ABSTRACT
Inaccurate or cumbersome clinical pathogen diagnosis between Gram-positive bacteria (G+) and Gram-negative (G-) bacteria lead to delayed clinical therapeutic interventions. Microelectrode-based electrochemical sensors exhibit the significant advantages of rapid response and minimal sample consumption, but the loading capacity and discrimination precision are weak. Herein, we develop reversible fusion-fission MXene-based fiber microelectrodes for G+/G- bacteria analysis. During the fissuring process, the spatial utilization, loading capacity, sensitivity, and selectivity of microelectrodes were maximized, and polymyxin B and vancomycin were assembled for G+/G- identification. The surface-tension-driven reversible fusion facilitated its reusability. A deep learning model was further applied for the electrochemical impedance spectroscopy (EIS) identification in diverse ratio concentrations of G+ and G- of (1:100-100:1) with higher accuracy (>93%) and gave predictable detection results for unknown samples. Meanwhile, the as-proposed sensing platform reached higher sensitivity toward E. coli (24.3 CFU/mL) and S. aureus (37.2 CFU/mL) in 20 min. The as-proposed platform provides valuable insights for bacterium discrimination and quantification.
Subject(s)
Microelectrodes , Gram-Positive Bacteria/isolation & purification , Gram-Negative Bacteria/isolation & purification , Escherichia coli/isolation & purification , Staphylococcus aureus/isolation & purification , Electrochemical Techniques/instrumentation , Vancomycin/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/analysis , Polymyxin B/chemistry , Polymyxin B/pharmacology , Dielectric SpectroscopyABSTRACT
Diabetic nephropathy (DN) is an important cause of death in diabetes patients, which is mainly due to its complex pathogenesis. Here, we explored the role of N6-methyladenosine (m6A) RNA methylation in DN development. Renal tubular epithelial cells from DN patients and experimental DN mice treated with streptozotocin (STZ) exhibited a considerable increase in METTL14 and WTAP expression as well as overall m6A methylation. Knocking down the expression of METTL14 and WTAP inhibited the migration and proliferation of tubular epithelial cells. MeRIP-seq analysis of the renal tissues of DN patients revealed that the genes with elevated m6A methylation were concentrated in the Wnt/ß-Catenin signaling pathway. Dickkopf homolog 3 (DKK3) was screened out as the gene with the most significant increase in m6A methylation. In addition, the expression change pattern of DKK3 under DN circumstances is in line with those of METTL14 and WTAP. DKK3's m6A methylation sites were confirmed to be located in the 3'UTR region, which is how METTL14 and WTAP improved DKK3's mRNA stability. Finally, YTHDF1, a m6A reader, was demonstrated to recognize m6A-methylated DKK3 and promote DKK3 expression.
ABSTRACT
Existing methods for differential network analysis could only infer whether two networks of interest have differences between two groups of samples, but could not quantify and localize network differences. In this work, a novel method, permutation-based Network True Discovery Proportions (NetTDP), is proposed to quantify the number of edges (correlations) or nodes (genes) for which the co-expression networks are different. In the NetTDP method, we propose an edge-level statistic and a node-level statistic, and detect true discoveries of edges and nodes in the sense of differential co-expression network, respectively, by the permutation-based sumSome method. Furthermore, the NetTDP method could further localize the differences by inferring the TDPs for edge or gene subsets of interest, which can be selected post hoc. Our NetTDP method allows inference on data-driven modules or biology-driven gene sets, and remains valid even when these sub-networks are optimized using the same data. Experimental results on both simulation data sets and five real data sets show the effectiveness of the proposed method in inferring the quantification and localization of differential co-expression networks. The R code is available at https://github.com/LiminLi-xjtu/NetTDP.
