bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patients With IBD Receiving Methotrexate Are at Higher Risk of Liver Injury Compared With Patients With Non-IBD Diseases: A Meta-Analysis and Systematic Review
Authors: Wang Yang , Li Yimin , Liu Yun , Zhang Yifan , Ke Ziliang , Zhang Yu , Liu Yulan 
Published: November 2021

Background: Methotrexate is well-known in treating inflammatory bowel disease (IBD), rheumatoid arthritis (RA), psoriasis (Ps), and psoriatic arthritis (PsA). Several reports have indicated a higher incidence of methotrexate (MTX)-related liver adverse events in patients with IBD. We aim to investigate the risk of liver injury in patients with IBD and those with non-IBD diseases treated with MTX.Methods: We searched PubMed, Embase, and the Cochrane Library for articles that reported liver adverse events in patients with IBD, RA, and Ps/PsA, receiving MTX therapy. Additional articles were obtained by screening the references of recent meta-analysis and reviews. Raw data from included articles were pooled to calculate the cumulative incidence of total liver injury (TLI), MTX discontinuation (MTX-D), and liver fibrosis (LF). RR (relative risk) was calculated to compare the difference between patients with IBD and those with non-IBD diseases.Results: A total of 326 articles with 128,876 patients were included. The patients with IBD had higher incidence of TLI [11.2 vs. 9.2%; relative risk (RR) = 1.22; P = 0.224] and MTX-D (2.6 vs. 1.8%; RR, 1.48; P = 0.089) than patients with non-IBD diseases. Due to the publication bias, trim-and-fill was performed. Afterwards, the patients with IBD showed significantly higher risk of TLI (11.2 vs. 3%; RR = 3.76; p &lt; 0.001), MTX-D (3.3 vs. 0.7%; RR = 5; p &lt; 0.001) and LF (3.1 vs. 0.1%; RR = 38.62; P = 0.001) compared with patients with non-IBD diseases.Conclusion: IBD is associated with a higher risk of MTX-related liver injury. The mechanism of MTX-induced hepatotoxicity might be different in IBD and non-IBD diseases, and needs to be verified in future research.
Radiological Characteristics of Patients With Anti-MDA5–Antibody-Positive Dermatomyositis in 18F-FDG PET/CT: A Pilot Study
Authors: Cao Heng , Liang Junyu , Xu Danyi , Liu Yinuo , Yao Yinan , Sun Yiduo , He Ye , Lin Jin 
Published: November 2021

Objective: To elucidate the 18F-fluorodeoxyglucose (FDG) PET/CT characteristics and its prognostic value in the patients with anti-melanoma differentiation associated protein 5 antibody positive (anti-MDA5+) dermatomyositis (DM).Methods: This retrospective cross-sectional study included 26 patients with anti-MDA5+ DM and 43 patients with anti-MDA5 negative (anti-MDA5–) idiopathic inflammatory myopathy (IIM) who were examined by 18F-FDG PET/CT from January 1, 2017 to December 31, 2020. The maximum standardized uptake value (SUVmax) of multiple organs and other clinical characteristics of the patients were measured and analyzed.Results: Compared with the anti-MDA5– group, the patients in the anti-MDA5+ group showed higher bilateral lung SUVmax (p = 0.029), higher SUVmax of spleen (p = 0.011), and bone marrow (p = 0.048). Significant correlations between the spleen SUVmax and serum ferritin levels (r = 0.398, p &lt; 0.001), erythrocyte sedimentation rate (ESR) (r = 0.274, p = 0.023), platelet count (r = −0.265, p= 0.028), myositis disease activity assessment score (r = 0.332, p = 0.005), bone marrow SUVmax (r = 0.564, p &lt; 0.001), and bilateral lung SUVmax (r = 0.393, p &lt; 0.001) were observed.Conclusion:18F-FDG PET/CT was found valuable in quantifying the pulmonary focal inflammation and potentially unveil the distinctive characteristics and pathophysiological mechanisms in the patients with anti-MDA5+ DM.
Dysregulated Serum Lipid Metabolism Promotes the Occurrence and Development of Diabetic Retinopathy Associated With Upregulated Circulating Levels of VEGF-A, VEGF-D, and PlGF
Authors: Zhang Xinyuan , Qiu Bingjie , Wang Qiyun , Sivaprasad Sobha , Wang Yanhong , Zhao Lin , Xie Rui , Li Lei , Kang Wenting 
Published: November 2021

