bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploration and validation of a combined immune and metabolism gene signature for prognosis prediction of colorectal cancer
Authors: Xiao Yitai , Zhang Guixiong , Wang Lizhu , Liang Mingzhu 
Published: November 2022

BackgroundColorectal cancer (CRC) is still one of the most frequently diagnosed malignancy around the world. The complex etiology and high heterogeneity of CRC necessitates the identification of new reliable signature to identify different tumor prognosis, which may help more precise understanding of the molecular properties of CRC and identify the appropriate treatment for CRC patients. In this study, we aimed to identify a combined immune and metabolism gene signature for prognosis prediction of CRC from large volume of CRC transcriptional data.MethodsGene expression profiling and clinical data of HCC samples was retrieved from the from public datasets. IRGs and MRGs were identified from differential expression analysis. Univariate and multivariate Cox regression analysis were applied to establish the prognostic metabolism-immune status-related signature. Kaplan-Meier survival and receiver operating characteristic (ROC) curves were generated for diagnostic efficacy estimation. Real-time polymerase chain reaction (RT-PCR), Western blot and immunohistochemistry (IHC) was conducted to verified the expression of key genes in CRC cells and tissues.ResultsA gene signature comprising four genes (including two IRGs and two MRGs) were identified and verified, with superior predictive performance in discriminating the overall survival (OS) of high-risk and low-risk compared to existing signatures. A prognostic nomogram based on the four-gene signature exhibited a best predictive performance, which enabled the prognosis prediction of CRC patients. The hub gene ESM1 related to CRC were selected via the machine learning and prognostic analysis. RT-PCR, Western blot and IHC indicated that ESM1 was high expressed in tumor than normal with superior predictive performance of CRC survival.ConclusionsA novel combined MRGs and IRGs-related prognostic signature that could stratify CRC patients into low-and high- risk groups of unfavorable outcomes for survival, was identified and verified. This might help, to some extent, to individualized treatment and prognosis assessment of CRC patients. Similarly, the mining of key genes provides a new perspective to explore the molecular mechanisms and targeted therapies of CRC.
Diagnostic performance of novel inflammatory biomarkers based on ratios of laboratory indicators for nonalcoholic fatty liver disease
Authors: Zhao Yanhua , Xia Junxiang , He He , Liang Shanshan , Zhang He , Gan Wei 
Published: November 2022

IntroductionThere is few effective biomarkers for diagnosing nonalcoholic fatty liver disease (NAFLD) in clinical practice. This study was aimed to investigate the predictive ability of novel inflammatory biomarkers, including the monocyte to high-density lipoprotein cholesterol ratio (MHR), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and lymphocyte to monocyte ratio (LMR), for NAFLD.MethodsA total of 4465 outpatients diagnosed with NAFLD and 3683 healthy controls were enrolled between May 2016 and November 2021 from the West China Hospital of Sichuan University, and anthropometric and laboratory examination data were collected. The two-sample Mann-Whitney U test and binary logistic regression analysis were used to evaluate the correlations between four inflammatory biomarkers and NAFLD. The areas under the curves (AUCs) of receiver operating characteristic were used to evaluate their predictive ability for NAFLD.ResultsThe MHR, NLR and LMR were higher in patients with NAFLD than in healthy controls (P&lt;0.001), whereas the PLR was remarkably lower (P&lt;0.001). The OR values of the MHR, NLR, PLR, and LMR were 1.599 (1.543-1.658), 1.250 (1.186-1.317), 0.987(0.986-0.988) and 1.111(1.083-1.139), respectively(P&lt;0.001). After adjusting for confounding factors, MHR was still the most relevant risk factor for NAFLD compared with other inflammatory markers (P&lt;0.001). The AUCs of the MHR, NLR, PLR, and LMR were as follows: 0.663 (0.651-0.675), 0.524 (0.512-0.537), 0.329 (0.318-0.341), and 0.543 (0.530-0.555), respectively (P&lt;0.001). Furthermore, the diagnostic model combining the MHR with alanine aminotransferase, aspartate aminotransferase, total cholesterol, triglycerides, fasting blood glucose, creatinine, uric acid, and body mass index had the best AUC of 0.931 (0.925-0.936).ConclusionsMHR was superior to NLR, PLR and LMR as an inflammatory biomarker in the prediction of NAFLD. When combined with relevant laboratory parameters, the MHR may improve the clinical noninvasive diagnosis of NAFLD.
Factors related to human-vector contact that modify the likelihood of malaria transmission during a contained Plasmodium falciparum outbreak in Praia, Cabo Verde
Authors: Stresman Gillian , DePina Adilson José , Nelli Luca , Monteiro Davidson D. S. , Leal Silvânia da Veiga , Moreira António Lima , Furtado Ullardina Domingos , Roka Jerlie C. Loko , Neatherlin John , Gomes Carolina , Tfeil Abderrahmane Kharchi , Lindblade Kimberly A. 
Published: November 2022

