bluuebunny/crossref_metadata_2025_split huggingface dataset:
The pattern of TSH and fT4 levels across different BMI ranges in a large cohort of euthyroid patients with obesity
Authors: Mele Chiara , Mai Stefania , Cena Tiziana , Pagano Loredana , Scacchi Massimo , Biondi Bernadette , Aimaretti Gianluca , Marzullo Paolo 
Published: October 2022

PurposeA multifold association relates the hypothalamo-pituitary-thyroid axis to body weight. The potential underlying mechanisms are incompletely understood. Further, the mild severity of obesity and the small proportion of individuals with obesity in so far published cohort studies provide little insights on metabolic correlates of thyroid function in obesity.MethodsWe retrospectively enrolled 5009 adults with obesity (F/M, 3448/1561; age range, 18-87 years; BMI range, 30.0-82.7 kg/m2), without known thyroid disease in a study on TSH and fT4 levels, lipid profile, glucose homeostasis and insulin resistance, anthropometric parameters including BIA-derived fat mass (%FM) and fat-free mass (FFM).ResultsThe overall reference interval for TSH in our obese cohort was 0.58-5.07 mIU/L. As subgroups, females and non-smokers showed higher TSH levels as compared to their counterparts (p&lt;0.0001 for both), while fT4 values were comparable between groups. There was a significant upward trend for TSH levels across incremental BMI classes in females, while the opposite trend was seen for fT4 levels in males (p&lt;0.0001 for both). Expectedly, TSH was associated with %FM and FFM (p&lt;0,0001 for both). TSH and fT4 showed correlations with several metabolic variables, and both declined with aging (TSH, p&lt;0.0001; fT4, p&lt;0.01). In a subgroup undergoing leptin measurement, leptin levels were positively associated with TSH levels (p&lt;0.01). At the multivariable regression analysis, in the group as a whole, smoking habit emerged as the main independent predictor of TSH (β=-0.24, p&lt;0.0001) and fT4 (β=-0.25, p&lt;0.0001) levels. In non-smokers, %FM (β=0.08, p&lt;0.0001) and age (β=-0.05, p&lt;0.001) were the main significant predictors of TSH levels. In the subset of nonsmokers having leptin measured, leptin emerged as the strongest predictor of TSH levels (β=0.17, p&lt;0.01).ConclusionsOur study provides evidence of a gender- and smoking-dependent regulation of TSH levels in obesity.
The value of radiomics to predict abnormal bone mass in type 2 diabetes mellitus patients based on CT imaging for paravertebral muscles
Authors: Qiu Hui , Yang Hui , Yang Zhe , Yao Qianqian , Duan Shaofeng , Qin Jian , Zhu Jianzhong 
Published: October 2022

ObjectiveTo investigate the value of CT imaging features of paravertebral muscles in predicting abnormal bone mass in patients with type 2 diabetes mellitus.MethodsThe clinical and QCT data of 149 patients with type 2 diabetes mellitus were collected retrospectively. Patients were randomly divided into the training group (n = 90) and the validation group (n = 49). The radiologic model and Nomogram model were established by multivariate Logistic regression analysis. Predictive performance was evaluated using receiver operating characteristic (ROC) curves.ResultsA total of 829 features were extracted from CT images of paravertebral muscles, and 12 optimal predictive features were obtained by the mRMR and Lasso feature selection methods. The radiomics model can better predict bone abnormality in type 2 diabetes mellitus, and the (Area Under Curve) AUC values of the training group and the validation group were 0.94(95% CI, 0.90-0.99) and 0.90(95% CI, 0.82-0.98). The combined Nomogram model, based on radiomics and clinical characteristics (vertebral CT values), showed better predictive efficacy with an AUC values of 0.97(95% CI, 0.94-1.00) in the training group and 0.95(95% CI, 0.90-1.00) in the validation group, compared with the clinical model.ConclusionThe combination of Nomogram model and radiomics-clinical features of paravertebral muscles has a good predictive value for abnormal bone mass in patients with type 2 diabetes mellitus.
Sex-specific regulation of IL-10 production in human adipose tissue in obesity
Authors: Subramanian Narmadha , Tavira Beatriz , Hofwimmer Kaisa , Gutsmann Beate , Massier Lucas , Abildgaard Julie , Juul Anders , Rydén Mikael , Arner Peter , Laurencikiene Jurga 
Published: October 2022

