bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictive Added Value of Selected Plasma Lipids to a Re-estimated Minimal Risk Tool
Authors: Bodini Antonella , Michelucci Elena , Di Giorgi Nicoletta , Caselli Chiara , Signore Giovanni , Neglia Danilo , Smit Jeff M. , Scholte Arthur J.H.A. , Mincarone Pierpaolo , Leo Carlo G. , Pelosi Gualtiero , Rocchiccioli Silvia 
Published: July 2021

Background: Lipidomics is emerging for biomarker discovery in cardiovascular disease, and circulating lipids are increasingly incorporated in risk models to predict cardiovascular events. Moreover, specific classes of lipids, such as sphingomyelins, ceramides, and triglycerides, have been related to coronary artery disease (CAD) severity and plaque characteristics. To avoid unnecessary testing, it is important to identify individuals at low CAD risk. The only pretest model available so far to rule out the presence of coronary atherosclerosis in patients with chest pain, but normal coronary arteries, is the minimal risk tool (MRT).Aim: Using state-of-the-art statistical methods, we aim to verify the additive predictive value of a set of lipids, derived from targeted plasma lipidomics of suspected CAD patients, to a re-estimated version of the MRT for ruling out the presence of coronary atherosclerosis assessed by coronary CT angiography (CCTA).Methods: Two hundred and fifty-six subjects with suspected stable CAD recruited from five European countries within H2020-SMARTool, undergoing CCTA and blood sampling for clinical biochemistry and lipidomics, were selected. The MRT was validated by regression methods and then re-estimated (reMRT). The reMRT was used as a baseline model in a likelihood ratio test approach to assess the added predictive value of each lipid from 13 among ceramides, triglycerides, and sphingomyelins. Except for one lipid, the analysis was carried out on more than 240 subjects for each lipid. A sensitivity analysis was carried out by considering two alternative models developed on the cohort as baseline models.Results: In 205 subjects, coronary atherosclerosis ranged from minimal lesions to overt obstructive CAD, while in 51 subjects (19.9%) the coronary arteries were intact. Four triglycerides and seven sphingomyelins were significantly (p &lt; 0.05) and differentially expressed in the two groups and, at a lesser extent, one ceramide (p = 0.067). The probability of being at minimal risk was significantly better estimated by adding either Cer(d18:1/16:0) (p = 0.01), SM(40:2) (p = 0.04), or SM(41:1) at a lesser extent (p = 0.052) to reMRT than by applying the reMRT alone. The sensitivity analysis confirmed the relevance of these lipids. Furthermore, the addition of SM(34:1), SM(38:2), SM(41:2), and SM(42:4) improved the predictive performance of at least one of the other baseline models. None of the selected triglycerides was found to provide an added value.Conclusions: Plasma lipidomics can be a promising source of diagnostic and prognostic biomarkers in cardiovascular disease, exploitable not only to assess the risk of adverse events but also to identify subjects without coronary atherosclerosis, thus reducing unnecessary further testing in normal subjects.
Interaction Effects of Temperature, Light, Nutrients, and pH on Growth and Competition of Chlorella vulgaris and Anabaena sp. Strain PCC
Authors: Meng Shun Long , Chen Xi , Wang Jing , Fan Li Min , Qiu Li Ping , Zheng Yao , Chen Jia Zhang , Xu Pao 
Published: July 2021

