bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanisms of chronic alcohol exposure-induced aggressiveness in cellular model of HCC and recovery after alcohol withdrawal
Authors: Marié Constance , Fouquet Gregory , Amrathlal Rabbind Singh , Jankovsky Nicolas , Bouhlal Hicham , Nguyen-Khac Eric , Naassila Mickael , MARCQ Ingrid 
Published: November 2021

Abstract
Alcohol-related liver disease is the most prevalent chronic liver disease worldwide, accounting for 30% of hepatocellular carcinoma (HCC) cases and HCC-specific deaths. However, the knowledge on mechanisms by which alcohol consumption leads to cancer progression and its aggressiveness is limited. Better understanding of the clinical features and the mechanisms of alcohol-induced HCC are of critical importance for prevention and the development of novel treatments.Early stage Huh-7 and advanced SNU449 liver cancer cell lines were subjected to Chronic Alcohol Exposure (CAE), at different doses for 6 months followed by one-month alcohol withdrawal period. ADH activity and ALDH expression were much lower in SNU449 compared with Huh-7 cells and at the 270mM dose, CAE decreased cell viability by about 50% and 80%, respectively in Huh-7 and SNU449 cells but induced mortality only in Huh-7 cells. Thus, Huh-7 may be more vulnerable to ethanol toxicity because of the higher levels of acetaldehyde. CAE induced a dose-dependent increase in cell migration and invasion and also in the expression of Cancer Stem Cells markers (CD133, CD44, CD90). CAE in Huh-7 cells selectively activated ERK1/2 and inhibited GSK3β signaling pathways. Most of the changes induced by CAE were reversed after alcohol withdrawal. Interestingly we confirmed the increase in CD133 mRNA levels in the tumoral tissue of patients with ethanol-related HCC compared to other HCC etiologies.Our results may explain the benefits observed in epidemiological studies showing a significant increase of overall survival in abstinent compared with non-abstinent patients.
Molecular Dynamic Simulations and Binding Free Energy Evaluations of Thiazolo-[2,3-b] Quinazolinone Derivatives With wtEGFR-TKD and "TMLR" Mutant EGFR-TKD
Authors: Mir Showkat , Nayak Binata 
Published: November 2021

Abstract
Cancer causes innumerable deaths every year globally. Breast cancer and non-small cell lung carcinoma (NSCLC) are the most prevalent worldwide. The epidermal growth factor receptor tyrosine kinases play a pivotal role in manifestations of cellular signals in carcinoma cells and thus are endorsed as therapeutic targets in cancer management. EGFR-TKD is a good option for the treatment of cancer, but the resistance shown by first-generation TKIs leads to hyperphosphorylation, overexpression, and mutations of EGFR-TKD. The new molecular scaffolds of thiazolo-[2,3-b] quinazolinones were evaluated against EGFR-TKD via molecular docking simulations and thereby linked with molecular dynamic simulations to identify the ligand stability with EGFR-TKD’s. The binding energy of thiazolo-[2,3-b] quinazolinones is approximately similar to that of reference molecules found against both wild type wtEGFR-TKD and EGFR-TKD mutant "TMLR" (T790M/L858R) in this study. According to ADMET analysis, thiazolo-[2,3-b] quinazolinone derivatives (5ab, 5aq, and 5bq) are safe. The stability was investigated at an atomistic level by molecular dynamic simulations, and the strength of the bindings was calculated by the molecular mechanics Poisson-Boltzmann surface areas continuum solvation MM-PBSA method. The RMSD, radius of gyration, and SASA trajectories were studied in detail. The ΔGbind generated by heterocyclic 5aq thiazolo-[2,3-b] quinazolinone was found to be -63.723 ± 0.419 kJ/mol against the EGFR-TKD mutant "TMLR" and it was -51.551 ± 0.409 kJ/mol against wtEGFR-TKD. This study concludes that the top ranked complexes 5ab, 5aq, and 5bq with both wild and mutated types of EGFR-TKD corroborate that thiazolo-[2,3-b] quinazolinone derivatives, like the FDA-approved drug erlotinib, may be potent inhibitors of EGFR-TKD for patients with NSCLC.
Thawing rate and heating temperature effects on immunoglobulin A and lysozyme activity in human milk
Authors: Li Xuejing , ongprasert krongporn , Siviroj Penprapa , Ruangsuriya Jetsada , Yousaibua Nitthinan 
Published: November 2021

