To identify isoniazid (INH)-resistance-associated mutations in the katG of Mycobacterium tuberculosis (MTB) using whole genome sequencing (WGS) and validate mutations through functional studies. Clinical MTB isolates from tuberculosis patients at Shijiazhuang Fifth Hospital (June 1, 2020-June 30, 2022) were stratified into INH-resistant and INH-susceptible groups based on minimum inhibitory concentration (MIC). 67 isolates from each group underwent WGS. Based on the WHO drug resistance database, select katG mutation sites that are not yet confirmed as resistance-conferring in the WHO 2024 catalog, and predict their interactions with INH through molecular docking and molecular dynamics simulations. Functional validation was performed by overexpressing mutant katG alleles in the model organism Mycobacterium smegmatis mc²155 and assessing MIC shifts. WGS revealed 15 katG mutation sites, including 9 variants not catalogued in WHO databases. Structural modeling demonstrated reduced binding stability between INH and the G124R mutant compared to wild-type katG. Functional assays confirmed that mc²155 overexpressing katG-G124R exhibited a two-fold MIC increase, while V151I and G124D mutants showed no significant resistance changes. 9 katG mutations were identified in INH-resistant MTB, with experimental validation confirming that the G124R substitution enhances INH resistance through impaired drug-target interaction.
Delirium is a frequent manifestation of acute brain dysfunction in critically ill patients with bloodstream infections (BSI). While the association between sepsis and delirium is well-established, pathogen-specific neurotoxic effects, particularly those induced by Staphylococcus aureus (S. aureus), remain inadequately elucidated. This study aimed to evaluate the independent association between S. aureus BSI and the risk of 7-day incident delirium in critically ill adults. A retrospective cohort study was conducted using the MIMIC-IV database, including 3,226 adult patients with confirmed BSI. To minimize confounding bias, a "doubly robust" estimation approach was employed, combining Inverse Probability of Treatment Weighting based on Covariate Balancing Propensity Scores (IPTW-CBPS) with multivariable adjustment. Fine-Gray proportional subdistribution hazard models were utilized to assess the association between pathogen status and 7-day delirium, accounting for death as a competing risk. Explainable machine learning using the eXtreme Gradient Boosting (XGBoost) algorithm and Shapley Additive exPlanations (SHAP) value analysis was performed to identify feature importance. Sensitivity analyses for the 3-day acute risk and methicillin-resistant Staphylococcus aureus (MRSA) phenotype were also conducted. Among 3,226 patients, 618 (19.2%) were identified with S. aureus BSI. In the fully adjusted Fine-Gray model, compared with Gram-negative infections, S. aureus BSI was robustly and independently associated with an increased risk of 7-day incident delirium (sHR 1.39; 95% CI 1.11-1.74; p = 0.005). This association was even more pronounced within the 3-day acute window (sHR 1.60; 95% CI 1.27-2.02; p < 0.001). Conversely, compared with Gram-negative BSI, the MRSA phenotype showed no significant independent association with delirium risk (sHR 1.12; 95% CI 0.81-1.55; p = 0.488). SHAP analysis identified S. aureus infection as the fourth most influential feature for delirium, surpassing age and sedative exposure. Subgroup analyses revealed that the pathogen-specific impact was significantly more prominent in patients with lower baseline illness severity (SOFA < 5) and those without a history of dementia (P for interaction < 0.001 and 0.004, respectively). SHAP value analysis further confirmed this finding by demonstrating a higher risk contribution of S. aureus in patients with lower SOFA scores. S. aureus BSI is a robust independent risk factor for 7-day incident delirium compared with Gram-negative BSI, with the hazard being more pronounced within the first 3 days of infection. Notably, compared with Gram-negative BSI, the MRSA phenotype was not independently associated with delirium risk. Identifying S. aureus as a critical driver of early brain dysfunction provides a pathogen-specific framework for risk stratification. Consequently, clinicians should prioritize early neurocognitive monitoring and targeted neuroprotection (e.g. the ABCDEF bundle) for all patients with S. aureus infection.
