Validation of the parent global assessment as a health-related quality of life measure in juvenile idiopathic arthritis: results from ReACCh-Out.

OBJECTIVES: To (i) validate the JIA parent global assessment (parent global) as a health-related quality of life (HRQoL) instrument; (ii) evaluate measurement properties of accepted HRQoL measures relative to those of the parent global; and (iii) assess causal pathways determining parent global scores. METHODS: Data from the Research in Arthritis in Canadian Children emphasizing outcomes (ReACCh-Out) cohort were used. Measurement properties were assessed in 344 patients at enrolment and 6 months later. Causal pathways were tested by structural equation modelling to understand root causes and mediators leading to parent global scores. RESULTS: Construct validity was supported by Spearman correlations of 0.53-0.70 for the parent global with the Juvenile Arthritis Quality of Life Questionnaire, Quality of My Life health scale (HRQoML), Pediatric Quality of Life Inventory (PedsQL)-Parent, and Child Health Questionnaire (CHQ)-Physical. Exceptions were PedsQL-Child (0.44) and CHQ-Psychosocial (0.31). Correlations were lower (0.14-0.49) with disease activity measures (physician global assessment of disease activity, active joint count, ESR). Responsiveness of the parent global to improvement according to parent ratings (0.51) was acceptable and within the range (0.32-0.71) of that of other measures. Reliability estimates and measurement errors for all measures were unsatisfactory, likely due to the prolonged time between assessments. Causal pathways for the parent global matched those previously reported for HRQoML. CONCLUSIONS: Our results offer support for the parent global as a valid measure of HRQoL for JIA. If confirmed, existing studies using the parent global may be re-interpreted, enhancing our knowledge of HRQoL in children with JIA.

Causal pathways to health-related quality of life in children with juvenile idiopathic arthritis: results from the ReACCh-Out cohort.

OBJECTIVE: Structural equation modelling was applied to data from the Research in Arthritis in Canadian Children emphasizing Outcomes (ReACCh-Out) cohort to help elucidate causal pathways to decreased health-related quality of life (HRQoL) in children with JIA. METHODS: Based on published literature and clinical plausibility, a priori models were constructed with explicit root causes (disease activity, treatment intensity) and mediators (pain, disease symptoms, functional impairments) leading to HRQoL [measured by the Quality of my Life (QoML) scale and the Juvenile Arthritis Quality of Life Questionnaire (JAQQ)] at five disease stages: (i) diagnosis, (ii) 3-9 months after diagnosis, (iii) flare, (iv) remission on medications, (v) remission off medications. Following structural equation modelling, a posteriori models were selected based on data fit and clinical plausibility. RESULTS: We included 561, 887, 137, 186 and 182 patients at each stage, respectively. In a posteriori models for active disease stages, paths from disease activity led through pain, functional impairments, and disease symptoms, directly or through restrictions in participation, to decreased QoML scores. Treatment intensity had detrimental effects through psychosocial domains; while treatment side effects had a lesser role. Pathways were similar for QoML and JAQQ, but JAQQ models provided greater specificity. Models for remission stages were not supported by the data. CONCLUSION: Our findings support disease activity and treatment intensity as being root causes of decreased HRQoL in children with JIA, with pain, functional impairments, and participation restrictions being mediators for disease activity; they support psychosocial effects and side effects as being mediators for treatment intensity.

Ensemble machine learning to evaluate the in vivo acute oral toxicity and in vitro human acetylcholinesterase inhibitory activity of organophosphates.

