bluuebunny/crossref_metadata_2025_split huggingface dataset:
Surgical Outcomes of Aldosterone-Producing Adenoma on the Basis of the Histopathological Findings
Authors: Wang Huiping , Wang Fen , Zhang Yushi , Wen Jin , Dong Dexin , Chang Xiaoyan , Sun Hao , Ma Xiaosen , Cui Yunying , Chen Shi , Lu Lin , Ren Weidong , Tong Anli , Li Yuxiu 
Published: September 2021

IntroductionPrevious studies on the surgical outcomes of aldosterone-producing adenoma (APA) patients were mainly based on the histopathological diagnosis of HE staining or adrenal venous sampling (AVS) instead of the functional pathology. The aim of the present study was to evaluate the surgical outcomes of APA patients based on the functional pathological diagnosis of APA according to HISTALDO (histopathology of primary aldosteronism) consensus.MethodsClinical data of 137 patients with suspected APA were analyzed retrospectively. All patients had hypertension and spontaneous hypokalemia. In all patients, CT showed a unilateral solitary hypodense adrenal lesion, and a contralateral adrenal gland of normal morphology. Tumors were removed and immunostained for CYP11B2, and their pathology were identified based on HISTALDO consensus. Patients were followed up 6 to 24 months after operation.ResultsAmong 137 cases of presumptive APA diagnosed by CT, 130 (95%) cases were pathologically diagnosed with classical pathology, including 123 APA(90%) and 7 aldosterone-producing nodule (APN) (5%). 7 cases (5%) had non-functioning adenoma (NFA) with aldosterone-producing micronodule (APM) or multiple aldosterone-producing micronodule (MAPM) in the surrounding adrenal tissue. In all 137 patients, hypertension was complete or partial clinical success postoperatively. Complete clinical success was achieved in 73 (53%), and partial clinical success was achieved in 64 (47%) cases. Serum potassium level recovered to normal in all. In 123 patients with APA, complete clinical success was reached in 67 (54%), and partial clinical success was reached in 56 (46%) cases. Gender, duration of hypertension and the highest SBP were significant independent predictors for cure of APA after surgery. A multiple logistic regression model integrating the three predictors was constructed to predict the outcome, which achieved a sensitivity of 72.4% and a specificity of 73.1%.ConclusionThe specificity of CT in the diagnosis of APA and APN patients with hypokalemia was 95%. All patients achieved complete or partial clinical success after surgery. Gender, duration of hypertension and the highest SBP were independent predictors for the postoperative cure of APA.
The Potential of Metabolomic Analyses as Predictive Biomarkers of Preterm Delivery: A Systematic Review
Authors: Ronde Emma , Reiss Irwin K. M. , Hankemeier Thomas , De Meij Tim G. , Frerichs Nina , Schoenmakers Sam 
Published: September 2021

Scopeas the leading cause of perinatal mortality and morbidity worldwide, the impact of premature delivery is undisputable. Thus far, non-invasive, cost-efficient and accurate biochemical markers to predict preterm delivery are scarce. The aim of this systematic review is to investigate the potential of non-invasive metabolomic biomarkers for the prediction of preterm delivery.Methods and ResultsDatabases were systematically searched from March 2019 up to May 2020 resulting in 4062 articles, of which 45 were retrieved for full-text assessment. The resulting metabolites used for further analyses, such as ferritin, prostaglandin and different vitamins were obtained from different human anatomical compartments or sources (vaginal fluid, serum, urine and umbilical cord) and compared between groups of women with preterm and term delivery. None of the reported metabolites showed uniform results, however, a combination of metabolomics biomarkers may have potential to predict preterm delivery and need to be evaluated in future studies.
Association of Pericardiac Adipose Tissue With Coronary Artery Disease
Authors: Li Mingxuan , Qi Lin , Li Yanglei , Zhang Shuyi , Lin Lei , Zhou Lijin , Han Wanlin , Qu Xinkai , Cai Junfeng , Ye Maoqing , Shi Kailei 
Published: September 2021