Purpose: This study aims to explore the correlations of arteriosclerosis-associated plasma indices with various severity levels of diabetic retinopathy (DR) and to test the hypothesis that elevated circulating level of known angiogenic cytokines induced by hyperglycemia is associated with dyslipidemia on DR.Methods: This cross-sectional study consists of 131 patients with type 2 diabetes. The patients were categorized based on their DR status into those with no DR (diabetes mellitus, DM), non-proliferative diabetic retinopathy (NPDR), and proliferative diabetic retinopathy (PDR) groups. The biochemical profile including fasting glucose, glycated hemoglobin (HbA1c), lipid profile were estimated, plasma angiogenic cytokines (vascular endothelial growth factor, VEGF-A, -C, -D) and placental growth factor (PlGF) were analyzed by protein microarrays. The atherogenic plasma index (API) was defined as low-density lipoprotein cholesterol/high-density lipoprotein cholesterol (LDL-C/HDL-C); atherogenic index (AI) was calculated as (TC-(HDL-C))/HDL-C and atherogenic index of plasma (AIP) was defined as log (TG/HDL-C).Results: No significant differences were detected in the duration of hypertension, age, and gender between the three groups. Serum TC and LDL-C, AI, and API in the NPDR group and PDR group were significantly higher than those in the DM group. The circulating level of PlGF, VEGF-A, and VEGF-C were significantly correlated with the severity of DR. VEGF-D is a risk factor independent of API (Z = −2.61, P = 0.009) and AI (Z = −2.40, P = 0.016). Multivariate logistic regression showed that AI and API are strong risk factors for the occurrence and severity of DR. Associated with AI and API, VEGF-D and PlGF contribute to DR: VEGF-D [AI: P = 0.038, odd ratio (OR) = 1.38; VEGF-D: P = 0.002, OR = 1.00. API: P = 0.027, OR = 1.56, VEGF-D:P = 0.002, OR = 1.00] and PlGF [AI: P = 0.021, OR = 1.43; VEGF-D: P = 0.004, OR = 1.50. API: P = 0.011, OR = 1.66; VEGF-D: P = 0.005, OR = 1.49].Conclusions: Total cholesterol (TC) and LDL-C are risk factors for presence of any DR. Atherogenic index and API are novel and better predictive indicators for the occurrence and severity of DR in comparion with the traditional lipid profiles. Abnormal lipid metabolism are associated with the upregulation of circulating cytokines that are linked to the severity of DR.
Current Practice of Imaging-Guided Interventional Procedures in Rheumatic and Musculoskeletal Diseases: Results of a Multinational Multidisciplinary Survey
Authors: Carubbi Francesco , Bosch Philipp , Machado Pedro M. , Scirè Carlo Alberto , Alunno Alessia , Proft Fabian , Baraliakos Xenofon , Dejaco Christian 
Published: November 2021

Objectives: To investigate opinion and routine practice of specialists from different disciplines on imaging techniques for interventional procedures related to rheumatic and musculoskeletal diseases (RMDs).Methods: An English-language questionnaire was developed by an international working group and distributed to health care providers of various disciplines involved in the care of people with RMDs via an online survey tool (SoSci Survey®) from December 2019 to May 2020.Results: A total of 1,105 respondents from 56 countries completed the survey, over 60% of participants were rheumatologists. The majority of respondents (88%) performed interventional procedures in RMDs patients and 90% of them used imaging guidance. Ultrasonography was the most frequently used technique, particularly among rheumatologists. X-ray and computed tomography were mainly used by radiologists. A discrepancy emerged between the importance assigned to certain items such as the availability of a second operator and their actual implementation in clinical practice. Local barriers, lack of resources and facilities were mentioned as the most relevant obstacles in this regard. Lack of training on imaging and/or imaging guided procedures did not emerge as a barrier to perform such interventions; in fact, 19% of respondents performing the procedures indicated not to have received adequate training in this field.Conclusions: This is the first multinational multidisciplinary survey exploring in detail the opinions and practice on imaging guidance for interventional procedures in RMDs. A harmonization of protocols based on international guidelines, along with adequate training programmes and interventions on barriers at national/local levels are the main unmet needs requiring attention.
Altered Resting-State Electroencephalography Microstates in Idiopathic Generalized Epilepsy: A Prospective Case-Control Study
Authors: Jiang YuBao , Zhu MingYu , Hu Ying , Wang Kai 
Published: November 2021

