bluuebunny/crossref_metadata_2025_split huggingface dataset:
A snapshot of public knowledge of novel coronavirus disease 2019: a web-based national survey
Authors: Liu Yu , Wang Dan , Xu Hao , Xiao Ying , Chen Cui , Chen Ru-Nan , Hu Liang-Hao , Li Zhao-Shen 
Published: March 2021

Abstract
Background
Although the number of existing cases of coronavirus disease 2019 (COVID-19) in China has been decreasing since late February 2020, the number of confirmed cases abroad is surging. Improving public knowledge of COVID-19 is critical to controlling the pandemic. This study aimed to determine China’s public knowledge of COVID-19 and the attitudes towards control measures.

Methods
A cross-sectional study was conducted over 48 h from 22:30 29 February 2020 to 22:30 2 March 2020 based on a self-administered web-based questionnaire. The survey was conducted on the WeChat network. Exponential non-discriminative snowball sampling was applied. The questionnaire was voluntarily completed by WeChat users. The questionnaire covered basic demographic information, public knowledge of the epidemiological and clinical characteristics of COVID-19, psychological state, and attitudes towards the overall control measures. The primary outcome was the China’s public knowledge of COVID-19 and the attitudes towards control measures and secondary outcome was the psychological state of the public during this pandemic.

Results
The study included 10,905 participants and 10,399 valid questionnaires were included for analysis. Participants with tertiary education, younger participants and healthcare workers had better overall knowledge than other participants (all P < 0.05). Approximately 91.9% of the participants believed in person-to-person transmission and 39.1% believed in animal-to-person transmission. No significant correlation between anxiety and the number of regional existing confirmed cases was found, while participants in Hubei were more anxious than those in other regions. In general, 74.1% of the participants acknowledged the effectiveness of the overall control measures, and the percentage of participants with agreement with the overall control measures was negatively correlated with the number of regional existing confirmed cases (r = − 0.492, P = 0.007).

Conclusions
In conclusion, the survey revealed that the Chinese public had overall good knowledge of COVID-19 except for those indeterminate knowledges. With dynamic changes in the global pandemic situation and more research, further studies should be conducted to explore changes in public knowledge and attitudes towards COVID-19 in the future. The media could be used in a strict and regular manner to publicize knowledge of such pandemics to halt their spread.
Hashimoto’s thyroiditis worsens ovaries in polycystic ovary syndrome patients compared to Anti-Müllerian hormone levels
Authors: Serin Aliye Nigar , Birge Özer , Uysal Aysel , Görar Süheyla , Tekeli Feyza 
Published: March 2021

Abstract
Background
The human ovary is the target of autoimmune attack in cases of autoimmune disorders, which can cause ovarian dysfunction. Due to the higher prevalence of Hashimoto’s Thyroiditis (HT) in Polycystic Ovary Syndrome (PCOS) patients, we aimed to evaluate ovarian reserve and the effect of autoimmune exposure time on ovarian reserve in PCOS patients with HT by Anti-Müllerian hormone (AMH) levels.

Methods
Forty-six PCOS patients and 46 PCOS with HT diagnosed patients who are between 18 and 35 years old were recruited for this study. Detailed medical histories were obtained from all participants. Polycystic ovary image was evaluated and antral follicles were counted by transvaginal ultrasound. Modified Ferriman Gallwey score, body mass index, waist/hip ratio of the patients were examined. Hormonal, biochemical profiles and AMH levels of the patients were evaluated during the early follicular phase. The data of both groups were statistically analyzed with SPSS 18.0.

Results
20 (43.5%) patients in the PCOS group were fertile, 8 (17.4%) patients in the PCOS + HT group were fertile, fertility rate was significantly lower in PCOS + HT group. The mean AMH value was 8.8 ± 8.8 in the PCOS + HT group and 12.4 ± 8.1 in the PCOS group and it was significantly lower in the PCOS + HT group (p = 0.043). AMH values were significantly negatively correlated with anti-thyroid peroxidase antibody (anti-TPO) level and the duration of HT. There was a significant positive correlation between the anti-TPO level and the duration of HT.

