bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bioinformatics analyses for the identification of tumor antigens and immune subtypes of gastric adenocarcinoma
Authors: Wei Shuxun , Sun Qiang , Chen Jinshui , Li Xinxing , Hu Zhiqian 
Published: December 2022

Background: Although mRNA vaccines have been effective against multiple cancers, their efficacy against stomach adenocarcinoma (STAD) remains undefined. Immunotyping can indicate the comprehensive immune status in tumors and their immune microenvironment, which is closely associated with therapeutic response and vaccination potential. The aim of this study was to identify potential antigens in STAD for mRNA vaccine development, and further distinguish immune subtypes of STAD to construct an immune landscape for selecting suitable patients for vaccination.Methods: The gene expression and clinicopathological features of patients with gastric cancer were downloaded from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression Program (GTEx). 729 samples from GSE66229 and GSE84437 were downloaded through GEO and were used as the validation cohorts. Differential gene expression, genetic alterations and prognosis were analyzed using the R package, cBioPortal program and Kaplan-Meier. The relationship between tumor antigens and immune cells was evaluated and plotted by TIMER. ConsensusClusterPlus was used for consistency matrix construction and data clustering, and graph learning-based dimensional reduction was used to depict immune landscape. WGCNA was used to estimate the relationship between the color modules and immune subtypes.Results: Two overexpressed and mutated tumor antigens associated with poor prognosis and infiltration of antigen presenting cells were identified in STAD, including RAI14 and NREP. The immune subtypes showed distinct molecular, cellular and clinical characteristics. IS1 and IS2 exhibited immune-activated phenotypes and correlated to better survival compared to IS3, while IS3 tumors was immunologically cold. Immunogenic cell death modulators, immune checkpoints, and CA125, and CEA were also differentially expressed among the three immune subtypes. Finally, the immune landscape of STAD showed a high degree of heterogeneity between individual patients.Conclusion: RAI14 and NREP are potential antigens for developing anti-STAD mRNA vaccine, and patients with IS1 and IS3 tumors may be suitable for vaccination.
A novel prognostic signature of cuproptosis-related genes and the prognostic value of FDX1 in gliomas
Authors: Zhu HuaXin , Wan Qinsi , Tan Jiacong , Ouyang Hengyang , Pan Xinyi , Li MeiHua , Zhao YeYu 
Published: December 2022

Background: Gliomas are the most common malignant tumors of the central nervous system, with extremely bad prognoses. Cuproptosis is a novel form of regulated cell death. The impact of cuproptosis-related genes on glioma development has not been reported.Methods: The TCGA, GTEx, and CGGA databases were used to retrieve transcriptomic expression data. We employed Cox’s regressions to determine the associations between clinical factors and cuproptosis-related gene expression. Overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) were evaluated using the Kaplan-Meier method. We also used the least absolute shrinkage and selection operator (LASSO) regression technique.Results: The expression levels of all 10 CRGs varied considerably between glioma tumors and healthy tissues. In glioma patients, the levels of CDKN2A, FDX1, DLD, DLAT, LIAS, LIPT1, and PDHA1 were significantly associated with the OS, disease-specific survival, and progression-free interval. We used LASSO Cox’s regression to create a prognostic model; the risk score was (0.882340) *FDX1 expression + (0.141089) *DLD expression + (–0.333875) *LIAS expression + (0.356469) *LIPT1 expression + (–0.123851) *PDHA1 expression. A high-risk score/signature was associated with poor OS (hazard ratio = 3.50, 95% confidence interval 2, –4.55, log-rank p &lt; 0.001). Cox’s regression revealed that the FDX1 level independently predicted prognosis; FDX1 may control immune cell infiltration of the tumor microenvironment.Conclusion: The CRG signature may be prognostic in glioma patients, and the FDX1 level may independently predict glioma prognosis. These data may afford new insights into treatment.
Serological, fragmentomic, and epigenetic characteristics of cell-free DNA in patients with lupus nephritis
Authors: Wang Fang , Miao Hai-bing , Pei Zhi-hua , Chen Zhen 
Published: December 2022

