bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lipid rafts act as a common platform for Aß oligomer-induced Alzheimer’s pathology
Authors: Kawarabayashi Takeshi , Nakamura Takumi , Sato Kaoru , Seino Yusuke , Ichii Sadanobu , Nakahata Naoko , Takatama Masamitsu , Westaway David , George-Hyslop Peter St. , Shoji Mikio 
Published: November 2021

Abstract
Background

Amyloid ß protein (Aß) oligomers induce the overproduction of phosphorylated tau and neurodegeneration. These cascades gradually cause cognitive impairment in Alzheimer’s disease (AD). While each pathological event in AD has been studied in detail separately, the spatial and temporal relationships between pathological events in AD remain unclear. Here, we demonstrated that lipid rafts function as a common platform for the pathological cascades of AD.
Methods

Cellular and synaptosomal lipid rafts were prepared from the brains of Aß amyloid model mice (Tg2576 mice) and double transgenic mice (Tg2576 x TgTauP301L mice) and longitudinally analyzed.
Results

Aß oligomers, the cellular prion protein (PrPc), and Aß oligomer/PrPc complexes were detected in the lipid rafts. The levels of Fyn, the phosphorylated NR2B subunit of the N-methyl-D-aspartate receptor, glycogen synthase kinase 3 beta, total tau, phosphorylated tau, and tau oligomers increased with Aß oligomer accumulation in both the cellular and synaptosomal lipid rafts. Increases in the levels of these molecules were first seen at 6 months of age and corresponded with the early stages of Aß accumulation in the amyloid model mice.
Conclusions

Lipid rafts act as a common platform for the progression of Alzheimer’s pathology. The findings of this study suggest a novel therapeutic approach to AD, involving the modification of lipid raft components and the inhibition of their roles in the sequential pathological events of AD.
Establishment of A Risk-Predicting Twenty-Two-Gene Signature Based on the Prognosis-Related RNA Binding Proteins of Breast Cancer
Authors: Zhu Tong , Zhu Xudong , Bu Jiawen , Jiang Yi , Xue Jinqi , Niu Nan , Gu Xi 
Published: November 2021

Abstract
Background

Breast cancer has been the leading cause of death among women worldwide. RNA-binding proteins (RBPs) are promising novel biomarkers for patients with malignant tumors, the abnormal expression of which is closely associated with the development of breast cancer. This study aimed to identify RBPs associated with the survival outcomes of breast cancer and to construct a prognostic model and a clinical prediction nomogram for breast cancer.
Methods

The transcriptome data of breast cancer were downloaded from TCGA database. GO and KEGG analyses were performed to clarify the gene functions and regulatory pathway. Cox and LASSO regression analyses were utilized to analyze the prognosis prediction effect of RBPs and clinical characteristics in breast cancer and create a risk score model. A nomogram was also built by merging the model and clinicaopatholigical characteristics, which was validated using calibration curves.
Results

A prognostic risk score model of the 22-RBP signature was established. This risk score predicted 3-, 5-, and 10-year overall survival rates sensitively and accurately. Compared to other clinicaopatholigical characteristics, this risk score had better predictive ability. We also constructed a nomogram based on risk scores and clinicaopatholigical characteristics. The nomogram may predict the 1-, 3-, and 5-year survival rates of patients with breast cancer.
Conclusions

RBPs play an important role in the development and survival outcomes of breast cancer by regulating multiple biological processes. Furthermore, this study identified and constructed a 22-RBP based signature and a clinical nomogram for predicting the survival probability of patients with breast cancer.
ARNTL2, an Immunoregulation-Related Prognostic Biomarker in Pan-Cancer and Lung Adenocarcinoma
Authors: Wu Gujie , Wang Wenmiao , Yang Zheng , Xue Qun 
Published: November 2021

Abstract
Background

ARNTL2 is a member of the PAS superfamily that promotes tumor progression. However, the role of ARNTL2 in lung adenocarcinoma (LUAD) remains unclear. The purpose of our study was to investigate the function of ARNTL2 in LUAD.
Methods

The expression, clinical features, and prognostic role of ARNTL2 in pan-cancer were evaluated using The Cancer Genome Atlas and Genotype-Tissue Expression data. GSEA and GSVA of ARNTL2 were performed using the R package “clusterProfiler.” The correlation between immune cell infiltration level and ARNTL2 expression was analyzed using two sources of immune cell infiltration data, including the TIMER2 and ImmuCellAI database. Finally,we analyzed the correlation between ARNTL2 and IC50 of 192 drugs.
Results