Reliable and valid assessment tools are critical for evaluating and improving primary school students' hand hygiene behaviors, yet corresponding adaptable assessment methods are currently limited. We aimed to develop and validate a Hand Hygiene Behavior Questionnaire for Primary School Students (HHBQ-PSS). Cluster sampling recruited 376 Grade 4-5 students from two central primary schools. The 15-item HHBQ-PSS encompasses three dimensions (capability, opportunity, motivation) of hand hygiene, using a 5-point Likert scale. HHBQ-PSS was evaluated through internal consistency reliability, split-half reliability, exploratory factor analysis (EFA), and confirmatory factor analysis (CFA). The Cronbach's α coefficient of HHBQ-PSS was 0.844, and all Cronbach's α coefficients remained above 0.750 after corresponding dimensions were deleted. The Spearman-Brown coefficient was 0.784. EFA extracted four common factors (cumulative variance contribution rate = 58.67%). CFA confirmed adequate model fit (χ2/df = 2.832, CFI = 0.905, GFI = 0.927, AGFI = 0.893, and RMSEA = 0.070). The reliable and valid HHBQ-PSS may inform the implementation of targeted health interventions and the improvement of hand hygiene levels among primary school students. HHBQ-PSS demonstrates good reliability and validity to assess hand hygiene behaviors in Chinese primary school students.
To prepare hydroxyapatite/chitosan (HA/CTS) nanocomposites at four weight ratios (85/15, 70/30, 50/50, 30/70) and two concentrations (3 and 5 wt.%), incorporate them into conventional glass ionomer cement (GIC), and evaluate their effect on compressive strength, shear bond strength to dentin, and antibacterial activity. HA/CTS nanocomposites were synthesized by co-precipitation and characterized by TEM and FTIR. Nine groups were prepared (n = 10): one unmodified control (Group I) and eight modified groups (Groups II-IX). Compressive strength was tested per ISO 9917-1:2007; shear bond strength to human dentin and antibacterial activity (agar diffusion against Streptococcus mutans, Staphylococcus aureus, and Escherichia coli) were also evaluated. One-way and two-way ANOVA with Tukey's HSD were applied (P ≤ 0.05). TEM confirmed nanoscale particles (7-50 nm) with dispersion improving at higher chitosan content. FTIR verified dual-phase incorporation and Ca2+-NH2 coordination bonding. Compressive strength (F(8,81) = 177.509; P < 0.0001) and shear bond strength (F(8,81) = 202.262; P < 0.0001) differed significantly among groups. A significant ratio × concentration interaction was confirmed for both properties (P < 0.0001). Only the 70/30 nanocomposite at 3 wt.% exceeded the control compressive strength (133.44 vs. 115.02 MPa; P < 0.05). All eight modified groups showed significantly higher shear bond strength than the control (6.04 MPa), with the 85/15 at 5 wt.% achieving the highest value (13.30 MPa). No inhibition zones were detected in any group. The 70/30 HA/CTS nanocomposite at 3 wt.% optimizes compressive strength, while the 85/15 at 5 wt.% optimizes dentin adhesion. Overall, the 70/30 HA/CTS nanocomposite at 3 wt.% demonstrated the most favorable balanced performance profile across both mechanical outcomes. The absence of detectable antibacterial activity under the present agar diffusion testing conditions may be related to chitosan immobilization within the nanocomposite matrix and the diffusion limitations of the assay method. Findings suggest the potential for application-specific optimization of HA/CTS-modified GIC under controlled in vitro conditions, pending further long-term and in vivo validation. HA/CTS nanocomposite modification enhanced the mechanical and adhesive performance of conventional GIC under the present experimental conditions. The observed improvement in compressive and shear bond strength across the modified formulations may support improved marginal integrity in esthetic GIC restorations. Two application-specific optimal formulations were identified based on the functional demands of the restoration site, with the 70/30 HA/CTS nanocomposite at 3 wt.% representing the most favorable overall formulation combining enhanced compressive strength with clinically acceptable dentin adhesion; however, further long-term and in vivo validation remains necessary before definitive clinical translation.
