-lethality persistency. One-size-fits-all national policies may be inadequate. These findings advocate for precision public health, urging the deployment of decentralized, data-driven interventions and specialized resource allocation based on high-risk subnational hotspot identification.
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The deltoid ligament (DL) is the primary stabilizer of the medial ankle, but its injury mechanisms remain poorly understood. This study aimed to investigate the injury risk and mechanisms of individual DL bundles under both acute and chronic conditions to inform prevention and treatment strategies. A validated finite element model of the human foot was used to examine peak stresses in DL bundles under four acute loading scenarios. Chronic loading was simulated by applying gait loads after transecting the lateral ligaments, and the resulting DL stresses were compared with those of the intact model. Additionally, thirty-nine rats were assigned to three groups: a lateral ligament rupture group (LR, n = 13), a tibialis posterior tendon rupture group (TPR, n = 13), and a sham group (n = 13). After 6 weeks of treadmill running, the mechanical properties and histological characteristics of the DL, along with ankle joint morphology and articular stresses, were evaluated to further verify the hypothesized mechanisms of chronic injury. Under acute loadings, the tibiocalcaneal ligament (TCL), anterior tibiotalar ligament (ATTL), and deep posterior tibiotalar ligament (dPTTL) showed the highest stress under pronation-external rotation loading. Lateral ligament rupture increased DL stress during gait. After 6 weeks of treadmill running, the LR and TPR groups showed roughened articular surfaces with osteophyte formation, increased articular stress, decreased talar bone volume fraction, lower failure load and stiffness ratios of the DL (p < 0.01), reduced fluorescence intensity of COL1, and elevated levels of COL3, MMP-2 and IL-1β compared with the sham group (p < 0.01). The TCL, ATTL, and dPTTL bundles are particularly susceptible to acute injury, with pronation-external rotation posing the greatest risk. Chronic degeneration of the DL occurs following rupture of the lateral ligament or tibialis posterior tendon, with a more pronounced effect after lateral ligament rupture.
Expanded hemodialysis (HDx) using medium cut-off dialyzers has been associated with lower all-cause hospitalization rates compared to conventional high-flux hemodialysis. Reductions in hospitalization frequency represent a major driver of healthcare expenditures and may contribute to improved budget sustainability in resource-constrained healthcare systems. The objective of this study was to estimate the budget impact of adopting HDx from the perspective of the Colombian healthcare system, using real-world evidence. A budget impact analysis was developed according to the ISPOR guidelines using a tool built in Microsoft Excel. Clinical effectiveness inputs were derived from a multicenter cohort study (COREXH-E), including an extended dataset and a difference-in-differences analysis to estimate the effect of HDx on hospitalization rate while accounting for unobserved confounding. Cost inputs were obtained from national administrative databases, including hospitalization costs and bundled dialysis payments. The analysis adopted a one-year time horizon and a third-party payer perspective representing the Colombian healthcare system. Budget impact scenarios were evaluated, assuming HDx market uptake rates of 5%, 10%, 20%, and 50%. Deterministic and probabilistic sensitivity analyses were performed to assess parameter uncertainty. Adoption of HDx was associated with net cost savings for the Colombian healthcare system across all uptake scenarios. Under hospitalization rates observed in the real-world cohort, estimated annual savings ranged from USD 472,756 to USD 4,727,564 as HDx uptake increased from 5% to 50%. In scenarios reflecting higher hospitalization rates observed in the general Colombian hemodialysis population, annual savings ranged from USD 1,344,401 to USD 13,444,010. Cost savings were primarily driven by reductions in hospitalization frequency. Probabilistic sensitivity analysis showed that HDx was cost-saving in 97.8% of simulations. This study suggests that expanded hemodialysis could result in short-term cost savings for the Colombian healthcare system by reducing hospitalization-related costs without increasing dialysis expenses.
