bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection of EGFR Mutation of Pulmonary Adenocarcinoma in Sputum Using Droplet Digital PCR
Authors: Isaka Tetsuya , Yokose Tomoyuki , Ito Hiroyuki , Nakayama Haruhiko , Miyagi Yohei , Saito Haruhiro , Masuda Munetaka 
Published: December 2020

Abstract
Background It is still unclear whether epidermal growth factor receptor (EGFR) mutation of primary lung adenocarcinoma can be detected accurately on sputum samples. This study aimed to examine EGFR mutations of primary lung adenocarcinoma in sputum samples using droplet digital polymerase chain reaction (ddPCR) and compare it with an EGFR mutation in surgically resected lung cancer. Methods Sputum was collected preoperatively from patients with primary lung cancer who were scheduled for complete resection of lung tumor at Kanagawa Cancer Center from September 2014 to May 2016. ddPCR was performed to detect EGFR exon 21 L858R point mutation (Ex21 mutation) and EGFR exon 19 deletion mutation (Ex19 mutation) in the sputum samples. The concordance of EGFR mutation status in sputum samples and tumors in surgically resected specimen was evaluated for each positive and negative cytology group.Results One hundred and eighteen patients with primary lung adenocarcinoma provided sputum samples. Sputum cytology was positive in 13 patients (11.0%). ddPCR detected two cases of Ex21 mutation and two cases of Ex19 mutation. Compared to surgically resected specimens, the sensitivity, specificity, and positive predictive value of EGFR mutation detection were 80.0%, 100%, and 92.3%, respectively. The sensitivity of EGFR mutation detection was 3.1% in sputum cytology negative cases. Logistic regression model analysis revealed that tumor size ≥ 29 mm determined using computed tomography (CT) was an independent potential predictive factor for positive sputum cytology (odds ratio = 10.6, 95% confidence interval: 1.85–61.0, p=0.008).Conclusions EGFR mutation of primary lung adenocarcinoma was accurately detected in sputum samples using ddPCR if the sputum cytology was positive. Sputum samples should be collected in patients with CT tumor size ≥ 29 mm for EGFR mutation analysis.
Plasma neurofilament light is associated with white matter damage in Alzheimer's disease
Authors: Nabizadeh Fardin , Balabandian Mohammad , Rostami Mohammad Reza , Kankam Samuel Berchi , Ranjbaran Fetemeh , Ranjbaran Fetemeh 
Published: December 2020

Abstract
The most replicated blood biomarker for monitoring Alzheimer’s disease is neurofilament light (NFL). Recent evidence revealed that the plasma level of the NFL has a strong predictive value in cognitive decline and is elevated in AD patients. The Diffusion Tensor Imaging (DTI) is understood to reflect white matter disruption, neurodegeneration, and synaptic damage in AD. However, few investigations have been carried out on the association between plasma NFL and white matter microstructure integrity. We have investigated the cross-sectional associations of plasma NFL, CSF total tau, phosphorylated tau, and Amyloid β with white matter microstructural changes as measured by DTI in 92 mild cognitive impairment (MCI) participants. We investigated potential correlations of the DTI values of each region of the MNI atlas, with plasma NFL, separately using a partial correlation model controlled for the effect of age, sex, and APOE ε4 genotype. Our findings revealed a significant correlation between plasma and CSF biomarkers with altered white matter microstructural changes in widespread brain regions. Plasma NFL negatively correlates with FA and the positive correlation with RD, DA, and MD values in different regions. Our findings showed that plasma NFL is associated with white matter changes and AD-related features, including atrophy and hypometabolism. Plasma NFL promises to be an early biomarker of microstructural changes in MCI and MCI progression to AD.
Plasma p tau 181 levels is associated with white matter microstructural changes in across the Alzheimer’s disease stages
Authors: Nabizadeh Fardin , Jameie Seyed Behnamedin , Khani Saghar , Rezaei Aida , Ranjbaran Fatemeh , Deravi Niloofar 
Published: December 2020

