bluuebunny/crossref_metadata_2025_split huggingface dataset:
Additional prognostic value of stress cardiovascular magnetic resonance for cardiovascular risk stratification after a cryptogenic ischemic stroke
Authors: Toupin Solenn , Pezel Théo , Sanguineti Francesca , Kinnel Marine , Hovasse Thomas , Unterseeh Thierry , Champagne Stéphane , Garot Philippe , Garot Jérôme 
Published: September 2022

BackgroundOne-third of ischemic strokes are “cryptogenic” without clearly identified etiology. Although coronary artery disease (CAD) is the main cause of death after stroke, the interest in CAD screening in patients with cryptogenic stroke is still debated.AimThe aim of the study was to assess the incremental prognostic value of stress cardiovascular magnetic resonance (CMR) beyond traditional risk factors for predicting cardiovascular events in patients with a prior cryptogenic ischemic stroke.Materials and methodsBetween 2008 and 2021, consecutive patients with prior cryptogenic strokes referred for stress CMR were included and followed for the occurrence of major adverse cardiovascular events (MACEs), defined by cardiovascular death or non-fatal myocardial infarction (MI). Univariable and multivariable Cox regressions were performed to determine the prognostic value of unrecognized MI and silent ischemia.ResultsOf 542 patients (55.2% male, mean age 71.4 ± 8.8 years) who completed the follow-up (median 5.9 years), 66 (12.2%) experienced MACE. Silent ischemia and unrecognized MI were detected in 18 and 17% of patients, respectively. Using Kaplan–Meier analysis, silent ischemia and unrecognized MI were associated with the occurrence of MACE [hazard ratio, HR: 8.43 (95% CI: 5.11–13.9); HR: 7.87 (95% CI: 4.80–12.9), respectively, p &lt; 0.001]. In multivariable analysis, silent ischemia and unrecognized MI were independent predictors of MACE [HR: 8.08 (95% CI: 4.21–15.5); HR: 6.65 (95% CI: 3.49–12.7), respectively, p &lt; 0.001]. After adjustment, stress CMR findings showed the best improvement in model discrimination and reclassification above traditional risk factors (C-statistic improvement: 0.13; NRI = 0.428; IDI = 0.048).ConclusionIn patients with prior cryptogenic stroke, stress CMR findings have an incremental prognostic value to predict MACE over traditional risk factors.
Automatic view classification of contrast and non-contrast echocardiography
Authors: Zhu Ye , Ma Junqiang , Zhang Zisang , Zhang Yiwei , Zhu Shuangshuang , Liu Manwei , Zhang Ziming , Wu Chun , Yang Xin , Cheng Jun , Ni Dong , Xie Mingxing , Xue Wufeng , Zhang Li 
Published: September 2022

BackgroundContrast and non-contrast echocardiography are crucial for cardiovascular diagnoses and treatments. Correct view classification is a foundational step for the analysis of cardiac structure and function. View classification from all sequences of a patient is laborious and depends heavily on the sonographer’s experience. In addition, the intra-view variability and the inter-view similarity increase the difficulty in identifying critical views in contrast and non-contrast echocardiography. This study aims to develop a deep residual convolutional neural network (CNN) to automatically identify multiple views of contrast and non-contrast echocardiography, including parasternal left ventricular short axis, apical two, three, and four-chamber views.MethodsThe study retrospectively analyzed a cohort of 855 patients who had undergone left ventricular opacification at the Department of Ultrasound Medicine, Wuhan Union Medical College Hospital from 2013 to 2021, including 70.3% men and 29.7% women aged from 41 to 62 (median age, 53). All datasets were preprocessed to remove sensitive information and 10 frames with equivalent intervals were sampled from each of the original videos. The number of frames in the training, validation, and test datasets were, respectively, 19,370, 2,370, and 2,620 from 9 views, corresponding to 688, 84, and 83 patients. We presented the CNN model to classify echocardiographic views with an initial learning rate of 0.001, and a batch size of 4 for 30 epochs. The learning rate was decayed by a factor of 0.9 per epoch.ResultsOn the test dataset, the overall classification accuracy is 99.1 and 99.5% for contrast and non-contrast echocardiographic views. The average precision, recall, specificity, and F1 score are 96.9, 96.9, 100, and 96.9% for the 9 echocardiographic views.ConclusionsThis study highlights the potential of CNN in the view classification of echocardiograms with and without contrast. It shows promise in improving the workflow of clinical analysis of echocardiography.
Case Report: Composite pheochromocytoma with ganglioneuroma component: A report of three cases
Authors: Araujo Paula B. , Carvallo Mirna S. , Vidal Ana P. , Nascimento João B. , Wo Julia M. , Naliato Erika O. , Cunha Neto Silvio H. , Conceição Flavia L. , Fontes Rosita , de Lima Vinicius V. , Carvalho Denise P. , Soares Paula , Lima Jorge , Lourenço Delmar M. , Violante Alice Helena D. 
Published: September 2022

