Publications by authors named "Wenyu Chen"

34 Publications

Correlation Analysis between the Viral Load and the Progression of COVID-19.

Comput Math Methods Med 2021 8;2021:9926249. Epub 2021 Jun 8.

Department of Infectious Disease, Affiliated Hospital of Jiaxing University/The First Hospital of Jiaxing, Jiaxing 314000, China.

Objectives: This study is aimed at exploring the relationship of the viral load of coronavirus disease 2019 (COVID-19) with lymphocyte count, neutrophil count, and C-reactive protein (CRP) and investigating the dynamic change of patients' viral load during the conversion from mild COVID-19 to severe COVID-19, so as to clarify the correlation between the viral load and progression of COVID-19.

Methods: This paper included 38 COVID-19 patients admitted to the First Hospital of Jiaxing from January 28, 2020, to March 6, 2020, and they were clinically classified according to the Guidelines on the Novel Coronavirus-Infected Pneumonia Diagnosis and Treatment. According to the instructions of the Nucleic Acid Detection Kit for the 2019 novel coronavirus (SARS-CoV-2), respiratory tract specimens (throat swabs) were collected from patients for nucleic acid testing. Patients' lymphocyte count and neutrophil count were determined by blood routine examination, and CRP was measured by biochemical test.

Results: The results of our study suggested that the cycle threshold (Ct) value of Nucleocapsid protein (N) gene examined by nucleic acid test was markedly positively correlated with lymphocyte count ( = 0.0445, = 0.1203), but negatively correlated with neutrophil count ( = 0.0446, = 0.1167) and CRP ( = 0.0393, = 0.1261), which indicated that patients with a higher viral load tended to have lower lymphocyte count but higher neutrophil count and CRP. Additionally, we detected the dynamic change of Ct value in patients who developed into a severe case, finding that viral load of 3 patients increased before disease progression, whereas this phenomenon was not found in 2 patients with underlying diseases.

Conclusion: The results of this study demonstrated that viral load of SARS-CoV-2 is significantly negatively correlated with lymphocyte count, but markedly positively correlated with neutrophil count and CRP. The rise of viral load is very likely to be the key factor leading to the overloading of the body's immune response and resulting in the disease progression into severe disease.
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http://dx.doi.org/10.1155/2021/9926249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8189785PMC
June 2021

RNF144A suppresses ovarian cancer stem cell properties and tumor progression through regulation of LIN28B degradation via the ubiquitin-proteasome pathway.

Cell Biol Toxicol 2021 May 11. Epub 2021 May 11.

Department of Gastroenterology, The Yancheng Clinical College of Xuzhou Medical University, The First People's Hospital of Yancheng, No. 66, Renmin South Road, Yancheng, 224001, Jiangsu, China.

Objective: Cancer stem cells (CSCs) are the main driving force of tumorigenesis, metastasis, recurrence, and drug resistance in epithelial ovarian cancer (EOC). The current study aimed to explore the regulatory effects of ring finger protein 144A (RNF144A), an E3 ubiquitin ligase, in the maintenance of CSC properties and tumor development in EOC.

Methods: The expressions of RNF144A in EOC tissue samples and cells were examined. The knockdown or overexpression of a target gene was achieved by transfecting EOC cells with short hairpin RNA or adenoviral vectors. A mouse xenograft model was constructed by inoculating nude mice with EOC cells. Co-immunoprecipitation was used to determine the interaction between RNF144A and LIN28B.

Results: Downregulated RNF144A expression was observed in ovarian tumor tissues and EOC cells. Low RNF144A expression was positively associated with poor survival of EOC patients. RNF144A knockdown significantly enhanced sphere formation and upregulated stem cell markers in EOC cells, while RNF144A overexpression prevented EOC cells from acquiring stem cell properties. Also, the upregulation of RNF144A inhibited ovarian tumor growth and aggressiveness in cell culture and mouse xenografts. Further analysis revealed that RNF144A induced LIN28B degradation through ubiquitination in EOC cells. LIN28B upregulation restored the expressions of stem cell pluripotency-associated transcription factors in EOC cells overexpressing RNF144A.

Conclusion: Taken together, our findings highlight the therapeutic potential of restoring RNF144A expression and thereby suppressing LIN28B-associated oncogenic signaling for EOC treatment. • Ring finger protein 144A (RNF144A) is downregulated in epithelial ovarian cancer (EOC) tissues and cell lines. • The overexpression of RNF144A prevents EOC cells from acquiring stem cell properties and inhibits ovarian tumor growth. • RNF144A induces LIN28B degradation through ubiquitination in EOC cells. • LIN28B upregulation restores the expressions of stem cell pluripotency-associated transcription factors in EOC cells overexpressing RNF144A.
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http://dx.doi.org/10.1007/s10565-021-09609-wDOI Listing
May 2021

Bioinformatics and system biology approach to identify the influences of SARS-CoV-2 infections to idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease patients.

Brief Bioinform 2021 Apr 13. Epub 2021 Apr 13.

University of New South Wales, Australia.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), better known as COVID-19, has become a current threat to humanity. The second wave of the SARS-CoV-2 virus has hit many countries, and the confirmed COVID-19 cases are quickly spreading. Therefore, the epidemic is still passing the terrible stage. Having idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) are the risk factors of the COVID-19, but the molecular mechanisms that underlie IPF, COPD, and CVOID-19 are not well understood. Therefore, we implemented transcriptomic analysis to detect common pathways and molecular biomarkers in IPF, COPD, and COVID-19 that help understand the linkage of SARS-CoV-2 to the IPF and COPD patients. Here, three RNA-seq datasets (GSE147507, GSE52463, and GSE57148) from Gene Expression Omnibus (GEO) is employed to detect mutual differentially expressed genes (DEGs) for IPF, and COPD patients with the COVID-19 infection for finding shared pathways and candidate drugs. A total of 65 common DEGs among these three datasets were identified. Various combinatorial statistical methods and bioinformatics tools were used to build the protein-protein interaction (PPI) and then identified Hub genes and essential modules from this PPI network. Moreover, we performed functional analysis under ontologies terms and pathway analysis and found that IPF and COPD have some shared links to the progression of COVID-19 infection. Transcription factors-genes interaction, protein-drug interactions, and DEGs-miRNAs coregulatory network with common DEGs also identified on the datasets. We think that the candidate drugs obtained by this study might be helpful for effective therapeutic in COVID-19.
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http://dx.doi.org/10.1093/bib/bbab115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8083324PMC
April 2021

PreDTIs: prediction of drug-target interactions based on multiple feature information using gradient boosting framework with data balancing and feature selection techniques.