Abstract
BackgroundThe rate of infants receiving frozen HM is increasing, allowing critically ill preterm infants and infants with working mothers to benefit from the advantages of their mother's milk. The effects of thawing and warming on secretory immunoglobulin A (SIgA) and lysozyme activity in frozen human milk (HM) should be investigated to identify optimal methods for preserving immune factors in frozen HM.MethodsForty mothers that delivered full-term infants provided milk that was frozen and stored at -18°C two months before analyses. We compared the methods involving placing the container in a 4°C refrigerator overnight (slow thawing, ST) and placing it in a container of warm water (rapid thawing, RT). Additionally, we investigated the effect of warming temperature using room temperature (25°C) and physiological temperature (37°C). SIgA concentrations and lysozyme activities in the milk samples were determined by ELISA kits and fluorometric lysozyme activity assay kits, respectively. Data were analyzed by paired t-tests.ResultsSIgA concentrations and lysozyme activity were reduced by 16.5-52.1% and 16.8-39.3% in frozen HM compared to fresh HM, respectively. Significantly higher SIgA concentrations were maintained with slow thawing and warming at 37°C than with rapid thawing and warming at 25°C (p <0.001). Greater lysozyme activity was retained at 25°C with slow thawing than with rapid thawing (p <0.001) and more was preserved at 25°C than at 37°C with slow thawing (p <0.01).ConclusionsThawing HM overnight in the refrigerator before warming has the potential to preserve SIgA levels and lysozyme activity better than thawing immediately after removal from the freezer. Broader temperatures ranges should be analyzed to determine the temperature that minimizes HM SIgA and lysozyme activity losses.Trial registrationNot applicable
Integrative Chinese and Western Medicine for patients after Percutaneous Coronary Intervention (ICWM-PCI): A Prospective Observational Real-World Cohort Study
Authors: YAN Siyu , Yang Wei-Xian , Lu Pei-Pei , Guo Xuan-Tong , Guo Cai-Xia , Su Yan-Ni , Ma Li-Hong 
Published: November 2021

Abstract
Background Integrative Chinese and Western Medicine (ICWM) is widely used in coronary artery disease (CAD) patients after percutaneous coronary intervention (PCI) in China. However, the evidence-based on the long-term prognosis and large sample on this topic are weak. The purpose of this study is to evaluate the correlation between the therapeutic effect of ICWM and the prognosis of patients after PCI.Methods This study is a prospective observational real-world cohort study that was conducted from September 2016 to August 2019 in Fuwai Hospital. The study was reviewed and approved by the Ethics Review Committee of Fuwai Hospital, Chinese Academy of Medical Sciences. We consecutively screened 6000 patients after PCI and they were followed up for 2 years. ICWM were related to prognostic outcomes using unadjusted (Kaplan-Meier curves) and risk-adjusted (multivariable Cox regression) analyses. The primary endpoint was a composite of all-cause death, revascularization, and myocardial infarction.Results A total of 5942 patients after PCI were enrolled in this study, 5453 patients were included in the final analysis (4189[76.8%] were male; mean [SD] age, 61.91[9.91] years). There were 2932 patients (53.8%) in western medicine group (WMG) and 2521 patients (46.2%) in integrated medicine group (IMG). Cox regression analysis showed that IMG had a 27% lower cumulative risk of the major adverse cardiovascular event (MACE) than WMG (hazard ratio [HR], 0.73; 95% CI, 0.63-0.85; P＜0.0001), especially in all-cause mortality and revascularization.Conclusions Among patients after PCI, ICWM compared with conventional western medicine was correlated with a lower risk of 2-year MACE. Further research is needed to provide higher levels of evidence.
Unique Combinations of epigenetic modifiers synergistically impair the viability of the U87 glioblastoma cell line while exhibiting minor or moderate effects on normal stem cell growth
Authors: Alexanian Arshak R , Brannon Avonlea 
Published: November 2021

