Incident ticket classification plays an important role in the complex system maintenance. However, low classification accuracy will result in high maintenance costs. To solve this issue, this paper ...proposes a fuzzy output support vector machine (FOSVM) based incident ticket classification approach, which can be implemented in the context of both two-class SVMs and multi-class SVMs such as one-versus-one and one-versus-rest. Our purpose is to solve the unclassifiable regions of multi-class SVMs to output reliable and robust results by more fine-grained analysis. Experiments on both benchmark data sets and real-world ticket data demonstrate that our method has better performance than commonly used multi-class SVM and fuzzy SVM methods.
The fermentation of non-starch polysaccharides by colonic microflora is popular as a triggering mechanism to achieve colon-specific drug delivery in that the existence of colonic microflora is ...independent of gastrointestinal transit time, pH, and disease conditions, and various delivery systems were developed using this strategy. One of such delivery systems, COLAL technology, has advanced into late stage of product development. However,
in vitro characterization of these delivery systems remains a challenge in part because the critical performance indicator is colonic specificity of drug release. Moreover, the dynamic and ecologically diverse features of the colon are difficult to be incorporated into USP dissolution methods. As a result, alternative dissolution approaches have been designed to better represent the colonic conditions, such as utilizing polysaccharide-degrading enzymes, rat caecal contents, human fecal slurries, and multi-stage culture systems. The primary focus of this article is to summarize and review the dissolution testing currently used in characterizing colon-specific delivery systems activated by microflora. A brief description of physiological parameters of the colon relevant to colonic drug release is also presented.
Bladder cancer (BC) is a molecular heterogeneous malignant tumor; the treatment strategies for advanced-stage patients were limited. Therefore, it is vital for improving the clinical outcome of BC ...patients to identify key biomarkers affecting prognosis. Ferroptosis is a newly discovered programmed cell death and plays a crucial role in the occurrence and progression of tumors. Ferroptosis-related genes (FRGs) can be promising candidate biomarkers in BC. The objective of our study was to construct a prognostic model to improve the prognosis prediction of BC.
The mRNA expression profiles and corresponding clinical data of bladder urothelial carcinoma (BLCA) patients were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. FRGs were identified by downloading data from FerrDb. Differential analysis was performed to identify differentially expressed genes (DEGs) related to ferroptosis. Univariate and multivariate Cox regression analyses were conducted to establish a prognostic model in the TCGA cohort. BLCA patients from the GEO cohort were used for validation. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and single-sample gene set enrichment analysis (ssGSEA) were used to explore underlying mechanisms.
Nine genes (
, and
) were identified to construct a prognostic model. Patients were classified into high-risk and low-risk groups according to the signature-based risk score. Receiver operating characteristic (ROC) and Kaplan-Meier (K-M) survival analysis confirmed the superior predictive performance of the novel survival model based on the nine-FRG signature. Multivariate Cox regression analyses showed that risk score was an independent risk factor associated with overall survival (OS). GO and KEGG enrichment analysis indicated that apart from ferroptosis-related pathways, immune-related pathways were significantly enriched. ssGSEA analysis indicated that the immune status was different between the two risk groups.
The results of our study indicated that a novel prognostic model based on the nine-FRG signature can be used for prognostic prediction in BC patients. FRGs are potential prognostic biomarkers and therapeutic targets.
Little is known about the benefits of adjuvant endocrine therapy (ET) in low ER-positive breast cancer (1%–10%) patients. We analyzed the association between ET and breast cancer-specific survival ...(BCSS) in these patients with respect to the regimen and the duration of ET.
Patients were classified into three groups based on the regimen and duration of ET. The regimens included aromatase inhibitor (AI) monotherapy or sequential tamoxifen followed by an AI (AI/T + AI), or only tamoxifen and no ET. The duration of ET included 2–3 years and >3 years. Multivariate Cox regression analysis was employed to calculate the hazard ratios (HRs) with 95% confidence intervals (CIs).
Of the 10,696 patients diagnosed with breast cancer between 2010 and 2020, 407 women were identified with ER-low positive disease and met the inclusion criteria. During a median follow-up of 5.2 years, patients who received ET improved BCSS. Of them, those with AI/T + AI had increased BCSS compared to patients without ET, after adjusting for demographics and tumor characteristics, especially in ER-low/HER-2-positive breast cancer. After additional adjustment for treatment mode, the association maintained a similar trend. Patients who received >3 years of ET was associated with a better DFS. There was no significant difference in BCSS between patients with 2–3 years and >3 years of ET.