Brief Bioinform 2021 Mar 12. Epub 2021 Mar 12.

UNSW Digital Health, WHO Center for eHealth, School of Public Health and Community Medicine, Faculty of Medicine, The University of New South Wales, Sydney, Australia.

Discovering drug-target (protein) interactions (DTIs) is of great significance for researching and developing novel drugs, having a tremendous advantage to pharmaceutical industries and patients. However, the prediction of DTIs using wet-lab experimental methods is generally expensive and time-consuming. Therefore, different machine learning-based methods have been developed for this purpose, but there are still substantial unknown interactions needed to discover. Furthermore, data imbalance and feature dimensionality problems are a critical challenge in drug-target datasets, which can decrease the classifier performances that have not been significantly addressed yet. This paper proposed a novel drug-target interaction prediction method called PreDTIs. First, the feature vectors of the protein sequence are extracted by the pseudo-position-specific scoring matrix (PsePSSM), dipeptide composition (DC) and pseudo amino acid composition (PseAAC); and the drug is encoded with MACCS substructure fingerings. Besides, we propose a FastUS algorithm to handle the class imbalance problem and also develop a MoIFS algorithm to remove the irrelevant and redundant features for getting the best optimal features. Finally, balanced and optimal features are provided to the LightGBM Classifier to identify DTIs, and the 5-fold CV validation test method was applied to evaluate the prediction ability of the proposed method. Prediction results indicate that the proposed model PreDTIs is significantly superior to other existing methods in predicting DTIs, and our model could be used to discover new drugs for unknown disorders or infections, such as for the coronavirus disease 2019 using existing drugs compounds and severe acute respiratory syndrome coronavirus 2 protein sequences.
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http://dx.doi.org/10.1093/bib/bbab046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7989622PMC
March 2021

Overexpression of STAT4 under hypoxia promotes EMT through miR-200a/STAT4 signal pathway.

Life Sci 2021 May 23;273:119263. Epub 2021 Feb 23.

Department of Obstetrics and Gynecology, The Yancheng Clinical College of Xuzhou Medical University, The First People's Hospital of Yancheng, Yancheng, Jiangsu, 224001, P.R.China.

Aims: Previous reports have found that STAT4 is involved in the epithelial-mesenchymal transition (EMT), thereby regulating the metastasis and invasion of ovarian cancer. However, the mechanisms underlying remain unclear.

Main Methods: We first established hypoxia-induced in vivo and in vitro models. The expression levels of signal transducer and activator of transcription 4 (STAT4), the markers of EMT and microRNA-200a (miR-200a) were assessed by western blot and qRT-PCR analysis, respectively. Through the bioinformatics analysis and luciferase assay, the relationship between miR-200a and SATA4 was performed. The gain- and loss-function experiments were performed to examine the role of miR-200a/STAT4 axis.

Key Findings: The results showed that the protein level of STAT4 was significantly up-regulated in our hypoxia-exposed models, and contributed to the regulating of EMT. Besides, we found STAT4 was a direct target of miR-200a. Overexpression of miR-200a repressed the expression of STAT4, and inhibited EMT progress, whereas the silencing of miR-200a promoted the STAT4-mediated EMT regulation both in vitro and in vivo.

Significance: Our results provided a potential molecular mechanism by which miR-200a involved in hypoxia-induced metastasis and invasion in ovarian cancer, suggesting a possible target for the treatment of ovarian cancer.
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http://dx.doi.org/10.1016/j.lfs.2021.119263DOI Listing
May 2021

Summarization With Self-Aware Context Selecting Mechanism.

IEEE Trans Cybern 2021 Jan 11;PP. Epub 2021 Jan 11.

In the natural language processing family, learning representations is a pioneering study, especially in sequence-to-sequence tasks where outputs are generated, totally relying on the learning representations of source sequence. Generally, classic methods infer that each word occurring in the source sequence, having more or less influence on the target sequence, should all be considered when generating outputs. As the summarization task requires the output sequence to only retain the essence, classic full consideration of the source sequence may not work well on it, which calls for more suitable methods with the ability to discard the misleading noise words. Motivated by this, with both relevance retaining and redundancy removal in mind, we propose a summarization learning model by implementing an encoder with copious contextual information represented and a decoder with a selecting mechanism integrated. Specifically, we equip the encoder with an asynchronous bi directional parallel structure, in order to obtain abundant semantic representation. The decoder, different from the classic attention-based works, employs a self-aware context selecting mechanism to generate summary in a more productive way. We evaluate the proposed methods on three benchmark summarization corpora. The experimental results demonstrate the effectiveness and applicability of the proposed framework in relation to several well-practiced and state-of-the-art summarization methods.
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http://dx.doi.org/10.1109/TCYB.2020.3042230DOI Listing
January 2021

Value of Plasma Methylated SFRP2 in Prognosis of Gastric Cancer.

Dig Dis Sci 2020 Nov 20. Epub 2020 Nov 20.

Oncology Department, Third Affiliated Hospital of Soochow University, Changzhou, 213003, People's Republic of China.

Background: Secreted frizzled-related protein 2 (SFRP2) in circulating tumor DNA (ctDNA) is related to gastric cancer (GC) proliferation. However, whether methylated SFRP2 in ctDNA serves as the biomarker in GC patients remains unknown.

Aims: To investigate the relationship between methylated SFRP2 and the clinical outcomes of GC patients.

