bluuebunny/crossref_metadata_2025_split huggingface dataset:
YKL-40 Aggravates Early-Stage Atherosclerosis by Inhibiting Macrophage Apoptosis in an Aven-dependent Way
Authors: Huan Wei , Yandong Liu , Chao Wang , Sili Zou , Jun Bai , Mingfang Liao , Yu Chen , Lefeng Qu 
Published: December 2021

Objective: programmed cell removal in atherosclerotic plaques plays a crucial role in retarding lesion progression. Macrophage apoptosis has a critical role in PrCR, especially in early-stage lesions. YKL-40 has been shown to be elevated as lesions develop and is closely related to macrophages. This study aimed to determine the effect of YKL-40 on regulating macrophage apoptosis and early-stage atherosclerosis progression.Research design and Methods: The correlations among the expression level of YKL-40, the area of early-stage plaque, and the macrophage apoptosis rate in plaques have been shown in human carotid atherosclerotic plaques through pathological and molecular biological detection. These results were successively confirmed in vivo (Ldlr−/- mice treated by YKL-40 recombinant protein/neutralizing antibody) and in vitro (macrophages that Ykl40 up-/down-expressed) experiments. The downstream targets were predicted by iTRAQ analysis.Results: In early-stage human carotid plaques and murine plaques, the YKL-40 expression level had a significant positive correlation with the area of the lesion and a significant negative correlation with the macrophage apoptosis rate. In vivo, the plaque area of aortic roots was significantly larger in the recomb-YKL-40 group than that in IgG group (p = 0.0247) and was significantly smaller in the anti-YKL-40 group than in the IgG group (p = 0.0067); the macrophage apoptosis rate of the plaque in aortic roots was significantly lower in the recomb-YKL-40 group than that in IgG group (p = 0.0018) and was higher in anti-YKL-40 group than that in VC group. In vitro, the activation level of caspase-9 was significantly lower in RAW264.7 with Ykl40 overexpressed than that in controls (p = 0.0054), while the expression level of Aven was significantly higher than that in controls (p = 0.0031). The apoptosis rate of RAW264.7 treated by recomb-YKL40 was significantly higher in the Aven down-regulated group than that in the control group (p &lt; 0.001). The apoptosis inhibitor Aven was confirmed as the target molecule of YKL-40. Mechanistically, YKL-40 could inhibit macrophage apoptosis by upregulating Aven to suppress the activation of caspase-9.Conclusion: YKL-40 inhibits macrophage apoptosis by upregulating the apoptosis inhibitor Aven to suppress the activation of caspase-9, which may impede normal PrCR and promote substantial accumulation in early-stage plaques, thereby leading to the progression of atherosclerosis.
A Novel lncRNA Panel Related to Ferroptosis, Tumor Progression, and Microenvironment is a Robust Prognostic Indicator for Glioma Patients
Authors: He Yikang , Ye Yangfan , Tian Wei , Qiu Huaide 
Published: December 2021

Objective: To establish a lncRNA panel related to ferroptosis, tumor progression, and microenvironment for prognostic estimation in patients with glioma.Methods: LncRNAs associated with tumor progression and microenvironment were screened via the weighted gene co-expression network analysis (WGCNA). Overlapped lncRNAs highlighted in WGCNA, related to ferroptosis, and incorporated in Chinese Glioma Genome Atlas (CGGA) were identified as hub lncRNAs. With expression profiles of the hub lncRNA, we conducted the least absolute shrinkage and selection operator (LASSO) regression and built a ferroptosis-related lncRNA signature to separate glioma patients with distinct survival outcomes. The lncRNA signature was validated in TCGA, the CGGA_693, and CGGA_325 cohorts using Kaplan-Meier survival analysis and ROC curves. The ferroptosis-related lncRNA panel was validated with 15 glioma samples using quantitative real-time PCR (qRT-PCR). Multivariate Cox regression was performed, and a nomogram was mapped and validated. Immune infiltration correlated to the signature was explored using TIMER and CIBERSORT algorithms.Results: The present study identified 30 hub lncRNAs related to ferroptosis, tumor progression, and microenvironment. With the 30 hub lncRNAs, we developed a lncRNA signature with distinct stratification of survival chance in patients with glioma in two independent cohorts (HRs&gt;1, p &lt; 0.05). The lncRNA signature revealed a panel of 14 lncRNAs, i.e., APCDD1L-AS1, H19, LINC00205, LINC00346, LINC00475, LINC00484, LINC00601, LINC00664, LINC00886, LUCAT1, MIR155HG, NEAT1, PVT1, and SNHG18. These lncRNA expressions were validated in clinical specimens using qRT-PCR. Robust predictive accuracies of the signature were present across different datasets at multiple timepoints. With univariate and multivariate regressions, we demonstrated that the risk score based on the lncRNA signature is an independent prognostic indicator after clinical factors were adjusted. A nomogram was constructed with these prognostic factors, and it has demonstrated decent classification and accuracy. Additionally, the signature-based classification was observed to be correlated with multiple clinical characteristics and molecular subtypes. Further, extensive immune cells were upregulated in the high-risk group, such as CD8+ T cell, neutrophil, macrophage, and myeloid dendritic cell, indicating increased immune infiltrations.Conclusion: We established a novel ferroptosis-related lncRNA signature that could effectively stratify the prognosis of glioma patients with adequate predictive performance.
BBS7–SHH Signaling Activity Regulates Primary Cilia for Periodontal Homeostasis
Authors: Chang Pi En , Li Shujin , Kim Hyun-Yi , Lee Dong-Joon , Choi Yoon Jeong , Jung Han-Sung 
Published: December 2021

