bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Systematic Review Protocol of The Antiviral Activity of Chloroquine and Hydroxychloroquine Against COVID-19.
Authors: Mensah Kofi Boamah , Mensah Adwoa Bemah Boamah , Bangalee Varsha , Oosthuizen Frasia 
Published: July 2020

Abstract
Background: The recent outbreak of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), or COVID-19 with no approved medicines has led to global health threat. Currently, repositioning of old medicines seems the most responsible strategy for potential cure and prevention COVID-19. Hydroxychloroquine and chloroquine have shown promising efficacy against COVID-19 related pneumonia in clinical studies. However, the mode of drug action of chloroquine and hydroxychloroquine against SARS-CoV-2 infection is not clear. This review aims to gather evidence on antiviral activity and possible mechanism of drug action of chloroquine and hydroxychloroquine on SARS-CoV-2, including in-vitro, animal studies, and studies in humans.Method: A structured search of five bibliographic databases namely; Medline, Web of Science, PubMed, Cochrane CENTRAL, and Google Scholar will be undertaken to retrieve studies that describe the antiviral activity and possible mechanism of drug action of chloroquine and hydroxychloroquine on SARS-CoV-2. No restrictions will be placed on publication date, but studies will be limited to only publications in English. Duplication of studies will be removed using EndNote reference manager. Three authors will screen the citations independently based on inclusion criteria. Data extraction and assessment of risk of bias will be done independently. Meta-analysis of selected studies will be done wherever suitable.Discussion: We expect that data that will be synthesis will provide enough information to inform COVID-19 care pathways and help clinicians caring for COVID-19 patients. Furthermore, this systematic review will expand our knowledge on the benefits and risks of chloroquine and hydroxychloroquine in management of COVID-19 patients and identify areas of controversies, and quality assessment. This review will provide vital information needed in the development of contextualized guidelines for the management of COVID-19 patients.Systematic review registration: https://doi.org/10.17605/OSF.IO/7DJMU
Overexpression of TC2N is associated with poor prognosis in gastric cancer
Authors: Xu Jianbo , Ou Xinde , Li Jin , Cai Qinbo , Sun Kaiyu , Ye Jingning , Peng Jianjun 
Published: July 2020

Abstract
Background

Tac2-N (TC2N) is a tandem C2 domain-containing protein, acting as a novel oncogene or suppressor in different kinds of cancers. However, the status of TC2N expression and its significance in gastric cancer (GC) is still unclear. The present study is aimed to elucidate the clinicopathological significance and prognostic value of TC2N level in GC.
Methods

We used sequencing data from the Cancer Genome Atlas (TCGA) database to analyze TC2N expression in GC by UALCAN database and Gene Expression Profiling Interactive Analysis tools (GEPIA). TC2N expression level in 12 pairs of fresh GC tissues and adjacent nontumorous tissues was detected by quantitative real-time reverse-transcription polymerase chain reaction(RT-PCR)and Western blot(WB) assays. Immunohistochemical (IHC) staining was used to detect TC2N protein expression in Paraffin-embedded tissues in our center. In vitro proliferation, migration and invasion assays were used to evaluate the effect of TC2N on functional capability of gastric cancer cells. LinkedOmics was used to identify gene expressions associated with TC2N.
Results

The mRNA and protein expression of TC2N in gastric cancer were both significantly higher than normal gastric mucosa. It was also elevated in gastric cancer cells compared with normal gastric epithelium cell. In vitro assays suggested that TC2N facilitated proliferation, migration and invasion of gastric cancer cells. Bioinformatic analysis showed a widespread impact of TC2N on the transcriptome and a strong interaction with tumor associated genes. We also found that TC2N was an independent prognostic factor for long-term survival in GC patients and its high expression was significantly associated with poor overall survival and recurrence-free survival.
Conclusions

Our results show that high level of TC2N correlates with poor prognosis in patients with gastric cancer and promotes the development of gastric cancer. Thus, TC2N expression can serve as a prognostic biomarker for patients with gastric cancer.
Artificial Neural Network-Based Predicting the Risk of Complicating Ventricular Tachyarrhythmia after Acute Myocardial Infarction During Hospitalization
Authors: Zheng Xifeng , Nong Weidong , Feng Dehui , Wang Junxian , He Yan 
Published: July 2020