Abstract
Alzheimer’s Disease (AD) is characterized by cognitive impairments and memory difficulties, which hinder daily activities and lead to personal and behavioral problems. In recent years, blood-based biomarkers like plasma phosphorylated tau protein at threonine 181 (p tau 181) emerged as new tools and showed sufficient power in detecting AD patients from healthy people. Here we investigate the correlation between p tau 181 and white matter microstructural changes in AD. We add 41 patients diagnosed with Alzheimer’s, 119 patients with mild cognitive impairments and 43 healthy controls with baseline plasma p tau 181 level and DTI values for each region of interest from the ADNI database. The analysis revealed that the plasma level of p tau 181 could predict changes of MD (Mean Diffusivity), RD (Radial Diffusivity), DA (Axial Diffusivity) and FA (Fractional Anisotropy) parameters in widespread regions and there is a significant association between white matter pathway alteration in different regions and p tau 181 plasma measurements within each group. In conclusion, our findings showed that plasma p tau 181 levels are associated with cellular and molecular changes in AD, which enhance the biomarkers for diagnostic procedures and support the application of plasma p tau 181 as a biomarker for white matter changes and neurodegeneration. Longitudinal studies are also necessary for proving the efficacy of these biomarkers and predicting the role in structural changes.
Stability and Ocular Biodistribution of Topically Administered PLGA Nanoparticles
Authors: Swetledge Sean , Carter Renee , Stout Rhett , Astete Carlos E. , Jung Jangwook P. , Sabliov Cristina 
Published: December 2020

Abstract
The spatiotemporal distribution profile of polymeric nanoparticles (NPs) in the eye is important as it will determine their effectiveness as topical ocular drug delivery systems for specific eye diseases. Physical stability of the nanoparticles in an ophthalmic formulation and thermal stability of the entrapped drug are critical as well to the applicability of polymeric nanoparticles as drug delivery to the eye. To investigate these characteristics, Cy5-labeled, poly(lactic-co-glycolic acid) (PLGA) NPs (ζ-potential: -14.1±1.5 mV, size: 241.7±0.6 nm) and lutein-loaded PLGA NPs (ζ-potential: -6.7±0.3 mV, size: 210.6±3.3 nm) were synthesized, and their stability and biodistribution were assessed. Lutein-loaded NPs were stable at 4°C without significant changes in size and morphology, without significant lutein degradation, and 26% release after 5 weeks in suspension. In contrast, lutein-loaded NPs stored at 25°C and 37°C experienced significant changes in size, likely due to aggregation and surfactant dissociation; these NPs showed signs of bulk degradation based on transmission electron microscopy (TEM), and had significant lutein degradation and over 40% release after 5 weeks. Lutein loaded in NPs was more resistant to photodegradation compared to a free lutein solution when exposed to UV for 6 h, degrading 5 times slower than free lutein. To test the performance of NP therapeutics in vivo, Cy5-labled NPs were applied topically to the eyes of rats and incubated for 15 min, 30 min, or 60 min. Exterior eye tissues including the cornea, episcleral tissue, and sclera showed the highest fluorescence intensity in animals that received fluorescent nanoparticles, while the choroid was the only inner eye tissue that was significantly higher in a treatment group compared to the control group. Additionally, decreases of fluorescence in all exterior eye tissues and the choroid at 1 h compared to 30 min, indicated rapid elimination of NPs from the eye.
The Role of NbTMP1, a Surface Protein of Sporoplasm, in Nosema Bombycis Infection
Authors: Zheng Shiyi , Huang Yukang , Huang Hongyun , Yu Bin , Zhou Ni , Wei Junhong , Pan Guoqing , Li Chunfeng , Zhou Zeyang 
Published: December 2020

Abstract
Background: Nosema bombycis is a unicellular eukaryotic pathogen of the silkworm, Bombyx mori, and a hazard to the silkworm industry. Because of its long incubation period and horizontal and vertical transmission, it is a quarantine pathogen in sericulture. The microsporidian life cycle includes a dormant extracellular phase and intracellular proliferation phase. The proliferation period is the most active period of the microsporidian. This period lacks spore wall protection and may be the most susceptible stage for control. Results: The N. bombycis protein (NBO_76g0014) was identified as a transmembrane protein and named NbTMP1. It is not homologous with proteins from other microsporidia and species. NbTMP1 has a transmembrane region of 23 amino acids at the N-terminus. Indirect immunofluorescence analysis (IFA) results suggest that NbTMP1 is secreted on the plasma membrane as the spores develop. Western blot and qRT-PCR analysis showed that NbTMP1 expressed in all development stages of N. bombycis in infected cells and in the silkworm midgut. Down-regulation of NbTMP1 expression resulted in significant inhibition of N. bombycis proliferation. Conclusions: We confirmed that NbTMP1 is a membrane protein of N. bombycis. Reduction of the transcription level of NbTMP1 significantly inhibited N. bombycis proliferation, and this protein may be a target for the selective breeding of N. bombycis resistant silkworm strains.
Public Knowledge about Monogenic Diseases and Attitudes Toward Expanded Carrier Screening in China
Authors: Yang Jing , Chen Min , Wu Heli , Shen Wei , Han Jianmei , Fu Yuxia , Sun Jimei , Wu Wenyan 
Published: December 2020