Conclusıon
We pointed out that the coexistence of PCOS and HT, two prevalent diseases of reproductive age, further diminished ovarian reserve. More exposure of the ovaries to autoantibodies can cause ovarian destruction, similar to the thyroid gland like HT. Because of all these close relations with PCOS and thyroid dysfunctions, we recommend evaluating both thyroid autoantibodies and hormone levels in PCOS patients at the first visit. Patients with PCOS + HT should be monitored more closely to determine the fertility treatment options and control premature ovarian failure (POF) table.
Antitumor activities of Aspiletrein A, a steroidal saponin from Aspidistra letreae, on non-small cell lung cancer cells
Authors: Nguyen Hien Minh , Nguyen Hoai Thi , Seephan Suthasinee , Do Hang Bich , Nguyen Huy Truong , Ho Duc Viet , Pongrakhananon Varisa 
Published: March 2021

Abstract
Background
Lung cancer is one of the leading causes of death worldwide due to its strong proliferative and metastatic capabilities. The suppression of these aggressive behaviors is of interest in anticancer drug research and discovery. In recent years, many plants have been explored in order to discover new bioactive secondary metabolites to treat cancers or enhance treatment efficiency. Aspiletrein A (AA) is a steroidal saponin isolated from the whole endemic species Aspidistra letreae in Vietnam. Previously, elucidation of the structure of AA and screening of its cytotoxic activity against several cancer cell lines were reported. However, the antitumor activities and mechanisms of action have not yet been elucidated. In this study, we demonstrated the anti-proliferative, anti-migrative and anti-invasive effects of AA on H460, H23 and A549 human lung cancer cells.

Methods
MTT, wound healing and Transwell invasion assays were used to evaluate the anti-proliferation, anti-migration and anti-invasion effects of AA, respectively. Moreover, the inhibitory effect of AA on the activity of protein kinase B (Akt), a central mediator of cancer properties, and apoptotic regulators in the Bcl-2 family proteins were investigated by Western blotting.

Results
AA exhibits antimetastatic effects in human lung cancer cells through the inhibition of the pAkt/Akt signaling pathway, which in turn resulted in a significant inhibitory effect of AA on the migration and invasion of the examined lung cancer cells.

Conclusions
Aspiletrein A may be a potent inhibitor of protein kinase B (Akt). Hence, AA could be further explored as a potential antimetastatic lead compound.
Trichosanthin cooperates with Granzyme B to restrain tumor formation in tongue squamous cell carcinoma
Authors: Zhu Zeyao , Ying Zhenguang , Zeng Meiqi , Zhang Qiang , Liao Guiqing , Liang Yunliu , Li Chunman , Zhang Chengfei , Wang Xia , Jiang Weipeng , Luan Ping , Sha Ou 
Published: March 2021

Abstract
Background
Tongue squamous cell carcinoma (TSCC) is a common type of oral cancer, with a relatively poor prognosis and low post-treatment survival rate. Various strategies and novel drugs to treat TSCC are emerging and under investigation. Trichosanthin (TCS), extracted from the root tubers of Tian-Hua-Fen, has been found to have multiple biological and pharmacological functions, including inhibiting the growth of cancer cells. Granzyme B (GrzB) is a common toxic protein secreted by natural killer cells and cytotoxic T cells. Our group has reported that TCS combined with GrzB might be a superior approach to inhibit liver tumor progression, but data relating to the use of this combination to treat TSCC remain limited. The aim of this study was to examine the effectiveness of TCS on TSCC processes and underlying mechanisms.

Methods
First, we screened the potential antitumor activity of TCS using two types of SCC cell lines. Subsequently, a subcutaneous squamous cell carcinoma xenograft model in nude mice was established. These model mice were randomly divided into four groups and treated as follows: control group, TCS treatment group, GrzB treatment group, and TCS/GrzB combination treatment group. Various tumorigenesis parameters, such as Ki67, PCNA, caspase-3, Bcl-2 and VEGFA, et al., were performed to determine the effects of these treatments on tumor development.