ObjectivesThe biological characteristics of plasma circulating cell-free DNA (cfDNA) are related to the pathogenesis of lupus nephritis (LN). The aim of this study was to explore the biological characteristics of cfDNA in patients with LN in terms of serology, fragment omics, and epigenetics, and to discuss the possibility of liquid biopsy for cfDNA as an alternative to conventional tissue biopsy.MethodscfDNA was extracted from plasma samples of 127 patients with systemic lupus erythematosus (64 with LN, 63 without LN). The cfDNA concentration was determined using the Qubit method. Next-generation sequencing cfDNA methylation profiling was performed for three LN patients and six non-LN patients. The methylation panel was designed based on data from The Cancer Genome Atlas cohort. The fragmentation index, motif score, and DELFI score were calculated to explore the fragmentation profile of cfDNA in patients with LN. Statistical and machine learning methods were used to select features to calculate the methylation scores of the samples.ResultsPatients with LN had significantly lower cfDNA concentrations (P = 0.0347) than those without LN. This may be associated with the presence of anti-double-stranded DNA antibodies (r = –0.4189; P = 0.0296). The mean DELFI score (proportion of short fragments of cfDNA) in patients with LN was significantly higher than that in patients without LN (P = 0.0238). Based on the pan-cancer data, 73, 66, 8, and 10 features were selected and used to calculate the methylation scores. The mean methylation scores of these features in patients with LN differed significantly from those in patients without LN (P = 0.0238).ConclusionsThe specificity of cfDNA in patients with LN was identified using serological, fragmentomic, and epigenetic analyses. The findings may have implications for the development of new molecular markers of LN.
Innate immune function during antineoplastic treatment is associated with 12-months survival in non-small cell lung cancer
Authors: Ryssel Heidi , Egebjerg Kristian , Nielsen Susanne Dam , Lundgren Jens , Pøhl Mette , Langer Seppo W. , Kjaer Andreas , Ostrowski Sisse Rye , Fischer Barbara Malene 
Published: December 2022

IntroductionThe immune system has proven to be a key player in the progression as well as containment of cancer with new treatment strategies based on immunotherapy targeting this interaction. Assessing immune function could reveal critical information about the immune response to therapeutic interventions, revealing predictive biomarkers for tailored care and precision medicine.MethodsWe investigated immune function in 37 patients with inoperable non-small cell lung cancer (NSCLC) undergoing treatment with PD-L1 immune checkpoint inhibitor (ICI), chemotherapy (CT) or chemo-radiotherapy (CT/RT). Blood samples before (day 0) and during therapy (day 7, 21 and 80) were investigated by a standardized immunoassay, TruCulture®.ResultsOutcomes revealed a developing innate immune response induced by both immunotherapy and chemotherapy. NSCLC-patients displayed evidence of chronic innate immune activation and exhaustion prior to treatment. This pattern was particularly pronounced during treatment in patients dying within 12-months follow-up. Compared to treatment with CT, ICI demonstrated a higher ex vivo-stimulated release of proinflammatory cytokines.DiscussionThese preliminary findings may pave the way for tailored treatment and immune-monitoring.
Chikungunya patient transcriptional signatures faithfully recapitulated in a C57BL/6J mouse model
Authors: Bishop Cameron R. , Caten Felipe Ten , Nakaya Helder I. , Suhrbier Andreas 
Published: December 2022

IntroductionAn adult wild-type C57BL/6J mouse model of chikungunya virus (CHIKV) infection and disease has been extensively used to study the alphaviral arthritic immunopathology and to evaluate new interventions. How well mouse models recapitulate the gene expression profiles seen in humans remains controversial.MethodsHerein we perform a comparative transcriptomics analysis using RNA-Seq datasets from the C57BL/6J CHIKV mouse model with datasets obtained from adults and children acutely infected with CHIKV.ResultsDespite sampling quite different tissues, peripheral blood from humans and feet from mice, gene expression profiles were quite similar, with an overlap of up to ≈50% for up-regulated single copy orthologue differentially expressed genes. Furthermore, high levels of significant concordance between mouse and human were seen for immune pathways and signatures, which were dominated by interferons, T cells and monocyte/macrophages. Importantly, predicted responses to a series of anti-inflammatory drug and biologic treatments also showed cogent similarities between species.DiscussionComparative transcriptomics and subsequent pathway analysis provides a detailed picture of how a given model recapitulates human gene expression. Using this method, we show that the C57BL/6J CHIKV mouse model provides a reliable and representative system in which to study CHIKV immunopathology and evaluate new treatments.
Coronavirus disease 2019 in patients with rheumatic immune-mediated diseases in a single University Hospital, matched case-control study and literature review
Authors: Martínez-López David , Ferraz-Amaro Ivan , Prieto-Peña Diana , Sánchez-Bilbao Lara , Herrero-Morant Alba , Álvarez-Reguera Carmen , Benavides-Villanueva Fabricio , Corrales-Selaya Cristina , Trigueros-Vázquez Martín , González-Gay Miguel Ángel , Blanco Ricardo 
Published: December 2022