Subject(s)
Computational Biology , Gene Regulatory Networks , Computational Biology/methods , Algorithms , Computer SimulationABSTRACT
MOTIVATION: Survival analysis is an important tool for modeling time-to-event data, e.g. to predict the survival time of patient after a cancer diagnosis or a certain treatment. While deep neural networks work well in standard prediction tasks, it is still unclear how to best utilize these deep models in survival analysis due to the difficulty of modeling right censored data, especially for multi-omics data. Although existing methods have shown the advantage of multi-omics integration in survival prediction, it remains challenging to extract complementary information from different omics and improve the prediction accuracy. RESULTS: In this work, we propose a novel multi-omics deep survival prediction approach by dually fused graph convolutional network (GCN) named FGCNSurv. Our FGCNSurv is a complete generative model from multi-omics data to survival outcome of patients, including feature fusion by a factorized bilinear model, graph fusion of multiple graphs, higher-level feature extraction by GCN and survival prediction by a Cox proportional hazard model. The factorized bilinear model enables to capture cross-omics features and quantify complex relations from multi-omics data. By fusing single-omics features and the cross-omics features, and simultaneously fusing multiple graphs from different omics, GCN with the generated dually fused graph could capture higher-level features for computing the survival loss in the Cox-PH model. Comprehensive experimental results on real-world datasets with gene expression and microRNA expression data show that the proposed FGCNSurv method outperforms existing survival prediction methods, and imply its ability to extract complementary information for survival prediction from multi-omics data. AVAILABILITY AND IMPLEMENTATION: The codes are freely available at https://github.com/LiminLi-xjtu/FGCNSurv.
Subject(s)
Multiomics , Neural Networks, Computer , HumansABSTRACT
MOTIVATION: The development of single-cell RNA sequencing (scRNA-seq) technology makes it possible to study the cellular dynamic processes such as cell cycle and cell differentiation. Due to the difficulties in generating genuine time-series scRNA-seq data, it is of great importance to computationally infer the pseudotime of the cells along differentiation trajectory based on their gene expression patterns. The existing pseudotime prediction methods often suffer from the high level noise of single-cell data, thus it is still necessary to study the single-cell trajectory inference methods. RESULTS: In this study, we propose a branched local tangent space alignment (BLTSA) method to infer single-cell pseudotime for multi-furcation trajectories. By assuming that single cells are sampled from a low-dimensional self-intersecting manifold, BLTSA first identifies the tip and branching cells in the trajectory based on cells' local Euclidean neighborhoods. Local coordinates within the tangent spaces are then determined by each cell's local neighborhood after clustering all the cells to different branches iteratively. The global coordinates for all the single cells are finally obtained by aligning the local coordinates based on the tangent spaces. We evaluate the performance of BLTSA on four simulation datasets and five real datasets. The experimental results show that BLTSA has obvious advantages over other comparison methods. AVAILABILITY AND IMPLEMENTATION: R codes are available at https://github.com/LiminLi-xjtu/BLTSA. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
Subject(s)
Gene Expression Profiling , Software , Gene Expression Profiling/methods , Single-Cell Analysis/methods , Computer Simulation , Cell Differentiation , Sequence Analysis, RNA/methodsABSTRACT
Short beak and dwarfism syndrome (SBDS) is attributed to Novel Goose Parvovirus (NGPV), which has inflicted significant economic losses on farming in China. Despite its significant impact, limited research has been conducted on the pathogenesis of this disease. The SD strain, a parvovirus variant isolated from ducks in Shandong province, was identified and characterized in our study. Phylogenetic analysis and sequence comparisons confirmed the classification of the SD strain as a member of NGPV. Based on this information, we established an animal model of SBDS by inoculating Cherry Valley ducks with the SD strain. Our findings indicate that infection with the SD strain leads to a reduction in body weight, beak length, width, and tibia length. Notably, significant histopathological alterations were observed in the thymus, spleen, and intestine of the infected ducks. Furthermore, the SD strain induces bone disorders and inflammatory responses. To evaluate the impact of NGPV on intestinal homeostasis, we performed 16S rDNA sequencing and gas chromatography to analyze the composition of intestinal flora and levels of short-chain fatty acids (SCFAs) in the cecal contents. Our findings revealed that SD strain infection induces dysbiosis in cecal microbial and a decrease in SCFAs production. Subsequent analysis revealed a significant correlation between bacterial genera and the clinical symptoms in NGPV SD infected ducks. Our research providing novel insights into clinical pathology of NGPV in ducks and providing a foundation for the research of NGPV treatment targeting gut microbiota.
