bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effects and Underlying Mechanisms of Hepatitis B Virus X Gene Mutants on the Development of Hepatocellular Carcinoma
Authors: Pu Rui , Liu Wenbin , Zhou Xinyu , Hou Xiaomei , Cai Shiliang , Chen Xi , Chen Liping , Wu Jianfeng , Yang Fan , Tan Xiaojie , Yin Jianhua , Wang Xin , Cao Guangwen 
Published: August 2021

Abstract
Background: We aimed to elucidate the mechanism by which hepatitis B virus X (HBx) gene mutations increase the risk of hepatocellular carcinoma (HCC) and identify novel therapeutic targets.Methods: Wild-type and four HBx mutants (M1, A1762T/G1764A; M2, T1674G+T1753C+A1762T/G1764A; M3, C1653T+T1674G+A1762T/G1764A; Ct-HBx, carboxylic acid-terminal truncated HBx) were delivered into the livers of fumarylacetoacetate hydrolase-deficient mice by using the Sleeping Beauty (SB) transposon system, respectively. Seven liver tissues and seven tumor tissues of the SB mouse models were subjected to HBV-capture sequencing. Three liver tissues from WT-HBx mice, three tumor tissues from M3-HBx mice, and three tumor tissues from Ct-HBx mice were subjected to cDNA microarray analysis. HeLa cells stably expressing WT-HBx and the four HBx mutants were also subjected to cDNA microarray assay.Results: The incidence of HCC was higher in the mice injected with M3-HBx or Ct-HBx. M3-HBx had a stronger capacity of upregulating inflammatory cytokines than other HBx variants. HBV-capture sequencing showed that the HBx fragments were mainly integrated into intergenic and intron regions. No significant difference was observed in the number of insertion sites between tumors and liver tissues. Ectopic expression of the HBx mutants, especially M3-HBx and Ct-HBx, significantly increased cell proliferation and the S phase proportion of HepG2 and HeLa cells, compared to WT-HBx. Liver tissues of the SB mice and the transfected cells were subjected to cDNA microarray analysis. Plasminogen activator inhibitor-1 (PAI1) and cell division cycle 20 (CDC20) were identified as novel effectors. M3-HBx and Ct-HBx significantly upregulated the expression of PAI1 and CDC20 in HepG2 and HeLa cells as well as the livers of the SB mice. PAI1 silencing attenuated the effect of M3-HBx and Ct-HBx on the growth of HepG2 cells and greatly decreased the growth of HeLa cells with Ct-HBx. Conclusion: HBx C1653T+T1674G+A1762T/G1764A mutant and Ct-HBx promote carcinogenesis via upregulating PAI1 and CDC20. PAI1, an important player bridging the HBx mutants and HCC, should be a promising candidate as a predictive and prognostic biomarker and therapeutic target in HBV-related HCC.
An Orally Available Small Molecule BCL6 Inhibitor Effectively Suppresses Diffuse Large B Cell Lymphoma Cells Growth in Vitro and in Vivo
Authors: Xing Yajing , Guo Weikai , Wu Min , Xie Jiuqing , Huang Dongxia , Hu Pan , Zhou Miaoran , Zhang Lin , Zhang Qiansen , Wang Peili , Wang Xin , Wang Guixue , Wu Huangan , Zhou Cili , Chen Yihua , Liu Mingyao , Yi Zhengfang , Sun Zhenliang 
Published: August 2021