Objectives: Mechanical stimuli are essential for the maintenance of periodontal ligament (PDL) homeostasis. Although there are several studies on atrophic changes in PDL due to occlusal hypofunction, the underlying mechanism is still unknown. Here, we aimed to explore the changes of gene expression in occlusal hypofunctional PDL and elucidate the related role in maintaining the PDL homeostasis.Methods: To investigate the transcriptomic difference between control and hypofunctional PDL tissue from patients, RNA sequencing was performed on 34 human teeth. The atrophic changes in PDL were evaluated by histological analysis. The effect of the Bardet-Biedl syndrome 7 (BBS7) knockdown was evaluated by the RT-qPCR, Western blot, wound healing, and tubule formation assay.Results: We detected that the expression of BBS7 was downregulated in occlusal hypofunctional PDL through RNA sequencing. Dynamic changes, including the number of periodontal ligament cells, alignment of collagen fibers, diameter of blood vessels, appearance of primary cilia, and torturous oxytalan fibers, were observed following occlusal hypofunction. Furthermore, Sonic hedgehog signaling (Shh) activity was closely associated with BBS7 expression in PDL cells. In addition, the cell migration and angiogenesis were also suppressed by BBS7 knockdown in vitro.Conclusion: We suggest that BBS7 plays an essential role in maintaining Shh signaling activity for PDL homeostasis.
The Clinical Course of Alcohol Use Disorder Depicted by Digital Biomarkers
Authors: Zetterström Andreas , Hämäläinen Markku D. , Winkvist Maria , Söderquist Marcus , Öhagen Patrik , Andersson Karl , Nyberg Fred 
Published: December 2021

Aims: This study introduces new digital biomarkers to be used as precise, objective tools to measure and describe the clinical course of patients with alcohol use disorder (AUD).Methods: An algorithm is outlined for the calculation of a new digital biomarker, the recovery and exacerbation index (REI), which describes the current trend in a patient's clinical course of AUD. A threshold applied to the REI identifies the starting point and the length of an exacerbation event (EE). The disease patterns and periodicity are described by the number, length, and distance between EEs. The algorithms were tested on data from patients from previous clinical trials (n = 51) and clinical practice (n = 1,717).Results: Our study indicates that the digital biomarker-based description of the clinical course of AUD might be superior to the traditional self-reported relapse/remission concept and conventional biomarkers due to higher data quality (alcohol measured) and time resolution. We found that EEs and the REI introduce distinct tools to identify qualitative and quantitative differences in drinking patterns (drinks per drinking day, phosphatidyl ethanol levels, weekday and holiday patterns) and effect of treatment time.Conclusions: This study indicates that the disease state—level, trend and periodicity—can be mathematically described and visualized with digital biomarkers, thereby improving knowledge about the clinical course of AUD and enabling clinical decision-making and adaptive care. The algorithms provide a basis for machine-learning-driven research that might also be applied for other disorders where daily data are available from digital health systems.
Risk for Cardiovascular Adverse Events Associated With Sphingosine-1-Phosphate Receptor Modulators in Patients With Multiple Sclerosis: Insights From a Pooled Analysis of 15 Randomised Controlled Trials
Authors: Zhao Zhao , Lv Yang , Gu Zhi-Chun , Ma Chun-Lai , Zhong Ming-Kang 
Published: December 2021