Abstract
An artificial neural network (ANN) model was developed to predict the risks of complicating ventricular tachyarrhythmia (VTA) in patients with acute myocardial infarction (AMI). We enrolled information of 503 patients with 13 risk factors from the affiliated hospital of Guangdong medical university from January 2017 to December 2019. Risk factors were dimensionally reduced and simplified as new variables by principal component analysis (PCA). The cohort were randomly divided into a training set and a testing set at the ratio of 70%:30%. Training set was used to develop a model for the prediction of VTA while testing set was used to evaluate the performance of the model. Three new comprehensive variables by PCA are able to reflect all information of the original data. We determined the prediction model with optimizing parameters by cyclic searching which includes an input layer of three comprehensive variables, a single hidden layer composed of two neurons and a output layer. The area under curve (AUC) is 0.812 in training set and confusion matrix with accuracy 94.60%, sensitivity 63.04%, specificity 99.35%, positive predicative value 93.55%, negative predictive value 94.70%. The model displayed a decreased but medium discrimination with an AUC of 0.688 in the independent testing cohort, confusion matrix with accuracy 87.42%, Sensitivity 39.26%, specificity 98.37%, positive predicative value 84.62%, negative predictive value 87.68%. The research suggests that ANN model could be used to predict the risk of complicating ventricular tachyarrhythmia after acute myocardial infarction while should be further improved.
Randomized Longitudinal Study Comparing 3 Nasal Respiratory Support Modes to Prevent Intermittent Hypoxia in Very Preterm Infants
Authors: Gross Maximilian , Poets Anette , Steinfeldt Renate , Urschitz Michael S. , Böckmann Katrin , Haase Bianca , Poets Christian F. 
Published: July 2020

Abstract
Background: Nasal continuous positive airway pressure (NCPAP) devices using variable (vf-) and continuous (cf-) flow or synchronized nasal intermittent positive pressure ventilation (s-NIPPV) are used to prevent or treat intermittent hypoxia (IH) in preterm infants. Results on which is most effective vary. We aimed to investigate the effect of s-NIPPV and vf-NCPAP compared to cf-NCPAP on the rate of IH episodes.Methods: Preterm infants with a gestational age of 24.9-29.7 weeks presenting with IH while being treated with cf-NCPAP were monitored for 8 hours, then randomized to 8 h of treatment with vf-NCPAP or s-NIPPV. Data from 16 infants were analyzed. Due to an unexpectedly low sample size, results are only reported descriptively.Results: No relevant changes in the rate of IH events were detected between cf- vs. vf-NCPAP or between cf-NCPAP vs. s-NIPPV.Conclusion: Although limited by its small sample size, s-NIPPV, vf- and cf-NCPAP seemed to be similarly effective in the treatment of IH in these infants.Trial registration: This study was registered with the German Clinical Trials register - DRKS00005387. Registered 12 November 2013, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00005387
Inhibition of Autophagy by 3-Methyladenine restricts Murine Cytomegalo virus Replication
Authors: Zhang Xinyan , Zhang Linlin , Bi Yidan , Xi Ting , Zhang Zhan , Huang Yuan , Lu Yuanyuan , Liu Xinglou , Fang Feng 
Published: July 2020

Abstract
Background:Cytomegalovirus (CMV) could induce autophagy early upon infection, which might have an impact on virus replication and the survival of host cells. The purpose ofthe present study was to determine how autophagy effects virus replication and whether it is associated with caspase-3 dependent apoptosis duringmurine cytomegalovirus (MCMV) infection. Methods:The eyecup isolated from adultC57BL/6J mice (6-8 weeks old) and mouse embryo fibroblast cells (MEFs) were cultured and infected with MCMV K181 strain, following by treated with 3-methyladenine (3-MA)or rapamycin to block or activate autophagy.Immunofluorescence staining and western blot were used to detect the expression of early antigen (EA) of MCMV, autophagy and cell death related factors. Plaque assay was performed to detect the virus titer in different groups. TUNEL assay was used to measure the percentage of cell death.Results: Results showed that autophagy was induced at 24,72 and 96hours post infection (hpi)with MCMV in MEFs. In the eyecup culture, it also showed that autophagy was induced at 4 and 7days post infection (dpi).In addition, caspase-3 dependent apoptosis and receptor-interacting kinase 1/ receptor-interacting kinase 3/mixed lineage kinase domain-like protein (RIPK1/RIPK3/MLKL) dependent necroptosis were induced by MCMV infection in eyecup.In MEFs, caspase-3 dependent apoptosis was inhibited, whileRIPK1/RIPK3/MLKL dependent necroptosis was activated with MCMV infection. Once treatment with 3-MA, there were significantly less active virus particles released in MEFs and eyecup, also EA expression was significantly inhibited in the eyecup. However, treatment with rapamycin have no such significant influence on either virus titer or EA expression in MEFs and eyecup. Furthermore, cleaved caspase-3 was elevated, while RIPK1/RIPK3/MLKL pathway was inhibited with treatment of 3-MA both in MEFs and eyecup. Conclusion:Inhibition of autophagy by 3-MA could both restrict virus replication and promote caspase-3 dependent apoptosis in the eyecup and MEFs with MCMV infection.It can be explained that on the early periodof MCMV infection, suppressed autophagy process directly reduced virus release.Thereafter, caspase-3 dependent apoptosis was activated and resulted in decreased virus replication.
Bi-parametric MRI/TRUS fusion targeted repeat biopsy after systematic 10-12 core TRUS-guided biopsy reveals more significant prostate cancer especially in anteriorly located tumours
Authors: Häggman Michael , Ahlberg Mats , Dahlman Pär , Liss Per , Ahlman Rafaele Cantera , Röbeck Pontus , Dragomir Anca , Jorulf Håkan , Ladjevardi Sam 
Published: July 2020