ARNTL2 was substantially overexpressed in LUAD and pan-cancer. High ARNTL2 expression predicted poor survival in patients with LUAD. We also found that ARNTL2 expression was positively associated with the infiltration levels of immunosuppressive cells, such as tumor associated macrophages, cancer associated fibroblasts and Tregs. Among the 192 anti-cancer drugs, ARNTL2 expression was positively correlated with IC50 of 114 anti-cancer drugs, such as SB505124, Doramapimod, Nutlin-3a (-), Sabutoclax, AZD5991, PF-4708671, Elephantin, PRIMA-1MET, Sorafenib, Vorinostat, and MK-2206.
Conclusions

Our results revealed that ARNTL2 is a potential prognostic biomarker in LUAD. An elevated ARNTL2 expression indicates an immunosuppressive microenvironment, and targeted therapies against ARNTL2 have excellent potential.
Greenspace availability or greenspace usability, which matters on PM2.5-related premature deaths: evidence from 360 cities in China
Authors: Yang Jingru , Wang Yijin , Li Fangzheng , Xie Yuge , Wang Xiaoli 
Published: November 2021

Abstract
Greenspace exposure is confirmed to reduce air pollution-related negative health impact. However, which type of greenspace exposure matters more on mitigating air pollution-related deaths and whether this effect is regionally different remain unclear. Here we show, greenspace usability exposure plays a more significant role in mitigating PM2.5-related premature deaths in 360 China cities generally speaking. By clustering 360 cities into urban-rural and Deprivation Index groups, we further find that greenspace availability and usability together work on respiratory health in rural regions, and greenspace availability matters more in very low deprived areas or urban and rural regions. Our results that increasing greenspace usability exposure is more helpful in reducing air pollution-related premature deaths may inform more effective and equitable greenspace planning policies in rapidly developing countries like China.
Assessing Spinal Movement During Four Extrication Methods: A Biomechanical Study using Healthy Volunteers
Authors: Nutbeam Tim , Fenwick Rob , May Barbara , Stassen Willem , Smith Jason , Bowdler Jono , Wallis Lee , Shippen James 
Published: November 2021

Abstract
BackgroundMotor vehicle collisions are a common cause of death and serious injury. Many casualties will remain in their vehicle following a collision. Trapped patients have more injuries and are more likely to die than their untrapped counterparts. Current extrication methods are time consuming and have a focus on movement minimisation and mitigation. The optimal extrication strategy and the effect this extrication method has on spinal movement is unknown. The aim of this study was to evaluate the movement at the cervical and lumbar spine for four commonly utilised extrication techniques. MethodsBiomechanical data was collected using inertial Measurement Units on 6 healthy volunteers. The extrication types examined were: roof removal, b-post rip, rapid removal and self-extrication. Measurements were recorded at the cervical and lumbar spine, and in the anteroposterior (AP) and lateral (LAT) planes. Total movement (travel), maximal movement, mean, standard deviation and confidence intervals are reported for each extrication type.ResultsData from a total of 230 extrications were collected for analysis. The smallest maximal and total movement (travel) were seen when the volunteer self-extricated (AP max = 2.6mm, travel 4.9mm). The largest maximal movement and travel were seen in rapid extrication extricated (AP max = 6.21mm, travel 20.51 mm). The differences between self-extrication and all other methods were significant (p<0.001), small non-significant differences existed between roof removal, b-post rip and rapid removal.Self-extrication was significantly quicker than the other extrication methods (mean 6.4s).ConclusionsIn healthy volunteers, self-extrication is associated with the smallest spinal movement and the fastest time to complete extrication. Rapid, B-post rip and roof off extrication types are all associated with similar movements and time to extrication in prepared vehicles.
Baicalein Alleviates Fibrosis and Inflammation in Scleroderma Through Regulating B Cell Abnormalities
Authors: Peng Bo , Hu Qin , He Rong , Hou Hongping , Chen Ying , Li Jianrong , Zhang Guangping , Hu Xiaoru 
Published: November 2021

Abstract
Background

Scleroderma (Systemic sclerosis, SSc) is an autoimmune disorder characterized by multisystem extensive fibrosis, vascular changes and immunological dysregulation. B cell abnormalities play an essential role in the fibrotic pathogenesis of scleroderma by promoting autoantibodies and cytokines release as well as modulating the inflammatory processes. Baicalein, a phenolic flavonoid derived from the Chinese herb Scutellaria baicalensis Georgi, has been used in the treatment of the pathological processes of various fibrotic and inflammatory diseases. Here, we aimed to investigate the effect of baicalein on the major pathological characteristics of SSc both in vitro and in vivo, including fibrosis, B cell abnormalities and inflammation.
Methods

