bluuebunny/crossref_metadata_2025_split huggingface dataset:
Visceral Adiposity Index Plays an Important Role in Prognostic Prediction in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome and Type 2 Diabetes Mellitus Undergoing Percutaneous Coronary Intervention
Authors: Zhao Qi , Cheng Yu-Jing , Xu Ying-Kai , Zhao Zi-Wei , Liu Chi , Sun Tie-Nan , Zhou Yu-Jie 
Published: November 2021

Background: Visceral adiposity index (VAI), a surrogate marker of adiposity and insulin resistance, has been demonstrated to be significantly related to cardiovascular disease. It remains indistinct whether VAI predicts adverse prognosis after percutaneous coronary intervention (PCI) for patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and type 2 diabetes mellitus (T2DM).Methods: A total of 798 participants who met the enrollment criteria were finally brought into this study. VAI was determined by waist circumference, body mass index, fasting triglyceride, and high-density lipoprotein cholesterol as previously reported. Adverse prognosis included all-cause death, non-fatal myocardial infarction, non-fatal ischemic stroke, and ischemia-driven revascularization, the composite of which was defined as the primary endpoint.Results: Higher VAI maintained as a significant and independent risk predictor for the primary endpoint, regardless of the adjustment for the various multivariate models [hazard ratio (95% CI) for fully adjusted model: 2.72 (2.02–3.68), p &lt; 0.001]. The predictive value of VAI was further confirmed in sensitivity analysis where VAI was taken as a continuous variate. There was a dose-response relationship of VAI with the risk of the primary endpoint (p for overall association &lt; 0.001). Moreover, the ability of VAI on the prediction of the primary endpoint was consistent between subgroups stratified by potential confounding factors (all p for interaction &gt; 0.05). VAI exhibited a significant incremental effect on risk stratification for the primary endpoint beyond existing risk scores, expressed as increased Harrell's C-index, significant continuous net reclassification improvement, and significant integrated discrimination improvement.Conclusion: VAI is a significant indicator for predicting worse prognosis and plays an important role in risk stratification among patients with NSTE-ACS and T2DM undergoing elective PCI. The present findings require further large-scale, prospective studies to confirm.
Phenotypic Clustering of Patients With Newly Diagnosed Coronary Artery Disease Using Cardiovascular Magnetic Resonance and Coronary Computed Tomography Angiography
Authors: Pezel Théo , Unterseeh Thierry , Hovasse Thomas , Asselin Anouk , Lefèvre Thierry , Chevalier Bernard , Neylon Antoinette , Benamer Hakim , Champagne Stéphane , Sanguineti Francesca , Toupin Solenn , Garot Philippe , Garot Jérôme 
Published: November 2021

