bluuebunny/crossref_metadata_2025_split huggingface dataset:
N6-methyladenine regulator-mediated RNA methylation modification patterns in immune microenvironment regulation of osteoarthritis
Authors: Gu Yong , Wang Zhengming , Wang Rui , Yang Yunshang , Tong Peijian , Lv Shuaijie , Xiao Long , Wang Zhirong 
Published: January 2023

Background: Osteoarthritis is a common chronic degenerative disease, and recently, an increasing number of studies have shown that immunity plays an important role in the progression of osteoarthritis, which is exacerbated by local inflammation. The role of N6-methyladenine (m6A) modification in immunity is being explored. However, the role of m6A modification in regulating the immune microenvironment of osteoarthritis remains unknown. In this study, we sought to discuss the association between the N6-methyladenine (m6A) modification and the immune microenvironment of osteoarthritis.Methods: First, the data and gene expression profiles of 139 samples, including 33 healthy samples and 106 osteoarthritis samples, were obtained from the Genetics osteoARthritis and Progression (GARP) study. Then the differences in m6A regulators between healthy individuals and osteoarthritis patients were analyzed. The correlation between m6A regulators and immune characteristics was also investigated by single-sample gene set enrichment analysis (ssGSEA). Principal component analysis (PCA), Gene Set Variation Analysis (GSVA) enrichment analysis, weighted gene coexpression network analysis (WGCNA), and Associated R packages were used to identify the m6A phenotype and its biological functions.Results: A total of 23 m6A regulators were involved in this study. We found a close correlation between most m6A regulators in all samples as well as in osteoarthritis samples. VIRMA and LRPPRC were the most highly correlated m6A regulators and showed a positive correlation, whereas VIRMA and RBM15B were the most negatively correlated. M6A regulators are associated with osteoarthritis immune characteristics. For example, MDSC cell abundance was strongly correlated with RBM15B and HNRNPC. Meanwhile, RBM15B and HNRNPC were important effectors of natural killer cell immune responses. IGFBP3 is an important regulator of cytolytic activity immune function. We performed an unsupervised consensus cluster analysis of the osteoarthritis samples based on the expression of 23 m6A regulators. Three different m6A subtypes of osteoarthritis were identified, including 27 samples in subtype C1, 21 samples in subtype C2, and 58 samples in subtype C3. Different m6A subtypes have unique biological pathways and play different roles in the immune microenvironment of osteoarthritis.Conclusion: The m6A modification plays a crucial role in the diversity and complexity of the immune microenvironment in osteoarthritis.
Genome-wide analysis of dysregulated RNA-binding proteins and alternative splicing genes in keloid
Authors: Zhu Zhen , Ni Shuangying , Zhang Jiali , Yuan Ying , Bai Yun , Yin Xueli , Zhu Zhengwei 
Published: January 2023

Introduction: The pathogenesis of keloids remains unclear.Methods: In this study, we analyzed RNA-Seq data (GSE113619) of the local skin tissue of 8 keloid-prone individuals (KPI) and 6 healthy controls (HC) before and 42 days after trauma from the gene expression omnibus (GEO) database. The differential alternative splicing (AS) events associated with trauma healing between KPIs and HCs were identifified, and their functional differences were analyzed by gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) pathways. The co-expression relationship of differentially alternative splicing genes and differentially expressed RNA binding proteins (RBPs) was established subsequently.Results: A total of 674 differential AS events between the KD42 and the KD0 and 378 differential AS events between the HD42 and the HD0 were discovered. Notably, most of the differential genes related to keloids are enriched in actin, microtubule cells, and cortical actin cytoskeletal tissue pathway. We observed a signifificant association between AS genes (EPB41, TPM1, NF2, PARD3) and trauma healing in KPIs and HCs. We also found that the differential expression of healthy controls-specifific trauma healing-related RBPs (TKT, FDPS, SAMHD1) may affect the response of HCs to trauma healing by regulating the AS of downstream trauma healing-related genes such as DCN and DST. In contrast, KPIs also has specifific differential expression of trauma healing related RBPs (S100A9, HspB1, LIMA1, FBL), which may affect the healing response of KPIs to trauma by regulating the AS of downstream trauma healing-related genes such as FN1 and TPM1.Discussion: Our results were innovative in revealing early wound healing-related genes (EPB41, TPM1, NF2, PARD3) in KPI from the perspective of AS regulated by RBPs.
Identification of PDCD1 as a potential biomarker in acute rejection after kidney transplantation via comprehensive bioinformatic analysis
Authors: Wang Yucheng , Lin Xiaoli , Wang Cuili , Liu Xinyu , Wu Xiaoying , Qiu Yingying , Chen Ying , Zhou Qin , Zhao Haige , Chen Jianghua , Huang Hongfeng 
Published: January 2023

