bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Case for Montelukast in COVID-19: "The use of Computational Docking to estimate the effects of Montelukast on potential viral main protease catalytic site"
Authors: Mansoor Salman , Saadat Shoab , Amin Aitzaz , Ali Imran , Ghaffar Muhammad Tauseef , Amin Usman , Mukhtar Mohsin 
Published: May 2020

Abstract
This article explores the possible role of Montelukast in management of SARS-CoV-2 infection after reviewing the available literature and further uses computational docking to estimate the effects of Montelukast on the main protease inhibitor site of SARS-CoV-2.Methodology: In this study, we used molecular docking to estimate the direct effects of Montelukast on the main protease (Mpro) inhibitor site of the SARS-CoV-2. While other studies have been performed on the homology models, we obtained the Mpro crystalized structure, A-chain (304 amino acid residues) from protein data bank (PDB code 5REK) for this analysisResults:The best docked Montelukast conformer had a mfscore of -71.68 and was seen to be making multiple hydrogen bonds with the neighbouring residues (T24, T24, T26, S46) with the closest bond with T24 (Distance= 1.71 angstrom). Important finding was its hydrogen bond with H41 and hydrophobic interactions with C145 as these residues for important members of the active catalytics site.Conclusion:The computational model which was used against the crystalized Mpro structure suggested a possible inhibitory role of Montelukast in binding to the Mpro catalytic site which may modulate and inhibit the viral replication.
Fluid expansion improve ventriculo-arterial coupling in preload patients: a prospective observational study
Authors: Huette Pierre , Arab Osama Abou , Longrois Dan , Guinot Pierre-Grégoire 
Published: May 2020

Abstract
Background
Given that the ventricular and arterial systems operate simultaneously, ventricular-arterial (V-A) coupling (i.e the EA/Ees ratio) determines the stroke volume and ejection pressure (i.e. arterial blood pressure).
Methods
30 patients admitted to cardio-thoracic ICU in whom the physician decided to perform FC were included. Arterial pressure, cardiac output (CO), EA, and ELV, were measured before and after FC with 500 ml of lactated Ringer's solution. Fluid responders were defined as patients with more than a 15% increase in SV after fluid challenge. V-A coupling was evaluated by the ratio EA/Ees.
Results
Twenty-three (77%) of the 30 patients included in the study were fluid responders. Before FC, responders had higher mean EA and EA/Ees ratio. FC significantly increased mean arterial pressure, LVEF, SV and CO, and significantly decreased SVRi, EA and consequently the EA/Ees ratio. A pre-challenge EA/Ees ratio greater than 1.4 was predictive of fluid responsiveness (area under the curve [95% confidence interval]: 0.84 [0.66‒1]; p < 0.0001).
Conclusions
In FC responders, V-A coupling was characterized by a higher pre-challenge EA/Ees ratio (due to a higher EA). FC improve V-A coupling ratio by decreasing EA but not Ees.
The feasibility and safety of complete laparoscopic extended right hemicolectomy with preserving the ileocecal junction in right-transverse colon cancer
Authors: Su Hao , Wu Hongliang , Mu Bing , Bao Mandula , Luo Shou , Zhao Chuanduo , Liu Qian , Wang Xishan , Zhou Zhixiang , Zhou Haitao 
Published: May 2020

Abstract
Background: To evaluate the feasibility and safety of a new surgical method, complete laparoscopic extended right hemicolectomy with preserving the ileocecal junction in right-transverse colon cancer.Methods: We retrospectively analyzed and compared the data of consecutive patients with right-transverse colon cancer who underwent complete laparoscopic extended right hemicolectomy with preserving the ileocecal junction (n=23) and conventional complete laparoscopic extended right hemicolectomy (n=34) in our hospital between October 2017 to May 2019, respectively.Results: The overall operation time of the ileocecal junction-preserved group was significantly shorter than that of the control group (p=0.024). There was no difference in the number of harvested lymph nodes, metastatic lymph nodes and rate of metastatic lymph nodes (p＞0.05). The ileocecal junction-preserved group showed shorter time of first flatus, lower frequency of postoperative diarrhea and shorter duration of postoperative hospitalization. Furthermore, it also showed that the defecation frequency was lower in the ileocecal junction-preserved group than control group on the 1st, 3rd and 6th month (p＜0.05), and the number of patients who defecated at night or defecated four times or more a day were less in the ileocecal junction-preserved group than control group on the 1st month (p＜0.05).Conclusion: The complete laparoscopic extended right hemicolectomy with preserving the ileocecal junction promises as a safe and feasible surgical procedure for right-transverse colon cancer, associated with earlier recovery of bowel function, shorter operation time and similar pathological outcomes when compared to the conventional laparoscopic procedure.
Symptomatic Cholelithiasis Patients Have Increased Pancreatic Cancer Risk- A Population Based Study
Authors: Wang Chi- Chih , Tseng Ming-Hseng , Wu Sheng-Wen , Yang Tzu-Wei , Chen Hsuan-Yi , Sung Wen-Wei , Su Chang-Cheng , Wang Yao-Tung , Chen Wei-Liang , Lai Hsueh-Chou , Lin Chun-Che , Tsai Ming-Chang 
Published: May 2020

