bluuebunny/crossref_metadata_2025_split huggingface dataset:
Soluble programmed cell death-ligand 1 as a new potential biomarker associated with acute coronary syndrome
Authors: Li Shuping , Yi Ling , Wei Xiqing , Zhang Jinguo , Wang Xiaojue , Jiang Chang , Yan Zhuohong , Song Liwei , Yang Bin , Wei Panjian , Gao Xiang , Wang Jinghui , Zhang Hongtao , Zhang Jian 
Published: September 2022

BackgroundSoluble programmed cell death-ligand 1 (sPD-L1) has been well documented to activate immunosuppression and is considered an essential predictor of negative clinical outcomes for several malignances and inflammatory conditions. However, the clinical significance of sPD-L1 in the peripheral blood of patients with coronary artery disease (CAD) remains unclear. The aim of this study was to assess the correlations of sPD-L1 with clinical features in CAD patients and evaluate the diagnostic value of this protein in CAD.MethodsA total of 111 CAD patients and 97 healthy volunteers who served as healthy controls (HCs) were consecutively enrolled. Plasma levels of sPD-L1 were measured with an amplified enzyme-linked immunosorbent assay (ELISA), and hs-CRP was measured with a C-reactive protein assay kit. The levels of other inflammatory cytokines were assessed in 88 CAD patients and 47 HCs by a multiparameter immunoluminescence flow cytometry detection technique. A logistic regression model was used to assess the independent association of sPD-L1 with acute coronary syndrome (ACS). The correlation between sPD-L1 and inflammatory cytokines in ACS was also assessed.ResultsPlasma levels of sPD-L1 were significantly increased in CAD patients, especially those with ACS. Univariate logistic regression analysis revealed that sPD-L1 (OR: 3.382, 95% CI: 2.249–5.084,p&lt; 0.001), BMI, hypertension, diabetes, dyslipidemia, previous MI, and the levels of HDL-C, LDL-C and hs-CRP were significantly associated with ACS. sPD-L1 (OR: 3.336, 95% CI: 1.084–6.167,p= 0.001) was found to be independently and significantly associated with ACS in the subsequent multivariable logistic regression analysis. Additionally, elevated plasma sPD-L1 levels were associated with increased interleukin-6 and interleukin-8 levels in ACS patients. Receiver operating characteristic (ROC) analysis showed that the AUC of sPD-L1 for diagnosing ACS was 0.778, with a sensitivity of 73.9% and a specificity of 73.4%, which was comparable with that of the inflammatory biomarker hs-CRP.ConclusionThe plasma sPD-L1 level reflects the severity of CAD, is associated with inflammatory responses and is a potential new biomarker for the diagnosis of ACS.
Provenance of the lower jurassic quartz-rich conglomerate in northwestern sichuan basin and its link with the pre-collisional unroofing history of the north longmen shan thrust belt, NE tibetan plateau margin
Authors: Lv Fan , Ran Bo , Liu Shugen , Wang Zijian , Sun Tong , Li Xianghui , Han Yuyue , Liang Ke 
Published: September 2022

The research on the pre-collisional tectonic evolution of basin-mountain system at the margin of Tibetan plateau provides insights into the upward and outward growth mechanism of the plateau in the Cenozoic. Lower Jurassic Baitianba Formation quartz-rich conglomerate exposed along the edge of the northwest Sichuan Basin whereas these deposits were incompatible with peripheral carbonatite-dominated orogenic belts, which aroused our great interest. To better understand the origin of quartz-rich conglomerate and early erosional unroofing history of northeastern Tibetan Plateau margin, this study focuses on sandstone petrography analysis along with U-Pb age dating of the detrital zircons of Baitianba Formation gravel and sandstone sample from northwestern Sichuan Basin, which is located to north Longmen Shan thrust belt. In the distinctive Lower Jurassic quartz gravel samples, there are at least two distinct provenance sources. One is characterized by a unimodal age population at ca. 400–1,000 Ma but the absence of younger detrital zircons (&lt;395 Ma), resembling the Early Paleozoic marine quartz sandstone due to the uplift and erosion of the Paleozoic basement of the Longmen Shan thrust belt. The other yield age clusters of ca. 1.8 Ga, 950–750 Ma, 450–420 Ma, 280–240 Ma, which is identical to the detrital zircons from the Upper Triassic strata. Furtherly, detrital zircon dating of our sandstone samples also exhibit strong similarity to the Upper Triassic strata detrital record. Detrital zircons linked with the sedimentological data show these quartz-rich conglomerate mainly recycled from the underlying Upper Triassic through long-term weathering.
Identifying key genes of classic papillary thyroid cancer in women aged more than 55 years old using bioinformatics analysis
Authors: Li Chang-Chun , Ullah Muhammad Hasnain Ehsan , Lin Xiao , Shan Su-Kang , Guo Bei , Zheng Ming-Hui , Wang Yi , Li Fuxingzi , Yuan Ling-Qing 
Published: September 2022

