bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigating the Effect of Hydrogen-Rich Water on Liver Cell Injury and Liver Cancer by Regulating GP73/ TGF-β Pathway
Authors: Gao Yuanren , Jiang Shuai , Xing Ying , Hou Yingwen , Yang Yi , Hou Xunbo , Chen Wanbin , Zhang Jingwen , Chen Luhao , Liu Yan
Published: February 2021

BackgroundLiver cancer is an extremely heterogeneous malignant disease among tumors identified to date. In recent years, a large number of studies have found that low-concentration hydrogen or hydrogen-rich water or hydrogen-saturated physiological saline has a protective effect on many diseases. Observing the intervention effect of hydrogen-rich water and speculate whether its effect is regulated by GP73/TGF-β signaling pathway would provide a basis for clinical treatment using hydrogen in liver cancer.MethodThe(N-nitrosodiethylamine) DEN-induced LX-2 hepatocyte injury model, hepatocarcinoma cell(HepG2 cells), and normal hepatic stellate cell LX-2 and HepG2 co-culture system were treated with hydrogen-rich water, and the cell viability was measured by the Cell Counting Kit-8(CCK-8)method. Also, the supernatant was collected to determination the transforming growth factor (TGF-β), tumor necrosis factor (TNF-α), and osteopontin (OPN) content. Subsequently, qPCR method was employed to detect the expression of GP73, TGF-β, and Smad2 mRNA in the cell. Total cell protein was extracted, and the level of GP73, TGF-β, and Smad2 proteins in the cells was detected by Western blot.ResultAfter the intervention of hydrogen-rich water, DEN increases the activity of LX-2 hepatocytes, inhibits the secretion of TGF-β, downregulate the expression of GP73, TGF-β, and Smad2 mRNA in the injured LX-2 cells, inhibits the expression of GP73 and TGF-β proteins, and exerts a protective effect on injured cells. The intervention with hydrogen-rich water in HepG2 liver cancer cells inhibits the expression of GP73 mRNA and protein in the cells, upregulates the expression of TGF-β mRNA and protein, inhibits the expression of OPN, and exerts an anti-proliferation effect on liver cancer cells. In the co-culture system of LX-2 and HepG2, the effect of hydrogen-rich water showed different effects with the altered ratio of the two cells in the system.ConclusionHydrogen-rich water has a protective effect on liver cell damage and an inhibitory effect on liver cancer cells, which is effectuated by regulating the GP73/TGF-β signaling pathway.
Measurement of Green Total Factor Productivity on Chinese Pig Breeding: From the Perspective of Regional Differences
Authors: Zhong Shen , Li Junwei , Zhang Dehua
Published: February 2021

China has a vast territory and abundant resources, and there are significant differences in the development of pig breeding in different regions. As the main component of Chinese residents’ daily meat consumption, it is of great significance to improve people's living standards and conform to the national sustainable development strategy to raise pork production and reduce pollution emissions. In view of this, based on the minimum distance to weak efficient frontier model, this paper constructs Metafrontier-Malmquist-Luenberger index considering negative output under the common frontier to comprehensively evaluate pig breeding green total factor productivity (PBG). The results manifest that: (1) No matter under the common frontier or the group frontier, PBG presents large temporal and spatial differentiation characteristics. Compared with the eastern region and the central region, the western region has obvious advantages in PBG. (2) PBG has shown a downward trend as a whole, which is mainly due to the technical retrogression. (3) Compared with small-scale and medium-sized PBG, large-scale PBG has apparent superiorities. Based on the above outcomes, combined with the actual situation of China, this paper finally raises policy recommendations for improving PBG.
Analysis of Discharge Channel Characteristics Based on Three-Phase Flow Dielectric Characteristics in USV-MF Assisted WEDM-LS
Authors: Wang Yan , Yang Jie , Xiong Wei , Chai Hua-Yi , Wang Rui
Published: February 2021

In this paper, considering the effects of the characteristics of the three-phase flow dielectric in the discharge gap flow field on the discharge channels in the ultrasonic vibration and magnetic field assisted low speed WEDM, the model of discharge channel including discharge position and size of discharge channel is established and analyzed. Firstly, given working conditions of cutting workpiece with large thickness, a mechanism of bubble-particle bridging breakdown was proposed. Then a prediction model of the discharge point position in USV-MF assisted WEDM-LS under three-phase flow dielectric characteristics based on the breakdown mechanism was performed, and FEM software COMSOL was used to simulate and analyze this model. By comparing with the experimental results of discharge point position captured by high speed camera, the accuracy of the prediction results of discharge point position in USV-MF assisted WEDM-LS was verified, showing that this model can more accurately explain the dielectric breakdown in cutting workpiece with large thickness. Next, the model of radius of discharge channel including magnetic field intensity, electric field intensity, medium pressure and surface tension of discharge channel was established, and the influence of ultrasound and magnetic field on the size of discharge channel was analyzed theoretically. The radius of discharge channel in USV-MF assisted WEDM-LS was obtained by solving the partial differential equation in MATLAB. According to discharge point position and radius of the plasma discharge channel, surface morphology of workpiece was simulated by COMSOL. Finally, the experiment of photographing the discharge channel in USV-MF assisted WEDM-LS was carried out to verify the above model. It shows that the trend of the simulated results of discharge channel position is the same as that of the experimental results, and the error between the peak height value of the simulated surface morphology of workpiece and that of the experimental surface morphology of workpiece is within 6%.
Molecular Dynamics Examination of Sliding History-Dependent Adhesion in Si-Si Nanocontacts: Connecting Friction, Wear, Bond Formation, and Interfacial Adhesion
Authors: Schall J. David , Milne Zachary B. , Carpick Robert W. , Harrison Judith
Published: February 2021

