bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relation Between Plasma Proteomics Analysis and Major Adverse Cardiovascular Events in Patients With Stable Coronary Artery Disease
Authors: Dregoesc Mihaela Ioana , Ţigu Adrian Bogdan , Bekkering Siroon , van der Heijden Charlotte D. C. C. , Bolboacǎ Sorana Daniela , Joosten Leo A. B. , Visseren Frank L. J. , Netea Mihai G. , Riksen Niels P. , Iancu Adrian Corneliu 
Published: February 2022

ObjectiveDespite the advances in the control of traditional risk factors, coronary artery disease (CAD) remains the greatest cause of morbidity and mortality. Our aim was to establish the relation between plasma proteomics analysis and the risk of cardiovascular events in patients with stable CAD.Materials and MethodsPatients with stable CAD and documented coronary atherosclerosis were screened for inclusion. Using proximity extension assays, 177 plasma proteins were simultaneously measured. The endpoint consisted of the first major adverse cardiovascular event (MACE) and was the composite of cardiovascular death, acute coronary syndrome, stroke, transient ischemic attack, or acute limb ischemia at 18 months follow-up. Cox proportional-hazards regression with adjustment for multiple comparisons was used to identify biomarkers for the outcomes of interest.ResultsThe cohort consisted of 229 patients. Six mediators were associated with MACE (p &lt; 0.001). For these markers, the risk of MACE was calculated: tumor necrosis factor receptor superfamily member 13B (HR = 1.65; 95% CI: 1.30–2.10), C-C motif chemokine-3 (HR = 1.57; 95% CI: 1.23–1.98), decorin (HR = 1.65; 95% CI: 1.26–2.16), fibroblast growth factor-23 (HR = 1.56; 95% CI: 1.23–1.99), tumor necrosis factor-related apoptosis-inducing ligand-receptor 2 (TRAIL-R2) (HR = 1.61; 95% CI: 1.23–2.11), and tumor necrosis factor receptor superfamily member 10A (HR = 1.69; 95% CI: 1.25–2.29). Except for TRAIL-R2, the other proteins were associated with MACE independent of age, sex, diabetes mellitus, or estimated glomerular filtration rate.ConclusionsIn patients with stable CAD, five novel biomarkers were identified as independent risk factors for adverse outcomes. Novel biomarkers could represent pharmacological targets for the prevention of adverse cardiovascular events.
Cognitive Behavioral Training Reduces Socially Anxious Classroom Behavior in Primary School Students
Authors: Casale Gino , Haarhoff Daniel 
Published: February 2022

Many students show symptoms of social anxiety. Cognitive behavioral training (CBT) has been shown to be effective in reducing symptom behavior in therapeutic and school contexts, but there are hardly any single-case studies that examine the individual effectiveness in school settings. Furthermore, the extent to which differential responsivity effects are exhibited by students has not been examined yet. This single-case study with AB design investigates the effects of a CBT on the socially anxious classroom behavior of students with severe symptoms of social anxiety. Two female and two male students (9–10 years old) of an inclusive primary school in Germany participated in the CBT over a period of twelve weeks. Socially anxious behaviors were measured daily with Direct Behavior Rating-Multi Item Scales. Visual analyses, overlap indices, and regression models show a substantial behavioral improvement for all students during the intervention. However, there are differences between the students in terms of which specific behaviors were improved and whether the behavioral improvements took place immediately after the implementation of the intervention or continuously from measurement to measurement in the B phase. The results highlight the relevance of specific and individualized behavioral goals for CBT in school, although the effects should be replicated in experimental studies.
Physical Activity and Systemic Lupus Erythematosus Among European Populations: A Two-Sample Mendelian Randomization Study
Authors: Huang Shuo , Tian Fengyuan , Yang Xiaoxuan , Fang Sijia , Fan Yongsheng , Bao Jie 
Published: February 2022

