bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptome analysis reveals pathogenesis-related gene 1 pathway against salicylic acid treatment in grapevine (Vitis vinifera L)
Authors: Rahman Faiz Ur , Khan Irshad Ahmad , Aslam Ali , Liu Ruitao , Sun Lei , Wu Yandi , Aslam Muhammad Muzammal , Khan Asad Ullah , Li Peng , Jiang Jianfu , Fan Xiucai , Liu Chonghuai , Zhang Ying 
Published: October 2022

Salicylic acid (SA) is a well-studied phenolic plant hormone that plays an important role in plant defense against the hemi-biothrophic and biothrophic pathogens and depends on the living cells of host for the successful infection. In this study, a pathogenesis test was performed betweenVitis davidiiandV. viniferacultivars against grape white rot disease (Coniella diplodiella).V. davidiiwas found to be resistant against this disease. SA contents were found to be higher in the resistant grape cultivar after different time points. RNA-seq analysis was conducted on susceptible grapevine cultivars after 12, 24, and 48 h of SA application with the hypothesis that SA may induce defense genes in susceptible cultivars. A total of 511 differentially expressed genes (DEGs) were identified from the RNA-seq data, including some important genes,VvWRKY1/2, VvNPR1,VvTGA2, andVvPR1,for the SA defense pathway. DEGs related to phytohormone signal transduction and flavonoid biosynthetic pathways were also upregulated. The quantitative real-time PCR (qRT-PCR) results of the significantly expressed transcripts were found to be consistent with the transcriptome data, with a high correlation between the two analyses. The pathogenesis-related gene 1 (VvPR1), which is an important marker gene for plant defense, was selected for further promoter analysis. The promoter sequence showed that it contains some important cis-elements (W-box, LS7, as-1, and TCA-element) to recruit the transcription factorsVvWRKY, VvNPR1, andVvTGA2to express theVvPR1gene in response to SA treatment. Furthermore, theVvPR1promoter was serially deleted into different fragments (−1,837, −1,443, −1,119, −864, −558, −436, and −192 ) bp and constructed vectors with the GUS reporter gene. Deletion analysis revealed that theVvPR1promoter between −1837 bp to −558 bp induced significant GUS expression with respect to the control. On the basis of these results, the −558 bp region was assumed to be an important part of theVvPR1promoter, and this region contained the important cis-elements related to SA, such as TCA-element (−1,472 bp), LS7 (−1,428 bp), andas-1(−520 bp), that recruit the TFs and induce the expression of theVvPR1gene. This study expanded the available information regarding SA-induced defense in susceptible grapes and recognized the molecular mechanisms through which this defense might be mediated.
Immunophenotyping of pulmonary sarcomatoid carcinoma
Authors: Ma Yu , Li Wensheng , Li Zhenzhen , Chen Jie , Wang Hongtao , Jiang Tao , Zhu Jianfei 
Published: October 2022

BackgroundPrevious studies have suggested that patients with pulmonary sarcomatoid carcinoma (PSC)may benefit from immune checkpoint inhibitors (ICIs); however, relevant data are lacking. This study aimed to establish the immunophenotype of PSC by assessing PD-L1 and CD8+ T-cell infiltration.MethodsA retrospective analysis of pathologically confirmed PSC cases from two centers was performed from January 2009 to May 2021. According to the infiltration of CD8+ T cells in different spatial regions, patients were classified into three types: immune-inflamed, immune-excluded, and immune desert. PD-L1 staining was also performed on the intratumoral region and the tumor proportion score (TPS) was used for scoring. Combined with CD8+ T-cell infiltration and PD-L1 expression in the intratumoral region, immunophenotyping can be divided into four types: type I (PD-L1+/CD8+, adaptive immune resistance), type II (PD-L1-/CD8-, immunologic ignorance), type III (PD-L1+/CD8-, intrinsic induction), and type IV (PD-L1-/CD8+, tolerance). Finally, correlation analysis was performed on the immunophenotype, clinicopathological characteristics, and outcomes of the patients.ResultsA total of 32 patients with PSC were included in the final analysis. Of these patients, 65.6% (21/32), 15.6% (5/32), and 18.8% (6/32) were classified as immune-inflamed, immune-excluded, and immune-desert, respectively. Notably, the immune-inflamed type is predominantly observed in pleomorphic carcinomas (PC, 66.7%). Moreover, among these participants, 19 (59.4%) were classified as PD-L1 positive according to the TPS score. In particular, 11 (34.4%) patients had PD-L1 TPS scores &gt;50%. Next, we immunophenotyped patients with PSC based on CD8+ T cell infiltration and tumor cell PD-L1 expression (types I–IV). Type I (PD-L1+/CD8+, adaptive immune resistance) was the most prevalent subtype, accounting for 46.9% (15/32), followed by type II (PD-L1-/CD8-, immunological ignorance) (21.9%), type IV (PD-L1-/CD8+, tolerance) (18.7%), and type III (PD-L1+/CD8-, intrinsic induction) (12.5%). Finally, we performed a survival analysis and found that neither immunophenotype was a predictor of prognosis in patients with PSC. Multivariate analysis showed that pneumonectomy increased the risk of death by four times compared with lobectomy (RR: 4.1; 95% CI:1.3-12.4, P=0.014).ConclusionPatients with PSC are characterized by immune-inflamed type and type I (PD-L1+/CD8+, adaptive immune resistance), explaining the intrinsic reasons for their high response rate to immunotherapy.
Comprehensive analysis of cuproptosis-related genes and tumor microenvironment infiltration characterization in breast cancer
Authors: Song Shaoran , Zhang Miao , Xie Peiling , Wang Shuhong , Wang Yaochun 
Published: October 2022

