bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deciphering Novel SARS CoV-2 specific Disease Pathways from RNA Sequencing Data of COVID-19 Infected A549 Cells and Potential Therapeutics using Next Generation Knowledge Discovery Platforms
Authors: Pushparaj Peter Natesan , Damiati Laila Abdullah , Denetiu Luliana , Bakhashab Sherin , Asif Muhammad , Hussain Abrar , Ahmed Sagheer , Hamdard Mohammed Hammid , Rasool Mahmood 
Published: June 2021

Abstract
BackgroundThe coronavirus (CoV) disease identified in Wuhan, China in 2019 (COVID-19) was chiefly characterized by atypical pneumonia and severe acute respiratory syndrome (SARS) and caused by SARS CoV-2 that belongs to the family Coronaviridae. COVID-19 symptoms vary from a mild cold to more severe illnesses such as SARS, thrombosis, stroke, organ failure, and in some patients even cause mortality. Deciphering the underlying disease mechanisms is pivotal for the identification and development of COVID-19 specific drugs for effective treatment and prevent human-to-human transmission, disease complications, and mortality. Methodology: Here, the Next Generation RNA Sequencing (RNA Seq) data using Illumina Next Seq 500 from SARS CoV-infected A549 cells and mock-treated A549 cells, were obtained from the gene expression omnibus (GEO) (GSE147507) and the Quality Control (QC) were evaluated using the CLC Genomics Workbench 20.0 (Qiagen, USA) before the RNA Seq analysis. The DEGs were imported into BioJupies to analyze to decipher COVID-19 induced biological, molecular, and cellular processes, pathways, and small molecules derived from chemical synthesis or natural sources to mimic or reverse COVID-19-specific gene signatures. Besides, we have used the iPathwayGuide (Advaita Bioinformatics USA) to identify COVID-19 specific pathways, biological, molecular, and cellular processes, and “druggable” candidates for future therapy. Results: 141 DEGs were identified out of a total of 9665 DEGs obtained from BioJupies analysis of the RNASeq reads of the SARS CoV infected A549 cells and mock-treated A549 cells based on a p-value cut off (0.05) and a fold change cut off 1.5.Conclusion: In conclusion, the present study unravels a novel approach of using next-generation knowledge discovery platforms to discover specific drugs for the amelioration of COVID-19 related disease pathologies.
SLC6A14 Modulates Lung Disease Severity in Cystic Fibrosis and Affects mTOR Phosphorylation and Bronchial Epithelial Repair
Authors: Mercier Julia , Calmel Claire , Mésinèle Julie , Sutanto Erika , Merabtene Fatiha , Longchampt Elisabeth , Sage Edouard , Kicic Anthony , Boëlle Pierre-Yves , Corvol Harriet , Ruffin Manon , Guillot Loic 
Published: June 2021

Abstract
Cystic fibrosis (CF), due to variants in CFTR gene, is associated with chronic infection/inflammation responsible for airway epithelium alteration and lung function decline. Modifier genes induce phenotype variability between people with CF (pwCF) carrying the same CFTR variants. Among these, the gene encoding for the amino acid transporter SLC6A14 has been associated with lung disease severity and age of primary airway infection by the bacteria Pseudomonas aeruginosa. In this study, we investigated whether the single nucleotide polymorphism (SNP) rs3788766, located within SLC6A14 promoter, is associated with lung disease severity in a large French cohort of pwCF. We also studied the consequences of this SNP on SLC6A14 promoter activity and the role of SLC6A14 in mammalian target of rapamycin (mTOR) signaling pathway and airway epithelial repair. We confirm that SLC6A14 SNP rs3788766 is associated with lung disease severity in pwCF (p=0.020; n=3,257, pancreatic insufficient, aged 6 to 40 years old), with the minor allele G being deleterious. In bronchial epithelial cell lines deficient for CFTR, SLC6A14 promoter activity is reduced in the presence of the rs3788766 G allele. SLC6A14 inhibition with a specific pharmacological blocker reduced 3H-arginine transport, mTOR phosphorylation and bronchial epithelial repair rates in wound healing assays. In conclusion, SLC6A14 rs3788766 G allele is associated with lower lung function in pwCF. SLC6A14, whose transcriptional promoter activity varies according to rs3788766 genotype, is involved in mTOR signaling and bronchial epithelial repair. This study suggests that SLC6A14 might influence CF lung phenotype via mTOR and epithelial repair mechanisms modulation.
Postnatal lymph node expansion of stromal progenitors towards reticular and CD34+ stromal cell subsets is determined by distinct transcriptional programs
Authors: Pezoldt Joern , Wiechrs Carolin , Litovchenko Maria , Biočanin Marjan , Zou Mangge , Sitnik Katarzyna , Beckstette Michael , Chen Wanze , Gardeux Vincent , Floess Stefan , Ebel Maria , Russeil Julie , Arampatzi Panagiota , Vafardanejad Ehsan , Saliba Antoine-Emmanuel , Deplancke Bart , Huehn Jochen 
Published: June 2021