Non‑small cell lung cancer (NSCLC) remains a leading cause of cancer‑related mortality worldwide. Baicalein, a natural flavonoid, has shown anti‑cancer activity but its molecular targets and cell‑type‑specific effects in the tumor microenvironment (TME) are incompletely understood. We integrated network pharmacology, single‑cell RNA‑seq, bulk transcriptomics, spatial transcriptomics, machine learning, and in vitro experiments to identify baicalein‑responsive genes in NSCLC. Single‑cell analysis resolved 21 cell populations, revealing that baicalein targets were enriched in a 32‑gene core set. Consensus clustering defined three molecular subtypes (cluster 1-cluster 3) with distinct immune infiltration; cluster 1 showed an immune‑cold phenotype with upregulation of cell cycle and metabolic pathways, while cluster 3 was immune‑hot. Machine learning selected a 10‑gene signature (TOP2A, CDH1, CCNB1, SATB2, CA9, HMGB2, MB, NQO1, AURKB, CCNB2) with high diagnostic accuracy. SHAP analysis identified TOP2A as the most influential contributor. Spatial transcriptomics confirmed significantly elevated expression of all ten genes in tumor versus adjacent/normal tissues. Cell‑cell communication analysis highlighted enhanced MIF pathway signaling in the TME, with epithelial cells and SPP1+ TAMs acting as key senders. Molecular docking showed strong binding affinities (ΔG ≤ -8.5 kcal/mol) between baicalein and AURKB, MB, TOP2A, and CCNB2, and molecular dynamics simulations further confirmed the stability of these complexes. In vitro, baicalein (30 μM, 24 h) differentially modulated signature gene expression in PC‑9 and A549 cells and suppressed viability in a dose‑ and time‑dependent manner. This integrative study provides a comprehensive single‑cell and spatial atlas of baicalein‑responsive genes in NSCLC, identifies a robust diagnostic signature, and offers mechanistic insights for developing baicalein as a potential therapeutic agent.
ObjectiveThis study aimed to systematically investigate the independent predictive value of the platelet-to-neutrophil ratio and platelet-to-lymphocyte ratio for 28-day all-cause mortality in patients with sepsis and to further evaluate their incremental discriminatory capacity when added to conventional prognostic scoring models.MethodsThis single-center retrospective cohort study involved 287 adult patients diagnosed with sepsis according to the Sepsis-3 criteria. Patients were stratified into high- and low-level groups based on the median values of platelet-to-neutrophil ratio and platelet-to-lymphocyte ratio, and baseline characteristics, and clinical outcomes were compared between groups. Univariate and multivariate Cox proportional hazards regression models were used to assess the independent associations of platelet-to-neutrophil ratio and platelet-to-lymphocyte ratio with 28-day mortality risk. To evaluate predictive performance, multiple models were constructed and compared, including Sequential Organ Failure Assessment score alone, Acute Physiology and Chronic Health Evaluation II score alone, each combined separately with platelet-to-neutrophil ratio or platelet-to-lymphocyte ratio, and a composite model integrating Acute Physiology and Chronic Health Evaluation II, day-3 lactate level, platelet-to-neutrophil ratio, and platelet-to-lymphocyte ratio. Model performance was rigorously assessed using receiver operating characteristic curves, calibration plots, decision curve analysis, integrated discrimination improvement, and net reclassification improvement, enabling a comprehensive evaluation of discrimination, calibration, clinical utility, and the incremental value of novel biomarkers.ResultsMultivariate Cox regression analysis revealed that lower platelet-to-neutrophil ratio (hazard ratio = 0.97, 95% confidence interval: 0.95-0.99, p = 0.012) and higher platelet-to-lymphocyte ratio (hazard ratio = 1.01, 95% confidence interval: 1.01-1.01, p = 0.043) were independently associated with increased 28-day all-cause mortality. Kaplan-Meier survival analysis confirmed significantly higher cumulative mortality in the low-platelet-to-neutrophil ratio and high-platelet-to-lymphocyte ratio groups (log-rank p < 0.05). The composite model incorporating Acute Physiology and Chronic Health Evaluation II, day-3 lactate level, platelet-to-neutrophil ratio, and platelet-to-lymphocyte ratio demonstrated superior predictive accuracy, with an area under the receiver operating characteristic curve (area under the curve) of 0.824 (95% confidence interval: 0.778-0.871), significantly outperforming both the Acute Physiology and Chronic Health Evaluation II only model (area under the curve: 0.746, p < 0.001) and the Sequential Organ Failure Assessment only model (area under the curve: 0.667, p < 0.001). Decision curve analysis showed that this model provided greater clinical net benefit across a broad range of threshold probabilities. Furthermore, both integrated discrimination improvement and net reclassification improvement analyses confirmed statistically significant improvements in discrimination and reclassification accuracy after the inclusion of platelet-to-neutrophil ratio and platelet-to-lymphocyte ratio (both p < 0.001).ConclusionPlatelet-to-neutrophil ratio and platelet-to-lymphocyte ratio are independent predictors of 28-day mortality in patients with sepsis. Incorporating these readily available and cost-effective inflammatory markers into traditional prognostic systems-such as Acute Physiology and Chronic Health Evaluation II-and combining them with dynamic lactate monitoring substantially enhances the discrimination, calibration, and clinical utility of risk prediction models. These findings provide robust evidence supporting the use of platelet-to-neutrophil ratio and platelet-to-lymphocyte ratio for early risk stratification and individualized prognostic assessment in clinical practice.
