bluuebunny/crossref_metadata_2025_split huggingface dataset:
Suppressing ERK Pathway Impairs Glycochenodeoxycholate-Mediated Survival and Drug-Resistance in Hepatocellular Carcinoma Cells
Authors: Li Bingxin , Zhou Maojun , Wang Jue , Xu Hongjuan , Yang Manyi 
Published: January 2021

Abstract
Background This research aims to examine the mechanism of glycochenodeoxycholate (GCDA)-mediated survival and drug-resistance in hepatocellular carcinoma cells (HCC). Extracellular signal-regulated kinase 1/2 (ERK1/2) were extensively expressed in liver cancer cells.Methods GCDA-induced survival of human liver carcinoma cells and chemoresistance was determined by CCK8 and flow cytometry, respectively. Functional of ERK1/2 and interaction of Bcl-2 family members was determined in western blot and immunofluorescence.Results Silencing ERK1/2 by RNA interference suppressed GCDA-stimulated survival and promoted apoptosis. Furthermore, phosphorylation of endogenous ERK1/2 could be potently stimulated by GCDA in combination with enhanced chemoresistance in QGY-7703 hepatocellular carcinoma cells. And such GCDA-mediated proliferation and chemoresistance could be impaired by PD98059, who acts as an inhibitor to block phosphorylation of ERK1/2. Mechanistically, PD98059 was able to potently suppress GCDA-stimulated nuclear aggregation of ERK1/2 and p-ERK1/2, up-regulation of pro-survival protein Mcl-1 and decrease of pro-apoptotic protein Bim.Conclusions Our work verified the function of ERK1/2 in GCDA-induced chemoresistance in hepatocellular carcinoma cells. Disruption of ERK1/2 by blocking phosphorylation or nuclear translocation may put forward new methods for treating of GCDA-related proliferation and drug-resistance in liver cancer.
Impact of Doxycycline on COVID-19 Patients with Risk Factors: DYNAMIC, a Multi-Centre, Randomised, Placebo-Controlled, Double-Blind Trial
Authors: Poinas Alexandra , Boutoille David , Vrignaud Florence , Nguyen Jean-Michel , Bonnet Fabrice , Rat Cédric , Garcia Gilles , Dompmartin Anne , Leccia Marie-Thérèse , Piroth Lionel , Maubec Eve , Gandon Pierre , Jobert Alexandra , Boinet Soizic , Cassecuel Julie , Flet Laurent , Khammari Amir , Dréno Brigitte 
Published: January 2021

Abstract
Background: The DYNAMIC study is based on three properties of tetracyclines. (1) Tetracyclines are known to chelate zinc from matrix metalloproteinases. It is possible their chelating activity may help inhibit COVID-19 infection by limiting its ability to replicate in the host. (2) As seen with dengue virus, tetracyclines may also be able to inhibit the replication of positive polarity single-stranded RNA viruses, such as COVID-19. (3) Tetracyclines are also modulators of innate immunity (anti-inflammatory activity), a property that has been used to treat inflammatory skin diseases for many years. They could therefore participate in limiting the cytokine storm induced by COVID-19. Moreover, the lipophilic nature of tetracyclines and their strong pulmonary penetration could allow them to inhibit viral replication at this level. Among the tetracyclines, doxycycline has three advantages: its long safety history (side effects are uncommon with no notable risks), its short treatment duration and its low cost.Methods: The trial will involve 330 patients who are positive for SARS-CoV-2 infection and have one or more risk factors for worsening the disease. These patients will be included as outpatients for early treatment of illness. For logistical reasons and in order to be able to standardise the study as much as possible, recruitment will take place in 6 hospital departments covering the whole of France. For 14 days they will be given either 200mg of doxycycline a day or placebo. Our hypothesis is a considerable reduction in the number of patients hospitalised due to COVID-19 thanks to the treatment of doxycycline.Discussion: This study could have an impact on the overcrowding of patients with COVID-19 at the hospital which is one of the major world-wide problems of this pandemic. This treatment would therefore contribute to supporting the deconfinement strategy by blocking the viral infection early and reducing the infectious period.Trial Registration: On ClinicalTrials.gov, registration number NCT04371952, first published on 30 April 2020.
Automatic Segmentation of Coronary Lumen and External Elastic Membrane in Intravascular Ultrasound Images Using 8-layer U-Net
Authors: Dong Liang , Jiang Wenbing , Lu Wei , Jiang Jun , Zhao Ya , Song Xiangfen , Leng Xiaochang , Zhao Hang , Wang Jian’an , Li Changling , Xiang Jianping 
Published: January 2021