The authors have requested that this preprint be removed from Research Square.
Effect of P10 Cemented Carbide Cutting Tools Subjected to Electromagnetic Coupling Field Treatment on the Surface Roughness of Machined 45 Steel
Authors: Zhong Fu , Yuan Min , Meng Dehao , Wang Li , Wang Jie , Liu Jian , Huang Kunlan , Tian Yankang
Published: February 2021

Reducing the surface roughness of machined workpieces is of great interest owing to its potential for improving the quality of finished items and decreasing the cost of machining processes by reducing the need for post processing. This paper contributes to this research by analyzing the effect of P10 cemented carbide cutting tools subjected to pulsed electromagnetic coupling field processing (EMCFP) treatment on the surface roughness of machined 45 steel workpieces. The effects of untreated and EMCFP-treated cutting tools on workpiece surface roughness, tool lifetime, friction coefficient, electron paramagnetic resonance (EPR) spectra, dislocation density and residual stress are compared. The experimental results demonstrate that EMCFP treatment can reduce the average surface roughness of workpieces by 39.2%, enhance tool lifetime by a factor of 1.92, reduce the friction coefficient by 11.4%, increase the intensities of peak EPR signals, increase the dislocation density by 38% and decrease the residual stress of the tool flank face by 51.4% . This research provides scientific data and technical support for EMCFP technology with important scientific significance.
Seasonal Prediction Skills in the CAMS-CSM Climate Forecast System
Authors: Liu Bo , SU Jingzhi , MA Libin , TANG Yanli , RONG Xinyao , LI Jian , CHEN Haoming , LIU Boqi , HUA Lijuan , WU Renguang
Published: February 2021

The seasonal predictability in the CAMS-CSM climate forecast system is evaluated with a set of retrospective forecast experiments during the period of 1981-2019. The CAMS-CSM, which has been registered for the sixth phase of the coupled model intercomparison project (CMIP6), is an atmosphere-ocean-land-sea ice fully coupled general model. The assimilation scheme used in the forecast system is the 3-dimentional nudging, including both the atmospheric and oceanic components. The analyses mainly focus on the seasonal predictable skill of sea surface temperature, 2-m air temperature, and precipitation anomalies. The analyses revealed that the model shows a good prediction skill for the SST anomalies, especially in the tropical Pacific, such as El Niño-Southern Oscillation (ENSO) events. The anomaly correlation coefficient (ACC) score for ENSO can reach 0.75 at 6-month lead time. Furthermore, the extreme warm/cold Indian Ocean dipole (IOD) events are successfully predicted at 3- and even 6-month lead times. The whole ACC of IOD events between the observation and the prediction can reach 0.51 at 2-month lead time. There are reliable seasonal prediction skills for 2-m air temperature anomalies over most of the Northern Hemisphere, where the correlation is mainly above 0.4 at 2-month lead time, especially over the East Asia, North America and South America. However, the seasonal prediction for precipitation still faces a big challenge. The source of precipitation predictability over the East Asia can be partly related to strong ENSO events. Additionally, the anomalous anticyclone over the western North Pacific (WPAC) which connects the ENSO events and the East Asian summer monsoon (EASM) can be well predicted at 6-month lead time.
Real-World Efficacy and Safety of Pangenotypic Direct-Acting Antivirals Against Hepatitis C Virus Infection in Taiwan
Authors: Chang Kao-Chi , Tung Shui-Yi , Wei Kuo-Liang , Shen Chen-Heng , Hsieh Yung-Yu , Chen Wei-Ming , Chen Yi-Hsing , Chen Chun-Hsien , Yen Chi-Wei , Xu Huang-Wei , Tung Wei-Lin , Hung Chao-Hung , Lu Sheng-Nan , Chang Te-Sheng
Published: February 2021

Background/Purpose of StudyClinical trials have demonstrated excellent efficacy and safety of pangenotypic direct-acting antivirals (DAAs) for the treatment of hepatitis C virus (HCV). However, there are limited large-scale real-world data on these pangenotypic DAAs. This study examined the results of two pangenotypic regimens, glecaprevir/pibrentasvir (GLE/PIB) and sofosbuvir/velpatasvir (SOF/VEL), in a real-world setting in Taiwan.MethodsAll HCV patients treated with GLE/PIB or SOF/VEL from August 2018 to April 2020 at the Chiayi Chang Gung Memorial Hospital were included. The primary end point was sustained virologic response 12 weeks after treatment cessation (SVR12). Adverse events (AEs) were also reported.ResultsA total of 1 356 HCV patients received pangenotypic DAA treatment during the study period: 742 patients received GLE/PIB and 614 received SOF/VEL. The rates of SVR12 for GLE/PIB and SOF/VEL were 710/718 (98.9%) and 581/584 (99.5%), respectively, by per-protocol analysis, and 710/742 (95.7%) and 581/614 (94.6%), respectively, by evaluable population analysis. Eleven patients (GLE/PIB: 8, SOF/VEL: 3) did not achieve SVR12. The most common AEs for GLE/PIB and SOF/VEL were pruritus (17.4% vs. 2.9%), abdominal discomfort (5.8% vs. 4.4 %), dizziness (4.2% vs. 2%), and malaise (3.1% vs. 2.9%). Laboratory abnormalities were uncommon, with <1% of patients exhibiting elevated total bilirubin or aminotransferase levels with both regimens. There were five drug discontinuations owing to AEs (bilirubin elevation: 3, dermatological issues: 2).ConclusionIn real-world practice, the pangenotypic DAAs GLE/PIB and SOF/VEL are effective and well tolerated, achieving high SVR12 rates for patients with all HCV genotypes.
The impact of air quality on its Baidu index: grey model analysis
Authors: Tu Leping , Chen Yan
Published: February 2021

