bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel Nongenetic Murine Model of Hyperglycemia and Hyperlipidemia-Associated Aggravated Atherosclerosis
Authors: Gaul Susanne , Shahzad Khurrum , Medert Rebekka , Gadi Ihsan , Mäder Christina , Schumacher Dagmar , Wirth Angela , Ambreen Saira , Fatima Sameen , Boeckel Jes-Niels , Khawaja Hamzah , Haas Jan , Brune Maik , Nawroth Peter P. , Isermann Berend , Laufs Ulrich , Freichel Marc 
Published: March 2022

ObjectiveAtherosclerosis, the main pathology underlying cardiovascular diseases is accelerated in diabetic patients. Genetic mouse models require breeding efforts which are time-consuming and costly. Our aim was to establish a new nongenetic model of inducible metabolic risk factors that mimics hyperlipidemia, hyperglycemia, or both and allows the detection of phenotypic differences dependent on the metabolic stressor(s).Methods and ResultsWild-type mice were injected with gain-of-function PCSK9D377Y (proprotein convertase subtilisin/kexin type 9) mutant adeno-associated viral particles (AAV) and streptozotocin and fed either a high-fat diet (HFD) for 12 or 20 weeks or a high-cholesterol/high-fat diet (Paigen diet, PD) for 8 weeks. To evaluate atherosclerosis, two different vascular sites (aortic sinus and the truncus of the brachiocephalic artery) were examined in the mice. Combined hyperlipidemic and hyperglycemic (HGHCi) mice fed a HFD or PD displayed characteristic features of aggravated atherosclerosis when compared to hyperlipidemia (HCi HFD or PD) mice alone. Atherosclerotic plaques of HGHCi HFD animals were larger, showed a less stable phenotype (measured by the increased necrotic core area, reduced fibrous cap thickness, and less α-SMA-positive area) and had more inflammation (increased plasma IL-1β level, aortic pro-inflammatory gene expression, and MOMA-2-positive cells in the BCA) after 20 weeks of HFD. Differences between the HGHCi and HCi HFD models were confirmed using RNA-seq analysis of aortic tissue, revealing that significantly more genes were dysregulated in mice with combined hyperlipidemia and hyperglycemia than in the hyperlipidemia-only group. The HGHCi-associated genes were related to pathways regulating inflammation (increased Cd68, iNos, and Tnfa expression) and extracellular matrix degradation (Adamts4 and Mmp14). When comparing HFD with PD, the PD aggravated atherosclerosis to a greater extent in mice and showed plaque formation after 8 weeks. Hyperlipidemic and hyperglycemic mice fed a PD (HGHCi PD) showed less collagen (Sirius red) and increased inflammation (CD68-positive cells) within aortic plaques than hyperlipidemic mice (HCi PD). HGHCi-PD mice represent a directly inducible hyperglycemic atherosclerosis model compared with HFD-fed mice, in which atherosclerosis is severe by 8 weeks.ConclusionWe established a nongenetically inducible mouse model allowing comparative analyses of atherosclerosis in HCi and HGHCi conditions and its modification by diet, allowing analyses of multiple metabolic hits in mice.
Deep-Seated Deformation Mechanisms of Excavated Slope and Control Methods: A Case Study
Authors: Wu Yongjin , Zhang Qing , Ding Xiuli , Wang Hui , Huang Shuling , Yin Xiansong 
Published: March 2022

High slope stability control is a crucial technical issue in water conservancy and hydropower project construction. This issue is relevant throughout the entire engineering-related survey, design, construction, and operation process. This paper reports a recent case in which significant deep-seated deformation occurred during slope excavation. Several unfavorable structural surfaces were revealed throughout the slope’s undercutting process, particularly fault fz39, which ran diagonally through the entire slope from top to bottom. On the slope surface, damage such as cracking, bulging, and local slippage appeared. The measured value of multipoint displacement meters increased in a stepwise pattern with each blast, and the maximum measured value exceeded 100 mm. The studied slope’s whole excavation and reinforcement process is described in detail. We analyzed the deformation mechanism of the excavation slope by combining the geological conditions, real-time safety monitoring findings, and site deformation characteristics. The slope reinforcement scheme was optimized based on the preceding analyses. We used a three-dimensional numerical calculation program to simulate the slope excavation and unloading process to reproduce the current mechanical state of the slope, evaluate the reinforcement measures, and provide a useful reference for decision making. The analysis shows that the deformation behavior of the studied slope is closely related to fault fz39 and fracture L920, and presents a typical wedge failure mode. The deep-seated deformation of the excavation slope occurs at the junction of the wedge and bedrock, which is mainly affected by unfavorable geological structure surfaces, excavation unloading, and blasting vibration. The reinforcement scheme of unloading at the top of the slope and large-tonnage cables are established. The numerical analysis results showed that the design of the slope reinforcement measures was appropriate and ensured slope stability. The work described in this paper deepens our understanding of the occurrence of large deep-seated deformation on the structural-controlled slope under the action of excavation and improves the design philosophy.
Impact of Regional Climate Change on the Development of Lithium Resources in Zabuye Salt Lake, Tibet
Authors: Ding Tao , Zheng Mianping , Nie Zhen , Ma Lichun , Ye Chuanyong , Wu Qian , Zhao Yuanyi , Yang Donghui , Wang Kai 
Published: March 2022