Composite pheochromocytoma (CP) is a very rare tumor originating from neural crest cells, predominantly composed of pheochromocytoma (PCC), a chromaffin cell tumor arising in adrenal medulla, and ganglioneuroma, a tumor derived from autonomic ganglion cells of the nervous system. Moreover, CP may be present in the hereditary syndromes of which pheochromocytoma is part. Literature offers scarce data on this subject, and particularly about its biological behavior, clinical evolution, and molecular profile. We report the phenotype and outcome of three cases of CP (PCC and ganglioneuroma components), followed up at the Endocrine Service of the Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, UFRJ, Rio de Janeiro, Brazil. Two nonsyndromic patients (cases 1 and 2) were negative to germline mutations in genes VHL, SDHB, SDHC, SDHD, SDHAF2, TMEM127, and MAX, while the third case (case 3) had clinical diagnosis of neurofibromatosis syndrome. Cases 1, 2, and 3 were diagnosed at 29, 39, and 47 years old, respectively, and were followed up for 3, 17, and 9 years without no CP recurrence. All cases had apparent symptoms of catecholaminergic excess secreted by PCC. Ganglioneuroma, the neurogenic component present in all three cases, had a percentage representation ranging from 5% to 15%. Tumors were unilateral and large, measuring 7.0 cm × 6.0 cm × 6.0 cm, 6.0 cm × 4.0 cm × 3.2 cm, and 7.5 cm × 6.0 cm × 4.5 cm, respectively. All cases underwent adrenalectomy with no recurrence, metastasis, or development of contralateral tumor during follow-up. Genetic testing has been scarcely offered to CP cases. However, a similar frequency of genetic background is found when compared with classic PCC, mainly by the overrepresentation of NF1 cases in the CP subset. By literature review, we identified a notorious increase in cases reported with CP in the last decade, especially in the last 3 years, indicating a recent improvement in the diagnosis of this rare disorder in clinical practice.
Gastrointestinal adverse events of metformin treatment in patients with type 2 diabetes mellitus: A systematic review, meta-analysis and meta-regression of randomized controlled trials
Authors: Nabrdalik Katarzyna , Skonieczna-Żydecka Karolina , Irlik Krzysztof , Hendel Mirela , Kwiendacz Hanna , Łoniewski Igor , Januszkiewicz Kornelia , Gumprecht Janusz , Lip Gregory Y. H. 
Published: September 2022

IntroductionMetformin is the first choice drug in the treatment of type 2 diabetes mellitus but its administration may be linked to gastrointestinal adverse events limiting its use.ObjectivesThe objective of this systematic review and meta-analysis was to assess the risk of gastrointestinal adverse events related to metformin use in patients with type 2 diabetes treated with metformin.MethodsPUB MED/CINAHL/Web of Science/Scopus were searched from database inception until 08.11.2020 for articles in English and randomized controlled trials related to patients with type 2 diabetes treated with metformin were included.ResultsFrom 5315 publications, we identified 199 potentially eligible full-text articles. Finally, 71 randomized controlled trials were included in the meta-analysis. In these studies, metformin use was associated with higher risk of abdominal pain, diarrhea and nausea comparing to control. The risks of abdominal pain and nausea were highest comparing to placebo. Bloating risk was only elevated when metformin treatment was compared to DPP4i.ConclusionsThe risk of gastrointestinal adverse events such as abdominal pain, nausea and diarrhea is higher in type 2 diabetes patients treated with metformin compared to other antidiabetic drugs. There is a higher risk of bloating and diarrhea with metformin immediate-release than with metformin extended release formulation.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021289975, identifier CRD42021289975.
Association between lncRNAs in plasma exosomes and diabetic retinopathy
Authors: Ye Qingqing , Li Lian , Shao Zhoujie , Xu Miao , Li Li , Yan Qianqian , Huang Bin , Zhao Tian 
Published: September 2022