To investigate the relationship between air quality and its Baidu index, we collect the annual Baidu index of air pollution hazards, causes and responses. Grey correlation analysis, particle swarm optimization and grey multivariate convolution model are used to simulate and forecast the comprehensive air quality index. The result shows that the excessive growth of the comprehensive air quality index will lead to an increase in the corresponding Baidu index. The number of search for the causes of air quality has the closest link with the comprehensive air quality index. Strengthening the awareness of public about air pollution is conducive to the improvement of air quality. The result provides a reference for relevant departments to prevent and control air pollution.
Classification of Pavement Climatic Regions through Unsupervised and Supervised Machine Learnings
Authors: Dong Qiao , Chen Xueqin , Dong Shi , Zhang Jun
Published: February 2021

This study extracted 16 climatic data variables including annual temperature, freeze thaw, precipitation, and snow fall conditions from the Long-term Pavement Performance (LTPP) program database to evaluate the climatic regionalization for pavement infrastructure. The effect and significance of climate change were firstly evaluated using time as the only predictor and t-test. It was found that both the temperature and humidity increased in most States. Three unsupervised machine learning including Principle Component Analysis (PCA), factor analysis and cluster analysis were conducted to identify the main component and common factors for climatic variables, and then to classify datasets into different groups. Then, two supervised machine learning methods including Fisher’s discriminant analysis and Artificial Neural Networks (ANN) were adopted to predict the climatic regions based on climatic data. Results of PCA and factor analysis show that temperature and humidity are the first two principle components and common factors, accounting for 71.6% of the variance. The 4-means clusters include wet no freeze, dry no freeze, dry freeze and snow freeze. The best k-mean clustering suggested 9 clusters with more temperature clusters. Both the Fisher’s linear discriminant analysis and ANN can effectively predict climatic regions with multiple climatic variables. ANN performs better with higher R square and low misclassification rate, especially for those with more layers and nodes.
Clinical Manifestations, Mutational Analysis, and Immunological Phenotype in Patients With RAG1/2 Mutations: First Cases Series From Mexico and Description of Two Novel Mutations.
Authors: Cruz-Munoz Mario Ernesto , Lugo-Reyes Saul Oswaldo , Pastor Nina , González-Serrano Edith , Yamazaki-Nakashimada Marco , Scheffer-Mendoza Selma , Berron-Ruiz Laura , Wakida Guillermo , Nuñez-Nuñez Maria Enriqueta , Macias-Robles Ana Paola , Staines-Boone Aide Tamara , Venegas-Montaya Edna , Alaez-Verson Carmen , Molina-Garay Carolina , Flores-Lagunes Luis Leonardo , Carrillo-Sánchez Karol , Niemela Julie , Rozensweig Sergio , Gaytan Paul , Yañez Jorge , Martinez-Duncker Ivan , Notarangelo Luigi , Espinosa-Padilla Sara
Published: February 2021

Mutations in Recombinase Activating Genes 1 and 2 (RAG1/2) results in human severe combined immunodeficiency (SCID). The products of these genes, are essential for V(D)J rearrangement of the antigen receptors during lymphocyte development. Nonsense mutations in RAG1 or RAG2 are associated with the most severe clinical and immunological phenotypes, whereas patients with missense mutations may develop leaky SCID or Omenn syndrome (OS). A group of non-previously recognized clinical phenotypes associated with granulomata and/or autoimmunity have been described as a consequence of hypomorphic mutations. Here we present six patients from unrelated families with missense variants in RAG1 or RAG2. Phenotypes observed in these patients ranged from OS to severe mycobacterial infections and granulomatous disease. Moreover, we report the first evidence of two previously unidentified variants as causative of pathological manifestations associated to immunodeficiency. This study represents the first case series of RAG1 or RAG2 deficient patients from Mexico and Latin America.
Application of Bioelectrochemical Technique in Energy Recovery and CH4 Control From Constructed Wetland (CW) and Associated Biochemical Mechanisms
Authors: Zhang Ke , Wu Xiangling , Wang Wei , Luo Hongbing , Chen Wei , Chen Jia
Published: February 2021