Subject(s)
Ducks , Parvoviridae Infections , Phylogeny , Poultry Diseases , Animals , Ducks/virology , Parvoviridae Infections/veterinary , Parvoviridae Infections/virology , Parvoviridae Infections/pathology , Poultry Diseases/virology , Poultry Diseases/pathology , China , Parvovirinae/genetics , Parvovirinae/isolation & purification , Parvovirinae/pathogenicity , Gastrointestinal Microbiome , Intestines/pathology , Intestines/virology , RNA, Ribosomal, 16S/genetics , Disease Models, Animal , Dysbiosis/virology , Dysbiosis/veterinary , Fatty Acids, Volatile/metabolism , Geese/virology , Spleen/pathology , Spleen/virology , Beak/virology , Beak/pathologyABSTRACT
BACKGROUND: Compensation for medical damage liability disputes (CMDLD) seriously hinders the healthy development of hospitals and undermines the harmony of the doctor-patient relationships (DPR). Risk management in the DPR has become an urgent issue of the day. The study aims to provide a comprehensive description of CMDLD in China and explore its influencing factors, and make corresponding recommendations for the management of risks in the DPR. METHODS: This study extracted data from the China Judgment Online - the official judicial search website with the most comprehensive coverage. Statistical analysis of 1,790 litigation cases of medical damage liability disputes (COMDLD) available from 2015 to 2021. RESULTS: COMDLD generally tended to increase with the year and was unevenly distributed by regions; the compensation rate was 52.46%, the median compensation was 134,900 yuan and the maximum was 2,234,666 yuan; the results of the single factor analysis showed that there were statistically significant differences between the compensation for different years, regions, treatment attributes, and trial procedures (P < 0.05); the correlation analysis showed that types of hospitals were significantly negatively associated with regions (R=-0.082, P < 0.05); trial procedures were significantly negatively correlated with years (R=-0.484, P < 0.001); compensat- ion was significantly positively correlated with years, regions, and treatment attributes (R = 0.098-0.294, P < 0.001) and negatively correlated with trial procedures (R=-0.090, P < 0.01); regression analysis showed that years, treatment attributes, and regions were the main factors affecting the CMDLD (P < 0.05). CONCLUSIONS: Years, regions, treatment attributes, and trial procedures affect the outcome of CMDLD. This paper further puts forward relevant suggestions and countermeasures for the governance of doctor-patient risks based on the empirical results. Including rational allocation of medical resources to narrow the differences between regions; promoting the expansion and sinking of high-quality resources to improve the level of medical services in hospitals at all levels; and developing a third-party negotiation mechanism for medical disputes to reduce the cost of medical litigation.
Subject(s)
Liability, Legal , Malpractice , Physician-Patient Relations , Risk Management , Humans , China , Malpractice/legislation & jurisprudence , Malpractice/statistics & numerical data , Malpractice/economics , Compensation and Redress/legislation & jurisprudence , Dissent and Disputes/legislation & jurisprudence , Empirical ResearchABSTRACT
Xanthine-functionalized molybdenum oxide nanodots (X-MoO3-x NDs) with peroxidase (POD)-like activity were developed for selective, sensitive, and facile colorimetric quantification of xanthine oxidase (XO). Xanthine functionalization can not only be favorable for the successful nanozyme preparation, but also for the specific recognition of XO as well as the simultaneous generation of hydrogen peroxide, which was subsequently transformed into hydroxyl radical to oxidize the chromogenic reagent based on the POD-like catalysis. Under the optimized conditions, the colorimetric biosensing platform was established for XO assay without addition of further substrates, showing good linearity relationship between absorbance difference (ΔA) and XO concentrations in the range 0.05-0.5 U/mL (R2 = 0.998) with a limit of detection (LOD) of 0.019 U/mL. The quantification of XO occurs in 25 min, which is superior to the previously reported and commercial XO assays. The proposed method has been successfully used in the assay of human serum samples, showing its high potential in the field of clinical monitoring.
