bluuebunny/crossref_metadata_2025_split huggingface dataset:
LncRNA-MEG3 functions as ferroptotic promoter to mediate OGD combined high glucose-induced death of rat brain microvascular endothelial cells via the p53-GPX4 axis
Authors: Chen Cheng , Huang Yan , Xia Pingping , Zhang Fan , Li Longyan , Wang E , Guo Qulian , Ye Zhi 
Published: May 2020

Abstract
Background

Individuals with diabetes are exposed to a higher risk of perioperative stroke than non-diabetics mainly due to persistent hyperglycemia. lncRNA-MEG3 (long non-coding RNA maternally expressed gene 3) has been considered as an important mediator in regulating ischemic stroke. However, the functional and regulatory roles of lncRNA-MEG3 in diabetic brain ischemic injury remain unclear.

Results

In this study, RBMVECs (the rat brain microvascular endothelial cells) were exposed to 6 h of OGD (oxygen and glucose deprivation), and subsequent reperfusion via incubating cells with glucose of various high concentrations for 24 h to imitate in vitro diabetic brain ischemic injury. It was shown that the marker events of ferroptosis and increased lncRNA-MEG3 expression occurred after the injury induced by OGD combined with hyperglycemic treatment. However, all ferroptotic events were reversed with the treatment of MEG3-siRNA. Moreover, in this in vitro model, p53 was also characterized as a downstream target of lncRNA-MEG3. Furthermore, p53 knockdown protected RBMVECs against OGD + hyperglycemic reperfusion-induced ferroptosis, while the overexpression of p53 exerted opposite effects, implying that p53 served as a positive regulator of ferroptosis. Additionally, the overexpression or knockdown of p53 significantly modulated GPX4 expression in RBMVECs exposed to the injury induced by OGD combined with hyperglycemic treatment. Furthermore, GPX4 expression was suppressed again after the introduction of p53 into cells silenced by lncRNA-MEG3. Finally, ChIP assay uncovered that p53 was bound to GPX4 promoter.

Conclusions

Altogether, these data revealed that, by modulating GPX4 transcription and expression, the lncRNA-MEG3-p53 signaling pathway mediated the ferroptosis of RBMVECs upon injury induced by OGD combined with hyperglycemic treatment.
A novel panel based on Immune infiltration and tumor mutational burden for prognostic prediction in hepatocellular carcinoma
Authors: Wu Hewei , Zheng Xingrong , Pan Tao , Yang Xiaoan , Zhang Genglin , Lian Yunwen , Lin Jiaxin , Peng Liang , Xie Chan 
Published: May 2020

Abstract
Background : Tumor mutation burden (TMB) was associated with prognosis in various malignancies, but it remains to be elucidated in hepatocellular carcinoma (HCC). We aimed to investigate the prognostic effects of TMB and its relationship with immune infiltration so as to establish a panel model capable of predicting prognosis.

Methods : TMB was calculated in all 374 HCC patients from the Cancer Genome Atlas, and high TMB and low TMB groups were determined based on propensity score matching and X-tile analysis. WCGNA was utilized to screen out genes related to immune cells and TMB, followed by multivariate analysis to generated the final TMB-Infiltration (TMB-IF) panel. 453 HCC patients from ICGC-LIRI-JP, GSE76427 and GSE20017 verified the robustness and extensibility of TMB-IF. Additionally, whole-exome sequencing (WES) was performed in 8 follow-up patients to investigate the relationship between HCC recurrence and TMB.

Results : Patients in high TMB group had worse prognosis than those in low TMB group, with a cutoff TMB value of 4.9. Enrichment analysis demonstrated that differentially expressed genes were mainly related to T cell activation, cell membrane localization and matrix composition. Tumor immune infiltration analysis revealed the infiltrations of Th2, Th17, and Tgd were up-regulated in high TMB group, while those of Tr1, MAIT, and DC were up-regulated in low TMB group. And TMB-IF fit well with the actual survival observation, with a C-index 0.785 (0.700-0.870), which verified in ICGC-LIRI-JP was 0.670 (0.573-0.767), and 0.774 (0.670-0.877) in GSE76427. In addition, TMB-IF showed a good performance in predicting tumor vascular invasion with a C-index of 0.847 (0.778-0.916).

