bluuebunny/crossref_metadata_2025_split huggingface dataset:
LncRNA DRAIC inhibits proliferation and metastasis of gastric cancer cells through interfering with NFRKB deubiquitination mediated by UCHL5
Authors: Zhang Zheng , Hu Xiaoxuan , Kuang Jia , Liao Jinmao , Yuan Qi 
Published: April 2020

Abstract
Background
Long non-coding RNA (lncRNA) as a widespread and pivotal epigenetic molecule participates in the occurrence and progression of malignant tumors. DRAIC, a kind of lncRNA whose coding gene location is on 15q23 chromatin, has been found to be weakly expressed in a variety of malignant tumors and acts as a suppressor, but its characteristics and role in gastric cancer (GC) remain to be elucidated.

Methods
Sixty-seven primary GC tissues and paired paracancerous normal tissues were collected. Bioinformatics is used to predict the interaction molecules of DRAIC. DRAIC and NFRKB were overexpressed or interfered exogenously in GC cells by lentivirus or transient transfection. Quantitative real-time PCR (qPCR) and western blotting were used to evaluate the expression of DRAIC, UCHL5 and NFRKB. The combinations of DRAIC and NFRKB or UCHL5 and NFRKB were verified by RNA-IP and Co-IP assays. Ubiquitination-IP and the treatment of MG132 and CHX were used to detect the ubiquitylation level of NFRKB. The CCK-8 and transwell invasion and migration assays measured the proliferation, migration and invasion of GC cells.

Results
DRAIC is down-regulated in GC tissues and cell lines while its potential interacting molecules UCHL5 and NFRKB are up-regulated, and DRAIC is positively correlated with NFRKB protein instead of mRNA. Lower DRAIC and higher UCHL5 and NFRKB indicated advanced progression of GC patients. DRAIC could increase NFRKB protein significantly instead of NFRKB mRNA and UCHL5, and bind to UCHL5. DRAIC combined with UCHL5 and attenuated binding of UCHL5 and NFRKB, meanwhile promoting the degradation of NFRKB via ubiquitination, and then inhibited the proliferation and metastasis of GC cells, which can be rescued by oeNFRKB.

Conclusion
DRAIC suppresses GC proliferation and metastasis via interfering with the combination of UCHL5 and NFRKB and mediating ubiquitination degradation.
GiniClust3: a fast and memory-efficient tool for rare cell type identification
Authors: Dong Rui , Yuan Guo-Cheng 
Published: April 2020

Abstract
Background
With the rapid development of single-cell RNA sequencing technology, it is possible to dissect cell-type composition at high resolution. A number of methods have been developed with the purpose to identify rare cell types. However, existing methods are still not scalable to large datasets, limiting their utility. To overcome this limitation, we present a new software package, called GiniClust3, which is an extension of GiniClust2 and significantly faster and memory-efficient than previous versions.

Results
Using GiniClust3, it only takes about 7 h to identify both common and rare cell clusters from a dataset that contains more than one million cells. Cell type mapping and perturbation analyses show that GiniClust3 could robustly identify cell clusters.

Conclusions
Taken together, these results suggest that GiniClust3 is a powerful tool to identify both common and rare cell population and can handle large dataset. GiniCluster3 is implemented in the open-source python package and available at https://github.com/rdong08/GiniClust3.
High dimensional model representation of log-likelihood ratio: binary classification with expression data
Authors: Foroughi pour Ali , Pietrzak Maciej , Dalton Lori A , Rempała Grzegorz A. 
Published: April 2020

Abstract
Background
Binary classification rules based on a small-sample of high-dimensional data (for instance, gene expression data) are ubiquitous in modern bioinformatics. Constructing such classifiers is challenging due to (a) the complex nature of underlying biological traits, such as gene interactions, and (b) the need for highly interpretable glass-box models. We use the theory of high dimensional model representation (HDMR) to build interpretable low dimensional approximations of the log-likelihood ratio accounting for the effects of each individual gene as well as gene-gene interactions. We propose two algorithms approximating the second order HDMR expansion, and a hypothesis test based on the HDMR formulation to identify significantly dysregulated pairwise interactions. The theory is seen as flexible and requiring only a mild set of assumptions.

Results
We apply our approach to gene expression data from both synthetic and real (breast and lung cancer) datasets comparing it also against several popular state-of-the-art methods. The analyses suggest the proposed algorithms can be used to obtain interpretable prediction rules with high prediction accuracies and to successfully extract significantly dysregulated gene-gene interactions from the data. They also compare favorably against their competitors across multiple synthetic data scenarios.