BackgroundObesity-associated metabolic complications display sexual dimorphism and can be impacted by cytokines. We previously showed that interleukin-10 (IL-10) was upregulated in white adipose tissue (WAT) of obese women with type 2 diabetes (T2D). Whether this pertains to men is unknown. The aim of this study was to compare the impact of obesity and T2D on WAT IL-10 levels in men versus women.MethodsPlasma and subcutaneous WAT biopsies were obtained from 108 metabolically well-characterized individuals. WATIL10expression/secretion and WAT-resident IL-10-secreting macrophage number were measured. Circulating sex hormone levels were correlated to WATIL10expression in 22 individuals and sex hormone effects on macrophageIL10expression were investigatedin vitro.ResultsObese women with T2D showed increasedIL10expression/secretion and IL-10-secreting WAT macrophage number compared to other female groups. This difference was absent in men. Non-obese women and men with T2D showed similar IL-10 levels compared to healthy controls, indicating that T2D alone does not regulate IL-10. Although WATIL10expression correlated with serum estrone (E1) concentrations, recombinant E1 did not affect macrophageIL10expressionin vitro.ConclusionWAT IL-10 levels are higher in women with obesity and T2D, but not in men and this effect is primarily attributed to obesityper se. This is less likely to be driven by circulating sex hormones. We propose that the WAT IL-10 might exert protective effects in obesity-associated chronic inflammation in women which could be one of the contributing factors for the decreased morbidity observed in women during obesity than men.
RNA-sequencing analysis reveals the long noncoding RNA profile in the mouse myopic retina
Authors: Li Yuanjun , Lu Ying , Du Kaixuan , Yin Yewei , Hu Tu , Fu Qiuman , Zhang Yanni , Wen Dan , Wu Xiaoying , Xia Xiaobo 
Published: October 2022

Aim: Myopia is a prevalent public health problem. The long noncoding RNA (lncRNA) mechanisms for dysregulated retinal signaling in the myopic eye have remained elusive. The aim of this study was to analyze the expression profiles and possible pathogenic roles of lncRNAs in mouse form-deprived myopia (FDM) retinas.Methods: A mouse FDM model was induced and retinas from the FDM right eyes and the contralateral eyes were collected for RNA sequencing. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and lncRNA-mRNA coexpression network analyses were conducted to explore the biological functions of the differentially expressed lncRNAs. In addition, the levels of differentially expressed lncRNAs in the myopic retinas were validated by quantitative real-time PCR (qRT–PCR). Fluorescence in situ hybridization (FISH) was used to detect the localization of lncRNAs in mouse retinas.Results: FDM eyes exhibited reduced refraction and increased ocular axial length compared to control fellow eyes. RNA sequencing revealed that there were 655 differentially expressed lncRNAs between the FDM and control retinas. Functional enrichment analysis indicated that the differentially expressed RNAs were mostly enriched in cellular processes, cytokine-cytokine receptor interactions, retinol metabolism, and rhythmic processes. Differentially expressed lncRNAs were validated by qRT–PCR. Additionally, RNA FISH showed that XR_384718.4 (Gm35369) localized in the ganglion cell (GCL) and inner nuclear layers (INL).Conclusion: This study identified the differential expression profiles of lncRNAs in myopic mouse retinas. Our results provide scientific evidence for investigations of myopia and the development of putative interventions in the future.
Depletion of PARP10 inhibits the growth and metastatic potential of oral squamous cell carcinoma
Authors: Zhou Zihui , Wei Bing , Liu Yu , Liu Tian , Zeng Sien , Gan Jinfeng , Qi Guangying 
Published: October 2022