Conclusions : Higher TMB means worse prognosis in HCC patients. Patients with higher frequency of immune-related gene mutations and TMB are prone to relapse after radical treatment.
Upregulation of EMID1 accelerates to a favorable prognosis and immune infiltration in lung adenocarcinoma.
Authors: Li Chengrui , Wan Yufeng , Deng Weijun , Fei Fan , Wang Linlin , Qi Fuwei , Zheng Zhong 
Published: May 2020

Abstract
Background Lung cancer is a kind of refractory cancer. Lung adenocarcinoma (LUAD) is the main subtype of lung cancer. Although there are many ways to treat lung cancer, the survival rate of patients has not improved. Therefore, more new molecules need to be found for the diagnosis and treatment of LUAD. Methods The data from The Cancer Genome Atlas (TCGA) database were used to analyze the value of EMID1 in diagnosis and prognosis of LUAD. The relationship between clinic pathological features and EMID1 was analyzed with the Wilcoxon signed-rank test and logistic regression by R (v.3.5.1). Gene Set Enrichment Analysis (GSEA) was performed to investigate the potential mechanism of EMID1 expression on the prognosis of LUAD. The correlation between tumor infiltrating immune cells and genes was assessed by CIBERSORT. In addition, GEPIA and Gene Expression Omnibus (GEO) database were used to verify the results. Results The decreased expression of EMID1 was significantly related to the late stage and metastasis of lung cancer. Kaplan Meier survival analysis showed that patients with low expression of EMID1 had worse prognosis than those with high expression of EMID1. Notch signaling pathway may be an important biological pathway for EMID1 to play a role in LUAD. In addition, CIBERSORT also found that the infiltration level of B cells was positively correlated with the expression of EMID1, which played an important role in the immune environment of LUAD. All results were validated in GEO and GEPIA database. Conclusion The analysis of EMID1 was helpful to understand the immune microenvironment of LUAD and improve the survival status of patients with LUAD. All the results suggested that EMID1 might be a new immune related prognostic marker of LUAD.
A Recursive Frequency Smoothing Method of Cyclic Spectrum Density Estimation
Authors: Dai Jianzhong , Feng Xuzhe , Chen Jianyun , Yan Shuhua , Jia Aiai 
Published: May 2020

Abstract
Cyclic spectrum density estimation plays a significant role in cyclostationary signals analysis. Generally, the methods of cyclic spectrum density estimation are mainly focus in time-domain, such as FFT Accumulation Method (FAM) and Strip Spectral Correlation Algorithm (SSCA). In this paper, based on the principle of frequency smoothing methods, an improved method in frequency-domain was proposed, which could reduce the computational cost greatly by using recursion. The recursive method was based on the fact that the range difference of smoothing window was small when window slid. In other words, we could get a new point of cyclic spectrum density just by computing the complex conjugate products of newly coming into window. In addition, the simulation results were given at last, which showed the good performance of our proposed method.
Cost-effectiveness analysis of malaria rapid diagnostic test in the elimination setting
Authors: Du Yanqiu , Ling Xiaoxiao , Jin Jiajie , Zhou Huayun , Zhu Si , Zhu Guoding , Wang Wei , Cao Jun , Huang Jiayan 
Published: May 2020

Abstract
Background As more and more countries approaching the goal of malaria elimination, malaria rapid diagnostic tests (RDT) was recomendated to be a diagnostic strategy to achieve and maintain the statute of malaria free, as it’s less requirments on equipment and experitise than microscopic examination. But there are very few economic evaluations to confirm whether RDT was cost-effective in the setting of malaria elimination. Methods A cost-effectiveness analysis, based on data from Jiangsu province, China, was conducted to compare RDT with microscopy examination for malaria diagnosis. There were three strategies of malaria diagnostic testing evaluated using a decision tree model, 1) microscopy, 2) RDT, 3) RDT followed by microscopy. The effects were measured by the number of malaria cases treated appropriately. Based on the joint perspective of health sector and patient, costs data were collected from hospital information systems, key informant interviews, and patient surveys. Epidemiological data were obtained from local malaria surveillance reports. A hypothetical cohort of 300,000 febrile patients were simulated to calculate the total cost and effect of each strategy. One-way, two-way, and probabilistic sensitivity analysis were performed to test the robustness of the result. Results The results showed that RDT strategy was the most effective (245 cases) but also the most costly (4.47 million USD) compared to using microscopy alone (238 cases, 3.63 million USD), and RDT followed by microscopy (221 cases, 2.75 million USD). There was no strategy dominated. One-way sensitivity analysis reflected that the result was sensitive to the change in labor cost and two-way sensitivity analysis indicated that the result was not sensitive to the proportion of falciparum malaria. The result of Monte Carlo simulation showed that RDT strategy had higher effects and higher cost than other strategies with a high probability. Conclusions Compared to microscopy and RDT followed by microscopy, RDT strategy had higher effects and higher cost in the setting of malaria elimination. This conclusion still would be held when the change in the proportion of falciparum and the cost fluctuations were accounted.
The Effect of Huyang Yangkun Formula on N6-methyladenosine Modification in 4-vinylcyclohexene diepoxide Induced Premature Ovarian Insufficiency Rats
Authors: Li Meifang , Li Yang , Liu Jian , Nie Guangning , Jia Wenyu , Yang Hongyan 
Published: May 2020