Subject(s)
Colorimetry , Xanthine Oxidase , Humans , Molybdenum , Antioxidants , XanthineABSTRACT
Singlet oxygen (1 O2 ) plays a significant role in environmental and biomedical disinfection fields. Electrocatalytic processes hold great potential for 1 O2 generation, but remain challenging. Herein, a facile Ni doping converted spin-state transition approach is reported for boosting 1 O2 production. Magnetic analysis and theoretical calculations reveal that Ni occupied at the octahedral site of Co3 O4 can effectively induce a low-to-high spin-state transition. The high-spin Ni-Co3 O4 generate appropriate binding strength and enhance electron transfer between the Co centers with oxygen intermediates, thereby improving the catalytic activity of Ni-Co3 O4 for effective generating 1 O2 . In neutral conditions, 1×106 â CFU mL-1 Gram-negative ESBL-producing Escherichia coli (E. coli) could be inactivated by Ni-Co3 O4 system within 5â min. Further antibacterial mechanisms indicate that 1 O2 can lead to cell membrane damage and DNA degradation so as to irreversible cell death. Additionally, the developed Ni-Co3 O4 system can effectively inactivate bacteria from wastewater and bioaerosols. This work provides an effective strategy for designing high-spin electrocatalysis to boost 1 O2 generation for disinfection process.
Subject(s)
Disinfection , Singlet Oxygen , Escherichia coli , Nucleic Acid Hybridization , Hybridization, Genetic , OxygenABSTRACT
MOTIVATION: Gene set enrichment analysis (GSEA) has been widely used to identify gene sets with statistically significant difference between cases and controls against a large gene set. GSEA needs both phenotype labels and expression of genes. However, gene expression are assessed more often for model organisms than minor species. Also, importantly gene expression are not measured well under specific conditions for human, due to high risk of direct experiments, such as non-approved treatment or gene knockout, and then often substituted by mouse. Thus, predicting enrichment significance (on a phenotype) of a given gene set of a species (target, say human), by using gene expression measured under the same phenotype of the other species (source, say mouse) is a vital and challenging problem, which we call CROSS-species gene set enrichment problem (XGSEP). RESULTS: For XGSEP, we propose the CROSS-species gene set enrichment analysis (XGSEA), with three steps of: (1) running GSEA for a source species to obtain enrichment scores and $p$-values of source gene sets; (2) representing the relation between source and target gene sets by domain adaptation; and (3) using regression to predict $p$-values of target gene sets, based on the representation in (2). We extensively validated the XGSEA by using five regression and one classification measurements on four real data sets under various settings, proving that the XGSEA significantly outperformed three baseline methods in most cases. A case study of identifying important human pathways for T -cell dysfunction and reprogramming from mouse ATAC-Seq data further confirmed the reliability of the XGSEA. AVAILABILITY: Source code of the XGSEA is available through https://github.com/LiminLi-xjtu/XGSEA.
Subject(s)
Brain Neoplasms/genetics , Machine Learning , Melanoma/genetics , Ovarian Neoplasms/genetics , Skin Neoplasms/genetics , Animals , Brain Neoplasms/immunology , Brain Neoplasms/pathology , Computational Biology/methods , Datasets as Topic , Embryo, Mammalian , Female , Gene Expression Regulation, Neoplastic , Humans , Melanoma/immunology , Melanoma/pathology , Mice , Ovarian Neoplasms/immunology , Ovarian Neoplasms/pathology , Skin Neoplasms/immunology , Skin Neoplasms/pathology , T-Lymphocytes/immunology , T-Lymphocytes/pathology , ZebrafishABSTRACT
BACKGROUND: Fibrosis and inflammation are major pathological changes of Crohn's disease (CD). Early detection and accurate severity evaluation of CD are critical for patient's prognosis. Endoscopy is widely used to evaluate CD progression. Herein, we evaluated the efficacy of [68Ga]Ga-FAPI-04 PET/CT to identify lesions and assess the progression of CD. METHODS: All CD patients received computed tomography enterography (CTE), [68Ga]Ga-FAPI-04 PET/CT examination, and ileocolonoscopy within 1 week. Two independent gastroenterologists computed the Crohn's disease activity index (CDAI) of all patients. Two radiology physicians assessed the CTE images separately, and the CTE scores were calculated. Lastly, two nuclear medicine physicians independently examined the [68Ga]Ga-FAPI-04 