Results
Screening confirmed that the SCC25 line exhibited greater sensitivity than the SCC15 line to TCS in vitro studies. TCS or GrzB treatment significantly inhibited tumor growth compared with the inhibition seen in the control group. The TCS/GrzB combination inhibited tumor growth more than either drug alone. TCS treatment inhibited tumor proliferation by downregulating Ki67 and Bcl2 protein expression while accelerating tumor apoptosis. In the TCS/GrzB-treated group, expression of Ki67 was further downregulated, while the level of activated caspase-3 was increased, compared with their expression in either of the single drug treatment groups.

Conclusion
These results suggest that the TCS/GrzB combination could represent an effective immunotherapy for TSCC.
A novel model to label delirium in an intensive care unit from clinician actions
Authors: Coombes Caitlin E. , Coombes Kevin R. , Fareed Naleef 
Published: March 2021

AbstractBackgroundIn the intensive care unit (ICU), delirium is a common, acute, confusional state associated with high risk for short- and long-term morbidity and mortality. Machine learning (ML) has promise to address research priorities and improve delirium outcomes. However, due to clinical and billing conventions, delirium is often inconsistently or incompletely labeled in electronic health record (EHR) datasets. Here, we identify clinical actions abstracted from clinical guidelines in electronic health records (EHR) data that indicate risk of delirium among intensive care unit (ICU) patients. We develop a novel prediction model to label patients with delirium based on a large data set and assess model performance.MethodsEHR data on 48,451 admissions from 2001 to 2012, available through Medical Information Mart for Intensive Care-III database (MIMIC-III), was used to identify features to develop our prediction models. Five binary ML classification models (Logistic Regression; Classification and Regression Trees; Random Forests; Naïve Bayes; and Support Vector Machines) were fit and ranked by Area Under the Curve (AUC) scores. We compared our best model with two models previously proposed in the literature for goodness of fit, precision, and through biological validation.ResultsOur best performing model with threshold reclassification for predicting delirium was based on a multiple logistic regression using the 31 clinical actions (AUC 0.83). Our model out performed other proposed models by biological validation on clinically meaningful, delirium-associated outcomes.ConclusionsHurdles in identifying accurate labels in large-scale datasets limit clinical applications of ML in delirium. We developed a novel labeling model for delirium in the ICU using a large, public data set. By using guideline-directed clinical actions independent from risk factors, treatments, and outcomes as model predictors, our classifier could be used as a delirium label for future clinically targeted models.
Conservation and trans-regulation of histone modification in the A and B subgenomes of polyploid wheat during domestication and ploidy transition
Authors: Lv Zhenling , Li Zijuan , Wang Meiyue , Zhao Fei , Zhang Wenjie , Li Changping , Gong Lei , Zhang Yijng , Mason Annaliese S. , Liu Bao 
Published: March 2021

Abstract
Background
Polyploidy has played a prominent role in the evolution of plants and many other eukaryotic lineages. However, how polyploid genomes adapt to the abrupt presence of two or more sets of chromosomes via genome regulation remains poorly understood. Here, we analyzed genome-wide histone modification and gene expression profiles in relation to domestication and ploidy transition in the A and B subgenomes of polyploid wheat.

Results
We found that epigenetic modification patterns by two typical euchromatin histone markers, H3K4me3 and H3K27me3, for the great majority of homoeologous triad genes in A and B subgenomes were highly conserved between wild and domesticated tetraploid wheats and remained stable in the process of ploidy transitions from hexaploid to extracted tetraploid and then back to resynthesized hexaploid. However, a subset of genes was differentially modified during tetraploid and hexaploid wheat domestication and in response to ploidy transitions, and these genes were enriched for particular gene ontology (GO) terms. The extracted tetraploid wheat manifested higher overall histone modification levels than its hexaploid donor, and which were reversible and restored to normal levels in the resynthesized hexaploid. Further, while H3K4me3 marks were distally distributed along each chromosome and significantly correlated with subgenome expression as expected, H3K27me3 marks showed only a weak distal bias and did not show a significant correlation with gene expression.