BackgroundLong noncoding RNA (lncRNA) in plasma exosomes is a potential non-invasive diagnostic biomarker for diabetic retinopathy (DR). However, the changes in plasma exosomal lncRNAs and diagnostic relevance in patients with DR patients remain unclear.MethodsA case–control study with type 2 diabetes mellitus (T2DM) and patients with comorbid DR were enrolled, and their clinical information and blood samples were collected. Plasma exosomes were extracted, and the relative expression levels of representative differentially expressed exosomal lncRNAs were determined. A logistic regression model was used to analyze the relationships of DR with relative lncRNA expression and DR-related factors, and receiver operating characteristic (ROC) curve analysis was used to evaluate the value of exosomal lncRNAs for DR diagnosis.ResultsSixty-two patients with T2DM and sixty-two patients with DR were matched by age, sex, and disease duration. The fasting blood glucose concentration, glycosylated hemoglobin level (HbA1c), and relative expression of the plasma exosomal lncRNA DLX6-AS1 were significantly higher in the DR group than in the T2DM group, whereas the 2-h C-peptide concentration and relative expression of the lncRNAs PRINS and FAM190A-3 were lower in the DR group. After adjusting for relevant confounders, the fasting blood glucose concentration, HbA1c level, 2-h C-peptide concentration, and relative expression of lncRNA DLX6-AS1, PRINS, and FAM190A-3 were found to be associated with DR. Both DLX6-AS1 [area under the curve (AUC): 0.658 (0.562–0.754)], PRINS [AUC: 0.798 (0.722–0.873)], and FAM190A-3 [AUC: 0.603 (0.503-0.702)] expression had predictive value for DR diagnosis. The combination of DLX6-AS1 and PRINS yielded an AUC of 0.813 (0.740–0.886). In males, the combination of DLX6-AS1 and PRINS yielded an AUC of 0.860 (0.780–0.940).ConclusionThe fasting blood glucose concentration, HbA1c level, and exosomal DLX6-AS1 expression were identified as risk factors for DR, whereas the 2-h C-peptide concentration and exosomal PRINS and FAM190A-3 were identified as protective against DR. The combination of exosomal DLX6-AS1 and PRINS had good diagnostic value for DR in the general population and males. More attention should be paid to the role of exosomal PRINS expression as a predictive and diagnostic DR biomarker in females.
Single-cell transcriptome sequencing reveals potential novel combination of biomarkers for antibody-based cancer therapeutics in hepatocellular carcinoma
Authors: Tang Hong , Yuan Jun , Gong Yuan-Feng , Zhang Cheng-Yang , Liu Ming , Luo Su-Xia 
Published: September 2022

Background: Antibody-based cancer therapeutics is developing rapidly in recent years for its advantages in precisely targeting the tumor cells. However, tumor-specific cell surface antigens are still lacking, and the heterogeneity of tumor mass greatly impeded the development of effective drugs.Methods: In the present study, single-cell RNA sequencing was used to dissect tumor heterogeneity in human hepatocellular carcinoma (HCC). Tissues from different spatial regions including the tumor, para-tumor, and distant normal liver tissues were dissociated into single cells, and the gene expressions were compared in a different subpopulation of cells from these regions and validated in independent cohorts.Results: A total of 28 cell clusters with different distribution patterns and gene expression profiles were identified within a heterogenous tumor and its paired liver tissues. Differentially expressed genes encoding the plasma membrane in cells with hepatic lineage were further extracted from single-cell transcriptome sequencing and validated in TCGA database. A 3-gene signature was identified to be significantly upregulated in dominant HCC tumor cell subpopulations with prognostic significance and validated in multiple independent patient cohorts.Conclusion: The composition of the three plasma membrane proteins on the surface of HCC tumor cells within a heterogenous tumor might indicate poor prognostic tumor subpopulations during cancer evolution and potential therapeutic targets.
Screening and validation of platelet activation-related lncRNAs as potential biomarkers for prognosis and immunotherapy in gastric cancer patients
Authors: Yuan Mingjie , Jia Yanfei , Xing Yuanxin , Wang Yunshan , Liu Yunyun , Liu Xiangdong , Liu Duanrui 
Published: September 2022