BackgroundThe incidence rate of thyroid carcinoma (THCA) markedly increased in the recent few decades and has been likely over-diagnosed, especially papillary thyroid cancer (PTC) in women. However, the incidence of advanced-stage papillary thyroid cancer is also rising. According to earlier studies, tumors with identical pathology might have different clinical outcomes, which implies some variances in papillary thyroid cancer. Although the mortality of thyroid cancer has remained stable or declined, there is still an important problem in estimating whether it is benign or needs surgery for patients with papillary thyroid cancer.MethodsAfter obtaining data from The Cancer Genome Atlas (TCGA) Project-THCA database by R package TCGA bio links, 18 samples (11 at stage IV as high-risk group and 7 at stage I as low-risk group) were obtained using survival package and edgeR to ensure differential expression; ClusterProfiler package was used to carry on gene set enrichment analysis and searched the possible pathways in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. STRING and Cytoscape were used to construct and modify the protein–protein interaction (PPI) network to get hub genes of differentially expressed genes. Next, the pROC package was used to get the receiver operating characteristic (ROC) curves of hub genes’ disease-free survival (DFS). Then, transcription factors (TFs) and miRNAs of key genes were predicted by ENCORI and AnimalTFDB. In the end, TF–target genes–miRNA regulatory network was also constructed by Cytoscape.ResultsOur research obtained the top 9 candidate genes from the whole network (IFNA1, MRC1, LGALS3, LOX, POSTN, TIMP1, CD276, SDC4, and TLR2). According to the ROC results, TIMP1, LOX, CD276, IFNA1, TLR2, and POSTN were considered to play a more critical role in malignant papillary thyroid cancer or immature cancer of papillary thyroid cancer. Our analysis concludes that TIMP1, LOX, CD276, IFNA1, TLR2, and POSTN are identified as thyroid cancer biomarkers, which lead to the different clinical courses of a woman older than 55 years old with papillary thyroid cancer. Especially CD276, POSTN, and IFNA1 may be considered as new biomarkers associated with the prognosis of thyroid cancer.ConclusionsTIMP1, LOX, CD276, IFNA1, TLR2, and POSTN have different expressions in PTCs, which lead to the various clinical courses of a woman older than 55 years old with papillary thyroid cancer. Especially CD276, POSTN, and IFNA1 may be considered as new potential biomarkers associated with the prognosis of thyroid cancer. In addition, TF–miRNA–target gene regulatory network may help further reach for PTC.
Soil column experiment and numerical simulation research of Pb migration process in the groundwater fluctuation zone based on HYDRUS
Authors: Qu Jihong , Jiang Jueyan , Zhang Yifeng , Li Yuepeng , Yan Tiangang , Guo Wei , Lu Shibao 
Published: September 2022

Groundwater level fluctuation alters hydrodynamic conditions and hydrogeochemical action, thus affecting the migration and transformation of pollutants. This study investigated the effect of groundwater level fluctuations on Pb migration processes. We selected two typical media, coarse sand and medium sand, for the soil column experiments and numerical simulations of the Pb migration process in the groundwater level fluctuation zone. The soil column experiments showed that when the contaminants were distributed at a 30–40 cm depth in the soil column, the Pb migrated into the water in the range of 20–45 cm in coarse sand, while the range of Pb migration in medium sand decreased to 30 cm–40 cm. We constructed a numerical model of Pb migration in the aeration zone–saturation zone coupled with water transport and solute transport by HYDRUS-1D. The model simulated the migration process of Pb in different amplitude and frequency of water level fluctuation and initial concentration of pollutants. The results showed that the coarse sand column and medium sand column showed relatively noticeable changes in Pb concentration in water at 30–40 cm and 30–35 cm, respectively. The migration range and concentration of Pb in water are proportional to the medium particle size and the frequency of water level fluctuation, and inversely proportional to the magnitude of water level fluctuation. The Pb concentration in the water increased or decreased as the initial pollutant concentration of the medium increased or decreased. Its variation is basically the same as the variation of the initial contaminant concentration. The research results can provide a scientific basis for the remediation of heavy metal pollution in groundwater.
Signature based on RNA-binding protein-related genes for predicting prognosis and guiding therapy in non-small cell lung cancer
Authors: Miao Ti-Wei , Chen Fang-Ying , Du Long-Yi , Xiao Wei , Fu Juan-Juan 
Published: September 2022

