bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative Evaluation of Six Molecular Assays based on RT-PCR and Cross Primer Isothermal Amplification for SARS-CoV-2 Detection
Authors: Wu Shuang , Shi Xiaolu , Chen Qiongcheng , Jiang Yixiang , Zuo Le , Wang Lei , Jiang Min , Lin Yiman , Fang Shisong , Peng Bo , Wu Weihua , Liu Hui , Zhang Renli , Kwan Patrick S.L. , Hu Qinghua 
Published: May 2020

Abstract
SARS-CoV-2 is a newly emerged coronavirus that was isolated from human infections in recent months. Since drugs and vaccines of Covid-19 are still being developed, accurate pathogen detection plays a crucial role in the current public health crisis. Quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay has been reliably used for the detection and confirmation of SARS-CoV-2 since the beginning of outbreak, whereas isothermal nucleic acid amplification based point of care automated assays has also been considered as a simpler and rapid alternative. However, since these assays have only been developed and applied for clinical use within a short timeframe, their analytical performance has not been adequately compared to-date. We describe a comparative study between a newly developed cross primer isothermal amplification (CPA) assay (Kit A) and five RT-PCR assays (Kits B to F), using clinical diagnosis as the reference standard to evaluate their sensitivity, specificity, predictive values and accuracy analysis. Clinical samples used (n=52) included throat swabs (n=30), nasal swabs (n=7), nasopharyngeal swabs (n=7) and sputum specimens (n=8), comprised of positive (n=26) and cleared cases (n=26) by clinical diagnosis. For the CPA assay (Kit A), the sensitivity, specificity, positive and negative predictive values and accuracy were 100%. Among the five RT-PCR kits, Kits B, C and F had good agreement with clinical diagnosis (Kappa≥0.75), Kits D and E were less congruent (0.4≤Kappa<0.75). Differences between all assays were statistically significant (P<0.001). The reproducibility of RT-PCR assays was determined using a positive sample that was verified by all assays, with standard deviations (SD) between 0.35 and 0.87, and coefficients of variation (CV) between 0.95% and 2.57%, indicating good reproducibility. To further evaluate the CPA assay (Kit A) compared to Kits B and F, throat swabs from close contacts of cases (n=200) were analyzed. All three kits identified the same positive samples and showed total agreement. This is the first comparative study to evaluate a CPA assay and RT-PCR assays for SARS-CoV-2 detection, which could serve as a reference for clinical laboratories and inform testing protocols amid the rapidly evolving COVID-19 pandemic.
Clinical symptoms, comorbidities and complications features in severe and non-severe patients with COVID-19: a systematic review and meta-analysis without cases duplication
Authors: Wang Zhufeng , Deng Hongsheng , Ou Changxing , Liang Jingyi , Wang Yingzhi , Jiang Mei , Li Shiyue 
Published: May 2020

Abstract
Background: The pandemic of COVID-19 posed a challenge to global healthcare. The mortality rates of severe cases range from 8.1% to 31.8%, and it is particularly important to identify risk factors that aggravate the disease.Methods: We performed a systematic review of the literature with meta-analysis, using 7 databases to assess clinical characteristics, comorbidities and complications in severe and non-severe patients with COVID-19. All the observational studies were included. We performed a random or fixed effects model meta-analysis to calculate the pooled proportion and 95% CI. Measure of heterogeneity was estimated by Cochran’s Q statistic, I2 index and P value.Results: 4881 cases from 25 studies related to COVID-19 were included. The most prevalent comorbidity was hypertension (severe: 33.4%, 95% CI: 25.4% - 41.4%; non-severe 21.6%, 95% CI: 9.9% - 33.3%), followed by diabetes (severe: 14.4%, 95% CI: 11.5% - 17.3%; non-severe: 8.5%, 95% CI: 6.1% - 11.0%). The prevalence of ARDS, AKI and shock were all higher in severe cases, with 41.1% (95% CI: 14.1% - 68.2%), 16.4% (95% CI: 3.4% - 29.5%) and 19.9% (95% CI: 5.5% - 34.4%), rather than 3.0% (95% CI: 0.6% - 5.5%), 2.2% (95% CI: 0.1% - 4.2%) and 4.1% (95% CI -4.8% - 13.1%) in non-severe patients, respectively. The death rate was higher in severe cases (30.3%, 95% CI: 13.8% - 46.8%) than non-severe cases (1.5%, 95% CI: 0.1% - 2.8%).Conclusions: Hypertension, diabetes and cardiovascular diseases may be risk factors for COVID-19 patients to develop into severe cases.
Rapid Identification of COVID-19 Severity in CT Scans through Classification of Deep Features
Authors: Yu Zekuan , Li Xiaohu , Sun Haitao , Wang Jian , Zhao Tongtong , Chen Hongyi , Ma Yichuan , Zhu Shujin , Xie Zongyu 
Published: May 2020