Abstract
Gut-draining mesenteric lymph nodes (mLN) provide the framework and microenvironment to shape intestinal adaptive immune responses. We previously delineated transcriptional signatures in LN stromal cells (SC), pointing to tissue-specific variability in composition and immuno-modulatory function of SCs.
Here, we dissect the tissue-specific epigenomic DNA accessibility and CpG methylation landscape of LN non-endothelial SCs and identify a microbiota-independent core epigenomic signature of LN SCs. By combined analysis of transcription factor (TF) binding sites together with the gene expression profiles of non-endothelial SCs, we delineated TFs poising skin-draining peripheral LN (pLN) SCs for pro-inflammatory responses. Furthermore, using scRNA-seq, we dissected the developmental trajectory of mLN SCs derived from postnatal to aged mice, identifying two distinct putative progenitors, namely CD34+SC and fibroblastic reticular stromal cell (FRC) progenitors, which both feed the rapid postnatal LN expansion. Finally, we identified Irf3 as a key differentiation TF inferred from the epigenomic signature of mLN SCs that is dynamically expressed along the differentiation trajectories of FRCs, and validated Irf3 as a regulator of Cxcl9+ FRC differentiation.
Together, our data constitute a comprehensive transcriptional and epigenomic map of mLN development and dissect location-specific, microbiota-independent properties of mLN non-endothelial SCs. As such, our findings represent a valuable resource to identify core transcriptional regulators that impinge on the developing mLN early in life, thereby shaping long-lasting intestinal adaptive immune responses.
Effects Of Early-Stage Blood Pressure Variability On The Functional Outcome In Acute Ischemic Stroke Patients With Symptomatic Intracranial Arterial Stenosis Or Occlusion Receiving Intravenous Thrombolysis
Authors: Yao Mian-Xuan , Qiu Dong-Hai , Zhao Jiang-Hao , Yin Han-Peng , Liu Yong-Lin , Chen Yang-Kun 
Published: June 2021

Abstract
Background: Studies exploring on the relationship between blood pressure fluctuations and outcome in acute ischemic stroke (AIS) patients treated with intravenous thrombolysis (IVT) are limited. We aimed to investigate the influence of blood pressure variability (BPV) during the first 24 hours after IVT on neurological deterioration (END) and 3-month outcome after IVT in patients with symptomatic intracranial arterial stenosis or occlusion (SIASO).Methods: Clinical data from consecutive AIS patients with SIASO who received IVT were retrospectively analyzed. The hourly systolic BP of all patients were recorded during the first 24 hours following IVT. We calculated three syslolic BPV parameters including coefficient of variability (CV), standard deviation of mean BP (SD) and successive variation (SV). The SV was categorized into four grades based on quartiles. The END was defined as neurological deterioration with an increase in the National Institutes of Health Stroke Scale (NIHSS) score ≥ 4 points within the first 72 hours after admission. Follow-ups was performed at 90 days after onset were performed, and favorable and poor outcome were defined as a modified Rankin Scale scores of ≤1 or ≥2, respectively.Results: A total of 110 patients were included, with a mean age of 62.0 ± 12.5 years. 86 patients (78.2%) were male. Twenty patients (18.2%) experienced END, and 37 patients (33.6%) had a favorable outcome. Compared with patients with in the poor outcome group, age ([64.8 ± 10.9] vs [56.7 ± 13.8]), NIHSS on admission (11.0 [7.0 -16.0] vs 6.0 [3.5 - 9.0]), SV ([14.5 ± 4.3] vs [11.8 ± 3.2]) and SD ([12.7 ± 3.8] vs [10.9 ± 3.3]) were lower in the favorable outcome group (all p < 0.05). No BPV parameters were associated with END. In the multivariable logistic regression analysis, compared with the lowest SV (SV<25% quartile), SV50%-75% (odds rato [OR] = 4.449, 95% confidence interval [CI] = 1.231-16.075, p = 0.023) and SV>75% (OR = 8.676, 95% CI = 1.892-39.775, p = 0.005) were significantly associated with poor outcome at 3 months. Conclusions: SV had a negative relationship with the 3-month outcome in AIS patients with SIASO treated with IVT, indicating that BPV may affect the outcome of AIS.
The Water Incident Database (WAID) 2012 to 2019: A Systematic Evaluation of the Documenting of UK Drownings
Authors: Hills Samuel , Hobbs Matthew , Tipton Michael , Barwood Martin 
Published: June 2021