Background: Studies have reported that RNA-binding proteins (RBPs) are dysregulated in multiple cancers and are correlated with the progression and prognosis of disease. However, the functions of RBPs in non-small cell lung cancer (NSCLC) remain unclear. The present study aimed to explore the function of RBPs in NSCLC and their prognostic and therapeutic value.Methods: The mRNA expression profiles, DNA methylation data, gene mutation data, copy number variation data, and corresponding clinical information on NSCLC were downloaded from The Cancer Genome Atlas, Gene Expression Omnibus, and the University of California Santa Cruz Xena databases. The differentially expressed RBPs were identified between tumor and control tissues, and the expression and prognostic value of these RBPs were systemically investigated by bioinformatics analysis. A quantitative polymerase chain reaction (qPCR) was performed to validate the dysregulated genes in the prognostic signature.Results: A prognostic RBP-related signature was successfully constructed based on eight RBPs represented as a risk score using least absolute shrinkage and selection operator (LASSO) regression analysis. The high-risk group had a worse overall survival (OS) probability than the low-risk group (p &lt; 0.001) with 1-, 3-, and 5-year area under the receiver operator characteristic curve values of 0.671, 0.638, and 0.637, respectively. The risk score was associated with the stage of disease (p &lt; 0.05) and was an independent prognostic factor for NSCLC when adjusted for age and UICC stage (p &lt; 0.001, hazard ratio (HR): 1.888). The constructed nomogram showed a good predictive value. The P53, focal adhesion, and NOD-like receptor signaling pathways were the primary pathways in the high-risk group (adjusted p value &lt;0.05). The high-risk group was correlated with increased immune infiltration (p &lt; 0.05), upregulated relative expression levels of programmed cell death 1 (PD1) (p = 0.015), cytotoxic T-lymphocyte-associated protein 4 (CTLA4) (p = 0.042), higher gene mutation frequency, higher tumor mutational burden (p = 0.034), and better chemotherapy response (p &lt; 0.001). The signature was successfully validated using the GSE26939, GSE31210, GSE30219, and GSE157009 datasets. Dysregulation of these genes in patients with NSCLC was confirmed using the qPCR in an independent cohort (p &lt; 0.05).Conclusion: An RBP-related signature was successfully constructed to predict prognosis in NSCLC, functioning as a reference for individualized therapy, including immunotherapy and chemotherapy.
T cell proliferation-related genes: Predicting prognosis, identifying the cold and hot tumors, and guiding treatment in clear cell renal cell carcinoma
Authors: Huang Haoran , Cai Yanmin , Hong Xitao , Gao Wenzong , Tang Jun , Zhang Shujuan , Xu Zhe 
Published: September 2022

Background: Immunotherapy has become a new direction of current research because the effect of traditional radiotherapy and chemotherapy on clear cell renal cell carcinoma (ccRCC) is not satisfactory. T cell proliferation-related genes (TRGs) play a pivotal role in tumor progression by regulating the proliferation, activity, and function of immune cells. The purpose of our study is to construct and verify a prognostic model based on TRGs and to identify tumor subtypes that may guide treatment through comprehensive bioinformatics analyses.Methods: RNA sequencing data, clinical information, and somatic mutation data of ccRCC are obtained from The Cancer Genome Atlas (TCGA) database. We identified the prognosis-related TRGs which were differentially expressed between normal and tumor tissues. After dividing the patients into a train set and a test set according to proportion 1:1 randomly, the least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analysis were performed to construct a risk-stratified model. Its prediction performance was verified. Then, Gene Set Enrichment Analysis (GSEA), principal component analysis (PCA), tumor microenvironment (TME) analysis, and the half-maximal inhibitory concentration (IC50) prediction were performed between the different groups of patients. To further discuss the immunotherapy between hot and cold tumors, we divided all patients into two clusters based on TRGs through unsupervised learning. Analyzing the gene mutation and calculating the tumor mutation burden (TMB), we further explored the relationship between somatic mutations and grouping or clustering.Results: Risk-stratified model and nomogram predict the prognosis of ccRCC patients accurately. Functional enrichment analyses suggested that TRGs mainly focused on the biological pathways related to tumor progression and immune response. Different tumor microenvironment, drug resistance, and TMB can be distinguished clearly according to both risk stratification and tumor subtype clustering.Conclusion: In this study, a new stratification model of ccRCC based on TRGs was established, which can accurately predict the prognosis of patients. IC50 prediction may guide the application of anti-tumor drugs. The distinction between hot and cold tumors provides a reference for clinical immunotherapy.
Disruption of cellular immune response among male rotating night shift workers in Spain– The HORMONIT study
Authors: Harding Barbara N. , Aguilar Ruth , Espinosa Ana , Castaño-Vinyals Gemma , Papantoniou Kyriaki , Navarrete José Maria , Such Faro Patricia , Torrejón Antonio , Dobaño Carlota , Moncunill Gemma , Kogevinas Manolis 
Published: September 2022