Oral lichen planus is a chronic disease of the oral mucosa, with pain as one of its main symptoms. This study aimed to assess the correlation between the results of four pain intensity measures-including the Visual Analog Scale (VAS), Numeric Rating Scale (NRS), Short Form McGill Pain Questionnaire (SF-MPQ), and Verbal Rating Scale (VRS)- in a population of patients diagnosed with oral lichen planus. In this prospective observational study, 66 patients with oral lichen planus participated. Four pain assessment scales were used, including VAS, NRS, VRS, and SF-MPQ. Participants completed these assessments at baseline and again after two weeks of treatment. A paired t-test, Spearman correlation, linear regression analysis, and adjusted multiple regression analysis (regarding age and level of education) were used to analyze the data. All four scales were sensitive to changes in pain after treatment and a significant reduction in pain scores was observed (p < 0.001). There was a strong positive correlation between all scales (p < 0.001). Regression analysis showed that scores on each scale could significantly predict scores on the other scales (p < 0.001). Multiple regression analysis adjusted for age and level of education, showed the correlations between the pain scales remained strong and significant (p < 0.001). These commonly used pain assessment scales showed strong correlation with each other, and it seems that the results obtained from each might be comparable with the others. However, further researches in larger studies and different populations are needed.
Postoperative gastrointestinal (GI) bleeding is a serious complication after hip fracture surgery in older adults, yet perioperative risk stratification remains limited because commonly used GI-bleeding scores are not tailored to orthopedic settings. This study aimed to develop and internally validate an interpretable model to predict postoperative GI bleeding risk in elderly hip fracture patients, using data routinely available during the perioperative period. We retrospectively included 342 elderly patients who underwent hip fracture surgery at the Third Hospital of Hebei Medical University from January to December 2023. The outcome was GI bleeding within 1 month after surgery, confirmed by medical records and/or telephone follow-up. Patients were randomly split into a training set (n = 242) and a validation set (n = 100). Predictors were screened using LASSO with 10-fold cross-validation, followed by multivariable logistic regression to identify independent risk factors. Ten prediction algorithms were trained and compared. Model performance was assessed by AUC, calibration, and decision curve analysis, and interpretability was evaluated using SHAP. GI bleeding occurred in 38 patients (11.1%). Multivariable analysis identified four independent predictors: alcohol consumption history (OR 8.109, 95% CI 2.463-26.69), glucocorticoid use (OR 4.922, 95% CI 1.055-22.97), NSAID use (OR 6.851, 95% CI 1.811-25.915), and higher systemic immune-inflammation index (SII) (OR 1.001, 95% CI 1.000-1.002). Among the tested models, LightGBM showed the best overall performance, with AUCs of 0.843 (training) and 0.817 (validation), good calibration, and the highest net benefit on decision curve analysis. SHAP results ranked feature importance as SII, NSAID use, alcohol consumption history, and glucocorticoid use, consistent with regression findings. We developed and validated an interpretable LightGBM model that predicts postoperative GI bleeding risk in elderly hip fracture patients using routinely available clinical data. The final model incorporates only preoperative variables, systemic inflammation, NSAID use, alcohol history, and glucocorticoid use, supporting its application for early risk stratification prior to surgery.
The association between preoperative peripheral nerve block (PNB), major adverse cardiovascular events (MACE), and postoperative length of hospital stay (LOS) in elderly patients who underwent major thoracic and abdominal surgery remains unclear. This study aims to explore the potential mediating effect of MACE on the association between preoperative PNB and postoperative LOS using a statistical mediation framework. In this retrospective cohort study, perioperative data were collected from elderly patients (aged over 65 years) who underwent major thoracic and abdominal surgery. Mediation analysis was employed to examine the relationships between PNB, MACE, and postoperative LOS. A total of 1915 patients were included in the analysis, with 68.7% (1316/1915) receiving preoperative PNB. Compared to patients who did not receive PNB, those who did had a significantly lower incidence of MACE (P < 0.001) and a shorter postoperative LOS (P < 0.001). The adjusted total and direct associations of PNB with postoperative LOS were - 0.809 days (95% confidence interval [CI], -1.236 to -0.390; P < 0.001) and - 0.661 days (95% CI, -1.077 to -0.250; P = 0.003), respectively. A statistically significant indirect association via MACE was observed (adjusted β=-0.149 days; 95% CI, -0.271 to -0.060; P < 0.001), indicating that 18.1% (95% CI, 6.7% to 41.0%) of the total association was statistically attributable to the indirect pathway through MACE under the model assumptions. A sensitivity analysis excluding postoperative covariates yielded consistent results (proportion mediated: 25.3%). Our findings suggest that the observed association between preoperative PNB and reduced postoperative LOS in elderly patients following major thoracic and abdominal surgery may be partly explained by a statistically significant indirect pathway through a reduction in MACE, potentially accounting for approximately 18% of the total effect. These findings are hypothesis-generating and represent statistical associations rather than demonstrated causal mechanisms. ChiCTR2400087610; https://www.chictr.org.cn.