Obesity is associated with metabolic dysfunction-associated steatotic liver disease (MASLD), for which drugs and nutraceuticals are being developed. We investigated whether camelina seeds from the Brassicaceae family and their components can attenuate metabolic disorders in animal models of genetic obesity, including fatty liver. In two separate 5-week experiments, female obese (fa/fa) Zucker rats and female db/db mice were used. By appropriately incorporating camelina seeds or their oil into the diet, we investigated, in the rat model, the effects of the oil and non-oil fractions on intestinal and liver function, as well as on lipid metabolism. Subsequently, in a mouse model, oral administration of glucocamelinin, the main camelina glucosinolate, was performed to determine whether this group of compounds might be responsible for the observed beneficial effects. Dietary camelina seeds counteracted liver hypertrophy and steatosis in obese rats, as confirmed by macroscopic and histological images, along with a several-fold lower content of total fat, triglycerides, and cholesterol (p < 0.01 for each). The rat experiment indicated that the non-oil fraction of camelina seeds was responsible for these beneficial effects. Oral glucocamelinin attenuated liver hypertrophy and steatosis in obese mice, as confirmed by macroscopic and histological images, along with considerably lower total fat (p < 0.05) and cholesterol (p < 0.01) contents. In both obese rats and mice, these and other beneficial effects were associated with alterations in the hepatic expression of genes crucial to lipid and glucose metabolism, including a higher expression of those encoding thyroid hormone receptor β (THR-β; p < 0.01 and p < 0.05) and fibroblast growth factor 21 (FGF21; p < 0.01 and p < 0.05). These findings indicate that camelina seeds may be considered both a dietary component and a source of bioactive glucosinolates relevant to MASLD. The mechanism behind the lipid-lowering effect of glucocamelinin may involve hepatic activation of FGF21 signaling through THR-β.
Managing small Lung-RADS 4 pulmonary nodules is clinically challenging. While CT-guided TTFNAB is standard, its efficacy and safety for lesions ≤2 cm require further evaluation to optimize outcomes and reduce unnecessary surgeries. This study aimed to evaluate the diagnostic accuracy, safety, and factors influencing the outcomes of CT-guided TTFNAB in Lung-RADS category 4 pulmonary nodules measuring ≤2 cm. Retrospective study. Single-center, a tertiary referral center. A retrospective analysis was performed on 95 patients who underwent CT-guided TTFNAB between January 2021 and April 2024. Data included demographics, lesion characteristics (size, location, density, and pleural proximity), histopathological findings, and procedural outcomes. The primary endpoints were diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and factors influencing TTFNAB results, alongside procedural complications-specifically pneumothorax and chest tube requirement. 95 patients. Of the 95 nodules, 26 (27%) were benign and 69 (73%) were malignant according to TTFNAB. Final pathology confirmed 18 (19%) benign and 77 (81%) malignant lesions. All biopsies yielded sufficient material. Sensitivity, specificity, and overall diagnostic accuracy were 83%, 94%, and 89%, respectively. The PPV was 98%, while the NPV was 65%. Pleural thickening was significantly more frequent in both the TTFNAB benign group (38% vs. 13%, P=.006) and final benign diagnosis group (44% vs. 14%, P=.008). Pneumothorax occurred in 30% of cases, with 24% of these requiring chest tube drainage. No significant associations were found between diagnostic accuracy or complications and variables such as age, emphysema, Lung-RADS category, or nodule size. CT-guided TTFNAB is an effective diagnostic method for confirming malignancy in pulmonary nodules ≤2 cm classified as Lung-RADS 4, providing an overall accuracy of 89% and a PPV of 98%. However, a benign TTFNAB result cannot be considered diagnostically safe: the NPV of 65% and false-negative rate of 35% indicate that a negative biopsy does not reliably exclude malignancy. Clinicians must not rely on a negative result alone; close radiological follow-up or surgical biopsy is essential for these high-risk lesions. The retrospective single-center design, small sample size, and limited generalizability. 2024/010.99/6/23 (Date: 26.07.2024).