Conclusions
Our results reveal overall high stability of histone modification patterns in the A and B subgenomes of polyploid wheat during domestication and in the process of ploidy transitions. However, modification levels of a subset of functionally relevant genes in the A and B genomes were trans-regulated by the D genome in hexaploid wheat.
Quantifying the potential value of antigen-detection rapid diagnostic tests for COVID-19: a modelling analysis
Authors: Ricks Saskia , Kendall Emily A. , Dowdy David W. , Sacks Jilian A. , Schumacher Samuel G. , Arinaminpathy Nimalan 
Published: March 2021

Abstract
Background
Testing plays a critical role in treatment and prevention responses to the COVID-19 pandemic. Compared to nucleic acid tests (NATs), antigen-detection rapid diagnostic tests (Ag-RDTs) can be more accessible, but typically have lower sensitivity and specificity. By quantifying these trade-offs, we aimed to inform decisions about when an Ag-RDT would offer greater public health value than reliance on NAT.

Methods
Following an expert consultation, we selected two use cases for analysis: rapid identification of people with COVID-19 amongst patients admitted with respiratory symptoms in a ‘hospital’ setting and early identification and isolation of people with mildly symptomatic COVID-19 in a ‘community’ setting. Using decision analysis, we evaluated the health system cost and health impact (deaths averted and infectious days isolated) of an Ag-RDT-led strategy, compared to a strategy based on NAT and clinical judgement. We adopted a broad range of values for ‘contextual’ parameters relevant to a range of settings, including the availability of NAT and the performance of clinical judgement. We performed a multivariate sensitivity analysis to all of these parameters.

Results
In a hospital setting, an Ag-RDT-led strategy would avert more deaths than a NAT-based strategy, and at lower cost per death averted, when the sensitivity of clinical judgement is less than 90%, and when NAT results are available in time to inform clinical decision-making for less than 85% of patients. The use of an Ag-RDT is robustly supported in community settings, where it would avert more transmission at lower cost than relying on NAT alone, under a wide range of assumptions.

Conclusions
Despite their imperfect sensitivity and specificity, Ag-RDTs have the potential to be simultaneously more impactful, and have a lower cost per death and infectious person-days averted, than current approaches to COVID-19 diagnostic testing.
The ESCRT-III molecules regulate the apical targeting of bile salt export pump
Authors: Wu Shang-Hsin , Chang Mei-Hwei , Chen Ya-Hui , Wu Hui-Lin , Chua Huey-Huey , Chien Chin-Sung , Ni Yen-Hsuan , Chen Hui-Ling , Chen Huey-Ling 
Published: March 2021

AbstractBackgroundThe bile salt export pump (BSEP) is a pivotal apical/canalicular bile salt transporter in hepatocytes that drives the bile flow. Defects in BSEP function and canalicular expression could lead to a spectrum of cholestatic liver diseases. One prominent manifestation of BSEP-associated cholestasis is the defective canalicular localization and cytoplasmic retention of BSEP. However, the etiology of impaired BSEP targeting to the canalicular membrane is not fully understood. Our goal was to discover what molecule could interact with BSEP and affect its post-Golgi sorting.MethodsThe human BSEP amino acids (a.a.) 491-630 was used as bait to screen a human fetal liver cDNA library through yeast two-hybrid system. We identified a BSEP-interacting candidate and showed the interaction and colocalization in the co-immunoprecipitation in hepatoma cell lines and histological staining in human liver samples. Temperature shift assays were used to study the post-Golgi trafficking of BSEP. We further determine the functional impacts of the BSEP-interacting candidate on BSEP in vitro. A hydrodynamically injected mouse model was established for in vivo characterizing the long-term impacts on BSEP.ResultsWe identified that charged multivesicular body protein 5 (CHMP5), a molecule of the endosomal protein complex required for transport subcomplex-III (ESCRT-III), interacted and co-localized with BSEP in the subapical compartments (SACs) in developing human livers. Cholestatic BSEP mutations in the CHMP5-interaction region have defects in canalicular targeting and aberrant retention at the SACs. Post-Golgi delivery of BSEP and bile acid secretion were impaired in ESCRT-III perturbation or CHMP5-knockdown hepatic cellular and mouse models. This ESCRT-III-mediated BSEP sorting preceded Rab11A-regulated apical cycling of BSEP.ConclusionsOur results showed the first example that ESCRT-III is essential for canalicular trafficking of apical membrane proteins, and provide new targets for therapeutic approaches in BSEP associated cholestasis.
CircNEIL3 regulatory loop promotes pancreatic ductal adenocarcinoma progression via miRNA sponging and A-to-I RNA-editing
Authors: Shen Peng , Yang Taoyue , Chen Qun , Yuan Hao , Wu Pengfei , Cai Baobao , Meng Lingdong , Huang Xumin , Liu Jiaye , Zhang Yihan , Hu Weikang , Miao Yi , Lu Zipeng , Jiang Kuirong 
Published: March 2021