Conclusion
The proposed HDMR-based approach appears to produce a reliable classifier that additionally allows one to describe how individual genes or gene-gene interactions affect classification decisions. Both real and synthetic data analyses suggest that our methods can be used to identify gene networks with dysregulated pairwise interactions, and are therefore appropriate for differential networks analysis.
Effect of number of annual rings and tree ages on genomic predictive ability for solid wood properties of Norway spruce
Authors: Zhou Linghua , Chen Zhiqiang , Olsson Lars , Grahn Thomas , Karlsson Bo , Wu Harry X. , Lundqvist Sven-Olof , García-Gil María Rosario 
Published: April 2020

AbstractBackgroundGenomic selection (GS) or genomic prediction is considered as a promising approach to accelerate tree breeding and increase genetic gain by shortening breeding cycle, but the efforts to develop routines for operational breeding are so far limited. We investigated the predictive ability (PA) of GS based on 484 progeny trees from 62 half-sib families in Norway spruce (Picea abies(L.) Karst.) for wood density, modulus of elasticity (MOE) and microfibril angle (MFA) measured with SilviScan, as well as for measurements on standing trees by Pilodyn and Hitman instruments.ResultsGS predictive abilities were comparable with those based on pedigree-based prediction. Marker-based PAs were generally 25–30% higher for traits density, MFA and MOE measured with SilviScan than for their respective standing tree-based method which measured with Pilodyn and Hitman. Prediction accuracy (PC) of the standing tree-based methods were similar or even higher than increment core-based method. 78–95% of the maximal PAs of density, MFA and MOE obtained from coring to the pith at high age were reached by using data possible to obtain by drilling 3–5 rings towards the pith at tree age 10–12.ConclusionsThis study indicates standing tree-based measurements is a cost-effective alternative method for GS. PA of GS methods were comparable with those pedigree-based prediction. The highest PAs were reached with at least 80–90% of the dataset used as training set. Selection for trait density could be conducted at an earlier age than for MFA and MOE. Operational breeding can also be optimized by training the model at an earlier age or using 3 to 5 outermost rings at tree age 10 to 12 years, thereby shortening the cycle and reducing the impact on the tree.
Noise exposure alters MMP9 and brevican expression in the rat primary auditory cortex
Authors: Park Sung-su , Lee Da-hye , Lee So Min , Lee Chang Ho , Kim So Young 
Published: April 2020

Abstract
Background
This study aimed to investigate the changes in molecules related to perineuronal nets (PNNs) and synaptic transporters in the primary auditory cortices of rats with noise-induced hearing loss. Female Sprague–Dawley rats at postnatal day 7 were divided into the noise and control groups. Four hours of 115 dB SPL white noise was delivered for 10 days to the noise group. Thirty days after noise exposure, the primary auditory cortex and the inferior colliculus were harvested. The expression levels of vesicular glutamatergic transporter (VGLUT)1, VGLUT2, vesicular GABA transporter (VGAT), glutamate decarboxylase (GAD)67, brevican, aggrecan, MMP9, and MMP14 were evaluated using real-time reverse transcription polymerase chain reaction or western blot. An immunofluorescence assay was conducted to assess parvalbumin (PV), Wisteria floribunda agglutinin (WFA), and brevican. The immune-positive cells were counted in the primary auditory cortex.

Results
The expression level of VGLUT1 in the primary auditory cortex was decreased in the noise group. The expression level of VGLUT2 in the inferior colliculus was elevated in the noise group. The expression levels of brevican and PV + WFA in the primary auditory cortex were decreased in the noise group. The expression level of MMP9 in the primary auditory cortex was increased in the noise group.

Conclusion
Noise-induced hearing loss during the precritical period impacted PNN expression in the primary auditory cortex. Increased MMP9 expression may have contributed to the decrease in brevican expression. These changes were accompanied by the attenuation of glutamatergic synaptic transporters.
Improvement of growth performance of Amorpha fruticosa under contrasting regime of water and fertilizer in coal-contaminated spoils using response surface methodology
Authors: Roy Rana , Mostofa Mohammad Golam , Wang Jinxin , Sikdar Ashim , Sarker Tanwne 
Published: April 2020

Abstract
Background
Water availability and nutrient-status of soils play crucial roles in seedling establishment and plant survival in coal-spoiled areas worldwide. Restoration of spoils pertains to the application of proper doses of nutrients and water, and selection of particular plant species for efficient revegetation. This study aimed at examining the potential effects of different combinations of soil-water and fertilizers (nitrogen, N and phosphorus, P) on morpho-physiological and biochemical attributes of Amorpha fruticosa grown in coal-mined spoils. Three factors five-level central-composite-design with optimization technique response surface methodology (rsm) was used to optimize water irrigation and fertilizer application strategies.