Background: Although poly (ADP-ribose) polymerase family member 10 (PARP10) has been implicated in the progression of multiple cancer types, its role in oral squamous cell carcinoma (OSCC) remains unknown. This study aimed to examine the function of PARP10 in OSCC and investigate the underlying mechanisms.Methods: The expression of PARP10 in OSCC was investigated in OSCC patient cohorts. Kaplan-Meier curve analysis was performed to assess the association between PARP10 and prognosis in OSCC. Correlation between PARP10 expression and the related variables was analyzed by χ2 test. CKK-8, transwell assay, western blot, immunohistochemistry, immunofluorescence, and bioinformatic analysis, were applied to clarify the role of PARP10 in OSCC.Results: PARP10 was found to be markedly elevated in OSCC tissues. The upregulation of PARP10 predicted shorter overall survival and disease-specific survival and was significantly correlated with several malignant features. Moreover, depletion of PARP10 markedly inhibited the proliferation, migration, and invasion of OSCC cells, and promoted OSCC cell apoptosis, and resulted in alterations of relevant proteins. Furthermore, a positive correlation was observed between the expression of PARP10 and Ki67, PARP1, MMP2, and VEGF. In addition, depletion of PARP10 impaired the PI3K-AKT and MAPK signaling pathways.Conclusion: PARP10 is involved in the progression of OSCC via regulation of PI3K-AKT and MAPK signaling pathways.
Pan-cancer analysis of the prognostic and immunological roles of DEAD-box helicase 5 (DDX5) in human tumors
Authors: Liu Shixuan , Liu Yanbin , Zhang Xi , Song Xuanlin , Zhang Boxiang , Zhang Yong 
Published: October 2022

Background: Recent studies have demonstrated the significance of the DEAD-box helicase 5 (DDX5) gene, which is involved in pathways concerning the modification of RNA structures. DDX5 functions as a coregulator of cellular transcription and splicing, and participates in the processing of small noncoding RNAs. The aberrant regulation of DDX5 expression possibly plays a significant role in the genesis of cancer. However, there are no comprehensive pan-cancer studies on DDX5. This study is the first to conduct a pan-cancer analysis of DDX5 for aiding the diagnosis and treatment of cancer.Methods: The gene expression, genetic alterations, protein phosphorylation, promoter methylation, immune infiltration, and enrichment analyses of DDX5 were performed using data retrieved from The Cancer Genome Atlas (TCGA), Genotype-tissue Expression (GTEx), Human Protein Atlas (HPA), Tumor Immunological Estimation Resource 2.0 (TIMER2.0), Gene Expression Profiling Interactive Analysis (GEPIA), DNA methylation interactive visualization database (DNMIVD), and Search Tool for the Retrieval of Interaction Genes/Proteins (STRING). Data analyses were performed with the R software and other webtools.Results: The expression of DDX5 mRNA decreased significantly in 17 cancer types, but increased significantly in eight cancer types. The enhanced expression of DDX5 mRNA in the tumor samples was related to decreased overall survival (OS), progression-free interval (PFI), and disease-specific survival (DSS) in three cancers, but increased OS, PFI, and DSS in other cancers. The DNA promoter methylation level was significantly reduced in eight cancer types, and there were exceptions in the methylation levels of the DDX5 promoter in four cancer types. The expression of DDX5 mRNA was highly correlated with the infiltration of CD8+ T cells, cancer-associated fibroblasts, and B cells in a wide variety of malignancies. The findings revealed a strong association between DDX5 and its co-expressed genes in numerous cancer types. Enrichment analysis suggested that DDX5 was associated with multiple cellular pathways, including RNA splicing, Notch signaling pathway, and viral carcinogenesis, which was consistent with the results of previous studies.Conclusion: The findings obtained herein provide further information on the oncogenic potential of DDX5 in diverse tumor types. We propose that DDX5 has important roles in tumor immunity and the diagnosis of cancer.
Prognostic model and immunotherapy prediction based on molecular chaperone-related lncRNAs in lung adenocarcinoma
Authors: Xu Yue , Tao Tao , Li Shi , Tan Shuzhen , Liu Haiyan , Zhu Xiao 
Published: October 2022