Background: The causal relationship between physical activity (PA) and systemic lupus erythematosus (SLE) remains uncertain. We aimed to assess the causal effect of PA on SLE by two-sample Mendelian randomization (MR) study.Methods: Summary statistics of SLE were obtained from a genome-wide association study (GWAS) meta-analysis of European descent, including 4,036 cases and 6,959 controls. Genetic instruments for PA, including MVPA, VPA, SSOE, and average acceleration, were identified from a large-scale GWAS meta-analysis among 377,234 individuals of European ancestry from United Kingdom biobank and Atherosclerosis Risk in Communities (ARIC) study, and another GWAS with 91,105 European participants was employed for sedentary behavior. The two-sample MR study was conducted to estimate causal relationship between PA and SLE, with the inverse-variance weighted (IVW) method, simple- and weighted-median method. Moreover, MR-Egger regression, MR-PRESSO and leave-one-out analysis were performed to evaluate the potential pleiotropy effect.Results: In the end, we totally selected 37 SNPs (15 SNPs for MVPA, 5 SNPs for VPA, 9 SNPs for SSOE, 5 SNPs for average acceleration and 3 SNPs for sedentary behavior). According to the IVW results, as the primary method, we found that genetically predicted PA was not causally associated with risk of SLE (MVPA: OR 0.44, 95% CI 0.09–2.10, p = 0.305; VPA: OR 0.20, 95% CI 0.00–18.97, p = 0.490; SSOE: OR 0.96, 95% CI 0.03–29.24, p = 0.983; average acceleration: OR 0.91, 95% CI 0.79–1.05, p = 0.190; sedentary behavior: OR 1.54, 95% CI 0.35–6.81, p = 0.572). MR-Egger, MR-PRESSO, and leave-one-out analysis did not indicate horizontal pleiotropy.Conclusions: Our MR study suggested that genetically predicted PA was not causally associated with SLE among the European populations.
Immune ULBP1 is Elevated in Colon Adenocarcinoma and Predicts Prognosis
Authors: Ruan Guo-Tian , Xie Hai-Lun , Zhu Li-Chen , Ge Yi-Zhong , Yan Lin , Liao Cun , Gong Yi-Zhen , Shi Han-Ping 
Published: February 2022

Background: Colon adenocarcinoma (COAD) is still the main cause of cancer deaths worldwide. Although immunotherapy has made progress in recent years, there is still a need to improve diagnosis, prognosis, and treatment tools. UL-16 binding protein 1 (ULBP1) is a ligand that activates the receptor natural killer cell group 2 receptor D (NKG2D) and plays an important immunomodulatory role. We aimed to investigate the clinical significance of ULBP1 in COAD.Methods: We obtained the relevant data from The Cancer Genome Atlas (TCGA). A total of 438 patients with COAD were included in this study, with a mean age of 67.1 ± 13.03 years old, of which 234 (53.42%) were male. The diagnostic value of COAD tumor tissues and adjacent tissues was analyzed by ROC curve. Univariate and multivariate survival analysis investigated the prognostic value of ULBP1 gene, and Gene Set Enrichment Analysis (GSEA) curve was performed to analyze the biological process and enriched enrichment pathway of ULBP1 in COAD. Combination survival analysis investigated the combined prognostic effect of prognostic genes.Results:ULBP1 gene had a high diagnostic value in COAD [AUC (TCGA) = 0.959; AUC (Guangxi) = 0.898]. Up-regulated ULBP1 gene of patients with COAD predicted a worse prognosis compared to those patients with down-regulated ULBP1 gene (Adjusted HR = 1.544, 95% CI = 1.020–2.337, p = 0.040). The GSEA showed that ULBP1 was involved in the apoptotic pathway and biological process of T cell mediated cytotoxicity, regulation of natural killer cell activation, and T cell mediated immunity of COAD. The combination survival analysis showed that the combination of high expression of ULBP1, AARS1, and DDIT3 would increase the 2.2-fold death risk of COAD when compared with those of low expression genes.Conclusion: The immune-related ULBP1 gene had diagnostic and prognostic value in COAD. The combination of ULBP1, AARS1, and DDIT3 genes could improve the prognostic prediction performance in COAD.
Chloroquine Suppresses Effector B-Cell Functions and Has Differential Impact on Regulatory B-Cell Subsets
Authors: Ma Xin , Dai Yang , Witzke Oliver , Xu Shilei , Lindemann Monika , Kribben Andreas , Dolff Sebastian , Wilde Benjamin 
Published: February 2022