Abstract
Background: Intravascular ultrasound (IVUS) is the golden standard in accessing the coronary lesions, stenosis, and atherosclerosis plaques. In this paper, a fully-automatic approach by an 8-layer U-Net is developed to segment the coronary artery lumen and the area bounded by external elastic membrane (EEM), i.e. cross section area (EEM-CSA). The database comprises of single-vendor and single-frequency IVUS data. Particularly, the proposed data augmentation of MeshGrid combined with flip and rotation operations is implemented, improving the model performance without pre- or post-processing of the raw IVUS images.Results: The mean intersection of union (MIoU) of 0.937 and 0.804 for the lumen and EEM-CSA respectively were achieved, which exceeded the manual labeling accuracy of the clinician. Conclusion: The accuracy shown by the proposed method is sufficient for subsequent reconstruction of 3D IVUS images, which is essential for doctors’ diagnosis in the tissue characterization of coronary artery walls and plaque compositions, qualitatively and quantitatively.
Association of spectroscopically determined leaf nutrition related traits and breeding selection in Sassafras tzumu
Authors: Liu Jun , Sun Yang , Liu Wenjian , Tan Zifeng , Jiang Jingmin , Li Yanjie 
Published: January 2021

Abstract
Background: Plant traits related to nutrition have an influential role on tree growth, tree production and nutrient cycling. Therefore, the breeding program should consider the genetics of the traits. However, the measurement methods could seriously affect the progress of breeding selection program. In this study, we tested the ability of spectroscopy to quantify the specific leaf nutrition traits including Anthocyanins (ANTH), flavonoids (FLAV) and Nitrogen balance index (NBI), and estimated the genetic variation of these leaf traits based on the spectroscopic predicted data. Live fresh leaves of Sassafras tzumu were selected for spectral collection, after which concentrations of ANTH, FLAV and NBI were analyzed by standard analytical methods. Partial least squares regression (PLSR), five spectra pre-processing methods, and four variable selection algorisms were conducted for the optimal prediction model selection. Each trait model was simulated 200 times for error estimation.
Results: The Standard Normal Variate (SNV) to the ANTH model and 1st derivatives to the FLAV and NBI models, combined with significant Multivariate Correlation (sMC) algorithm variable selection are finally regarded as the best performance model. The ANTH model produced the highest accuracy of prediction with a mean R2 of 0.72 and mean RMSE of 0.10 %, followed by FLAV and NBI model (mean R2 =0.58, mean RMSE = 0.11 % and mean R2 =0.44, mean RMSE = 0.04 %). High heritability was found of ANTH FLAV and NBI with h2 of 0.78, 0.58 and 0.61 respectively. It shows that it is benefitting and possible of breeding selection for the improvement of leaf nutrition traits.
Conclusions: Spectroscopy can successfully characterize the leaf nutrition traits in living tree leaves and the ability to simultaneous multiple plant traits provides a promising and high-throughput tool for the quick analysis of large size samples and serves for genetic breeding program.
Clinicopathological factors affecting the effect of neoadjuvant chemotherapy in patients with gastric cancer
Authors: Jiang Lin , Ma Zhiqiang , Ye Xin , Kang Weiming , Yu Jianchun 
Published: January 2021