Interaction effects of temperature, light, nutrients, and pH on growth and competition of Chlorella vulgaris and Anabaena sp. strain PCC were evaluated using an orthogonal design method to elucidate how these environment factors promote the growth of beneficial algae and limit the growth of harmful algae. The optimal conditions for the growth of C. vulgaris in the mono-culture system were as follows: temperature, 35°C; light, 660 lx; N concentration, 0.36 mg L−1; P concentration, 0.1 mg L−1; and pH, 9.0; and those for Anabaena were as follows: temperature, 30°C; light, 6,600 lx; N concentration, 0.18 mg L−1; P concentration, 0.1 mg L−1; and pH, 7.0. The optimal conditions for the growth of C. vulgaris in the co-culture system were as follows: temperature, 25°C; light, 4,400 lx; N concentration, 0.18 mg L−1; P concentration, 0.5 mg L−1; and pH, 6.0; and those for Anabaena were as follows: temperature, 35°C; light, 4,400 lx; N concentration, 0.36 mg L−1; P concentration, 0.5 mg L−1; and pH, 6.0. Both competition-inhibition parameters of Anabaena against C. vulgaris and those of C. vulgaris against Anabaena were the largest under the following conditions: temperature, 30°C; light intensity, 6,600 lx; N concentration, 0.36 mg L−1; P concentration, 0.025 mg L−1; and pH, 8.0. According to the Lotka–Volterra competition model, Anabaena won in the competition in the co-culture system with the following conditions: 1) temperature, 15°C; light, 660 lx; total N (TN), 0.18 mg L−1; total P (TP), 0.025 mg L−1; pH, 6; 2) temperature, 15°C; light, 2,200 lx; TN, 0.36 mg L−1; TP, 0.025 mg L−1; pH, 7; 3) temperature, 15°C; light, 6,600 lx; TN, 3.6 mg L−1; TP, 0.5 mg L−1; pH, 9; 4) temperature, 30°C; light, 4,400 lx; TN, 0.18 mg L−1; TP, 0.05 mg L−1; pH, 9; 5) temperature, 35°C; light, 660 lx; TN, 3.6 mg L−1; TP, 0.05 mg L−1; pH, 8; and 6) temperature, 35°C; light, 2,200 lx; TN, 0.72 mg L−1; TP, 0.025 mg L−1; pH, 9. However, C. vulgaris could not win in the competition in the co-culture system under all conditions tested.
Comprehensive Evaluation of Non-invasive Prenatal Screening to Detect Fetal Copy Number Variations
Authors: Wang Jing , Zhang Bin , Zhou Lingna , Zhou Qin , Chen Yingping , Yu Bin 
Published: July 2021

ObjectiveTo evaluate the effectiveness of non-invasive prenatal screening (NIPS) in prenatal screening of fetal pathogenic copy number variants (CNVs).Materials and MethodsWe evaluated the prenatal screening capacity using traditional and retrospective approaches. For the traditional method, we evaluated 24,613 pregnant women who underwent NIPS; cases which fetal CNVs were suggested underwent prenatal diagnosis with chromosomal microarray analysis (CMA). For the retrospective method, we retrospectively evaluated 47 cases with fetal pathogenic CNVs by NIPS. A systematic literature search was performed to compare the evaluation efficiency.ResultsAmong the 24,613 pregnant women who received NIPS, 124 (0.50%) were suspected to have fetal CNVs. Of these, 66 women underwent prenatal diagnosis with CMA and 13 had true-positive results. The positive predictive value (PPV) of NIPS for fetal CNVs was 19.7%. Among 1,161 women who did not receive NIPS and underwent prenatal diagnosis by CMA, 47 were confirmed to have fetal pathogenic CNVs. Retesting with NIPS indicated that 24 of these 47 cases could also be detected by NIPS, representing a detection rate (DR) of 51.1%. In total, 10 publications, namely, six retrospective studies and four prospective studies, met our criteria and were selected for a detailed full-text review. The reported DRs were 61.10–97.70% and the PPVs were 36.11–80.56%. The sizes of CNVs were closely related to the accuracy of NIPS detection. The DR was 41.9% (13/31) in fetuses with CNVs ≤ 3 Mb, but was 55.0% (11/20) in fetuses with CNVs &gt; 3 Mb. Finally, to intuitively show the CNVs accurately detected by NIPS, we mapped all CNVs to chromosomes according to their location, size, and characteristics. NIPS detected fetal CNVs in 2q13 and 4q35.ConclusionThe DR and PPV of NIPS for fetal CNVs were approximately 51.1% and 19.7%, respectively. Follow-up molecular prenatal diagnosis is recommended in cases where NIPS suggests fetal CNVs.
Follistatin-Like 3 Correlates With Lymph Node Metastasis and Serves as a Biomarker of Extracellular Matrix Remodeling in Colorectal Cancer
Authors: Yang Chao , Cao Fengyu , Huang Shuoyang , Zheng Yongbin 
Published: July 2021