In the context of global warming, the bioelectrochemical method (microbial fuel cell MFC) was proposed for CH4 control from CWs. The main focus is to further explore the effect of plant roots location at the electrode, plant species on CH4 emissions, bioelectricity generation and the mechanism underlying competition between electrogenesis and methanogenesis at the anode. The results showed that the operation of MFC effectively reduced the CH4 emissions and promoted COD removal rates. CH4 emission was significantly higher in open circuit (6.2 mg m-2 h-1) than in closed circuit reactors (3.1 mg m-2 h-1). Plant roots at the cathode had the highest electricity generation and the lowest CH4 emissions. The highest power generation (0.49 V, 0.33 w m-3) and the lowest CH4 emissions (2.3 mg m-2 h-1) were observed in the reactors where Typha Orientalis was planted with plant roots at the cathode. The role of plants in strengthening electron acceptor was greater than that of plant rhizodeposits in strengthening electron donors. q-PCR and correlation analysis indicated that the mcrA genes and CH4 emissions were positively correlated (r=0.98, p<0.01), while no significant relationship between CH4 emissions and pmoA genes was observed. More nanowires, which are conductive to electron transfer, were found when plant roots were in cathode by scanning electron microscope (SEM). Illumina sequencing revealed that more abundant exoelectrogens and denitrifying bacteria (Geobacter, Desulfobulbu, Nitrospira and Anaerolinea) were observed when plant roots located in cathodes. Strictly acetotrophic archae (Methanosaetaceae) were likely main electron donor competitors with exoelectrogens. In addition, plant species played a more important role in CH4 emissions and electricity generation than the plant roots location at the electrode. Therefore, it is necessary to strengthen plant configuration to reduce CH4 emissions, so as to promote sustainable development of wastewater treatment.
Microstructure and Properties of h-BN-Reinforced Titanium Alloy Matrix Composite Fabricated with Optimized Spark Plasma Sintering Parameters
Authors: Abe John Olorunfemi , Popoola Olawale , Popoola Patricia , Ajenifuja Emmanuel
Published: February 2021

The authors have requested that this preprint be removed from Research Square.
Silica-coated Magnetic Nanoparticles Activate Microglia and Induce Neurotoxic D-Serine Secretion
Authors: Shin Tae Hwan , Lee Da Yeon , Manavalan Balachandran , Basith Shaherin , Na Yun-Cheol , Yoon Cheolho , Lee Hyeon-Seong , Paik Man Jeong , Lee Gwang
Published: February 2021

BackgroundNanoparticles have been studied for brain imaging, diagnosis, and drug delivery owing to their versatile properties due to their small sizes. However, there are growing concerns that nanoparticles may exert toxic effects in the brain. In this study, we assessed direct nanotoxicity on microglia, the resident macrophages of the central nervous system, and indirect toxicity on neuronal cells exerted by silica-coated magnetic nanoparticles containing rhodamine B isothiocyanate dye [MNPs@SiO2(RITC)]. MethodsWe investigated MNPs@SiO2(RITC)-induced biological changes in BV2 murine microglial cells via RNA-sequencing-based transcriptome analysis and gas chromatography-mass spectrometry-based intracellular and extracellular amino acid profiling. Morphological changes were analyzed by transmission electron microscopy. Indirect effects of MNPs@SiO2(RITC) on neuronal cells were assessed by Transwell-based coculture with MNPs@SiO2(RITC)-treated microglia. MNPs@SiO2(RITC)-induced biological changes in the mouse brain in vivo were examined by immunohistochemical analysis.ResultsBV2 murine microglial cells were morphologically activated and the expression of Iba1, an activation marker protein, was increased after MNPs@SiO2(RITC) treatment. transmission electron microscopy analysis revealed lysosomal accumulation of MNPs@SiO2(RITC) and the formation of vesicle-like structures in MNPs@SiO2(RITC)-treated BV2 cells. The expression of several genes related to metabolism and inflammation were altered in 0.1 µg/µl MNPs@SiO2(RITC)-treated microglia when compared with that in non-treated (control) and 0.01 µg/µl MNPs@SiO2(RITC)-treated microglia. Combined transcriptome and amino acid profiling analyses revealed that the transport of serine family amino acids, including glycine, cysteine, and serine, was enhanced. However, only serine was increased in the growth medium of activated microglia; especially, excitotoxic d-serine secretion from primary rat microglia was the most strongly enhanced. Activated primary microglia reduced intracellular ATP levels and proteasome activity in cocultured neuronal cells, especially in primary cortical neurons, via d-serine secretion. Moreover, ubiquitinated proteins accumulated and inclusion bodies were increased in primary dopaminergic and cortical neurons cocultured with activated primary microglia. In vivo, MNPs@SiO2(RITC), d-serine, and ubiquitin aggresomes were distributed in the MNPs@SiO2(RITC)-treated mouse brain. ConclusionsMNPs@SiO2(RITC)-induced activation of microglia triggers excitotoxicity in neurons via d-serine secretion, highlighting the importance of neurotoxicity mechanisms incurred by nanoparticle-induced microglial activation.
Visualization Analysis of Publication Trends and Research Hotspots on the Tumor Microenvironment of Pancreatic Cancer Between 2010 and 2020: a Bibliometric Study
Authors: Wu Kaiwen , Liu Ye , Liu Lei , Peng Yunlan , Pang Honglin , Sun Xiaobin , Xia Demeng
Published: February 2021