The effect of baicalein on collagen accumulation and expression of fibrogenic markers in human dermal fibroblasts were analyzed. The antifibrotic features of baicalein and its mechanisms were investigated in the bleomycin (BLM)-induced dermal fibrosis mice model by histologic examination, hydroxyproline assay, enzyme-linked immunosorbent assay and flow cytometry.
Results

5-120 µM baicalein significantly abrogated total collagen deposition, decreased soluble collagen secretion, and inhibited the expression of various fibrogenesis molecules, including collagen(COL)1A1, COL1A2, COL3A1, connective tissue growth factor (CTGF), fibronectin, transforming growth factor β1 (TGF-β1) and alpha-smooth muscle actin (α-SMA) in both TGF β1- and PDGF-induced human CCC-ESF-1 dermal fibroblasts. In BLM-induced dermal fibrosis mice model, 25-100 mg/kg baicalein markedly attenuated dermal thickness and collagen accumulation in dose-dependent manners. Baicalein reduced the proportion of B220+ B cells, while increased the percentage of CD27+ memory B cells in the spleen of BLM-induced mice. Consistent with reversing B cell abnormalities, baicalein treatment potently attenuated serum levels of cytokines(IL-1β, IL-2, IL-4, IL6, IL-17A, TNF-α), chemokines (MCP-1, MIP-1β) and autoantibodies (anti-Scl-70, anti-PM-Scl, anti-centromeres and anti-dsDNA).
Conclusions

Baicalein inhibits TGF-β1 and PDGF- mediated ECM accumulation in human dermal fibroblasts and alleviates the development of experimental dermal fibrosis by reversing B cell abnormalities, reducing autoantibody production and ameliorating inflammation. Baicalein may have the potential to be further developed as a therapeutic candidate against SSc.
Methodology For Assessing The Effectiveness of Regional Infrastructure Facilities to Support Scientific, Technical and Innovation Activities In The Context of The Synergy Effect: Analysis, Formation and Study
Authors: Byvshev Vladimir , Parfenteva Kristina , Panteleeva Irina , Uskov Danil , Demin Vadim 
Published: November 2021

Abstract
The aim of the study is to develop a methodology for assessing the effectiveness of the regional infrastructure facilities to support scientific, technical and innovation activities, taking into account the synergy effect. The article analyses methods existing in Russia and other countries and identifies their benefits and drawbacks. Based on the analysis conducted, the authors have determined a list of indicators characterising this area, developed a system for calculating the integral indicator, identified a list of regions that provided for the most objective assessment and testing of the developed methodology, and drew conclusions based on the calculations results. As a result, the effectiveness and perspectiveness of the developed methodology have been indicated. Even though the composite index is in the stability zone, its individual components may be in the zone of catastrophic risk and contain potential threats to further innovative development of a region. At the same time, it has been determined that regulatory support, as well as closed nature of the innovation cycle (synergy effect) play an important role in the efficient functioning of the infrastructure for supporting scientific, technical, and innovation activities.
Increased Lateral Femoral Condyle Ratio Measured by MRI Is Associated with Higher Risk of Noncontact Anterior Cruciate Ligament Injury
Authors: He Miao , Li Jie 
Published: November 2021