BackgroundAs a heterogeneous disease, colorectal cancer (CRC) presents a great challenge to individualized treatment due to its lymph node metastasis (LNM). Existing studies have shown that immune and stromal components in extracellular matrix (ECM) act as important part in tumorigenicity and progression, while their roles in LNM have not been fully elucidated. Here, crucial ECM-related genes responsible for LNM in CRC were selected by multi-omics analysis.MethodsFirstly, we characterized the immune infiltration landscape of CRC samples from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases by using ssGSEA algorithm. The CRC patients were divided into several immune subgroups by hierarchical clustering analyses. Then, differential genes were identified among immune subgroups and CRC vs. normal tissues in TCGA and GEO GSE39582 cohorts, respectively. Next, weighted correlation network analysis (WGCNA) was employed to construct a co-expression network to find LNM-related modules and hub genes. Subsequently, we evaluated the clinical value of hub gene in prognostic prediction and chemotherapy/immunotherapy. Besides, the protein level of key gene was verified in an external cohort from our center. Finally, we explored the underlying mechanism of FSTL3-mediated LNM by Gene function annotation and correlation analysis.ResultsTwo immune subgroups, namely Immunity_High and Immunity_Low, were defined among the two CRC cohorts using ssGSEA algorithm, respectively. Based on the two immune subgroups, 2,635 overlapping differentially expressed genes were obtained from two cohorts, which were sequentially subjected to WGCNA and univariate Cox regression analysis. Ultimately, FSTL3 was selected as the key gene. Here, we first confirmed that overexpression of FSTL3 correlated with LNM and worse prognosis in CRC and was verified at the protein level in the external validation cohort. Moreover, FSTL3 expression showed strongly positive correlation with immune and stromal components in ECM. We furthermore found that FSTL3 may accelerate LNM through the formation of inhibitory immune microenvironment via promoting macrophage and fibroblast polarization and T cell exhaustion. Interestingly, high FSTL3 expression is linked to chemoresistance, but immunotherapy-sensitive.ConclusionFSTL3 is identified as a biomarker for ECM remodeling and worse clinical outcomes for the first time in CRC and is also a potential immunotherapeutic target to block LNM for CRC.
Refractory Head and Neck Lymphatic Malformation in Infants Treated With Sirolimus: A Case Series
Authors: Wu Changhua , Song Dan , Guo Lei , Wang Liang 
Published: July 2021

BackgroundExtensive and complex head and neck lymphatic malformations (LMs) are challenging to manage through traditional therapy. The purpose of this retrospective study was to assess the efficacy and safety of sirolimus in infants with refractory head and neck LMs.MethodsSirolimus was administered orally on a continuous dosing schedule. Patients were seen every month for the first three months and then subsequently every three months. The primary endpoints were safety and efficacy based on clinical and radiological evaluations.ResultsEight patients, refractory to standard care, were enrolled and received sirolimus continuously. After 12 months of follow-up, the response and safety to medication was evaluated: all patients experienced reductions in LMs bulk, ranging from modest to significant. Some minor adverse effects were reported: mouth sores, eczema, gastrointestinal reaction, dyslipidemia, and neutropenia.ConclusionSirolimus was efficient in children with refractory head and neck LMs and was well tolerated.
Prediction of Survival and Analysis of Prognostic Factors for Patients With Combined Hepatocellular Carcinoma and Cholangiocarcinoma: A Population-Based Study
Authors: Wang Jitao , Li Zhi , Liao Yong , Li Jinlong , Dong Hui , Peng Hao , Xu Wenjing , Fan Zhe , Gao Fengxiao , Liu Chengyu , Liu Dengxiang , Zhang Yewei 
Published: July 2021