Abstract
Background
A growing number of studies have focused on investigating circRNAs as crucial regulators in the progression of multiple cancer types. Nevertheless, the biological effects and underlying mechanisms of circRNAs in pancreatic ductal adenocarcinoma (PDAC) remain unclear.

Methods
Differentially expressed circRNAs between cancerous tissue and adjacent normal tissues were identified by RNA sequencing in PDAC. Subsequently, in vitro and in vivo functional experiments were performed to investigate the functional roles of circNEIL3 in PDAC tumour growth and metastasis. Furthermore, RNA pull-down, dual-luciferase reporter assays, RNA immunoprecipitation (RIP) assays, fluorescent in situ hybridization (FISH) and Sanger sequencing assays were performed to examine the circular interaction among circNEIL3, miR-432-5p and adenosine deaminases acting on RNA 1 (ADAR1).

Results
CircNEIL3 was upregulated in PDAC and promoted the progression of PDAC cells both in vitro and in vivo. Mechanistically, circNEIL3 was shown to regulate the expression of ADAR1 by sponging miR-432-5p to induce RNA editing of glioma-associated oncogene 1 (GLI1), ultimately influencing cell cycle progression and promoting epithelial-to-mesenchymal transition (EMT) in PDAC cells. Moreover, we discovered that the circNEIL3/miR-432-5p/ADAR1 axis was correlated with the PDAC clinical stage and overall survival of PDAC patients, while ADAR1 may reduce the biogenesis of circNEIL3.

Conclusions
Our findings reveal that circNEIL3 facilitates the proliferation and metastasis of PDAC through the circNEIL3/miR-432-5p/ADAR1/GLI1/cell cycle and EMT axis and that its expression is regulated by ADAR1 through a negative feedback loop. Therefore, circNEIL3 may serve as a prognostic marker and a therapeutic target for PDAC.
Effect of Buyang Huanwu decoction for the rehabilitation of ischemic stroke patients: a meta-analysis of randomized controlled trials
Authors: Gao Li , Xiao Zhuoran , Jia Chunhua , Wang Wei 
Published: March 2021

AbstractPurposeBuyang Huanwu decoction (BHD) is a widely used traditional Chinese medicine for the rehabilitation of ischemic stroke patients in China, but its clinical efficacy and safety have not been adequately assessed. In this paper, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of BHD.MethodsWe searched seven electronic databases from inception to 31 March 2019. The language was limited to Chinese and English. Randomized controlled trials evaluating the efficacy and safety of BHD for the rehabilitation of ischemic stroke patients were included in the meta-analysis. Reviewers independently performed the screening, data extraction, bias assessment, and data analysis. The treatment efficacy was pooled in a meta-analysis using RevMan 5.3 software with a random-effect model. Any disagreement was resolved by discussion among all reviewers. The PRISMA statement was used in the review process.ResultsA total of 11 studies with 1084 patients were included in the meta-analysis. The results suggested that BHD was superior to other treatments in terms of clinical efficacy in symptoms and daily activities (n = 684, RR = 1.12, 95% CI: 0.99 to 1.27), clinical efficacy in TCM symptoms (n = 280, RR = 1.45, 95% CI: 1.03 to 2.03), National Institute of Health stroke scale (n = 192, MD = 1.66, 95% CI: -1.08 to 4.40), and activities of daily living (n = 200, MD = 8.20, 95% CI: -3.95 to 20.35).ConclusionsThe results supported the clinical use of BHD for the rehabilitation of ischemic stroke patients. However, the methodological qualities of the included studies were relatively low, and there were limited reports on adverse events. The clinical efficacy and safety of BHD need to be further confirmed by more well-designed and high-quality randomized controlled trials to warrant the clinical recommendation of BHD for the rehabilitation of ischemic stroke patients.