Severe pertussis in children can deteriorate rapidly, and early identification of patients likely to require intensive care remains challenging. We aimed to develop and internally validate an admission-time prediction model for ICU admission among hospitalized children with PCR-confirmed pertussis. We conducted a single-center retrospective prediction-model study based on a hospitalized cohort at a provincial pediatric infectious disease center. Consecutive hospitalized children with PCR-confirmed pertussis between 6 June 2020 and 24 June 2025 were screened. Two children were excluded because admission white blood cell count (WBC), a prespecified core predictor, was unavailable in the retrievable admission-time record, leaving 662 children aged 24 days to 14 years for analysis. The primary outcome was ICU admission, defined a priori as ICU length of stay > 0 days. We prespecified a multivariable logistic regression model using seven admission-time predictors: age (months), sex, symptom duration before admission (days), paroxysmal cyanosis documented at presentation, imaging consolidation/atelectasis, admission WBC scaled per 5 × 109 /L, and any recorded pertussis-containing vaccine dose. Internal validation used 5-fold cross-validation with out-of-fold predictions; model performance was assessed by discrimination (AUC), overall prediction error (Brier score), calibration, and decision curve analysis. ICU admission occurred in 61/662 (9.2%) children. Compared with non-ICU patients, ICU-admitted children were younger (median 2.0 vs 60.0 months) and had higher admission WBC (median 18.7 vs 10.0 × 109 /L). Paroxysmal cyanosis (49.2% vs 6.0%) and imaging consolidation/atelectasis (23.0% vs 10.5%) were more frequent, whereas recorded vaccination was less common (23.0% vs 87.9%). On internal validation, the model showed excellent discrimination (AUC 0.953; 95% CI 0.933-0.972) with low overall prediction error (Brier score 0.045). Calibration was good (intercept -0.017; slope 0.992), and decision curve analysis suggested positive net benefit over clinically relevant threshold probabilities. An admission-time multivariable model showed good internal performance for predicting ICU admission in pediatric pertussis and may support early risk stratification. External validation is required before routine implementation.
We report observations of an energetic-particle mode (EPM) in a linear plasma device that corresponds to an axial bounce resonance of fast ions sourced from neutral-beam injection (NBI). In our experiment, novel dynamic shaping of a magnetic mirror field reduces the distance between the turning points of fast ions while introducing a minimum in the expected bounce frequency; this method decouples the plasma length from the fast-ion motion. We observe an axisymmetric magnetic mode with frequency evolution and axial extent that matches the predicted bounce motion. This experiment is repeated for two different NBI configurations with distinct bounce motions, thus confirming the mode's origin as an axial bounce resonance. We then show that the EPM persists during a transition from a magnetic mirror to a field-reversed configuration (FRC), making this the first observation of an axial bounce resonance in an FRC. Additionally, we use the spatial structure of the EPM to diagnose the change in magnetic topology from mirror to FRC. Finally, a 2D simulation of the FRC formation accurately models the experimental observations and confirms that the mode arises from the clustering of resonant fast ions. These results have insightful implications for the control and design of linear fusion devices with substantial populations of fast ions.
Menke-Hennekam syndrome (MKHK) is a rare autosomal dominant disorder caused by mutations in the CREBBP and EP300 genes. The absence of established diagnostic criteria and non-specific clinical manifestations complicate timely diagnosis and management. This report presents a case of MKHK in which early diagnosis and intervention were achieved through the application of rapid whole-genome sequencing (rWGS), a tool that offers superior speed and genomic coverage compared to whole-exome sequencing (WES). This case report describes a male Han Chinese neonate who presented at birth (0 days) with intrauterine growth restriction, respiratory distress, and feeding difficulties. During follow-up, he developed hearing loss and demonstrated global developmental delay. Clinical examination revealed craniofacial dysmorphism. Trio rWGS was performed in the neonatal period, with results returned within 72 h of sample submission at 23 days of age. Trio rWGS identified a de novo missense variant in the CREBBP gene (c.5570A > C, p.His1857Pro). Sanger sequencing confirmed its absence in both parents, and the variant was classified as likely pathogenic despite no prior documented cases. Based on integrated genetic and clinical findings, a neonatal diagnosis of MKHK-ID4 was established. Following this diagnosis, early targeted interventions were initiated, including hearing aid fitting, enrollment in a comprehensive rehabilitation program, and planning for necessary surgical corrections. Significant developmental improvement was observed at the 15-month follow-up assessment. In this case, rWGS facilitated a neonatal diagnosis of MKHK-ID4 and enabled early multidisciplinary intervention during a critical neurodevelopmental window. This experience suggests that such an approach may contribute to improved developmental outcomes in this rare disorder, though further studies are required to confirm its broader applicability and long-term benefits.