BackgroundCOVID-19 may present different degrees of severity. Viral infections in patients with rheumatic inflammatory diseases (R-IMID) trend to present more severe disease. However, data comparing the severity of the disease between R-IMID and the general population are scarce.ObjectivesTo compare predisposing factors, clinical, serological features, and severity of COVID-19 infection in patients with and without R-IMID.MethodsCase-control study in a single University Hospital. We included all consecutive patients with a diagnosis of an R-IMID and COVID-19 infection up to March 31st, 2021. This cohort was compared to patients without R-IMID and not receiving immunosuppressive therapy, matched for sex and age (±5 years). Confirmed infection was defined if a patient had a positive nasopharyngeal swab for SARS-CoV-2. Severity was divided into mild, moderate, severe and critical according to the United States National Institute of Health (NIH) guidelines.ResultsWe included 274 R-IMID patients (185 women/89 men), mean age 59.1 ± 18 years. More frequent R-IMID were: Rheumatoid arthritis (28.8%), Psoriatic Arthritis (20.1%), axial Spondyloarthritis (12.4%), Polymyalgia Rheumatica (8%) and Systemic Lupus Erythematosus (8%). Hypertension and dyslipidemia were more frequent in patients with R-IMID. Although most of the cases were mild, critical cases and deaths were more frequent in R-IMID. When adjusted by comorbidities, no statistical differences were observed.ConclusionR-IMID have a very similar clinical presentation when compared to the general population. There is a trend to an increased severity of the disease in patients with R-IMID.
Gene expression, molecular docking, and molecular dynamics studies to identify potential antifungal compounds targeting virulence proteins/genes VelB and THR as possible drug targets against Curvularia lunata
Authors: Kamboj Himanshu , Gupta Lovely , Kumar Pawan , Sen Pooja , Sengupta Abhishek , Vijayaraghavan Pooja 
Published: December 2022

Curvuluria lunata is a melanized fungus pathogenic to both plants and animals including humans, causing from mild, febrile to life-threatening illness if not well treated. In humans, it is an etiological agent of keratomycosis, sinusitis, and onychomycosis in immunocompromised and immunocompetent patients. The development of multiple-drug-resistant strains poses a critical treatment issue as well as public health problem. Natural products are attractive prototypes for drug discovery due to their broad-spectrum efficacy and lower side effects. The present study explores possible targets of natural antifungal compounds (α-pinene, eugenol, berberine, and curcumin) against C. lunata via gene expression analysis, molecular docking interaction, and molecular dynamics (MD) studies. Curcumin, berberine, eugenol, and α-pinene exhibited in vitro antifungal activity at 78 μg/ml, 156 μg/ml, 156 μg/ml, and 1250 μg/ml, respectively. In addition, treatment by these compounds led to the complete inhibition of conidial germination and hindered the adherence when observed on onion epidermis. Several pathogenic factors of fungi are crucial for their survival inside the host including those involved in melanin biosynthesis, hyphal growth, sporulation, and mitogen-activated protein kinase (MAPK) signalling. Relative gene expression of velB, brn1, clm1, and pks18 responsible for conidiation, melanin, and cell wall integrity was down-regulated significantly. Results of molecular docking possessed good binding affinity of compounds and have confirmed their potential targets as THR and VelB proteins. The docked structures, having good binding affinity among all, were further refined, and rescored from their docked poses through 100-ns long MD simulations. The MDS study revealed that curcumin formed a stable and energetically stabilized complex with the target protein. Therefore, the study concludes that the antifungal compounds possess significant efficacy to inhibit C. lunata growth targeting virulence proteins/genes involved in spore formation and melanin biosynthesis.
Acupuncture and acupressure with improved cancer-related depression of retrospective studies
Authors: Wang Feiqing , Zhao Jianing , Li Yanju , Yang Xu , Wu Dan , Yang Bo , Zhang Chike , He Zhixu , Du Liang , Zhu Xiaodong , Ming Dong , Liu Yang , Tang Dongxin 
Published: December 2022