Abstract
Background: The transcription factor B cell lymphoma 6 (BCL6) is an oncogenic driver of diffuse large B cell lymphoma (DLBCL) and mediates lymphomagenesis through transcriptional repression of its target genes by recruiting corepressors to its N-terminal broad-complex/tramtrack/bric-a-brac (BTB) domain. Blocking the protein-protein interactions of BCL6 and its corepressors has been proposed as an effective approach for the treatment of DLBCL. However, BCL6 inhibitors with excellent drug-like properties are rare. Hence, the development of BCL6 inhibitors is worth pursuing. Methods: We screened our internal chemical library by luciferase reporter assay and Homogenous Time Resolved Fluorescence (HTRF) assay and a small molecule compound named WK500B was identified. The binding affinity between WK500B and BCL6 was evaluated by surface plasmon resonance (SPR) assay and the binding mode of WK500B and BCL6 was predicted by molecular docking. The function evaluation and anti-cancer activity of WK500B in vitro and in vivo was detected by immunofluorescence assay, Real-Time Quantitative PCR, cell proliferation assay, cell cycle assay, cell apoptosis assay, enzyme-linked immunosorbent assay (ELISA), germinal centre (GC) formation mouse model and mouse xenograft model. Results: WK500B engaged BCL6 inside cells, blocked BCL6 repression complexes, reactivated BCL6 target genes, killed DLBCL cells and caused apoptosis as well as cell cycle arrest. In animal models, WK500B inhibited germinal centre formation and DLBCL tumor growth without toxic and side effects. Moreover, WK500B showed favourable pharmacokinetics and presented superior druggability compared to other BCL6 inhibitors. Conclusions: WK500B showed strong efficacy and favourable pharmacokinetics and presented superior druggability compared to other BCL6 inhibitors. So, WK500B is a promising candidate that could be developed as an effective orally available therapeutic agent for DLBCL.
CORONA (COre ultRasOund of Covid in iNtensive Care &amp; Acute Medicine) Study: National Service Evaluation of Lung and Heart Ultrasound in Intensive Care Patients With Suspected or Proven COVID-19
Authors: Parulekar Prashant , Powys-Lybbe James , Knight Thomas , Smallwood Nicholas , Lasserson Daniel , Rudge Gavin , Miller Ashley , Peck Marcus , Aron Jonathon 
Published: August 2021

Abstract
Background:
Combined Lung Ultrasound (LUS) and Focused UltraSound for Intensive Care heart (FUSIC heart - formerly Focused Intensive Care Echocardiography, FICE) can aid diagnosis, risk stratification and management in COVID-19. However, data on its application and results are limited to small studies in varying countries and hospitals. This United Kingdom (UK) national service evaluation study assessed how combined LUS and FUSIC Heart were used in COVID-19 Intensive Care Unit (ICU) patients during the first wave of the pandemic.
Method:
12 trusts across the UK registered for this prospective study. LUS and FUSIC Heart data were obtained, using a standardised data set including scoring of abnormalities, between 1st of February 2020 to the 30th July 2020. The scans were performed by intensivists with FUSIC Lung and Heart competency as a minimum standard. Data was anonymised locally prior to transfer to a central database.
Results:
372 studies were performed on 265 patients. There was a small but significant relationship between LUS score > 8 and 30-day mortality (OR 1.8). Progression of score was associated with an increase in 30-day mortality (OR 1.2). 30-day mortality was increased in patients with right ventricular (RV) dysfunction (49.4% vs 29.2%). Severity of LUS score correlated with RV dysfunction (p < 0.05). Change in management occurred in 65% of patients following a combined scan.
Conclusions:
In COVID-19 patients there is an association between lung ultrasound score severity, RV dysfunction and mortality identifiable by combined LUS and FUSIC Heart. Our findings suggest that serial combined LUS and FUSIC Heart on COVID-19 ICU patients may aid in clinical decision making and prognostication.
Electrical And Electrochemical Characteristics of Withania Somnifera Leaf Extract Incorporation Sodium Alginate Polymer Film For Energy Storage Applications
Authors: Chinnaiah K. , Theivashanthi T. , Kannan Karthik , Revathy M.S. , Parangusan Hemalatha , Jeyaseelan S. Christopher , Gurushankar K. 
Published: August 2021

Abstract
The current investigation address the Alternating current (AC) electrical properties, electrochemical characteristics on biopolymer as Withania somnifera leaf extract incorporated sodium alginate polymer film prepared by solution casting method. Some crystallinity along with amorphous nature of sodium alginate emerged due to the incorporation of Withania somnifera leaf extract. The more amount of strain occurred in crystallization provides broaden peak in X-ray Diffraction (XRD) pattern. With aid of guluronic and mannuronic acids in sodium alginate making hydroxyl bond formation with leaf extract due to the cross linking process can be analyzed from Fourier transform Infrared Spectroscopy (FTIR). At room temperature, the prepared 5 ml of leaf extract incorporated sodium alginate film has demonstrated highest ionic conductivity in the typical value of 2.80×10-6 S/Cm. The electrochemical window of the prepared polymer film in the range of -0.4 to 0.4 V suggesting that used as an electrolyte for supercapacitor applications.
Discovery and identification of potential anti-melanogenic active constituents of Bletilla striata by zebrafish model and molecular docking
Authors: Luo Yiyuan , Wang Juan , Li Shuo , Wu Yue , Wang Zhirui , Chen Shaojun , Chen Hongjiang 
Published: August 2021