Results
Our results revealed a strong correlation between experimental data and predicted values developed from the rsm model. The best responses of A. fruticosa in terms of plant height, stem diameter, root length, and dry biomass were observed under a high-water regime. Low-water regime caused a notable reduction in growth-associated parameters, and fertilization with either N or P did not show positive effects on those parameters, indicating that soil-water was the most influential factor for growth performance. Leaf water potential, gas-exchange parameters, and chlorophyll content significantly increased under high levels of soil-water, N and P, suggesting a synergistic effect of these factors for the improvement of photosynthesis-related parameters. At low soil-water contents and N-P fertilizer application levels, enhanced accumulation of malondialdehyde and proline indicated that A. fruticosa suffered from oxidative and osmotic stresses. Amorpha fruticosa also responded to oxidative stress by accelerating the activities of superoxide dismutase, catalase, and peroxidase. The effects of both fertilizers relied on soil-water, and fertilization was most effective under well-watered conditions. The maximum growth of A. fruticosa was observed under the combination of soil-water, N-dose and P-dose at 76% field capacity, 52.0 mg kg− 1 and 49.0 mg kg− 1, respectively.

Conclusion
Our results demonstrate that rsm effectively designed appropriate doses of water and N-P fertilizer to restore coal-spoiled soils. Furthermore, A. fruticosa responded to low-water and fertilizer-shortage by upregulating defensive mechanism to avoid damage induced by such deficiencies. Finally, our findings provide effective strategies for revegetation of coal-contaminated spoils with A. fruticosa using appropriate doses of water and N-P fertilizers.
Transcriptomic profiling and discovery of key genes involved in adventitious root formation from green cuttings of highbush blueberry (Vaccinium corymbosum L.)
Authors: An Haishan , Zhang Jiaying , Xu Fangjie , Jiang Shuang , Zhang Xueying 
Published: April 2020

Abstract
Background
Propagation of cuttings is frequently used in various plant species, including blueberry, which shows special root characteristics that may hinder adventitious root (AR) formation. AR formation is influenced by various factors, and auxin is considered to play a central role; however, little is known of the related regulatory mechanisms. In this study, a comparative transcriptome analysis of green cuttings treated with or without indole-butyric acid (IBA) was performed via RNA_seq to identify candidate genes associated with IBA-induced AR formation.

Results
Rooting phenotypes, especially the rooting rate, were significantly promoted by exogenous auxin in the IBA application. Blueberry AR formation was an auxin-induced process, during which adventitious root primordium initiation (rpi) began at 14 days after cutting (DAC), root primordium (rp) was developed at 21 DAC, mature AR was observed at 28 DAC and finally outgrowth from the stem occurred at 35 DAC. Higher IAA levels and lower ABA and zeatin contents might facilitate AR formation and development. A time series transcriptome analysis identified 14,970 differentially expressed genes (DEGs) during AR formation, of which there were 7467 upregulated and 7503 downregulated genes. Of these, approximately 35 candidate DEGs involved in the auxin-induced pathway and AR formation were further identified, including 10 auxin respective genes (ARFs and SAURs), 13 transcription factors (LOB domain-containing protein (LBDs)), 6 auxin transporters (AUX22, LAX3/5 and PIN-like 6 (PIL6s)) and 6 rooting-associated genes (root meristem growth factor 9 (RGF9), lateral root primordium 1 (LRP1s), and dormancy-associated protein homologue 3 (DRMH3)). All these identified DEGs were highly upregulated in certain stages during AR formation, indicating their potential roles in blueberry AR formation.

