bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modelling the Paucity of COVID-19 Pandemic Spread Incidence across the India Nation
Authors: Rodriguez-Morales Alfonso J. , Singh Ram Kumar , Singh S. S. , Pandey A. K. , Kumar Vinod , Jha Ramadhar , Bala Raj , Sah Ranjit , Sharma Pardeep , Mandal Vinay Prasad , Kalita Himangshu , Nandan Rajiv , Singh Susheel Kumar , Rabaan Ali A. , Rani Meenu , Kumar Pavan , Kumar Manoj 
Published: May 2020

Abstract
Background: The highly contagious Co rona vi rus d isease (COVID-19) pandemic affected nearly all nations across the world. It was emerged as most swiftly affected disease across the world and more than 2934 lakhs population suffered in four months of the time period as on date April 26, 2020. Its first epicenter was at Wuhan city of China during the month of December 2019. Currently, the most affected people and new epicenter of Coronavirus is at the United States of America (USA). Various nation’s administration including the India government called for the regional and local lockdown. We predicted the confirmed COVID-19 cases for next May-2020 month, map the magnitude of COVID-19 disease for Indian states and model the paucity of COVID-19 disease with statistical confirmatory data analysis model for declining rate for the cases represented for the Indian proportion of population. Method: The ARIMA model used to predict for next short-term cases, based moving average of past confirmed cases. The restriction of COVID-19 pandemic disease analyzed with predicted cases for month May 2020 data at 95 percent confidence is more than 2.5 lakh cases. Results: The confirmatory data analysis model for the time estimation for the paucity of cases it takes in between six to eighteen months of time frame. The Confirmatory model which considers recovery rate, social, economic and government policy. To complete recovery from the COVID-19 cases it takes on an average more than next ten months. Conclusion: The disease impacts also depend upon administrative and local people support for self-quarantine and other measures. The India nation Gross Domestic Product (GDP) based on more than 17% of its agriculture production, due to longer affect of the disease and extended lockdown period it will be severely affected. However, all the economic activities with full of its intensity takes-up after complete paucity of COVID-19 disease spread. Keywords: SARS-CoV-2; Lockdown; GDP; Nobel-Corona; Confirmatory data model
KLF5-mediated Eppk1 expression promotes cell proliferation in cervical cancer via the p38 signaling pathway
Authors: Pan Zhe , Liu Xiao , Chang Quan , Zhang Jin-jin , Hua Na , Li Guo-Hua , Ma Dong 
Published: May 2020

Abstract
Background: Epiplakin1 (Eppk1) is part of the EGF signal and is involved in cytoskeleton reorganization and cell proliferation. However, the role of Eppk1 in cervical cancer remains unknown. Objective: To determine the role of EPPK1 on cell proliferation in cervical cancer. Methods: The expression of Eppk1 and KLF5 as well as their correlation were assessed by RNA-seq, qRT-PCR, TCGA database and immunofluorescence staining. In CC cell lines, adenovirus-mediated overexpression or knockdown of KLF5 and Eppk1 as well as corresponding assessment of cell proliferation and signaling were determined by western blot and CCK8 experiments. Assays of lucifase reporter gene and CHIP were used to investigate mechanism between KLF5 and Eppk1 . Results: Eppk1 expression was markedly in CC tissues and cell lines companied by KLF5 upregulation. The results of immunofluorescence staining further showed that the increased expression of Eppk1 and KLF5 correlated with progression of cervical tumorigenesis. Overexpression of KLF5 significantly increased Eppk1 expression at transcription and translation levels. Conversely, the knockdown of KLF5 by siRNA against KLF5 decreased Eppk1 expression. Mechanical studies showed that KLF5 activated Eppk1 transcription by direct binding to the Eppk1 promoter. Gain- and loss-of-function experiments showed that KLF5 promoted cell proliferation in Hela by upregulating Eppk1 expression. Moreover, KLF5-mediated the activation of EGFR and p38 signaling significantly decreased after Eppk1 knockdown companied with reduction of proliferating activity, suggesting that Eppk1 lies upstream of p38 signaling affecting cell proliferation in CC. Finally, the expression of Eppk1 positively correlated with tumor size. Conclusions: Eppk1 may be an effective therapeutic target on affecting EGFR-associated p38 signaling pathway and cell proliferation in cervical cancer.
The Inhibition of Autophagy Flux Mediated by Neferine Promoted the Apoptosis of HNSCC through the Accumulation of p62/SQSTM1
Authors: Zhu Fengshuo , Li Xiaoguang , Tang Xiao , Jiang Junjian , Han Yu , Li Yinuo , Liu Zhonglong , He Yue 
Published: May 2020