Climate change has important implication for the ecological environment and human social activities. The Qinghai-Tibet Plateau is a sensitive area for climate change, and the lakes on the Qinghai-Tibet Plateau are known as the “guardians” of climate change. However, there are few studies on the impact of climate variations on the exploitation of lithium resources in salt lakes. In this work, the collected data from Zabuye Salt Lake Observation Station and the experimental data of brine at different temperatures were employed as the research objects to investigate the relationship between regional climate change and lithium resources in salt lakes. The results indicated that Zabuye Salt Lake had abundant solar energy resources from 1991 to 2020 with the annual average sunshine duration of 3,122.4 h, the average annual evaporation of 2,579.07 mm/yr, and the annual average precipitation of 168.65 mm/yr. The average annual evaporation is around 15.3 times the average annual precipitation, owing to the short rainy season and the low rainfall. The phase diagram displayed that two lithium carbonate precipitation peaks clearly appeared at 25°C, and no obvious precipitation peak appeared at 15°C, indicating that a high-grade lithium carbonate mixed salt was prone to be formed at a higher temperature while lithium ions was more inclined to enrich in brine at a lower temperature. Therefore, Zabuye Salt Lake with the characteristics of low temperature, large temperature difference, less precipitation, strong radiation and large evaporation could be applied as unique lithium resources in the salt gradient solar pond, which would play a positive role in the development of salt lake resources.
Increased Central and Peripheral Thyroid Resistance Indices During the First Half of Gestation Were Associated With Lowered Risk of Gestational Diabetes—Analyses Based on Huizhou Birth Cohort in South China
Authors: Liu Zhao-min , Li Guoyi , Wu Yi , Zhang Di , Zhang Sujuan , Hao Yuan-Tao , Chen Weiqing , Huang Qi , Li Shuyi , Xie Yaojie , Ye Mingtong , He Chun , Chen Ping , Pan Wenjing 
Published: March 2022

ObjectivesThe study aimed to explore the relationship of thyroid function and resistance indices with subsequent risk of gestational diabetes (GDM).DesignThis was a longitudinal study embedded in the Huizhou Birth Cohort.MethodsA total of 2,927 women of singleton pregnancy were recruited from January to October of 2019. Thyroid central resistance indices were evaluated by Thyroid Feedback Quartile-Based index (TFQI), Thyrotrophy T4 Resistance Index (TT4RI), and TSH Index (TSHI) based on plasma-free thyroxine (FT4) and thyroid-stimulating hormone (TSH) levels during the first half of pregnancy. Thyroid peripheral sensitivity was assessed by free triiodothyronine (FT3) to FT4 ratio (FT3/FT4), a proxy of deiodinase activity. GDM was diagnosed between 24 and 28 weeks of gestation by a standardized 75 g oral glucose tolerance test. Multivariable linear and logistic regression was applied to examine the associations of thyroid markers with GDM risk.ResultsFT3 and FT3/FT4 were positively associated with both fasting and post-load glucose levels, while TSH, TSHI, TT4RI, and TFQI were negatively associated with 1 and 2 h post-load glucose levels. Compared with the lowest quartile, GDM risk in the highest quartile increased by 44% [odds ratio (OR) = 1.44; 95%CI, 1.08–1.92; ptrend = 0.027] for FT3 and 81% (OR = 1.81; 95%CI, 1.33–2.46; ptrend &lt; 0.001) for FT3/FT4, while it lowered by 37% (OR = 0.63; 95%CI, 0.47–0.86; ptrend = 0.002] for TSHI, 28% for TT4RI (OR = 0.72; 95%CI, 0.54–0.97; ptrend = 0.06), and 37% for TFQI (OR = 0.63; 95%CI, 0.46–0.85; ptrend &lt; 0.001).ConclusionsThis longitudinal study indicated that higher FT3 and FT3/FT4 and lower central thyroid resistance indices were associated with increased risk of GDM.
Mechanism Analysis of LINC00665 and Its Peptides CIP2A-BP in Hepatocellular Carcinoma
Authors: Li Yi-Ran , Zong Rui-Qing , Zhang Hong-Yan , Meng Xiao-Yan , Wu Fei-Xiang 
Published: March 2022