Introduction: Molecular chaperones and long non-coding RNAs (lncRNAs) have been confirmed to be closely related to the occurrence and development of tumors, especially lung cancer. Our study aimed to construct a kind of molecular chaperone-related long non-coding RNAs (MCRLncs) marker to accurately predict the prognosis of lung adenocarcinoma (LUAD) patients and find new immunotherapy targets.Methods: In this study, we acquired molecular chaperone genes from two databases, Genecards and molecular signatures database (MsigDB). And then, we downloaded transcriptome data, clinical data, and mutation information of LUAD patients through the Cancer Genome Atlas (TCGA). MCRLncs were determined by Spearman correlation analysis. We used univariate, least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analysis to construct risk models. Kaplan-meier (KM) analysis was used to understand the difference in survival between high and low-risk groups. Nomogram, calibration curve, concordance index (C-index) curve, and receiver operating characteristic (ROC) curve were used to evaluate the accuracy of the risk model prediction. In addition, we used gene ontology (GO) enrichment analysis and kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses to explore the potential biological functions of MCRLncs. Immune microenvironmental landscapes were constructed by using single-sample gene set enrichment analysis (ssGSEA), tumor immune dysfunction and exclusion (TIDE) algorithm, “pRRophetic” R package, and “IMvigor210” dataset. The stem cell index based on mRNAsi expression was used to further evaluate the patient’s prognosis.Results: Sixteen MCRLncs were identified as independent prognostic indicators in patients with LUAD. Patients in the high-risk group had significantly worse overall survival (OS). ROC curve suggested that the prognostic features of MCRLncs had a good predictive ability for OS. Immune system activation was more pronounced in the high-risk group. Prognostic features of the high-risk group were strongly associated with exclusion and cancer-associated fibroblasts (CAF). According to this prognostic model, a total of 15 potential chemotherapeutic agents were screened for the treatment of LUAD. Immunotherapy analysis showed that the selected chemotherapeutic drugs had potential application value. Stem cell index mRNAsi correlates with prognosis in patients with LUAD.Conclusion: Our study established a kind of novel MCRLncs marker that can effectively predict OS in LUAD patients and provided a new model for the application of immunotherapy in clinical practice.
Association between genetic variants (rs920778, rs4759314, and rs217727) in LncRNAs and cervical cancer susceptibility in Chinese population: A systematic review and meta-analysis
Authors: Liu Yi , Zhang Qian , Ni Rong 
Published: October 2022

Objective: The relationship between gene polymorphisms in long non-coding RNAs (LncRNAs) and cervical cancer susceptibility has been thoroughly analyzed; however, the conclusions are inconsistent. Therefore, this systematic review and meta-analysis aimed to accurately assess the relationship between them.Method: Eligible literatures were retrieved from PubMed, Medline, China National Knowledge Infrastructure (CNKI), and WanFang databases before 1 April 2022. The odds ratios with the corresponding 95% confidence intervals were used to evaluate the strength of these relationships. Sensitivity analysis for publication bias was conducted to assess the stability and reliability of included literatures.Results: A total of 59 SNPs in 11 LncRNAs were summarized for a systematic review in this study, and then, a meta-analysis of rs920778 and rs4759314 polymorphisms in HOTAIR and rs217727 polymorphisms in H19 was conducted. The results demonstrated that rs920778 and rs4759314 polymorphisms were significantly correlated with cervical cancer susceptibility. Further subgroup analysis of rs920778 polymorphism showed that both small sample size and large sample size subgroups were associated with cervical cancer susceptibility. However, no association was found between rs217727 polymorphism and cervical cancer risk in all five genetic models.Conclusion: In conclusion, the rs4759314, rs920778, and rs217717 polymorphisms of HOTAIR and H19 may be associated with cervical cancer. However, the results should be interpreted with caution due to the limited sample and heterogeneity in this study. Large-scale and well-designed studies need to be practiced to validate our results.
Bibliometric and visualization analysis of mesenchymal stem cells and rheumatoid arthritis (from 2012 to 2021)
Authors: Liu Jiaxi , Gao Jinfang , Niu Qing , Wu Fengping , Wu Zewen , Zhang Liyun 
Published: October 2022

BackgroundRheumatoid arthritis (RA) is a chronic autoimmune disease that can lead to joint deformity and loss of function. Recent studies have shown great progress in the research of mesenchymal stem cells (MSCs) in RA. However, thus far, there have been no bibliometric or visualization analyses in this field. This bibliometric analysis provides a comprehensive overview of the general information and research hotspots of MSCs and RA.MethodsArticles relevant to MSCs and RA, published between 2012 and 2021, were searched using the Web of Science Core Collection database. Irrelevant publications were excluded from the analysis. Bibliometric and visualization analyses were conducted using VOSviewer, CiteSpace, and Scimago Graphica.ResultsA total of 577 articles were analyzed. The annual number of publications increased from 2012 to 2017 and plateaued from 2017 to 2021. China and the USA had the largest number of publications. Collaboration among different organizations mainly occurs between institutes of the same country. Stem Cell Research and Therapy and Frontiers in Immunology were the most popular journals in this field. All the top 20 co-cited authors had a positive co-citation relationship. The top references indicate that MSCs can contribute to RA research and treatment mainly via immunomodulation. From 2012 to 2021, “collagen-induced arthritis,” “immunomodulation,” and “therapy” were some of the keywords associated with MSCs and RA, while “extracellular vesicles” showed a strong keyword burst from 2019 to 2021.ConclusionMSCs and RA have been widely studied in different countries and institutions and by different authors over the last ten years. China and the USA had the largest number of publications. Different types of journals provide admirable sources for researchers. Some keywords, including immunomodulation and extracellular vesicles, may be hot spots in the near future. There will be more basic research and clinical translation of MSCs and RA, and substantial new treatments for RA will soon be developed.
The commonness in immune infiltration of rheumatoid arthritis and atherosclerosis: Screening for central targets via microarray data analysis
Authors: Wang Zuoxiang , Xia Qingyue , Su Wenxing , Zhang Mingyang , Gu Yiyu , Xu Jialiang , Chen Weixiang , Jiang Tingbo 
Published: October 2022