Abstract
Background: To implement the real-time diagnosis of the severity of patients infected with novel coronavirus 2019 (COVID-19) and guide the follow-up therapeutic treatment, We collected chest CT scans of 202 patients diagnosed with the COVID-19 from three hospitals in Anhui Province, China.Methods: A total of 729 2D axial plan slices with 246 severe cases and 483 non-severe cases were employed in this study. Four pre-trained deep models (Inception-V3, ResNet-50, ResNet-101, DenseNet-201) with multiple classifiers (linear discriminant, linear SVM, cubic SVM, KNN and Adaboost decision tree) were applied to identify the severe and non-severe COVID-19 cases. Three validation strategies (holdout validation, 10-fold cross-validation and leave-one-out) are employed to validate the feasibility of proposed pipelines. Results and conclusion: The experimental results demonstrate that classification of the features from pre-trained deep models show the promising application in COVID-19 screening whereas the DenseNet-201 with cubic SVM model achieved the best performance. Specifically, it achieved the highest severity classification accuracy of 95.20% and 95.34% for 10-fold cross-validation and leave-one-out, respectively. The established pipeline was able to achieve a rapid and accurate identification of the severity of COVID-19. This may assist the physicians to make more efficient and reliable decisions.
Time to Lactate Measurement Affects Efficacy of Initial Lactate on Mortality in critically ill patients with sepsis.
Authors: Luo Xueying , Zheng Xiaobo , Rao Xi , Li Ya , Zheng Sujing , Chen Weicai , He Jinsong 
Published: May 2020

Abstract
Background: Evidence regarding the effect of time to lactate measurement on the relationship between the initial lactate level and mortality is limited. We aimed to investigate the relationships between time to lactate measurement, initial lactate level, and in-hospital mortality in critically ill patients with sepsis.Methods and Results: Of the 14339 eligible adult patients with recognized sepsis upon admission to the ICU based on the MIMIC-III database, the median value of initial lactate was 1.70 mmol/L (interquartile range [IQR] 1.20-2.80), and its detection time was 3.50 hours ([IQR] 1.31-10.24). The results of fully adjusted multivariate analyses demonstrated that lactate was positively associated with in-hospital mortality (odds ratio: 1.126, 95% confidence interval: 1.090 to 1.163, P<0.001), and there was an increase in the odds of death with hourly delays in lactate measurement (OR: 1.006, 95% CI: 1.004 to 1.008, P<0.001). In stratified analyses, delays in lactate measurement significantly interfered with the impact of increased lactate level on mortality (P-value for interaction<0.001). The hospital mortality rate substantially increased by 43.5% for each unit increase in lactate when measurement was delayed by 24 hours (OR: 1.435, 95% CI: 1.260 to 1.635, P<0.001).Discussion: The association of initial lactate with in-hospital mortality is likely to vary with delays in detection time (grouping based on the “1-hour bundle”) in critically ill patients with recognized sepsis upon admission to the ICU.
WITHDRAWN: PADI4 regulates osteosarcoma proliferation primarily via Wnt/β-catenin and MEK/ERK signaling pathway
Authors: Guo Jianping , Yin Lei , Zhang Xuezhong , Su Peng , Zhai Qiaoli 
Published: May 2020