Background: Epidemiological characteristics and prognostic profiles of patients with newly diagnosed coronary artery disease (CAD) are heterogeneous. Therefore, providing individualized cardiovascular (CV) risk stratification and tailored prevention is crucial.Objective: Phenotypic unsupervised clustering integrating clinical, coronary computed tomography angiography (CCTA), and cardiac magnetic resonance (CMR) data were used to unveil pathophysiological differences between subgroups of patients with newly diagnosed CAD.Materials and Methods: Between 2008 and 2020, consecutive patients with newly diagnosed obstructive CAD on CCTA and further referred for vasodilator stress CMR were followed for the occurrence of major adverse cardiovascular events (MACE), defined by cardiovascular death or non-fatal myocardial infarction. For this exploratory work, a cluster analysis was performed on clinical, CCTA, and CMR variables, and associations between phenogroups and outcomes were assessed.Results: Among 2,210 patients who underwent both CCTA and CMR, 2,015 (46% men, mean 70 ± 12 years) completed follow-up [median 6.8 (IQR 5.9–9.2) years], in which 277 experienced a MACE (13.7%). Three mutually exclusive and clinically distinct phenogroups (PG) were identified based upon unsupervised hierarchical clustering of principal components: (PG1) CAD in elderly patients with few traditional risk factors; (PG2) women with metabolic syndrome, calcified plaques on CCTA, and preserved left ventricular ejection fraction (LVEF); (PG3) younger men smokers with proximal non-calcified plaques on CCTA, myocardial scar, and reduced LVEF. Using survival analysis, the occurrence of MACE, cardiovascular mortality, and all-cause mortality (all p &lt; 0.001) differed among the three PG, in which PG3 had the worse prognosis. In each PG, inducible ischemia was associated with MACE [PG1, Hazards Ratio (HR) = 3.09, 95% CI, 1.70–5.62; PG2, HR = 3.62, 95% CI, 2.31–5.7; PG3, HR = 3.55, 95% CI, 2.3–5.49; all p &lt; 0.001]. The study presented some key limitations that may impact generalizability.Conclusions: Cluster analysis of clinical, CCTA, and CMR variables identified three phenogroups of patients with newly diagnosed CAD that were associated with distinct clinical and prognostic profiles. Inducible ischemia assessed by stress CMR remained associated with the occurrence of MACE within each phenogroup. Whether automated unsupervised phenogrouping of CAD patients may improve clinical decision-making should be further explored in prospective studies.
Positive Association Between Plasma Aldosterone Concentration and White Matter Lesions in Patients With Hypertension
Authors: Yuan Yujuan , Li Nanfang , Liu Yan , Zhu Qing , Heizhati Mulalibieke , Zhang Weiwei , Yao Xiaoguang , Zhang Deilian , Luo Qin , Wang Menghui , Chang Guijuan , Cao Mei , Zhou Keming , Wang Lei , Hu Junli , Maimaiti Nuerguli 
Published: November 2021

Background and ObjectiveWhite matter lesions (WMLs) are imaging changes in MRI of cerebral small vessel disease associated with vascular risk factors, increasing the risk of dementia, depression, and stroke. Aldosterone (ALD) or activation of mineralocorticoid receptor (MR) causes cerebrovascular injury in a mouse model. We aimed to analyze the relationship between ALD and WMLs in a population with hypertension.MethodsWe conducted a retrospective review of all patients screened for causes of secondary hypertension. We enrolled 547 patients with WMLs and matched these to controls without WMLs at a 1:1 ratio. White matter lesion load was assessed by using a modified Scheltens’ scale.ResultsAmong the analytic sample (N = 1,094) with ages ranging from 30 to 64 years, 62.2% were male. We divided plasma ALD concentration (PAC), plasma renin activity (PRA), and ALD–renin ratio (ARR) into the third tertile (Q3), second tertile (Q2), and first tertile (Q1). We also analyzed them simultaneously as continuous variables. Multivariate logistic regression analysis showed that participants in Q3 (&gt;17.26 ng/dl) of PAC (OR 1.59, 95% CI 1.15, 2.19), Q3 (&lt;0.80 ng/dl) of PRA (OR 2.50, 95% CI 1.81, 3.44), and Q3 (&gt;18.59 ng/dl per ng/ml*h) of ARR (OR 2.90, 95% CI 2.10, 4.01) had a significantly higher risk of WMLs than those in Q1 (&lt;12.48) of PAC, Q1 (&gt;2.19) of PRA, and Q1 (&lt;6.96) of ARR. In linear regression analysis, we separately analyzed the correlation between the modified Scheltens’ scale score and log(PAC) (β = 2.36; 95% CI 1.30, 3.41; p &lt; 0.001), log(PRA) (β = −1.76; 95% CI −2.09, −1.43; p &lt; 0.001), and log(ARR) (β = 1.86; 95% CI 1.55, 2.17; p &lt; 0.001), which were all significantly correlated with white matter lesion load, after adjusting for confounding factors. Simple mediation analyses showed that systolic blood pressure (SBP) or diastolic blood pressure (DBP) mediated −3.83% or −2.66% of the association between PAC and white matter lesion load, respectively. In stratified analyses, there was no evidence of subgroup heterogeneity concerning the change in the risk of WMLs (p &gt; 0.05 for interaction for all).ConclusionHigher PAC, especially in PAC &gt;17.26 ng/dl, increased the risk of WMLs. PAC was positively associated with white matter lesion load independent of SBP or DBP.
A Novel Immune and Stroma Related Prognostic Marker for Invasive Breast Cancer in Tumor Microenvironment: A TCGA Based Study
Authors: Huang Yizhou , Chen Lizhi , Tang Ziyi , Min Yu , Yu Wanli , Yang Gangyi , Zhang Lili 
Published: November 2021