Abstract
Discoveries made over the last decade have shown that critical changes in cancer cells, such as activation of oncogenes and silencing of tumor suppressor genes are caused not only by genetic but also by epigenetic mechanisms. While epigenetic alterations are somatically heritable, in contrast to genetic changes, they are potentially reversible, making them perfect targets for therapeutic intervention. Covalent modifications of chromatin, such as methylation of DNA and acetylation and methylation of histones, are important components of epigenetic machinery. Multiple recent studies have shown that epigenetic modifiers are candidates for potent new drugs in multiple cancers’ therapies, including gliomas, and several clinical trials are ongoing. However, as with other chemotherapeutic drugs, toxicity is one of the main concerns with some of the potent epigenetic drugs. Synergistic combinations of these agents are one approach to overcoming toxicity issues while enhancing efficacy. In this study we demonstrated that while individually BIX01294, an inhibitor of histone methyltransferase G9a, DZNep, an inhibitor of lysine methyltransferase EZH2, and Trichostatin A (TSA), an inhibitor of histone deacetylase at their low concentrations showed a moderate effect on the viability of U87 glioblastoma cells, in combinations they exhibited a synergistic effect. Importantly, these combinations exhibited minimal effect on adipose mesenchymal stem cells (AD-MSCs) growth. Thus, unique combinations and concentrations of epigenetic modifiers, that synergistically attenuated the U87 glioblastoma cells while exhibiting minor or moderate effects on normal stem cell growth, have been discovered.
Double-Stranded RNA Dependent Protein Kinase (PKR) Deficiency Protects the Liver Against Ischemia/reperfusion Injury
Authors: Tang Da , Jiang Youxiang , Tang Yiting , Qiu Xianhui , Cheng Xiaoye , Li Wenbo , Cai Wenwu , Li Daming , Billiar Timothy R , Lu Ben 
Published: November 2021

Abstract
Background: Interruption of hepatic blood inflow to reduce intraoperative blood loss during liver surgery such as elective liver surgical procedures and organ transplantation causes hepatic ischemia and subsequent reperfusion that leads to liver damage and dysfunction. Double-stranded RNA dependent protein kinase (PKR) is an important regulator of immune responses in the settings of infection and tissue injury. However, little is known about the function of PKR in liver ischemia/reperfusion (I/R) injury. Methods: Wild-type (WT) and PKR knockout (PKR-/-) mice were subjected to partial (70%) hepatic I/R injury. In another set of experiments, mice were pretreated intraperitoneally with C16, a specific PKR inhibitor, or fludarabine, a specific inhibitor of STAT1 (signal transducer and activator of transcription 1), then subjected to I/R in-vivo. In-vitro investigations were conducted by subjecting primary mouse hepatocytes with hypoxia. The role of PKR in I/R-induced liver injury and the potential underlying molecular mechanisms were clarified through biological and phenotypic analyses. Results: Liver PKR protein levels were increased during the ischemic and reperfusion stages in both the mouse liver I/R model and the livers of humans who were subjected to liver resection. PKR inactivation by genetic deletion or pharmacological inhibition exhibited less liver damage than their respective control. PKR deficiency was also associated with lower levels of inflammatory cytokines and less apoptotic cell death. Mechanistically, STAT1 signaling was inhibited in livers of PKR-/- mice but was activated in WT mice. Most importantly, WT mice treated with STAT1 specific inhibitor fludarabine were protected from hepatic I/R injury. PKR also regulated the release of HMGB1 in hepatic I/R injury.Conclusions: Our novel findings document PKR is a modulator in I/R-induced liver damage. Inhibition of PKR by using the specific inhibitor, C16, may represent a promising therapeutic target for the management of I/R injury-related diseases.
Flexible and Transparent Pressure Sensor Based on CNTs Film Microstructure
Authors: Liu Liangliang , Yan Xin 
Published: November 2021

Abstract
In recent years, capacitive flexible pressure sensors have been widely studied in electronic skin and wearable devices. The traditional capacitive pressure sensor has a higher production cost due to micro-nano machining technology such as lithography. This paper presents a flexible transparent capacitive pressure sensor based on a PDMS/CNT composite electrode, simple, transparent, flexible, and arrays without lithography. The sensitivity of the device has been tested to 0.0018 kpa -1 with a detection range of 0-30 kPa. The sensor is capable of rapidly detecting different pressures and remains stable after 100 load-unload tests.
Systemic Inflammation with Sarcopenia Predict Survival in Patients with Gastric
Authors: Liu Yuying , Ruan Guotian , Ge Yizhong , Li Qinqin , Zhang Qi , Zhang Xi , Tang Meng , Song Mengmeng , Zhang Xiaowei , Li Xiangrui , Zhang Kangping , Yang Ming , Hu Chunlei , Liu Tong , Xie Hailun , Liu Xiaoyue , Lin Shiqi , Weng Min , Yao Qinghua , Wang Zhengping , Cong Minghua , Shi Hanping 
Published: November 2021