IntroductionAcupuncture and acupressure are widely used for treating cancer pain and depression and recognized as safe and effective by the international medical community. In this study, we systematically evaluated the efficacy, safety, and clinical significance of acupuncture and acupressure in treating cancer-related depression.MethodsWe searched MEDLINE, PubMed, Science Direct, Google Scholar, Web of Science and Embase and Chinese-language databases for randomized clinical trials (RCTs). To assess efficacy, rating scales administered by clinicians or experts were preferred, including the Hamilton Depression Rating Scale (HAMD), Self-rating Depression Scale (SDS), Self-rating Anxiety Scale (SAS), and Quality of Life Questionnaire-Core 30 (QLQ-C30) and the total effective rate after treatment. In all, Sixteen RCTs involving 1019 cancer patients were included in the Meta-analysis.ResultsEleven (69%) of these studies reported the post-treatment total effective rate. Three hundred fifty-three patients received antidepressants; the total effective rate was 72.5%. Three hundred sixty-one patients underwent acupuncture and acupressure; the total effective rate was 90%. Meta-analysis results showed I2 = 0%, no heterogeneity, (Z = 5.84, p &lt; 0.00001); and combined OR = 3.55, (95% CI = 2.32 to 5.43).DiscussionThis study found that acupuncture and acupressure are as effective as medication in the treatment of cancer-related depression, provide a reliable basis for the clinical use of acupuncture to treat cancer-related depression, help promote nonpharmacological treatment for cancer-related complications. These approaches thus help reduce drug resistance and adverse reactions and improve patients’ quality of life.
The enigmatic helicase DHX9 as a candidate prognostic biomarker for resected pancreatic ductal adenocarcinoma
Authors: Chen Le-gao , Cui Ying , Lu Wei-qin , Wu Hao , Jiang Jin-song , Ding Ke-feng 
Published: December 2022

BackgroundPancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, and current therapies have limited efficacy on PDAC. The DEAH-box helicase 9 (DHX9) is widely reported to influence cell biological behavior via regulating DNA replication, genomic stability, transcription, translation, and microRNA biogenesis. However, the prognostic role of DHX9 in PDAC remains unclear. Thus, the objective of this study is to investigate the prognostic value of DHX9 expression in PDAC patients.MethodsTumor specimens from PDAC patients with surgical resection were obtained, and DHX9 was stained and analyzed in this study. Univariate and multivariate Cox regression analyses were utilized to identify independent risk factors of overall survival (OS) and recurrence-free survival (RFS). The prognostic nomograms for predicting OS and RFS were established to obtain superior predictive power.ResultsAmong the enrolled 110 patients, 61 patients were identified as having high expression of DHX9. The correlation analysis revealed that higher DHX9 expression in PDAC was prone to have advanced N stage (p = 0.010) and TNM stage (p = 0.017). For survival, the median OS (21.0 vs. 42.0 months, p &lt; 0.001) and RFS (12.0 vs. 24.0 months, p &lt; 0.001) of patients in the high DHX9 group were significantly shorter than those in the low DHX9 group. Within the univariate and multivariate analyses, American Joint Committee on Cancer (AJCC) N stage (p = 0.036) and DHX9 expression (p = 0.041) were confirmed as independent prognostic factors of OS, while nerve invasion (p = 0.031) and DHX9 expression (p = 0.005) were independent prognostic factors of RFS. Finally, the novel prognostic nomograms for OS and RFS were established and showed superior predictive accuracy.ConclusionThis study identified the independent prognostic value of DHX9 for RFS and OS in resected PDAC patients, and higher DHX9 expression was prone to have an earlier recurrence and shorter OS. Therefore, DHX9 may be a promising and valuable biomarker and a potential target for treating PDAC. More accurate and promising predictive models would be achieved when DHX9 is incorporated into nomograms.
Vascular invasion and lymph node metastasis mediate the effect of CA242 on prognosis in hilar cholangiocarcinoma patients after radical resection
Authors: Heng Gang , Huang Benqi , Shen Yanbing , wang Dan , Lan Zhen , Yao Yuxuan , Zhang Jianxin , Jia Jiankun , Zhang Chengcheng 
Published: December 2022