BackgroundDetermining the reproductive rate and how it varies over time and space (RT) provides important insight to understand transmission of a given disease and inform optimal strategies for controlling or eliminating it. Estimating RT for malaria is difficult partly due to the widespread use of interventions and immunity to disease masking incident infections. A malaria outbreak in Praia, Cabo Verde in 2017 provided a unique opportunity to estimate RT directly, providing a proxy for the intensity of vector-human contact and measure the impact of vector control measures.MethodsOut of 442 confirmed malaria cases reported in 2017 in Praia, 321 (73%) were geolocated and informed this analysis. RT was calculated using the joint likelihood of transmission between two cases, based on the time (serial interval) and physical distance (spatial interval) between them. Log-linear regression was used to estimate factors associated with changes in RT, including the impact of vector control interventions. A geostatistical model was developed to highlight areas receptive to transmission where vector control activities could be focused in future to prevent or interrupt transmission.ResultsThe RT from individual cases ranged between 0 and 11 with a median serial- and spatial-interval of 34 days [interquartile range (IQR): 17–52] and 1,347 m (IQR: 832–1,985 m), respectively. The number of households receiving indoor residual spraying (IRS) 4 weeks prior was associated with a reduction in RT by 0.84 [95% confidence interval (CI) 0.80–0.89; p-value &lt;0.001] in the peak-and post-epidemic compared to the pre-epidemic period.ConclusionsIdentifying the effect of reduced human-vector contact through IRS is essential to determining optimal intervention strategies that modify the likelihood of malaria transmission and can inform optimal intervention strategies to accelerate time to elimination. The distance within which two cases are plausibly linked is important for the potential scale of any reactive interventions as well as classifying infections as imported or introduced and confirming malaria elimination.
Prognostic necroptosis-related gene signature aids immunotherapy in lung adenocarcinoma
Authors: Song Yuqi , Zhang Jinming , Fang Linan , Liu Wei 
Published: November 2022

Background: Necroptosis is a phenomenon of cellular necrosis resulting from cell membrane rupture by the corresponding activation of Receptor Interacting Protein Kinase 3 (RIPK3) and Mixed Lineage Kinase domain-Like protein (MLKL) under programmed regulation. It is reported that necroptosis is closely related to the development of tumors, but the prognostic role and biological function of necroptosis in lung adenocarcinoma (LUAD), the most important cause of cancer-related deaths, is still obscure.Methods: In this study, we constructed a prognostic Necroptosis-related gene signature based on the RNA transcription data of LUAD patients from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases as well as the corresponding clinical information. Kaplan-Meier analysis, receiver operating characteristic (ROC), and Cox regression were made to validate and evaluate the model. We analyzed the immune landscape in LUAD and the relationship between the signature and immunotherapy regimens.Results: Five genes (RIPK3, MLKL, TLR2, TNFRSF1A, and ALDH2) were used to construct the prognostic signature, and patients were divided into high and low-risk groups in line with the risk score. Cox regression showed that risk score was an independent prognostic factor. Nomogram was created for predicting the survival rate of LUAD patients. Patients in high and low-risk groups have different tumor purity, tumor immunogenicity, and different sensitivity to common antitumor drugs.Conclusion: Our results highlight the association of necroptosis with LUAD and its potential use in guiding immunotherapy.
A network meta-analysis to evaluate the efficacy of traditional Chinese medicine on intestinal flora in patients with gastrointestinal cancer
Authors: Feng Niran , Wang Shurui , Liu Chengjiang , Xu Zixin , Song Zhijie , Li Kunyang , Yu Zhifeng 
Published: November 2022