The production of monoclonal antibodies (mAbs) in Chinese hamster ovary (CHO) cells is often affected by position-effect variegation and the gradual loss of transgene expression over time. Hence, we have designed a dual-promoter IgG expression vector and compared versions that either contained or lacked a CHO-derived matrix-attachment region (MAR). Stable CHO-S pools, cultured in serum-free conditions, revealed that the MAR-containing construct produced higher and more consistent antibody levels across ten passages, as confirmed by Western blot and Protein A Octet analysis. Product-quality analysis by size-exclusion chromatography and reducing SDS-PAGE confirmed formation of properly assembled, mainly monomeric antibodies in both cases. Quantitative PCR indicated greater transgene copy numbers in MAR pools (+ 48% for the light chain and + 71% for the heavy chain), and RT-qPCR showed roughly fourfold higher transcript levels for both chains relative to controls. Bioinformatic analysis revealed several SATB1 binding motifs within the MAR sequence, and ChIP-qPCR demonstrated SATB1 association with the MAR-linked transgene locus. Overall, the data suggested that a CHO-native MAR could enhance transgene dosage and transcriptional activity, while preserving product integrity, possibly through SATB1-mediated chromatin organization. Ongoing work includes chromatin-mark profiling and process-level productivity measurements to better define the impact of MAR-based vector design on biomanufacturing performance.
We aimed to explore the predictive role of radiomic features of body compositions in the occurrence of delayed awakening after flexible ureteroscopic lithotripsy, and further develop a predictive model to identify patients at higher risk. We analyzed the data from 314 admitted patients undergoing total intravenous general anesthesia at two institutions. Binary logistic regression was used to assess univariable and multivariable associations of clinical factors with delayed awakening. Radiomic features of body compositions were deeply extracted from preoperative computed tomography (CT) scans using ResNet50 model. We developed a combined model by integrating significant clinical variables with radiomic score. SHapley Additive explanation (SHAP) method was adopted for model interpretation and helping clinicians understand the predictive results. At multivariable analysis, CT-derived visceral adipose tissue area and skeletal muscle index were independent predictors of postoperative delayed awakening. The combined model had area under curves (AUCs) of 0.85(95%CI: 0.82, 0.89), 0.83(95%CI: 0.80, 0.87) and 0.80(95%CI: 0.76, 0.84) in the derivation, internal and external test datasets, respectively. 8 radiomic features were selected using Spearman rank correlation test and the least absolute shrinkage and selection operator logistic regression analysis. This combined model showed better discrimination and calibration than clinical model alone. Furthermore, SHAP plots quantified the impact of key variables on prediction at the global level. The combined model may allow estimation of the risk of postoperative delayed awakening after flexible ureteroscopic lithotripsy.
This study aimed to examine 8th-grade students' views on the concepts of nanotechnology and nanoscience through the use of the Metaverse in science courses. The study group sample consists of five students from both the before- and after-experience groups, all of whom are in 8th grade. This study employed a qualitative research method with a case study design. Observation, interview, and document analysis were used as data collection tools. Necessary measures have been taken to ensure the validity and reliability of the research within its scope. The data were analyzed using a content analysis approach. As a result of the interviews, data were collected and analyzed. As a result of the textual examinations, code, category, and theme were determined. The findings were presented in categories through tables, and the participants' answers were included in direct quotations. Upon reviewing the literature, it becomes apparent that most studies in nanotechnology and nanoscience are conducted for informational purposes, typically presented as presentations or reports. Given the limited availability of nanotechnology and metaverse education, the study was divided into two groups: a before-experience group and an after-experience group. As a result of the survey, 8th-grade students experience the metaverse and have future expectations for nanotechnology and nanoscience. Their cognitive and affective interests have increased, as evidenced by their questioning why these applications cannot be applied to all courses and by their correct expression of the concepts. At the same time, it has been concluded that using rich materials to concretize abstract concepts, such as nanotechnology, facilitates their teaching. The study provides qualitative evidence that Metaverse-based instruction can enhance both cognitive and affective dimensions of science learning, offering design implications for integrating immersive technologies into middle school curricula to teach abstract concepts.