Background: Platelets (PLT) have a significant effect in promoting cancer progression and hematogenous metastasis. However, the effect of platelet activation-related lncRNAs (PLT-related lncRNAs) in gastric cancer (GC) is still poorly understood. In this study, we screened and validated PLT-related lncRNAs as potential biomarkers for prognosis and immunotherapy in GC patients.Methods: We obtained relevant datasets from the Cancer Genome Atlas (TCGA) and Gene Ontology (GO) Resource Database. Pearson correlation analysis was used to identify PLT-related lncRNAs. By using the univariate, least absolute shrinkage and selection operator (LASSO) Cox regression analyses, we constructed the PLT-related lncRNAs model. Kaplan-Meier survival analysis, univariate, multivariate Cox regression analysis, and nomogram were used to verify the model. The Gene Set Enrichment Analysis (GSEA), drug screening, tumor immune microenvironment analysis, epithelial-mesenchymal transition (EMT), and DNA methylation regulators correlation analysis were performed in the high- and low-risk groups. Patients were regrouped based on the risk model, and candidate compounds and immunotherapeutic responses aimed at GC subgroups were also identified. The expression of seven PLT-related lncRNAs was validated in clinical medical samples using quantitative reverse transcription-polymerase chain reaction (qRT-PCR).Results: In this study, a risk prediction model was established using seven PLT-related lncRNAs -(AL355574.1, LINC01697, AC002401.4, AC129507.1, AL513123.1, LINC01094, and AL356417.2), whose expression were validated in GC patients. Kaplan-Meier survival analysis, the receiver operating characteristic (ROC) curve analysis, univariate, multivariate Cox regression analysis verified the accuracy of the model. We screened multiple targeted drugs for the high-risk patients. Patients in the high-risk group had a poorer prognosis since low infiltration of immune killer cells, activation of immunosuppressive pathways, and poor response to immunotherapy. In addition, we revealed a close relationship between risk scores and EMT and DNA methylation regulators. The nomogram based on risk score suggested a good ability to predict prognosis and high clinical benefits.Conclusion: Our findings provide new insights into how PLT-related lncRNAs biomarkers affect prognosis and immunotherapy. Also, these lncRNAs may become potential biomarkers and therapeutic targets for GC patients.
Circulating pyruvate is a potent prognostic marker for critical COVID-19 outcomes
Authors: Ceperuelo-Mallafré Victòria , Reverté Laia , Peraire Joaquim , Madeira Ana , Maymó-Masip Elsa , López-Dupla Miguel , Gutierrez-Valencia Alicia , Ruiz-Mateos Ezequiel , Buzón Maria José , Jorba Rosa , Vendrell Joan , Auguet Teresa , Olona Montserrat , Vidal Francesc , Rull Anna , Fernández-Veledo Sonia 
Published: September 2022

BackgroundCoronavirus-19 (COVID-19) disease is driven by an unchecked immune response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus which alters host mitochondrial-associated mechanisms. Compromised mitochondrial health results in abnormal reprogramming of glucose metabolism, which can disrupt extracellular signalling. We hypothesized that examining mitochondrial energy-related signalling metabolites implicated in host immune response to SARS-CoV-2 infection would provide potential biomarkers for predicting the risk of severe COVID-19 illness.MethodsWe used a semi-targeted serum metabolomics approach in 273 patients with different severity grades of COVID-19 recruited at the acute phase of the infection to determine the relative abundance of tricarboxylic acid (Krebs) cycle-related metabolites with known extracellular signaling properties (pyruvate, lactate, succinate and α-ketoglutarate). Abundance levels of energy-related metabolites were evaluated in a validation cohort (n=398) using quantitative fluorimetric assays.ResultsIncreased levels of four energy-related metabolites (pyruvate, lactate, a-ketoglutarate and succinate) were found in critically ill COVID-19 patients using semi-targeted and targeted approaches (p&lt;0.05). The combined strategy proposed herein enabled us to establish that circulating pyruvate levels (p&lt;0.001) together with body mass index (p=0.025), C-reactive protein (p=0.039), D-Dimer (p&lt;0.001) and creatinine (p=0.043) levels, are independent predictors of critical COVID-19. Furthermore, classification and regression tree (CART) analysis provided a cut-off value of pyruvate in serum (24.54 µM; p&lt;0.001) as an early criterion to accurately classify patients with critical outcomes.ConclusionOur findings support the link between COVID-19 pathogenesis and immunometabolic dysregulation, and show that fluorometric quantification of circulating pyruvate is a cost-effective clinical decision support tool to improve patient stratification and prognosis prediction.
Development of a novel hypoxia-immune–related LncRNA risk signature for predicting the prognosis and immunotherapy response of colorectal cancer
Authors: Luan Likun , Dai Youguo , Shen Tao , Yang Changlong , Chen Zhenpu , Liu Shan , Jia Junyi , Li Zhenhui , Fang Shaojun , Qiu Hengqiong , Cheng Xianshuo , Yang Zhibin 
Published: September 2022