Background and Purpose: Traditional Chinese medicine (TCM) can regulate intestinal flora so as to affect the occurrence, progression, and prognosis of gastrointestinal cancer. According to clinical studies, TCM oral administration, TCM external treatment, and TCM injections, can adjust intestinal flora disorders in patients with gastrointestinal cancer. This network meta-analysis aims to evaluate the effect of three treatments on the intestinal flora in gastrointestinal cancer patients.Methods: This meta-analysis was registered in PROSPERO (CRD42022332553). Six electronic databases, namely CNKI, Wanfang, CSTJ, PubMed, Cochrane Library, and EMBASE, were searched from their inception to 1 April 2022. We identified randomized controlled trials (RCT) used to compare the efficacy of three TCM treatment methods—oral administration, external therapy and injections—on the intestinal flora in gastrointestinal cancer patients. The main outcome indicators were Bifidobacteria, Lactobacilli, Escherichia coli, and Enterococci. Stata (15.1) and the Cochrane risk of bias assessment tool were employed.Results: We identified 20 eligible RCTs with a total of 1,774 patients. According to network meta-analysis results, TCM injection plus common treatment (CT) or oral administration of TCM plus CT was superior to CT alone for supporting Bifidobacterium. In supporting Lactobacillus, TCM injection plus CT demonstrated more obvious effect relative to oral administration of TCM plus CT; TCM injection plus CT was more effective than CT only; and oral administration of TCM plus CT was superior to CT only.The inhibitory effect of TCM injection plus CT on Escherichia coli was better compared with CT only. In terms of inhibiting Enterococci, oral administration of TCM plus CT was superior to CT only.The difference in efficacy among the above treatments was statistically significant. In the SUCRA probability ranking, TCM injection plus CT had the best ranking curve among the three treatments and was the most effective in supporting Bifidobacteria (Sucra = 90.08%), Lactobacilli (Sucra = 96.4%), and regulating Escherichia coli (Sucra = 86.1%) and Enterococci (Sucra = 87.1%).Conclusion: TCM injections plus CT is the most effective therapy in balancing the intestinal flora of gastrointestinal cancer patients. However, the current results deserve further validation through high-quality research.Systematic Review Registration: http://www.prisma-statement.org/, identifier 10.1136/bmj.n71.
Assessing the efficacy of immunotherapy in lung squamous carcinoma using artificial intelligence neural network
Authors: Li Siqi , Li Wei , Ma Tianyu , Fu Siyun , Gao Xiang , Qin Na , Wu Yuhua , Zhang Xinyong , Wang Jinghui , Pan Yuanming , Liu Zhidong 
Published: November 2022

BackgroundAt present, immunotherapy is a very promising treatment method for lung cancer patients, while the factors affecting response are still controversial. It is crucial to predict the efficacy of lung squamous carcinoma patients who received immunotherapy.MethodsIn our retrospective study, we enrolled lung squamous carcinoma patients who received immunotherapy at Beijing Chest Hospital from January 2017 to November 2021. All patients were grouped into two cohorts randomly, the training cohort (80% of the total) and the test cohort (20% of the total). The training cohort was used to build neural network models to assess the efficacy and outcome of immunotherapy in lung squamous carcinoma based on clinical information. The main outcome was the disease control rate (DCR), and then the secondary outcomes were objective response rate (ORR), progression-free survival (PFS), and overall survival (OS).ResultsA total of 289 patients were included in this study. The DCR model had area under the receiver operating characteristic curve (AUC) value of 0.9526 (95%CI, 0.9088–0.9879) in internal validation and 0.9491 (95%CI, 0.8704–1.0000) in external validation. The ORR model had AUC of 0.8030 (95%CI, 0.7437–0.8545) in internal validation and 0.7040 (95%CI, 0.5457–0.8379) in external validation. The PFS model had AUC of 0.8531 (95%CI, 0.8024–0.8975) in internal validation and 0.7602 (95%CI, 0.6236–0.8733) in external validation. The OS model had AUC of 0.8006 (95%CI, 0.7995–0.8017) in internal validation and 0.7382 (95%CI, 0.7366–0.7398) in external validation.ConclusionsThe neural network models show benefits in the efficacy evaluation of immunotherapy to lung squamous carcinoma patients, especially the DCR and ORR models. In our retrospective study, we found that neoadjuvant and adjuvant immunotherapy may bring greater efficacy benefits to patients.
Insights into prognosis and immune infiltration of cuproptosis-related genes in breast cancer
Authors: Huang Tingting , Liu Yankuo , Li Jiwei , Shi Bingbing , Shan Zhengda , Shi Zhiyuan , Yang Zhangru 
Published: November 2022