Abstract
Background

To demonstrate possible advantages with Bi-parametric MRI fusion-guided repeat biopsy over systematic 10-12-core biopsy for diagnosis of prostate cancer.
Methods

All patients who underwent fusion guided biopsy between February 2015 to February 2017 were included. Four hundred twenty-three consecutive men, with previous systematic10-12-core TRUS-guided biopsy, with suspicion of or low-risk prostate cancer underwent fusion-guided prostate biopsy. The material was retrospectively assessed. In 220 cases no previous cancer was diagnosed and in 203 cases confirmatory fusion guided biopsy was performed prior to active monitoring. MRI was done and classified according to PI-RADS. Region of Interest (ROI) was marked. Systematic biopsy was compared to fusion guided biopsy for detection of cancer, as well as PI-RADS was compared to Gleason score.
Results

Fusion guided biopsy detected significantly more cancers than systematic (p < 0.001). Gleason scores were higher in the fusion biopsy group (p < 0,001). PI-RADS score correlated with the presence of cancer in fusion biopsies. PI-RADS 2 yielded 19% cancer and PI-RADS 3 56%, PI-RADS 4–5 were cancerous in 83%. Only 3 out of 53 biopsies from PI-RADS 2 lesions showed high grade cancer (Gleason score 4 + 3 and higher) compared to 10/133 (7,5%) from PI-RADS 3 lesions and 54/239 (23%) from PI-RADS 4–5.
Conclusion

These results show superior detection rate and grading of bi-parametric MRI/TRUS fusion targeted repeat biopsy over systematic 10–12 core biopsies. Fusion guided biopsy detects more significant cancers despite using fewer cores. There is significant impact on known cases of low-risk PCa with change of risk group for many patients initially selected for active surveillance.
Performance of RIPASA and AIR scores in an Egyptian subset of patients with suspected diagnosis of acute Appendicitis
Authors: Faisal Mohamed , Bayoumi Ahmed A , Bakr Ahmed Abo , Edlehamre Marcus , Khaled Islam 
Published: July 2020

Abstract
Background

Early and definitive acute appendicitis (AA) diagnosis remains a great challenge in clinical practice worldwide. Currently, several risk scores are available for the clinical assessment of AA, although there are differences in their accuracy rates.

Aim

To assess and analyze the accuracy of the acute inflammatory response (AIR) and Raja Isteri Pengiran Anak Saleha Appendicitis (RIPASA) scores in an Egyptian population.

Methods

A series of 310 patients, 61% male with a median age of 18 years, with Rt. Iliac fossa pain were clinically evaluated for suspicion of AA. All patients were assessed using both the AIR and RIPASA scores. Following evaluation, all patients underwent appendectomy. A final diagnosis of AA was based on histopathology. Two predetermined cutoff values for the AIR score and one cutoff value for the RIPASA score was evaluated for sensitivity, specificity, and accuracy.

Results

The sensitivities of the RIPASA score cutoff value of ≥7.5 and AIR score cutoff values of >4 and >8 were 83.8%, 92.2%, and 33.1%, accordingly, while the specificities were 69.2%, 76.7%, and 84.6%, respectively. AIR score of >4 (91%) was more accurate compared to AIR score of >8 (37.4%) and RIPASA score of ≥7.5 (82.5%).