For ER-low patients, findings suggest that ET with AI/T + AI may be a reasonable treatment alternative. This effect should be assessed in randomized studies.
•Patients with mono- or sequential aromatase inhibitor therapy have better survival.•It seems that >3 years of adjuvant ET should be standard for ER-low patients.•Aromatase inhibitor is an option for low estrogen receptor-positive breast cancer.
Atherosclerosis (AS) is closely associated with chronic low-grade inflammation and gut dysbiosis. Metformin (MET) presents pleiotropic benefits in the control of chronic metabolic diseases, but the ...impacts of MET intervention on gut microbiota and inflammation in AS remain largely unclear. In this study,
ApoE
-/-
mice with a high-fat diet (HFD) were adopted to assess the MET treatment. After 12 weeks of MET intervention (100mg·kg
-1
·d
-1
), relevant indications were investigated. As indicated by the pathological measurements, the atherosclerotic lesion was alleviated with MET intervention. Moreover, parameters in AS including body weights (BWs), low-density lipoprotein (LDL), triglyceride (TG), total cholesterol (TC) and malondialdehyde (MDA) were elevated; whereas high-density lipoprotein (HDL) and total superoxide dismutase (T-SOD) levels were decreased, which could be reversed by MET intervention. Elevated pro-inflammatory interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α and lipopolysaccaride (LPS) in AS were decreased after MET administration. However, anti-inflammatory IL-10 showed no significant difference between AS group and AS+MET group. Consistently, accumulated macrophages in the aorta of AS were conversely lowered with MET treatment. The results of 16S rRNA sequencing and analysis displayed that the overall community of gut microbiota in AS was notably changed with MET treatment mainly through decreasing
Firmicutes
,
Proteobacteria
,
Romboutsia
,
Firmicutes/Bacteroidetes
, as well as increasing
Akkermansia
,
Bacteroidetes
,
Bifidobacterium
. Additionally, we found that microbiota-derived short-chain fatty acids (SCFAs) including acetic acid, propionic acid, butyric acid and valeric acid in AS were decreased, which were significantly up-regulated with MET intervention. Consistent with the attenuation of MET on gut dysbiosis, decreased intestinal tight junction protein zonula occludens-1 (ZO)-1 in AS was restored after MET supplementation. Correlation analysis showed close relationships among gut bacteria, microbial metabolites SCFAs and inflammation. Collectively, MET intervention ameliorates AS in
ApoE
-/-
mice through restoring gut dysbiosis and anti-inflammation, thus can potentially serve as an inexpensive and effective intervention for the control of the atherosclerotic cardiovascular disease.
We aimed to analyse the discrepancy in clinical features and prognosis between molecular subtypes in primary ductal carcinoma in situ (DCIS) patients with lumpectomy.
Primary DCIS patients were ...identified from the Surveillance, Epidemiology, and End Results registries database from 2010 to 2017. Based on immunohistochemistry markers of hormone receptor (HR) and human epidermal growth factor receptor-2 (HER2), enrolled DCIS cases were divided into four molecular subtypes, HR-HER2-, HR-HER2+, HR + HER2+, and HR + HER2-. Clinical features and prognosis were compared between molecular subtypes. Radiotherapy (RT) effects on prognosis were also analysed in each molecular subtype.
A total of 5,628 DCIS cases were retrospectively enrolled in this study. HR-HER2-, HR-HER2+, HR+HER2+, and HR+HER2- are 299 (5.3%), 498 (8.8%), 1,086 (19.3%), and 3,745 (66.5%), respectively. HR + HER2- cases have smaller tumor size (72.6%, P < 0.001) and lower grade (23.5%, P < 0.001). Comedo necrosis is more frequent in HR-HER2- (24.4%, P < 0.001) and HR-HER2+ DCIS cases (24.3%, P < 0.001). In univariate analyses, HR-HER2+ cases have significantly higher ipsilateral breast event (IBE) recurrence than HR+HER2- cases (P = 0.010). HR-HER2- cases show higher disease-specific mortality than HR+HER2+ cases (P = 0.021). In high-risk DCIS cases, RT reduces the absolute 5-year IBE incidence by 1.3%, 0.7%, 1.9%, and 2.6%, respectively in HR-HER2-, HR-HER2+, HR+HER2+, and HR+HER2- cases, respectively.
In this population-based study, DCIS cases have diverse clinical and prognostic features for different molecular subtypes. Adjusting treatment strategies according to DCIS molecular subtypes is worth advancing.