BackgroundAlthough increasing evidence has reported an increased risk of atherosclerosis (AS) in rheumatoid arthritis (RA), the communal molecular mechanism of this phenomenon is still far from being fully elucidated. Hence, this article aimed to explore the pathogenesis of RA complicated with AS.MethodsBased on the strict inclusion/exclusion criteria, four gene datasets were downloaded from the Gene Expression Omnibus (GEO) database. After identifying the communal differentially expressed genes (DEGs) and hub genes, comprehensive bioinformatics analysis, including functional annotation, co-expression analysis, expression validation, drug-gene prediction, and TF-mRNA-miRNA regulatory network construction, was conducted. Moreover, the immune infiltration of RA and AS was analyzed and compared based on the CIBERSORT algorithm, and the correlation between hub genes and infiltrating immune cells was evaluated in RA and AS respectively.ResultsA total of 54 upregulated and 12 downregulated communal DEGs were screened between GSE100927 and GSE55457, and functional analysis of these genes indicated that the potential pathogenesis lies in immune terms. After the protein-protein interaction (PPI) network construction, a total of six hub genes (CCR5, CCR7, IL7R, PTPRC, CD2, and CD3D) were determined as hub genes, and the subsequent comprehensive bioinformatics analysis of the hub genes re-emphasized the importance of the immune system in RA and AS. Additionally, three overlapping infiltrating immune cells were found between RA and AS based on the CIBERSORT algorithm, including upregulated memory B cells, follicular helper T cells and γδT cells.ConclusionsOur study uncover the communal central genes and commonness in immune infiltration between RA and AS, and the analysis of six hub genes and three immune cells profile might provide new insights into potential pathogenesis therapeutic direction of RA complicated with AS.
Non-invasive measurement of tumor immune microenvironment and prediction of survival and chemotherapeutic benefits from 18F fluorodeoxyglucose PET/CT images in gastric cancer
Authors: Li Junmeng , Zhang Chao , Guo Huihui , Li Shuang , You Yang , Zheng Peiming , Zhang Hongquan , Wang Huanan , Bai Junwei 
Published: October 2022

BackgroundThe tumor immune microenvironment could provide prognostic and predictive information. It is necessary to develop a noninvasive radiomics-based biomarker of a previously validated tumor immune microenvironment signature of gastric cancer (GC) with immunohistochemistry staining.MethodsA total of 230 patients (training (n = 153) or validation (n = 77) cohort) with gastric cancer were subjected to (Positron Emission Tomography-Computed Tomography) radiomics feature extraction (80 features). A radiomics tumor immune microenvironment score (RTIMS) was developed to predict the tumor immune microenvironment signature with LASSO logistic regression. Furthermore, we evaluated its relation with prognosis and chemotherapy benefits.ResultsA 8-feature radiomics signature was established and validated (area under the curve=0.692 and 0.713). The RTIMS signature was significantly associated with disease-free survival and overall survival both in the training and validation cohort (all P&lt;0.001). RTIMS was an independent prognostic factor in the Multivariate analysis. Further analysis revealed that high RTIMS patients benefitted from adjuvant chemotherapy (for DFS, stage II: HR 0.208(95% CI 0.061-0.711), p=0.012; stage III: HR 0.321(0.180-0.570), p&lt;0.001, respectively); while there were no benefits from chemotherapy in a low RTIMS patients.ConclusionThis PET/CT radiomics model provided a promising way to assess the tumor immune microenvironment and to predict clinical outcomes and chemotherapy response. The RTIMS signature could be useful in estimating tumor immune microenvironment and predicting survival and chemotherapy benefit for patients with gastric cancer, when validated by further prospective randomized trials.