Abstract
Background
Bletilla striata was the main medicine of many skin whitening classic formulas in traditional Chinese medicine (TCM) and was widely used in cosmetic industry recently. However, its active ingredient was still unclear and its fibrous roots were not used effectively. The aim of the present study was to discover and identify its potential anti-melanogenic active constituents by zebrafish model and molecular docking.
Methods
The antioxidant activities were evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, 2,2’-azino-bis-(3-ethylbenthiazoline-6-sulphonic acid) (ABTS) radical scavenging activity and ferric reducing antioxidant power (FRAP) assay. The anti-melanogenic activity was assessed by tyrosinase inhibitory activity in vitro and melanin inhibitory in zebrafish. The chemical profiles were performed by ultra-high-performance liquid chromatography combined with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS). Meanwhile, the potential anti-melanogenic active constituents were temporary identified by molecular docking.
Results
The 95% ethanol extract of B. striata fibrous roots (EFB) possesses the strongest DPPH, ABTS, FRAP and tyrosinase inhibition activity, with IC50 5.94 mg/L, 11.69 mg/L, 6.92 mmol FeSO4/g, and 58.92 mg/L, respectively. In addition, EFB and 95% ethanol extract of B. striata tuber (ETB) can significantly reduce the melanin synthesis of zebrafish embryos in dose-dependent manner. 39 chemical compositions, including 24 stilbenoids were tentatively identified from EFB and ETB. Molecular docking indicated that there were 83 (including 60 stilbenoids) and 85 (including 70 stilbenoids) compounds exhibit stronger binding affinities toward tyrosinase and adenylate cyclase.
Conclusion
The present findings supported the rationale for the use of EFB and ETB as natural skin-whitening agents in pharmaceutical and cosmetic industries.
Immunohistochemical Signatures as Predictors of Postsurgical Prognosis in Pulmonary Squamous Cell Carcinoma Patients
Authors: Lin Chengbin , Yu Hongyan , Chen Xiaohan , Shen Weiyu , Xi Yong 
Published: August 2021

Abstract
BackgroundWe aimed to evaluate the prognostic value of immunohistochemistry (IHC) markers and tumor-node-metastasis (TNM) stages in patients with pulmonary squamous cell carcinoma (SQCC). MethodsFrom January 2010 to December 2014, aA total of 556 patients with SQCC who underwent radical resection were included. The patients were grouped into a discovery group (n = 334) and a validation group (n = 222). Using the least absolute shrinkage and selection operator regression model, we extracted IHCs that were associated with progression-free survival (PFS) and then built a classifier. Clinicopathologic variables and the IHC-based classifier were analysed using univariable and multivariable logistic regression analysis. A nomogram to predict PFS was constructed and validated using bootstrap resampling.ResultsFollowingUsing the least absolute shrinkage and selection operator regression model, four IHC markers associated with progression-free survival (PFS) were identified. Furthermore, we developed a nomogram integrating IHC markers to predict 3- and 5-year PFS. We used the IHC-based classifiers to stratify patients in both groups into high- and low-risk groups. PFS was better in the low-risk group than in the high-risk group in both the discovery and validation groups. Multivariate analysis demonstrated that the IHC-based classifiers were independently prognostic in predicting the PFS of patients with SQCC. The performance of the nomogram was evaluated and proven to be clinically useful. Conclusions﻿We further developed a nomogram integrating the IHC-based classifiers and clinicopathological risk factors to predict PFS. Through combining the IHC-based classification and clinicopathology, we have a better insight into the prognosis assessment of patients with SQCC after surgery, which informs postoperative patient management.
A Practical Method of Optimal RSUs Deployment for Smart Internet of Vehicle
Authors: Zhang Honghan 
Published: August 2021

Abstract
The roadside units (RSUs) are absolutely indispensable elements in sparse highway senario for smart Internet of Vehicle (IoV). Most recent RSU deployment methods consider vehicle mobility, warning message reception probability and time delay respectively, do not mentioned the situation once the accident vehicle cant send the warning message. In this paper, we present a comprehensive analysis that integrates all these factors above. In particular, we model three kinds of common highway scenarios and give the closed-form expression of RSUs deployment number along the highway. The proposed method has been validated by extensive simulations using Matlab and NS2, its performance has been compared with TAPC method. Results reveal that our proposed method has better performance under the condition of high warning message probability.
Effect of Calcium Dobesilate (CaD) on Diabetic Macular Edema Treated by Intravitreal Ranibizumab
Authors: Wang Dongxuan , Wang Hui , Wu Shuang , Yang Xueqiu , Xu Jiansen 
Published: August 2021