BackgroundAcute rejection is a determinant of prognosis following kidney transplantation. It is essential to search for novel noninvasive biomarkers for early diagnosis and prompt treatment.MethodsGene microarray data was downloaded from the Gene Expression Omnibus (GEO) expression profile database and the intersected differentially expressed genes (DEGs) was calculated. We conducted the DEGs with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Distribution of immune cell infiltration was calculated by CIBERSORT. A hub gene marker was identified by intersecting the rejection-related genes from WGCNA and a selected KEGG pathway—T cell receptor signaling pathway (hsa04660), and building a protein-protein interaction network using the STRING database and Cytoscape software. We performed flow-cytometry analysis to validate the hub gene.ResultsA total of 1450 integrated DEGs were obtained from five datasets (GSE1563, GSE174020, GSE98320, GSE36059, GSE25902). The GO, KEGG and immune infiltration analysis results showed that AR was mainly associated with T cell activation and various T-cell related pathways. Other immune cells, such as B cells, Macrophage and Dendritic cells were also associated with the progress. After utilizing the WGCNA and PPI network, PDCD1 was identified as the hub gene. The flow-cytometry analysis demonstrated that both in CD4+ and CD8+ T cells, PD1+CD57-, an exhausted T cell phenotype, were downregulated in the acute rejection whole blood samples.ConclusionsOur study illustrated that PDCD1 may be a candidate diagnostic biomarker for acute kidney transplant rejection via integrative bioinformatic analysis.
Extended genomic HLA typing identifies previously unrecognized mismatches in living kidney transplantation
Authors: Lehmann Claudia , Pehnke Sarah , Weimann Antje , Bachmann Anette , Dittrich Katalin , Petzold Friederike , Fürst Daniel , de Fallois Jonathan , Landgraf Ramona , Henschler Reinhard , Lindner Tom H. , Halbritter Jan , Doxiadis Ilias , Popp Bernt , Münch Johannes 
Published: January 2023

IntroductionAntibody mediated rejection (ABMR) is the most common cause of long-term allograft loss in kidney transplantation (KT). Therefore, a low human leukocyte antigen (HLA) mismatch (MM) load is favorable for KT outcomes. Hitherto, serological or low-resolution molecular HLA typing have been adapted in parallel. Here, we aimed to identify previously missed HLA mismatches and corresponding antibodies by high resolution HLA genotyping in a living-donor KT cohort.Methods103 donor/recipient pairs transplanted at the University of Leipzig Medical Center between 1998 and 2018 were re-typed using next generation sequencing (NGS) of the HLA loci -A, -B, -C, -DRB1, -DRB345, -DQA1, -DQB1, -DPA1, and -DPB1. Based on these data, we compiled HLA MM counts for each pair and comparatively evaluated genomic HLA-typing with pre-transplant obtained serological/low-resolution HLA (=one-field) typing results. NGS HLA typing (=two-field) data was further used for reclassification of de novo HLA antibodies as “donor-specific”.ResultsBy two-field HLA re-typing, we were able to identify additional MM in 64.1% (n=66) of cases for HLA loci -A, -B, -C, -DRB1 and -DQB1 that were not observed by one-field HLA typing. In patients with biopsy proven ABMR, two-field calculated MM count was significantly higher than by one-field HLA typing. For additional typed HLA loci -DRB345, -DQA1, -DPA1, and -DPB1 we observed 2, 26, 3, and 23 MM, respectively. In total, 37.3% (69/185) of de novo donor specific antibodies (DSA) formation was directed against these loci (DRB345 ➔ n=33, DQA1 ➔ n=33, DPA1 ➔ n=1, DPB1 ➔ n=10).ConclusionOur results indicate that two-field HLA typing is feasible and provides significantly more sensitive HLA MM recognition in living-donor KT. Furthermore, accurate HLA typing plays an important role in graft management as it can improve discrimination between donor and non-donor HLA directed cellular and humoral alloreactivity in the long range. The inclusion of additional HLA loci against which antibodies can be readily detected, HLA-DRB345, -DQA1, -DQB1, -DPA1, and -DPB1, will allow a more precise virtual crossmatch and better prediction of potential DSA. Furthermore, in living KT, two-field HLA typing could contribute to the selection of the immunologically most suitable donors.
Bioinformatics analysis and consistency verification of a novel tuberculosis vaccine candidate HP13138PB
Authors: Cheng Peng , Jiang Fan , Wang Guiyuan , Wang Jie , Xue Yong , Wang Liang , Gong Wenping 
Published: January 2023