BackgroundCombined hepatocellular carcinoma and cholangiocarcinoma (CHC) is an uncommon subtype of primary liver cancer. Because of limited epidemiological data, prognostic risk factors and therapeutic strategies for patients with CHC tend to be individualized. This study aimed to identify independent prognostic factors and develop a nomogram-based model for predicting the overall survival (OS) of patients with CHC.MethodsWe recruited eligible individuals from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015 and randomly divided them into the training or verification cohort. Univariate and multivariate analyses were performed to identify independent variables associated with OS. Based on multivariate analysis, the nomogram was established, and its prediction performance was evaluated using the consistency index (C-index) and calibration curve.ResultsIn total, 271 patients with CHC were included in our study. The median OS was 14 months, and the 1-, 3-, and 5-year OS rates were 52.3%, 27.1%, and 23.3%, respectively. In the training cohort, multivariate analysis showed that the pathological grade (hazard ratio [HR], 1.26; 95% confidence interval [CI]: 0.96–1.66), TNM stage (HR, 1.21; 95% CI: 1.02 - 1.44), and surgery (HR, 0.26; 95% CI: 0.17 - 0.40) were independent indicators of OS. The nomogram-based model related C-indexes were 0.76 (95% CI: 0.72 - 0.81) and 0.72 (95% CI: 0.66 - 0.79) in the training and validation cohorts, respectively. The calibration of the nomogram showed good consistency of 1-, 3-, and 5-year OS rates between the actual observed survival and predicted survival in both cohorts. The TNM stage (HR, 1.23; 95% CI: 1.01 - 1.49), and M stage (HR, 1.87; 95% CI: 1.14 3.05) were risk factors in the surgical treatment group. Surgical resection and liver transplantation could significantly prolong the survival, with no statistical difference observed.ConclusionsThe pathological grade, TNM stage, and surgery were independent prognostic factors for patients with CHC. We developed a nomogram model, in the form of a static nomogram or an online calculator, for predicting the OS of patients with CHC, with a good predictive performance.
Application Research of Individualized Conditional Reprogramming System to Guide Treatment of Gastric Cancer
Authors: Zhao Weizhu , Liu Kai , Sun Zhikun , Wang Longgang , Liu Bing , Liu Luguang , Qu Xianlin , Cao Zhixiang , Sun Jujie , Chai Jie 
Published: July 2021

BackgroundGastric cancer (GC) is one of the most common causes of malignant tumors in the world. Due to the high heterogeneity of GC and lack of specificity of available chemotherapy regimens, these tumors are prone to resistance, recurrence, and metastasis. Here, we formulated an individualized chemotherapy regimen for GC using a modified individual conditional reprogramming (i-CR) system. We established a primary tumor cell bank of GC cells and completed drug screening in order to realize individualized and accurate GC treatment.MethodsWe collected specimens from 93 surgical or gastroscopy GC cases and established a primary tumor cell bank using the i-CR system and PDX models. We also completed in vitro culture and drug sensitivity screening of the GC cells using the i-CR system. Whole-exome sequencing (WES) of the i-CR cells was performed using P0 and P5. We then chose targeted chemotherapy drugs based on the i-CR system results.ResultsOf the 72 cases that were collected from surgical specimens, 26 cases were successfully cultured with i-CR system, and of the 21 cases collected from gastroscopy specimens, seven were successfully cultured. Among these, 20 cases of the PDX model were established. SRC ± G3 had the highest culture success rate. The i-CR cells of P0 and P5 appeared to be highly conserved. According to drug sensitivity screening, we examined the predictive value of responses of GC patients to chemotherapeutic agents, especially in neoadjuvant patients.ConclusionThe i-CR system does not only represent the growth characteristics of tumors in vivo, but also provides support for clinical drug use. Drug susceptibility results were relatively consistent with clinical efficacy.
Honeymoon Period in Newborn Rats With CDH Is Associated With Changes in the VEGF Signaling Pathway
Authors: Miura da Costa Karina , Fabro Alexandre Todorovic , Becari Christiane , Figueira Rebeca Lopes , Schmidt Augusto F. , Ruano Rodrigo , Sbragia Lourenço 
Published: July 2021