BackgroundColorectal cancer (CRC) is one of the most common digestive system tumors worldwide. Hypoxia and immunity are closely related in CRC; however, the role of hypoxia-immune–related lncRNAs in CRC prognosis is unknown.MethodsData used in the current study were sourced from the Gene Expression Omnibus and The Cancer Genome Atlas (TCGA) databases. CRC patients were divided into low- and high-hypoxia groups using the single-sample gene set enrichment analysis (ssGSEA) algorithm and into low- and high-immune groups using the Estimation of STromal and Immune cells in MAlignant Tumours using Expression data (ESTIMATE) algorithm. Differentially expressed lncRNAs (DElncRNAs) between low- and high-hypoxia groups, low- and high-immune groups, and tumor and control samples were identified using the limma package. Hypoxia-immune–related lncRNAs were obtained by intersecting these DElncRNAs. A hypoxia-immune–related lncRNA risk signature was developed using univariate Cox regression and least absolute shrinkage and selection operator (LASSO) analyses. The tumor microenvironments in the low- and high-risk groups were evaluated using ssGSEA, ESTIMATE, and the expression of immune checkpoints. The therapeutic response in the two groups was assessed using TIDE, IPS, and IC50. A ceRNA network based on signature lncRNAs was constructed. Finally, we used RT-qPCR to verify the expression of hypoxia-immune–related lncRNA signatures in normal and cancer tissues.ResultsUsing differential expression analysis, and univariate Cox and LASSO regression analyses, ZNF667-AS1, LINC01354, LINC00996, DANCR, CECR7, and LINC01116 were selected to construct a hypoxia-immune–related lncRNA signature. The performance of the risk signature in predicting CRC prognosis was validated in internal and external datasets, as evidenced by receiver operating characteristic curves. In addition, we observed significant differences in the tumor microenvironment and immunotherapy response between low- and high-risk groups and constructed a CECR7–miRNA–mRNA regulatory network in CRC. Furthermore, RT-qPCR results confirmed that the expression patterns of the six lncRNA signatures were consistent with those in TCGA-CRC cohort.ConclusionOur study identified six hypoxia-immune–related lncRNAs for predicting CRC survival and sensitivity to immunotherapy. These findings may enrich our understanding of CRC and help improve CRC treatment. However, large-scale long-term follow-up studies are required for verification.
Research hotspot and trend analysis in the diagnosis of inflammatory bowel disease: A machine learning bibliometric analysis from 2012 to 2021
Authors: Liu Chuan , Yu Rong , Zhang Jixiang , Wei Shuchun , Xue Fumin , Guo Yingyun , He Pengzhan , Shang Lining , Dong Weiguo 
Published: September 2022

AimsThis study aimed to conduct a bibliometric analysis of the relevant literature on the diagnosis of inflammatory bowel disease (IBD), and show its current status, hot spots, and development trends.MethodsThe literature on IBD diagnosis was acquired from the Science Citation Index Expanded of the Web of Science Core Collection. Co-occurrence and cooperation relationship analysis of authors, institutions, countries, journals, references, and keywords in the literature were carried out through CiteSpace software and the Online Analysis platform of Literature Metrology. At the same time, the relevant knowledge maps were drawn, and the keywords cluster analysis and emergence analysis were performed.Results14,742 related articles were included, showing that the number of articles in this field has increased in recent years. The results showed that PEYRIN-BIROULET L from the University Hospital of Nancy-Brabois was the author with the most cumulative number of articles. The institution with the most articles was Mayo Clin, and the United States was far ahead in the article output and had a dominant role. Keywords analysis showed that there was a total of 818 keywords, which were mainly focused on the research of related diseases caused or coexisted by IBD, such as colorectal cancer and autoimmune diseases, and the diagnosis and treatment methods of IBD. Emerging analysis showed that future research hotspots and trends might be the treatment of IBD and precision medicine.ConclusionThis research was the first bibliometric analysis of publications in the field of IBD diagnosis using visualization software and data information mining, and obtained the current status, hotspots, and development of this field. The future research hotspot might be the precision medicine of IBD, and the mechanism needed to be explored in depth to provide a theoretical basis for its clinical application.