BackgroundCuproptosis is a newly discovered programmed cell death dependent on overload copper-induced mitochondrial respiration dysregulation. The positive response to immunotherapy, one of the most important treatments for invasive breast cancer, depends on the dynamic balance between tumor cells and infiltrating lymphocytes in the tumor microenvironment (TME). However, cuproptosis-related genes (CRGs) in clinical prognosis, immune cell infiltration, and immunotherapy response remain unclear in breast cancer progression.MethodsThe expression and mutation patterns of 12 cuproptosis-related genes were systematically evaluated in the BRCA training group. Through unsupervised clustering analysis and developing a cuproptosis-related scoring system, we further explored the relationship between cuproptosis and breast cancer progression, prognosis, immune cell infiltration, and immunotherapy.ResultsWe identified two distinct CuproptosisClusters, which were correlated with the different patterns between clinicopathological features, prognosis, and immune cell infiltration. Moreover, the differences of the three cuproptosis-related gene subtypes were evaluated based on the CuproptosisCluster-related DEGs. Then, a cuproptosis-related gene signature (PGK1, SLC52A2, SEC14L2, RAD23B, SLC16A6, CCL5, and MAL2) and the scoring system were constructed to quantify the cuproptosis pattern of BRCA patients in the training cohort, and the testing cohorts validated them. Specifically, patients from the low-CRG_score group were characterized by higher immune cell infiltration, immune checkpoint expression, immune checkpoint inhibitor (ICI) scores, and greater sensitivity to immunotherapy. Finally, we screened out RAD23B as a favorable target and indicated its expression was associated with breast cancer progression, drug resistance, and poor prognosis in BRCA patients by performing real-time RT-PCR, cell viability, and IC50 assay.ConclusionsOur results confirmed the essential function of cuproptosis in regulating the progression, prognosis, immune cell infiltration, and response to breast cancer immunotherapy. Quantifying cuproptosis patterns and constructing a CRG_score could help explore the potential molecular mechanisms of cuproptosis regulating BRCA advancement and provide more effective immunotherapy and chemotherapy targets.
Chimeric immune checkpoint protein vaccines inhibit the tumorigenesis and growth of rat cholangiocarcinoma
Authors: Pan Yi-Ru , Wu Chiao-En , Huang Wen-Kuan , Chen Ming-Huang , Lan Keng-Hsueh , Yeh Chun-Nan 
Published: October 2022