Methods: One hundred and forty-eight GC patients receiving systemic chemotherapy were collected during 2015-2017. Aberrant SFRP2 methylation was detected before and after chemotherapy by digital PCR-based technologies.

Results: Baseline SFRP2 methylation positively correlated with lymph node status (P < 0.001), distant metastasis (P < 0.001) and TNM stage (P = 0.005). The top 50% methylated SFRP2 had shorter progression-free survival (PFS) and overall survival (OS) than those with bottom 50% in stage III GC patients (median PFS, 11.0 vs. NR months; HR 13.05; 95% CI 3.05-55.95; median OS 17.0 vs. NR months; HR 7.80; 95% CI 1.81-33.60) and stage IV GC patients (median PFS, 4.0 vs. 7.0 months; HR 2.74; 95% CI 1.58-4.78; median OS 12.0 vs. 16.0 months; HR 3.14; 95% CI 1.67-5.92). Besides, the increased methylated SFPR2 from baseline to post-treatment was related to the worse PFS and OS among stage IV patients (median PFS, 5.0 vs. 7.0 months; HR 2.17; 95% CI 1.25-3.76; median OS 12.0 vs. 15.5 months; HR 3.51; 95% CI 1.94-6.35), but not to stage III patients.

Conclusions: SFRP2 methylation and dynamic change are associated with GC prognosis. Our findings provide potential biomarker detection approach in ctDNA for prognosis prediction and dynamic monitoring among GC patients.
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http://dx.doi.org/10.1007/s10620-020-06710-8DOI Listing
November 2020

Development and Validation of a Seven-Gene Signature for Predicting the Prognosis of Lung Adenocarcinoma.

Biomed Res Int 2020 17;2020:1836542. Epub 2020 Aug 17.

Department of Respiration, The First Hospital of Jiaxing, Affiliated Hospital of Jiaxing University, Jiaxing 314000, China.

Background: Prognosis is a main factor affecting the survival of patients with lung adenocarcinoma (LUAD), yet no robust prognostic model of high effectiveness has been developed. This study is aimed at constructing a stable and practicable gene signature-based model via bioinformatics methods for predicting the prognosis of LUAD sufferers.

Methods: The mRNA expression data were accessed from the TCGA-LUAD dataset, and paired clinical information was collected from the GDC website. R package "edgeR" was employed to select the differentially expressed genes (DEGs), which were then used for the construction of a gene signature-based model via univariate COX, Lasso, and multivariate COX regression analyses. Kaplan-Meier and ROC survival analyses were conducted to comprehensively evaluate the performance of the model in predicting LUAD prognosis, and an independent dataset GSE26939 was accessed for further validation.

Results: Totally, 1,655 DEGs were obtained, and a 7-gene signature-based risk score was developed and formulated as risk_score = 0.000245∗NTSR1 + (7.13 - 05)∗RHOV + 0.000505∗KLK8 + (7.01 - 05)∗TNS4 + 0.000288∗C1QTNF6 + 0.00044∗IVL + 0.000161∗B4GALNT2. Kaplan-Meier survival curves revealed that the survival rate of patients in the high-risk group was lower in both the TCGA-LUAD dataset and GSE26939 relative to that of patients in the low-risk group. The relationship between the risk score and clinical characteristics was further investigated, finding that the model was effective in prognosis prediction in the patients with different age (age > 65, age < 65) and TNM stage (N0&N1, T1&T2, and tumor stage I/II). In sum, our study provides a robust predictive model for LUAD prognosis, which boosts the clinical research on LUAD and helps to explore the mechanism underlying the occurrence and progression of LUAD.
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http://dx.doi.org/10.1155/2020/1836542DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7641279PMC
May 2021

The Prognostic Value of the Prognostic Nutritional Index (PNI) in Radically Resected Esophagogastric Junction Adenocarcinoma.

Nutr Cancer 2020 Nov 2:1-8. Epub 2020 Nov 2.

Departments of Oncology, the Third Affiliated Hospital of Soochow University, Changzhou, China.

To determine the influence of preoperative prognostic nutritional index in adenocarcinoma of the esophagogastric junction, this study was conducted to analyze 420 patients with adenocarcinoma of the esophagogastric junction who underwent surgery. A total of 120 healthy volunteers were included as the healthy control group. The cutoff values of prognostic nutritional index for predicting survival were obtained according to the receiver operating characteristic curve. The clinic-pathological feature and survival were compared between low and high prognostic nutritional index group. Results showed that the prognostic nutritional index in the patient group was lower than that in the healthy control group ( < 0.05). The level of prognostic nutritional index was significantly associated with tumor differentiation, Siewert type, tumor size, body mass index, and hemoglobin levels ( < 0.05). The level of prognostic nutritional index was negatively correlated with age of onset, tumor differentiation, Siewert type, tumor size, depth of tumor, but positively associated with the levels of body mass index and hemoglobin. Multivariate analysis revealed that prognostic nutritional index was an independent factor associated with disease-free survival ( = 0.027) and overall survival ( = 0.003). In conclusion, low prognostic nutritional index may be considered as an independent adverse prognostic marker in patients with adenocarcinoma of the esophagogastric junction.
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http://dx.doi.org/10.1080/01635581.2020.1841252DOI Listing
November 2020

DeepACTION: A deep learning-based method for predicting novel drug-target interactions.

Anal Biochem 2020 12 6;610:113978. Epub 2020 Oct 6.

Center for Informational Biology, University of Electronic Science and Technology of China, Chengdu, 611731, China.