•HR-HER2+ DCIS shows the highest proportion of high-risk cases. HR + HER2- DCIS shows lowest proportion of high-risk cases.•HR-HER2+ DCIS shows high risk of IBE recurrence. The DSmortality has no differences among four molecular subtypes.•RT lowered the probability of IBE incidence in high-risk cases for each molecular subtype of DCIS.
To solve the problems of low prediction accuracy, poor stability, and low calculation efficiency in runoff forecasting, this study develops an extreme learning machine (ELM) model based on improved ...complete ensemble empirical mode decomposition adaptive noise (CEEMDAN). The model first uses orthogonal triangular decomposition (QR) to redefine the ELM hidden layer output to construct the orthogonal triangular ELM (QR-ELM). It then introduces the online sequence mechanism (OS) into the QR-ELM model to construct online sequence OR-ELM (OS-QR-ELM), which can effectively improve the efficiency of the ELM models. Then, it uses the correlation wave extension method to extend both ends of the original signal to solve the end effect of CEEMDAN. Finally, it integrates CEEMDAN and OS-QR-ELM combined with parallel computing ideas to construct a parallel CEEMDAN-OS-QR-ELM runoff prediction method. The experimental results show that compared with the support vector regression method combined with empirical mode decomposition, the accuracy and reliability of the parallel CEEMDAN-OS-QR-ELM model was 1.09% and 8% higher, respectively. Compared with the ELM model, the efficiency of OS-QR-ELM was 5%.
Pollution of soil by the heavy metal cadmium (Cd) is a global environmental problem. The glutathione (GSH)‐dependent phytochelatin (PC) synthesis pathway is one of the most important mechanisms ...contributing to Cd accumulation and tolerance. However, the regulation of this pathway is poorly understood. Here, we identified an Arabidopsis thaliana cadmium‐tolerant dominant mutant xcd1‐D (XVE system‐induced cadmium‐tolerance 1) and cloned XCD1 gene (previously called MAN3), which encodes an endo‐β‐mannanase. Overexpression of MAN3 led to enhanced Cd accumulation and tolerance, whereas loss‐of‐function of MAN3 resulted in decreased Cd accumulation and tolerance. In the presence of estradiol, enhanced Cd accumulation and tolerance in xcd1‐D was associated with GSH‐dependent, Cd‐activated synthesis of PCs, which was correlated with coordinated activation of gene expression. Cd stress‐induced expression of MAN3 and the consequently increased mannanase activity, led to increased mannose content in cell walls. Moreover, mannose treatment not only rescued the Cd‐sensitive phenotype of the xcd1‐2 mutant, but also improved the Cd tolerance of wild‐type plants. Significantly, this mannose‐mediated Cd accumulation and tolerance is dependent on GSH‐dependent PC concentrations via coordinated control of expression of genes involved in PC synthesis. Our results suggest that MAN3 regulates the GSH‐dependent PC synthesis pathway that contributes to Cd accumulation and tolerance in A. thaliana by coordinated control of gene expression.
•Fly ash was divided into four groups according to profile characteristics of dioxins.•Low-chlorinated PCDD/F homologs were dominated in the fly ash.•The concentration of 3,3′,4,4′-TePCB was highest ...among 12 dioxin-like PCBs.•The main contribution to the TEQ was from 1,2,3,7,8,-PeCDD and 2,3,4,7,8-PeCDF.
MSWI fly ashes sampled from 15 large-scale commercial municipal solid waste incineration plants in China were analyzed for seventeen polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/PCDFs) as well as twelve dioxin-like polychlorinated biphenyls (dl-PCBs). The concentration of PCDD/PCDFs and dl-PCBs in fly ash samples ranged from 2.8 to 190ngg−1, and 59.6ngg−1 on average. The toxic equivalent (TEQ) ranged from 34 to 2500ng WHO(2005)-PCDD/PCDF-PCB-TEQkg−1, and 790ng WHO(2005)-PCDD/PCDF-PCB-TEQkg−1 on average. For PCDDs, hexa-chlorinated homolog was the dominant compound except two fly ash samples. Tetra-chlorinated homolog was dominant for PCDFs except one sample. The ratio of PCDDs/PCDFs ranged from 0.32 to 2.44 (average 0.97). The contribution of dl-PCBs to total concentration and TEQ was relatively minimal. Correlation between the concentration of three congeners and total TEQ values of fly ashes was also established. The findings obtained in this work provided overview information on the PCDD/PCDF-PCB content characterization of MSWI fly ash in China, which can be available for MSWI fly ash management in the environment.
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