BackgroundAll agents engaging sphongosine-1-phospate receptors (S1PRs) will have some cardiovascular effect. This study aimed to elucidate the risk of cardiovascular adverse events (AEs) in patients with multiple sclerosis (MS) treated with S1PR modulators (S1PRMs).MethodsWe systematically searched the PubMed, EMBASE, and Cochrane Library databases for randomised controlled trials (RCTs) published through January 5, 2021. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated using the random-effects model. Sensitivity analyses and meta-regression were performed.ResultsSeventeen RCTs (12 for fingolimod; 3 for ozanimod; 2 for siponimod) involving 13,295 patients were included. Compared with the control treatment, S1PRMs significantly increased the risk of cardiovascular AEs (RR, 2.21; 95% CI, 1.58–3.10; I2, 75.6%). Notably, the high-risk cardiovascular AEs associated with S1PRMs were primarily bradyarrhythmia (RR, 2.92; 95% CI, 1.91–4.46; I2, 30.8%) and hypertension (RR, 2.00; 95% CI, 1.49–2.67; I2, 56.5%). Subgroup analysis results were consistent with the primary outcomes except that ozanimod was associated with a higher risk of hypertension only (RR, 1.76; 95% CI, 1.10–2.82; I2, 0.0%), while siponimod was associated with a higher risk of bradyarrhythmia only (RR, 2.75; 95% CI, 1.75–4.31; I2, 0.0%). No significant inter-subgroup differences were observed (Pinteraction &gt; 0.05).ConclusionsS1PRM use increased the risk of cardiovascular AEs by 1.21 times in patients with MS, and increased risks for bradyarrhythmia and hypertension were at 2.92- and 2.00-fold, respectively. These findings can help clinicians assess the risk of cardiovascular AEs in patients treated with S1PRMs.Systematic Review RegistrationThe PROSPERO ID is CRD42020183215.
Norepinephrine Dosage Is Associated With Lactate Clearance After Resuscitation in Patients With Septic Shock
Authors: Yu Chao , Fan Wenjing , Shao Min 
Published: December 2021

Background: Some septic shock patients have persistent hyperlactacidemia despite a normal systemic hemodynamics after resuscitation. Central venous oxygen saturation (ScvO2), mean arterial pressure (MAP), and central venous pressure (CVP) cannot be target in subsequent hemodynamic treatments. Vasoplegia is considered to be one of the main causes of oxygen metabolism abnormalities in septic shock patients, and norepinephrine (NE) is the first-line vasopressor in septic shock treatment; its dosage represents the severity of vasoplegia. This study was performed to determine whether vasoplegia, as assessed by NE dosage, can indicate patients' lactate clearance after the completion of resuscitation.Methods: A retrospective study was performed, and 106 patients with septic shock in an intensive care unit were analyzed. Laboratory values and hemodynamic variables were obtained upon completion of resuscitation (H 0) and 6 h after (H 6). Lactate clearance was defined as the percent decrease in lactate from H 0 to H 6. Student's t-test, Mann-Whitney U-test, Chi-square or Fisher's exact tests, logistic regression analysis, and receiver operating characteristic (ROC) curve analysis were performed for statistical analysis.Results: Patients with a mean age of 63.7 ± 13.8 years, baseline APACHE II score of 21.0 ± 5.1, and SOFA score of 12.7 ± 2.7 were enrolled. The study found that after 6-h of resuscitation, lactate clearance (LC) was &lt;10% in 33 patients (31.1%). Patients with 6-h LC &lt;10% compared with 6-h LC ≥ 10% had a higher NE dose (μg·kg−1·min−1) (0.55 [0.36–0.84] vs. 0.25 [0.18–0.41], p &lt; 0.001). Multivariate logistic regression analysis of statistically significant univariate variables showed that NE dose had a significant inverse relationship with 6-h LC &lt; 10%. The cutoff for NE was ≥ 0.32 μg·kg−1·min−1 for predicting 6-h lactate clearance after resuscitation, with a sensitivity of 75.76% and a specificity of 70.00%. Septic shock patients with an NE dose ≥ 0.32 μg·kg−1·min−1, relative to patients with an NE dose &lt; 0.32 μg·kg−1·min−1, had a greater 30-day mortality rate (69.8% vs. 26.4% p &lt; 0.001).Conclusion: Some patients with septic shock had persistent oxygen metabolism disorders after hemodynamic resuscitation. NE dose may indicate vasoplegia and oxygen metabolism disorder. After resuscitation, septic shock patients with high-dose NE have lower lactate clearance and a greater 30-day mortality rate than those with low-dose NE.
Development and Validation of a Scoring System for Early Diagnosis of Malignant Pleural Effusion Based on a Nomogram
Authors: Wu Aihua , Liang Zhigang , Yuan Songbo , Wang Shanshan , Peng Weidong , Mo Yijun , Yang Jing , Liu Yanqing 
Published: December 2021