Background: Patients with congenital diaphragmatic hernia (CDH) have a short postnatal period of ventilatory stability called the honeymoon period, after which changes in pulmonary vascular reactivity result in pulmonary hypertension. However, the mechanisms involved are still unknown. The aim of this study was to evaluate mechanical ventilation's effect in the honeymoon period on VEGF, VEGFR-1/2 and eNOS expression on experimental CDH in rats.Materials and Methods: Neonates whose mothers were not exposed to nitrofen formed the control groups (C) and neonates with left-sided defects formed the CDH groups (CDH). Both were subdivided into non-ventilated and ventilated for 30, 60, and 90 min (n = 7 each). The left lungs (n = 4) were evaluated by immunohistochemistry of the pulmonary vasculature (media wall thickness), VEGF, VEGFR-1/2 and eNOS. Western blotting (n = 3) was performed to quantify the expression of VEGF, VEGFR-1/2 and eNOS.Results: CDH had lower biometric parameters than C. Regarding the pulmonary vasculature, C showed a reduction in media wall thickness with ventilation, while CDH presented reduction with 30 min and an increase with the progression of the ventilatory time (honeymoon period). CDH and C groups showed different patterns of VEGF, VEGFR-1/2 and eNOS expressions. The receptors and eNOS findings were significant by immunohistochemistry but not by western blotting, while VEGF was significant by western blotting but not by immunohistochemistry.Conclusion: VEGF, its receptors and eNOS were altered in CDH after mechanical ventilation. These results suggest that the VEGF-NO pathway plays an important role in the honeymoon period of experimental CDH.
Large-Scale Transcriptome Analysis Identified a Novel Cancer Driver Genes Signature for Predicting the Prognostic of Patients With Hepatocellular Carcinoma
Authors: Li Gao , Du Xiaowei , Wu Xiaoxiong , Wu Shen , Zhang Yufei , Xu Jing , Wang Hao , Chen Tingsong 
Published: July 2021

Background: Hepatocellular carcinoma (HCC) is a common malignant tumor with high mortality and heterogeneity. Genetic mutations caused by driver genes are important contributors to the formation of the tumor microenvironment. The purpose of this study is to discuss the expression of cancer driver genes in tumor tissues and their clinical value in predicting the prognosis of HCC.Methods: All data were sourced from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), and Gene Expression Omnibus (GEO) public databases. Differentially expressed and prognostic genes were screened by the expression distribution of the cancer driver genes and their relationship with survival. Candidate genes were subjected to functional enrichment and transcription factor regulatory network. We further constructed a prognostic signature and analyzed the survival outcomes and immune status between different risk groups.Results: Most cancer driver genes are specifically expressed in cancer tissues. Driver genes may influence HCC progression through processes such as transcription, cell cycle, and T-cell receptor-related pathways. Patients in different risk groups had significant survival differences (p &lt; 0.05), and risk scores showed high predictive efficacy (AUC&gt;0.69). Besides, risk subgroups were also associated with multiple immune functions and immune cell content.Conclusion: We confirmed the critical role of cancer driver genes in mediating HCC progression and the immune microenvironment. Risk subgroups contribute to the assessment of prognostic value in different patients and explain the heterogeneity of HCC.
The Efficacy and Safety of Chinese Herbal Medicine Xianling Gubao Capsule Combined With Alendronate in the Treatment of Primary Osteoporosis: A Systematic Review and Meta-Analysis of 20 Randomized Controlled Trials
Authors: Chen Jiaru , Zheng Junju , Chen Mangmang , Lin Shenglei , Lin Zhou 
Published: July 2021