Background: More and more studies show that long non-coding RNAs (lncRNAs) have miniature open reading frames that can be translated into short peptides. Here, we identify the long non-coding gene LINC00665 and its short peptides (CIP2A-BP) in hepatocellular carcinoma (HCC) and explore how they contribute to HCC progression.Materials and methods: First, GSE101728 data were acquired through the Gene Expression Omnibus for identification of differentially expressed genes (DEGs), and gene set enrichment analysis (GSEA) was conducted to find enriched biological pathways. Then, further bioinformatics analysis was carried out on the screened long non-coding genes, and LINC00665 expression was detected in HCC and normal liver samples. The relations between LINC00665 expression, HCC prognosis, and clinical characteristics were studied. Receiver operating characteristic (ROC) analysis was also applied to verify the LINC00665 prediction in HCC prognosis. In addition, pertinent experiments on LINC00665 and CIP2A-BP were also carried out to explore their roles in the progression of HCC.Results: As a result, we screened out 332 DEGs in total, including 130 upregulated and 202 downregulated DEGs. These DEGs were mainly enriched in posttranscriptional regulation of gene expression, RNA processing, nucleolus, and gene silencing biological pathways. In addition, we found that LINC00665 was increased in HCC samples, which substantially indicated its poor prognosis. Compared with normal tissues, LINC00665 had higher expression in the pathological stages III and IV, tumor-free groups, people no more than 60 years old, and stages T3, T4, N0, N1, and M1. ROC curve indicated that the variable INC00665 had certain accuracy in predicting overall survival (OS). Moreover, in functional experiments, LINC00665 knockdown could significantly decrease HCC cell proliferation, migration, and invasion, while overexpressed CIP2A-BP could markedly increase HCC cell proliferation, invasion, and migration.Conclusion: Our findings not only disclose a unique mechanism by which CIP2A-BP encoded by LINC00665 promotes HCC carcinogenesis but suggest that these long non-coding genes and short peptides could be used as biomarkers for HCC diagnosis and prognosis and new targets for HCC therapy.
Low and High-Density Lipoprotein Cholesterol and 10-Year Mortality in Community-Dwelling Older Adults: The Shanghai Aging Study
Authors: Wu Wanqing , Xiao Zhenxu , Liang Xiaoniu , Zhao Qianhua , Luo Jianfeng , Ding Ding 
Published: March 2022

BackgroundThe relationship between serum cholesterol and mortality remains disputed. This study aimed to examine the association of low and high-density lipoprotein cholesterol (LDL-C and HDL-C) with all-cause mortality among community-dwelling older adults in the Shanghai Aging Study.MethodsWe followed 3,239 participants free of lipid-lowering agents for a median of 10 years. Levels of LDL-C and HDL-C were measured at baseline using fasting blood samples. Survival status was confirmed by the local mortality surveillance system. The associations between the levels of LDL-C, HDL-C, and all-cause mortality were assessed by Cox proportional hazards models.ResultsThe increment of LDL-C concentration was related to a lower risk of mortality (p for trend &lt; 0.05). Using the highest quintile of LDL-C (≥4.10 mmol/L) as a reference, the lowest quintile of LDL-C (&lt;2.61 mmol/L) was associated with the highest risk of mortality, after adjusting for confounders (HR 1.67; 95% CI 1.26–2.21), exclusion of death within the first 2 years of follow-up (HR 1.57; 95% CI 1.17–2.11), and exclusion of functionally impaired participants (HR 1.46; 95% CI 1.07–2.00). A U-shape relationship was found between HDL-C level and the mortality risk. Using the third quintile of HDL-C (1.21–1.39 mmol/L) as a reference, HR (95% CI) was 1.46 (1.09–1.95) for the lowest quintile (&lt;1.09 mmol/L) and 1.45 (1.07–1.96) for the highest quintile (≥1.61 mmol/L) of HDL-C, after adjusting for confounders; and 1.57 (1.15–2.15) for the lowest quintile and 1.45 (1.04–2.01) for the highest quintile of HDL-C, after exclusion of death within the first 2 years of follow-up; and 1.55 (1.11–2.16) for the lowest quintile and 1.42 (1.00–2.02) for the highest quintile of HDL-C, after exclusion of functionally impaired participants.ConclusionsWe found an inverse association of LDL-C and a U-shape relationship of HDL-C with long-term all-cause mortality in a cohort with community-dwelling older Chinese adults. Levels of LDL-C and HDL-C are suggested to be managed properly in late life.
Effect of Impaired Stereoscopic Vision on Large-Scale Resting-State Functional Network Connectivity in Comitant Exotropia Patients
Authors: Jin Han , Chen Ri-Bo , Zhong Yu-Lin , Lai Ping-Hong , Huang Xin 
Published: March 2022