Drug-target interactions (DTIs) play a key role in drug development and discovery processes. Wet lab prediction of DTIs is time-consuming, expensive, and tedious. Fortunately, computational approaches can identify new interactions (drug-target pairs) and accelerate the process of drug repurposing. However, a vast number of interactions remain undiscovered; therefore, we proposed a deep learning-based method (deepACTION) for predicting potential or unknown DTIs. Here, each drug chemical structure and protein sequence are transformed according to structural and sequence information using different descriptors to represent their features correctly. There have been some challenges, such as the high dimensionality and class imbalance of data during the prediction process. To address these problems, we developed the MMIB technique to balance the majority and minority instances in the dataset and utilized a LASSO model to handle the high dimensionality of the data. In addition, we trained the convolutional neural network algorithm with balanced and reduced features for accurate prediction of DTIs. In this study, the AUC is considered a primary evaluation metric for comparing the performance of the deep ACTION model with that of existing methods by a 5-fold cross-validation test. Our experiential dataset obtained from the DrugBank database and our deepACTION model achieved an AUC of 0.9836 for this dataset. The experimental results ensured that the model can predict significant numbers of new DTIs and provide complete information to motivate scientists to develop drugs.
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http://dx.doi.org/10.1016/j.ab.2020.113978DOI Listing
December 2020

Corrigendum to The detection and analysis of differential regulatory communities in lung cancer. Genomics. 2020; 112(3):2535-2540.

Genomics 2021 Jan 13;113(1 Pt 2):1277. Epub 2020 Jul 13.

Department of Respiration, The First Hospital of Jiaxing, The First Affiliated Hospital of Jiaxing University, Jiaxing, China. Electronic address:

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http://dx.doi.org/10.1016/j.ygeno.2020.07.016DOI Listing
January 2021

Structure learning with similarity preserving.

Neural Netw 2020 Sep 4;129:138-148. Epub 2020 Jun 4.

School of Computer Science and Technology, Harbin Institute of Technology, Shenzhen, China.

Leveraging on the underlying low-dimensional structure of data, low-rank and sparse modeling approaches have achieved great success in a wide range of applications. However, in many applications the data can display structures beyond simply being low-rank or sparse. Fully extracting and exploiting hidden structure information in the data is always desirable and favorable. To reveal more underlying effective manifold structure, in this paper, we explicitly model the data relation. Specifically, we propose a structure learning framework that retains the pairwise similarities between the data points. Rather than just trying to reconstruct the original data based on self-expression, we also manage to reconstruct the kernel matrix, which functions as similarity preserving. Consequently, this technique is particularly suitable for the class of learning problems that are sensitive to sample similarity, e.g., clustering and semisupervised classification. To take advantage of representation power of deep neural network, a deep auto-encoder architecture is further designed to implement our model. Extensive experiments on benchmark data sets demonstrate that our proposed framework can consistently and significantly improve performance on both evaluation tasks. We conclude that the quality of structure learning can be enhanced if similarity information is incorporated.
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http://dx.doi.org/10.1016/j.neunet.2020.05.030DOI Listing
September 2020

A study on clinical effect of Arbidol combined with adjuvant therapy on COVID-19.

J Med Virol 2020 11 19;92(11):2702-2708. Epub 2020 Jun 19.

Department of Orthopedics, Tongde Hospital of Zhejiang Province, Hangzhou, China.

This study aims to explore the clinical effect of Arbidol (ARB) combined with adjuvant therapy on patients with coronavirus disease 2019 (COVID-19). The study included 62 patients with COVID-19 admitted to the First Hospital of Jiaxing from January to March 2020, and all patients were divided into the test group and the control group according to whether they received ARB during hospitalization. Various indexes in the two groups before and after treatment were observed and recorded, including fever, cough, hypodynamia, nasal obstruction, nasal discharge, diarrhea, C-reactive protein (CRP), procalcitonin (PCT), blood routine indexes, blood biochemical indexes, time to achieve negative virus nucleic acid, and so on. The fever and cough in the test group were relieved markedly faster than those in the control group (P  <  .05); there was no obvious difference between the two groups concerning the percentage of patients with abnormal CRP, PCT, blood routine indexes, aspartate aminotransferase, and alanine aminotransferase (P > .05); the time for two consecutive negative nucleic acid tests in the test group were shorter than that in the control group; the hospitalization period of the patients in the test group and control group were (16.5  ±  7.14) days and (18.55  ±  7.52) days, respectively. ARB combined with adjuvant therapy might be able to relieve the fever of COVID-19 sufferers faster and accelerate the cure time to some degree, hence it's recommended for further research clinically.
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http://dx.doi.org/10.1002/jmv.26142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7300876PMC
November 2020

Development and Application of One Separation-Free Safety Tube on the Disposable Infusion Needle.

Comput Math Methods Med 2020 16;2020:6896517. Epub 2020 May 16.

Department of Cardiothoracic Surgery, First Hospital of Jiaxing (Affiliated Hospital of Jiaxing University), 314000 Jiaxing, China.

Objective: To develop a new type infusion set and apply it to the clinic, as well as explore its effectiveness in the prevention from needle stick injuries.

Methods: A total of 200 inpatients who were in need of intravenous infusion with a disposable infusion needle were included and randomly divided into two groups: intervention group and control group. Disposable infusion needles with a separation-free safety tube were used in the intervention group, whereas conventional ones were used in the control group. Then, effects of the two types of infusion sets were observed and compared.

Results: As for the operation time for infusion, it was (82.19 ± 1.80) seconds in the intervention group and (83.02 ± 1.83) seconds in the control group, with the difference statistically significant ( < 0.05). Besides, the exposure time of the needles after infusion in the intervention group was (3.36 ± 0.17) seconds while (18.85 ± 1.18) seconds in the control group; the difference between which was statistically significant ( < 0.05). In terms of the time for needle disposal, (18.60 ± 0.84) seconds was required in the intervention group, while for the control group, it took (18.85 ± 1.18) seconds, and the difference between two groups was of statistical significance as well ( < 0.05). Nevertheless, there was no statistically significant difference in the accidental slip rate of the needles as that turned out 0% in both groups ( > 0.05). It was worth noting that the block rate of the disposed needles in the intervention group was 100%.