Background: Pancreatic cancer (PC) is a serious disease with high mortality. The tumor microenvironment plays a key role in the occurrence and development of PC. The purpose of this study is to analyze the trends by year, country, institution, journal, and keywords in publications on the PC microenvironment and to predict the future hotspots.Methods: The Web of Science Core Collection was used to search for and download publications. We analyzed the contributions of various countries/regions, institutes, and authors and discerned the research hotspots and promising future trends by using the CiteSpace and VOSviewer programs. We also summarized relevant completed clinical trials.Results: A total of 1,766 papers on the PC microenvironment published between 2010 and 2020 were included in the study. The average number of citations per article was 28.7. The United States had the most publications, followed by China, and a total of five influential articles were identified through co-citation analysis. Clustering analysis revealed three clusters of keywords: carcinogenesis of PC, stroma of PC, and therapy of PC. The research hotspots included cancer-associated fibroblasts, exosomes, FOLFIRINOX [FOL – folinic acid (also called leucovorin, calcium folinate, or FA), F – fluorouracil (also called 5-FU), Irin – irinotecan, Ox – oxaliplatin], and immunotherapy.Conclusion: The number of publications and the research enthusiasm generally showed an upward trend, and the United States has made prominent contributions to the field of the tumor microenvironment of PC. The current research hotspots are mainly cancer-associated fibroblasts, exosomes, and the treatment of pancreatic cancer, which might be the directions of future research.
Longitudinal Analysis of Inflammatory Response to SARS-CoV-2 in the Upper Respiratory Tract Reveals an Association With Viral Load, Independent of Symptoms
Authors: Didierlaurent Arnaud , Diem-Lan Vu , Murillo Paola Martinez , Pigny Fiona , Vono Maria , Meyer Benjamin , Eberhardt Christiane S , Lemeille Sylvain , Dach Elodie Von , Blanchard-Rohner Geraldine , Eckerle Isabella , Huttner Angela , Siegrist Claire-Anne , Kaiser Laurent
Published: February 2021

BackgroundSARS-CoV-2 infection leads to high viral loads in the upper respiratory tract that may be determinant in virus dissemination. The extent of intranasal antiviral response in relation to symptoms is unknown. Understanding how local innate responses control virus is key in the development of therapeutic approaches.MethodsSARS-CoV-2-infected patients were enrolled in an observational study conducted at the Geneva University Hospitals, Switzerland, investigating virological and immunological characteristics. Nasal-wash and serum specimens from a subset of patients were collected to measure viral load and a cytokine panel at different time points after infection; cytokine levels were analyzed in relation to symptoms.ResultsSamples from 13 SARS-CoV-2-infected patients and six controls were analyzed. We found an increase in CXCL10 and IL-6, whose levels remained elevated for up to 3 weeks after symptom onset. SARS-CoV-2 infection also induced CCL2 and GM-CSF, suggesting local recruitment and activation of myeloid cells. Local cytokine levels correlated with viral load but not with serum cytokine levels, nor with specific symptoms, including anosmia.ConclusionsThe nasal epithelium is an active site of cytokine response against SARS-CoV-2 that can last more than 2 weeks; in this cohort, anosmia was not associated with increases in any locally produced cytokines.
Performance Investigation of Carbon Nanotube Based Temperature Compensated Piezoresistive Pressure Sensor
Authors: DEVI REKHA , Gill Sandeep Singh
Published: February 2021

In silicon-based piezoresistive pressure sensor, the accuracy of the sensor is affected mainly by thermal drift and the sensitivity of the sensor varies with the rise in temperature. Here, the temperature effects on the desired representation of the sensor are analysed .Use of smart material Carbon nanotubes ( CNT) and a few effective temperature compensation techniques are presented in this study to reduce the temperature effect on the accuracy of the sensor. Resistive compensation employed extra piezoresistors with Negative Temperature Coefficient of Resistivity (TCR) for temperature compensation. The attainment of the desired compensation techniques is highly compatible with the MEMS device fabrication. The compensated pressure sensor is supremacy for pressure measurement with temperature variations. Though various techniques have been suggested and put into actuality with successful attainment, the techniques featuring easy implementation and perfect compatibility with existing schemes are still blooming demanded to design a piezoresistive pressure sensor with perfect comprehensive performance. In this paper, CNT piezoresistive material has been employed as sensing elements for pressure sensor and compared with silicon in terms of output voltage and sensor performance degradation at higher temperature. Pressure sensors using CNT and silicon piezo resistive sensing materials were simulated on silicon (100) diaphragm by ANYSIS. Based on simulation results, silicon and CNT both pressure sensor also shows better results at near room temperature. With the increasing temperature it is observed that silicon pressure output underestimated by 23%.
Analysis of tumor microenvironment characteristics in bladder cancer: implications for immune checkpoint inhibitor therapy
Authors: Chen Xingyu , Chen Haotian , He Dong , Cheng YaXing , Zhu Yuxing , Xiao Mengqing , Lan Hua , Wang Zhanwang , Cao Ke
Published: February 2021

Background

The tumor microenvironment (TME) has a significant influence on prognosis and immunotherapy. There are no studies on the systematic analysis of bladder cancer TME and its effect on immune checkpoint inhibitor therapy.
Methods

We comprehensively evaluated the TME infiltration pattern of bladder cancer in 1,889 patients and conducted extensive immunogenomic analysis to explore the heterogeneity and prognostic significance of the TME of bladder cancer. The principal component analysis algorithm was used to calculate the immune cell (IC)score to quantify the level of IC infiltration. We used the receiver operating characteristic (ROC) curve, Tumor Immune Dysfunction and Exclusion (TIDE), and Subnetwork Mappings in Alignment of Pathways (SubMAP) algorithms to evaluate whether the ICscore can predict the benefits of immune checkpoint inhibitors in bladder cancer patients.
Results

We identified three different TME phenotypes using unsupervised clustering methods. To explore the potential biological pathways that drive the formation of these microenvironmental phenotypes, we demonstrated the clinical and pathological characteristics, biological signaling pathways, cancer immune circulation, copy number, and somatic mutation differences among the different subtypes. In addition, univariate and multivariate Cox regression analyses showed that the ICscore is a reliable and independent prognostic marker. The ICscore can also predict immune checkpoint inhibitor responsiveness as patients with higher ICscores showed a significant therapeutic advantage in immunotherapy.
Conclusions