ObjectivesChloroquine (CQ) is approved for treatment of B-cell mediated diseases such as rheumatoid arthritis and systemic lupus erythematosus. However, the exact mode of action in these diseases has not been studied and it remains unclear which effect CQ has on B-cells. Thus, it was the aim of this study to investigate to which extent CQ affects functionality of effector and regulatory B-cell.MethodsFor this purpose, B-cells were isolated from peripheral blood of healthy controls and renal transplant patients. B-cells were stimulated in presence or absence of CQ and Interleukin-10 (IL-10) and Granzyme B (GrB) secretion were assessed. In addition, effector functions such as plasma cell formation, and Immunoglobulin G (IgG) secretion were studied.ResultsCQ suppressed Toll-Like-Receptor (TLR)-9 induced B-cell proliferation in a dose-dependent manner. IL-10pos regulatory B-cells were suppressed by CQ already at low concentrations whereas anti-IgG/IgM-induced GrB secreting regulatory B-cells were less susceptible. Plasma blast formation and IgG secretion was potently suppressed by CQ. Moreover, purified B-cells from renal transplant patients were also susceptible to CQ-induced suppression of effector B-cell functions as observed by diminished IgG secretion.ConclusionIn conclusion, CQ had a suppressive effect on IL-10 regulatory B-cells whereas GrB secreting regulatory B-cells were less affected. Effector functions of B-cells such as plasma blast formation and IgG secretion were also inhibited by CQ. Effector B-cells derived from renal transplant patients already under immunosuppression could be suppressed by CQ. These findings may partly explain the clinical efficacy of CQ in B-cell mediated autoimmune diseases. The application of CQ in other disease contexts where suppression of effector B-cells could offer a benefit, such as renal transplantation, may hypothetically be advantageous.
The Predictive Potential of the Baseline C-Reactive Protein Levels for the Efficiency of Immune Checkpoint Inhibitors in Cancer Patients: A Systematic Review and Meta-Analysis
Authors: Han Cheng-Long , Meng Guang-Xiao , Ding Zi-Niu , Dong Zhao-Ru , Chen Zhi-Qiang , Hong Jian-Guo , Yan Lun-Jie , Liu Hui , Tian Bao-Wen , Yang Long-Shan , Xue Jun-Shuai , Li Tao 
Published: February 2022

BackgroundThe relationship between baseline C-reactive protein (CRP) level and the prognosis of cancer patients receiving immune checkpoint inhibitor (ICI) treatment remains controversial. The aim of this meta-analysis was to clarify whether baseline CRP level can serve as a biomarker to predict the efficiency of ICI therapy.MethodsAll associated articles published in the Cochrane Library, EMBASE, and PubMed databases from the inception of the database to December 30, 2021, were retrieved. Progression-free survival (PFS) and overall survival (OS) outcomes were meta-analyzed using the random-effects model and adjusted using the trim-and-fill method because of publication bias.ResultsThirty-three studies (6,124 patients) conducted between 2013 and 2021 were identified. The pooled outcomes implied that high baseline CRP level patients had significantly worse OS (adjusted pooled value for univariate and multivariate analysis outcomes: HR = 1.48, 95% CI = 1.41–1.56; HR = 1.46, 95% CI = 1.34–1.59) and PFS (adjusted pooled value for univariate and multivariate analysis outcomes: HR = 1.29, 95% CI = 1.15–1.45; HR = 1.20, 95% CI = 1.02–1.40) than low baseline CRP level patients, irrespective of cancer or ICI type. Further analysis indicated that 1 mg/dl was appropriate as a cutoff value for determining the low or high level of baseline CRP to predict the OS or PFS of cancer patients receiving ICI treatment (univariate analysis: HR = 1.56, 95% CI = 1.24–1.97, P = 0.909; multivariate analysis: HR = 1.58, 95% CI = 1.23–2.03, P = 0.521).ConclusionsHigh baseline CRP level (&gt;1 mg/dl) may be an indicator for worse OS and PFS of cancer patients treated with ICIs. More high-quality prospective studies are warranted to assess the predictive value of CRP for ICI treatment.
Effect of Rehydration on the Performance of Mechanically Loaded UHPC
Authors: Wang Yue , An Mingzhe , Lu Jing , Huang Hanfeng 
Published: February 2022