Abstract
Background. Death by drowning is a leading cause of accidental death in the United Kingdom (UK) and worldwide. The World Health Organization (WHO) states that effective documentation of drowning is required to describe drowning frequency and to underpin effective drowning prevention intervention, thus improving the quality of data describing drowning frequency represents a key initiative. The water incident database (WAID) has been used to document UK fatal and non-fatal water-based incidents since 2009. WAID has not undergone a systematic evaluation of its data or data collection procedures to establish if the database meets the WHO requirements. The present study investigated the characteristics of UK fatal drowning incidents and audited current WAID data capture procedures. Methods. Data for the fatal drowning cases recorded between 2012 and 2019 were reviewed. Summary statistics were produced to describe the prevalence of UK drownings and a two-phase blind audit was conducted to establish a) the completeness of each of the 22 WAID fields (i.e., columns) and b) the reliability of data entry processes by reviewing written data sources originally used to populate WAID. Results. A total of 5,501 fatalities were recorded between 2012-2019. Drowning was most frequent amongst males aged 35 to 60 years (n=1,346), whilst suspected accidents and suicides accounted for 44% and 35% of fatalitie. Suicide by drowning was at a peak in the most recent year of data analysed (i.e., 2019; 279 cases) highlighting an urgent need for targeted intervention. Audit phase one indicated that 16% of all fields were incomplete, thus indicating potential redundancy, duplication, or the need for onward review. Phase two indicated high levels of agreement (80±12%) between audited cases and the ‘true’ WAID entries. Conclusions. This study confirms WAID as a rigorous, transparent and effective means of documenting UK drownings thereby meeting WHO requirements for data quality. Such findings allow researchers and policy makers to use WAID to further investigate UK drowning with a view to improving public safety measures and drowning prevention interventions; our work these data is ongoing. Observations alongside several expert recommendations proposed in this manuscript have informed a revised version of the WAID database.
Research on bogie traction seat crack identification based on OvO multi-feature fusion
Authors: Chang Qi , Liu Yi , Li Lin , Man Junfeng , Peng Cheng , Liu Kai , Wu Han , Shen Yiping 
Published: June 2021

Abstract
Aimed at the problems of unsatisfactory feature extraction and low diagnostic accuracy in the identification process during train bogie traction seat operation status , an optimized method of the neural network model of back propagation based on OvO multi-feature fusion is proposed. Firstly, a simulated experimental platform is built to collect vibration signals, and the collected original vibration data are analyzed in time domain, frequency domain and time-frequency. Secondly, the principal component analysis is carried out on the proposed high-dimensional feature sets. Finally, the reduced dimensional features are fused into the optimal feature set based on OvO algorithm. The back propagation neural network model is constructed, and the time domain, frequency domain, time-frequency and optimal feature sets are taken as inputs respectively, and the results of output recognition are compared. The experimental results show that the recognition accuracy of back propagation neural network model based on OvO multi-feature fusion is higher, and the running state of bogie traction seat can be recognized accurately.
Investigating the Immune Function and Proteomic Profiles of Plasmal Exosomes in Lactobacillus Plantarum-treated Immunosuppressive Broilers
Authors: Liu Huawei , Zhao Fan , Zhang Kai , Zhao Jinshan , Wang Yang 
Published: June 2021