Objective: Idiopathic generalized epilepsy (IGE) involves aberrant organization and functioning of large-scale brain networks. This study aims to investigate whether the resting-state EEG microstate analysis could provide novel insights into the abnormal temporal and spatial properties of intrinsic brain activities in patients with IGE.Methods: Three groups of participants were chosen for this study (namely IGE-Seizure, IGE-Seizure Free, and Healthy Controls). EEG microstate analysis on the resting-state EEG datasets was conducted for all participants. The average duration (“Duration”), the average number of microstates per second (“Frequency”), as well as the percentage of total analysis time occupied in that state (“Coverage”) of the EEG microstate were compared among the three groups.Results: For microstate classes B and D, the differences in Duration, Frequency, and Coverage among the three groups were not statistically significant. Both Frequency and Coverage of microstate class A were statistically significantly larger in the IGE-Seizure group than in the other two groups. The Duration and Coverage of microstate class C were statistically significantly smaller in the IGE-Seizure group than those in the other two groups.Conclusions: The Microstate class A was regarded as a sensorimotor network and Microstate class C was mainly related to the salience network, this study indicated an altered sensorimotor and salience network in patients with IGE, especially in those who had experienced seizures in the past 2 years, while the visual and attention networks seemed to be intact.Significance: The temporal dynamics of resting-state networks were studied through EEG microstate analysis in patients with IGE, which is expected to generate indices that could be utilized in clinical researches of epilepsy.
Trends in Incidence and Mortality of Stroke in China From 1990 to 2019
Authors: Sun Tong , Chen Siyang , Wu Ke , Sun Min , Zhang Xianyan , You Chao 
Published: November 2021

Objective: Stroke is a leading cause of mortality and morbidity globally. This study aimed to analyze the burden and 30-year trends of ischemic stroke, intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH) in China.Methods: Data that include incidence and mortality of stroke in China from January 1, 1990 to December 31, 2019 were derived from the Global Burden of Disease (GBD) study 2019. The absolute numbers of incident cases and deaths over the time, and age-standardized rates per 100,000, such as age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR), were analyzed.Results: In 2019, there were 3.9 (95% uncertainty intervals (UI) 3.4–4.5) million incident cases and 2.1 (3.4–4.5) million deaths related to stroke in China. The ASIR and ASMR of stroke in China was 200 (176–230) and 127 (110–144). From 1990 to 2019, the ASIR of ischemic stroke had increased by 35.0% (29.0–40.0) while the ASIR of ICH and SAH had decreased by −53.0% (−56.0 to −50.0) and by −39.0% (−44.0 to −35.0), respectively. The ASMR of ischemic stroke had increased by 3.0% (−26.0 to 16.0) while the ASMR of ICH and SAH had decreased by −48.0% (−59.0 to −38.0) and by −84.0% (−89.0 to −69.0), respectively.Conclusion: Although the incidence and mortality rates of stroke in China were decreased from 1990 to 2019, the number of incident cases and deaths nearly doubled. A sharp increase in the incidence rate of ischemic stroke was observed. A higher incidence rate of ischemic stroke in the women was also observed.
Comorbid Autoimmune Diseases in Patients With Myasthenia Gravis: A Retrospective Cross-Sectional Study of a Chinese Cohort
Authors: Shi Jianquan , Huan Xiao , Zhou Lei , Xi Jianying , Song Jie , Wang Ying , Luo Sushan , Zhao Chongbo 
Published: November 2021

Introduction: The phenomenon of coexisting autoimmune diseases (ADs) in patients with myasthenia gravis (MG) has attracted considerable attention. However, few studies have investigated the burden and potential clinical associations of ADs in Chinese MG cohorts.Methods: In this retrospective cross-sectional study, we reviewed the records of 1,132 patients with MG who were admitted to Huashan Hospital Fudan University from August 2013 to August 2020. Patients were excluded if they had incomplete medical records (n = 336).Results: Comorbid ADs were found in 92 of 796 Chinese patients with MG (11.6%), among which, hyperthyroidism (6.7%), hypothyrosis (2.6%), and vitiligo (0.8%) were predominant. Patients with MG with ADs were predominantly female, younger at the onset of MG symptoms, and had a lower frequency of thymoma. Compared to the general population, we found a significantly higher percentage of hyperthyroidism (8.5-fold increase, p &lt; 0.001), hypothyrosis (2.6-fold increase, p &lt; 0.001), vitiligo (1.3-fold increase, p &lt; 0.001), rheumatoid arthritis (1.4-fold increase, p &lt; 0.001), immune thrombocytopenic purpura (193.1-fold increase, p &lt; 0.001), autoimmune hemolytic anemia (7.4-fold increase, p &lt; 0.001), autoimmune hepatitis (5.1-fold increase, p &lt; 0.001), and polymyositis (11.5-fold increase, p &lt; 0.001) in patients with MG with ADs. Patients with MG with ADs presented a lower proportion of previous history of MC (0 vs. 5.6%, p &lt; 0.05) than those without ADs. The proportion of MGFA Class I at onset in patients with MG with ADs was significantly higher than that in patients with MG without ADs (77.0 vs. 52.7%, p &lt; 0.05). The proportion of MuSK-positive in patients with MG with ADs was significantly lower than that in patients with MG without ADs (0 vs. 4.8%, p &lt; 0.05).Conclusion: In conclusion, we observed a higher frequency of concurrent ADs in a Chinese MG cohort. Furthermore, MG combined with ADs tended to have mild clinical presentation.
Associations Between Intake of Fermented Dairy Products and Blood Lipid Concentrations Are Affected by Fat Content and Dairy Matrix – The Tromsø Study: Tromsø7
Authors: Machlik Monika Lund , Hopstock Laila Arnesdatter , Wilsgaard Tom , Hansson Patrik 
Published: November 2021