Unhydrated cementitious materials in ultrahigh-performance concrete (UHPC) with a low water-to-binder ratio stop hydrating owing to water shortage but can continue to hydrate after re-exposure to water; this phenomenon is referred to as rehydration. This article discusses the effects of rehydration on the performance of mechanically loaded UHPC when subjected to continuous water exposure. For this purpose, UHPCs with a steel fiber content of 0 and 2% were prepared with a constant water–binder ratio of 0.20. A uniaxial compression load was applied to generate microcracks in the UHPC, where cube specimens were preloaded up to 50, 70, 90, and 100% of the ultimate compressive load. After preloading, UHPC specimens were stored in water for 90 days. Preloading is found to have a more significant effect on the splitting tensile strength than on the compressive strength. At different preload levels, the splitting tensile strength first increases and then decreases with increasing water curing time. The cumulative capillary water absorption decreases with increasing water curing time, and the percentage decrease increases with an increasing preload level. The chemically bound water content increases with increasing water curing time, and the increase becomes more significant at a higher preload level. The filling effect of the rehydration reduces the connectivity of the internal pores, which is the main reason for the increase in strength and decrease in permeability observed under water curing. These results provide a foundation for the application and life-cycle design of UHPC structures over long service periods in water environments.
SP-D and CC-16 Pneumoproteins' Kinetics and Their Predictive Role During SARS-CoV-2 Infection
Authors: Tiezzi Margherita , Morra Sofia , Seminerio Jimmy , Van Muylem Alain , Godefroid Audrey , Law-Weng-Sam Noémie , Van Praet Anne , Corbière Véronique , Orte Cano Carmen , Karimi Sina , Del Marmol Véronique , Bondue Benjamin , Benjelloun Mariam , Lavis Philomène , Mascart Françoise , van de Borne Philippe , Cardozo Alessandra K. 
Published: February 2022

BackgroundSurfactant protein D (SP-D) and pulmonary club cell protein 16 (CC-16) are called “pneumoproteins” and are involved in host defense against oxidative stress, inflammation, and viral outbreak. This study aimed to determine the predictive value of these pneumoproteins on the incidence of acute respiratory distress syndrome (ARDS) or death in patients with coronavirus disease-2019 (COVID-19).MethodsThis retrospective study included 87 patients admitted to an emergency department. Blood samples were collected on three time points (days 1, 5, and 14 from hospital admission). SP-D and CC-16 serum levels were determined, and univariate and multivariate analyses considering confounding variables (age, body mass index, tobacco use, dyspnea, hypertension, diabetes mellitus, neutrophil-to-lymphocyte ratio) were performed.ResultsBased on the multivariate analysis, SP-D level on D1 was positively and slightly correlated with subsequent development of ARDS, independent of body mass index, dyspnea, and diabetes mellitus. CC-16 level on D1 was modestly and positively correlated with fatal outcome. A rise in SP-D between D1 and D5 and D1 and D14 had a strong negative association with incidence of ARDS. These associations were independent of tobacco use and neutrophil-to-lymphocyte ratio.ConclusionsOverall, our data reveal that increase in SP-D levels is a good prognostic factor for patients with COVID-19, and that initial CC-16 levels correlated with slightly higher risk of death. SP-D and CC-16 may prove useful to predict outcomes in patients with COVID-19.
Anxiety, Depression, and Apathy as Predictors of Cognitive Decline in Patients With Parkinson's Disease—A Three-Year Follow-Up Study
Authors: Toloraia Ketevan , Meyer Antonia , Beltrani Selina , Fuhr Peter , Lieb Roselind , Gschwandtner Ute 
Published: February 2022

ObjectiveAnxiety, depression, and apathy are the most common neuropsychiatric symptoms in Parkinson's disease (PD) patients. They impair cognitive functioning and have a profound impact on quality of life. This follow-up study aims to investigate the predictive value of anxiety, depression, and apathy on the development of Mild Cognitive Impairment (MCI) in PD patients.MethodsTwenty-nine cognitively unimpaired PD patients (mean age 68.2 SD ± 7.12 years; 13 women) participated in this study. At Baseline (BL) levels of apathy (Apathy Evaluation Scale, AES), depression (Beck Depression Inventory, BDI-II), and anxiety (Beck Anxiety Inventory, BAI), were assessed. Cognitive status was reassessed three years later according to MCI/non-MCI status. For statistics, we used binary logistic regression and receiver operating characteristic curve (ROC) analysis to examine anxiety, apathy, and depression at BL as a predictor of MCI status three years later.ResultsEight of the 29 patients developed MCI. Anxiety level at BL was found to predict MCI status at three-year follow-up (OR = 1.20, CI = 1.02–1.41, p = 0.02), while depression (OR = 1.16, CI = 0.93–1.47, p = 0.20) and apathy (OR = 1.06, CI = 0.92–1.23, p = 0.40) did not predict MCI status. The area under the ROC curve (AUC) of BAI for discriminating PD-non-MCI from PD-MCI was 0.79 (CI = 0.61–0.98). The optimal classification threshold yielded a sensitivity of 75.0 % and a specificity of 76.2 %. Neither apathy nor depression at BL discriminated between PD-non-MCI patients from PD-MCI three years later.ConclusionsThis study shows an association between anxiety and the development of MCI in PD patients, although the association between apathy, depression, and MCI did not reach a significant level.
Long-Term Improvement in a Chinese Cohort of Glucocorticoid-Resistant Childhood-Onset Myasthenia Gravis Patients Treated With Tacrolimus
Authors: Bi Zhuajin , Cao Yayun , Lin Jing , Zhang Qing , Liu Chenchen , Gui Mengcui , Bu Bitao 
Published: February 2022