BackgroundWith the increasing incidence of tuberculosis (TB) and the shortcomings of existing TB vaccines to prevent TB in adults, new TB vaccines need to be developed to address the complex TB epidemic.MethodThe dominant epitopes were screened from antigens to construct a novel epitope vaccine termed HP13138PB. The immune properties, structure, and function of HP13138PB were predicted and analyzed with bioinformatics and immunoinformatics. Then, the immune responses induced by the HP13138PB were confirmed by enzyme-linked immunospot assay (ELISPOT) and Th1/Th2/Th17 multi-cytokine detection kit.ResultThe HP13138PB vaccine consisted of 13 helper T lymphocytes (HTL) epitopes, 13 cytotoxic T lymphocytes (CTL) epitopes, and 8 B-cell epitopes. It was found that the antigenicity, immunogenicity, and solubility index of the HP13138PB vaccine were 0.87, 2.79, and 0.55, respectively. The secondary structure prediction indicated that the HP13138PB vaccine had 31% of α-helix, 11% of β-strand, and 56% of coil. The tertiary structure analysis suggested that the Z-score and the Favored region of the HP13138PB vaccine were -4.47 88.22%, respectively. Furthermore, the binding energies of the HP13138PB to toll-like receptor 2 (TLR2) was -1224.7 kcal/mol. The immunoinformatics and real-world experiments showed that the HP13138PB vaccine could induce an innate and adaptive immune response characterized by significantly higher levels of cytokines such as interferon-gamma (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin-4 (IL-4), and IL-10.ConclusionThe HP13138PB is a potential vaccine candidate to prevent TB, and this study preliminarily evaluated the ability of the HP13138PB to generate an immune response, providing a precursor target for developing TB vaccines.
Machine learning of flow cytometry data reveals the delayed innate immune responses correlate with the severity of COVID-19
Authors: Zhu Jing , Chen Tunan , Mao Xueying , Fang Yitian , Sun Heqi , Wei Dong-Qing , Ji Guangfu 
Published: January 2023

IntroductionThe COVID-19 pandemic has posed a major burden on healthcare and economic systems across the globe for over 3 years. Even though vaccines are available, the pathogenesis is still unclear. Multiple studies have indicated heterogeneity of immune responses to SARS-CoV-2, and potentially distinct patient immune types that might be related to disease features. However, those conclusions are mainly inferred by comparing the differences of pathological features between moderate and severe patients, some immunological features may be subjectively overlooked.MethodsIn this study, the relevance scores(RS), reflecting which features play a more critical role in the decision-making process, between immunological features and the COVID-19 severity are objectively calculated through neural network, where the input features include the immune cell counts and the activation marker concentrations of particular cell, and these quantified characteristic data are robustly generated by processing flow cytometry data sets containing the peripheral blood information of COVID-19 patients through PhenoGraph algorithm.ResultsSpecifically, the RS between immune cell counts and COVID-19 severity with time indicated that the innate immune responses in severe patients are delayed at the early stage, and the continuous decrease of classical monocytes in peripherial blood is significantly associated with the severity of disease. The RS between activation marker concentrations and COVID-19 severity suggested that the down-regulation of IFN-γ in classical monocytes, Treg, CD8 T cells, and the not down-regulation of IL_17a in classical monocytes, Tregs are highly correlated with the occurrence of severe disease. Finally, a concise dynamic model of immune responses in COVID-19 patients was generalized.DiscussionThese results suggest that the delayed innate immune responses in the early stage, and the abnormal expression of IL-17a and IFN-γ in classical monocytes, Tregs, and CD8 T cells are primarily responsible for the severity of COVID-19.
Impact of blue economy sectors using causality, correlation and panel data models
Authors: Martínez-Vázquez Rosa María , Milán-García Juan , Pires Manso Jose Ramos , De Pablo Valenciano Jaime 
Published: January 2023