BackgroundCarbohydrate antigen 242 has been clinically used as a diagnostic biomarker for pancreatic cancer. However, the prognostic role of CA242 in hilar cholangiocarcinoma (HCCA) has not been identified. Also, it remains unclear to what extents the vascular invasion and lymph node metastasis mediate the effect of serum CA242 on prognosis.ObjectiveThis study aimed to investigate whether vascular invasion and lymph node metastasis mediate the relationship between CA242 levels and clinical prognosis in HCCA patients after radical resection.MethodsData of 234 HCCA patients who accepted radical resection from March 2008 to December 2014 were analyzed. Vascular invasion and lymph node metastasis were assessed by postoperative pathological examinations. Mediation analysis was performed to study the potential causal relationship between CA242 and overall survival (OS) and relapse-free survival (RFS). Survival analysis was performed using the Kaplan-Meier method.ResultsAmong 234 HCCA patients, 104 patients (44.4%) with normal CA242 levels (≤ 20 IU/ml) had significantly better OS (p=0.004) and RFS (p=0.001) than those 130 patients (55.6%) with elevated CA242 levels (&gt;20 IU/ml). The logistic analysis showed that elevated CA242 was an independent risk factor for vascular invasion (p=0.006) and lymph nodes metastasis (p=0.040). The causal mediation analysis indicated that the vascular invasion (p=0.012 for OS; p=0.036 for RFS) and lymph nodes metastasis (p=0.024 for OS; p=0.014 for RFS) played significant roles in mediating the effect of serum CA242 on OS and RFS.ConclusionSerum elevated CA242 could be a novel marker for prognosis prediction in HCCA patients. Vascular invasion and lymph node metastasis mediated the relationship between CA242 and clinical prognosis.
Use of period analysis to timely assess 5-year relative survival for breast cancer patients from Taizhou, Eastern China
Authors: Li Runhua , Zheng Yabing , Huang Jiajia , Lei Huijun , Xu Mingzhi , Wang Liangyou , Zhang Luyao , Cheng Yongran , Jiang Xiyi , Tang Huijuan , Shi Zheng , Chen Gang , Zhou Huijuan , Dai Zhijun , Lu Dalin , Chen Tianhui 
Published: December 2022

ObjectivesWhile timely assessment of long-term survival for patients with breast cancer is essential for evaluation on early detection and screening programs, those data are extremely scant in China. We aimed to derive most up-to-date survival estimates and to predict future survival using the cancer registry data from Taizhou city, Eastern China.MethodsPatients diagnosed with breast cancer during 2004-2018 from four cancer registries with high-quality data from Taizhou, Eastern China were included. Period analysis was used to calculate 5-year relative survival (RS) for the overall population and according to the stratification factors sex, age at diagnosis and geographic region. We further predict the upcoming 5-year RS during 2019-2023, using continuous data from three 5-year periods (2004-2008, 2009-2013 and 2014-2018) and a model-based period approach.ResultsOverall 6159 patients diagnosed with breast cancer during 2004-2018 were enrolled. The 5-year RS for breast cancer in 2014-2018 reached 88.8%, while women were higher compared to men (90.5% versus 83.7%) and urban areas were higher compared to rural areas (91.9% versus 86.7%). Additionally, we found a clear gradient by age at diagnosis, ranging from 94.8% for age&lt;45 years to 83.3% for age&gt;74 years. Projected overall 5-year RS for the upcoming 2019-2023 could reach 91.5% (84.8% for men and 93.5% for women).ConclusionsWe provided, for first time in China, using period analysis, most up-to-date 5-year RS (88.8%) for patients with breast cancer from Taizhou, Eastern China. We also demonstrate the 5-year RS has improved greatly over last 15 years, which has important implications for timely evaluation of early detection and screening programs.