Abstract
The aging of female reproductive system is mainly manifested by the decline of ovarian function, which is a physiological phenomenon. When it happens prematurely, it is called premature ovarian insufficiency(POI). Huyang Yangkun Formula(HYYKF) was developed according to theory of Chinese medicine and clinical experience and found to obviously relieve symptoms associated with menopause in POI patients. However, little is known about the effect of HYYKF on N6-methyladenosine (m 6 A) modification in ovaries of POI. In this study, VCD induced-POI model was established to investigate the effect of HYYKF on m 6 A modification. We found in the VCD-induced models, protein expressions of the m 6 A enzymes declined except that of FTO, and the expressions of METTL3, METTL14 and YTHDF1 declined very significantly. Interestingly, in naturally aging ovaries, the level of m 6 A declined very significantly at 9-week-old and 24-week-old, and the protein expression of METTL3, METTL14 and FTO in ovaries was down-regulated as mice aged. The date release that the level of m 6 A declines as the ovarian insufficiency occurs, which happens in both naturally aging ovaries and VCD-induced models. We found that HYYKF treatment promoted ovarian follicles development and the level of AMH in VCD induced-POI rats. Most importantly, HYYKF induced expressions of the m 6 A enzymes except that of FTO, and elevated the expressions of METTL3, METTL14, ALKBH5 and YTHDF1 significantly.
Associations of LDL-C-to-HDL-C and TG-to-HDL-C Ratios with Type 2 Diabetes Mellitus and Cardiovascular Disease: A Prospective Cohort Study with 6 years’ Follow-Up
Authors: Xu Jinjian , Hu Yiyan , Wei Qiaohui , Wu Qiong , Jin Ziqi , Zhou Yaohan , Zhang Xuhui , Zhu Yimin 
Published: May 2020

Abstract
Background: Traditional blood lipids play an important role in diabetes and cardiovascular diseases, but the evidences were not enough . The lipoprotein indices of low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) to high-density lipoprotein cholesterol (HDL-C) ratios may be the predictive parameters to diabetes and cardiovascular disease. Methods: A 6-year follow-up study was performed in 22,649 subjects (were aged 18–95 years old) without a history of cardiovascular disease (CVD) or diabetes. The information about cardiovascular disease and T2DM was extracted from the Disease Surveillance Points (DSP) system in 2019. Biochemical and demographic variables were acquired by laboratory test and the face-to-face interview with structured questionnaire, the response rate was 88.9%. Lipid ratios were stratified by tertile to ascertain the hazard ratio (HR) of diseases by Cox proportional hazard model. Results: The mean age of subjects was 54.9(14.5) years, 41.9% were males. LDL-C /HDL-C was strongly associated with coronary heart disease (CHD) ( second vs. first tertile: HR, 1.86; 95% CI, 1.03-3.37, p =0.04 ; third vs. first tertile: HR, 3.29; 95% CI, 1.91-5.69, p< 0.001), meanwhile the TG/HDL-C was specifically associated with type 2 diabetes mellitus (T2DM) (second vs. first tertile: HR, 1.56; 95% CI, 1.2-2.02, p =0.001; third vs. first tertile: HR, 2.7; 95% CI, 2.13-3.43, p< 0.001). Moreover, the HR, of diseases was increased with LDL-C, TG/HDL-C ratios. The results of sensitivity analysis revealed the associations of LDL-C, TG/HDL-C ratios with CHD and T2DM were independent on confounders. Conclusion: Our findings suggested that the LDL-C/HDL-C ratio and TG/HDL-C ratio associated with CHD and T2DM , and hazard ratio of disease increased with lipoprotein derived indices.
Genotype Spectrum and Hematological Features of β–Thalassemia with or without Different Forms of α-Thalassemia in Shenzhen
Authors: Luo Mingyue , Xiong Likuan , Chen Xu , Yan Zehao , Mai Guangxing , Shen Kai 
Published: May 2020