Conclusion: The separation-free safety tube on the disposable infusion needle could instantly block the sharp needle after infusion, which reduces the needle exposure time and lowers the risk of needle stick injuries. In the meantime, the safety tube is convenient to use, and its application can shorten the time for infusion and needle disposal, consequently improving the working efficiency of nurses. As the new type safety tube has above advantages and would not raise the risk of needle slippage, it is worthy of clinical promotion.
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http://dx.doi.org/10.1155/2020/6896517DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7246391PMC
April 2021

Effect of Danggui-Shaoyao-San-Containing Serum on the Renal Tubular Epithelial-Mesenchymal Transition of Diabetic Nephropathy.

Curr Pharm Biotechnol 2020 ;21(12):1204-1212

The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, China.

Objectives: To investigate the effect of Danggui-Shaoyao-San (DSS)-containing serum on the renal tubular Epithelial-Mesenchymal Transition (EMT) of Diabetic Nephropathy (DN) in high glucose- induced HK-2 cells and its mechanism.

Methods: 20 rats were randomly divided into four groups: blank control group, DSS low dose group (DSS-L), DSS middle dose group (DSS-M), and DSS high dose group (DSS-H). DSS was administrated to the corresponding group (7g/kg/d, 14g/kg/d and 21g/kg/d) for 7 consecutive days, and the same volume of saline was given to the blank control group by gavage. The rat drug-containing serum was successfully prepared. HK-2 cells were divided into five groups: blank control group, model group, DSS-L, DSS-M, DSS-H, according to the corresponding drug and dose of each treatment group. Protein and mRNA levels of Jagged1, Notch1, Hes5, Notch Intracellular Domain (NICD), E-cadherin, alpha- Smooth Muscle Actin (α-SMA) and vimentin at 24h, 48h and 72h were detected by Western Blot and RT-qPCR.

Results: The protein and mRNA levels of Jagged1, Notch1, Hes5, NICD, α-SMA and vimentin in the treatment groups were remarkably decreased compared with the model group (P<0.05), and the protein and mRNA levels of E-cadherin were notably increased (P<0.05) by Western Blot and RT-qPCR.

Conclusion: Our results demonstrated that DSS could prevent DN by ameliorating renal tubular EMT through inhibition of the Notch signaling pathway.
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http://dx.doi.org/10.2174/1389201021666200416094318DOI Listing
November 2020

The detection and analysis of differential regulatory communities in lung cancer.

Genomics 2020 05 8;112(3):2535-2540. Epub 2020 Feb 8.

Department of Respiration, The First Hospital of Jiaxing, The First Affiliated Hospital of Jiaxing University, Jiaxing, China. Electronic address:

The tumorgenesis process of lung cancer involves the regulatory dysfunctions of multiple pathways. Although many signaling pathways have been identified to be associated with lung cancer, there are little quantitative models of how inactions between genes change during the process from normal to cancer. These changes belong to different dynamic co-expressions patterns. We quantitatively analyzed differential co-expression of gene pairs in four datasets. Each dataset included a large number of lung cancer and normal samples. By overlapping their results, we got 14 highly confident gene pairs with consistent co-expression change patterns. Some of they, such as ARHGAP30 and GIMAP4, had been recorded in STRING network database while some of them were novel discoveries, such as C9orf135 and MORN5, TEKT1 and TSPAN1 were positively correlated in both normal and cancer but more correlated in normal than cancer. These gene pairs revealed the underlying mechanisms of lung cancer occurrence.
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http://dx.doi.org/10.1016/j.ygeno.2020.02.005DOI Listing
May 2020

Prediction of drug-target interaction based on protein features using undersampling and feature selection techniques with boosting.

Anal Biochem 2020 01 15;589:113507. Epub 2019 Nov 15.

Department of Internal Medicine, Rangpur Medical College, Rangpur, 5400, Bangladesh. Electronic address:

Accurate identification of drug-target interaction (DTI) is a crucial and challenging task in the drug discovery process, having enormous benefit to the patients and pharmaceutical company. The traditional wet-lab experiments of DTI is expensive, time-consuming, and labor-intensive. Therefore, many computational techniques have been established for this purpose; although a huge number of interactions are still undiscovered. Here, we present pdti-EssB, a new computational model for identification of DTI using protein sequence and drug molecular structure. More specifically, each drug molecule is transformed as the molecular substructure fingerprint. For a protein sequence, different descriptors are utilized to represent its evolutionary, sequence, and structural information. Besides, our proposed method uses data balancing techniques to handle the imbalance problem and applies a novel feature eliminator to extract the best optimal features for accurate prediction. In this paper, four classes of DTI benchmark datasets are used to construct a predictive model with XGBoost. Here, the auROC is utilized as an evaluation metric to compare the performance of pdti-EssB method with recent methods, applying five-fold cross-validation. Finally, the experimental results indicate that our proposed method is able to outperform other approaches in predicting DTI, and introduces new drug-target interaction samples based on prediction probability scores. pdti-EssB webserver is available online at http://pdtiessb-uestc.com/.
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http://dx.doi.org/10.1016/j.ab.2019.113507DOI Listing
January 2020

Partition level multiview subspace clustering.

Neural Netw 2020 Feb 6;122:279-288. Epub 2019 Nov 6.

School of Computer Science and Engineering, University of Electronic Science and Technology of China, Sichuan, 611731, China; Centre for Artificial Intelligence, Peng Cheng Lab, Shenzhen 518055, China. Electronic address:

Multiview clustering has gained increasing attention recently due to its ability to deal with multiple sources (views) data and explore complementary information between different views. Among various methods, multiview subspace clustering methods provide encouraging performance. They mainly integrate the multiview information in the space where the data points lie. Hence, their performance may be deteriorated because of noises existing in each individual view or inconsistent between heterogeneous features. For multiview clustering, the basic premise is that there exists a shared partition among all views. Therefore, the natural space for multiview clustering should be all partitions. Orthogonal to existing methods, we propose to fuse multiview information in partition level following two intuitive assumptions: (i) each partition is a perturbation of the consensus clustering; (ii) the partition that is close to the consensus clustering should be assigned a large weight. Finally, we propose a unified multiview subspace clustering model which incorporates the graph learning from each view, the generation of basic partitions, and the fusion of consensus partition. These three components are seamlessly integrated and can be iteratively boosted by each other towards an overall optimal solution. Experiments on four benchmark datasets demonstrate the efficacy of our approach against the state-of-the-art techniques.
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http://dx.doi.org/10.1016/j.neunet.2019.10.010DOI Listing
February 2020

A steroid-resistant nephrotic syndrome in an infant resulting from a consanguineous marriage with COQ2 and ARSB gene mutations: a case report.