IntroductionBlue economics research is a research field that is achieving more and more interest among international scientists. This study adds more knowledge as it aims to investigate the causal relationships between blue economic factors – living and non-living resources, ocean energy, port activities, shipbuilding and repair, maritime transport, coastal tourism, human development indicator, per capita income, fish capture, internal renewable water resources per capita, marine protected areas, greenhouse gas emissions and population density, all factors related to maritime activities – and the blue economy (BE) itself.MethodsIn order to reach these objectives, some special analytical and econometric methods are used. Among them the multivariate Granger causality theory, the correlation analysis and panel data techniques are employed. This set of methods helps us to study the complex set of relationships among the various factors related to the BE and their influence on per capita income (PCI) and economic growth. The data used to conduct this research were collected from the Eurostat, the E.U. statistical database. Several European countries and the span period 2010-2018 are used too.ResultsThe analysis showed evidence that per capita income is associated to other factors of the blue economy, that PCI (Granger) causes coastal tourism and population density, and that there are five other factors that positively influence PCI growth, namely, greenhouse gas emissions (GHG), maritime transport, nonliving resources and ports’ activities. This paper adds some new understandings to theory and calls the attention to society, in general, and the blue economics, in particular. For instance, if policymakers want to increase income per capita of these regions, they should take action on some variables such as human development indicator (HDI), greenhouse gas (GHG) emissions, living resources, maritime transport and ocean energy. The results reveal that blue economy is a good alternative to promote both economic growth and PCI.DiscussionThe concerns that make up the blue economy, such as ocean energy, port activities, ship building and repair, maritime transport, coastal tourism, HDI, maritime fish capture, marine protected areas, and GHG reductionare good factors to stimulate economic growth. Among these, the most influencing are maritime transport, living resources and the production of ocean energy. This study adds knowledge to theory, innovates in the methods and techniques used, in the results discovered, in its discussion, and in the mixture of blue economic factors, too. As far as we know, it is one of the first papers that fills this gap in the literature regarding the more and more important blue economy.
The development and validation of screening tools for semi-automated surveillance of surgical site infection following various surgeries
Authors: Shitrit Pnina , Chowers Michal Y. , Muhsen Khitam 
Published: January 2023

BackgroundSurveillance of surgical site infections (SSIs) is essential for better prevention. We developed a screening method for SSIs in adults.MethodsThe training dataset included data from patients who underwent orthopedic surgeries (N = 1,090), colorectal surgeries (N = 817), and abdominal hysterectomies (N = 523) during 2015–2018. The gold standard for the validation of the screening tool was the presence of SSI as determined by a trained infection control practitioner, via manual full medical record review, using the US Center for Disease Control and Prevention criteria. Using multivariable regression models, we identified the correlates of SSI. Patients who had at least one of these correlates were classified as likely to having SSI and those who did not have any of the correlates were classified as unlikely to have SSI. We calculated the sensitivity and specificity of this tool compared to the gold standard and applied the tool to a validation dataset (N = 1,310, years 2019–2020).ResultsSSI was diagnosed by an infection control specialist in 8.2, 5.2, and 31.2% of the patients in the training dataset who underwent hysterectomies, orthopedic surgeries and colorectal surgeries, respectively, vs. 6.2, 6.6, and 25.5%, respectively, in the validation dataset. The correlates of SSI after abdominal hysterectomy were prolonged hospitalization, ordering wound or blood culture, emergency room visit and reoperation; in orthopedic surgery, emergency room visit, wound culture, reoperation, and documentation of SSI, and in colorectal surgeries prolonged hospitalization, readmission, and ordering wound or blood cultures. Area under the curve was &gt;90%. The sensitivity and specificity (95% CI) of the screening tool were 98% (88–100) and 58% (53–62), for abdominal hysterectomy, 91% (81–96) and 82% (80–84) in orthopedic surgeries and 96% (90–98) and 62% (58–66) in colorectal surgeries. The corresponding values for the validation dataset were 89% (67–97) and 75% (69–80) in abdominal hysterectomy; 85% (72–93) and 83% (80–86) in orthopedic surgeries and 98% (93–99) and 59% (53–64) in colorectal surgeries. The number of files needed to be fully reviewed declined by 61–66.ConclusionThe presented semi–automated simple screening tool for SSI surveillance had good sensitivity and specificity and it has great potential of reducing workload and improving SSI surveillance.
Proteolysis modification targeting protein corona affects ultrasound-induced membrane homeostasis of saccharomyces cerevisiae: Analysis of lipid relative contributions on membrane properties
Authors: Zheng Zi-Yi , Xie Guo , Tan Gui-Liang , Liu Wen-Li 
Published: January 2023