PET/CT images. Once the FAPI uptake of the intestinal segment was equal or higher relative to the liver (considered FAPI-positive), the target-to-background ratio (TBR) and global FAPI PET/CT score were computed, representing the independent intestinal activity and activity of all intestinal segments, respectively. Levels of fecal calprotectin (FCP) and C-reactive protein (CRP) were determined before the endoscopy. The Crohn's disease endoscopy index of severity (CDEIS) and the simple endoscopic score for Crohn's disease (SES-CD) were calculated during the endoscopy. Finally, all data were obtained and analyzed. RESULTS: There were 74 intestinal segments in 16 patients were assessed. [68Ga]Ga-FAPI-04 PET/CT identified 42 of 45 endoscopically lesioned segments (endoscopic lesions detection sensitivity: 93.3%), while CTE identified 39 of them (endoscopic lesions detection sensitivity: 86.7%). According to the receiver operating characteristic (ROC) analysis, [68Ga]Ga-FAPI-04 PET/CT showed better performance in the detection of endoscopic lesions compared with CTE (P < 0.05). The TBR was significantly associated with the CTE score (r = 0.81; (95% CI): 0.736-0.869; P < 0.0001) and SES-CD values (r = 0.86; (95% CI): 0.776-0.908; P < 0.0001). In addition, the global FAPI PET/CT score was significantly correlated with FCP (r = 0.52; 95% CI, 0.02-0.81; P = 0.039), CRP (r = 0.60; 95% CI, 0.13-0.85; P = 0.014), CDEIS (r = 0.55; 95% CI, 0.06-0.83; P = 0.028), and CDAI (r = 0.81; 95% CI, 0.50-0.93; P < 0.0001). CONCLUSION: In summary, [68Ga]Ga-FAPI-04 PET/CT correlated well with endoscopic, CTE, clinical, and biomarkers of CD. It was also highly sensitive in the detection of different classes of lesions in all intestinal segments, and unlike other examinations, this technique required no patient fasting or bowel preparation. Therefore, [68Ga]Ga-FAPI-04 PET/CT may be a promising method for assessing the activity of CD.
Subject(s)
Crohn Disease , Quinolines , Humans , Crohn Disease/diagnostic imaging , Positron Emission Tomography Computed Tomography , Gallium Radioisotopes , C-Reactive Protein/analysisABSTRACT
OBJECTIVES: This study aimed to compare the YHLO chemiluminescence immunoassay (CLIA) with the Crithidia luciliae immunofluorescence test (CLIFT) to detect anti-dsDNA antibodies and its correlation with disease activity in systemic lupus erythematosus (SLE). METHOD: In total, 208 patients diagnosed with SLE, 110 other autoimmune patients, 70 infectious disorders patients, and 105 healthy people were enrolled in this study. Serum samples were tested using CLIA in a YHLO chemiluminescence system and CLIFT. RESULTS: The overall agreement between YHLO CLIA and CLIFT was 76.9% (160/208), with a moderate correlation (kappa = 0.530, p < 0.001). The sensitivity of YHLO CLIA and CLIFT were 58.2% and 55.3%, respectively. The specificity of YHLO CLIA and CLIFT were 95.1% and 99.3%, respectively. The sensitivity of YHLO CLIA was increased to 66.8% with a specificity of 93.6% when the cut-off value was set at 24 IU/mL. Spearman's correlation coefficient between the quantitative results of YHLO CLIA and the titers of CLIFT was 0.59 (p < .01). A significant correlation was found between the anti-dsDNA results detected by YHLO CLIA and the SLE Disease Activity Index 2000 (SLEDAI-2K). Spearman's correlation coefficient between YHLO CLIA and SLEDAI-2K (r = 0.66, p < .01) was higher than that of CLIFT (r = 0.60, p < .01). CONCLUSIONS: Good correlation and agreement were found between YHLO CLIA and CLIFT. In addition, there was a significant correlation between YHLO CLIA and the SLE Disease Activity Index, which was superior to that of CLIFT. The YHLO chemiluminescence system is recommended for the assessment of disease activity.
Subject(s)
Crithidia , Lupus Erythematosus, Systemic , Humans , Sensitivity and Specificity , Luminescence , Antibodies, Antinuclear , Fluorescent Antibody Technique , Immunoassay , Enzyme-Linked Immunosorbent Assay/methodsABSTRACT
Herein, we report a concise asymmetric total synthesis of isopavine alkaloids, which feature a special azabicyclo[3.2.2]nonane tetracyclic skeleton. The key steps include iridium-catalyzed asymmetric hydrogenation of unsaturated carboxylic acids, Curtius rearrangement, and Eschweiler-Clarke methylation, which enable an enantioselective approach to isopavine alkaloids in 6-7 linear steps. Furthermore, for the first time, isopavine alkaloids, especially (-)-reframidine (3), are found to display effective antiproliferative effects on various cancer cell lines.