Cholangiocarcinoma (CCA) is the second most common primary liver malignancy and carries a dismal prognosis due to difficulties in achieving an optimal resection, and poor response to current standard-of-care systemic therapies. We previously devised a CTLA4-PD-L1 DNA cancer vaccine (DNA vaccine) and demonstrated its therapeutic effects on reducing tumor growth in a thioacetamide (TAA)-induced rat intrahepatic CCA (iCCA) model. Here, we developed a CTLA4-PD-L1 chimeric protein vaccine (Protein vaccine), and examined its effects in the rat iCCA model. In a therapeutic setting, iCCA-bearing rats received either DNA plus Protein vaccines or Protein vaccine alone, resulting in increased PD-L1 and CTLA-4 antibody titers, and reduced iCCA tumor burden as verified by animal positron emission tomography (PET) scans. Treating iCCA-bearing rats with Protein vaccine alone led to the increase of CTAL4 antibody titers that correlated with the decrease of tumor SUV ratio, indicating regressed tumor burden, along with increased CD8 and granzyme A (GZMA) expression, and decreased PD-L1 expression on tumor cells. In a preventive setting, DNA or Protein vaccines were injected in rats before the induction of iCCA by TAA. Protein vaccines induced a more sustained PD-L1 and CTLA-4 antibody titers compared with DNA vaccines, and was more potent in preventing iCCA tumorigenesis. Correspondingly, Protein vaccines, but not DNA vaccines, downregulated PD-L1 gene expression and hindered the carcinogenesis of iCCA. Taken together, the CTLA4-PD-L1 chimeric protein vaccine may function both as a therapeutic cancer vaccine and as a preventive cancer vaccine in the TAA-induced iCCA rat model.
Identification and validation of a tyrosine metabolism-related prognostic prediction model and characterization of the tumor microenvironment infiltration in hepatocellular carcinoma
Authors: Zhou Yangying , Li Xuanxuan , Long Guo , Tao Yongguang , Zhou Ledu , Tang Jianing 
Published: October 2022

BackgroundHepatocellular carcinoma (HCC) is an aggressive and heterogeneous disease characterized by high morbidity and mortality. The liver is the vital organ that participates in tyrosine catabolism, and abnormal tyrosine metabolism could cause various diseases, including HCC. Besides, the tumor immune microenvironment is involved in carcinogenesis and can influence the patients’ clinical outcomes. However, the potential role of tyrosine metabolism pattern and immune molecular signature is poorly understood in HCC.MethodsGene expression, somatic mutations, copy number variation data, and clinicopathological information of HCC were downloaded from The Cancer Genome Atlas (TCGA) database. GSE14520 from the Gene Expression Omnibus (GEO) databases was used as a validation dataset. We performed unsupervised consensus clustering of tyrosine metabolism-related genes (TRGs) and classified patients into distinct molecular subtypes. We used ESTIMATE algorithms to evaluate the immune infiltration. We then applied LASSO Cox regression to establish the TRGs risk model and validated its predictive performance.ResultsIn this study, we first described the alterations of 42 TRGs in HCC cohorts and characterized the clinicopathological characteristics and tumor microenvironmental landscape of the two distinct subtypes. We then established a tyrosine metabolism-related scoring system and identified five TRGs, which were highly correlated with prognosis and representative of this gene set, namely METTL6, GSTZ1, ADH4, ADH1A, and LCMT1. Patients in the high-risk group had an inferior prognosis. Univariate and multivariate Cox proportional hazards regression analysis also showed that the tyrosine metabolism-related signature was an independent prognostic indicator. Besides, receiver operating characteristic curve (ROC) analysis demonstrated the predictive accuracy of the TRGs signature that could reliably predict 1-, 3-, and 5-year survival in both TCGA and GEO cohorts. We also got consistent results by performing clone formation and invasion analysis, and immunohistochemical (IHC) assays. Moreover, we also discovered that the TRGs signature was significantly associated with the different immune landscapes and therapeutic drug sensitivity.ConclusionOur comprehensive analysis revealed the potential molecular signature and clinical utilities of TRGs in HCC. The model based on five TRGs can accurately predict the survival outcomes of HCC, improving our knowledge of TRGs in HCC and paving a new path for guiding risk stratification and treatment strategy development for HCC patients.
Improving the tensile strength of non-keyhole friction stir lap welding joint of 2024-T4 Al alloy by radial basis function neural network and improved particle swarm optimization algorithm
Authors: Li Yuting , Sun Zelin , Qi Xin , Gong Peng , Ji Shude , Wang Baoguang , Zhang Zhiqing , Zhang Jiaqi 
Published: October 2022