BackgroundComitant exotropia (CE) is a common eye movement disorder, characterized by impaired eye movements and stereoscopic vision. CE patients reportedly exhibit changes in the central nervous system. However, it remains unclear whether large-scale brain network changes occur in CE patients.PurposeThis study investigated the effects of exotropia and stereoscopic vision dysfunction on large-scale brain networks in CE patients via independent component analysis (ICA).MethodsTwenty-eight CE patients (mean age, 15.80 ± 2.46 years) and 27 healthy controls (HCs; mean age, 16.00 ± 2.68 years; closely matched for age, sex, and education) underwent resting-state magnetic resonance imaging. ICA was applied to extract resting-state networks (RSNs) in both groups. Two-sample’s t-tests were conducted to investigate intranetwork functional connectivity (FC) within RSNs and interactions among RSNs between the two groups.ResultsCompared with the HC group, the CE group showed increased intranetwork FC in the bilateral postcentral gyrus of the sensorimotor network (SMN). The CE group also showed decreased intranetwork FC in the right cerebellum_8 of the cerebellum network (CER), the right superior temporal gyrus of the auditory network (AN), and the right middle occipital gyrus of the visual network (VN). Moreover, functional network connectivity (FNC) analysis showed that CER-AN, SMN-VN, SN-DMN, and DMN-VN connections were significantly altered between the two groups.ConclusionComitant exotropia patients had abnormal brain networks related to the CER, SMN, AN, and VN. Our results offer important insights into the neural mechanisms of eye movements and stereoscopic vision dysfunction in CE patients.
A Risk Scoring System Utilizing Machine Learning Methods for Hepatotoxicity Prediction One Year After the Initiation of Tyrosine Kinase Inhibitors
Authors: Han Ji Min , Yee Jeong , Cho Soyeon , Kim Min Kyoung , Moon Jin Young , Jung Dasom , Kim Jung Sun , Gwak Hye Sun 
Published: March 2022

BackgroundThere is currently no method to predict tyrosine kinase inhibitor (TKI) -induced hepatotoxicity. The purpose of this study was to propose a risk scoring system for hepatotoxicity induced within one year of TKI administration using machine learning methods.MethodsThis retrospective, multi-center study analyzed individual data of patients administered different types of TKIs (crizotinib, erlotinib, gefitinib, imatinib, and lapatinib) selected in five previous studies. The odds ratio and adjusted odds ratio from univariate and multivariate analyses were calculated using a chi-squared test and logistic regression model. Machine learning methods, including five-fold cross-validated multivariate logistic regression, elastic net, and random forest were utilized to predict risk factors for the occurrence of hepatotoxicity. A risk scoring system was developed from the multivariate and machine learning analyses.ResultsData from 703 patients with grade II or higher hepatotoxicity within one year of TKI administration were evaluated. In a multivariable analysis, male and liver metastasis increased the risk of hepatotoxicity by 1.4-fold and 2.1-fold, respectively. The use of anticancer drugs increased the risk of hepatotoxicity by 6.0-fold. Patients administered H2 blockers or PPIs had a 1.5-fold increased risk of hepatotoxicity. The area under the receiver-operating curve (AUROC) values of machine learning methods ranged between 0.73-0.75. Based on multivariate and machine learning analyses, male (1 point), use of H2 blocker or PPI (1 point), presence of liver metastasis (2 points), and use of anticancer drugs (4 points) were integrated into the risk scoring system. From a training set, patients with 0, 1, 2-3, 4-7 point showed approximately 9.8%, 16.6%, 29.0% and 61.5% of risk of hepatotoxicity, respectively. The AUROC of the scoring system was 0.755 (95% CI, 0.706-0.804).ConclusionOur scoring system may be helpful for patient assessment and clinical decisions when administering TKIs included in this study.
Upregulation of MTA1 in Colon Cancer Drives A CD8+ T Cell-Rich But Classical Macrophage-Lacking Immunosuppressive Tumor Microenvironment
Authors: Zhou Yantong , Nan Peng , Li Chunxiao , Mo Hongnan , Zhang Ying , Wang Haijuan , Xu Dongkui , Ma Fei , Qian Haili 
Published: March 2022