Conclusions
The transcriptome profiling results indicated candidate genes or major regulatory factors that influence adventitious root formation in blueberry and provided a comprehensive understanding of the rooting mechanism underlying the auxin-induced AR formation from blueberry green cuttings.
Circulating heat shock protein 27 as a novel marker of subclinical atherosclerosis in type 2 diabetes: a cross-sectional community-based study
Authors: Wang Xinru , Shi Jie , Lu Bin , Zhang Weiwei , Yang Yehong , Wen Jie , Hu Renming , Yang Zhen , Wang Xuanchun 
Published: April 2020

Abstract
Background
Heat shock protein 27 (HSP27) has been proposed as a vital protective factor in atherosclerosis. The objective of the present study was to evaluate the association between circulating HSP27 and carotid intima–media thickness (IMT) in individuals with type 2 diabetes and to determine whether HSP27 represents an independent marker of subclinical atherosclerosis in this patient population.

Methods
We performed a cross-sectional community-based study in 186 Chinese subjects with a median duration of type 2 diabetes of 8.2 years who underwent ultrasound carotid IMT measurement. Serum HSP27 levels were assessed by ELISA.

Results
Serum HSP27 levels were significantly higher in the IMT (+, > 1.0 mm) group than in the IMT (−, ≤1.0 mm) group, with the median values of 8.80 ng/mL (5.62–12.25) and 6.93 ng/mL (4.23–9.60), respectively (P = 0.006). The discriminative value of HSP27 to evaluate IMT was 7.16 ng/mL and the area under the curve was 0.72 (95%CI = 0.64–0.80, P = 0.0065). Spearman’s rank correlation analysis demonstrated that the concentrations of circulating HSP27 were positively associated with carotid IMT (r = 0.198, P = 0.007) and blood urea nitrogen (r = 0.170, P < 0.05). Furthermore, in the logistic model, serum HSP27 levels were found to be independent predictors for carotid IMT in type 2 diabetic patients after adjustment for onset age of diabetes, blood pressure, total cholesterol and C-reactive protein (OR = 1.085, P = 0.022).

Conclusions
Circulating HSP27, positively correlates with carotid IMT, is an independent predictor for early atherosclerotic changes in diabetes, and may represent a novel marker of subclinical atherosclerosis in type 2 diabetes.
Evaluation and comparison of six GRACE models for the stratification of undifferentiated chest pain in the emergency department
Authors: Zheng Wen , Wang Guangmei , Ma Jingjing , Wu Shuo , Zhang He , Zheng Jiaqi , Xu Feng , Wang Jiali , Chen Yuguo 
Published: April 2020

Abstract
Background
The Global Registry of Acute Coronary Events (GRACE) score is recommended for stratifying chest pain. However, there are six formulas used to calculate the GRACE score for different outcomes of acute coronary syndrome (ACS), including death (Dth) or composite of death and myocardial infarction (MI), while in hospital (IH), within 6 months after discharge (OH6m) or from admission to 6 months later (IH6m). We aimed to perform the first comprehensive evaluation and comparison of six GRACE models to predict 30-day major adverse cardiac events (MACEs) in patients with acute chest pain in the emergency department (ED).

Methods
Patients with acute chest pain were consecutively recruited from August 24, 2015 to September 30, 2017 from the EDs of two public hospitals in China. The 30-day MACEs included death, acute myocardial infarction (AMI), emergency revascularization, cardiac arrest and cardiogenic shock. The correlation, calibration, discrimination, reclassification and diagnostic accuracy at certain cutoff values of six GRACE models were evaluated. Comparisons with the History, ECG, Age, Risk Factors, and Troponin (HEART) and Thrombolysis in Myocardial Infarction (TIMI) scores were conducted.

Results
A total of 2886 patients were analyzed, with 590 (20.4%) patients experiencing outcomes. The GRACE (IHDthMI), GRACE (IH6mDthMI), GRACE (IHDth), GRACE (IH6mDth), GRACE (OH6mDth) and GRACE (OH6mDthMI) showed positive linear correlations with the actual MACE rates (r ≥ 0.568, P < 0.001). All these models had good calibration (Hosmer-Lemeshow test, P ≥ 0.073) except GRACE (IHDthMI) (P < 0.001). The corresponding C-statistics were 0.83(0.81,0.84), 0.82(0.81,0.83), 0.75(0.73,0.76), 0.73(0.72,0.75), 0.72(0.70,0.73) and 0.70(0.68,0.71), respectively, first two of which were comparable to HEART (0.82, 0.80–0.83) and superior to TIMI (0.71, 0.69–0.73). With a sensitivity ≥95%, GRACE (IHDthMI) ≤81 and GRACE (IH6mDthMI) ≤79 identified 868(30%) and 821(28%) patients as low risk, respectively, which were significantly better than other GRACEs and HEART ≤3(22%). With a specificity ≥95%, GRACE (IHDthMI) > 186 and GRACE (IH6mDthMI) > 161 could recognize 12% and 11% patients as high risk, which were greater than other GRACEs, HEART ≥8(9%) and TIMI ≥5(8%).