IntroductionPreliminary studies suggest that night shift work is associated with a desynchronization of rhythmic immune markers, possibly explaining the increased risk of infection, cardiometabolic disorders, and cancer in shift workers.MethodsThis study included 51 male rotating shift workers from a car industry in Barcelona, Spain, sampled twice toward the end of a 3-week night shift (22:00-06:00 h) and a 3-week day shift (06:00-14:00 h) rotation. We collected four blood samples per worker, at the start and end of each shift. We measured 27 cytokines, chemokines and growth factors in plasma samples by luminex using the Cytokine Human Magnetic 30-Plex Panel LHC6003M and applied linear mixed models to examine within-person associations between shift work and analytes’ concentrations, comparing samples taken at 06:00 h on a day and night shift. We also conducted a factor analysis using analyte concentrations from all 4 time points for each individual to identify common factors and determine if these factors were altered by shift work.ResultsWe observed lower levels of 15 analytes in the night shift compared to the day shift including cytokines (pro-inflammatory TNF-α, IL-2R; anti-inflammatory IL1-RA; Th1 IL-2, Th2 IL-4 and Th17 Il-17), chemokines (IP-10, MIP-1α, MIP-1β, RANTES) and growth factors (EGF, G-CSF, HGF, VEGF, FGF). In a factor analysis, three factors were identified. The main factor (Factor 1), explaining 57% of the variance and including IL-1β, IL-12, IL-15, MIP-1α, MIP-1β, EGF and FGF; and another factor (Factor 3) explaining 10% of the variance and including the Th1 cytokine IL-12, were inversely associated with the night shift (coefficient: -0.17, 95%CI -0.32 to -0.01 and coefficient: -0.22, 95%CI -0.38, -0.06, for Factors 1 and 3, respectively). Our results indicate that night shift disrupts the levels of several immune markers, which could contribute to the increased risk of infections and cancer reported in night shift workers.ConclusionNight shift is associated with disruption of multiple immune response pathways.
SARS-CoV-2 vaccination in androgen sensitive phenotypes – A study on associated factors for SARS-CoV-2 vaccination and its adverse effects among androgenetic alopecia and benign prostate hyperplasia patients
Authors: Fan Zhihua , Duan Shixin , Liu Fangfen , Shi Wei , Yang Ziye , Bai Ruiyang , Li Tao , Chen Jingxian , Xie Hongfu , Li Ji , Tang Yan 
Published: September 2022