Abstract
Background: Monogenic diseases affect about 10 in 1000 live births globally and account for 20% of infant mortality and 18% of pediatric hospitalizations. Many monogenic disorders could be prevented by offering expanded carrier screening (ECS) to the general population. The purpose of our study was to assess knowledge about monogenic diseases and attitudes toward ECS in China.Methods: Chinese individuals were invited to complete an online survey from July 11 to September 10, 2020. A total of 1663 questionnaires were collected. Statistical analysis was performed using IBM SPSS Statistics 26. Descriptive statistics were computed for all items. Categorical data were reported as frequencies and percentages with differences assessed by chi-square test.Results: The respondents’ total awareness rate ranged from 3.3% to 55.2%. Medical practitioners had more knowledge than non-medical practitioners. Knowledge about monogenic diseases was positively correlated with educational level. Most respondents showed a positive attitude toward ECS: 54.4% of respondents thought ECS was necessary, and 80.5% wanted to know more about monogenic diseases.Conclusions: Although the public had little knowledge about monogenic disease and ECS, most of them showed a positive attitude. Lack of knowledge is a barrier to application of ECS. Since pre-test counseling by a genetic counselor before ECS may not always be feasible, pre-test information may not be delivered by a trained genetic counselor. If clinicians are going to be the primary counselors, further education is necessary to improve their comfort and competence with this role.
Plant Availability of Magnesium in Typical Tea Plantation Soils&nbsp;
Authors: Zhang Qunfeng , Tang Dandan , Yang Xiangde , Geng Saipan , He Ying , Chen Yupei , Yi Xiaoyun , Ni Kang , Liu Meiya , Ruan Jianyun 
Published: December 2020

Abstract
Background and aims: Magnesium (Mg) plays important roles in improving the yield and quality of tea. However, Mg deficiency frequently occurs in acidic tea plantation soil. Methods: Tea plants were pot-cultivated in 12 typical tea plantations soils amended with and without Mg fertilizer. Exchangeable Mg (Ex-Mg) concentration in soils were quantitatively extracted using four extraction solutions (Mehlich-3, BaCl2, CaCl2 and NH4OAC). Plant availability of Mg was evaluated by Mg uptake and use efficiency, as well as its association with quality-components in tea plants.Results: Ex-Mg in soils were extracted most efficiently by Mehlich-3, while Mg concentrations in tea plant tissue higher correlated with Ex-Mg extracted by CaCl2 than other extraction solutions. Mg fertilizer use efficiency in tea plant varied from 6.08% to 29.56 %, and Mg fertilization significantly improve green tea quality by decreasing the ratio of total polyphenol to amino acid in tea leaves (24-60%). Moreover, the effect of Mg application on tea quality improvement and the use efficiency of Mg fertilizer both negatively correlated with total Mg concentration (r = -0.94 and -0.63, respectively) and nitrogen (N) level (r = -0.61 and -0.51, respectively) in soils prior to tea plant cultivation.Conclusions: CaCl2 could be recommended for plant-available Mg extraction in tea plantation soil, and Mg fertilizer use efficiency could be affected and predicted by total N and Mg status in soils prior to tea plant cultivation, providing a potential theoretical for guidance of Mg fertilization for tea yield and quality improvement in tea plantation management.
A Novel QTL&nbsp;Controlling Flag Leaf Width Located on Chromosome Arm 7AS&nbsp;in Bread Wheat (Triticum Aestivum L.)
Authors: Ye Xueling , Li Jian , Zheng Zhi , Zhou Hong , Xiang Dabing 
Published: December 2020