Abstract
Background: Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignancies worldwide. Patients usually have very poor prognosis because of metastasis and chemoresistance. There is an imperative need to explore more effective chemotherapeutic agents. Neferine, a bisbenzylisoquinoline alkaloid isolated from the seed embryo of Lotus, exerts antitumor effects via regulating apoptosis and autophagy pathways, which becomes a potential therapeutic option for HNSCC. Methods: Cell viability and proliferation was determined by the CCK8 and colony formation assay. Cell cycle and apoptosis analysis were assessed by flow cytometry with Annexin V-FITC/PI staining. Intracellular ROS levels were determined by the DCFH-DA fluorescence. Autophagy flux was detected by transmission electron microscopy, transfected GFP-RFP-LC3 fluorescence and western blot for related markers in the presence or absence of neferine and chloroquine. Results: Neferine inhibited the growth and induce the apoptosis of HNSCC cells both in vitro and vivo. Further analysis revealed that neferine activated ASK1/JNK pathway by increasing reactive oxygen species, then induced apoptosis of and regulated canonical autophagy in HNSCC cells. The study also revealed the novel pro-apoptosis mechanism through the activation of Caspase8 mediated by p62 due to the inhibition of autophagy flux. Conclusions: These findings explore the anti-cancer effect of neferine, providing new insights into the crosstalk between apoptosis and autophagy mediated by p62 in HNSCC. The inhibition of autophagy flux by neferine might be a potential adjuvant therapy to HNSCC.
Spike protein amino acid variants increased miRNA binding and hence reduced virulence of SARS-CoV-2 in Jordan, Middle East
Authors: Haddad Hazem , Foudeh Ramzi , Al-Zyoud Walid 
Published: May 2020

Abstract
Initial epidemiological studies inform the central COVID-19 disease prophet. Some papers have been studying miRNA and viral RNA interaction target predictions over the past few years. In this work, via the miRDB database, we determined the target scores of predicted miRNA to bind with the ss-RNA of SARS-CoV-2 in general and spike gene in specific. Our predicted miRNA targets of the ss-RNA of SARS-CoV-2 might destabilize and hence inhibit the ss-RNA translation of SARS-CoV-2 and prevent viral replication that has been established by more than 80% of asymptomatic infected cases in Jordan due to host miRNA interactions. In respiratory epithelial cells, the high scoring miRNAs prediction covers the RNA from 5' to 3' that explain successful antiviral defenses against ss-RNA of SARS-CoV-2 and lead to new nucleotide deletion mechanisms. The exciting finding here that the substitution 1841A>G at the viral genomic RNA level or the D614G at spike protein level showed a change in the predicted miRNA sequence and an increase in the target score (from 91 to 92) (hsa-miR-4793-5p to hsa-miR-3620-3p).
Fast and low-cost detection of SARS-CoV-2 peptides by tandem mass spectrometry in clinical samples
Authors: Cardozo Karina Helena Morais , Lebkuchen Adriana , Okai Guilherme Goncalves , Schuch Rodrigo Andrade , Viana Luciana Godoy , Olive Aline Nogueira , Lazari Carolina dos Santos , Fraga Ana Maria , Granato Celso , Carvalho Valdemir Melechco 
Published: May 2020

Abstract
The current outbreak of severe acute respiratory syndrome associated with coronavirus 2 (SARS-CoV-2) is pressing public health systems around the world, and large population testing is a key step to control this pandemic disease. Real-time reverse-transcription PCR (real-time RT-PCR) is the gold standard test for virus detection but the soaring demand for this test resulted in shortage of reagents and instruments, severely limiting its applicability to large-scale screening. To be used either as an alternative, or as a complement, to real-time RT-PCR testing, we developed a high-throughput targeted proteomics assay to detect SARS-CoV-2 proteins directly from clinical respiratory tract samples. Sample preparation was fully automated by using a modified magnetic particle-based proteomics approach implemented on a robotic liquid handler, enabling a fast processing of samples. The use of turbulent flow chromatography included four times multiplexed on-line sample cleanup and UPLC separation. MS/MS detection of three peptides from SARS-CoV-2 nucleoprotein and a 15N-labeled internal global standard was achieved within 2.5 min, enabling the analysis of more than 500 samples per day. The method was validated using 562 specimens previously analyzed by real-time RT-PCR and was able to detect over 83% of positive cases. No interference was found with samples from common respiratory viruses, including other coronaviruses (NL63, OC43, HKU1, and 229E). The strategy here presented has high sample stability and low cost and should be considered as an option to large population testing.
A practical nomogram from the SEER database to predict the prognosis of hepatocellular carcinoma patients with lymph node metastasis
Authors: Zhang Kai , Tao Changcheng , Wu Jianxiong , Rong Weiqi 
Published: May 2020