Abstract
Background :Pancreatic cancer is a fatal disease, andthe current risk factor survey is not suitable for sporadic pancreatic cancerthat lacks obvious family history orgenetic analysis data.The aim of the present study was to evaluate the roles of cholelithiasis and cholelithiasis treatmentson pancreatic cancer risk.Methods: Symptomatic adult patients with an index admission ofcholelithiasis diagnosis were selectedfrom one million random samples of National Health Insurance Research Database (NHIRD)obtained between January 2005 andDecember 2009. Exclusion criteria included pancreatic cancer, benign neoplasm or anomalies of the pancreas, orendoscopic sphincterotomy/endoscopic papillary balloon dilatation (ES/EPBD), cholecystectomy (CCY) before 2004. The control group was matched in a 1:1 ratio for sex, age,chronic pancreatitis and pancreatic cystic disease. The study group was divided into ES/EPBD, CCY, ES/EPBD&CCY, and no-intervention groupsfor subsequent pancreatic cancer evaluation.Results: Both the cholelithiasis group and the matched control group included 8,265 adult cases. The cholelithiasis group contained 86 (1.04%) cases of diagnosed pancreatic cancer and the control group contained8 (0.10%) cases (p<0.001). Exclusion of pancreatic cancer cases diagnosed in the first 6 months still resulted in asignificantly higher pancreatic cancer rate in the cholelithiasis group (0.22%) thanin the control group (0.05%)(p=0.003). The subsequent pancreatic cancer rates weresimilar,at0.17%, 0.11%, 0.26%, and 0.29%, in the ES/EPBD, CCY, ES/EPBD&CCY, and no-intervention groups, respectively.Conclusion:Symptomatic cholelithiasis is a risk factor for pancreatic cancer, and the risk is similar regardless of the intervention of cholelithiasis.Trial registration: This study was resisted on 23th August 2019 with registration number CS18136. The study design of this study is a retrospective database study.
COVID-19 in Teriflunomide-Treated Patients with Multiple Sclerosis
Authors: Maghzi Amir-Hadi , Houtchens Maria K. , Preziosa Paolo , Ionete Carolina , Beretich Biljana D , Stankiewicz James M , Tauhid Shahamat , Cabot Ann , Berriosmorales Idanis , Schwartz Tamara HW , Sloane Jacob A , Freedman Mark S , Filippi Massimo , Weiner Howard L , Bakshi Rohit 
Published: May 2020

Abstract
The outbreak of a severe acute respiratory syndrome caused by a novel coronavirus (COVID-19), has raised health concerns for patients with multiple sclerosis (MS) who are commonly on long-term immunotherapies. Managing MS during the pandemic remains challenging with little published experience and no evidence-based guidelines. We present five teriflunomide-treated patients with MS who subsequently developed active COVID-19 infection. The patients continued teriflunomide therapy and had self-limiting infection, without relapse of their MS. These observations have implications for the management of MS in the setting of the COVID-19 pandemic.
An improved multivariate model that distinguishes COVID-19 from seasonal flu and other respiratory diseases
Authors: Guo Xing , Li Yanrong , Chang Xu , Li Junfeng , Li Kefeng 
Published: May 2020