Abstract
Background: Wheat is an important cereal crop and improving wheat production is essential for meeting the food demand from the growing population worldwide. Flag leaf width (FLW) is an important trait affecting plant architecture and contributing to grain yield. To detect loci conferring FLW, we assessed a population of recombinant inbred lines (RILs) from a cross of EGA Wylie/Sumai 3 in different environments.Results: A total of six QTL were detected from the population. Two of them located on chromosome 2B and the other four located on chromosomes 2D, 4B, 7A, and 7B, respectively. The percentage of phenotypic variation (PEV) explained by these loci ranged from 14.6% to 33.8%, with LOD scores varying from 3.01 to 7.81. Of them, the locus located on chromosome arm 7AS is likely novel. Significant effects of this locus were detected in multiple trials conducted and the PEV explained by this QTL varied from 14.6% to 19.8% among the different trials. An orthologous analysis based on rice and Arabidopsis identified 3 putative genes underlying this potentially novel locus.Conclusion: This study identified a stable potentially novel QTL in multiple environments and predicted three candidate genes of it, which laid the foundation for further fine-mapping and cloning the gene(s) underlying QFlw.WS-7A with the contribution to grain yield.
Acupoint Application Therapeutic Mechanism for Novel Coronavirus Pneumonia: A Network Pharmacology Analysis
Authors: Liu Shan , Zhang Chi , Zhang Zexin , Guo Wei , Xia Jiangnan , Li Jing , Wang Zhijie 
Published: December 2020

Abstract
Background: Acupoint application (AA) therapy, a traditional Chinese medicine external treatment method, is recommended as a complementary Chinese medicine therapy for treating new coronavirus pneumonia (COVID-19), and can help improve curative effects, promote patient recovery, and improve immunity to prevent disease, but the mechanism is not clear. We sought to explore the key targets and mechanisms of Ephedra and Asarum, the main components used in AA, in the treatment of COVID-19 in this study.Methods: The active compounds and related targets of Ephedra and Asarum used in AA were screened by searching four databases. COVID-19-related target genes were identified from three disease databases, and the key targets of treating COVID-19 were obtained by Venn diagram using Cytoscape 3.2.1 software, gene ontology (GO) enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were used to explore possible mechanisms and pathways. The verification of the binding force between the compounds and target genes was completed by performing molecular docking with Autodock and pymol software.Results: Twenty-four active components of AA corresponded to 252 targets, with 713 target genes related to COVID-19, and 56 key genes were selected. GO analysis results showed that biological processes mainly included the inflammatory and immune responses, and cell components were mainly the plasma membrane and nucleus, with molecular functions including protein binding and identical protein binding. The top pathways included Immune System, Cytokine Signaling in Immune System, Adaptive Immune System, Signaling by Interleukins, Innate Immune System, and Signaling by GPCR.Conclusion: The results of this study preliminarily verified that Ephedra and Asarum used in AA therapy could treat COVID-19 via multiple compounds and multi-pathways, which provided a basis for clinical application and further research.
High Oil Accumulation in Tuber of Yellow Nutsedge Compared to Purple Nutsedge is Associated with More Abundant Expression of Genes Involved in Fatty Acid Synthesis and Triacylglycerol Storage
Authors: Ji Hongying , Liu Dantong , Yang Zhenle 
Published: December 2020

Abstract
Background: Yellow nutsedge is a specific plant species that can accumulate up to 35% oil of tuber dry weight, perhaps the highest level observed in the tuber tissues of plant kingdom. To gain insight into the molecular mechanism that leads to high oil accumulation in yellow nutsedge, gene expression profiles of oil production pathways involved carbon metabolism, fatty acid synthesis, triacylglycerol synthesis, and triacylglycerol storage during tuber development were compared with purple nutsedge, a very close relative of yellow nutsedge that is poor in oil accumulation. Results: Compared with purple nutsedge, the high oil content in yellow nutsedge was associated with much higher transcripts for seed-like oil-body proteins, almost all fatty acid synthesis enzymes, and specific key enzymes of plastid Rubisco bypass as well as malate and pyruvate metabolism. However, transcript levels for carbon metabolism toward pyruvate generation were comparable and for triacylglycerol synthesis were similar in both species. Two seed-like master transcription factors ABI3 and WRI1 were found to display similar temporal transcript patterns but be expressed at 6.5- and 14.3-fold higher levels in yellow nutsedge than in purple nutsedge, respectively. A weighted gene co-expression network analysis revealed that ABI3 is in strong transcriptional coordination with WRI1 and other key oil-related genes. Conclusions: Together, these results implied that plastidial pyruvate availability and fatty acid synthesis, along with triacylglycerol storage in oil body, rather than triacylglycerol synthesis in endoplasmic reticulum, are the major factors responsible for high oil production in tuber of yellow nutsedge, and ABI3 is most likely to play a critical role in regulating oil accumulation. This study is of significance in deep understanding the molecular mechanism controlling carbon partitioning toward oil production in oil-rich tuber and provides a valuable reference for enhancing oil accumulation in non-seed tissues of crops through genetic breeding or metabolic engineering.
Barbaloin Alleviates Cerebral Ischemia and Reperfusion Injury in Rats and Inhibits Lipopolysaccharide-stimulated Inflammatory Responses in BV2 Microglial Cells
Authors: Wang Lin , Zhang Lijuan 
Published: December 2020