Background and AimCoronary artery disease (CAD) poses a worldwide health threat. Compelling evidence shows that pericardial adipose tissue (PAT), a brown-like adipose adjacent to the external surface of the pericardium, is associated with CAD. However, the specific molecular mechanisms of PAT in CAD are elusive. This study aims to characterize human PAT and explore its association with CAD.MethodsWe acquired samples of PAT from 31 elective cardiac surgery patients (17 CAD patients and 14 controls). The transcriptome characteristics were assessed in 5 CAD patients and 4 controls via RNA-sequencing. Cluster profile R package, String database, Cytoscape were applied to analyze the potential pathways and PPI-network key to DEGS, whereas the hubgenes were predicted via Metascape, Cytohubba, and MCODE. We use Cibersort, ENCORI, and DGIDB to predict immunoinfiltration, mRNA-miRNA target gene network, and search potential drugs targeting key DEGs. The predictable hubgenes and infiltrating inflammatory cells were validated in 22 patients (12 CAD samples and 10 control samples) through RT-qPCR and immunohistochemistry.ResultsA total of 147 different genes (104 up-regulated genes and 43 down-regulated genes) were identified in CAD patients. These different genes were associated with immunity and inflammatory dysfunction. Cibersort analysis showed monocytes and macrophages were the most common subsets in immune cells, whereas immunohistochemical results revealed there were more macrophages and higher proportion of M1 subtype cells in PAT of CAD patients. The PPI network and module analysis uncovered several crucial genes, defined as candidate genes, including Jun, ATF3, CXCR4, FOSB, CCl4, which were validated through RT-qPCR. The miRNA-mRNA network implicated hsa-miR-185-5p as diagnostic targets and drug-gene network showed colchicine, fenofibrate as potential therapeutic drugs, respectively.ConclusionThis study demonstrates that PAT is mainly associated with the occurrence of CAD following the dysfunction of immune and inflammatory processes. The identified hubgenes, predicted drugs and miRNAs are promising biomarkers and therapeutic targets for CAD.
Prevalence of Pathogenic Germline DICER1 Variants in Young Individuals Thyroidectomised Due to Goitre – A National Danish Cohort
Authors: Altaraihi Mays , Hansen Thomas van Overeem , Santoni-Rugiu Eric , Rossing Maria , Rasmussen Åse Krogh , Gerdes Anne-Marie , Wadt Karin 
Published: September 2021

IntroductionDICER1 syndrome encompasses a variety of benign and malignant manifestations including multinodular goitre, which is the most common manifestation among individuals carrying pathogenic DICER1 variants. This is the first study estimating the prevalence of pathogenic DICER1 variants in young individuals with multinodular goitre.MethodsDanish individuals diagnosed with nodular goitre based on thyroidectomy samples in 2001-2016 with the age limit at time of operation being ≤ 25 years were offered germline DICER1 gene testing.ResultsSix of 46 individuals, 13% (CI [3.3;22.7], p &lt;0.05), diagnosed with nodular goitre on the basis of thyroidectomy samples under the age of 25 years had pathogenic germline variants in DICER1. They were found in different pathoanatomical nodular goitre cohorts i.e. nodular goitre (n=2), colloid nodular goitre (n=3) and hyperplastic nodular goitre (n=1).ConclusionsWe recommend referral of patients thyroidectomised due to goitre aged &lt;21 years and patients thyroidectomised due to goitre aged &lt;25 years with a family history of goitre to genetic counselling. Patients of all ages thyroidectomised due to goitre, who are affected by another DICER1 manifestation should be referred to genetic counselling.
Predicting the Survival and Immune Landscape of Colorectal Cancer Patients Using an Immune-Related lncRNA Pair Model
Authors: Ma Chao , Zhang Xin , Zhao Xudong , Zhang Nan , Zhou Sixin , Zhang Yonghui , Li Peiyu 
Published: September 2021

BackgroundAccumulating evidence has demonstrated that immune-related long non-coding ribonucleic acids (irlncRNAs) can be used as prognostic indicators of overall survival (OS) in patients with colorectal cancer (CRC). Our aim in this research, therefore, was to construct a risk model using irlncRNA pairs with no requirement for a specific expression level, in hope of reliably predicting the prognosis and immune landscape of CRC patients.MethodsClinical and transcriptome profiling data of CRC patients downloaded from the Cancer Genome Atlas (TCGA) database were analyzed to identify differentially expressed (DE) irlncRNAs. The irlncRNA pairs significantly correlated with the prognosis of patients were screened out by univariable Cox regression analysis and a prognostic model was constructed by Lasso and multivariate Cox regression analyses. A receiver operating characteristic (ROC) curve was then plotted, with the area under the curve calculated to confirm the reliability of the model. Based on the optimal cutoff value, CRC patients in the high- or low-risk groups were distinguished, laying the ground for evaluating the risk model from the following perspectives: survival, clinicopathological traits, tumor-infiltrating immune cells (TIICs), antitumor drug efficacy, kinase inhibitor efficacy, and molecules related to immune checkpoints.ResultsA prognostic model consisting of 15 irlncRNA pairs was constructed, which was found to have a high correlation with patient prognosis in a cohort from the TCGA (p &lt; 0.001, HR = 1.089, 95% CI [1.067–1.112]). According to both univariate and multivariate Cox analyses, this model could be used as an independent prognostic indicator in the TCGA cohort (p &lt; 0.001). Effective differentiation between high- and low-risk patients was also accomplished, on the basis of aggressive clinicopathological characteristics, sensitivity to antitumor drugs, and kinase inhibitors, the tumor immune infiltration status, and the expression levels of specific molecules related to immune checkpoints.ConclusionThe prognostic model established with irlncRNA pairs is a promising indicator for prognosis prediction in CRC patients.
COL3A1 and MMP9 Serve as Potential Diagnostic Biomarkers of Osteoarthritis and Are Associated With Immune Cell Infiltration
Authors: Li Shushan , Wang Haitao , Zhang Yi , Qiao Renqiu , Xia Peige , Kong Zhiheng , Zhao Hongbo , Yin Li 
Published: September 2021