Lignocellulosic biomass can be converted into biofuels and other valuable bioproducts, but it must first undergo physicochemical and enzymatic degradation. Among the various enzymes involved in lignocellulose degradation, thermophilic glycoside hydrolase family 5 (GH5) cellulases have gained significant attention given their ability to sustain enzymatic activity at temperatures exceeding 60 °C. These high temperatures not only accelerate enzymatic reactions, improving reaction rates and process efficiency, but also enhance substrate solubility and reduce the risk of microbial contamination, making them highly valuable for the paper, food, feed, pharmaceutical, and biofuel industries. In this work, we identified five GH5 cellulases with predicted thermophilic properties from termite gut metagenomes and evaluated their structural features using machine-learning classification, comparative structural modeling, interatomic contact analysis, and temperature-dependent flexibility simulations. The candidates, spanning GH5 subfamilies 2, 25, 37, 39, and 40, displayed high structural confidence (pLDDT > 90) and aliphatic indices comparable to those of thermophilic references. Analysis of amino acid composition analysis revealed enrichment in aromatic and charged residues. Hydrophobic contact densities were consistently higher than in mesophilic controls and aligned with thermophilic benchmarks. Temperature-dependent flexibility simulations showed restrained RMSF profiles, more closely resembling the thermophilic reference enzyme than to the mesophilic control. These findings are consistent with a thermophilic profile, pending experimental confirmation, and provide useful insights for the selection and engineering of GH5 cellulases for high-temperature biotechnological applications.
Microscopic colitis (MC) is a colonic inflammatory bowel disease diagnosed via histology. There are no universally accepted guidelines defining treatment goals in MC. Our study evaluated the prognostic significance of histologic normalization in MC. This retrospective cohort study identified patients with histologically confirmed MC who had at least one repeat colonoscopy with available histology. Outcomes included medical therapy use (anti-diarrheals, steroids, mesalamine, and immunosuppressants), hospitalizations, and surgeries (1) prior to or during first repeat colonoscopy or (2) after first repeat colonoscopy. Multivariable adjusted models were created for medical therapy use after first repeat colonoscopy. This study included 380 MC patients. On first repeat colonoscopy, 164 (43.2%) patients normalized by histology and were more likely than those with persistent MC changes to have lymphocytic colitis (56.7% vs 43.3%, P = .036). There were no differences in hospitalization or surgery rates before or after first repeat colonoscopy for patients who normalized and those who did not. When compared to patients with MC at first repeat colonoscopy, those who normalized had statistically significant lower odds of steroids use after their first repeat colonoscopy (OR 0.26; 0.13-0.53) after multivariate adjustment. This association remained significant when restricted to patients with symptoms at first repeat colonoscopy (OR 0.22; 0.08-0.59) but was weaker for patients without symptoms (OR 0.45; 0.16-1.29). In patients with MC, histologic normalization at first repeat colonoscopy was associated with reduced need for corticosteroids on follow-up. The effect was slightly attenuated in asymptomatic patients. Future studies of histologic normalization as a treatment target in MC are warranted. We evaluated the prognostic significance of histologic normalization in microscopic colitis (MC). Persistent histologic MC activity was associated with a more active subsequent disease course, supporting potential for treatment to histologic remission as a mechanism to reduce relapses in MC.
The sustainable management and valorization of industrial solid wastes remain a critical challenge for environmental protection and resource efficiency, particularly under aggressive service conditions that may compromise long-term stability. In this study, a red mud-coal metakaolin geopolymer was developed as a waste-derived material and its degradation behavior under saline corrosion and wet-dry cycling was systematically investigated to evaluate its environmental adaptability and service reliability. Changes in mechanical properties, permeability and multiscale pore structure were monitored. The long-term performance evolution was further assessed using a Gamma process model. The results show that wet-dry cycling significantly accelerates material degradation. Although the residual mass remains nearly constant (∼99.8%), the dynamic elastic modulus and compressive strength decrease by 4.17% and 5.15%, indicating that deterioration is more sensitively reflected by mechanical and transport properties than by mass loss. The continuously increasing permeability coefficient suggests enhanced pore connectivity. Microstructural analyses reveal a transition from a dense gel matrix to a cracked and porous framework driven by gel dissolution. Nuclear magnetic resonance results further confirm a gradual increase in total porosity (from 11.57% to 12.13%). Gamma process model indicates that dynamic elastic modulus and compressive strength reach their thresholds at approximately 30 and 34 cycles, while permeability requires far more cycles to reach its threshold. These findings provide critical insights into the durability and degradation mechanisms of red mud-based geopolymers in saline environments, offering practical implications for risk assessment and lifecycle management of sustainable construction materials derived from industrial wastes in diverse environmental conditions.