Abstract
Background: Exosomes are extracellular membranous nanovesicles that carry functional molecules, such as proteins, to mediate local and systemic cell-to-cell communication. Exosomes released by cells can present in the plasma and involved in the regulation of immunity. Probiotics play a beneficial role in improving the immune function of host through many mechanisms. However, whether probiotics can increase the immune function of broilers by regulating plasmal exosomal cargo is unclear. Methods: Three hundred broilers were allocated to three treatments: control diet (CON group), control diet + dexamethasone (DEX) injection (DEX group), control diet containing 1 × 108 cfu/g Lactobacillus plantarum P8 + DEX injection (P8+DEX group). The immune function of broilers was detected by measuring the levels of inflammatory cytokines and immunoglobulins in plasma and jejunal mucosa. Exosomes were isolated from the plasma via EIQ3 isolation kits and characterized via transmission electron microscopy, nanoparticle tracking analysis, and Western blot. Then, exosomal protein profile was determined by proteomic. At last, correlation analysis was performed to figure out the potential role of exosomal proteins in regulating immune function of P8-treated broilers.Results: P8+DEX treatment improved the immune function of DEX-induced immunosuppressive broiler through decreasing plasmal IL-1β, IL-6, TNF-α and jejunal IL-1β, as well as increasing plasmal IL-10 and jejunal IgM. The isolated extracellular vesicles had an average diameter of 125.8 nm, exhibited a cup-shaped morphology and expressed exosomal markers. A total of 784 proteins were identified in the exosomes. Among the 784 proteins, 126 differentially expressed proteins (DEPs) were found between DEX and CON groups, 102 DEPs were found between P8+DEX and DEX groups. Gene Ontology analysis indicated that DEPs between DEX and CON groups are mainly involved in metabolic process, cellular anatomical entity, cytoplasm, extracellular region and binding. DEPs between P8+DEX and DEX are mainly involved in multicellular organismal process, response to stimulus, cytoplasm, cell periphery, membrane, binding, protein binding and ion binding. Further, pathway analysis revealed that most of the DEPs between DEX and CON participated in the ECM-receptor interaction, focal adhesion, regulation of actin cytoskeleton, endocytosis and phagosome. Most of the DEPs between P8+DEX and DEX participated in the ErbB and PPAR signaling pathways. Moreover, many immunity-related DEPs were correlated with the altered immune parameters in plasma and jejunal in broilers fed with P8.Conclusions: Our findings demonstrated that plasmal exosomes in immunosuppressive broilers fed with P8 carry proteins related to immune function, and may have immunomodulatory effects on the plasma and intestinal immunity.
The Effects of Mismatch between SPECT and CT Images on Quantitative Activity Estimation – A Simulation Study
Authors: Lyu Yingqing , Chen Yue , Mok Greta 
Published: June 2021

Abstract

Background: Quantitative activity estimation is essential in targeted radionuclide therapy dosimetry. Misregistration between SPECT and CT images at the same imaging time point due to patient movement degrades accuracy. This work aims to study the mismatch effects between CT and SPECT data on attenuation correction (AC), volume-of-interest (VOI) delineation and registration for activity estimation.Methods: Nine 4D XCAT phantoms were generated at 1, 24, and 144 hrs post In-111 Zevalin injection, varying in activity distributions, body and organ sizes. Realistic noisy SPECT projections were generated by an analytical projection and reconstructed with quantitative OS-EM method. CT images were shifted from -5 to 5 voxels as well as according to clinical reference corresponding to SPECT images at each time point. For AC effect, mismatched CT images were used for AC in SPECT reconstruction while VOIs were mapped out from matched CTs. For VOI effect, target organs were mapped out using mismatched CTs with matched CTs for AC. For registration effect, non-rigid registrations were performed on sequential mismatched CTs to align corresponding SPECT images, with no AC and VOI mismatch. Bi-exponential curve fitting was performed to obtain time-integrated activity (TIA). Organ activity errors (%OAE) and TIA errors (%TIAE) were calculated.Results: According to clinical reference, %OAE was larger for organs near ribs for AC effect, e.g., -2.58%±0.81% for liver. For VOI effect, %OAE was larger for small and low uptake organs, e.g., -11.94%±10.34% for spleen. %OAE was proportional to mismatch magnitude, e.g., 4.77%±1.41%, 12.01%±3.97% and 42.81%±6.38% for 1-, 2-, and 5-voxel mismatch for lungs. For registration effect, %TIAE were larger when mismatch existed in more numbers of SPECT/CT images, while no substantial difference was observed when using mismatched CT at different time points for registration reference. %TIAE was highest for VOI, followed by registration and AC, e.g., 37.61%±5.08%, 14.25%±7.07% and 1.13%±0.90% respectively for kidneys.Conclusions: The mismatch between CT and SPECT images poses a significant impact on accuracy of quantitative activity estimation in dosimetry, attributed particularly from VOI delineation errors. It is recommended to perform registration between emission and transmission images at the same time point to ensure dosimetric accuracy.
Spatiotemporal single-cell analysis reveals critical roles of mechano-sensing genes at the border zone in remodeling after myocardial infarction
Authors: Yamada Shintaro , Ko Toshiyuki , Hatsuse Satoshi , Nomura Seitaro , Zhang Bo , Dai Zhehao , Inoue Shunsuke , Kubota Masayuki , Sawami Kosuke , Yamada Takanobu , Sassa Tatsuro , Katagiri Mikako , Fujita Kanna , Katoh Manami , Ito Masamichi , Harada Mutsuo , Toko Haruhiro , Takeda Norifumi , Morita Hiroyuki , Aburatani Hiroyuki , Komuro Issei 
Published: June 2021