Objective: Herein, we purposed to evaluate the efficacy along with the safety of Xianling Gubao capsule (XLGB) combined with alendronate (ALE) for primary osteoporosis (POP) from the current literature.Materials and Methods: We carried out a search for electronic literature in the PubMed, Chinese National Knowledge Infrastructure, EMBASE, Wanfang Web of Science, Chinese Biomedical Literature Database, Cochrane Library, as well as Chinese VIP databases targeting articles published from inception to December 2020. Only randomized controlled trials (RCTs) were enrolled into the study. Alkaline phosphatase (ALP), visual analogue scale (VAS), serum phosphorus (S-P), bone gla protein (BGP), serum calcium (S-Ca) and bone mineral density (BMD) were the primary outcome variable. The total clinical effective rate along with the adverse drug reaction (ADR) were the secondary outcome variables. The meta-analysis was conducted using RevMan 5.3 and STATA 12.0. GRADE pro3.6.1 software was used for the assessment of evidence quality.Results: Overall, 20 RCTs focusing on 1911 patients were enrolled into the study. Our meta-analysis demonstrated that XLGB combined with ALE remarkably increased BMD (p &lt; 0.001), BGP (p &lt; 0.001), S-Ca (p &lt; 0.001), S-P (p &lt; 0.001) and effective rate (p &lt; 0.001) than ALE alone in patients with POP. Moreover, ALP (p &lt; 0.001) and VAS (p &lt; 0.001) were overtly by decreased XLGB. However, XLGB combined with ALE would not markedly increase the rate of ADR in contrast with ALE alone (p = 0.499).Conclusion: The results of our study demonstrated that XLGB is a potential candidate for OP treatment. We recommend that rigorous, as well as high-quality trials involving large samples sizes should be conducted to confirm our findings.
mRNA Levels of MAOA and 5-HT2A Receptor in Patients With Pathological Internet Use: Correlations With Comorbid Symptoms
Authors: Qiu Mimi , Zhang Chenchen , Dai Yu , Zhang Lingrui , Wang Yang , Peng Wei , Chen Yalin , Wen Chao , Li Hui , Zhu Tianmin 
Published: July 2021

Objective: Uncontrolled internet use may lead to the emergence of pathological internet use (PIU). PIU has become a global public health concern that can cause a range of psychotic symptoms, including anxiety, depression, and impulse control disorder. To date, we know very little about the principal biological factors related to PIU. Monoamine oxidase type A (MAOA) and serotonin (5-HT) 5-HT2A receptor (5-HT2AR) play critical roles in the development of behavioural and drug addictions. Thus, the aim of this study was to measure the relative expression of mRNA of MAOA and 5-HT2AR in peripheral blood mononuclear cells (PBMCs) of patients with PIU and to determine the correlations between these biological indicators and the comorbid symptoms of patients with PIU.Methods: In this study, the mRNA of MAOA and 5-HT2AR was detected using real-time PCR in PBMCs of the patients with PIU (n = 24) and healthy controls (HCs, n = 25). The relationship between the mRNA levels of MAOA and 5-HT2AR and clinical symptoms in patients with PIU was further investigated.Results: MAOA mRNA in PBMCs was significantly upregulated in patients with PIU compared with that in HCs. mRNA levels of 5-HT2AR were not found to differ significantly between HCs and patients with PIU. Correlation analyses further revealed a significant positive correlation between the relative expression of MAOA mRNA in PBMCs of patients with PIU and the Young's Internet Addiction Test and Self-Rating Depression Scale scores.Conclusion: The present study revealed upregulated expression of MAOA mRNA in patients with PIU and an association between the expression of MAOA mRNA and clinical symptoms of PIU, suggesting that the neurobiological changes may be similar between PIU and substance addiction. Additionally, this study demonstrated a potential association between comorbid symptoms and mRNA levels of MAOA.