BMC Med Genet 2019 10 28;20(1):165. Epub 2019 Oct 28.

Department of Pathology, Tianjin Children's Hospital, 238 Longyan Road, Beichen District, Tianjin, China.

Background: Treatment of steroid-resistant nephrotic syndrome (SRNS) remains a challenge for paediatricians. SRNS accounts for 10~20% of childhood cases of nephrotic syndrome (NS). Individuals with SRNS overwhelmingly progress to chronic kidney disease (CKD) and end-stage kidney disease (ESRD). Genetic research is of great significance for diagnosis and treatment. More than 39 recessive or dominant genes have been found to cause human SRNS, including COQ2. COQ2 gene mutations not only cause primary coenzyme Q10 deficiency but also cause SRNS without extrarenal manifestations. The concept of COQ2 nephropathy has been proposed for a long time. Mutations in the COQ2 gene have rarely been reported. Worldwide, only 5 cases involving 4 families have been reported.

Case Presentation: We present the case of a 6-month-old girl with steroid-resistant glomerulopathy due to a COQ2 defect with no additional systemic symptoms. The patient was identified as a homozygote for the c.832 T > C (p. Cys278Arg) missense mutation and a single base homozygous mutation in ARSB gene in c.1213 + 1G > A. The father and mother were heterozygous mutation carriers in both COQ2 and ARSB, and her healthy sister was only a heterozygous mutation carrier in COQ2. In this case, hormone therapy was ineffective, and progressive deterioration of renal function occurred within 1 week after onset, leading to acute renal failure and eventual death.

Conclusions: We reported a consanguinity married family which had COQ2 and ARSB dual mutant. Kidney diseases caused by COQ2 gene mutations can manifest as SRNS, with poor prognosis. The C. 832 T > c (p.csc 278arg) is a new mutation site. Genetic assessment for children with steroid-resistant nephrotic syndrome, especially in infancy, is very important. Families with a clear family history should receive genetic counselling and prenatal examinations, and children without a family phenotype should also receive genetic screening as early as possible.
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http://dx.doi.org/10.1186/s12881-019-0898-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6816174PMC
October 2019

Knockdown of lncRNA BLACAT1 reverses the resistance of afatinib to non-small cell lung cancer via modulating STAT3 signalling.

J Drug Target 2020 03 5;28(3):300-306. Epub 2019 Aug 5.

Department of Respiratory, the First Hospital of Jiaxing (the Affiliated Hospital of Jiaxing University), Jiaxing, PR China.

Afatinib, a second-generation irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), has been approved as EGFR, HER2, HER3 and HER4 inhibitor for non-small cell lung cancer (NSCLC) treatment. However, acquired resistance to afatinib has been found in most EGFR mutant NSCLC patients. Bladder cancer associated transcript 1 (BLACAT1) is a novel long non-coding RNAs (lncRNA) that play a functional role as an oncogenic lncRNA and is associated with chemoresistance. We aimed to identify the role of BLACAT1 in afatinib-resistant NSCLC and underlying mechanisms. Afatinib-resistant NSCLC cells were established. MTT assay, colony formation assay, apoptosis analysis, qRT-PCR and western blot analysis, immunohistochemistry, and in vivo study were carried out. BLACAT1 was up-regulated in afatinib-resistant NSCLC cells. Knockdown of BLACAT1 reversed the resistance of afatinib to NSCLC cells by modulating STAT3 signalling. The results provided a potential strategy for afatinib-resistant NSCLC by targeting BLACAT1.
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http://dx.doi.org/10.1080/1061186X.2019.1650368DOI Listing
March 2020

Vapocoolant spray versus placebo spray/no treatment for reducing pain from intravenous cannulation: A meta-analysis of randomized controlled trials.

Am J Emerg Med 2018 11 27;36(11):2085-2092. Epub 2018 Mar 27.

School of Nursing, Shandong University, Ji'nan, China. Electronic address:

Background: Intravenous cannulation is a routine procedure in hospitalized patients, and pain can occur during the cannulation process. Vapocoolant spray is an advantageous analgesic alternative for intravenous cannula insertion.

Objectives: The objective of our meta-analysis is to compare the effectiveness of vapocoolant spray and placebo spray/no treatment for pain reduction during intravenous cannulation.

Design: A meta-analysis to identify evidence from randomized controlled trials.

Methods: We searched Web of Science, PubMed, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, and Wanfang Data for publications before January 2018. The outcomes measured included pain during intravenous cannulation, patients' anxiety due to the spray, first attempt success rate, technical ease of the attempt, adverse events, and participant satisfaction.

Results: We included 11 studies with 1410 patients. The meta-analysis results showed that vapocoolant spray significantly decreased pain during intravenous cannulation compared with placebo spray or no treatment in both adults and children. In addition, vapocoolant spray significantly increased the technical ease of the attempt and participants' satisfaction. However, patients' anxiety due to spray, first attempt success rate, and adverse events were not associated with vapocoolant spray.

Conclusions: This meta-analysis suggests that vapocoolant spray significantly decreased pain during intravenous cannulation when compared with placebo spray or no treatment in both adults and children. We recommend the use of vapocoolant spray during intravenous cannulation to decrease pain. Future research may help to unify pain measurement standards. Patients' anxiety due to spray and technical ease of the attempt should be explored in future research.
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http://dx.doi.org/10.1016/j.ajem.2018.03.068DOI Listing
November 2018

Polyphyllin I modulates MALAT1/STAT3 signaling to induce apoptosis in gefitinib-resistant non-small cell lung cancer.