This study increases our understanding of the characteristics of TME infiltration in bladder cancer and provides guidance on more effective personalized immunotherapeutic strategies.
ALK-Negative Lung Inflammatory Myofibroblastic Tumor in a Young Adult: a Case Report and Literature Review of Molecular Alterations
Authors: Debonis Silvia Angela , Bongiovanni Alberto , Pieri Federica , Fausti Valentina , Vita Alessandro De , Riva Nada , Gurrieri Lorena , Vanni Silvia , Diano Danila , Mercatali Laura , Ibrahim Toni
Published: February 2021

Background: Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal tumor and is prevalent among children and adolescents. Surgery is the most important therapeutic approach for IMT and complete resection is recommended. Although 50% of IMTs present anaplastic lymphoma kinase (ALK) rearrangements, an efficacy has been shown by the use of Crizotinib . However the genetic landscape of this tumor is not fully understood and the therapeutic options are limited in particular for the remaining percentage of negative ALK tumors. Case presentation: In our case, we detail the clinical history of 18-year-old female patient diagnosed with pulmonary IMT negative for ALK, subjected to surgery and subsequently to follow-up. The initial pathology report oriented for a salivary gland lung cancer. Afterwards due to a second look by another pathologist an ALK negative IMT of the lung was diagnosed. We also perform a literature review based on IMT and other kinase fusions found in addition to ALK such as ROS proto-oncogene 1 (ROS1), rearranged during transfection (RET), neurotrophic receptor tyrosine kinases (NTRKs) and platelet derived growth factor receptor (PDGFR beta). Conclusions: IMT is a very rare disease involving children and adolescents. Little is known about the clinical and molecular characteristics, pathological diagnosis, prognosis and optimal management strategy of IMT. Since there is no "standard of care" therapy for IMT, identifying feasible genomic alterations could redefine the management of patients with negative ALK disease.
Ethanol and cocaine increases microtubule stability and decreases [11C]MPC-6827 uptake in SH-SY5Y cells
Authors: Damuka Naresh , Orr Miranda E , Czoty Paul W , Weiner Jeffrey L , Martin Thomas J , Nader Michael A , Bansode Avinash H , Pathirannahel Buddhika S Liyana , Mintz Akiva , Macauley Shannon L , Craft Suzanne , Sai Kiran Kumar Solingapuram
Published: February 2021

Microtubules (MTs) are structural units in the cytoskeleton. In brain cells they are responsible for axonal transport, information processing, and signaling mechanisms. Proper function of these processes is critical for healthy brain functions. Alcohol and substance use disorders (AUD/SUDs) affects the function and organization of MTs in the brain, making them a potential neuroimaging marker to study the resulting impairment of overall neurobehavioral and cognitive processes. Our lab reported the first brain-penetrant MT-tracking Positron Emission Tomography (PET) ligand [11C]MPC-6827 and demonstrated its in vivo utility in rodents and non-human primates. To further explore the in vivo imaging potential of [11C]MPC-6827, we need to investigate its mechanism of action. Here, we report preliminary in vitro binding results in SH-SY5Y neuroblastoma cells exposed to ethanol (EtOH) or cocaine in combination with multiple agents that alter MT stability. EtOH and cocaine treatments increased MT stability and decreased free tubulin monomers. Our initial cell-binding assay demonstrated that [11C]MPC-6827 selectively bound to free/unbound tubulin units. Consistent with this mechanism of action, we observed lower [11C]MPC-6827 uptake in SH-SY5Y cells after EtOH and cocaine treatments (e.g., fewer free tubulin monomers). We are currently performing in vivo PET imaging and ex vivo biodistribution studies in rodent and nonhuman primate models of AUD and SUDs.
Ecological contacts and host specificity promote replacement of nutritional endosymbionts in ticks
Authors: Buysse Marie , Binetruy Florian , Leibson Raz , Gottlieb Yuval , Duron Olivier
Published: February 2021

Symbiosis with vitamin-provisioning microbes is essential for the nutrition of animals with specialized feeding habits. While coevolution stabilizes the interactions between symbiotic partners, their associations are not necessarily permanent: Recently acquired symbionts can replace ancestral symbionts. In this study, we demonstrate successful replacement dynamics of Francisella-Like Endosymbionts (-LE), a group of invasive B-vitamin-provisioning endosymbionts, across tick communities driven by a complex web of horizontal transfers. Using a broad collection of Francisella-LE-infected tick species, we determined the diversity of Francisella-LE haplotypes through a multi-locus strain typing approach, and further characterized their phylogenetic relationships and their association with biological traits of their tick hosts. The patterns observed showed that Francisella-LE commonly transfer through similar ecological networks and geographic distributions shared among different tick species, and, in certain cases, through preferential shuffling across congeneric tick species. Altogether, these findings reveal the importance of both routes in shaping the invasive pattern in which new nutritional symbioses are initiated.
Limits of Temperature Adaptation and Thermopreferendum
Authors: Aslanidi Konstantin Borisovich , Kharakoz Dmitry Petrovich
Published: February 2021