ObjectivesTo evaluate the long-term outcome of tacrolimus for childhood-onset myasthenia gravis (CMG) with an inadequate response to glucocorticoids, and investigate factors associated with favorable outcomes following tacrolimus treatment.MethodsA retrospective, observational cohort study was performed for CMG patients who had not improved satisfactorily after sufficient prednisone therapy for at least 8 weeks. All patients were given tacrolimus in doses of 2–3 mg for more than 6 months. The primary efficacy outcome was assessed using the prednisone dose, quantitative MG (QMG), and MG-activity of daily living (ADL) scores. The participants were divided into improved and unimproved groups based on changes in QMG scores to investigate the risk factors that affected tacrolimus efficacy.ResultsA total of 149 glucocorticoid resistant CMG patients were finally enrolled in our study, with 113 (75.8%) responding well to tacrolimus (defined as minimal manifestation status or better). One month after initiating tacrolimus, there was a noticeable improvement in prednisone dose, QMG, and ADL scores, which continued to improve throughout the study. More importantly, the prednisone was eventually stopped in 89 of the patients (78.8%). Thymus type [odds ratio (OR) = 3.156, 95% confidence interval (CI) 1.427–6.978; P = 0.005] and pre-intervention status (OR = 0.284, 95%CI 0.109–0.741; P = 0.010) were independent predictors of tacrolimus efficacy after controlling for confounding factors in multiple logistic regression.ConclusionThe majority of glucocorticoid-resistant CMG patients have a good long-term prognosis after adding tacrolimus. Thymus type and pre-intervention status can serve as potential predictors affecting the efficacy of tacrolimus.
Gender and Emotional Representation Matter: Own Illness Beliefs and Their Relationship to Obesity
Authors: Henning Carmen , Schroeder Stefanie , Steins-Loeber Sabine , Wolstein Joerg 
Published: February 2022

BackgroundCurrent treatments of obesity often fail to consider gender and psychological aspects, which are essential for weight loss and weight maintenance. The aim of our study was to analyze subjective illness representations (SIRs) of adults with obesity according to the Common-Sense Self-Regulation Model (CSM) by assessing their associations with weight-related variables and gender.MethodsData was collected via online self-assessment between April 2017 and March 2018. SIRs were operationalized by the revised Illness Perception Questionnaire (IPQ-R) and illness outcomes according to the CSM were defined as BMI, eating behaviour, physical wellbeing, bodyweight satisfaction, and shape concerns. The sample consisted of 427 adults (M = 42.2 years, SD = 10.9; 82% female) with obesity (BMI: M = 42.3 kg/m2, SD = 9.0). Student's t-tests and multiple hierarchical regression analyses were conducted with the control variables (age and BMI) and subjective illness representations and gender as independent variables.ResultsThe explanation of outcome variances was moderate to high (21-43%) except for restraint eating behaviour (10%). Subjective illness representations showed several significant associations with weight-related variables, especially timeline and emotional representations. Female gender was significantly associated with more restraint eating behaviour [F(1, 400) = 4.19, p &lt; 0.001] and females had unfavourable values of the weight-related variables as well as a more cyclic [t(425) = 3.68, p &lt; 0.001], and more emotional representation [t(100) = 5.17, p &lt; 0.001] of their obesity.ConclusionThe results of this study indicate that gender and subjective illness representations, especially the emotional representation, play an important role for weight-related variables. Therefore, the assessment of SIRs may constitute an economic tool to identify specific individual deficits of self-regulation.