Abstract
Objective: The levels of platelet-related inflammation indicators and sarcopenia have been reported to affect the survival of patients with cancer. To evaluate the prognostic influence of platelet count (PLT), platelet–lymphocyte ratio (PLR), and systemic immune inflammation index (SII), and SII combined with sarcopenia on the survival of patients with gastric cancer (GC).Methods: A total of 1131 patients with GC (811 men and 320 women, average age: 59.45 years) were evaluated. Receiver operating characteristic curves were used to determine the best cut-off values of PLT, PLR, and SII, and univariate and multivariate Cox risk regression models were used to evaluate whether SII is an independent predictor of overall survival (OS). The prognostic SS (SII-sarcopenia) was established based on SII and sarcopenia. Finally, a comprehensive analysis of the prognostic SS was performed. Results: SII had the strongest prognostic effect. The SII and OS of patients with GC were in an inverted U-shape (adjusted HR = 1.06; 95% CI: 0.95-1.18; adjusted P = 0.271). In patients with SII >1800, SII was negatively correlated with OS (adjusted HR = 0.57; 95% CI: 0.29-1.12; adjusted P = 0.102), however, there is no statistical difference. Interestingly, a high SS was associated with a poorer prognosis. The higher the SS score, the worse the OS (P<0.001).Conclusion: SII is an independent prognostic indicator of GC, and high SII is related to poor prognosis. A Higher SS score had worse survival. Thus, the prognostic SS is a reliable predictor of OS in patients with GC.
A Reference Map of Microbiome Composition in Crop Production Across 8 Chinese Provinces
Authors: Hu Haiyang , Liu Yunli , Xu Zhaoyong , Huang Yiqun , Tang Hongzhi 
Published: November 2021

Abstract
Background: Although microbiome profiling of crop leaves is a relatively new research area, we know that leaf microorganism communities affect the leaf chemical composition, promote growth, and confer protection against deleterious microbes.Results: Here, we used 16S rDNA sequencing to profile the microbiomes of 78 primary dried tobacco leaf samples from plants grown at 26 locations in 8 Chinese provinces. After analyzing leaf microbial communities and identifying 4,473 operational taxonomic units (OTU) representing 1,234 species, we obtained a national core microbiome with 14 OTU representing 9 species, with functions for processes including nitrogen fixation, detoxification of diverse pollutants, and heavy-metal reduction. Although there are no obvious impacts from single environmental factors (e.g., temperature, precipitation), there are significant differences in microbial community structures among provinces and clear clustering by region. Finally, LEfSe analysis screened the significantly different species between different sampling locations.Conclusions: Our study demonstrates that both climactic and industrial factors drive microbial diversity on crop plant leaves, and many potentially useful functional bacterial resources present on tobacco leaves are still waiting for harnessing for a variety of bioprocess, agricultural, and environmental detoxification applications.
Acupoint Autohemotherapy Attenuates DNCB-induced Atopic Dermatitis Lesions by Regulating Th1/Th2 Cytokine Balance in BALB/c Mice
Authors: Zeng Zhiwen , Huang Jinquan , Chen Yong , Yu Xiao , Zhu Wei , Zhang Dongshu 
Published: November 2021

Abstract
Objective

Acupoint autohemotherapy (A-AHT) is considered an effective therapy for atopic dermatitis (AD) with few side-effects. Previous experiments showed the treatment had the potential to regulate T helper (Th) 1 and Th2 cytokines, like interferon (IFN)- gamma and interleukin (IL)- 4. This study focuses on the effects of A-AHT on the AD-like skin lesions through regulating Th1/Th2 immune responses.
Methods

The treatments of A-AHT, sham acupoint autohemotherapy and acupoint injection of normal saline were administered in the AD mice once every other day for 4 weeks. The total immunoglobulin (Ig) E, IL-4 and IFN-γ cytokine levels in the serum were examined after animal sacrifice. Th1/Th2 expression was analyzed in murine spleen cells via flow cytometry and immunohistochemical analysis of GATA-3 and T-bet in skin lesions were further assessed.
Results