Background Managing the limits of temperature adaptation is relevant both in medicine and in biotechnology. There are numerous scattered publications on the identification of the temperature limits of existence for various organisms and using different methods. It was shown earlier that each cycle of synaptic exocytosis includes reversible phase transitions of lipids of the presynaptic membrane due to the entry and subsequent removal of calcium ions from the synaptic terminal. Violation of cyclic changes in membrane fluidity caused by a sharp increase or decrease in ambient temperatures will lead to the termination of synaptic transmission, which can be recorded by the loss of righting reflex.Results The viability polygon for Danio rerio was determined by the minimum temperature of cold shock (about 6 o C), maximum temperature of heat shock (about 43 o C), and thermopreferendum temperature (about 27 o C). The ratio of the temperature range of cold shock to the temperature range of heat shock was about 1.3. Conclusions The experimental values of the temperatures of cold shock and heat shock and the temperature of the thermal preferendum correspond to the temperatures of phase transitions of the lipid-protein composition of the synaptic membrane between the liquid and solid states. The viability range for zebrafish coincides with the temperature range, over which enzymes function effectively and also coincides with the viability polygons for the vast majority of organisms. The boundaries of the viability polygon are characteristic biological constants. The viability polygon of a particular organism is determined not only by the genome, but also by the physicochemical properties of lipids that make up the membrane structures of synaptic endings. The limits of temperature adaptation of any biological species are determined by the temperature range of the functioning of its nervous system.
Evaluation of Left Atrial Function in Uremic Patients by Speckle Tracing Imaging Evaluation of LA Function in Uremic Pts by STI
Authors: Ye Fuyong , Yang Yuwen , Liang Yinting , Liu Jianhua
Published: February 2021

Objective: This study aimed to explore the value of speckle tracing imaging (STI) for assessment of left atrial (LA) function in uremic patients.Methods: One hundred uremic patients were divided into four groups according to the New York Heart Association (NYHA) criteria. Thirty healthy participants were enrolled as a control group. LA functional parameters were determined using conventional echocardiography. The strain rate (SR) curve of LA wall was prepared using STI, and SR in different phases of cardiac cycle were obtained.Results: The LA maximal volume (LAVmax) increased and LA passive ejection fraction (LAPEF) decreased. The LA active ejection fraction (LAAEF) showed an initial increase followed by a decrease (all p<0.05). The SR of LA lateral wall and interatrial septum (IAS) in systole (SRs-LA, SRs-IAS) and early diastole (SRe-LA, SRe-IAS) showed a steady decrease; the SR of LA lateral and IAS in late diastole (SRa-LA, SRa-IAS) showed an initial increase followed by a decrease. Compared with control group, the SRs-LA and SRs-IAS decreased in four groups with uremia (all p<0.05). A positive correlation was observed between LAPEF and the absolute value of mean peak early diastolic SR (|mSRe|) (r=0.862, p<0.05), and between LAAEF and the absolute value of mean peak late diastolic SR (|mSRa|) (r=0.756, p<0.05). LAVmax showed a negative correlation with mean peak systolic SR (mSRs) (r=-0.878, p<0.05).Conclusion: There was a significant correlation between LA function and LA strain rate in uremic patients. STI can allow for an objective and accurate evaluation of LA function in uremic patients.
Transforaminal Percutaneous Endoscopic Discectomy for Symptomatic Gas-filled Discal Cysts
Authors: Zhu Kejun , He Dengwei
Published: February 2021

Objective The aim of this retrospective study is to review our experience in the diagnosis and role of transforaminal percutaneous endoscopic discectomy (TPED) for symptomatic gas-filled discal cysts. Methods Between May 2014 and June 2017, 3 patients from Lishui Center Hospital (Lishui China), who underwent TPED for symptomatic gas-filled discal cysts, were analyzed. The clinical features, imaging findings, operative findings and treatment outcomes are presented. In addition, relevant literature regarding gas-filled discal cysts were searched using PubMed, and their characteristics, clinical features, therapeutic strategies and survival outcomes were reviewed. Results The median age of the patients was 56.7 years (range, 55-60 years). In all patients, a discal cyst was located in the lumbar region, and the patients presented with backache and numbness in the lower extremities. The diagnosis was made by lumbar 3 dimensional-computed tomography (3D-CT) or magnetic resonance imaging (MRI). All patients underwent TPED. All patients recovered successfully and were eventually discharged. Eighteen articles were identified from the searches of the database, and a total of 41 patients were included. There were 32 males and 9 females. The mean age was 58.1 years, ranging from 27 to 85 years. Lower back pain was the major symptom. Twenty-four patients underwent surgery, 4 patients underwent percutaneous needle aspiration, and 2 patients underwent drug therapy.Conclusion TPED for gas-filled discal cysts is feasible, effective and successful, although it should be performed by an experienced surgeon with awareness of the potential risk of severe nerve root injury.
Changes in Multidrug-resistant Escherichia Coli of Neonatal Meningitis During 2001–2019: a Study in Eastern China
Authors: Liu Yanli , Zhu Minli , Fu Xiaoqin , Cai Jiaojiao , Chen Shangqin , Lin Yuanyuan , Jiang Na , Lin Zhenlang , Chen Si
Published: February 2021