Abstract
Background: In many countries, the COVID-19 pandemic is occurring in the middle of flu season. Since the responses to COVID-19 are dramatically different, it is critical to accurately discriminate COVID-19 from seasonal flu and pneumonia caused by other common respiratory pathogens. Methods: Fifty patients (eight patients with COVID-19, eight with influenza, and 34 with community-acquired pneumonia) were included in our study. Sixteen features, such as clinical symptoms, results of routine blood tests, first reverse transcription-polymerase chain reaction (RT-PCR), and chest CT, were collected. The importance of each feature in discriminating COVID-19 from others was ranked by the random forest algorithm. Models with single or multiple features were evaluated using receiver operating characteristic (ROC) curves, the F1 score, and Matthews correlation coefficient (MCC). Results: An integrated multi-feature model (RT-PCR, CT features and blood lymphocyte percentage) yielded an area under the ROC curve of 0.97 (95% CI: 0.86 – 1, P < 0.01), an F1 score of 0.81 and an MCC of 0.78 in the training cohort as well as an F1 score of 0.86 and an MCC of 0.85 in the validation set. Conclusion: The developed multivariate model showed better accuracy than the current nucleic acid-based method for the differentiation of COVID-19 from influenza and pneumonia caused by other common respiratory pathogens.
Using Short Read Sequencing to Characterise Balanced Reciprocal Translocations in Pigs
Authors: Bouwman Aniek Cornelia , Derks Martijn F.L. , Broekhuijse Marleen L.W.J. , Harlizius Barbara , Veerkamp Roel F. 
Published: May 2020

Abstract
Background A balanced constitutional reciprocal translocation (RT) is a mutual exchange of terminal segments of two non-homologous chromosomes without any loss or gain of DNA in germline cells. Carriers of balanced RTs are viable individuals with no apparent phenotypical consequences. These animals produce, however, unbalanced gametes and show therefore reduced fertility and offspring with congenital abnormalities. This cytogenetic abnormality is usually detected using chromosome staining techniques. The aim of this study was to test the possibilities of using paired end short read sequencing for detection of balanced RTs in boars and investigate their breakpoints and junctions.Results Balanced RTs were recovered in a blinded analysis, using structural variant calling software DELLY, in 6 of the 7 carriers with 30 fold short read paired end sequencing. In 15 non-carriers we did not detect any RTs. Reducing the coverage to 20 fold, 15 fold and 10 fold showed that at least 20 fold coverage is required to obtain good results. One RT was not detected using the blind screening, however, a highly likely RT was discovered after unblinding. This RT was located in a repetitive region, showing the limitations of short read sequence data. The detailed analysis of the breakpoints and junctions suggested three junctions showing microhomology, three junctions with blunt-end ligation, and three micro-insertions at the breakpoint junctions. The RTs detected also showed to disrupt genes.Conclusions We conclude that paired end short read sequence data can be used to detect and characterize balanced reciprocal translocations, if sequencing depth is at least 20 fold coverage. However, translocations in repetitive areas may require large fragments or even long read sequence data.
Community-based Intervention for Cervical Cancer Screening Uptake in a Semi-urban Area of Pokhara Metropolitan, Nepal (Cobin-c): Study Protocol for a Cluster-randomized Controlled Trial
Authors: Shrestha Aamod Dhoj , Neupane Dinesh , Ghimire Sarita , Campbell Christine , Kallestrup Per 
Published: May 2020

Abstract
Background:Previous studies suggest that health intervention designed to increase cervical cancer screening has been effective to reduce cervical cancer incidence and mortality.The aim of this study is to determine the effect of a home-based health education intervention for increasing cervical cancer screening uptake delivered by trained Female Community Health Volunteers (FCHVs), a category of community health worker in Nepal. Methods:A community-based, open-label, two-armed, cluster-randomized trial [seven clusters (geographical wards) randomized for the intervention, and seven for the control arm]. The participants are recruited from a population-basedsurvey with a sample size of 884. Based on population proportionsize, 277women will be recruited for the intervention group and 413 women recruited for the control group.A 12-month community-based health education intervention will be administered mobilizing the FCHVs, based on the Health Belief Model. The primary outcomemeasure of the study will be the difference in percentage of cervical cancer screening uptake between the two study arms.The primary outcomes will be modelled by using mixed-effect logistic regression analysis.Discussion: COBIN-C is the first study investigating the effect of a community-based health education intervention by FCHVs on increasing cervical cancer screening uptake among women in Nepal. The purposeof this study is to develop and implement a home-based, culturally sensitive program to increase cervical cancer screening coverage at the community level.Trial registration: ClinicalTrials.govNCT03808064. Registered on January 14, 2019. (https://clinicaltrials.gov/ct2/show/NCT03808064).
Effects of Variable Frequencies of Combined Proprioceptive and Kinesthesia, Balance and Agility Exercise Program in Adults With Knee Osteoarthritis: a Study Protocol for Randomized Controlled Trial
Authors: Adhama Aysha I. , Akindele Mukadas O. , Ibrahim Aminu A. 
Published: May 2020