Organophosphates (OPs) are hazardous chemicals widely used in industry and agriculture. Distribution of their residues in nature causes serious risks to humans, animals, and plants. To reduce hazards from OPs, quantitative structure-activity relationship (QSAR) models for predicting their acute oral toxicity in rats and mice and inhibition constants concerning human acetylcholinesterase were developed according to the bioactivity data of 456 unique OPs. Based on robust, two-dimensional molecular descriptors and quantum chemical descriptors, which accurately reflect OP electronic structures and reactivities, the influences of eight machine-learning algorithms on the prediction performance of the QSAR models were explored, and consensus QSAR models were constructed. Several strict model validation indices and the results of applicability domain evaluations show that the established consensus QSAR models exhibit good robustness, practical prediction abilities, and wide application scopes. Poor correlation was observed between acute oral toxicity at the mammalian level and the inhibition constants at the molecular level, indicating that the acute toxicity of OPs cannot be evaluated only by the experimental data of enzyme inhibitory activity, their toxicokinetic characteristics must also be considered. The constructed QSAR models described herein provide rapid, theoretical assessment of the bioactivity of unstudied or unknown OPs, as well as guidance for making decisions regarding their regulation.

Non-Enzymatic Glucose Sensing Based on Incorporation of Carbon Nanotube into Zn-Co-S Ball-in-Ball Hollow Sphere.

Zn-Co-S ball-in-ball hollow sphere (BHS) was successfully prepared by solvothermal sulfurization method. An efficient strategy to synthesize Zn-Co-S BHS consisted of multilevel structures by controlling the ionic exchange reaction was applied to obtain great performance electrode material. Carbon nanotubes (CNTs) as a conductive agent were uniformly introduced with Zn-Co-S BHS to form Zn-Co-S BHS/CNTs and expedited the considerable electrocatalytic behavior toward glucose electro-oxidation in alkaline medium. In this study, characterization with scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), and X-ray diffraction (XRD) was used for investigating the morphological and physical/chemical properties and further evaluating the feasibility of Zn-Co-S BHS/CNTs in non-enzymatic glucose sensing. Electrochemical methods (cyclic voltammetry (CV) and chronoamperometry (CA)) were performed to investigate the glucose sensing performance of Zn-Co-S BHS/CNTs. The synergistic effect of Faradaic redox couple species of Zn-Co-S BHS and unique conductive network of CNTs exhibited excellent electrochemical catalytic ability towards the glucose electro-oxidation, which revealed linear range from 5 to 100 µM with high sensitivity of 2734.4 µA mM-1 cm-2, excellent detection limit of 2.98 µM, and great selectivity in the presence of dopamine, uric acid, ascorbic acid, and fructose. Thus, Zn-Co-S BHS/CNTs would be expected to be a promising material for non-enzymatic glucose sensing.

[Predictive value of Pv-aCO2/Ca-vO2 combined blood lactate concentration for primary peritonitis-related septic shock in children].

OBJECTIVE: To investigate the prognostic value of the ratio of veno-arterial carbon dioxide partial pressure difference to arterio-venous oxygen content difference (Pv-aCO2/Ca-vO2) in children with primary peritonitis-related septic shock. METHODS: A retrospective study was conducted. Sixty-three children with primary peritonitis-related septic shock admitted to department of intensive care unit of the Children's Hospital Affiliated to Xi'an Jiaotong University from December 2016 to December 2021 were enrolled. The 28-day all-cause mortality was the primary endpoint event. The children were divided into survival group and death group according to the prognosis. The baseline data, blood gas analysis, blood routine, coagulation, inflammatory status, critical score and other related clinical data of the two groups were statistics. The factors affecting the prognosis were analyzed by binary Logistic regression, and the predictability of risk factors were tested by the receiver operator characteristic curve (ROC curve). The risk factors were stratified according to the cut-off, Kaplan-Meier survival curve analysis compared the prognostic differences between the groups. RESULTS: A total of 63 children were enrolled, including 30 males and 33 females, the average age (5.6±4.0) years old, 16 cases died in 28 days, with mortality was 25.4%. There were no significant differences in gender, age, body weight and pathogen distribution between the two groups. The proportion of mechanical ventilation, surgical intervention, vasoactive drug application, and procalcitonin, C-reactive protein, activated partial thromboplastin time, serum lactate (Lac), Pv-aCO2/Ca-vO2, pediatric sequential organ failure assessment, pediatric risk of mortality III in the death group were higher than those in the survival group. Platelet count, fibrinogen, mean arterial pressure were lower than those in the survival group, and the differences were statistically significant. Binary Logistic regression analysis showed that Lac and Pv-aCO2/Ca-vO2 were independent risk factors affecting the prognosis of children [odds ratio (OR) and 95% confidence interval (95%CI) were 2.01 (1.15-3.21), 2.37 (1.41-3.22), respectively, both P < 0.01]. ROC curve analysis showed that the area under curve (AUC) of Lac, Pv-aCO2/Ca-vO2 and their combination were 0.745, 0.876 and 0.923, the sensitivity were 75%, 85% and 88%, and the specificity were 71%, 87% and 91%, respectively. Risk factors were stratified according to cut-off, and Kaplan-Meier survival curve analysis showed that the 28-day cumulative probability of survival of Lac ≥ 4 mmol/L group was lower than that in Lac < 4 mmol/L group [64.29% (18/28) vs. 82.86% (29/35), P < 0.05]. Pv-aCO2/Ca-vO2 ≥ 1.6 group 28-day cumulative probability of survival was less than Pv-aCO2/Ca-vO2 < 1.6 group [62.07% (18/29) vs. 85.29% (29/34), P < 0.01]. After a hierarchical combination of the two sets of indicator variables, the 28-day cumulative probability of survival of Pv-aCO2/Ca-vO2 ≥ 1.6 and Lac ≥ 4 mmol/L group significantly lower than that of the other three groups (Log-rank test, χ2 = 7.910, P = 0.017). CONCLUSIONS: Pv-aCO2/Ca-vO2 combined with Lac has a good predictive value for the prognosis of children with peritonitis-related septic shock.