BackgroundBreast cancer (BC) is the most frequent cancer in women. The tumor microenvironment (TME), consisting of blood vessels, immune cells, fibroblasts, and extracellular matrix, plays a pivotal role in tumorigenesis and progression. Increasing evidence has emphasized the importance of TME, especially the immune components, in patients with BC. Nevertheless, we still lack a deep understanding of the correlation between tumor invasion and TME status.MethodsTranscriptome and clinical data were retrieved from The Cancer Genome Atlas (TCGA) database. ESTIMATE algorithm was applied for quantifying stromal and immune scores. Then we screened out the differentially expressed genes (DEGs) through the intersection analysis. Furthermore, the establishment of protein-protein interaction (PPI) network and univariate COX regression analysis were utilized to determine the core genes in DEGs. In addition, we also performed Gene Set Enrichment Analysis (GSEA) and CIBERSORT analysis to distinguish the function of crucial gene expression and the proportion of tumor-infiltrating immune cells (TICs), respectively.ResultsA total of 1178 samples (112 normal samples and 1066 tumor samples) were extracted from TCGA for calculation, and 226 DEGs were obtained from this assessment. Further intersection analysis revealed eight key genes, including ITK, CD3E, CCL19, CD2, SH2D1A, CD5, SLAMF6, SPN, which were proven to correlate with BC status. Moreover, ITK was picked out for further study. The results illustrated that high expression of BC patients had a more prolonged overall survival (OS) time than ITK low expression BC patients (p = 0.009), and ITK expression also presented the statistical significance in age, TNM staging, tumor size classification, and metastasis classification. Additionally, GSEA and CIBERSORT analysis indicated that ITK expression had an association with immune activity in TME.ConclusionITK may be a potential indicator for prognosis prediction in patients with BC, and its biological behavior may promote our understanding of the molecular mechanism of tumor progression and targeted therapy.
Roles of Oxygen Vacancies in NiMoO4: A First-Principles Study
Authors: Wen Yuanbin , Wang Pengcheng , Ding Xinying , Feng Xiaobo , Qing Chen 
Published: November 2021

Oxygen vacancy has been suggested to play a role in the electrochemical ability of NiMoO4. The band structure and density of state of NiMoO4 bulks with different concentrations of oxygen vacancy were investigated by the first-principles calculation. Original NiMoO4 shows semiconductive properties with a direct band gap of 0.136 eV. When one to three oxygen vacancies were introduced in the NiMoO4 supercell, the band structure of NiMoO4 transforms to metallic properties, and oxygen vacancies formation energy increases with the increased number of oxygen vacancies. The oxygen vacancies in NiMoO4 lead to the increased electron localization of Ni 3d and Mo 3d state nearby the Fermi level, resulting in higher concentration of carriers in NiMoO4 and thus increase in its electrical conductivity. The results demonstrate that introducing oxygen vacancies can improve the conductive property of NiMoO4.
Postnatal Mental Health, Hand Washing Practices, and Infant Illness in Rural China
Authors: Jiang Qi , Cohen Nourya , Ohtori Mika , Gao Jie , Wang Qingzhi , Zhang Evelyn , Zhu Sabrina , Johnstone Hannah , Guo Yian , Dill Sarah-Eve , Zhou Huan , Rozelle Scott 
Published: November 2021