Abstract
Background: The presence of lymph node metastases is related to poor survival outcomes in hepatocellular carcinoma patients and because of the reported low probability of lymph node metastasis, research into the prognoses of such patients is difficult to conduct. In this study, we aimed to develop a nomogram model to predict the prognosis of HCC patients with lymph node metastasis and provided a reasonable basis for the choice of follow-up treatment.Methods: HCC patients diagnosed with LN metastasis from 2010 to 2015 were enrolled from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate Cox regression and lasso regression were used to screen prognostic factors. Cox multiple-factor analysis was employed to investigate the independent prognostic factors for survival. The concordance index (C-index) and calibration curve were used to evaluate the predictive performance of our model. The clinical benefit was assessed via decision curve analysis (DCA). The survival was analyzed using Kaplan-Meier method and the differences among survival curves were compared by the log-rank test.Results: Patients were randomized into the training group (944 patients) and the validation group (402 patients) in a 70:30 ratio. Grade, T stage, surgery to the liver, chemotherapy, radiation recode, AFP, fibrosis score, tumor size group, M stage were selected as independent prognostic factors, and we developed nomograms using these variables. The c-indices of the training and validation groups were 0.70 and 0.73, respectively. The calibration curves for probability of survival showed good agreement. The DCA indicated that the nomogram had positive net benefits. Patients were divided into two risk groups according to our model, survival curves were drawn, and the log-rank test was performed, the p-value of which was <0.001.Conclusions: The nomogram can accurately predict the prognosis of HCC patients with lymph nodes metastasis and provide a reasonable basis for treatment.
Surgical Management of Bladder Cancer During First Month of COVID-19 Outbreak: Lessons Learned Across Italy
Authors: Maccagnano Carmen , Rocchini Lorenzo , Montanari Emanuele , Conti Giario Natale , Contieri Roberto , Bryan Kadi-Anna , Hurle Rodolfo 
Published: May 2020

Abstract
Objectives: Real-life overview of bladder cancer (BC) surgical management in Italy during the first month of COVID-19 pandemic (March 2020) with head to head comparison of the data from March 2019, considered “usual activity” period. The aim is to confront performance of Academic Centers (AC) vs Non Academic Centers (NAC) as well as non-COVID Centers (nCC) and COVID Centers (CC). Patients and methods: During April 2020, an e-mail survey was sent to 32 Sections of Urology across Italy. It contained 14 multiple-choice questions focused on activities during March 2019 and March 2020. Statistical analysis was performed using IBM SPSS Statistics (v26) software. Results28 centers answered to survey. AC and NAC showed statistically significant differences (chi-square test p<0.05) about number of physicians assigned to Covid wards (p=0.001), Trans-Urethral Resection of Bladder Tumour (TURBT) (p=0.046) and cystectomies (p=0.037) performed in March 2020 (p=0.037). In 2020, AC performed more surgical procedures compared to NAC. In 2019, AC had more procedures per Operating Block (OB) (p=0.015) and greater number of emergent Trans-Urethral Resections (TUR) (p=0.014), while NAC had more TURBTs. CC had more patients (pts) both evaluated for gross hematuria (p=0.017) and requiring haemostatic Trans-Urethral Resection (hTUR) in 2019. In 2020 nCC had more surgeries per OB (p=0.001), TURBTs (p=0.030) and cystectomies (p=0.034) than CC. ConclusionThe COVID-19 pandemic represents an important challenge for cancer centers, in the context of an extremely dynamic clinical and political situation which requires maximum flexibility to be appropriately managed.
Evaluating extremely low plasma ascorbate levels and reduction of plasma ascorbate levels by dialysis in Japanese hemodialysis patients
Authors: Doshida Yuta , Itabashi Mitsuyo , Takei Takashi , Takino Yuka , Sato Ayami , Yatsu Tomofumi , Yumura Wako , Maruyama Naoki , Ishigami Akihito 
Published: May 2020