BackgroundAndrogen sensitivity, which was established as the leading etiology of androgenetic alopecia (AGA) and benign prostatic hyperplasia (BPH), plays an important role in SARS-CoV-2 infection. Vaccination is essential for AGA and BPH patients in view of the high risk from SARS-CoV-2 infection.PurposeWe aimed to investigate the associated factors for SARS-CoV-2 vaccination and its side effects in populations with AGA and BPH.MethodWe collected the data on SARS-CoV-2 vaccination and adverse reactions of male AGA and BPH patients visited the outpatient of Xiangya hospital by telephone and web-based questionnaires. Vaccination rate and adverse reactions were compared by different vaccine types and use of anti-androgen therapy.ResultA total of 457 AGA patients and 397 BPH patients were recruited in this study. Among which, 92.8% AGA patients and 61.0% BPH patients had at least the first dose of SARS-CoV-2 vaccination (p &lt; 0.001). Having comorbidities and use of anti-androgen therapy increased the risk of un-vaccination among AGA by 2.875 and 3.729 times, respectively (p &lt; 0.001). Around 31.1% AGA patients and 9.5% BPH patients presented adverse reactions, which were mostly mild. Anti-androgen therapy increased the inclination of injection site pain after vaccination (18.7% vs 11.9%; OR: 1.708, 95% CI: 1.088-2.683, p = 0.019).ConclusionCo-existence of other systemic diseases and anti-androgen therapy were the limiting factors for SARS-CoV-2 unvaccination, especially in AGA patients. The importance of SARS-CoV-2 vaccines should be strengthened and popularized in androgen sensitive phenotypes.
Host inflammatory response is the major factor in the progression of Chlamydia psittaci pneumonia
Authors: Zhang Zhenjie , Wang Peihan , Ma Chuanmin , Wang Jing , Li Wenxin , Quan Chuansong , Cao Huae , Guo Hongfeng , Wang Liang , Yan Chengxin , Carr Michael J. , Meng Ling , Shi Weifeng 
Published: September 2022

PurposeChlamydia psittaci(C. psittaci) has caused sporadic, but recurring, fatal community-acquired pneumonia outbreaks worldwide, posing a serious threat to public health. Our understanding of host inflammatory responses toC. psittaciis limited, and many bronchitis cases of psittaci have rapidly progressed to pneumonia with deterioration.MethodsTo clarify the host inflammatory response in psittacosis, we analyzed clinical parameters, and compared transcriptomic data, concentrations of plasma cytokines/chemokines, and changes of immune cell populations in 17 laboratory-confirmed psittacosis cases, namely, 8 pneumonia and 9 bronchitis individuals, in order to assess transcriptomic profiles and pro-inflammatory responses.ResultsPsittacosis cases with pneumonia were found to have abnormal routine blood indices, liver damage, and unilateral pulmonary high-attenuation consolidation. Transcriptome sequencing revealed markedly elevated expression of several pro-inflammatory genes, especially interleukins and chemokines. A multiplex-biometric immunoassay showed that pneumonia cases had higher levels of serum cytokines (G-CSF, IL-2, IL-6, IL-10, IL-18, IP-10, MCP-3, and TNF-α) than bronchitis cases. Increases in activated neutrophils and decreases in the number of lymphocytes were also observed in pneumonia cases.ConclusionWe identified a number of plasma biomarkers distinct toC. psittacipneumonia and a variety of cytokines elevated with immunopathogenic potential likely inducing an inflammatory milieu and acceleration of the disease progression of psittaci pneumonia. This enhances our understanding of inflammatory responses and changes in vascular endothelial markers in psittacosis with heterogeneous symptoms and should prove helpful for developing both preventative and therapeutic strategies.
The influence of antibody humanization on shark variable domain (VNAR) binding site ensembles
Authors: Fernández-Quintero Monica L. , Fischer Anna-Lena M. , Kokot Janik , Waibl Franz , Seidler Clarissa A. , Liedl Klaus R. 
Published: September 2022

Sharks and other cartilaginous fish produce new antigen receptor (IgNAR) antibodies, as key part of their humoral immune response and are the phylogenetically oldest living organisms that possess an immunoglobulin (Ig)-based adaptive immune system. IgNAR antibodies are naturally occurring heavy-chain-only antibodies, that recognize antigens with their single domain variable regions (VNARs). In this study, we structurally and biophysically elucidate the effect of antibody humanization of a previously published spiny dogfish VNAR (parent E06), which binds with high affinity to the human serum albumin (HSA). We analyze different humanization variants together with the parental E06 VNAR and the human Vκ1 light chain germline DPK9 antibody to characterize the influence of point mutations in the framework and the antigen binding site on the specificity of VNARs as reported by Kovalenko et al. We find substantially higher flexibility in the humanized variants, reflected in a broader conformational space and a higher conformational entropy, as well as population shifts of the dominant binding site ensembles in solution. A further variant, in which some mutations are reverted, largely restores the conformational stability and the dominant binding minimum of the parent E06. We also identify differences in surface hydrophobicity between the human Vκ1 light chain germline DPK9 antibody, the parent VNAR E06 and the humanized variants. Additional simulations of VNAR-HSA complexes of the parent E06 VNAR and a humanized variant reveal that the parent VNAR features a substantially stronger network of stabilizing interactions. Thus, we conclude that a structural and dynamic understanding of the VNAR binding site upon humanization is a key aspect in antibody humanization.