BackgroundThe diagnostic value of clinical and laboratory features to differentiate between malignant pleural effusion (MPE) and benign pleural effusion (BPE) has not yet been established.ObjectivesThe present study aimed to develop and validate the diagnostic accuracy of a scoring system based on a nomogram to distinguish MPE from BPE.MethodsA total of 1,239 eligible patients with PE were recruited in this study and randomly divided into a training set and an internal validation set at a ratio of 7:3. Logistic regression analysis was performed in the training set, and a nomogram was developed using selected predictors. The diagnostic accuracy of an innovative scoring system based on the nomogram was established and validated in the training, internal validation, and external validation sets (n = 217). The discriminatory power and the calibration and clinical values of the prediction model were evaluated.ResultsSeven variables [effusion carcinoembryonic antigen (CEA), effusion adenosine deaminase (ADA), erythrocyte sedimentation rate (ESR), PE/serum CEA ratio (CEA ratio), effusion carbohydrate antigen 19-9 (CA19-9), effusion cytokeratin 19 fragment (CYFRA 21-1), and serum lactate dehydrogenase (LDH)/effusion ADA ratio (cancer ratio, CR)] were validated and used to develop a nomogram. The prediction model showed both good discrimination and calibration capabilities for all sets. A scoring system was established based on the nomogram scores to distinguish MPE from BPE. The scoring system showed favorable diagnostic performance in the training set [area under the curve (AUC) = 0.955, 95% confidence interval (CI) = 0.942–0.968], the internal validation set (AUC = 0.952, 95% CI = 0.932–0.973), and the external validation set (AUC = 0.973, 95% CI = 0.956–0.990). In addition, the scoring system achieved satisfactory discriminative abilities at separating lung cancer-associated MPE from tuberculous pleurisy effusion (TPE) in the combined training and validation sets.ConclusionsThe present study developed and validated a scoring system based on seven parameters. The scoring system exhibited a reliable diagnostic performance in distinguishing MPE from BPE and might guide clinical decision-making.
Association Between Household Income and Self-Perceived Health Status and Poor Mental and Physical Health Among Cancer Survivors
Authors: Su L. Joseph , O'Connor Sarah N. , Chiang Tung-Chin 
Published: December 2021

Background: Health-related quality of life (HRQoL) is multidimensional and is composed of, at a minimum, self-perceived health status, physical functioning, and psychological well-being. HRQoL measures reflect the extent of disability and dysfunction associated with a chronic disease such as cancer. The objective of this study is to examine factors associated with HRQoL among cancer survivors.Methods: Data from the 2009 Behavioral Risk Factor Surveillance System survey was used to examine factors associated with HRQoL among participants who reported having ever been diagnosed with cancer. Four questions associated with HRQoL included self-perceived health status, number of bad physical health days, and number of bad mental health days per month. Least square regression and logistic regression models, adjusted for confounding variables, were used for an ordinal and dichotomous [5 (bad) vs. 1–4 (excellent, very good, good, fair)] scale of HRQoL, respectively.Results: Fifty nine thousand one hundred seventy three participants reported having ever been diagnosed with cancer. Adjusted mean self-perceived health status (5-point scale) among survivors of thyroid, colon, lung, cervical, breast, prostate, and ovarian cancer was 3.83 (0.05), 4.02 (0.04), 4.36 (0.06), 3.77 (0.03), 3.88 (0.03), 3.78 (0.04), and 3.96 (0.05), respectively. After adjusting for confounders, a positive dose-response effect was observed between income range and all three HRQoL measures across all seven cancer sites. Income was consistently and inversely associated with a higher chance for reporting poorer HRQoL [OR: 0.64, 95% CI: 0.57–0.71], [OR: 0.63, 95% CI: 0.48–0.82], [OR: 0.67, 95% CI: 0.56–0.80], [OR: 0.69, 95% CI: 0.56–0.86], [OR: 0.55, 95% CI: 0.49–0.62], [OR:0.55, 95% CI: 0.44–0.69], [OR: 0.75, 95% CI: 0.62–0.91] among those with thyroid, colon, lung, cervical, breast, prostate, and ovarian cancer, respectively.Discussion: This study found that income range was associated with HRQoL among cancer survivors. It is plausible that financial resources may lessen the overall burden of cancer survivors, which could improve health-related quality of life among cancer survivors.
Relationship Between Polycyclic Aromatic Hydrocarbons and Cardiovascular Diseases: A Systematic Review
Authors: Mallah Manthar Ali , Mallah Mukhtiar Ali , Liu Yang , Xi He , Wang Wei , Feng Feifei , Zhang Qiao 
Published: December 2021