Abstract
Background: The effects of different forms of α–thalassemia on β-thalassemia phenotype has not been clearly described thus far. Methods: Genotype spectrum and hematological features of 873 female diagnosed as β-thalassemia carriers with or without different forms of α-thalassemia was retrospectively analyzed. Results: Thirteen kinds of genotypes were found in the 755 β-thalassemia carriers, including four kinds of β+-thalassemia, eight kinds of β0 -thalassemia and one kind of βE-thalassemia. The values of hemoglobin (Hb), mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) decreased and red blood cell (RBC) increased in the order of βE, β+- and β0 group (p＜0.05). Nine genotypes were determined from the 43 carriers with concurrent α- and β+-thalassemia and seventeen genotypes were determined from the 75 carriers with concurrent α- and β0 -thalassemia. Significant higher Hb, MCV and MCH values were noted in β+–thalassemia or β0–thalassemia co-inherited with α+-thalassemia or α0-thalassemia as compared to the only β+–thalassemia or β0–thalassemia heterozygosity with normal alpha globin gene (p＜0.05). Moreover, the values of Hb, MCV and MCH increased much more when β0–thalassemia co-inheritance of α0-thalassemia than that of α+-thalassemia (p＜0.05). Conclusion: The β-thalassemia presented diverse molecular heterogeneity and hypochromic microcytosis at various degrees. Co-inherited with α–thalassemia could alleviate phenotype of anemic in β+- or β0-thalassemia, and β0-thalassemia demonstrated milder phenotype with two deletion or mutation in α-globin gene than one.
On the Bound of Cumulative Return in Trading Series
Authors: Can Yang , Zhai Junjie , Li Helong 
Published: May 2020

Abstract
There is no doubt that cumulative return is one of fundamental concerns in financial markets. In this paper, we first reveal the upper bound of cumulative return, and then propose a method to evaluate the performance of trading strategies by using proposed upper bound. Furthermore, with the help of bootstrap methodology, we conduct numerous experiments on distinct international stock markets, including developed markets and emerging markets, to verify the validity of the proposed upper bound. And both the theoretical and empirical results show that the effectiveness of the proposed upper bound and reveal its significant potentials on evaluating performance of trading rules.
Fuzzy Modelling of Clinical and Epidemiological Factors for COVID-19
Authors: Poonam  , Mangla Monika , Sharma Nonita , Reena  
Published: May 2020

Abstract
During this pandemic outbreak of COVID-19, the whole world is getting severely affected in respect of population health and economy. This novel virus has brought the whole world including the most developed countries to a standstill in a very short span like never before. The prime reason for this unexpected outburst of COVID-19 is lack of effective medicine and lack of proper understanding of the influencing factors. Here, authors aim to find the effect of epidemiological factors that influence its spread using a fuzzy approach. For the same, a total of 9 factors have been considered which are classified into Risk and Preventive factors. This fuzzy model supports to understand and evaluate the impact of these factors on the spread of COVID-19. Also, the model establishes a basis for understanding the effect of risk factors on preventive factors and vice versa. It is worth mentioning that this is the first attempt to analyze the effect of Clinical and Epidemiological factors with respect to COVID-19 using a fuzzy approach.
Clinical Characteristics and Risk Factors for Bloodstream Infection due to Carbapenem-Resistant Klebsiella Pneumoniae in Patients with Hematologic Malignancies
Authors: Zhang Piaopiao , Wang Jie , Hu Hangbin , Zhang Sheng , Wei Juying , Yang Qing , Qu Tingting 
Published: May 2020