BackgroundThe MTA1 protein encoded by metastasis-associated protein 1 (MTA1) is a key component of the ATP-dependent nucleosome remodeling and deacetylase (NuRD) complex, which is widely upregulated in cancers. MTA1 extensively affects downstream gene expression by participating in chromatin remodeling. Although it was defined as a metastasis-associated gene in first reports and metastasis is a process prominently affected by the tumor microenvironment, whether it affects the microenvironment has not been investigated. In our study, we elucidated the regulatory effect of MTA1 on tumor-associated macrophages (TAMs) and how this regulation affects the antitumor effect of cytotoxic T lymphocytes (CTLs) in the tumor microenvironment of colorectal cancer.MethodsWe detected the cytokines affected by MTA1 expression via a cytokine antibody array in control HCT116 cells and HCT116 cells overexpressing MTA1. Multiplex IHC staining was conducted on a colorectal cancer tissue array from our cancer cohort. Flow cytometry (FCM) was performed to explore the polarization of macrophages in the coculture system and the antitumor killing effect of CTLs in the coculture system. Bioinformatics analysis was conducted to analyze the Cancer Genome Atlas (TCGA) colorectal cancer cohort and single-cell RNA-seq data to assess the immune infiltration status of the TCGA colorectal cancer cohort and the functions of myeloid cells.ResultsMTA1 upregulation in colorectal cancer was found to drive an immunosuppressive tumor microenvironment. In the tumor microenvironment of MTA1-upregulated colorectal cancer, although CD8+ T cells were significantly enriched, macrophages were significantly decreased, which impaired the CTL effect of the CD8+ T cells on tumor cells. Moreover, upregulated MTA1 in tumor cells significantly induced infiltrated macrophages into tumor-associated macrophage phenotypes and further weakened the cytotoxic effect of CD8+ T cells.ConclusionUpregulation of MTA1 in colorectal cancer drives an immunosuppressive tumor microenvironment by decreasing the microphages from the tumor and inducing the residual macrophages into tumor-associated microphage phenotypes to block the activation of the killing CTL, which contributes to cancer progression.
Identifying Language Disorder Within a Migration Context: Development and Performance of a Pre-school Screening Tool for Children With German as a Second Language
Authors: Holzinger Daniel , Weber Christoph , Jezek Magdalena 
Published: March 2022

BackgroundThere is a lack of accurate and practicable instruments for identifying language disorders in multilingual children in pre-school settings.ObjectiveTo develop a language screening instrument for pre-school children who are growing up with German as their second language.DesignAfter the development and initial validation of a language screening tool, the new instrument (LOGiK-S) was administered to three cohorts of children (2014, 2015, 2017) with a non-German first language attending a variety of public pre-schools in Upper Austria. The screening instrument measures expressive and receptive grammatical skills in German. The final validation study included the results for 270 children for the screening measure and reference tests. A combination of a standardized comprehensive language test of grammatical skills developed for children acquiring German as a second language and a test of expressive vocabulary with the use of specific cutoffs for second language learners was applied as the gold standard for identifying language disorders.ResultsThe LOGiK-S screening of expressive grammar demonstrated excellent accuracy (AUC.953). The screening subscale of receptive grammar did not improve the prediction of language disorders. Using an optimized cutoff yielded a fail rate of 17%, excellent sensitivity (0.940), and specificity (0.936). Time economy and acceptance of the screening by children and screeners were mostly rated as high.ConclusionThe LOGiK-S language screening instrument assessing expressive German grammar development using bilingual norms is a valid and feasible instrument for the identification of language disorders in second language learners of German at the pre-school age.