Abstract
Background: Calcium dobesilate (CaD) had been used in the treatment of diabetic retinopathy (DR) due to its potential in protecting against retinal vascular damage. However, it did not reduce the risk of development of diabetic macular edema (DME). The aim of this study was to investigate the effect of CaD plus intravitreal ranibizumab in the treatment of DME.Methods: This retrospective, observational, consecutive case control study enrolled patients newly diagnosed with DME who received intravitreal ranibizumab (IVR) administration with 3-monthly loading dose injection followed by pro re nata (3+PRN) regimen with or without CaD orally daily for at least 12-month follow-up. Medical records and optical coherence tomography (OCT) results were reviewed and compared at baseline and at 3, 6, and 12 months after injection.Results: A total of 102 eyes from 102 patients were enrolled in this study. Fifty-four patients received IVR combined with CaD orally (IVR+CaD group), while forty-eight patients received IVR solely (IVR group). No statistically significant differences were found in the general condition of patients between the two groups at baseline (P > 0.05). At every follow-up, 3, 6 and 12 months after injection, the best corrected visual acuity (BCVA) improved and the central macular thickness (CMT) decreased in both groups when compared with those at baseline (P < 0.05), while there were no significant differences in BCVA improvement and CMT reduction between the two groups (P > 0.05). The mean number of ranibizumab injections in R+C group was significantly lower than that in R group (5.4 ± 1.1 injections versus 6.7 ± 1.6 injections, P<0.05) within 1-year treatment. No adverse events were found in neither groups.Conclusions: Adding oral CaD to intravitreal ranibizumab was demonstrated to have similar effectiveness and safety for improving visual function and restoring the anatomy of the retina in macular with fewer injections in DME patients.
A Satellite-linked Tag for the Long-term Monitoring of Diving Behavior in Large Whales
Authors: Palacios Daniel M. , Irvine Ladd M. , Lagerquist Barbara A. , Fahlbusch James A. , Calambokidis John , Tomkiewicz Stanley M. , Mate Bruce R. 
Published: August 2021

Abstract

Despite spending much of their time on activities underwater, the technology in use to track whales over large geographic ranges via satellite has been largely limited to locational data, with most applications focusing on characterizing their horizontal movements. We describe the development of the RDW tag, a new Argos-based satellite telemetry device that incorporates sensors for monitoring the movements and dive behavior of large whales over several months without requiring recovery. Based on an implantable design, the tag features a saltwater conductivity switch, a tri-axial accelerometer, and an optional pressure transducer, along with onboard software for data processing and detection of behavioral events or activities of interest for transmission. We configured the software to detect dives and create per-dive summaries describing behavioral events associated with feeding activities in rorqual whales. We conducted a validation by proxy of the dive summary and event detection algorithms using data from a medium-duration archival tag. The dive summary algorithm accurately reported dive depth and duration, while the accuracy of the lunge-feeding event detection algorithm was dependent on the precision of the accelerometer data that was used, with a predicted accuracy of 0.74 for correctly classifying feeding dives from 1/64-G precision data and 0.95 from 1-mG precision data. We also present data from field deployments of the tag on seven humpback whales ( Megaptera novaeangliae ) and one blue whale ( Balaenoptera musculus ). The eight tags transmitted over a median tracking period of 17.5 d (range: 3.9-76.4 d) across both species. The median proportion of the tracking period summarized by received dives for the eight tags was 50.4% (range: 11.1-88.7%). The median number of received dives per day was 76.5 (range: 1-191). The results documented diel and longer-term variability in diving and feeding behavior, showing marked differences within and among individuals tracked contemporaneously. By monitoring the per-dive behavior of large whales over multi-month timescales of movement, the RDW tags provided some of the first assessments of previously unobservable behaviors across entire geographic ranges, linking local-scale behavior to broader, ecosystem-scale processes. The RDW tag extends the applications of whale satellite telemetry to new areas of physiology, ecology, and conservation.
Single-Cell Transcriptome Analysis Reveals Heterogeneity and Convergence of the Tumor Microenvironment in CRC
Authors: Xie Siyuan , Cai Yangke , Chen Delong , Xiang Yu , Cai Wen , Yang Bin , Mao Jianshan , Ye Jun 
Published: August 2021