Toxicol Appl Pharmacol 2018 10 1;356:1-7. Epub 2018 Aug 1.

Department of Oncology, Zhejiang Hospital, Hangzhou, Zhejiang 310013, PR China. Electronic address:

Non-small cell lung cancer (NSCLC) patients harboring EGFR mutation who initially respond to EGFR-TKI will gradually develop acquired resistance. There is still a challenge to treat EGFR-TKI resistant NSCLC patients. Polyphyllin I (PP I), a steroidal saponin isolated from Paris polyphylla., has been exhibited antitumor activities against various carcinomas. However, its mechanism in treating EGFR-TKI resistant NSCLC has not been well elucidated. In this study, we found that PP I suppressed the cell viability and induced apoptosis of gefitinib-resistant NSCLC cells and xenograft models. These therapeutic efficacies were associated with down-regulated level of MALAT1, leading to inactivation of STAT3 signaling pathway. The cell viability inhibition and apoptosis inducing in gefitinib-resistant NSCLC triggered by PP I were abolished by MALAT1 overexpression, while the cell viability inhibition and apoptosis inducing triggered by PP I were potentiated by MALAT1 knockdown. These findings suggest that, in vitro and in vivo, PP I inhibits the viability and induces apoptosis of gefitinib-resistant NSCLC by down-regulating MALAT1 and inactivating STAT3 signaling pathway. Thus, PPI could serve a promising therapeutic agent for the treatment of gefitinib-resistant NSCLC.
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http://dx.doi.org/10.1016/j.taap.2018.07.031DOI Listing
October 2018

Directional Transport of a Liquid Drop between Parallel-Nonparallel Combinative Plates.

Langmuir 2018 04 5;34(15):4484-4493. Epub 2018 Apr 5.

State Key Laboratory of Fluid Power & Mechatronic Systems , Zhejiang University , 38 Zheda Road , Hangzhou 310027 , China.

Liquids confined between two parallel plates can perform the function of transmission, support, or lubrication in many practical applications, due to which to maintain liquids stable within their working area is very important. However, instabilities may lead to the formation of leaking drops outside the bulk liquid, thus it is necessary to transport the detached drops back without overstepping the working area and causing destructive leakage to the system. In this study, we report a novel and facile method to solve this problem by introducing the wedgelike geometry into the parallel gap to form a parallel-nonparallel combinative construction. Transport performances of this structure were investigated. The criterion for self-propelled motion was established, which seemed more difficult to meet than that in the nonparallel gap. Then, we performed a more detailed investigation into the drop dynamics under squeezing and relaxing modes because the drops can surely return in hydrophilic combinative gaps, whereas uncertainties arose in gaps with a weak hydrophobic character. Therefore, through exploration of the transition mechanism of the drop motion state, a crucial factor named turning point was discovered and supposed to be directly related to the final state of the drops. On the basis of the theoretical model of turning point, the criterion to identify whether a liquid drop returns to the parallel part under squeezing and relaxing modes was achieved. These criteria can provide guidance on parameter selection and structural optimization for the combinative gap, so that the destructive leakage in practical productions can be avoided.
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http://dx.doi.org/10.1021/acs.langmuir.8b00172DOI Listing
April 2018

LncRNA-MALAT1 contributes to the cisplatin-resistance of lung cancer by upregulating MRP1 and MDR1 via STAT3 activation.

Biomed Pharmacother 2018 May 22;101:536-542. Epub 2018 Mar 22.

Department of Oncology, Zhejiang Hospital, Hangzhou, Zhejiang, 310013, PR China. Electronic address:

Multiple drug resistance is the main reason for chemotherapeutic failure in lung cancer patients with complex molecular mechanisms. LncRNA-MALAT1 plays functional roles in the progression of carcinomas and development of drug resistance. We aimed to identify the role of MALAT1 in DDP-resistant non-small cell lung cancer as well as potential mechanisms. Human lung cancer cell line A549 and the DDP-resistant cell line A549/DDP were used. Cell transfection was performed to establish A549/MALAT1 and A549/DDP/shMALAT1 cells. The qRT-PCR analysis was performed to detect lncRNA-MALAT1 level. Cell viability, colony formation assay, apoptosis analysis, western blot analysis, immunohistochemistry, and animal study were carried out. MALAT1 was upregulated in DDP-resistant A549 cell line. MALAT1 decreased DDP sensitivity in vitro and in vivo by upregulating MRP1 and MDR1 via STAT3 activation. Overexpression of MALAT1 contributed to the DDP resistance and might confer a potently poor prognosis.
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http://dx.doi.org/10.1016/j.biopha.2018.02.130DOI Listing
May 2018

Drop Encapsulated in Bubble: A New Encapsulation Structure.

Phys Rev Lett 2018 Feb;120(5):054503

The State Key Laboratory of Fluid Power and Mechatronic Systems, Zhejiang University, 38 Zheda Road, Hangzhou 310027, China.

A new fluid encapsulation structure, which is characterized by a bubble encapsulating a drop, is reported. It is stably generated from the breakup of a liquid column inside a bubble, which is achieved via the injection of Taylor flow into liquid. A model is constructed to explain the liquid column breakup mechanism. A dimensionless control guidance, which enables the possibility to create different-scale capsules, is provided. The encapsulation stability in external flows is verified, and a method to trigger the release of the encapsulated drop is provided, which supports potential applications with great advantages such as fluid transport.
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http://dx.doi.org/10.1103/PhysRevLett.120.054503DOI Listing
February 2018

Pinning Effects of Wettability Contrast on Pendant Drops on Chemically Patterned Surfaces.

Langmuir 2016 11 4;32(45):11780-11788. Epub 2016 Nov 4.

State Key Laboratory of Fluid Power & Mechatronic Systems, Zhejiang University , Hangzhou 310058, China.