IntroductionBreast cancer (BC) has been ranking first in incidence and the leading cause of death among female cancers worldwide based on the latest report. Regulated cell death (RCD) plays a significant role in tumor initiation and provides an important target of cancer treatment. Cuproptosis, a novel form of RCD, is ignited by mitochondrial stress, particularly the lipoylated mitochondrial enzymes aggregation. However, the role of cuproptosis-related genes (CRGs) in tumor generation and progression remains unclear.MethodsIn this study, the mRNA expression data of CRGs in BC and normal breast tissue were extracted from TCGA database, and protein expression patterns of these CRGs were analyzed using UALCAN. The prognostic values of CRGs in BC were explored by using KaplanMeier plotter and Cox regression analysis. Genetic mutations profiles were evaluated using the cBioPortal database. Meanwhile, we utilized CIBERSORT and TIMER 2.0 database to perform the correlation analysis between CRGs and immune cell infiltration.ResultsOur results indicated that CRGs expression is significantly different in BC and normal breast tissues. Then we found that upregulated PDHA1 expression was associated with worse endpoint of BC. Moreover, we also performed immune infiltration analysis of CRGs, and demonstrated that PDHA1 expression was closely related to the infiltration levels of CD4+ memory T cell, macrophage M0 and M1 cell and mast cell in BC.ConclusionsOur results demonstrated the prognostic and immunogenetic values of PDHA1 in BC. Therefore, PDHA1 can be an independent prognostic biomarker and potential target for immunotherapy of BC.
Machine learning links different gene patterns of viral infection to immunosuppression and immune-related biomarkers in severe burns
Authors: Wang Peng , Zhang Zexin , Lin Rongjie , Lin Jiali , Liu Jiaming , Zhou Xiaoqian , Jiang Liyuan , Wang Yu , Deng Xudong , Lai Haijing , Xiao Hou’an 
Published: November 2022

IntroductionViral infection, typically disregarded, has a significant role in burns. However, there is still a lack of biomarkers and immunotherapy targets related to viral infections in burns.MethodsVirus-related genes (VRGs) that were extracted from Gene Oncology (GO) database were included as hallmarks. Through unsupervised consensus clustering, we divided patients into two VRGs molecular patterns (VRGMPs). Weighted gene co-expression network analysis (WGCNA) was performed to study the relationship between burns and VRGs. Random forest (RF), least absolute shrinkage and selection operator (LASSO) regression, and logistic regression were used to select key genes, which were utilized to construct prognostic signatures by multivariate logistic regression. The risk score of the nomogram defined high- and low-risk groups. We compared immune cells, immune checkpoint-related genes, and prognosis between the two groups. Finally, we used network analysis and molecular docking to predict drugs targeting CD69 and SATB1. Expression of CD69 and SATB1 was validated by qPCR and microarray with the blood sample from the burn patient.ResultsWe established two VRGMPs, which differed in monocytes, neutrophils, dendritic cells, and T cells. In WGCNA, genes were divided into 14 modules, and the black module was correlated with VRGMPs. A total of 65 genes were selected by WGCNA, STRING, and differential expression analysis. The results of GO enrichment analysis were enriched in Th1 and Th2 cell differentiation, B cell receptor signaling pathway, alpha-beta T cell activation, and alpha-beta T cell differentiation. Then the 2-gene signature was constructed by RF, LASSO, and LOGISTIC regression. The signature was an independent prognostic factor and performed well in ROC, calibration, and decision curves. Further, the expression of immune cells and checkpoint genes differed between high- and low-risk groups. CD69 and SATB1 were differentially expressed in burns.DiscussionThis is the first VRG-based signature (including 2 key genes validated by qPCR) for predicting survival, and it could provide vital guidance to achieve optimized immunotherapy for immunosuppression in burns.
Transcription factor ZNF22 regulates blood-tumor barrier permeability by interacting with HDAC3 protein
Authors: Zhu Baicheng , Zhang Lu , Zhou Xinxin , Ning Hao , Ma Teng 
Published: November 2022