Abstract
Background
Peptidylarginine deiminase 4 (PADI4), an important modification enzyme of proteins, has received increased attention for its role in tumorigenesis of several human cancers. However, the effect of PADI4 on osteosarcoma remains largely unknown. Here, we evaluated the impact and mechanism of PADI4 on osteosarcoma proliferation.
Methods
Impact of PADI4 on proliferation of osteosarcoma cells is detected by the method of CCK8 and colony formation assay. Expression of PADI4 as well as Wnt/β-catenin and MEK/ERK signaling markers after knocking down or ectopically expressing PADI4 or PADI4 inhibitor treatment is investigated by Western blot and RT-PCR. Then we investigated relevance of the expression level of the PADI4 in osteosarcoma samples and paired normal tissues by Western blot and RT-PCR. To further confirm whether PADI4 affect osteosarcoma tumorigenesis in vivo, we performed tumor formation experiments in nude mice.
Results
Firstly, ectopically expressing PADI4 showed positive regulation on colony formation capacity of osteosarcoma cells. Secondly, PADI4 stimulated Wnt/β-catenin and MEK/ERK signaling in osteosarcoma cells. Thirdly, PADI4 is highly expressed in osteosarcoma samples compared with normal tissues. In vivo experiment also verified the positive effect of PADI4 on the growth of transplanted tumors in nude mice.
Conclusions
Taken together, our results revealed PADI4 promoted proliferation of osteosarcoma via Wnt/β-catenin and MEK/ERK signaling pathway. This study may expand our understanding of osteosarcoma tumorigenesis and identify PADI4 as a potential target for diagnosis and treatment of osteosarcoma.
Association between DPP-4 inhibitors and events of colorectal and liver cancers in patients with diabetes receiving second-line agents: a nested case-control study
Authors: Chou Chu-Lin , Juan Shu-Hui , Chen Hsi-Hsien , Kao Chih-Chin , Wu Yueh-Lin , Yeh Shu-Ching , Chen Li-Ying , Chen Jin-Shuen , Chien Li-Nien , Fang Te-Chao 
Published: May 2020

Abstract
Background and aim:

Several studies showed plasma dipeptidyl peptidase-4 (DPP4) levels were significantly lower in patients with colorectal and liver cancers, and animal studies also showed DPP4 inhibitors (DPP4is) have procarcinogenic effects in colorectal cancer. The aims of this study were to investigate the association between cumulative defined daily dose (cDDD) of DPP4is exposure and risks of liver and colorectal cancers in patients with type 2 diabetes mellitus.
Methods

In this nested case-control study, we identified 268,520 patients with diabetes receiving DPP4is as second-line agents between March 1, 2009, and December 31, 2013, from Taiwan’s National Health Insurance Research Database, Taiwan Cancer Registry, and National Death Registry of Taiwan. Of these, 948 and 990 patients newly were diagnosed with liver and colorectal cancer, respectively. The amount of DPP4is were divided into three groups (low, medium, and high) based on the interquartile range of the cDDD of the DPP4is. Results: The data showed that the low cDDD of DPP-4is was associated with a reducing risk of colorectal cancer [adjusted odds ratio (OR), 0.49; 95% CI, 0.32–0.75; P = 0.001]. However, the high cDDD of DPP-4is was associated with an increasing risk of colorectal cancer (adjusted OR, 1.86; 95% CI, 1.32–2.61; P < 0.001). No association between DPP4is use and liver cancer risk was observed.
Conclusions

The novel finding of this nested case study revealed a J-shaped association between the cDDD of DPP-4is and colorectal cancer risk, but not liver cancer risk. A large-based longitudinal investigation is necessary to determine whether long-term DPP4is exposure increase colorectal cancer risk.
Appropriateness of Antibiotic use for the Management of Acute Diarrhea Among Under-Five Children Treated at Primary Care Centers in Northwest Ethiopia: A Cross-Sectional Study
Authors: Abegaz Sumeya Tadesse , Zeleke Addisu Jember , Tesfaye Zelalem Tilahun 
Published: May 2020

Abstract
Background Acute diarrhea management is solely aimed at fluid replacement and nutritional support while antibiotics have a very limited role. Antibiotic treatment is recommended only for bloody diarrhea (dysentery), cholera and invasive bacterial diarrhea. This study is launched to assess the appropriateness of antibiotic use for the management of acute diarrhea among under-five children in Gondar town primary care centers.Methods Institutional based cross-sectional study was conducted in three primary care centers located in Gondar town, Northwest Ethiopia. Children aged from 2–59 months who visited the three primary care centers from September 12, 2015 to September 10, 2016 and received treatment for acute diarrhea were included in the study. We selected 176 cases from Azezo Health Center, 166 from Poly Health Center and 80 from Woleka Health Center. Cases were drawn using systematic random sampling technique. The findings of the study were summarized using tables and figures; binary logistic analysis was used to identify association between the independent and outcome variables at 95% confidence level where p < 0.05 was considered as statistically significant.Results The mean age of the study participants was 19.1 ± 12.8 months. The majority (60.8%) were males. Appropriate antibiotic use was recorded in less than half (47.2%) of the study subjects. Almost all (98.1%) of children subjected to inappropriate antibiotic use were those with watery diarrhea treated with antibiotics. Out of 253 children who received antidiarrheal antibiotics 202 (79.8%) had acute watery diarrhea which should not be treated with antibiotics. Children diagnosed with acute watery diarrhea were less likely to receive treatment qualified as appropriate antibiotic use [AOR: 0.003 (0.001,0.017)]. Conversely, receiving no antibiotic [AOR: 391.00 (92.46, 1653.37)] and prescriber’s profession of Clinical Nurse [AOR: 3.57 (1.02, 12.51)] were positive predictors for appropriate antibiotic use.Conclusion The findings of the study confirm the prevalence of widespread inappropriate antibiotic use on under-five children presenting with acute diarrhea. The findings can be used by stakeholders as input for promoting appropriate antibiotic use in the healthcare system as well as to deter antimicrobial resistance.
Next-generation sequencing of tissue and circulating tumor DNA: Resistance mechanisms to EGFR targeted therapy in a cohort of patients with advanced non-small cell lung cancer
Authors: Zhang Yujun , Xiong Liwen , Xie Fangfang , Zheng Xiaoxuan , Li Ying , Zhu Lei , Sun Jiayuan 
Published: May 2020