Conclusion

An AIR score of >4 had better sensitivity, specificity, and accuracy compared to a RIPASA score of ≥7.5 for the Egyptian population. However, an AIR score of >8 was more specific.
Erythropoietin Promotes the Differentiation of Fetal Neural Stem Cells into Glial Cells Partly via EPOR-βCR/Syne-1/H3K9me3 Pathway
Authors: Zhang Sijia , Wang Rongliang , Li Fangfang , Tao Zhen , Yang Zhenhong , Zhao Haiping , Luo Yumin 
Published: July 2020

Abstract
Erythropoietin (EPO) treatment has achieved a remarkable improvement of cognition in neonatal hypoxic-ischae mic encephalopathy (HIE) in clinical settings, however, it did not lower the severe neurodevelopmental impairment to extremely preterm infants, however, the primary cause of this discrepant phenomenon is still puzzling. Here, we explore the effect of EPO on post-hypoxic neurogenesis using fetal neural stem cells (NSCs)/neural progenitors (NPs) and whether the effect is mediated by EPOR/βCR heteromimer. Fetal NSCs/NPs was treated with EPO at different time point after oxygen and glucose deprivation/reoxygenation (OGD/R). Cell viability, proliferation, and differentiation of NSCs/NPs were detected by CellTiter-Glo, Edu assay, flow cytometry and RT-PCR. We found that EPO treatment at different time point increased the cell viability without affecting the proliferation. EPO treatment immediately after OGD/R promoted the oligodendrocyte and astrocyte differentiation, while decreased neuronal differentiation of NSCs/NPs. Furthermore, immunofluorescence and co-immunoprecipitation proved the existence of EPOR/βCR heterodimer on NSCs/NPs, and EPO treatment significantly increase the mRNA expression of βCR and elevated the correlation between levels of EPOR and βCR. Moreover, EPOR and βCR receptors were both correlated with markers of oligodendrocytes. In addition, mass spectrometer analysis identified Syne-1 as one downstream signaling of EPOR/βCR heterodimer. Immunofluorescence and western blot indicated that βCR/Syne-1/H3K9me3 pathway was possibly involved in the function of EPO. Collectively, our data revealed that EPO treatment immediately after OGD/R was not a good time point for neurogenesis, and EPO could promote the formation of EPOR/βCR on fetal NSCs/NPs which mediates its function on glia differentiation.
A Pilot Study of the Ultrathin Cryoprobe in the Diagnosis of Peripheral Pulmonary Ground-Glass Opacity Lesions
Authors: Liu Xiaojun , Jiang Simin , Chen Junxiang , Ma Haifeng , Xie Fangfang , Sun Jiayuan 
Published: July 2020

Abstract
Background: It is very difficult to obtain samples of peripheral pulmonary ground-glass opacity lesions (GGOs) by traditional transbronchial biopsy. This study was conducted to evaluate the diagnostic efficacy and safety of transbronchial cryobiopsy (TBCB) for GGOs by a newly developed ultrathin cryoprobe whose outer diameter was 1.1 mm.Methods: Twenty patients with 23 GGOs received TBCB using the ultrathin cryoprobe were retrospectively analyzed from October 2018 to November 2019 in Shanghai Chest Hospital. TBCB was performed under the guidance of virtual bronchoscopic navigation (VBN), electromagnetic navigation bronchoscopy (ENB), endobronchial ultrasound and fluoroscopy. We collected baseline information of subjects, reported diagnostic yield and complications, analyzed factors may affect the diagnostic yield.Results: Twenty-three GGOs (12 pure GGOs, 11 mixed GGOs), with an average diameter of 21.58 ± 11.88mm, received TBCB and the diagnostic yield was 82.61% (19/23). Of the 19 GGOs diagnosed by TBCB, 12 were adenocarcinoma, 5 were inflammation, one was occupational interstitial lung disease, one was pulmonary meningothelial-like nodule. The undiagnosed 4 lesions confirmed to be adenocarcinomas by further analysis. None of the factors, including size (GGOs ≥ 20mm, GGOs < 20mm), navigation (VBN, ENB), fluoroscopic visibility (visible, invisible), GGO-component (pure GGOs, mixed GGOs) and guide sheath (K-201, K203), changed the diagnostic yield. No pneumothorax or severe hemorrhage presented.Conclusions: The ultrathin cryoprobe is feasible and safe for the diagnosis of pulmonary GGOs with high diagnostic yield, which provided a huge potential tool for the diagnosis of GGOs, especially for those suspicious of early-stage lung cancer.Trial registration: Clinical Trials.gov. No: NCT03716284. Registered: 20 October, 2018. URL: Clinical Trials.gov.
Pharmacokinetic Analysis of Dynamic [18F]FAZA PET Imaging in Pancreatic Cancer Patient
Authors: Li Fiona , Taylor Edward , Yeung Ivan , Jaffray David , Metser Ur , Dhani Neesha , Hedley David W , Lee Ting-Yim 
Published: July 2020