Abstract
Background: Neoadjuvant chemotherapy is an important part of the comprehensive treatment of advanced gastric cancer (GC). The effect of neoadjuvant chemotherapy plays a key role in the prognosis of GC patients. Pathological response can represent the effect of neoadjuvant chemotherapy. However, evidence focused on pathological response and associated clinicopathological factors in GC patients is quite little. In this retrospective study, the clinicopathological factors affecting the effect of neoadjuvant chemotherapy in GC patients were investigated, and suggestions were proposed to improve the effect of neoadjuvant chemotherapy on GC.Methods: Retrospective analysis was performed on GC patients who received radical surgery after neoadjuvant chemotherapy from February 2016 to December 2019 at Peking Union Medical College Hospital. Relevant clinicopathological data was collected to analyze the factors influencing the effect of neoadjuvant chemotherapy. Chi-square test was used for univariate analysis. Logistic regression was used for multivariate analysis. Receiver operating characteristic curve (ROC) was used to determine the cut-off value of variables which significantly influenced the effect of neoadjuvant chemotherapy.Results: A total of 203 GC patients were included in the study. Analyses showed that patients <60 years old (OR=1.840[1.016-3.332], P=0.044), histological type of poor differentiation or signet-ring cell carcinoma (OR=2.606[1.321-5.140], P=0.006), and weight loss during neoadjuvant chemotherapy (OR=2.110[1.161-3.834], P=0.014) were independent risk factors for neoadjuvant chemotherapy effect. In ROC analysis of weight change and neoadjuvant chemotherapy effect, area under the curve (AUC) was 0.593(P=0.024) and cut-off value of weight change was -2.95%. Chi-square test showed patients without weight loss during neoadjuvant chemotherapy had a higher rate of oral nutritional supplement (ONS) than patients with weight loss (P=0.039).Conclusions: Patients <60 years old, histological type of poor differentiation or signet-ring cell carcinoma, and weight loss during neoadjuvant chemotherapy were independent risk factors for neoadjuvant chemotherapy effect in GC patients. Patients with weight loss >2.95% during neoadjuvant may have a worse chemotherapy effect. Timely nutritional support such as ONS to maintain patients’ body weight is crucial for improving the effect of neoadjuvant chemotherapy.
Association of vitamin D receptor gene polymorphisms with gestational diabetes mellitus-a case control study in Wuhan, China
Authors: Liu jianqiong , Dai Qiong , Li Wei , Guo Yan , Dai Anna , Wang Yanqing , Deng Mengyao , Tang Zhao , She Lu , Chen Xiaohong , Yang Mei 
Published: January 2021

Abstract
Background: Gestational diabetes mellitus (GDM) increased risk for perinatal complications to both the women and the fetuses. The association between the vitamin D receptor (VDR) gene and GDM has not been thoroughly investigated in Chinese pregnant women. Therefore, we aimed to determine whether VDR gene single nucleotide polymorphisms (SNPs) rs154410, rs7975232, rs731236, rs2228570 and rs739837 contribute to GDM risk in Wuhan, China. In addition, we aimed to explore their combined effect on the risk of GDM. Methods: Pregnant women who had prenatal examination at 24 to 28 weeks’ gestation in our hospital from January 15, 2018 to March 31, 2019 were included in this case-control study. After exclusion, a total of 1684 pregnant women (826 GDM patients and 858 non-diabetic controls) were recruited. The clinical information and blood sample were collected by trained interviewers and nurses. Genotyping of candidate SNPs was conducted by the Sequenom MassARRAY platform. Statistical analyses including t-test, ANOVA, chi-square test and logistic regression were performed to the data with SPSS Software to evaluate diﬀerences in genotype distribution and association of genotypes with GDM risk. Multifactor dimensionality reduction method was used to explore the gene-gene interactions on the risk of GDM. Results: Differences in age, pre-pregnancy BMI, family history of diabetes and previous history of GDM between the case and control groups were statistically significant (P<0.05), whereas no significant differences were found in height, gravidity, parity, and age of menarche (P>0.05). There were no significant differences at genotype distributions of the examined VDR gene SNPs (P>0.05). After adjusting by age, pre-pregnancy BMI, family history of diabetes, the results of logistic regression analysis showed no associations of the five SNPs with GDM in all the four genotype models(P>0.05). Furthermore, there were no gene-gene interactions on the GDM risk among the five examined VDR gene SNPs. Conclusion: The VDR gene SNPs rs154410, rs7975232, rs731236, rs2228570 and rs739837 showed neither significant associations nor gene-gene interactions with GDM in Wuhan, China.
Effect of Probiotic Supplementation along with Calorie Restriction on Metabolic Endotoxemia, and Inflammation Markers in Coronary Artery Disease Patients: A Double Blind Placebo Controlled Randomized Clinical Trial
Authors: moludi jalal , Kafil Hossein Samadi , Qaisar Shaimaa A. , Gholizadeh Pourya , Alizadeh Mohammad , Vayghyan Hamed Jafari 
Published: January 2021