Either type of repeated autologous whole blood (AWB) injection (into acupoint or sham acupoint) reduced the severity of AD-like symptoms and level of serum IgE. All of the three treatments had the similar inhibitory effect on levels of IL-4 and upregulation on the ratio of IFN-γ/IL-4, while differed on Th1/Th2 ratio as A-AHT regulates the body’s Th1/Th2 shift. This treatment also increased the related transcription factors T-bet expression, and upregulated T-bet/GATA3 ratio compared with the DNCB group. These differences were significant only in A-AHT group.
Conclusion

A-AHT effectively reduces AD symptoms and serum IgE levels in a mouse model and may act by regulating Th1/Th2 immune responses.
Trends in compound extremes of air temperature and precipitation in Eastern Europe
Authors: Vyshkvarkova Elena , Sukhonos Olga 
Published: November 2021

Abstract
The spatial distribution of compound extremes of air temperature and precipitation was studied over the territory of Eastern Europe for the period 1950–2018 during winter and spring. Using daily data on air temperature and precipitation, we calculated the frequency and trends of the four indices – cold/dry, cold/wet, warm/dry and warm/wet. Also, we studying the connection between these indices and large-scale processes in the ocean-atmosphere system such as North Atlantic Oscillation, East Atlantic Oscillation and Scandinavian Oscillation. The results have shown that positive trends in the region are typical of the combinations with the temperatures above the 75th percentile, i.e., the warm extremes in winter and spring. Negative trends were obtained for the cold extremes. Statistically significant increase in the number of days with warm extremes was observed in the northern parts of the region in winter and spring. The analysis of the impacts of the large-scale processes in oceans-atmosphere system showed that the North Atlantic Oscillation index has a strong positive and statistically significant correlation with the warm indices of compound extremes in the northern part of Eastern Europe in winter, while the Scandinavian Oscillation shows the opposite picture.
Effect of Gastrodin on Cognitive Dysfunction in Diabetes by Inhibiting PAK2 Phosphorylation
Authors: Mu Zhi-Hao , Zhao Zhi-Min , Yang Su-Su , Zhou Lei , Qian Zhong-Yi , Liu Yi-Dan , Liu Xin-Jie , Zhao Peng-Chao , Tang Ren-Bo , Li Jia-Yin , Zeng Jing-Yao , Ruan Yong-Hua , Yang Zhi-Hong , Zeng Yue-Qin , Zou Ying-Ying 
Published: November 2021

Abstract
Diabetes and cognitive dysfunction are highly prevalent disorders, while the underlying mechanism is still elusive. The effects of Gastrodin on central nervous system have been emphasized recently. In this study, we aim to explore the potential mechanism leading to cognitive dysfunction in diabetes and the therapeutic effect of Gastrodin. Diabetes was induced by a single injection of streptozotocin. RNA sequencing technique was used to identify the potential factors involved. Western blot and immunofluorescence were applied to detect the protein expression. Our results have shown that spatial learning was impaired and hippocampal pyramidal neurons were damaged in diabetic rats, which could be ameliorated by Gastrodin intervention. Transcriptional analysis identified differential expression genes, which were confirmed by qPCR and western blot. Furthermore, p21 activated kinase 2 (PAK2) was selected and its inhibitor could promote the survival of primary hippocampal neurons. It suggested that PAK2 pathway may be involved in cognitive dysfunction in diabetes and a therapeutic target for Gastrodin intervention.
A Spectrogram Based Novel Approach for Arrhythmia Detection with Convolutional Neural Networks
Authors: Rao Sneha , Singh Vishwa Mohan , Kulkarni Siddhivinayak , Saran Vibhor 
Published: November 2021

Abstract

ECG is one of the most important medical scans which is used for diagnosis of various heart related conditions and diseases. One of the most common of these is arrhythmia, which is caused by the irregularity of the heart beats. Artificial Intelligence has had a major impact in the field of vital monitoring and autonomous medical diagnosis. Therefore, a lot of work has demonstrated its effectiveness in arrhythmia detection. In this paper, we propose a method that tries to improve upon the accuracy of such models with the help of a light weight deep learning architecture that utilized 2D Separable CNN with a group of graphical representations of the ECG signals like the STFT, CWT and MFCC. Our model has achieved an accuracy of 97.41 and an F1 score of 88.20 on a processed version of the MIT-BIH dataset and takes on an average 7.93 times less calculations compared to a simple 2D Convolution model.