Abstract
Background: Barbaloin (BAR) is a bioactive anthracycline derived from the leaf exudates of aloe plants with a variety of biological and pharmacological properties. The present study was performed to investigate the neuroprotective effects of BAR against cerebral ischemia and reperfusion (I/R) injury in rats as well as the possible underlying mechanisms. Middle cerebral artery occlusion followed by reperfusion was used to induce cerebral I/R injury in rats, and BAR was administered intraperitoneally after the onset of ischemia. Results: We found that BAR remarkably improved neurological scores, reduced brain infarct volume, and inhibited neuronal apoptosis in cerebral I/R rats. Furthermore, BAR up-regulated Bcl-2 protein levels and down-regulated Bax, active caspase-3, and inducible nitric oxide synthase (iNOS) in ischemic cortex. I/R injury-induced increases in malondialdehyde content and decreases in glutathione peroxidase, glutathione, and superoxide dismutase activities were significantly attenuated by BAR administration. In vitro, BAR pretreatment inhibited the contents of proinflammatory cytokines (tumor necrosis factor-α, iNOS, and interleukin-6) and reduced protein levels of iNOS and nuclear expression of nuclear factor-κB p65 in lipopolysaccharide-stimulated BV-2 microglial cells. Conclusion: Taken together, our data suggest that BAR possesses neuroprotective effects against cerebral I/R injury through anti-oxidative, anti-apoptotic, and anti-inflammatory activities.
Adaptive evolution of interferon induced protein with tetratricopeptide repeats 5(IFIT5) in birds
Authors: Zhang Bei , Zhang Chuansheng , Meng Jie , Ren Yifan , Gong Jing , Yang Qing , Li Xianglong , Geng Liying 
Published: December 2020

Abstract
Background : Previous studies have revealed that wild birds are reservoirs and mobile vectors of viruses, many of which cause illness and mortality in domestic bird and humans. In birds, the invasion of viruses will quickly trigger the innate immune mechanism induced by interferon (IFN). As IFN-stimulated genes (ISGs), the IFIT gene family plays an important role in innate immunity. However, only IFIT5 of the IFIT gene family exists in birds, and the direction and strength of selection acting on IFIT5 are largely unknown. Results : Here, we studied the selection on IFIT5 based on the coding sequence (CDS) data of 20 birds. We identified 12 persistent positive selection sites (PSS), other sites suffered purifying selection and neutral selection; probably due to functional constraints. We also found humans have only 3PSS (189,197and 295), likely due to having more IFIT gene family member that can cooperate to resist virus invasion. The 12 PSS located in the closed clamp structure of the IFIT5 protein, except for position 45. In particular, 3 PSS (335, 342 and 367) were located in the TPR domain, which implied their important roles in virus recognition. We only found 2 episodic PSS (30,332) in Passeriformes, indicating episodic selection pressure in Passeriformes lineage. The positive selection of IFIT5 might provide a theoretical basis for the pathogen-host interaction in birds. Conclusions : We found that the diversity of IFIT5 domains in birds, and that the PSS of IFIT5 is the joint influence of functional domain conservation and the pressure of virus evolution.We speculated that persistent PSS may affect the antiviral function of IFIT5, especially in the region of closed clamp structure. These results lay a theoretical foundation for the further study of the antiviral immune mechanism of IFIT5 in birds.
Ultimate 0.34 nm Gate-length Side-Wall Transistors with Atomic Level Channel
Authors: Ren Tian-Ling , Wu Fan , Shen Yang , Tian He , Ren Jie , Gou Guangyang , Yang Yi 
Published: December 2020

Abstract
Despite 55 years of efforts into short gate length transistors following the Moore’s law, the gate length below 1 nm has not been realized. Here, we demonstrated a side-wall monolayer MoS2 transistors with ultimate 0.34 nm gate length using the edge of graphene as gate electrode. Moreover, large area of chemical vapor deposition graphene and MoS2 are used for 2-inch wafer production. These ultrashort devices show excellent ON/OFF current ratio of 2 × 105. Simulation results indicate that the MoS2 side-wall effective channel length approaches 0.34 nm in the ON state. This graphene edge gate combined with MoS2 vertical channel structure provides an efficient gate control ability and enables the physical gate length scaling down to atomic level, which shows great potential to build next generation electronics.