Subject(s)
Alkaloids , Alkaloids/pharmacology , Carboxylic Acids , Hydrogenation , Iridium , StereoisomerismABSTRACT
BACKGROUND: Although the ABC method for gastric cancer (GC) screening has been widely adopted in Japan, it may not be suitable for other countries due to population heterogeneity and different tumor histology. We aim to develop a modified ABC method to improve GC screening performance, especially among Helicobacter pylori (Hp) infected but serum pepsinogen (sPG) test-negative individuals. METHODS: A total of 4745 participants were recruited from Tianjin, China, and were classified into four groups by combined assay for Hp infection and sPG concentrations: Group A (Hp [-], PG [-]), Group B (Hp [+], PG [-]), Group C (Hp [+], PG [+]), and Group D (Hp [-], PG [+]). We used receiver-operating characteristic (ROC) curves analysis and minimum p value method to determine the optimal cutoff point for PG II in Group B. We performed logistic regressions to examine the risk of GC across different subgroups. In addition to the derivation set, the performance of the modified ABC method was also evaluated in an external set involving 16,292 participants from Liaoning, China. RESULTS: In the modified ABC method, we further classified Group B as low-risk (Group B1) and high-risk subgroups (Group B2) using optimal sPG II cutoff point (20.0 ng/mL) by ROC curves analysis and minimum p value method. Compared with Group B1, Group B2 had a significantly higher risk of GC (adjusted OR = 2.54, 95% CI = 1.94-3.33). The modified ABC method showed good discrimination for GC (AUC = 0.61, 95% CI = 0.59-0.63) and improved risk reclassification (NRI = 0.11, p < .01). Similar results were observed in the validation dataset. CONCLUSIONS: The modified ABC method can effectively identify high-risk population for GC among Hp-infected but sPG test-negative participants in China.
Subject(s)
Helicobacter Infections , Helicobacter pylori , Stomach Neoplasms , Humans , Pepsinogen A , Helicobacter Infections/diagnosis , Risk Factors , ROC Curve , Stomach Neoplasms/diagnosisABSTRACT
Euphorlactone A (1), a rare rearranged ent-atisane norditerpenoid with an undescribed 3-nor-2,4-olide-ent-atisane scaffold, and euphorlactone B (2), a new ent-atisane diterpenoid with an unprecedented seven-membered lactone ring C, were isolated from the roots of Euphorbia fischeriana. Their planar structures with absolute configurations were extensively elucidated by analysis of 1D and 2D NMR data, electronic circular dichroism (ECD) calculations, Rh2(OCOCF3)4-induced ECD curves, and single-crystal X-ray diffraction. Euphorlactone A (ELA) showed a remarkable AChE (acetylcholinesterase) inhibitory activity (IC50 = 2.13 ± 0.06 µM and Ki = 0.058 µM), which was five times stronger than that of the positive control (rivastigmine, IC50 = 12.46 ± 0.82 µM), and further in vitro enzyme inhibition kinetic analysis and molecular docking studies were performed to investigate the AChE inhibitory mechanism.