BackgroundOsteoarthritis (OA) is one of the most common age-related degenerative diseases. In recent years, some studies have shown that pathological changes in the synovial membrane occur earlier than those in the cartilage in OA. However, the molecular mechanism of synovitis in the pathological process of OA has not been elucidated. This study aimed to identify novel biomarkers associated with OA and to emphasize the role of immune cells in the pathogenesis of OA.MethodsMicroarray datasets were obtained from the Gene Expression Omnibus (GEO) and ArrayExpress databases and were then analyzed using R software. To determine differential immune cell subtype infiltration, the CIBERSORT deconvolution algorithm was used. Quantitative reverse transcription PCR (qRT-PCR) was used to determine the relative expressions of selected genes. Besides, Western blotting was used to assess the protein expression levels in osteoarthritic chondrocytes.ResultsAfter analyzing the database profiles, two potential biomarkers, collagen type 3 alpha 1 chain (COL3A1), and matrix metalloproteinase 9 (MMP9), associated with OA were discovered, which were confirmed by qRT-PCR and Western blotting. Specifically, the results revealed that, as the concentration of IL-1β increased, so did the gene and protein expression levels of COL3A1 and MMP9.ConclusionThe findings provide valuable information and direction for future research into novel targets for OA immunotherapy and diagnosis and aids in the discovery of the underlying biological mechanisms of OA pathogenesis.
Construction on of a Ferroptosis-Related lncRNA-Based Model to Improve the Prognostic Evaluation of Gastric Cancer Patients Based on Bioinformatics
Authors: Pan Jiahui , Zhang Xinyue , Fang Xuedong , Xin Zhuoyuan 
Published: September 2021

BackgroundGastric cancer is one of the most serious gastrointestinal malignancies with bad prognosis. Ferroptosis is an iron-dependent form of programmed cell death, which may affect the prognosis of gastric cancer patients. Long non-coding RNAs (lncRNAs) can affect the prognosis of cancer through regulating the ferroptosis process, which could be potential overall survival (OS) prediction factors for gastric cancer.MethodsFerroptosis-related lncRNA expression profiles and the clinicopathological and OS information were collected from The Cancer Genome Atlas (TCGA) and the FerrDb database. The differentially expressed ferroptosis-related lncRNAs were screened with the DESeq2 method. Through co-expression analysis and functional annotation, we then identified the associations between ferroptosis-related lncRNAs and the OS rates for gastric cancer patients. Using Cox regression analysis with the least absolute shrinkage and selection operator (LASSO) algorithm, we constructed a prognostic model based on 17 ferroptosis-related lncRNAs. We also evaluated the prognostic power of this model using Kaplan–Meier (K-M) survival curve analysis, receiver operating characteristic (ROC) curve analysis, and decision curve analysis (DCA).ResultsA ferroptosis-related “lncRNA–mRNA” co-expression network was constructed. Functional annotation revealed that the FOXO and HIF-1 signaling pathways were dysregulated, which might control the prognosis of gastric cancer patients. Then, a ferroptosis-related gastric cancer prognostic signature model including 17 lncRNAs was constructed. Based on the RiskScore calculated using this model, the patients were divided into a High-Risk group and a low-risk group. The K-M survival curve analysis revealed that the higher the RiskScore, the worse is the obtained prognosis. The ROC curve analysis showed that the area under the ROC curve (AUC) of our model is 0.751, which was better than those of other published models. The multivariate Cox regression analysis results showed that the lncRNA signature is an independent risk factor for the OS rates. Finally, using nomogram and DCA, we also observed a preferable clinical practicality potential for prognosis prediction of gastric cancer patients.ConclusionOur prognostic signature model based on 17 ferroptosis-related lncRNAs may improve the overall survival prediction in gastric cancer.
SARS-CoV-2 Antibody Isotypes in Systemic Lupus Erythematosus Patients Prior to Vaccination: Associations With Disease Activity, Antinuclear Antibodies, and Immunomodulatory Drugs During the First Year of the Pandemic
Authors: Sjöwall Johanna , Azharuddin Mohammad , Frodlund Martina , Zhang Yuming , Sandner Laura , Dahle Charlotte , Hinkula Jorma , Sjöwall Christopher 
Published: September 2021