The non-keyhole friction stir lap welding (N-KFSLW) technology assisted by the outer stationary shoulder and the inner upper half-thread rotating pin was proposed to obtain the welding joint without keyhole through one-time process. Choosing 2024 aluminum alloys as the research object, the formation, microhardness and tensile strength of N-KFSLW joint were investigated. The improved particle swarm optimization (IPSO) algorithm was newly developed and had the advantages of large convergence speed and strong search ability, by which the radial basis function (RBF) neural network was optimized to enhance its prediction accuracy. After that, the RBF and IPSO (IPSO-RBF) system was used to predict the joint strength and optimize the process parameters combination. The results showed that the lap joint had not only the SZ with the thickness almost equal to the thickness of upper sheet but also the cold lap with a very small height, thereby leading to the high tensile strength of joint. The optimized parameters of welding speed, rotating speed and pin type by the IPSO-RBF system were respectively 612 rpm, 80 mm/min, and upper half-thread pin, and the tensile strength of lap joint reached 11.88 kN/mm. The N-KFSLW technology assisted by upper half-thread pin provides an effective way to obtain the lap joint with high performance, and the IPSO-RBF system can be used to maximize the strength of welding joint.
Practice patterns and adherence to society guidelines for suspected choledocholithiasis: A comparison of academic and community settings from a large US healthcare system
Authors: Rashtak Shahrooz , Goyal Hemant , Chandran Aswathi , Dedania Bhavtosh , Patil Prithvi , Wadhwa Vaibhav , Guha Sushovan , Davee Tomas , Ramireddy Srinivas , Thosani Nirav 
Published: October 2022

BackgroundThe American Society of Gastrointestinal Endoscopy (ASGE) has proposed practice guidelines for evaluating patients with suspected choledocholithiasis. This study aims to assess and compare practice patterns for following ASGE guidelines for choledocholithiasis in a large academic vs. community hospital setting.MethodsA total of one thousand ER indicated for choledocholithiasis were randomly selected. Patients’ demographics, total bilirubin, imaging studies including magnetic resonance cholangiopancreatography (MRCP), intraoperative cholangiogram (IOC), endoscopic ultrasound (EUS), and ERCP results were retrospectively collected. Patients with prior sphincterotomy were excluded. We examined the following practice deviations from the current ASGE guidelines; (1) ERCP was potentially delayed in high probability cases while awaiting additional imaging studies, (2) ERCP was performed without additional imaging studies in cases of low/intermediate-risk, or (3) ERCP was performed in low/intermediate-risk cases when additional imaging studies were negative.ResultsA total of 640 patients with native papilla who underwent ERCP were included in the final analysis. Overall, the management of 43% (275) of patients was deviated from the applicable ASGE guidelines. Academic and community provider rates of non-adherence were 32 vs. 45%, respectively (p-value: &lt; 0.01). Of 381 high-risk cases, 54.1% had additional imaging before ERCP. (Academic vs. community; 11.7 vs. 88.3%, p-value: &lt; 0.01). In 26.7% (69/258) of low/intermediate risk cases, ERCP was performed without additional studies; academic (14.5%) vs. community (85.5%) (p-value: &lt; 0.01). Finally, in 11.2% (19/170) of patients, ERCP was performed despite intermediate/low probability and negative imaging; academic (26.3%) vs. community (73.7%) (p-value: 0.02).ConclusionOur study results show that providers do not adhere to ASGE practice guidelines in 43% of suspected choledocholithiasis cases. The rate of non-adherence was significantly higher in community settings. It could be due to various reasons, including lack/delays for alternate studies (i.e., MRCP, EUS), concern regarding the length of stay, patient preference, or lack of awareness/understanding of the guidelines. Increased availability of alternate imaging and educational strategies may be needed to increase the adoption of practice guidelines across academic and community settings to improve patient outcomes and save healthcare dollars.
Application of Jiawei Maxing Shigan Tang in the treatment of COVID-19: An observational study
Authors: Wu Jia , Tang Feng , Zhang Xiao-Qiang , Fu Zai-Lin , Fu Shui 
Published: October 2022