Abstract
Purpose: Alterations in the gut microbiome (dysbiosis) has been associated with increased microbial translocation, leading to chronic inflammation in coronary artery disease (CAD). It has been proposed that modulation of gut microbiota by probiotic might modify metabolic endotoxemia. Therefore, the purpose of this study was to examine the effects of Lactobacillus rhamnosus GG (LGG) on endotoxin level, and biomarkers of inflammation in CAD participants. Methods: This study was a 12-weeks randomized, double-blind, and intervention on 44 patients with CAD. Patients were randomly allocated to receive either one LGG capsule 1.6 ×109 colony-forming unit (CFU) or the placebo capsules for 12 weeks. In addition, all the participants were also prescribed a calorie-restricted diet. Serum levels of interleukin-1β (IL-1β), Toll-like receptor 4 (TLR4), interleukin-10 (IL-10), and lipopolysaccharide (LPS), were assessed before and after the intervention. Results: A significant decrease in IL1-Beta concentration (-1.88 ± 2.25, vs. 0.56 ± 1.58 mmol/L, P=0.027), and LPS levels (-5.20 ±2.70 vs. 2.96+ 5.27 mg/L, P=0.016), was observed after the probiotic supplementation compared with the placebo. Participants who had ≥2.5 kg weight loss showed signiﬁcantly improved cardiovascular-related factors, compared to patients with <2.5 kg weight reduction, regardless of the supplement they took.Conclusion: These data provide preliminary evidence that probiotic supplementation has beneficial effects on metabolic endotoxemia, and mega inflammation in participants with CAD.
Association between Emergency Department Overcrowding and Mortality at a Teaching Hospital in Saudi Arabia
Authors: Khubrani Fatimah Yahyia , Al-Qahtani Mona Faisal 
Published: January 2021

Introduction: Emergency Departments (ED) are highly important in hospital settings because they offer 24-hour professional assistance to patients in need of healthcare. However, ED overcrowding has started to become a global healthcare crisis, such that the patient capacity of EDs is no longer sufficient to meet patient demand.

Aim:
Thus, this study aimed to determine the relationship between ED overcrowding and the mortality rate of patients to draw the attention of decision makers in Saudi Arabia toward this issue, with the hope of ultimately attaining a solution to this problem.

Methods:
Using patients’ electronic health records that were stored in the Quadra Med system in 2018, we calculated the occupancy rates of the ED of a target teaching hospital at different quarters and associated those figures with the mortality rates for the same quarters.

Results:
Our results showed that there was no significant association between mortality rate and crowding status in the ED. Nonetheless, we recommend increasing public awareness and bed capacity at EDs in Saudi Arabia because overcrowded EDs can lead to adverse patient outcomes.

Conclusion:
The present study showed that the highest percentage (38%) of deaths that occurred during the overcrowded period were mostly of patients between 30 and 44 years of age, while patients between 60 and 74 years of age accounted for 36% of deaths.
The current study also assessed patient triaging, revealing that the highest number of patients was associated with level four (62.7% of the total patients in the overcrowded ED) and level five (33.1% in the overcrowded ED) triaging.
We also discovered higher levels of admission in the critical care unit during the ED overcrowding period compared with other periods.
Urbanization, Climate Change and Environmental Resilience: Experiences in Sri Lanka
Authors: Zoysa Mangala De 
Published: January 2021