A Preliminary Study on the Improvement of Gangue/Tailing Cemented Fill by Bentonite: Flow Properties, Mechanical Properties and Permeability.

Backfill mining has significant advantages in safe mining, solid waste utilization and ecological environmental protection, but solid waste materials (tailings, gangue and coal gasification slag, etc.), as derivative residues of the chemical and metallurgical industries, contain a large number of heavy metal elements, which is posing great challenges to the underground environment after backfill. In order to study the feasibility of bentonite for reducing the permeability of gangue/tailing sand cemented backfill body, relevant tests were carried out from the basic performance index, flow performance and mechanical properties of paste backfill materials. The test results show that bentonite has a significant effect on the water secretion rate of cemented fillers, and also promotes the improvement of slump and diffusion diameter of backfill slurry. The enhancement effect of mechanical properties in the early stage is not obvious, mainly concentrated in the middle and late stages of specimen curing. With the increase of bentonite content, the 28-day uniaxial compressive strength increased from 7.1 MPa and 7.9 MPa to 8.7 MPa and 9.0 MPa, respectively. Bentonite is filled between the pores of the cemented backfill with its fine particles and water swelling, which can reduce the porosity and permeability of the gangue and tailings cemented backfill. Therefore, on the premise of satisfying the flow and mechanical properties of paste backfill, bentonite can be used to improve the permeability of cemented backfill and reduce the leaching and migration of heavy metal ions.

Construction and validation of a prognostic nomogram for predicting cancer-specific survival in patients with intermediate and advanced colon cancer after receiving surgery and chemotherapy.

BACKGROUND: Existing predictive models often focus solely on overall survival (OS), neglecting the bias that other causes of death might introduce into survival rate predictions. To date, there is no strict predictive model established for cancer-specific survival (CSS) in patients with intermediate and advanced colon cancer after receiving surgery and chemotherapy. METHODS: We extracted the data from the Surveillance, Epidemiology, and End Results (SEER) database on patients with stage-III and -IV colon cancer treated with surgery and chemotherapy between 2010 and 2015. The cancer-specific survival (CSS) was assessed using a competitive risk model, and the associated risk factors were identified via univariate and multivariate analyses. A nomogram predicting 1-, 3-, and 5-year CSS was constructed. The c-index, area under the curve (AUC), and calibration curve were adopted to assess the predictive performance of the model. Additionally, the model was externally validated. RESULTS: A total of 18 risk factors were identified by univariate and multivariate analyses for constructing the nomogram. The AUC values of the nomogram for the 1-, 3-, and 5-year CSS prediction were 0.831, 0.842, and 0.848 in the training set; 0.842, 0.853, and 0.849 in the internal validation set; and 0.815, 0.823, and 0.839 in the external validation set. The C-index were 0.826 (se: 0.001), 0.836 (se: 0.002) and 0.763 (se: 0.013), respectively. Moreover, the calibration curve showed great calibration. CONCLUSION: The model we have constructed is of great accuracy and reliability, and can help physicians develop treatment and follow-up strategies that are beneficial to the survival of the patients.