Introduction: Dairy fat is rich in saturated fatty acids known to increase serum low-density lipoprotein cholesterol (LDL-C) concentration, an important risk factor for cardiovascular disease (CVD). However, intake of fermented dairy products has been associated with reduced CVD risk in observational studies. How intakes of different fermented dairy products are associated with blood lipid concentrations may provide a possible explanation for the suggested reduced CVD risk.Aim: To examine the associations between different types of fermented dairy products, with various fat contents and dairy matrix structures, and blood lipid concentrations in a general population.Methods: In 11,377 women and men aged between 40-99 participating in the population-based Tromsø Study 2015-2016, multivariable linear regression was used to examine associations between total intake of fermented dairy products, intake of yogurt (including regular-fat, low-fat, and semi-solid yogurt), cheese (including regular-fat and low-fat), and liquid fermented dairy, and serum concentrations of total cholesterol, LDL-C, high-density lipoprotein cholesterol (HDL-C), and triglycerides. Dietary data was collected using a validated food frequency questionnaire. Analyses were adjusted for potential confounding factors, and cheese intake analyses were stratified by self-reported use of cholesterol-lowering drugs.Results: Cheese intake was positively associated with HDL-C [regression coefficient 0.02 mmol/l (95 % CI 0.01, 0.03)], and inversely associated with LDL-C [regression coefficient−0.03 mmol/l (95 % CI−0.04,−0.01)] and triglycerides [relative change −1.34 % (95 % CI: −2.29 %, −0.37 %)] per 25 g/day among non-users of cholesterol-lowering drugs, while no associations were found among users. Total intake of fermented dairy was inversely associated with triglycerides [relative change −1.11 % (95 % CI: −1.96 %, −0.24 %)] per 250 g/day, while no associations were found for yogurt intake. Intake of low-fat cheese was more favorably associated with blood lipids compared to regular-fat cheese, and semi-solid yogurt was inversely associated with LDL-C and triglycerides, while intake of liquid fermented dairy was not associated with any of the blood lipids.Conclusion: This study highlights the importance of investigating specific types of dairy products separately, based on fat content and dairy matrix, when examining effects on blood lipid concentrations, and stratifying statistical models by use of cholesterol-lowering drugs when relevant.
Metformin Downregulates PD-L1 Expression in Esophageal Squamous Cell Carcinoma by Inhibiting IL-6 Signaling Pathway
Authors: Lu Yao , Xin Dao , Guan Lulu , Xu Mengli , Yang Yalan , Chen Yu , Yang Yuanyuan , Wang-Gillam Andrea , Wang Li , Zong Shanggang , Wang Feng 
Published: November 2021

PurposeTo characterize the mechanism by which metformin inhibits PD-L1 expression in esophageal squamous cell carcinoma (ESCC) and to evaluate the effect of metformin on the antitumor immune response.MethodsThe Cancer Genome Atlas (TCGA) database was used to analyze the correlations between IL-6 and prognosis and between IL-6 and PD-L1 gene expression in esophageal cancer. Reverse transcription-quantitative polymerase chain reaction (RT-PCR), Western blotting and immunofluorescence were used to study the mechanism by which metformin affects PD-L1 expression. Additionally, T cell function was assessed in a coculture system containing ESCC cells and peripheral blood mononuclear cells (PBMCs) treated with metformin or IL-6. In an in vivo assay, we used a model established with NPIdKO™ mice, which have a reconstituted immune system generated by transplanting PBMCs through intravenous injection, to evaluate the effect of metformin on tumors.ResultsThe TCGA esophageal cancer data showed that IL-6 expression was positively correlated with PD-L1 expression and that patients with high IL-6 expression had a significantly lower overall survival rate than patients with low IL-6 expression. PD-L1 expression in ESCC cell lines was significantly inhibited by metformin via the IL-6/JAK2/STAT3 signaling pathway but was not correlated with the canonical AMPK pathway. In the coculture system, the metformin pretreatment group showed higher T cell activation and better T cell killing function than the control group. Animal experiments confirmed that metformin downregulated PD-L1 expression and that combination treatment with metformin and PD-1 inhibitors synergistically enhanced the antitumor response.ConclusionsMetformin downregulated PD-L1 expression by blocking the IL-6/JAK2/STAT3 signaling pathway in ESCC, which enhanced the antitumor immune response.
The Quantitative Assessment of Using Multiparametric MRI for Prediction of Extraprostatic Extension in Patients Undergoing Radical Prostatectomy: A Systematic Review and Meta-Analysis
Authors: Li Wei , Sun Yuan , Wu Yiman , Lu Feng , Xu Hongtao 
Published: November 2021