Abstract
Background:Knee osteoarthritis (OA) is a common painful and disabling condition that affects older individuals. Proprioceptive (PR) and kinesthesia, balance and agility (KBA) exercises are two neuromuscular training reported to be beneficial for individuals with knee OA. However, their combined effects have not been systematically evaluated. Moreover, the most optimal dosage of knee OA exercise-based programremains unclear. The aim of this study is to determine the combined effects of PR and KBA exercise program with different frequency of treatment sessions(i.e. twice weekly or thrice weekly) in adults with knee OA.Methods:A single (assessor) blind, three-arm parallel, multi-centerrandomized controlled trial will be conducted. Eighty-four adults with knee OA will be recruited from four tertiary hospitals in Northwestern Nigeria and randomly assigned into one of three intervention groups; group 1 (control or conventional physiotherapy; n = 28), group 2 (two sessions per week of combined PR and KBA exercise; n = 28), and group 3 (three sessions per week of combined PR and KBA exercise, n = 28). Participants in the conventional therapy group will receive two sessions of brief patient education, and 16 sessions of ultrasound therapy, and stretching, strengthening and aerobic exercise for 8 weeks. Participants in the two experimental groups will be treated for 8 weeks and will also receive the same conventional therapy. All groups will be assessed pre-intervention, immediately post-intervention and at 3-month, 4-month and 6-month post-randomization. The primary outcomes will be physical function and quality of life while the secondary outcomes will be pain intensity, knee stability and proprioception.Discussion:Findings of this study may provide evidence of effectiveness of combined PR and KBA exercise program for knee OA, which may serve as a basis for recommending the use of such multimodal exercise approachfor individuals with knee OA. The study may also provide evidence for the ideal number of sessions of knee OA exercise-based programsto achieve the highest effectiveness.Trial registration:Pan African Clinical Trials Registry, (PACTR201810713260138), Registered on 28 November 2017.
Study on the effect Mongolian Medicine Qiwei Qinggan Powder on Hepatic Fibrosis through JAK2/STAT3 Pathway
Authors: Liang Jie , Menggensilimu Menggensilimu , Wang Feng , Yuan Hongwei , Yan Yuxin , Bao Xiaomei , Xiao Rui , Wang Haisheng , Zhang Chunyan , Jin Rong , Ma Lijie , Zhang Jianyu , Hurilebagen Hurilebagen , Su Xiaoli , Ma Yuehong 
Published: May 2020

Abstract
Background: To study the anti-hepatic fibrosis effect and explore the mechanism of Qiwei Qinggan Powder (QGS-7) in vivo and in vitro. Methods: Carbon tetrachloride (CCl 4 )-treated rats and hepatic stellate cells (HSCs) were used. Alanine Aminotransferase (ALT), Aspartate transaminase (AST) and Alkaline Phosphatase (ALP) were detected in serum of rats in each group, hydroxyproline (HYP) was detected in liver tissue. Formalin-fixed liver specimens were stained with hematoxylin and eosin (H&E) reagent, Masson trichrome, and then analyzed. The expression of Alpha smooth muscle actin (α-SMA) in liver was detected by immunohistochemistry. The expression level of Collagen I, α-SMA, Janus kinase 2 (JAK2), and signal transducer and activator of transcription 3(STAT3) mRNA were determined by real Time polymerase chain reaction (RT-qPCR). Meanwhile, the protein expression levels of α-SMA, Collagen I, JAK2, phosphorylation-JAK2 (p-JAK2), STAT3 and phosphorylation-STAT3 (p-STAT3) were determined by Western Blot. The proliferation of HSC was detected by MTT and the apoptosis was detected by flow cytometry. Results: QGS-7 treatment significantly improved the liver function of rats as indicated by decreased serum enzymatic activities of ALT, AST and ALP. Meanwhile, the HYP of liver was significantly decreased. Histopathological results indicated that QGS-7 alleviated liver damage and reduced the formation of fibrosis septa. Moreover, QGS-7 significantly attenuated expressions of α-SMA, Collagen I, JAK2, p-JAK2, STAT3, p-STAT3 relative mRNA and protein level in the rat hepatic fibrosis model and HSCs. And QGS-7 can inhibit HSCs proliferation and promote it apoptosis. Conclusion: Mongolian medicine QGS-7 has the effect of treating hepatic fibrosis and can inhibit the activation, proliferation and promote apoptosis of HSCs. Meanwhile, in the process of anti-hepatic fibrosis, QGS-7 can reduce the expression of JAK2, p-JAK2, STAT3 and p-STAT3 in JAK2/STAT3 signaling pathway. Therefore, we speculate that QGS-7 may affect HSCs through JAK2/STAT3 signaling pathway, so as to play an anti-hepatic fibrosis role.
The Anti-RA Activities of a Couplet Medicinals, Gastrodia Elata and Radix Aconitic Lateralis preparata, Explored by Untargeted Metabolomics and Network Pharmacology.
Authors: Yang Jie , SHEN Xiang-Chun , LI Wei-Hong , FAN Guang-Zhong , GUO Bu-Fa , PENG Qi-Lun , YAO Wei-Yi , GONG Di-Hong , DING Wei-Jun 
Published: May 2020