Preparation of lightweight daisy-like magnetic molecularly imprinted polymers via etching synergized template immobilization for enhanced rapid detection of trace 17ß-estradiol.

17ß-estradiol (E2), as one of the pharmaceutical and personal care product, frequently contaminates environmental water as estrogen pollutant and possesses great risk to human survival as well as the sustainable development of the ecosystem. Herein, to achieve an effective adsorbent system for the selective removal of E2 from the environmental water, Fe3O4 nanoparticles are subjected to chemical etching to reduce the overall mass and then employed as carriers to prepare a novel type of lightweight daisy-like magnetic molecularly imprinted polymers (LD-MMIPs) adopting template immobilization strategy. The LD-MMIPs based etched magnetic nanoparticles not only exhibit light mass but also have plentiful imprinted sites in the etched channels, which significantly increases the adsorption capacity for E2. The daisy-like LD-MMIPs own strong magnetic responsiveness, well crystallinity, fast binding kinetics, high adsorption amount, and excellent selectivity. Moreover, combining with HPLC, the LD-MMIPs as adsorbents have been successfully used to specifically recognize and detect trace E2 in environmental water. Thus, the proposed LD-MMIPs with high adsorption capacity hold great potential in monitoring water pollution. Additionally, this work also provides an alternative strategy for improving the adsorption capacity of magnetic molecularly imprinted polymers through a convenient chemical etching technology.

Pan-cancer analysis reveals DDX21 as a potential biomarker for the prognosis of multiple tumor types.

Background: DExD-box helicase 21 (DDX21) is an essential member of the RNA helicase family. DDX21 is involved in the carcinogenesis of various malignancies, but there has been no comprehensive research on its involvement in different types of cancer. Method: This study used TCGA, CPTAC, GTEx, GEO, FANTOM5, BioGRID, TIMER2, GEPIA2, cBioPortal, STRING, and Metascape databases and Survival ROC software to evaluate DDX21 gene expression, protein expression, immunohistochemistry, gene mutation, immune infiltration, and protein phosphorylation in 33 TCGA tumor types, as well as the prognostic relationship between DDX21 and different tumors, by survival analysis and similar gene enrichment analysis. Furthermore, Cell Counting Kit-8 (CCK-8) and Transwell studies were employed to assess the effect of DDX21 expression on lung adenocarcinoma (LUAD) cell proliferation and migration. Result: The DDX21 gene was highly expressed in most cancers, and overexpression was associated with poor overall survival (OS) and disease-free survival (DFS). DDX21 mutations were most common in uterine corpus endometrial carcinoma (UCEC; >5%), and DDX21 expression was positively correlated with the degree of infiltration of CAF and CD8+ cells in several tumor types. Numerous genes were co-expressed with DDX21. Gene enrichment analysis revealed close links between DDX21, RNA metabolism, and ribosomal protein production. In vitro analysis of LUAD cells showed that DDX21 expression was positively correlated with cell proliferation and migration capacity, consistent with prior bioinformatics studies. Conclusions: DDX21 is overexpressed in a variety of cancers, and overexpression in some cancers is associated with poor prognosis. Immune infiltration and DDX21-related gene enrichment analyses indicated that DDX21 may affect cancer development through mechanisms that regulate tumor immunity, RNA metabolism, and ribosomal protein synthesis. This pan-cancer study revealed the prognostic value and the oncogenic role of DDX21.