PurposeTo investigate the diagnostic performance of using quantitative assessment with multiparametric MRI (mpMRI) for prediction of extraprostatic extension (EPE) in patients with prostate cancer (PCa).MethodsWe performed a computerized search of MEDLINE, Embase, Cochrane Library, Web of Science, and Google Scholar from inception until July 31, 2021. Summary estimates of sensitivity and specificity were pooled with the bivariate model, and quality assessment of included studies was performed with the Quality Assessment of Diagnostic Accuracy Studies-2. We plotted forest plots to graphically present the results. Multiple subgroup analyses and meta-regression were performed to explore the variate clinical settings and heterogeneity.ResultsA total of 23 studies with 3,931 participants were included. The pooled sensitivity and specificity for length of capsular contact (LCC) were 0.79 (95% CI 0.75–0.83) and 0.77 (95% CI 0.73–0.80), for apparent diffusion coefficient (ADC) were 0.71 (95% CI 0.50–0.86) and 0.71 (95% CI 059–0.81), for tumor size were 0.62 (95% CI 0.57–0.67) and 0.75 (95% CI 0.67–0.82), and for tumor volume were 0.77 (95% CI 0.68–0.84) and 0.72 (95% CI 0.56–0.83), respectively. Substantial heterogeneity was presented among included studies, and meta-regression showed that publication year (≤2017 vs. &gt;2017) was the significant factor in studies using LCC as the quantitative assessment (P=0.02).ConclusionFour quantitative assessments of LCC, ADC, tumor size, and tumor volume showed moderate to high diagnostic performance of predicting EPE. However, the optimal cutoff threshold varied widely among studies and needs further investigation to establish.
Modalities and Determinants of Career Paths in Pediatrics: A Survey of Former Pediatric Residents From Lille University Medical Center
Authors: Héritier-Laffargue Charlotte , Takvorian Chloé , Kyheng Maeva , Nguyen Sylvie , Dubos François , Martinot Alain 
Published: November 2021

There is currently a shortage of pediatricians in the Nord-Pas-de-Calais (NPC) area of France. The shortage affects both hospital positions (since many departures are not replaced) and private practice. The objectives of the present study were to (i) describe the career paths of former pediatric residents from Lille University Medical Center, (ii) identify factors associated with leaving NPC and leaving hospital-based practice, and (iii) compare the characteristics associated with the various types of practice.Methods: Pediatric residents having started their residency at Lille University Medical Center between 1993 and 2013 were invited to fill out an online questionnaire. Main outcomes were leaving NPC and leaving hospital practice. The event rate at different times over a 10-year period was determined using the Kaplan-Meier method.Results: The response rate was 92% (284 out of 310 invited respondents): 61% had changed their place or type of practice at least once, 54% had moved to a different city, and 41% had left NPC. Having trained elsewhere than in Lille and the lack of a chief assistant specialist position in NPC were independently associated with leaving NPC. 73% of the respondents were currently in hospital-based practice. Having started residency after 2003, taking a sabbatical during the residency and not training in a subspecialty (other than general pediatrics) were independently associated with leaving hospital-based practice. The stated reasons for leaving hospital-based practice were on-call duties (according to 71% of the respondents), overwork (46%), family reasons (34%), and a poor atmosphere at work (34%). Hospital-based pediatricians were more active in research and teaching. They worked an average of 13 h more per week than the other respondents, and were less satisfied with their choice of professional activity and their work-life balance.Conclusion: Changes in the place or type of practice have become frequent. With the recent resurgence of interest in private practice, leaving hospital is reportedly associated with better working conditions, greater satisfaction, and a better work-life balance.