Subject(s)
Diterpenes , Euphorbia , Euphorbia/chemistry , Molecular Docking Simulation , Acetylcholinesterase , Kinetics , Diterpenes/chemistry , Plant Roots/chemistry , Molecular StructureABSTRACT
BACKGROUND: A computer game-based epilepsy educational programme (Epigame) can potentially improve the awareness, knowledge and attitude (AKA) and quality of life (QOL) of children with epilepsy (CWE). Our study among Malaysian CWE aimed to assess the: i) baseline level of epilepsy AKA and potential characteristics associated with poor levels of AKA, ii) effectiveness of Epigame in improving AKA and QOL of CWE. METHOD: Prospective cohort study on CWE age 7-18 years old with no comorbidities. Epilepsy education was delivered using Epigame. CWE completed AKA questionnaire before (time point 1 [TP1]), immediately after (TP2), 3 months (TP3) after provision of Epigame. Child self-report Health-Related Quality of Life Measurement for Children with Epilepsy (CHEQOL-25) questionnaire was completed at TP1 and TP3. RESULTS: Total of 106 CWE participated in this study (mean age of 13.3 years). Baseline (TP1) AKA was rated "very low to moderate" for awareness domain in 95.3 %, "very low to moderate" for knowledge domain in 67 %, "negative to indifferent" for attitude domain in 54.7 %, and "very poor to moderate' for total AKA score domain in 84 %. "Positive to very positive" for child attitude domain was significantly associated with parents with "positive to very positive" for attitude domain (OR 10.6, 95 % CI 3.23-34.66). "Good to excellent" for total child AKA domain was significantly associated with parents with "Good to excellent" for total AKA domain (OR 5.2, 95 % CI 1.16-15.02) and with < 2 antiseizure medication (OR 5.0, 95 % CI 1.34-18.98). The scores in the knowledge, attitude and total AKA score domains improved significantly after the introduction of Epigame at TP3. There were no significant improvements in the CHEQOL-25 scores over time except for the "Quest for Normality" subscale score (mean of score difference between TP1 and TP3 = 1.0, 95 % CI 0.19-1.81). CONCLUSION: Majority of Malaysian CWE had low levels of epilepsy AKA, particularly among parents with "negative to indifferent" for attitude domain, parents with "very poor to moderate" for total AKA domain and on polytherapy. Introduction of Epigame was effective in improving scores of the knowledge, attitude and total AKA domains, and the QOL "Quest for Normality" domain of the CHEQOL-25.
Subject(s)
Epilepsy , Video Games , Child , Humans , Adolescent , Quality of Life , Prospective Studies , Epilepsy/therapy , Epilepsy/epidemiology , ComorbidityABSTRACT
This case series compared clinical variables and various combinations of immunotherapy received with outcomes of patients with severe acute necrotizing encephalopathy (ANE). We performed a retrospective review of clinical variables, immunotherapy received, and outcomes (based on the modified Rankin Scale) in Malaysia between February 2019 and January 2020. Twenty-seven children (12 male), aged 7 months to 14 years (mean 4 years) at diagnosis were included. Of these, 23 had an ANE severity score of 5 to 9 out of 9 (high risk). Eleven patients received tocilizumab (four in combination with methylprednisolone [MTP], seven with MTP + intravenous immunoglobulin [IVIG]) and 16 did not (two received MTP alone, 14 received MTP + IVIG). Nine died. Among the survivors, six had good outcomes (modified Rankin Score 0-2) at 6 months follow-up. All patients who received tocilizumab in combination with MTP + IVIG survived. Twenty children received first immunotherapy within 48 hours of admission. No significant association was found between the timing of first immunotherapy with outcomes. Those with brainstem dysfunction (p = 0.016) were observed to have poorer outcomes. This study showed a trend towards better survival when those with severe ANE were treated with tocilizumab in combination with MTP + IVIG. However, larger studies will be needed to determine the effect of this regime on the long-term outcomes.
Subject(s)
Brain Diseases , Leukoencephalitis, Acute Hemorrhagic , Child , Humans , Male , Immunoglobulins, Intravenous/therapeutic use , Malaysia , Methylprednisolone , Leukoencephalitis, Acute Hemorrhagic/therapy , Retrospective StudiesABSTRACT
BACKGROUND: This study aimed to explore the risk factors for BK virus (BKV) infection in renal transplant recipients (RTRs) routinely treated with tacrolimus. METHODS: Forty-two cases with BKV infections and 51 patients without BKV infections were enrolled in the study. Eighty-seven healthy individuals and 77 patients undergoing dialysis were randomly included as controls. A logistic regression model was used to analyze potential variables in order to evaluate factors related to BKV infection in the renal transplant recipients. RESULTS: The number of individuals with acute rejection in BKV positive RTRs is significantly higher than that in BKV negative RTRs. Hemoglobin levels in BKV positive RTRs were significantly lower than those in BKV negative RTRs (109.61 ± 20.11 vs. 130.16 ± 26.297, p < 0.001). There was a positive correlation between tacrolimus levels and hemoglobin concentration in RTRs (r = 0.329, p = 0.023). The results of a multivariate regression analysis indicated that a history of acute rejection (OR = 4.157, p = 0.031) and low hemoglobin (OR = 0.963, p < 0.001) were risk factors for BKV infection. CONCLUSIONS: Acute rejection and low hemoglobin were risk factors for BKV infection after renal transplantation.