Abstract
Background: Low plasma ascorbate levels in hemodialysis patients have been reported worldwide; hence, many end-stage kidney disease patients are forced to restrict their diets, especially potassium-rich fruits and vegetables, to prevent hyperkalemia. In this study, we aimed to clarify whether plasma ascorbate levels are low in Japanese dialysis patients and whether plasma ascorbate levels fluctuate before and after dialysis. In addition, we aimed to clarify whether there are clinical test items that have a causal relationship with plasma ascorbate levels.Methods: Plasma ascorbate levels in 27 chronic kidney disease (CKD) stage G3–G5 patients (mean age 84 years) and pre- and post-dialysis plasma ascorbate levels in 19 CKD stage G5D hemodialysis patients (mean age 79 years) were determined using high-performance liquid chromatography and electrochemical detection.Results: Pre-dialysis plasma ascorbate levels in hemodialysis patients (12.0 ± 1.4 µM) were significantly lower (by 56%) than those in CKD stage G3–G5 patients (27.1 ± 2.7 µM). After dialysis, there was a 40% reduction in plasma ascorbate levels. Moreover, pre-dialysis ascorbate levels correlated significantly with plasma potassium levels.Conclusions: The study results indicate that Japanese hemodialysis patients have lower plasma ascorbate levels than CKD stage G3–G5 patients and that these low plasma ascorbate levels in hemodialysis patients were further reduced by hemodialysis. To avoid the development of scurvy in hemodialysis patients, it is necessary to take sufficient ascorbate from supplements or medicines.
Cox Regression Analysis of 1739 Emergency Trauma Patients
Authors: Shen Jun , Xu Feng , Chen Du 
Published: May 2020

Abstract
BACKGROUND: Trauma is a damage caused by physical harm from external source. It has been one of the major causes of mortality. The purpose of this study was to explore the risk factors related to mortality among emergency trauma patients. METHODS: This was a retrospective study in trauma center of the First Affiliated Hospital of Soochow University. The data were obtained from trauma database with patients registered from November 1, 2016 to November 30, 2019.Shapiro–Wilk test, Mann-Whitney test and Likelihood-ratio Chi squared test were used to assess the survival pattern. Cox regressions were performed to calculate the hazard ratios (HRs) of variables for death. RESULTS: The total 1739 emergency trauma patients, 44 (2.53%) died during the study period and 1695 (97.47%) were survival. Through univariable and multivariable Cox regression analysis, three independent risk factors for emergency death were screened out: pulse (Crude HR: 0.97, 95% Confidence Interval [CI]: 0.96-0.98; Adjuste HR: 1.04, 95% CI: 1.02-1.06), pulse oxygen saturation (Crude HR: 0.96, 95% CI: 0.95-0.97; Adjuste HR: 0.94, 95% CI: 0.91-0.97) and Revised Trauma Score (Crude HR: 0.69, 95% CI: 0.65-0.74; Adjuste HR: 0.79, 95% CI: 0.64-0.97).CONCLUSION: The survival outcome of emergency trauma patients was influenced by many factors. Pulse, pulse oxygen saturation (SpO2 ) and Revised Trauma Score (RTS) were the independent risk factors for mortality. Accurate analysis and judgment of the risk factors can improve cure efficiency and long-term survival rate.
System Pharmacological Mechanism and Compatibility Laws of Jianghuang from Traditional Chinese Medicine In Blood-Regulating Formulae
Authors: Liu Zhiqiang , Wang Bolong 
Published: May 2020