Background: Maternal mental health problems play an important role in infant well-being. Although western countries have extensively studied the associations between maternal mental disorders, hygiene practices and infant health, little is known in developing settings. This study investigates the correlations between postnatal mental health problems, hand washing practices and infant illness in rural western China.Methods: A total of 720 mothers of infants aged 0–6 months from four poor counties in rural western China were included in the survey. Mental health symptoms were assessed using the Depression, Anxiety, and Stress Scale-21 (DASS-21). Questions about infant illness and hand washing practices followed evaluative surveys from prior studies. Adjusted ordinary least squares regressions were used to examine correlations between postnatal mental health (depression, anxiety, and stress) symptoms, hand washing practices, and infant illness outcomes.Results: Maternal depression, anxiety and stress symptoms were significantly associated with reduced hand washing overall and less frequent hand washing after cleaning the infant's bottom. Mental health symptoms were also associated with a higher probability of infants showing two or more illness symptoms and visiting a doctor for illness symptoms. Individual hand washing practices were not significantly associated with infant illness; however, a composite measure of hand washing practices was significantly associated with reduced probability of infant illness.Conclusion: Postnatal mental health problems are prevalent in rural China and significantly associated with infant illness. Policy makers and practitioners should investigate possible interventions to improve maternal and infant well-being.
Methotrexate Treatment of Newly Diagnosed RA Patients Is Associated With DNA Methylation Differences at Genes Relevant for Disease Pathogenesis and Pharmacological Action
Authors: Guderud Kari , Sunde Line H. , Flåm Siri T. , Mæhlen Marthe T. , Mjaavatten Maria D. , Norli Ellen S. , Evenrød Ida M. , Andreassen Bettina K. , Franzenburg Sören , Franke Andre , Rayner Simon , Gervin Kristina , Lie Benedicte A. 
Published: November 2021

BackgroundMethotrexate (MTX) is the first line treatment of rheumatoid arthritis (RA), and methylation changes in bulk T cells have been reported after treatment with MTX. We have investigated cell-type specific DNA methylation changes across the genome in naïve and memory CD4+ T cells before and after MTX treatment of RA patients. DNA methylation profiles of newly diagnosed RA patients (N=9) were assessed by reduced representation bisulfite sequencing.ResultsWe found that MTX treatment significantly influenced DNA methylation levels at multiple CpG sites in both cell populations. Interestingly, we identified differentially methylated sites annotated to two genes; TRIM15 and SORC2, previously reported to predict treatment outcome in RA patients when measured in bulk T cells. Furthermore, several of the genes, including STAT3, annotated to the significant CpG sites are relevant for RA susceptibility or the action of MTX.ConclusionWe detected CpG sites that were associated with MTX treatment in CD4+ naïve and memory T cells isolated from RA patients. Several of these sites overlap genetic regions previously associated with RA risk and MTX treatment outcome.
Clinical Value of 18F-FDG PET/CT Scan and Cytokine Profiles in Secondary Hemophagocytic Lymphohistiocytosis in Idiopathic Inflammatory Myopathy Patients: A Pilot Study
Authors: Liang Junyu , Cao Heng , Wu Bowen , Liu Yinuo , He Ye , Xu Bei , Sun Yiduo , Ye Bingjue , Lin Jin 
Published: November 2021