ObjectivesImpact of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic on individuals with arthritis has been highlighted whereas data on other rheumatic diseases, e.g., systemic lupus erythematosus (SLE), are scarce. Similarly to SLE, severe SARS-CoV-2 infection includes risks for thromboembolism, an unbalanced type I interferon response, and complement activation. Herein, SARS-CoV-2 antibodies in longitudinal samples collected prior to vaccination were analyzed and compared with SLE progression and antinuclear antibody (ANA) levels.MethodsOne hundred patients (83 women) with established SLE and a regular visit to the rheumatologist (March 2020 to January 2021) were included. All subjects donated blood and had done likewise prior to the pandemic. SARS-CoV-2 antibody isotypes (IgG, IgA, IgM) to the cell receptor-binding S1-spike outer envelope protein were detected by ELISA, and their neutralizing capacity was investigated. IgG-ANA were measured by multiplex technology.ResultsDuring the pandemic, 4% had PCR-confirmed infection but 36% showed SARS-CoV-2 antibodies of ≥1 isotype; IgA was the most common (30%), followed by IgM (9%) and IgG (8%). The antibodies had low neutralizing capacity and were detected also in prepandemic samples. Plasma albumin (p= 0.04) and anti-dsDNA (p= 0.003) levels were lower in patients with SARS-CoV-2 antibodies. Blood group, BMI, smoking habits, complement proteins, daily glucocorticoid dose, use of hydroxychloroquine, or self-reported coronavirus disease 2019 (COVID-19) symptoms (except fever, &gt;38.5°C) did not associate with SARS-CoV-2 antibodies.ConclusionOur data from early 2021 indicate that a large proportion of Swedish SLE patients had serological signs of exposure to SARS-CoV-2 but apparently with a minor impact on the SLE course. Use of steroids and hydroxychloroquine showed no distinct effects, and self-reported COVID-19-related symptoms correlated poorly with all antibody isotypes.
Heat Stress Alters the Intestinal Microbiota and Metabolomic Profiles in Mice
Authors: Wen Chaoyue , Li Siyu , Wang Jiaojiao , Zhu Yimin , Zong Xin , Wang Yizhen , Jin Mingliang 
Published: September 2021

BackgroundHeat stress has negative effects on the intestinal health of humans and animals. However, the impact of heat stress on intestinal microbial and metabolic changes remains elusive. Here, we investigated the cecal microbial and metabolic profiles in mice in response to heat stress.MethodsThe mouse heat stress model was constructed by simulating a high-temperature environment. Twenty mice were randomly assigned to two groups, the control group (CON, 25°C) and the heat treatment group (HS, 40°C from 13:00 to 15:00 every day for 7 days). Serum and cecal contents were collected from the mice for serum biochemical analysis, 16S rRNA high-throughput sequencing, and non-targeted metabolomics.ResultsBoth core body temperature and water intake were significantly increased in the HS group. Serum biochemical indicators were also affected, including significantly increased triglyceride and decreased low-density lipoprotein in the heat stress group. The composition and structure of intestinal microbiota were remarkably altered in the HS group. At the species level, the relative abundance of Candidatus Arthromitus sp. SFB-mouse-Japan and Lactobacillus murinus significantly reduced, while that of Lachnospiraceae bacterium 3-1 obviously increased after HS. Metabolomic analysis of the cecal contents clearly distinguished metabolite changes between the groups. The significantly different metabolites identified were mainly involved in the fatty acid synthesis, purine metabolism, fatty acid metabolism, cyanoamino acid metabolism, glyceride metabolism, and plasmalogen synthesis.ConclusionIn summary, high temperature disrupted the homeostatic balance of the intestinal microbiota in mice and also induced significant alterations in intestinal metabolites. This study provides a basis for treating intestinal disorders caused by elevated temperature in humans and animals and can further formulate nutritional countermeasures to reduce heat stress-induced damage.
Progressive Stroke Caused by Neurosyphilis With Concentric Enhancement in the Internal Cerebral Artery on High-Resolution Magnetic Resonance Imaging: A Case Report
Authors: Zhang Kejia , Chu Fengna , Wang Chao , Shi Mingchao , Yang Yi 
Published: September 2021