Abstract
The left ventricular remodeling after myocardial infarction (MI) causes heart failure, but its underlying mechanisms remain largely unknown. Here, we performed an integrative analysis of spatial transcriptomics and single cell RNA-seq in murine MI model and found that mechanical stress-response genes are expressed at the border zone and play a critical role in left ventricular remodeling after MI. Single-cardiomyocyte RNA-seq of the heart after MI divided cardiomyocytes into 8 clusters. We identified the cell cluster which was specifically derived from the ischemic area in an early stage after MI and expressed mechano-sensing genes such as Csrp3, Ankrd1 and Ankrd2. Spatial transcriptomic analysis demonstrated that cardiomyocytes with this gene expression profile were specifically localized at the border zone in post-MI day 1. AAV9-mediated gene silencing of Csrp3 exacerbated cardiac dilatation and dysfunction after MI. Collectively, our datasets and findings not only provide an insight into spatiotemporal molecular pathogenesis of myocardial infarction but also highlight mechano-sensing genes at the border zone as an adaptive regulator of left ventricular remodeling.
Ghrelin pretreatment enhanced the protective effect of bone marrow-derived mesenchymal stem cell conditioned medium on lipopolysaccharide-induced endothelial cells injury
Authors: Ge Shanhui , He Wanmei , Zhang Lishan , Lin Shan , Luo Yuling , Chen Qingui , Zeng Mian 
Published: June 2021

Abstract
Background
Lung endothelial barrier injury plays a crucial role in the pathophysiology of acute respiratory distress syndrome, and it has been demonstrated that bone marrow-derived mesenchymal stem cells conditioned medium (BMSCs-CM) and ghrelin both exert a potential protective impact. The study aimed to investigate whether ghrelin pretreatment enhanced the protective effect of BMSCs-CM on lipopolysaccharide (LPS)-induced endothelial cells injury.
Methods
BMSCs were isolated from rat bone marrow and used for the experiment after expanded and meeting the phenotypic criteria for defining MSCs identified by flow cytometry. The effect of conditioned medium derived from ghrelin pretreated BMSCs (BMSCsGhrelin pretreated-CM) on LPS injured endothelial cells was evaluated by examing its impact on the migration capability, apoptosis, and the release of pro-inflammatory factors (TNF-α, IL-1β, and IL-6) of endothelial cells. To further clarify the potential mechanisms, the activation of the AKT/GSK3β pathway in endothelial cells was examined by western blot and the gene expression profiles of BMSCs pretreated by ghrelin were examined by RNA sequencing.
Results
BMSCsGhrelin pretreated-CM showed a grtear protective effect on LPS-induced endothelial cells injury than BMSCs-CM by improving cell migration, alleviating apoptosis, and reducing the release of pro-inflammatory factors of endothelial cells. The mechanism partly related to the activation of the AKT/GSK3β pathway after BMSCsGhrelin pretreated-CM treatment. Five upregulated candidate genes (Wnt5a, S100b, Bmp2, Id4, and Pthlh) were identified in BMSCs after ghrelin treatment which were associated with the activation of AKT pathways and endothelial function.
Conclusions
Ghrelin pretreatment enhanced the protective effect of BMSCs-CM on LPS-induced endothelial cells injury partly by activating the AKT/GSK3β pathway.
Nonlinear Dynamic Analysis of Variable lead Preloaded Single Nut Ball Screw Considering the Variation of Working Parameters
Authors: Liu zhendong , xu mengtao , zhang hongzhuang , Li Changyou , Yao Guo , li zhenyuan , miao Huihui , wang chenyu , zhang yimin 
Published: June 2021

Abstract
In this study, a 5-degrees-of-freedom dynamic model of variable lead preloaded single nut ball screw is proposed. The proposed model considers the effect of excitation amplitude, deflection angle, the number of balls, and the preload into consideration. Moreover, to study the effect of working parameters on nonlinear dynamics, bifurcation diagram, 3-D frequency spectrum, phase diagram and Poincaré section with different system parameters are shown in discussion section. The numerical analysis indicates that the system can exhibits different motion states, and the continuous frequency component can be observed. Moreover, a series of experiments are conducted to estimate the dynamic parameters and validate the proposed dynamic model.