Abstract
Background

Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) has been considered as an effective treatment in epidermal growth factor receptor-mutant (EGFR-mutant) advanced non-small cell lung cancer (NSCLC). However, most patients develop acquired resistance eventually. Here, we compared and analyzed the genetic alterations between tissue assay and circulating tumor DNA (ctDNA), and further explored the resistance mechanisms after EGFR-TKI treatment.
Methods

Amplification refractory mutation system-polymerase chain reaction (ARMS-PCR), Cobas® ARMS-PCR and next-generation sequencing (NGS) were performed on tissue samples after pathological diagnosis. Digital droplet PCR (ddPCR) and NGS were performed on plasma samples. The association between genetic alterations and clinical outcomes was analyzed retrospectively.
Results

Thirty-seven patients were included. The success rate of re-biopsy was 91.89% (34/37). The total detection rate of EGFR T790M was 62.16% (23/37) and the consistency between tissue and ctDNA was 78.26% (18/23). Thirty-four patients were analyzed retrospectively. Twenty-four patients harbored concomitant mutations. Moreover, tissue re-biopsy at resistance showed 21 patients (21/34, 61.76%) had concomitant T790M mutation, 4 with MET amplification and 4 with PIK3CA mutation. Patients with T790M mutation (p = 0.010 & p = 0.017) or third-generation EGFR-TKI treatment (p < 0.0001 & p = 0.073) showed better progression-free survival (PFS) and overall survival (OS). Interestingly, concomitant genetic alterations were significantly associated with a worse prognosis for patients with T790M mutation receiving third-generation EGFR-TKIs (p = 0.037).
Conclusions

Multi-platforms are feasible and highly consistent for re-biopsy after EGFR-TKI resistance. Concomitant genetic alterations may be associated with a poor prognosis for patients with T790M mutation after third-generation EGFR-TKIs.
Trial Registration:

The clinical trial registration was carried out on ClinicalTrials.gov. (NCT03309462), registered on September 1st 2017. https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S0007G1B&selectaction=Edit&uid=U0001WUU&ts=2&cx=frpicv
Stimulation of Insulin Signaling Reverses Inflammation-Induced Cone Death in Retinal Detachment
Authors: CONART Jean-Baptiste , Blot Guillaume , Augustin Sébastien , Roubeix Christophe , Beguier Fanny , Charles-Messance Hugo , Touhami Sara , Sahel José-Alain , Berrod Jean-Paul , Guillonneau Xavier , Delarasse Cécile , Sennlaub Florian 
Published: May 2020

Abstract
Background Rhegmatogenous retinal detachment (RD) involving the macula is a major cause of visual impairment despite high surgical success rate, mainly because of cone death. We and others have shown that cone loss occurs secondary to chronic inflammation in many retinal diseases, including age-related macular degeneration and retinitis pigmentosa. We here investigated the yet unknown mechanisms of inflammation-induced cone death in RD.Methods Vitreous samples from patients with RD and from control patients with macular hole were analyzed to characterize the inflammatory response to RD. A mouse model of RD and retinal explants culture were then used to explore the mechanisms leading to cone death.Results Analysis of vitreous samples shows that RD induces a marked inflammatory response with increased cytokine and chemokine expression in humans, which is closely mimicked by experimental murine RD. In this model, we demonstrate that myeloid cells and T-lymphocytes directly contribute to cone loss, as the inhibition of their accumulation by Thrombospondin 1 increased cone survival. We show that cones are highly dependent on glucose and insulin signaling for survival in vitro and that insulin, and the insulin sensitizers rosiglitazone and metformin, prevent RD-induced cone loss in vivo, despite the persistence of inflammation.Conclusion Our results describe a new mechanism by which inflammation, likely through a combination of competition for glucose and the inhibition of insulin signaling, promotes cone death in RD. Therapeutic inhibition of inflammation and stimulation of insulin signaling might prevent RD-associated cone death until the RD can be surgically repaired and improve visual outcome after RD.Trial registration: ClinicalTrials.gov Identifier NCT03318588
Crowdsourcing Framework for QoE-Aware SD-WAN
Authors: Ellawindy Ibtihal , Heydari Shahram Shah 
Published: May 2020