The neutrophil CD64 (nCD64) index is a potent biomarker for infectious diseases; however, the lack of standardized reference intervals (RIs) limits its clinical utility. This study aimed to establish and validate reference intervals (RIs) for the nCD64 index specifically for the Guangxi population using flow cytometry. Cross-sectional study. Conducted in Guangxi, China. A total of 494 healthy adults (aged 18-83 years) were enrolled. Peripheral blood nCD64 expression was measured via flow cytometry. Reference intervals were determined using the non-parametric 95th percentile method (2.5th-97.5th) per CLSI EP28-A3c guidelines. Validation was performed in an independent cohort (n=30). The primary outcome was the 95% reference interval for the nCD64 index. Secondary outcomes included correlations between nCD64 index and sex, age, BMI, and primary hematological parameters. 494 healthy adults for establishment, plus 30 independent subjects for validation. No clinically significant differences in the nCD64 index were found between sexes or across age groups, and partitioning was not required. The nCD64 index exhibited a skewed distribution. Although sex showed a weak positive correlation with nCD64 expression (r=.115, P=.011), the standard normal deviation test (z<z*) indicated no requirement for sex-specific partitioning. No significant correlations were observed between nCD64 and age, BMI, or primary hematological parameters. The established 95% RI was .08-0.94, with the 90% confidence intervals (CI) for the lower and upper limits were .08-.09 and .92-1.04. Validation confirmed the RI's reliability, with 97% (29/30) of results falling within the range. We established a robust RI (.08-.94) for the nCD64 index in the Guangxi population, which remained consistent across age and sex groups. This provides a standardized baseline for the diagnosis of inflammatory and infectious conditions in Southern China. The study was limited to a single regional population (Guangxi) and did not include pediatric or pregnant populations. Additionally, potential confounding from subclinical inflammation or undiagnosed chronic infections cannot be completely excluded despite strict enrollment criteria.
Constructing fast and accurate surrogate models is a key ingredient for making robust predictions in many topics. We introduce a new model, the multiparameter eigenvalue problem (MEP) emulator. The new method connects emulators and can make predictions directly from observables to observables. We show that the MEP emulator can be trained with data from eigenvector continuation and parametric matrix model emulators. A simple simulation on a one-dimensional lattice confirms the performance of the MEP emulator. Using ^{28}O as an example, we also demonstrate that the predictive probability distribution of the target observables can be straightforwardly obtained through the new emulator.
Amid increasing social pressures, the importance of psychological resilience as a key resource for stress coping has become prominent. Although exercise is considered a potential means to enhance resilience, a systematic quantitative assessment of moderating factors influencing its effect is lacking. This meta-analysis aimed to systematically evaluate the effect of exercise interventions on enhancing psychological resilience and explore the moderating roles of intervention duration, age, and study design. Following PRISMA guidelines, relevant databases were searched up to January 2026. Randomized controlled trials or quasi-experimental studies were included. Study quality was assessed using standardized tools. Analyses were conducted using a random-effects model, subgroup analyses, and heterogeneity tests. Ten studies were included. Exercise intervention had a significant positive effect on psychological resilience (pooled SMD = 0.49, 95% CI: 0.33-0.65). Intervention duration was a statistically significant moderator (p = 0.01) that survived Bonferroni correction for multiple subgroup tests (α < sub > adjusted < /sub > = 0.017), with long-term interventions (> 8 weeks, SMD = 0.64) yielding significantly larger effects than short-term interventions (≤ 8 weeks, SMD = 0.30). The intervention was effective across all age groups. Randomized controlled trials yielded a numerically larger effect size (SMD = 0.56) than non-randomized studies (SMD = 0.35), but the subgroup difference was not statistically significant (p = 0.21). No publication bias was detected. Exercise intervention is an effective approach to enhancing psychological resilience. Subgroup analyses confirmed that intervention duration is a statistically significant moderator, with long-term interventions yielding significantly greater benefits. This provides an empirical basis for designing personalized, long-term exercise programs for different populations.