Abstract
Background: Jianghuang (JH) is a popular ingredient in blood-regulating traditional Chinese Medicine (TCM) that could be effective for the treatment of various diseases. We demonstrate the compatibility laws and system pharmacological mechanisms of the key formula containing JH by leveraging data mining of bioinformatics databases.Material/Methods: The compatibility laws of blood-regulating formulae containing JH from the Chinese Traditional Medicine Formula Dictionary were analyzed using a generalized rule induction (GRI) algorithm implemented. The putative target gene and miRNA were retrieved via a combination of the Arrowsmith knowledge discovery tool and FunRich 3.1.3. System pharmacological mechanisms are traced by their protein-protein interaction (PPI) network, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was conducted using Uniprot, the Human Protein Atlas (HPA), STRING 11.0, and KOBAS 3.0.Results: We found that the JH-CX-DG formula (Ligusticum chuanxiong-Angelica sinensis) could represent a key formula containing JH in blood-regulating TCM formulae. The JH-CX-DG formula was observed to directly target AKT, TLR4, caspase-3, PI3K, mTOR, p38 MAPK, VEGF, iNOS, Nrf2, BDNF, NF-κB, Bcl-2, and Bax 13 targets and regulate targets through 13 miRNA. The PPI network and KEGG pathway enrichment analysis showed that the JH-CX-DG formula possess potential pharmacological effects including anti-inflammatory, improving microcirculation, and anti-tumor through the regulation of multiple pathways including PI3K/Akt, MAPK, Toll-like receptor, T cell receptor, EGFR, VEGFR, Apoptosis, HIF-1 (p < 0.05).Conclusion: The JH-CX-DG formula can exert beneficial pharmacological effects through multi-target and multi-pathway interactions. It can be effectively administered for the treatment of inflammatory diseases, microcirculation disorders, cardiovascular disease, and cancer. We found a new effective drug formula through analyzing the compatibility law and systemic pharmacological mechanism of JH. Our study provides a theoretical basis and directions for subsequent research on the JH-CX-DG formula.
Placenta in SARS-CoV-2 infection: a new target for inflammatory and thrombotic events
Authors: Bertero Luca , Borella Fulvio , Botta Giovanni , Carosso Andrea , Cosma Stefano , Bovetti Marialuisa , Carosso Marco , Abbona Giancarlo , Papotti Mauro , Cassoni Paola , Benedetto Chiara 
Published: May 2020

Abstract
Infection by SARS-CoV-2 has been shown to involve a wide range of organs and tissues, leading to a kaleidoscope of clinical conditions. Within this spectrum, an increased rate of preterm deliveries has been reported in women with COVID-19. High expression of proteins (ACE2/TMPRSS2) required for SARS- CoV-2 cell entry has been observed in the maternal-fetal tissues, supporting the possibility of placental viral involvement. A consecutive series of 6 placentas, delivered by 5 women with COVID-19 have been investigated. Three out of six placentas showed changes consistent with chronic villitis, while in one case chronic histiocytic intervillositis was diagnosed. Vascular abnormalities consisting of thrombo- hemorrhagic alterations were identified in the three cases with chronic villitis. These pathological findings: i) provide a basis to explain the higher rate of obstetric complications in these patients; 2) suggest the need to investigate heparin use in COVID-19 affected pregnant patients to prevent adverse outcomes.
Inflammation, immunity, and vascular remodeling in pulmonary hypertension; Evidence for complement involvement?
Authors: Frid Maria G , Thurman Joshua M , Hansen Kirk C , Maron Bradley A , Stenmark Kurt R 
Published: May 2020

Pulmonary (arterial) hypertension (PH/PAH) is a life-threatening cardiopulmonary disorder. Experimental evidence suggests involvement of inflammatory and autoimmune processes in pathogenesis of PH/PAH, however the triggering and disease-promoting mechanisms remain unknown. The complement system is a key arm of innate immunity implicated in various pro-inflammatory and autoimmune diseases, yet, surprisingly little is known about the role of complement in PH/PAH pathogenesis. The preponderance of the existing data associates complement with PH/PAH via analysis of plasma and does not study the lung directly. Therefore, we aimed to resolve this by analyzing both the mechanisms of local lung-specific complement activation and the correlation of dysregulated plasma complement to clinical outcome in PAH patients. In our recent studies, reviewed herein, we show, for the first time, that immunoglobulin-driven activation of the complement cascade, specifically its alternative pathway, in the pulmonary perivascular areas, is a key mechanism initiating pro-inflammatory processes in the early stage of experimental hypoxic PH (a form of “sterile inflammation”). In human patients with end-stage PAH, we have demonstrated that perivascular deposition of immunoglobulin G (IgG) and activation of the complement cascade are “longitudinally” persistent in the disease. We also showed, using unbiased network analysis, that plasma complement signaling, including again the Alternative pathway, is a prognostic factor of survival in patients with idiopathic PAH (IPAH). Based on these initial findings, we suggest that vascular-specific, immunoglobulin-driven dysregulated complement signaling triggers and maintains pulmonary vascular remodeling and PH. Future experiments in this area would facilitate discoveries on whether complement signaling can serve both as a biomarker and therapeutic target in PH/PAH.