Background: Neurosyphilis can initially present as a stroke. However, the general management strategy for stroke may not be effective for this condition. Intracranial vessel wall imaging indicating arteritis can help differentiate neurosyphilis from other causes of stroke.Case presentation: A 59-year-old Chinese woman presented with an acute infarct in the left basal ganglia and multiple stenoses in the bilateral middle cerebral arteries, anterior cerebral artery, and basilar artery, which aggravated twice, despite antiplatelet treatment. High-resolution magnetic resonance imaging (HR-MRI) suggested concentric enhancement in the left middle cerebral artery. Treponema pallidum test results were positive, suggesting neurosyphilis.Conclusions: HR-MRI provides valuable information regarding arteritis, which is helpful in differentiating neurosyphilis from other causes of stroke. Antiplatelet medication should be used judiciously for neurosyphilis-related stroke.
Development and Validation of a Patient-Reported Outcome Scale for Tension-Type Headache
Authors: Huang Jinke , Guo Weichi , Li Hui , Xie Runsheng , Shen Min , Wang Huimin 
Published: September 2021

Objective: To validate a patient-reported outcome (PRO) measure for patients with tension-type headache (TTH).Methods: Literature analysis, interview, and group discussion were performed to develop an initial TTH-PRO. Thereafter, the initial scale was pre-evaluation in a small range of patients with TTH, and the expert panel made necessary adjustments based on the content feedback. The clinical test was carried out by using the adjusted initial scale. Based on the test results, the items were screened by the method of classical test theory to form the final scale, and the performance evaluation indicators such as validity, reliability, and responsiveness of the final scale were tested.Results: The final formed TTH-PRO scale contained three domains, six dimensions, and 30 items. The split-half reliability, Cronbach's α coefficients, and construct validity of the scale were acceptable, as was feasibility. The responsiveness in the physiological domain was fair, but the overall responsiveness still needed further clinical validation.Conclusions:The TTH-PRO scale has been developed with extensive patient input and demonstrates evidence for reliability and validity. It is complementary to existing evaluation indicators of TTH, emphasizing the patient's experience. Further studies are needed to optimize its items and to verify its clinical applicability for population in more regions and countries.
Endovascular Treatment With and Without Intravenous Thrombolysis in Large Vessel Occlusions Stroke: A Systematic Review and Meta-Analysis
Authors: Li Shuo , Liu Dan-Dan , Lu Guo , Liu Yun , Zhou Jun-Shan , Deng Qi-Wen , Yan Fu-Ling 
Published: September 2021

Background: Previous studies have shown conflicting results about the benefits of pretreatment with intravenous thrombolysis before endovascular treatment (EVT) in patients with acute ischemic stroke (AIS) with large vessel occlusions (LVOs). This study aimed to investigate the clinical efficacy and safety of EVT alone vs. bridging therapy (BT) in patients with AIS with LVOs.Methods: A systematic review with meta-analysis of all available studies comparing clinical outcomes between BT and EVT alone was conducted by searching the National Center for Biotechnology Information/National Library of Medicine PubMed and Web of Science databases for relevant literature from database inception to October 20, 2020.Results: A total of 93 studies enrolling 45,190 patients were included in the present analysis. In both unadjusted and adjusted analyses, BT was associated with a higher likelihood of 90-day good outcome (crude odds ratio [cOR] 1.361, 95% confidence interval [CI] 1.234–1.502 and adjusted OR [aOR] 1.369, 95% CI 1.217–1.540) and successful reperfusion (cOR 1.271, 95% CI 1.149–1.406 and aOR 1.267, 95% CI 1.095–1.465) and lower odds of 90-day mortality (cOR 0.619, 95% CI 0.560–0.684 and aOR 0.718, 95% CI 0.594–0.868) than EVT alone. The two groups did not differ in the occurrence of symptomatic intracranial hemorrhage (sICH) (cOR 1.062, 95% CI 0.915–1.232 and aOR 1.20, 95% CI 0.95–1.47), 24-h early recovery (cOR 1.306, 95% CI 0.906–1.881 and aOR 1.46, 95% CI 0.46–2.19), and number of thrombectomy device passes ≤ 2 (aOR 1.466, 95% CI 0.983–2.185) after sensitivity analyses and adjustment for publication bias.Conclusions: BT provides more benefits than EVT alone in terms of clinical functional outcomes without compromising safety in AIS patients with LVOs.