Urbanization in conjunction with climatic change affecting urban life and pose challenges to cities worldwide creating urban residents increasingly vulnerable to extreme weather and other natural disasters. Improvement of urban ecosystems provide cost-effective solution against negative impacts of climate change accelerated with high population pressure and promote resilience of urban dwellers. The cities in Sri Lanka are focused on improving land use planning and management of urban forest ecosystems for adaptation to and mitigation of climate change impacts with the rapid urbanization. This study attempts to ascertain the effects of urbanization, analyze the impacts of urbanization and climate change, and examine the environmental resilience with urban forests in Sri Lanka, reviewing the relevant literature. This paper explore the effects of urbanization in terms of increase population, land use change, rising greenhouse gas emissions and intensity of urban heat island. The impacts of urbanization and climate change are revealed as change of annual rainfall, urban warming, extreme weather events, and urban health hazards. Disaster resilient cities, sustainable urbanization, greening the cities, other environmental resilience strategies as well as institutional and policy setting are discussed for environmental resilience to urbanization and changing climate. Limiting CO2 emission, reducing land surface temperature, and controlling urban heat island effect are discussed under the other environmental resilience strategies. Institutional and policy setting is explained through popularizing urban forestry and developing policy support. Urban forestry strategies incorporating urban planning should be manifested in urban development policy in order to counteract the negative effects of climate change in the process of environmental resilience and sustainable urbanization.
One Pot Green Synthesis and Structural Characterisation of Bio-Silver Nanoparticles Using Prunus Persica L.
Authors: S.Shamina  , Dr.S.P.Suriyaraj  , V.Senjiskhan  
Published: January 2021

The Plant mediated green synthesis of nanoparticles has attracted more attention among the researchers due to their physicochemical and biological properties and their immense applications in environmental, biomedical, agriculture, textile, and energy storage. The biosynthesis of nanoparticles using plants provides more advantages such as easy operation, eco-friendly, utilization of non-hazardous chemicals, less temperature or energy usage, etc. when compared to physical and chemical synthesis methods. In the present study, we propose aqueous extracts from the endemic-medicinal fruit Prunus persica L. as an efficient bioproduct for the green synthesis of silver - nanoparticles (AgNPs). The biosynthesized AgNPs were characterized using UV-Visible spectroscopy, Fourier transforms Infrared spectroscopy (FTIR) High-Resolution Transmission electron microscopy (HR-TEM), Scanning electron microscopy, Atomic Force Microscopy (AFM), and X-ray diffractometer (XRD). HR-TEM gives the formation of monodispersed spherical shape with a mean diameter of 12.6 ± 3.8 nm. The SAED pattern of the nanoparticles showed that the particles were highly crystalline in nature. The purity of the synthesized AgNPs samples was studied by EDS and confirmed the presence of Ag elements corresponding to TEM images. The 2D and 3D structure images of the nanoparticle were studied and the average particle size calculation has been performed using NOVA-TX software in AFM. X-ray diffraction analysis showed that the particles were crystalline in nature with face - centered cubic structure. The antimicrobial efficacy was evaluated using the resazurin assay against both Escherichia coli and Bacillus subtilis bacteria. The antimicrobial assay of the silver nanoparticles showed higher activity against Bacillus subtilis than Escherichia coli. Results confirmed this protocol as rapid, simple, eco-friendly and alternative to conventional physical, and chemical methods.
An Overview of Extra Pulmonary Tuberculosis in Smear Negative Cases and their Analysis
Authors: TalluriRameshwari  K R  , Jayashree K  , Anuradha K  , Raghuraj Singh Chouhan  , Sumana K  
Published: January 2021

Mycobacterium tuberculosis (MTB), a bacterium which causes the tuberculosis disease, is one of the most trounce disease in the country. It mainly affects the lungs and other parts of the body. Currently smear-positive cases are further confirmed through chest radiography for PTB. These cases are further subjected for short course chemotherapy (SCC), followed by first line primary drugs, a scheme undertaken by National Tuberculosis Programme to overcome PTB infection. However, the identification of infection through smear-negative results are challenging as the cases may become positive over the time and progresses to cause the Extra Pulmonary Tuberculosis (EPTB). Such infections are asymptomatic and referred to as latent infection, where, MTBremains stable for many years at a specific site and later activates. Worldwide about 10-25% of latent infections progress to an active disease and if undiagnosed, the mortality rate may reach up to 50%. Twenty five percent of EPTB infection differs from organ to organ of the body. However, in such cases, diagnosis may be elusive and is usually delayed. The proper identification of infection that strongly focuses on the infection of either i.e., TB or EPTB is the need of the hour. The diagnosis of EPTB will be elusive, necessitating a high index of suspicion over TB or EPTB. However, smear-negative cases may be positive for EPTB infection, where the suspects are to be further subjected for molecular methods of EPTB detection and confirmation.