BackgroundSecondary hemophagocytic lymphohistiocytosis (sHLH) is a rare but fatal complication in idiopathic inflammatory myopathy (IIM) patients. The clinical value of radiological manifestations and serum cytokines remain unknown in this systemic crisis. This study aims to investigate the clinical value of PET/CT scan and cytokine profiles in predicting and understanding sHLH in IIM patients.MethodsAdult IIM patients who were admitted to the four divisions of the First Affiliated Hospital, Zhejiang University School of Medicine (FAHZJU) from January 1, 2017 to December 31, 2020 were reviewed. PET/CT scan, cytokine profiles, and other factors of patients who met the inclusion and exclusion criteria were collected and analyzed.ResultsSixty-nine out of 352 IIM patients were finally enrolled into the study. Ten patients developed sHLH and 70.0% of them died within 6 months. After false discovery rate (FDR) correction and multivariate logistic regression analysis, increased serum interferon (IFN)-γ level (p = 0.017), higher spleen mean standard uptake value (SUVmean, p = 0.035), and positivity of anti-MDA5 antibody (p = 0.049) were found to be significantly correlated with development of sHLH in IIM patients. The combination of serum IFN-γ, spleen SUVmean, and anti-MDA5 antibody found a balanced and satisfying predictor with a cutoff value of 0.047 and AUC of 0.946. A moderate correlation was identified between ferritin and spleen SUVmean (p = 0.001, r = 0.380) as well as serum IFN-γ(p = 0.001, r = 0.398). Before FDR correction, higher bilateral lung SUVmean (p = 0.034) and higher colon/rectum SUVmean (p = 0.013) were also observed in IIM patients who developed sHLH. By narrowing down to IIM patients with sHLH, anti-MDA5-antibody-positive DM patients tended to suffer from unfavorable outcome (p = 0.004) in Kaplan–Meier survival analysis.ConclusionIncreased serum level of IFN-γ, elevated splenic FDG uptake, and positivity of anti-MDA5 antibody were significantly correlated with development of sHLH in IIM patients. Lung and lower digestive tract might also be affected due to systemic immune activation in IIM patients with sHLH. In addition, splenic FDG uptake, in combination with serum IFN-γand anti-MDA5 antibody, was found valuable in predicting development of sHLH in IIM patients. Among IIM patients with sHLH, anti-MDA5-antibody-positive DM patients showed higher tendency for unfavorable outcome.
Candidate Biomarkers to Distinguish Spinal Tuberculosis From Mechanical Back Pain in a Tuberculosis Endemic Setting
Authors: Mann Theresa N. , Davis Johan H. , Walzl Gerhard , Beltran Caroline G. , du Toit Jacques , Lamberts Robert P. , Chegou Novel N. 
Published: November 2021

BackgroundSpinal tuberculosis (TB) may have a variable, non-specific presentation including back pain with- or without- constitutional symptoms. Further tools are needed to aid early diagnosis of this potentially severe form of TB and immunological biomarkers may show potential in this regard. The aim of this study was to investigate the utility of host serum biomarkers to distinguish spinal TB from mechanical back pain.MethodsPatients with suspected spinal TB or suspected mechanical back pain were recruited from a tertiary hospital in the Western Cape, South Africa, and provided a blood sample for biomarker analysis. Diagnosis was subsequently confirmed using bacteriological testing, advanced imaging and/or clinical evaluation, as appropriate. The concentrations of 19 host biomarkers were evaluated in serum samples using the Luminex platform. Receiver Operating Characteristic (ROC) curves and General Discriminant Analysis were used to identify biomarkers with the potential to distinguish spinal TB from mechanical back pain.ResultsTwenty-six patients with spinal TB and 17 with mechanical back pain were recruited. Seven out of 19 biomarkers were significantly different between groups, of which Fibrinogen, CRP, IFN-γ and NCAM were the individual markers with the highest discrimination utility (Area Under Curve ROC plot 0.88-0.99). A five-marker biosignature (CRP, NCAM, Ferritin, CXCL8 and GDF-15) correctly classified all study participants after leave-one-out cross-validation.ConclusionThis study identified host serum biomarkers with the potential to diagnose spinal TB, including a five-marker biosignature. These preliminary findings require validation in larger studies.
Disease Severity Determines Timing of Initiating Continuous Renal Replacement Therapies: A Systematic Review and Meta-Analysis
Authors: Xia Zi-Jing , He Lin-ye , Pan Shu-Yue , Cheng Rui-Juan , Zhang Qiu-Ping , Liu Yi 
Published: November 2021