The morphology and dynamics of the pendant drops attached to chemically patterned surfaces (pattern-pinned pendant drops) with different hydrophilic/hydrophobic contrasts were investigated experimentally and numerically. During the experiments, the evolution of the contact angle and the maximum drop volume were found to be different from those of traditional pendant drops, whose contact line is pinned on the edge of the tips (tip-pinned pendant drops), and the deviation is related to both the pattern radius and the wettability contrast. Then, a hypothesis was proposed to illustrate the behavior of the contact line after it reached the pattern boundary, based on the premise that the pattern boundary possessed a certain width or fuzziness. It was concluded that the special phenomena in this case were due to the movement of the contact line, and the maximum contact radius was presented as a key parameter for the pattern-pinned drops, which is directly related to the stability and the maximum volume of the drops. Furthermore, through a simulation study on pattern-pinned pendant drops, the vibration performance of the meniscus was revealed as a superposition of two vibration behaviors including a low-frequency vibration due to the inertia effects and a high-frequency vibration due to the surface tension gradient within the boundary region. In addition, the hypothesis proposed above was also verified. Finally, a forecasting model to predict the maximum contact radius for the pattern-pinned pendant drops was built for different liquids and pattern wettabilities. This allows us to effectively design and optimize chemically patterned surfaces to achieve a desired pinning function or a pendant drop with desired properties.
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http://dx.doi.org/10.1021/acs.langmuir.6b03318DOI Listing
November 2016

The role of EGFR-TKI for leptomeningeal metastases from non-small cell lung cancer.

Springerplus 2016 3;5(1):1244. Epub 2016 Aug 3.

School of Medicine, Jiaxing University, Jiaxing, 314000 Zhejiang People's Republic of China.

Leptomeningeal metastasis (LM) is a terminal event in the development of non-small cell lung cancer (NSCLC). It has a poor prognosis with median survival of 1.9 months if untreated. The improvement of OS in NSCLC patients relatively increases incidence of LM. While current therapeutic options for LM are limited. Epidermal growth factor receptor-tyrosine kinase inhibitors are a class of small molecules and show dramatic response in epidermal growth factor receptor mutated patients. It also has a distinct therapeutic potential against brain metastases. Although there are some studies on EGFR-TKIs and brain metastases, the role of EGFR-TKIs on LM are not fully clarified. In this review, we will summarize current evidences concerning the use and discuss the role of EGFR-TKIs on LM.
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http://dx.doi.org/10.1186/s40064-016-2873-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4972805PMC
August 2016

Longitudinal in-vivo volumetry study for porcine liver regeneration from CT data.

Annu Int Conf IEEE Eng Med Biol Soc 2014 ;2014:4743-6

The use of hepatic-like cloned cord lining epithelial cells (CLEC) to enhance liver regeneration has been proposed, but has not been properly investigated in a large animal study. The paper presents a system developed for the longitudinal in-vivo volumetry study on porcine liver regeneration from computed tomography (CT) data. In this system, a rough 3D liver volume is firstly automatically segmented by a 3D mesh deformation-based method. Then a refinement step to eliminate the segmentation error is carried out by a 3D post-editing tool, followed by mesh-volume conversion and volume calculation. This system was applied in a pilot study, which was composed of 4/4 pigs in the Experimental/Control Groups, to measure liver volumes over pre- to post-operative time course. Experimental results suggest that (1) the developed system can perform CT-based porcine liver volumetry efficiently, and (2) the infusion of CLEC to liver remnant may potentially enhance the liver regeneration.
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http://dx.doi.org/10.1109/EMBC.2014.6944684DOI Listing
September 2015

Volume Preserved Mass-Spring Model with Novel Constraints for Soft Tissue Deformation.

IEEE J Biomed Health Inform 2016 Jan 12;20(1):268-80. Epub 2014 Nov 12.

An interactive surgical simulation system needs to meet three main requirements, speed, accuracy, and stability. In this paper, we present a stable and accurate method for animating mass-spring systems in real time. An integration scheme derived from explicit integration is used to obtain interactive realistic animation for a multiobject environment. We explore a predictor-corrector approach by correcting the estimation of the explicit integration in a poststep process. We introduce novel constraints on positions into the mass-spring model (MSM) to model the nonlinearity and preserve volume for the realistic simulation of the incompressibility. We verify the proposed MSM by comparing its deformations with the reference deformations of the nonlinear finite-element method. Moreover, experiments on porcine organs are designed for the evaluation of the multiobject deformation. Using a pair of freshly harvested porcine liver and gallbladder, the real organ deformations are acquired by computed tomography and used as the reference ground truth. Compared to the porcine model, our model achieves a 1.502 mm mean absolute error measured at landmark locations for cases with small deformation (the largest deformation is 49.109 mm) and a 3.639 mm mean absolute error for cases with large deformation (the largest deformation is 83.137 mm). The changes of volume for the two deformations are limited to 0.030% and 0.057%, respectively. Finally, an implementation in a virtual reality environment for laparoscopic cholecystectomy demonstrates that our model is capable to simulate large deformation and preserve volume in real-time calculations.
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http://dx.doi.org/10.1109/JBHI.2014.2370059DOI Listing
January 2016

Segmentation of hepatic tumor from abdominal CT data using an improved support vector machine framework.

Annu Int Conf IEEE Eng Med Biol Soc 2013 ;2013:3347-50

An improved support vector machine (SVM) framework has been developed to segment hepatic tumor from CT data. By this method, the one-class SVM (OSVM) and two-class SVM (TSVM) are connected seamlessly by a boosting tool, to tackle the tumor segmentation via both offline and online learning. An initial tumor region was first pre-segmented by an OSVM classifier. Then the boosting tool was employed to automatically generate the negative (non-tumor) samples, according to certain criteria. The pre-segmented initial tumor region and the non-tumor samples generated were used to train a TSVM) classifier. By the trained TSVM classifier, the final tumor lesion was segmented out. Tested on 16 sets of CT abdominal scans, quantitative results suggested that the developed method achieved significantly higher segmentation accuracy than the OSVM and TSVM classifiers.
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http://dx.doi.org/10.1109/EMBC.2013.6610258DOI Listing
June 2015
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