Abstract
Background: Colorectal cancer (CRC) ranks second for mortality and third for morbidity among the most commonly diagnosed cancers worldwide. Tumor microenvironment (TME) has been reported to correlate with CRC outcomes and treatment efficacy. Single-cell RNA sequencing (scRNA-seq) is an indispensable tool for unravelling cellular heterogeneity and deconstructing tissues into cell types, offering enormous potential for new discoveries.Methods: The single-cell RNA-seq profiles included 10,398 cells from 10 human CRC samples (accession number GSE146771), which were obtained from the Gene Expression Omnibus (GEO, http://www.ncbi.nlm.nih.gov/geo/) database. We identified 8 major cell types and 25 subgroups of cells derived from tumors, para-tumors, and peripheral blood to investigate the intratumoral heterogeneity and convergence of CRC.Results: This study established the heterogeneity, convergence, and differentiation trajectory of immune cells and stromal cells within CRC tissues. We also identified the terminal stage of each cell type of metabolism remodeling and immunosuppressive phenotypes. SCENIC analysis revealed the potential targets of transcriptional factors to reverse this process. Based on the cell subgroup fractions calculated by CIBERSORTx and the clinical data in The Cancer Genome Atlas (TCGA), we constructed a new prognosis model of CRC. Conclusions: This study provides a new perspective for understanding the heterogeneity and convergence of the TME and will aid the development of immunotherapies and prognosis of CRC patients.
Estimating Cyclone Vulnerability and Its Linkages With Child Mortality Trajectories Along the Bay of Bengal Coast in India: a Geospatial Approach
Authors: Jana Arup , Shaw Subhojit , Chattopadhyay Aparajita 
Published: August 2021

Abstract
BackgroundThe coastal population of Indian subcontinent experience variety of coastal hazards of which cyclone is the most destructive one. Most recently, on 20th May 2020, the super cyclone Amphan lashed with 155 km/h, as tall as a two-story building on the Eastern coast and state of West Bengal in India. In the following year 2021, another cyclonic storm, named Yaas, intensified in the Bay of Bengal in May, and it has ravaged many parts of the apex of the BoB coast. Over the decades, the devastating tropical cyclones of the Bay of Bengal (BoB) have thrashed thousands of lives and properties. MethodsAn empirical study to assess the coastal population's vulnerability and mortality along the east coastal districts of India is the need of the hour. Using a set of data the paper estimates the hazard exposure, sensitivity, and adaptability. Further, to understand the association between vulnerability and neonatal and under-5 mortality, regressions are applied. ResultsA very high coastal vulnerability risk for poor socio-economic status and lack of infrastructure was observed in certain districts of the BoB coast. Women, children, elderly and agrarian population are more sensitive to the cyclone; while lack of accessibility and infrastructure and poor health care system impact the population's adaptive capacity. A strong association of child mortality with coastal vulnerability is observed in the study area. Other factors that also play marked role in child mortality are prevalence of diarrhoea, lack of improved water and sanitation. ConclusionThe study, first of its kind in India, has identified vulnerable districts of the east coast to help policymakers take measures for disaster planning and improving the basic facilities for a resilient society.
In Vitro Antibacterial Activities of Essential Oils and Extracts of Six Herbals Against Gram-positive and Gram-negative Bacteria
Authors: Amin Mansour , Akrami Sousan , Haghparasty Farkhondeh , Hakimi Atiyeh 
Published: August 2021

Abstract
Background: Today, due to the increasing use of chemical drugs and the spread of microbial resistance to synthetic antibiotics, as well as side effects of drugs, the identification and introduction of plant species with medicinal and antimicrobial properties is very important. In this study, the antimicrobial properties of essential oils and extracts of 6 medicinal plants from Ahvaz region, Iran against 12 Gram-positive and Gram-Negative Bacteria were evaluated. Methods: The EOs and extracts were extracted using water distillation with Clevenger apparatus. The antimicrobial properties and determination of the minimum concentration of growth inhibition of herbals were investigated by the modified E-test method. Results: All analyzed extracts and EOs showed antibacterial effects. The antimicrobial activity of Oliveria decumbens was strongest herbals with the least MIC ranges (0.008-0.1 mg/ml for EO, 0.9-20 mg/ml for extract), while the antibacterial effects of Artemisia vulgaris extract and Glycyrrhiza glabra EO with the highest MIC were weaker than the others. According to the effectiveness of plant extracts on bacteria, Pseudomonas aeruginosa was resistant to all extracts except Oliveria decumbens. In contrast, Bacillus cereus was more sensitive than other strains against analyzed EOs and extracts.Conclusions: It seems that due to the antimicrobial properties of the extracts and essential oils observed in this study, they can be used as an alternative to antimicrobial drugs after more extensive studies.