Background: Timing of initiating continuous renal replacement therapies (CRRTs) among the patients with acute kidney injury (AKI) in intensive care units (ICU) has been discussed over decades, but the definition of early and late CRRT initiation is still unclear.Methods: The English language randomized controlled trials (RCTs) and cohort studies were searched through MEDLINE, EMBASE, and Cochrane Library on July 19, 2019, by the two researchers independently. The study characteristics; early and late definitions; outcomes, such as all-cause, in-hospital, 28- or 30-, 60-, 90-day mortality; and renal recovery were extracted from the 18 eligible studies. Pooled relative risk ratios (RRs) and 95% CIs were estimated with the fixed effects model and random effects model as appropriate. This study is registered with PROSPERO (CRD 42020158653).Results: Eighteen studies including 3,914 patients showed benefit in earlier CRRT (n = 1,882) over later CRRT (n = 2,032) in all-cause mortality (RR 0.78, 95% CI 0.66–0.92), in-hospital mortality (RR 0.81, 95% CI 0.67–0.99), and 28- or 30-day mortality (RR 0.81, 95% CI 0.74–0.88), but in 60- and 90-day mortalities, no significant benefit was observed. The subgroup analysis showed significant benefit in the disease-severity-based subgroups on early CRRT initiation in terms of in-hospital mortality and 28- or 30-day mortality rather than the time-based subgroups. Moreover, early CRRT was found to have beneficial effects on renal recovery after CRRT (RR 1.21, 95% CI 1.01–1.45).Conclusions: Overall, compared with late CRRT, early CRRT is beneficial for short-term survival and renal recovery, especially when the timing was defined based on the disease severity. CRRT initiation on Acute Kidney Injury Network (AKIN) stage 1 or Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease (RIFLE)-Risk or less may lead to a better prognosis.
Association of Time–Varying Intensity of Ventilation With Mortality in Patients With COVID−19 ARDS: Secondary Analysis of the PRoVENT–COVID Study
Authors: Schuijt Michiel T. U. , van Meenen David M. P. , Martin–Loeches Ignacio , Mazzinari Guido , Schultz Marcus J. , Paulus Frederique , Serpa Neto Ary 
Published: November 2021

Background: High intensity of ventilation has an association with mortality in patients with acute respiratory failure. It is uncertain whether similar associations exist in patients with acute respiratory distress syndrome (ARDS) patients due to coronavirus disease 2019 (COVID−19). We investigated the association of exposure to different levels of driving pressure (ΔP) and mechanical power (MP) with mortality in these patients.Methods: PRoVENT–COVID is a national, retrospective observational study, performed at 22 ICUs in the Netherlands, including COVID−19 patients under invasive ventilation for ARDS. Dynamic ΔP and MP were calculated at fixed time points during the first 4 calendar days of ventilation. The primary endpoint was 28–day mortality. To assess the effects of time–varying exposure, Bayesian joint models adjusted for confounders were used.Results: Of 1,122 patients included in the PRoVENT–COVID study, 734 were eligible for this analysis. In the first 28 days, 29.2% of patients died. A significant increase in the hazard of death was found to be associated with each increment in ΔP (HR 1.04, 95% CrI 1.01–1.07) and in MP (HR 1.12, 95% CrI 1.01–1.36). In sensitivity analyses, cumulative exposure to higher levels of ΔP or MP resulted in increased risks for 28–day mortality.Conclusion: Cumulative exposure to higher intensities of ventilation in COVID−19 patients with ARDS have an association with increased risk of 28–day mortality. Limiting exposure to high ΔP or MP has the potential to improve survival in these patients.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT04346342.