ObjectiveThe primary goals of this study were to investigate the potential roles of ZNF22 and HDAC3 as a histone deacetylase in regulating an increases in blood-tumor barrier (BTB) permeability and some of the possible molecular mechanisms associated with this effect.MethodsThe expression of ZNF22 and HDAC3 in glioma-exposed endothelial cells (GECs) of BTB were detected transcription real-time PCR or western blot. The interaction of ZNF22 and HDAC3 in GECs associated with transcript effect was analyzed by means of Co-Immunoprecipitation and luciferase reporter assay.ResultsIn the present investigation, GECs expressed higher levels of ZNF22 as a zinc finger transcription factor and HDAC3 than endothelial cells. We then affirmed that silencing HDAC3 or ZNF22 led to a reduction in BTB permeability. By bioinformatics analysis, chromatin immunoprecipitation (ChIP) assays and luciferase assay, we found that ZNF22 had a target binding relationship with the promoter regions of ZO-1, Occludin, and Claudin-5 and negatively regulated the expression of ZO-1, Occludin, and Claudin-5. Furthermore, we revealed that HDAC3, as a co-transcript repressor with histone deacetylase activity, could interact with ZNF22 to hinder the expression of TJ-associated proteins, thereby further facilitating the permeability of BTB.ConclusionZNF22 acted as a transcription factor in conjunction with HDAC3 to modulate the expression of TJ-associated proteins, which was correlated with an increase in BTB permeability. These results may provide new strategies and targets for the chemotherapy of gliomas as well as intracranial infections.
Mapping of lymph node dissection determined by the epicenter location and tumor extension for esophagogastric junction carcinoma
Authors: Liang Rong , Bi Xiaogang , Fan Daguang , Du Qiao , Wang Rong , Zhao Baoyu 
Published: November 2022

BackgroundsPrevious studies identified the extent of lymph node dissection for esophagogastric junction (EGJ) carcinoma based on the metastatic incidence. The study aimed to determine the optimal extent and priority of lymphadenectomy based on the therapeutic efficacy from each station.MethodsThe studies on the lymph node metastasis (LNM) and therapeutic efficacy index (EI) for EGJ carcinomas were identified until April 2022. The obligatory stations with the LNM rates over 5% and therapeutic EI exceeding 2% should be routinely resected for D2 dissection, whereas the optional stations with EI between 0.5% and 2% should be resected for D3 dissection in selective cases.ResultsThe survey yielded 16 eligible articles including 6,350 patients with EGJ carcinoma. The metastatic rates exceeded 5% at no. 1, 2, 3, 7, 9, 11p, and 110 stations and were less than 5% in abdominal no. 4sa~6, 8a, 10, 11d, 12a, and 16a2/b1 and mediastinal no. 105~112 stations. Consequently, obligatory stations with EI over 2% were largely determined by the epicenter location and located at the upper perigastric, lower mediastinal, and suprapancreatic zones, corresponding to those with rates of LNM over 5%. Consistent with the LNM rates less than 5%, the optional stations with EI between 0.5% and 2% were largely dependent on the degree of tumor extension toward the lower perigastric, splenic hilar (grecurvature), para-aortic (less curvature of the cardia), and middle or upper mediastinal zones.ConclusionsThe obligatory stations can be resected as an “envelope-like” wrap by transhiatal proximal gastrectomy with lower esophagectomy, whereas the optional stations for dissection are indicated by the tumor extension. The extended gastrectomy is required for the lower perigastric in the stomach-predominant tumor with gastric involvement exceeding 5.0 cm, para-aortic dissection in the less curvature-predominant tumor and splenic hilar dissection in the grecurvature-predominant tumor whereas transthoracic subtotal esophagectomy is required for complete mediastinal dissection and adequate negative margin in the esophagus-predominant tumor with esophageal invasion exceeding 3.0 cm.