Abstract
The exponential increase in bandwidth-sensitive multimedia traffic on the Internet has created new challenges and opportunities. With the shifting focus from service availability to service quality, there is a need to have quality management measures to serve the high needs of efficient transmission and delivery in time-constrained environments over IP networks. Quality of Experience (QoE) is now considered the most important measure to achieve the twin goals of application efficiency and user satisfaction from a user perspective. In this paper, we propose a framework that can be used to collect real-time QoE feedback through crowdsourcing and forward it to SD-WAN controllers to enhance streaming routes based on real-time user quality perceptions. We analyze how QoE can be affected by different network conditions, and how different streaming protocols compare against each other when the network parameters change dynamically. We compare the real-time user feedback to predefined network changes to measure if participants will be able to identify all degradation events, and to examine which combination of degradation events are noticeable to the participants. These QoE timestamped feedback is sent back to the SD-WAN controller continuously in order to locate problems and bottlenecks in the current service paths and to enable network controllers to take corrective action by rerouting the streamed traffic. Our aim is to demonstrate that real-time QoE feedback can enhance cloud-based services and can adjust services quality based on real-time, active participants’ interaction.
Advances in Research on the circRNA-miRNA-mRNA regulatory network in lung adenocarcinoma by analysis of microarray data
Authors: Yao Qing , He Yong-Lai , Pang Li-Juan , Wang Ning , Dong Shuang-Shuang , Shi Mei Er Tu He Ta Mi , Feng Xiao , Zhou Wen-Hu , Qi Yan 
Published: May 2020

Abstract
Background: The present researches indicate that circular RNAs (circRNAs) play pivotal roles in the generation and development of human cancers. However, function of circRNAs in lung adenocarcinoma is still unknown. Herein, we focused our study on the regulation mechanism of circRNAs in lung adenocarcinoma (LUAC)Methods: CircRNAs-related data can be downloaded from Gene Expression Omnibus(GEO) microarray databases. Relevant expression data of miRNAs and mRNAs were obtained from The Cancer Genome Atlas (TCGA) databases. The differentially expressed circRNAs (DEcircRNAs) were obtained by the robust rank aggregation method, and constructed a ceRNA network with circRNA-miRNA pairs and miRNA-mRNA pairs. The function and pathway enrichment of different genes were analyzed, and the protein-protein interaction (PPI) was predicted by String software, and the subnetwork management module was constructed by MCODE plugin. The differentially expressed mRNAs (DEmRNAs) were used to establish survival analysis by R software.Results: A total of 19 up-regulated circRNAs, 45 down-regulated circRNAs, 98 up-regulated miRNAs, 18 down-regulated miRNAs, 2002 up-regulated mRNAs, and 553 down-regulated mRNAs were obtained in lung adenocarcinoma. The circRNA-miRNA-mRNA network was constructed by six circRNAs (hsa_circ_0003528, hsa_circ_0004315, hsa_circ_0005699, hsa_circ_0002588, hsa_circ_0005777, hsa_circ_0027033), 19 miRNAs and 33 mRNAs. GO and KEGG pathway analysis indicated that DEmRNAs might be related to the progression of LUAC. The PPI network was constructed and four hub genes (CEP55, CHEK1, CDC25A, KIF23) were obtained from the network, and four hub genes were found to be associated with the same miRNA and circRNA, including hsa_circ_0004315/hsa-miR-195/CEP55, CHEK1, CDC25A, KIF23. Three hub genes (CEP55, CHEK1, KIF23) were significantly associated with LUAC survival and prognosis, and the overall survival rate of lung adenocarcinoma was decreased in high-expression genes compared with low-expression genes.Conclusion: Our finding indicated that circRNA-miRNA- mRNA axis paly key role in the pathogenesis of lung adenocarcinoma, and some circRNAs could be considered as a biomarker and target for the diagnosis and therapy of LUAC patients.