Abstract
Background

The couplet Medicinals, Gastrodia Elata and Radix Aconitic Lateralis preparata (GERA), is an established formula extensively used in Chinese medicine for treating rheumatoid arthritis (RA). However, the anti-RA mechanisms of GERA are still unclear. This paper aims to explore the anti-RA mechanisms of GERA by a combined strategy of untargeted metabolomics and network pharmacology.
Methods

Three water extracts were prepared as propotions: Gastrodia Elata compared with Radix Aconitic Lateralis (w/w): 1:1, 3:2, or 2:3. The untargeted metabolomics were executed with UPLC-MS. The metabolites were annotated and identified by Human metabolome database (HMDB) and Lipid maps database. Finally, key genes and pathways related to anti-RA activities of GERA were mined by network pharmacology.
Results

The untargeted metabolomics profile displayed that four differentially expressed metabolites were involved in isoflavonoid biosynthesis and biosynthesis of unsaturated fatty acids (p < 0.05). Among these differential metabolites, the essential ingredients of GERA were linoleic acid, daidzein, and daidzin. The principal targets of anti-RA activities of GERA were IL-6, TNF, VEGFA, TP53, CASP3 and PTGS2. Thirty anti-RA targets of GERA were majorly belonged to pathways response for anti-inflammation, endothelial function and apoptosis, suggesting the fundamental process of RA treatment.
Conclusion

The anti-RA activities of GERA were based on the inhibition of inflammation and regulation of endothelial function and apoptosis.
The study of neuroprotective effects and underlying mechanism of Naoshuantong capsule on ischemia stroke mice
Authors: Luo Lvkeng , Wu Shuling , Chen Ruiqi , Rao Hongyu , Peng Wei , Su Weiwei 
Published: May 2020

Abstract
Background
Naoshuantong capsule (NSTC) is an oral Chinese medicine formula composed of Typhae Pollen (TP), Radix Paeoniae Rubra (PR), Curcumae Radix (CR), Gastrodiae Rhizoma (GR) and Radix Rhapontici (RR). It has been widely used at the acute and recovery stage of ischemic stroke since 2001. Comparing with its wide clinical application, there are only few studies emphasize on investigating its pharmacological effects.
Methods
To more generally elucidate the underlying mechanisms in this study, we identified active ingredients in NSTC by a network pharmacology approach based on transcriptomics analysis and pharmacological experiments. Modified neurological severity scores (mNSS) and morphometric analysis using Nissl staining were employed to evaluate the neuroprotective effects of NSTC on ischemia stroke in mice.
Results
The results showed that NSTC had preventive and protective effects on ischemia stroke, featuring repair of brain tissue during the sub-acute stage of stroke. This may attribute to the underlying mechanisms including anti-inflammatory, antioxidant, and anti-apoptotic activities, as well as an attenuation of excitatory amino acids (EAAs) toxicity of the active ingredients, especially the most active apigenin, from NSTC. Specifically, naringenin, calycosin, gastrodin, caffeic acid, paeoniflorin, and β -elemene seem to be also pharmacological active substances responsible for the anti-inflammatory effects. Meanwhile, 13-hydroxygemone, gastrodin, and p-hydroxybenzyl alcohol contributed to the attenuation of EAAs toxicity Furthermore, apigenin, naringenin, calycosin, gastrodin, and β-elemene accelerated the repair of brain ischemic tissue by up-regulating the expression of TGF-β1 levels.
Conclusions
The present study identifies the active ingredients of NSTC and illustrates the underlying mechanism using a combination of network pharmacology, transcriptomics analysis, and pharmacological experiments.