Malignant pericardial effusion as the initial presentation of lung cancer is rare, and its diagnosis can be challenging, particularly when clinical features mimic common infectious or cardiogenic conditions. This case highlights the value of echocardiography and pericardial fluid cytology in identifying occult malignancy in patients with persistent cardiorespiratory symptoms and inconclusive initial workup. It also draws attention to the atypical occurrence of lung adenocarcinoma in a female patient, in whom breast cancer is more commonly associated with malignant pericardial effusion. A 54-year-old Malaysian woman of Chinese ethnicity, presented with a 3-week history of productive cough, low-grade fever, and exertional dyspnea. She was initially treated for community-acquired pneumonia with right parapneumonic effusion. Despite intravenous antibiotics and pigtail drainage of an exudative pleural effusion, her symptoms persisted. Computed tomography pulmonary angiography (CTPA), performed to rule out pulmonary embolism, revealed subsegmental emboli and circumferential pericardial effusion with reflux into the inferior vena cava. Echocardiography confirmed tamponade physiology despite normotension. Urgent pericardiocentesis drained 600 mL of hemorrhagic fluid, with cytology revealing malignant adenocarcinoma cells. PET-CT subsequently identified a hypermetabolic right upper lobe lung mass with widespread metastases to the pleura, pericardium, bones, adrenal glands, and subcutaneous tissues. She was referred for further oncologic and respiratory management. This case demonstrates how subacute, normotensive cardiac tamponade can present subtly and be easily overlooked. In patients with persistent tachycardia and unexplained effusions, particularly when initial imaging and pleural fluid cytology are inconclusive, early echocardiographic assessment and pericardial fluid analysis are essential. Multidisciplinary collaboration enabled timely identification of an underlying malignancy, reinforcing the need for a high index of suspicion when evaluating hemorrhagic pericardial effusions.
Black women in the United States experience disproportionately high breast cancer mortality and have high rates of comorbid hypertension; however, the associations of hypertension and antihypertensive medication use with breast cancer survival are unclear. We examined these associations among 2474 Black Women's Health Study participants with invasive breast cancer. Hypertension and antihypertensive medication use were assessed biennially, and breast cancer diagnoses were confirmed through medical records and cancer registries. We used Cox proportional hazards models, adjusted for clinical and lifestyle factors and cancer treatment, to estimate hazard ratios (HR) for breast cancer-specific death. In the full study population, the HR for untreated hypertension compared to no hypertension was 1.17 (95% CI = 0.75-1.82), while the HR for treated hypertension compared to no hypertension was 0.81 (95% CI = 0.60-1.10). For ER+ cases, there was no association between untreated hypertension and breast cancer specific-death (HR = 0.96, 95% CI = 0.50-1.82), but a strong inverse association between treated hypertension and breast cancer-specific death (HR = 0.53, 95% CI = 0.34-0.83). In contrast, for ER- cases, we observed an increased risk of breast cancer specific death among those with untreated hypertension (HR = 2.19, 95% CI = 1.09-4.39), but there was little evidence of an association with treated hypertension (HR = 1.32, 95% CI = 0.80-2.19). Overall, our findings indicate that Black breast cancer patients with hypertension have better survival when their hypertension is treated, possibly due to regular healthcare engagement or the tumor suppressing actions of antihypertensive medications. Randomized trials are needed to establish causality and inform optimal cardiovascular management in oncology.
This study aimed to investigate the clinical utility of the C-reactive protein/albumin ratio (CAR) and the neutrophil/lymphocyte ratio (NLR) in evaluating the severity of sepsis in pediatric patients. A retrospective cohort study was conducted involving 174 pediatric patients hospitalized between June 2022 and November 2025. Sepsis and septic shock were defined according to the 2024 Phoenix criteria. Patients were stratified into a sepsis group (n = 123) and a septic shock group (n = 51). CAR and NLR were calculated from blood samples collected within 24 h of admission. A two-sided p < 0.05 was considered statistically significant. Independent associated factors for septic shock were identified using binary logistic regression analysis. Receiver operating characteristic (ROC) curves were constructed, and the area under the curve (AUC) was calculated to evaluate the diagnostic performance of CAR, NLR, and other relevant biomarkers.The study was conducted in accordance with the STROBE guidelines. Univariate analysis revealed significantly elevated white blood cell (WBC) count, CAR, and NLR levels in the septic shock group compared to the sepsis group (all p < 0.05). Binary logistic regression analysis confirmed that elevated CAR (OR = 2.893, p < 0.001) and NLR (OR = 1.232, p < 0.001) were independent associated factors for progression to septic shock. ROC curve analysis demonstrated that a model combining CAR and NLR exhibited superior discriminative performance compared to either biomarker alone, with a higher AUC (0.802), sensitivity (74.50%), and specificity (74.80%). CAR and NLR appear to be significant independent biomarkers for assessing severity and predicting septic shock in children with sepsis. The combination of CAR and NLR provides improved predictive accuracy compared with either marker alone, suggesting its potential utility in guiding early clinical decisions.