Construction of a Label-Free Electrochemical Immunosensor Based on Zn-Co-S/Graphene Nanocomposites for Carbohydrate Antigen 19-9 Detection.

Nanocomposites of the binary transition metal sulfide Zn-Co-S/graphene (Zn-Co-S@G) were synthesized through a one-step hydrothermal method. They may be useful in the construction of an electrochemical immunosensor for carbohydrate antigen 19-9 (CA19-9) detection. Zn-Co-S dot-like nanoparticles uniformly covered the surface of graphene to form an interconnected conductive network, ensuring strong interaction between transition metal sulfide and graphene, which can expose numerous electroactive sites leading to the improvement of the amplified electrochemical signal toward a direct reduction of H2O2. Thus, the construction of an electrochemical immunosensor using Zn-Co-S@G nanocomposites showed outstanding sensing properties for detecting CA19-9. The constructed electrochemical immunosensor exhibited a good linear relationship in the range of 6.3 U·mL-1-300 U·mL-1, with the limit of detection at 0.82 U·mL-1, which makes it a promising candidate for an electrochemical immunosensor.

Quantitative structure-toxicity relationship model for acute toxicity of organophosphates via multiple administration routes in rats and mice.

Organophosphates (OPs) are highly toxic compounds, with widespread application in agricultural and chemical industries, whose introduction into the environment poses serious hazards to humans and ecological systems. To assess and ultimately mitigate these hazards, this study predicted the acute toxicity of OPs according to their chemical structure and administration route. The acute toxicity data of 161 OPs in two species via six different administration routes were manually collected and used to develop a series of quantitative structure-toxicity relationship (QSTR) models with robust and practical predictive abilities. The random forest algorithm was used to develop the models, employing both quantum chemical and two-dimensional descriptors according to OECD guidelines. Correlation results and feature similarities indicated that whereas acute toxicity data from rats and mice via the same administration route were combinable for modeling, data from different routes were not. Six QSTR models for each route in a single species and two QSTR models for a single route in the two species were constructed, achieving practical predictive performance. Despite significant variances in their datasets, the prediction models could predict the acute toxicity of novel or unknown OPs, realize rapid assessment, and provide guidance for regulatory decisions to reduce the hazards of OPs.

Determination of Construction Parameters of Porous Ultra-Thin Overlays Based on Laboratory Compaction Studies.

To address the severe distresses of asphalt pavement, a new type of pavement maintenance treatment, porous ultra-thin overlay (PUTO) with small particle size was proposed. The PUTO has a thickness of 1.5-2.5 cm and a large void ratio of 18-25%. As a newly asphalt mixture, the structure characteristics differ from poor traditional pavement. Therefore, it is necessary to investigate the fabrication schemes in laboratory and on-site, respectively. In this study, the optimal fabrication schemes, including compaction temperature and number of blows of PUTO were determined based on Cantabro test and volumetric parameters. Then, the corresponding relationship between laboratory and on-site compaction work was then established based on the energy equivalent principle. On this basis, the numbers of on-site rolling passes and the combination method were calculated. The results show that increased compaction temperature and number of blows reduce the height and enhance the compaction of the Marshall sample. With the same temperature and number of blows, the raveling resistance of coarse gradation, Pavement Asphalt Concrete-1 (PAC-1) is better than that of fine gradation, Pavement Asphalt Concrete-2 (PAC-2), and the increased asphalt viscosity significantly improves the raveling resistance of the asphalt mixture. To ensure the scattering resistance and volumetric characteristic, the initial compaction temperature of the PAC-1 and PAC-2 should not be lower than 150 °C and 165 °C, respectively. Then, the laboratory compaction work and on-site compaction work were calculated and converted based on the principle of energy equivalence. Consequently, the on-site compaction combination of rolling machines for four asphalt mixtures was determined. According to the volumetric parameters, the paving test section proved that the construction temperature and the on-site rolling combination determined by laboratory tests are reasonable, and ultra-thin overlay has good structural stability, drainage, and skid resistance.