Conclusions
In this Chinese setting, certain strengths of GRACE models beyond HEART and TIMI scores were still noteworthy for stratifying chest pain patients. The validation and reasonable application of appropriate GRACE models in the evaluation of undifferentiated chest pain should be recommended.
Cardiopulmonary exercise capacity and quality of life of patients with heart failure undergoing a functional training program: study protocol for a randomized clinical trial
Authors: do Nascimento Daniela Meirelles , Machado Karina Costa , Bock Patrícia Martins , Saffi Marco Aurélio Lumertz , Goldraich Livia Adams , Silveira Anderson Donelli , Clausell Nadine , Schaan Beatriz D. 
Published: April 2020

Abstract
Background
Exercise intolerance is a common finding in heart failure that generates a vicious cycle in which the individual starts to limit his activities even more due to progressive fatigue. Regular physical exercise can increase the cardiopulmonary exercise capacity of these individuals. A new approach to physical exercise, known as functional training, could improve the oxygen consumption and quality of life of patients with heart failure; however, there is no information about the effect of this modality of exercise in this patient population. This randomized trial will compare the effects of 36 sessions of functional training versus strength training in heart failure patients.

Methods
This randomized parallel-design examiner-blinded clinical trial includes individuals of both sexes aged ≥40 years receiving regular follow-up at a single academic hospital. Subjects will be randomly allocated to an intervention group (for 12-week functional training) or an active comparator group (for 12-week strength training). The primary outcomes will be the difference from baseline to the 3-month time point in peak oxygen consumption on cardiopulmonary exercise testing and quality of life assessed by the Minnesota Living with Heart Failure Questionnaire. Secondary outcome measures will include functionality assessed by the Duke Activity Status Index and gait speed test; peripheral and inspiratory muscular strength, assessed by hand grip and manovacuometry testing, respectively; endothelial function by brachial artery flow-mediated dilation; lean body mass by arm muscle circumference; and participant adherence to the exercise programs classified as a percentage of the prescribed exercise dose.

Discussion
The functional training program aims to improve the functional capacity of the individual using exercises that relate to his specific physical activity transferring gains effectively to one’s daily life. In this context, we believe that that functional training can increase the cardiopulmonary exercise capacity and quality of life of patients with heart failure. The trial has been recruiting patients since October 2017.

Trial registration
NCT03321682. Registered on October 26, 2017.
Time trends analysis of statin prescription prevalence, therapy initiation, dose intensity, and utilization from the hospital information system of Jinshan Hospital, Shanghai (2012–2018)
Authors: Liu Yujuan , Lv Xiaoqun , Xie Ning , Fang Zhonghong , Ren Weifang , Gong Yuan , Jin Yan , Zhang Jun 
Published: April 2020

Abstract
Background
Statin remains a mainstay in the prevention and treatment of cardiovascular diseases. Statin utilization has evolved over time in many countries, but data on this topic from China are quite limited. This study aimed to investigate the changing trends of statins prescription, as well as detail the statin utilization through a successive longitudinal study.

Methods
The prescription database was established based on electronic health records retrieved from the hospital information system of Jinshan Hospital, Fudan University from January 2012 to December 2018 in Shanghai, China. The prescription rates and proportions of different statin types and doses among all patients were examined. Sub-analyses were performed when stratifying the patients by age, gender, dose intensity, and preventative intervention.

Results
During the study period, a total of 51,083 patients, who were prescribed for statins, were included in this study (mean [SD] age, 59.78 [±13.16] years; 53.60% male, n = 27, 378). The overall statins prescription rate in which patients increased from 2012 (1.24, 95% CI: 1.21-1.27%) to 2018 (3.16, 95% CI: 3.11–3.20%), P < 0.001. Over 90% of patients were given a moderate dose of statins. Patients with a history of coronary and cerebrovascular events (over 32%) were more likely to be prescribed with statins for preventative intervention. Furthermore, our study has witnessed a significant rise in statin therapy in primary and secondary prevention.

Conclusions
In conclusion, statins were frequently prescribed and steadily increased over time in our study period. There were also changes in statin drug choices and dosages. A coordinated effort among the patient, clinical pharmacist, stakeholders and health system is still needed to improve statin utilization in clinical practice in the future.