ObjectiveTo explore the clinical efficacy and adverse reactions of Jiawei Maxing Shigan Tang (JMST; a modified decoction of ephedra, apricot kernel, gypsum, and licorice) combined with western medicine in the symptomatic treatment of COVID-19.MethodsIn this study, we retrospectively collected the basic data of 48 patients with COVID-19 who were discharged from our hospital between January 20 and February 28, 2020. Besides, the blood routines, biochemical indexes, nucleic acid detection results, clinical symptoms, lung imaging improvements, adverse reactions, and other clinical data of these patients before and after treatment were recorded. Finally, we drew comparisons between the outcomes and adverse reactions of patients in the combined treatment group (therapeutic regimen recommended by authoritative guidelines and supplemented by JMST) and the conventional treatment group (therapeutic regimen recommended by authoritative guidelines).ResultsThere were no significant differences in age, gender, clinical classification, and underlying medical conditions between the combined treatment group (28 cases) and the conventional treatment group (20 cases). However, the combined treatment group presented superior results to the conventional treatment group in several key areas. For instance, patients produced negative nasal/throat swab-based nucleic acid detection results in a shorter time, clinical symptoms were more effectively alleviated, and the absorption time of lung exudation was shorter (P &lt; 0.05). Furthermore, the combined treatment group had a shorter length of stay (LOS) and faster lymphocyte recovery duration than the conventional treatment group, although the differences were not statistically significant. Moreover, there were no significant differences concerning gastrointestinal reaction, hepatic injury, renal impairment, myocardial injury, and other adverse reactions between the two groups.ConclusionThe results of this study indicate that JMST combined with the recommended therapeutic regimen enhances the recovery of COVID-19 patients without increasing the risk of adverse reactions. Therefore, this therapy promotes positive outcomes for COVID-19 patients.
Prognostic value, immune signature and molecular mechanisms of the APOBEC family members APOBEC1, APOBEC3A, APOBEC3G and APOBEC3H in pancreatic adenocarcinoma
Authors: Duan Yunjie , Du Yongxing , Gu Zongting , Zheng Xiaohao , Wang Chengfeng 
Published: October 2022

Background: Increasing evidence supports that the APOBEC family is associated with development of a variety of cancers. However, the function of APOBEC1/3A/3G/3H in pancreatic adenocarcinoma (PAAD) is still unclear.Methods: Comprehensive bioinformatic analysis using R (version 3.6.3), TISIDB, Metascape etc. were performed to study the clinicopathological characteristics, prognostic value, immune features and functional mechanisms of the APOBEC1/3A/3G/3H in PAAD.Results: APOBEC1/3A/3G/3H showed significantly elevated expression in PAAD than para-cancerous or normal tissues. Their high expression or amplification were significantly correlated with worse clinicopathological characteristics and prognosis in PAAD patients. In addition, the role of APOBEC1/3A/3G/3H in the immune regulation is diverse and complex, the high expression of APOBEC1 may inhibit the infiltration level of many kinds of immunoreactive tumor-infiltrating cells, which may be an important factor leading to immune escape of PAAD cells. Mechanistically, APOBEC1/3A/3G/3H played an activating role in multiple oncogenic pathways, including the EMT, RAS/MAPK and TSC/mTOR pathways. Moreover, we found that the expression level of APOBEC3G was positively correlated with the sensitivity of gemcitabine and doxorubicin.Conclusion: APOBEC1/3A/3G/3H play an oncogenic role in the development of PAAD and might serve as new biomarkers or therapeutic targets.
Exploring the mediating effects of negative and positive religious coping between resilience and mental well-being
Authors: Surzykiewicz Janusz , Skalski Sebastian Binyamin , Niesiobędzka Małgorzata , Konaszewski Karol 
Published: October 2022

Background:The purpose of the study was to examine more thoroughly the relationship between trait resilience and mental well-being. Although research demonstrates that this relationship is partially mediated by stress-related variables, no study has taken into account the mediating role of religious coping. We examined the mediating role of both variants of religious coping, positive and negative, along with specific strategies within the scope of religious coping strategies in a group of practicing Catholics.Method:Participants were 317 people aged 19–60 years (M = 24.34; SD = 6.30). The respondents indicated their gender and age, and then completed the RS-14 (trait resilience), RCOPE (religious coping), and WEMWBS (mental well-being) scales.Results:The results displayed a significant relationship between resilience and mental well-being (r = 0.67; p &lt; 0.001). The relationship between resilience and positive religious coping was negligible (r = 0.09; p = 0.74), contrary to the relationship between resilience and negative coping that was significant but weak (r = −0.29; p &lt; 0.001). Although the relationships between overall negative and positive religious coping with mental well-being were irrelevant, we found significant relationships between some strategies and mental well-being. The mediation analysis has demonstrated that the general negative religious coping and the strategies of demonic reappraisal, passive religious deferral, and spiritual discontent have enhanced the positive relationship between resilience and mental well-being. Contrary to expectation, positive strategies did not mediate the relationship between resilience and mental well-being, except religious practices (c′path totaled β = 0.66; t = 15.74, p &lt; 0.001). The insignificant mediation effect can stem from the fact that the relationship between positive religious coping and stress is noticeable only in the long term. We controlled age and sex as statistically significant covariates so that the mediation effects obtained were devoid of the influence of those critical variables on the models.Conclusion:This is the first study to investigate the role of religious coping as a mediator in the relationship between resilience and mental well-being.