Objective: The primary aim of this systematic review was to examine the relationship of polycyclic aromatic hydrocarbon (PAH) exposure with cardiovascular diseases (CVDs) and elaborate the current knowledge and recent advances in the area of PAH and its effects on CVDs and discuss the growing epidemiological evidence linking PAH to CVDs on the health of human populations. In this systematic review, the increased risk of cardiovascular diseases and their relationship with PAHs were discussed in detail.Methods: On 05th April 2021, a systematic literature search was conducted using PubMed/Medline and Web of Science search engines in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. The search was limited to articles that were written in English and dealt with human issues. All original peer-review publications were considered for inclusion. Comments, case reports, reviews, duplicated papers, and conference reports were excluded. Data was collected from included papers by two independent reviewers.Results: Conclusively, 20 research articles published between 2005 and 2021 were chosen for the final analysis. The systemic review included 20 studies with a variety of geographical studies. The most common research category among the nominated studies were time-series studies followed by retrospective cohort, cross-sectional, quasi-experimental, panel, and case-control studies. Most of the studies were conducted in the United States, whereas others were showed in various geographical countries around the world, such as Denmark, Germany, Finland, Netherlands, France, China, Norway, Korea, Sweden, Saudi Arabia, and Belgium. Eight studies assessed the association between PAH exposure and CVDs, four articles observed this relationship with blood pressure (BP), two observed association between atherosclerotic CVD and PAH, one congenital heart disease, cardiovascular events, and two with obesity. Furthermore, in some investigations, a favorable association between PAH exposure and hypertension as well as PAH exposure and obesity was found.Conclusion: In conclusion, this systematic review examined the relationship of PAH exposure with CVDs and CVD-related risk factors by searching several digital databases. After a comprehensive literature searches and summarizing findings from 20 articles, the authors concluded that a positive relationship was observed between PAH exposure and CVD risks.
A Ten-Week Motor Skills Training Program Increases Motor Competence in Children with Developmental Coordination Disorder
Authors: Saidmamatov Orifjon , Raximov Quvondiq , Rodrigues Paula , Vasconcelos Olga 
Published: December 2021

The present study aimed to investigate the effect of a motor skills training program in children with DCD considering their gender. The Movement Assessment Battery for Children (MABC-2) classified the children and assessed their skill changes over time. The study was implemented at four kindergartens in the Khorezm region of Uzbekistan. In the study, all the children suffered from DCD (5.17 ± 0.70 years; 10 girls), and all the indicators of MABC-2 were less than 16%. The participants were divided into an experimental group (n = 17), receiving ten weeks of motor skills training program for 45 min twice per week; and a control group (n = 7), which proceeded with exercises of everyday living. The ANCOVA showed differences between the groups in the post-test concerning each domain: manual dexterity (F (1, 20) = 18.703, p < 0.001; η2 = 0.471); aiming and catching (F (1, 20) = 9.734, p = 0.005; η2 = 0.317); balance (F (1, 20) = 35.140, p = 0.000; η2 = 0.626); and total MABC-2 test score (F (1, 20) = 66.093, p < 0.001; η2 = 0.759), with all the children in the EG exhibiting better results. The Wilcoxon test revealed statistically significant differences for the EG between moments for all the variables (p < 0.001) but not for the CG (p > 0.050). The effectiveness of the intervention program was similar across both genders. The study suggests that a 10 week motor skills training program can increase the quality of children’s motor competence and represent a valuable procedure for physical education specialists to enhance motor competence for children with DCD.