Abstract
Purpose

This study assessed the pharmacokinetics of the hypoxia PET tracer, [18F]fluoroazomycin arabinoside ([18F]FAZA), in pancreatic cancer (PCa) patients and determined the optimal kinetic parameters to distinguish cancerous from normal pancreatic tissue.

Method

Twenty patients with pancreatic ductal adenocarcinoma underwent dynamic [ 18 F]FAZA scans. The tissue time activity curve (TAC) was analyzed using graphical methods to determine reversibility of tracer binding and with standard compartment (S2TC) model and flow modified two tissue compartment (F2TC) model, developed to incorporate transit time of tracer through the blood vessel, to estimate the kinetic parameters. The optimal parameter set to distinguish hypoxic tumors from normal tissues was determined using logistic regression.

Results

Both graphical and kinetic model analysis indicated that tracer was reversibly bound. According to the Akaike Information Criteria, the F2TC model fitted the tumor TAC better than the S2TC model. Total distribution volume, V T , estimated by the F2TC model for both tumor and normal pancreatic tissue was not significant but that estimated by the S2TC model was significantly different from Logan graphical analysis. The extravascular distribution volume ( DV ) and tracer dissociation rate constant ( k 4 ) can classify hypoxic PCa from normal tissue with sensitivity of 95% and negative predictive value of 89% (P<0.01).

Conclusions

Kinetic analysis of dynamic [ 18 F]FAZA PET can distinguish PCa from normal tissue with high sensitivity. The reversibility of [ 18 F]FAZA binding in hypoxic cells could be due to glutathionylation of the nitroreductase reduced products and their subsequent efflux from same cells via the ATP mediated multidrug resistant protein (MRP-1) efflux pump.
Identification of an appropriate cell line for the renal cell carcinoma model
Authors: Chang In Youb , Ohn Takbum , Moon Daeun , Maeng Young Hee , Jang Bo Gun , Yoon Sang-Pil 
Published: July 2020

Abstract
Background

Although renal cell carcinoma (RCC) is known to be susceptible to ferroptosis, we found primary RCC cells showed resistance to ferroptosis and aimed to investigate a feasible candidate for an appropriate cell line for the RCC model.

Methods

Glutathione peroxidase 4 (GPX4) immunostaining was adopted in the RCC tissue microarrays. Normal human proximal tubule cells (HK-2) and RCC cell lines were used for the MTT assay, Western blotting, sphere-forming assay, and orthotopic injection of athymic Balb/c-nude mice.

Results

GPX4 immunostaining showed low intensity compared to the normal kidney, which coincided with the ferroptosis-susceptibility of RCC. Primary RCC cell lines (Caki-2, SNU-333, SNU-349, and SNU-1272) showed resistance to 5-fluorouracil and a GPX4 inhibitor compared to the HK-2 cells and to metastatic RCC cells (Caki-1). The Caki-2 cells showed increased GPX4 and xCT, and the SNU-333 cells showed increased ferritin heavy chain (FTH1) compared to the other RCC cells. The Caki-2 cells showed increased aSMA, fibronectin, vimentin, and SNAIL, and the SNU-333 cells showed increased aSMA, E-cadherin, and EpCAM. The Caki-2 cells showed increased Sox-2 and CD105, and the SNU-333 cells showed increased c-Myc and Lgr5. The Caki-1 and SNU-333 cells formed spheres in vitro and orthotopic RCC masses in vivo. The injected SNU-333 tumor only showed high intensities of CD10 and PAX8, consistent with the diagnostic criteria for RCC.

Conclusions

The primary RCC cell lines used in this study were more resistant to ferroptosis and 5-fluorouracil, and the SNU-333 cells showed tumor-initiating capacities in vitro and in vivo. These results suggest that SNU-333 might be suitable as a orthotopic RCC model for future research.