Abstract
Background: Carbapenem-resistant Klebsiella pneumoniae (CRKP) associated infections are a major threat to patient safety. Methods: A single-center, retrospective case-control study representing 734 patients with hematologic malignancies between January 1, 2017 and December 31, 2018 was conducted. Demographic and clinical data were collected from the hospital electronic medical records system. Results: Among the 734 patients with hematologic malignancies, 3% (22/734) of the patients developed CRKP BSI during their hospitalization. Overall 28-day all-cause mortality reached 77.3% (17/22). Patients with Pitt Bacteremia Score (PBS) >4, pneumonia and septic shock were more frequent in the non-survivors versus the survivors . Compared with the non-survivors in antimicrobial treatment, combination therapy of tigecycline and polymyxin B was more common in the survivors. The independent risk factors associated with CRKP BSI were CRKP rectal colonization (OR,11.067; CI=4.43-27.644; P<0.001; 3 points), severe neutropenia (OR,4.095; CI=0.876-19.141; P=0.073; 1 point) and invasive mechanical ventilation (IMV) within the previous 30 days to onset of BSI (OR,18.444; CI=1.787-190.343; P=0.014; 4 points). The total risk score of ≥5 indicated that the probability of CRKP BSI occurrence was above 48%. Conclusions: CRKP BSI in patients with hematologic malignancies is associated with high mortality. The risk factor–based prediction model might help clinicians to start prompt effective anti-infective therapy in patients with suspicion of CRKP BSI and improve outcomes. Keywords: Carbapenem-resistant Klebsiella pneumoniae ; bloodstream infection; hematologic malignancy; risk factors; prediction
Can Climatic Factors Explain The Differences In Covid-19 Incidence And Severity Across The Spanish Regions?: An Ecological Study
Authors: Muñoz-Cacho Pedro , Hernandez Jose Luis , Lopez-Hoyos Marcos , Martínez-Taboada Víctor M. 
Published: May 2020

Abstract
Background: Environmental factors play a central role in seasonal epidemics. SARS-CoV-2 infection in Spain has shown a heterogeneous geographical pattern This study aimed to assess the influence of several climatic factors on the infectivity of SARS-CoV-2 and the COVID-19 severity among the Spanish Autonomous Communities (AA.CC.).Methods: Data on coronavirus infectivity and severity of COVID-19 disease, as well as the climatic variables were obtained from official sources (Ministry of Health and Spanish Meteorological Agency, respectively). To assess the possible influence of climate on the development of the disease, data on ultraviolet ration (UVR) were collected during the months before the start of the pandemic. To analyze its influence on the infectivity of SARS-CoV-2, data on UVR, temperature, and humidity were obtained from the months with the highest contagiousness to the pandemic peak.Results: From October 2019 to January 2020, mean UVR was significantly related not only to SARS-CoV-2 infection (cumulative incidence -previous 14 days- x105 habitants, rho=-0.0,666; p=0.009), but also with COVID-19 severity, assessed as hospital admissions (rho=-0.626; p=0.017) and ICU admissions (rho=-0.565; p=0.035). Besides, temperature (February: rho=-0.832; p<0.001 and March: rho=-0.904; p<0.001), was the main climatic factor responsible for the infectivity of the coronavirus and directly contributed to a different spread of SARS-CoV-2 across the Spanish regions. Conclusions: Climatic factors may partially explain the differences in COVID-19 incidence and severity across the different Spanish regions. The knowledge of these factors could help to develop preventive and public health actions against upcoming outbreaks of the disease.
Estimating COVID-19 pandemic severity in Indian context
Authors: Mandal Manisha , Mandal Shyamapada 
Published: May 2020

Abstract
The case fatality rate (CFR) represents one of the most vital factors in demonstrating the severity of novel infectious disease, COVID-19. Various estimates of COVID-19 fatalities (based on the publicly and published information and data in Indian context of COVID-19): confirmed CFR, asymptomatic CFR, symptomatic CFR, and hospitalized CFR were 2.32% (2.05-2.59), 0.14% (0.12-0.16), 0.32% (0.27-0.36), 1.86% (1.64-2.07) respectively. The relative susceptibility of developing symptoms (RSODS) and relative susceptibility of developing infection (RSODI) of COVID-19 were ~33 times higher among people aged <45 years. The RSODS estimates were 1.97 (0.47-3.47), 0.62 (0.15-1.09), 0.29 (0.07-0.52), 0.06 (0.02-0.10) respectively, for patients <45 years, 45-60, 60-75, >75 years. Similar trend, for RSODI were found, with relatively higher value, compared to RSODS, which decreased with the increase of age. The 14-day lag estimate of CFR were 18.07 (15.67-20.47), and outcome (deaths plus recoveries)-based estimate of CFR were 16.57 (14.65-18.49). The growth rate, serial interval, reproduction number and average time from onset of COVID-19 infection to death were 6.12% (5.30%-6.99%), 11.4 days (9.91-12.85), 1.03 (1.01-1.05), and 11.85 days (10.55-13.15), respectively. Among 1,673,688 samples tested, 62,939 (3.76%) were positive for COVID-19 accounting 1,228 tests per million population of India, as of May 10, 2020. The average daily recovery was 19.45% (14.75- 24.15) and average cumulative recovery was 12.68% (10.70- 14.66) among COVID-19 patients. As per our belief and knowledge, this is the first study of its kind in reporting COVID-19 severity in Indian context during pandemic.