Background and objective: Neonatal meningitis (NM) caused by Escherichia coli remains a major health problem in industrialized countries. The purpose of this study was to investigate changes in antimicrobial resistance of E. coli causing neonatal meningitis in a perinatal center in eastern China over the past 19 years.Methods: This survey was investigated during three periods: 2001–2006, 2007–2012, and 2013–2019. NM is diagnosed according to the number of white blood cells in the cerebrospinal fluid and the presence of a single potential pathogenic bacterium in culture extracted from blood or cerebrospinal fluid of any newborn baby. Changes in the antimicrobial resistance of E. coli were analyzed.Results: A total of 209 cases of NM were identified. E. coli was identified from 69 cases, of which extended-spectrum beta-lactamase (ESBL) production was found in 21 cases. E. coli was the main cause of neonatal meningitis in this study. The overall resistance rate of E. coli to third-generation cephalosporins such as cefotaxime increased from 0% in 2001–2006 to 50% in 2007–2012 and subsequently decreased to 29.0% in 2013–2019. This pattern of change is similar to that of ESBL production. Only 15.0% E. coli found in samples from infants with early-onset meningitis (EOM) produced ESBL, while 40.0% of E. coli from children with late-onset meningitis (LOM) produced ESBL. Conclusion: We concluded that E. coli remains the primary pathogen of NM. Compared to LOM, the percentage of ESBL-producing multi-drug resistant E. coli isolated from EOM is significantly decreased. Clinicians should consider this trend when choosing appropriate and effective antibiotics as empirical treatments for NM.
Application of Circulating Genetically Abnormal Cells in the Early-stage Diagnosis of Lung Cancer
Authors: qiu xiaochang , Zhang haoran , Zhao yongheng , Wan yunyan , Li dezhi , Yao zhouhong , Lin dianjie
Published: February 2021

Background Lung cancer is the primary cause of cancer related death worldwide, early detection of the disease contributes to early diagnosis and reduce the incidence of death from lung cancer. Therefore, an effective and non-invasive method for early diagnosis of lung cancer is urgently needed.Methods To evaluate the diagnostic performance of circulating genetically abnormal cells(CAC) in early lung cancer, a total of 63 participants who completed CAC detection by ZHUHAI SANMED BIOTECH INC. and obtained pathological results from January to December 2020 were included in our study, which were divided into 50 cases of lung cancer ,13 cases of benign lung disease. The levels of lung cancer-related markers in peripheral blood and chest computed tomography(CT) imaging characteristics of these patients were collected before pathological acquisition.Results The positive rate of CAC was 90.0% in lung cancer group and 23.1% in benign lung disease group, the difference was statistically significant (P＜0.01).The area under the receiver operating characteristic (ROC) curve of CAC was 0.837, the sensitivity was 90%, and the specificity was 76.9%.The area under the ROC curve and sensitivity were both higher than the combined or single serum tumor marker test.Conclusions This study preliminarily concludes that CAC, as a non-invasive test, has high sensitivity and specificity for early diagnosis of lung cancer, which is expected to help early detection of disease in lung cancer patients and has certain help and guiding significance for clinical work.
Patterns of Wasting Among Pregnant and Lactating Women in Uganda, 2015-2018: Analysis of Nutrition Surveillance Data
Authors: Kyamwine Irene Byakatonda , Namukose Samalie , Wibabara Yvette , Bulage Lilian , Kwesiga Benon , Ario Alex Riolexus , Harris Julie R.
Published: February 2021

Background: Maternal nutrition is closely linked to the survival and development of children during the first 1000 days of life. Maternal wasting, a measure of malnutrition, is measured using the mid-upper arm circumference. However, in 2019, the rate and distribution of wasting among pregnant and lactating women was not known. We described annual trends and distribution of wasting among pregnant and lactating women (PLW), Uganda, 2015-2018, to inform programming on targeted nutritional interventions.Methods: We analyzed nutrition surveillance data from the District Health Information System for all PLW from 2015 to 2018. We used the World Health Organization standard thresholds to determine wasting among PLW by year and region, drawing choropleth maps to demonstrate the geographic distribution of wasting among PLW. We used logistic regression to assess wasting trends. Results: During 2015-2018, 268,636 PLW were wasted (prevalence=5.5%). Of the 15 regions of Uganda, Karamoja (prevalence=21%) and Lango (prevalence=17%) registered the highest prevalence while Toro (prevalence=2.7%) and Kigezi (prevalence=2.0%) registered the lowest prevalence. The national annual prevalence of wasting among PLW declined by 31% from 2015-2018 (OR=0.69, p<0.001). Regions in the north had increasing trends of wasting over the period [Lango (OR=1.6, p<0.001) and Acholi (OR=1.2, p<0.001)], as did regions in the east [(Bugisu (OR=3.4, p<0.001), Bukedi (OR=1.4, p<0.001), and Busoga (OR=1.3, p<0.001)]. The other 11 regions showed declines.Conclusion: The trend of wasting among PLW nationally declined during the study period. Lango and Acholi regions, both of which were experiencing a state of emergency during this period, had both high and rising rates of wasting, as did the Karamoja region, which experienced the highest wasting rates. We recommended that the Ministry of Health increases its focus on nutrition monitoring for PLW and conduct an analysis to clearly identify the factors underlying malnutrition specific for PLW in these regions.
Signs of ultra-high-energy electrons emission with energy up to 105 times of beam energy are detected at downstream of the RF cavity of storage ring
Authors: Qian Dapeng
Published: February 2021

In a new version of special relativity that absorbed the uncertainty principle, the Einstein-Lorentz mass formula proved to be a special case of a more universal equation. The new equation indicates that there is a “high speed but low mass” weak effect in particle motion, which will cause the generation of abnormal ultra-high energy electrons with a small probability when an electron beam passes through an accelerating electric field. The author used the method of long-times accumulation detection to test it on the BEPCII, which results show that there is indeed emission of abnormal electrons with energy up to 105 times of the beam energy at the downstream of the RF cavity of the electron storage ring. Therefor, it is suggested to use the detector with an online real-time display function, such as the “Shashlyk calorimeter”, to detect the single event of ultra-high energy electron, so to fully verify this previously unknown phenomenon and further discover new physics.