Subject(s)
BK Virus , Kidney Transplantation , Polyomavirus Infections , Tumor Virus Infections , Humans , Kidney Transplantation/adverse effects , Kidney Transplantation/methods , Tacrolimus/therapeutic use , Tumor Virus Infections/diagnosis , Tumor Virus Infections/epidemiology , Tumor Virus Infections/etiology , Polyomavirus Infections/diagnosis , Polyomavirus Infections/epidemiology , Polyomavirus Infections/complications , HemoglobinsABSTRACT
Traditional Chinese medicine (TCM) is still considered a global complementary or alternative medical system, but exogenous hazardous contaminants remain in TCM even after decocting. Besides, it is time-consuming to conduct a risk assessment of trace elements in TCMs with a non-automatic approach due to the wide variety of TCMs. Here, we present MRTCM, a cloud-computing infrastructure for automating the probabilistic risk assessment of metals and metalloids in TCM. MRTCM includes a consumption database and a pollutant database involving forty million rows of consumption data and fourteen types of TCM potentially toxic elements concentrations. The algorithm of probabilistic risk assessment was also packaged in MRTCM to assess the risks of eight elements with Monte Carlo simulation. The results demonstrated that 96.64% and 99.46% had no non-carcinogenic risk (hazard indices (HI) were < 1.0) for animal and herbal medicines consumers, respectively. After twenty years of exposure, less than 1% of the total carcinogenic risk (CRt) was > 10-4 for TCM consumers, indicating that they are at potential risk for carcinogenicity. Sensitivity analysis revealed that annual consumption and concentration were the main variables affecting the assessment results. Ultimately, a priority management list of TCMs was also generated, indicating that more attention should be paid to the non-carcinogenic risks of As, Mn, and Hg and the carcinogenic risks of As and Cr in Pheretima and Cr in Arcae Conch. In general, MRTCM could significantly enhance the efficiency of risk assessment in TCM and provide reasonable guidance for policymakers to optimize risk management.
Subject(s)
Mercury , Metalloids , Metals, Heavy , Animals , Metals, Heavy/toxicity , Metals, Heavy/analysis , Medicine, Chinese Traditional , Metalloids/analysis , Mercury/analysis , Risk Assessment , Carcinogens/analysis , Environmental Monitoring/methodsABSTRACT
BACKGROUND: In the present meta-analysis, the efficacy and safety of perampanel (PER) for the treatment of adolescents with epilepsy were assessed. METHODS: Keyword searches were performed in Embase, PubMed, Cochrane Library, Web of Science, EBSCO and CNKI from 1 January 2020 to 10 October 2020. The randomized controlled trials (RCTs) and case-control studies in which PER was compared with other Anti-seizure drugs (ASDs) and/or placebo in children with epilepsy, were considered eligible studies. Odds ratio (OR) with 95% confidence interval (95% CI) for the dichotomous outcome statistic was calculated using a fixed-effects or random-effects model. RESULTS: Three RCTs with a total of 372 adolescents' patients were included in this meta-analysis. Placebo was used as a control in these studies. Compared with placebo, PER showed better efficacy in median seizure frequency reduction from baseline per 28 days (OR = 2.49, 95% CI: 1.25-4.96, p = 0.009) and in responder rate (OR = 1.87, 95% CI: 1.15-3.05, p = 0.01); both were considered statistically increased in PER group. Regarding adverse effects (AEs), significant differences between PER and placebo (OR = 1.47, 95% CI: 0.92-2.41, p = 0.11) were not found, and the most common AEs of PER were dizziness (24.0%), somnolence (15.9%), headache (11.2%), nasopharyngitis (9.7%), upper respiratory tract infection (7.0%) and aggression (7.0%). CONCLUSION: Based on the results in this study, PER showed better efficacy than placebo therapy in children with epilepsy and the AEs were similar in PER group and placebo group. PER showed good efficacy and a low risk of AEs, and might be a promising medication for the treatment of pediatric epilepsy. In the future, well-designed and large-scale RCTs are necessary to validate the present findings.