IntroductionProtein corona (PCN) adsorbed on the surface of nanoparticles has brought new research perspectives for the interaction between nanoparticles and microorganisms. In this study, the responses of saccharomyces cerevisiae’ membrane lipid composition, the average length of the fatty acyl chains and the average number of unsaturation of fatty acids to ultrasound combined with nano-Fe3O4@PCN with time-limited proteolysis (nano-Fe3O4@TLP-PCN) was investigated.MethodsLipidomic data was obtained using Ultra-high performance liquid chromatography coupled with a Q-Exactive plus mass spectrometer. The membrane potential, proton motive force assay and the membrane lipid oxidation were measured using Di-BAC4(3), DISC3(5) and C11-BODIPY581/591 as the probes. Combined with the approach of feasible virtual samples generation, the back propagation artificial neural network (BP-ANN) model was adopted to establish the mapping relationship between lipids and membrane properties.ResultsThe time-limited proteolysis targeting wheat PCN-coated Fe3O4 nanoparticles resulted in regular changes of hydrodynamic diameters, ζ-potentials, and surface hydrophobicity. In addition, with the prolongation of PCN proteolysis time, disturbances of 3 S.cerevisiae membrane characteristics, and membrane lipidomic remodeling in response to ultrasound+ nano-Fe3O4@PCN were observed. The analysis of relative importance which followed revealed that ergosterol, phosphatidylserine, and phosphatidylinositol phosphate had the greatest influence on membrane potential. For membrane lipid oxidation, ceramide, phosphatidylethanolamine, and sitosterol ester contribute 16.2, 14.9, and 13.1%, respectively. The relative contributions of six lysolecithins to the dissipation of proton motive force remained limited.DiscussionAn adaptation mechanism of cell membrane to proteolyzed PCN, wherein lipidome remodeling could preserved functional membrane phenotypes was revealed. Furthermore, it is highlighted that the relative importances of SiE, Cer, PE and PIP in determining membrane potential, PMF dissipation and membrane lipid oxidation by establishing FVSG-BP-ANN model.
Soil bacterial community response to continuous cropping of cotton
Authors: Ma Zheng , Li Peng , Yang Chuanzhen , Feng Zili , Feng Hongjie , Zhang Yalin , Zhao Lihong , Zhou Jinglong , Zhu Heqin , Wei Feng 
Published: January 2023

IntroductionLong-term continuous cropping may result in the outbreak and proliferation of soil-borne diseases, as well as reduction in annual crop production. Overcoming the obstacles of continuous cropping is critical for the long-term growth of modern agriculture. Soil microbes are essential for plant health, but the consequences of continuous cropping on soil microbiome are still poorly understood.MethodsThis study analyzed changes in soil bacterial community composition of Aksu (AKS) and Shihezi (SHZ) in Xinjiang Province during 1–20  years of continuous cropping by 16S amplicon sequencing. The results showed that the incidence of cotton Verticillium wilt rose with the number of cropping years. The bacterial alpha diversity in the AKS soil grew as the number of continuous cropping years increased, however it declined in the SHZ soil.ResultsThe results of beta diversity analysis showed that there were significant differences in soil bacterial communities between different continuous cropping years and between different soils. The results of community composition changes at the level of main phyla and genus showed that the relative abundance of Actinobacteria, Bacteroidetes and Streptomyces decreased with the increase of continuous cropping years in the AKS and the SHZ soils. In addition, Actinobacteria, Propionibacteriales, and Nocardioidaceae were significantly enriched during the early stages of continuous cropping. Network analysis showed that long-term (≥8  years) continuous cropping interfered with the complexity of soil bacterial co-occurrence networks and reduced collaboration between OTUs.DiscussionThese findings suggested that continuous cropping and soil origin jointly affected the diversity and structural of bacterial communities, and the loss of Nocardioidaceae and Streptomyces in Actinobacteria might be one of the reasons of continuous cropping obstacles.