Abstract
Background
Studies have shown a significant association between the radiographically measured lateral femoral condyle ratio (LFCR) and anterior cruciate ligament (ACL) injury. However, it is unclear whether the the LFCR measured by magnetic resonance imaging (MRI) is associated with risk of noncontact ACL injury.
Objective
1 To investigate the effect of the LFCR on the risk of noncontact ACL injury by MRI. 2 To investigate the association of the LFCR measured by MRI with multiple bone morphological risk factors and evaluate the most sensitive risk predictors of noncontact ACL injury.
Methods
A total of 116 patients, including 58 subjects with noncontact ACL injury and 58 age-matched and sex-matched controls with only meniscus injury, were included in this retrospective case-control study. The LFCR, lateral tibial slope (LTS), lateral tibial height (LTH), medial tibial slope (MTS), and medial tibial depth (MTD) were measured on MRI. The differences in each index between the two groups were compared, and risk factors were screened by single-factor logistic regression analysis. Indicators with P values <0.1 were included in the logistic regression equation. The critical values and areas under the curve (AUCs) of independent risk factors were determined by receiver operating characteristic (ROC) curve analysis. Finally, the diagnostic performance of each risk factor was evaluated by the Z-test.
Results
A total of 116 patients who met the inclusion criteria were included in the final analysis (58 cases in the noncontact ACL injury group and 58 cases in the control group). Patients with noncontact ACL injury had a higher femoral LFCR (63.5±2.7%) than patients with simple meniscus tear. Among all the risk factors for ACL injury, the AUC for the LFCR was the largest, at 0.81 (95% CI, 0.73-0.88), and when the critical value was 61.35%, the sensitivity and specificity for the diagnosis of ACL injury were 79% and 67%, respectively. Combined with the LTH (> 2.35 mm), the diagnostic performance was improved. The AUC was 0.85 (95% CI, 0.78-0.92), the sensitivity was 0.83, and the specificity was 0.76
Conclusion
This study shows that an increased LFCR is related to an increased risk of noncontact ACL injury by MRI. The LFCR and LTH are the most sensitive risk factors for noncontact ACL injury and may help clinicians identify individuals prone to ACL injury, allowing prevention and intervention measures to be applied.
Intensive versus conservative glycaemic control in patients undergoing coronary artery bypass graft surgery: a protocol for systematic review and meta-analysis of randomized controlled trials
Authors: Liu Yi , Lv Meng , Sun Xia-xuan , Du Wen-ya , Chen Ting-ting , Wang Yuelan 
Published: November 2021

Abstract
Background
Coronary artery bypass graft (CABG) surgery has become the most common surgical procedure among all cardiac surgeries. Hyperglycaemia and hypoglycaemia occur frequently during this type of surgery and are associated with a variety of postoperative outcomes. Therefore, intraoperative glycaemic control is an important issue for patients undergoing CABG surgery. This systematic review and meta-analysis aim to evaluate the effects of different intraoperative glycaemic control strategies on postoperative outcomes.
Methods
We will perform a systematic review and meta-analysis of randomized controlled trials (RCTs) according to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Relevant studies will be searched in the Medline, Embase, Cochrane Library and Web of Science databases. Two independent reviewers will conduct study selection, data extraction, risk of bias assessment and quality of evidence assessment. The primary outcome will be postoperative mortality, and the secondary outcomes will include time on a ventilator in the intensive care unit (ICU), incidence of postoperative myocardial infarction (MI), incidence of postoperative atrial fibrillation (AF), rate of postoperative infection, incidence of acute kidney failure (AKF), length of stay (LOS) in the ICU, and LOS in the hospital. χ2 (Cochran Q) and I2 methods will be used to assess statistical heterogeneity. Sensitivity analysis will also be performed to explore the source of clinical heterogeneity, and subgroup analyses will be performed to detect possible heterogeneity of the results. Review Manager (RevMan) 5.4 will be used for data management and statistical analysis. The Cochrane risk-of-bias tool 2.0 and GRADEpro will be applied for risk of bias and quality assessment of the evidence.
Discussion
We assume that intensive glycaemic control in patients undergoing CABG will reduce postoperative mortality and complications, which seriously compromise a patient’s quality of life and may even cause premature death. To address limitations in our study, corresponding methodologies will be adopted to optimize the results as much as possible. The results of our study are expected to provide strong evidence supporting the relationship between intensive intraoperative glycaemic control strategies and the reduction of postoperative complications in patients undergoing CABG surgery.
Systematic review registration
PROSPERO CRD42021240841.
Analysis and Appraisal of Fascine in Shahe Ancient Bridge Ruins, Xi’an, Shaanxi, China
Authors: Mai Bingjie , Liu Naiming , Liu Jiaojiao , Liu Dan , Li Jin , Wang Juanli , Chen Aidong , Cao Jing , Li Yuhu 
Published: November 2021

Abstract
The Chinese civilization has a long history, and the Chinese ancestors invented the "aquatic engineering technology" for flood control and water management as early as two thousand years ago: Fascine Body. The Fascine Body is a structure used to protect the bank and block the breach in the ancient Chinese flood control project. The excavation of the Shahe Ancient Bridge Ruins in Xi’an City, Shaanxi Province, China discovered the existence of a fascine body structure. Through C14 dating, fiber slice observation, infrared spectroscopy, X-ray diffraction, thermogravimetric analysis and SEM energy spectrum analysis of the fascine material, at the same time, conduct the microbial identification on it and the surrounding soil, analyze its dominant bacterial community, and control its microbial diseases in a targeted manner. The research on the fascine bank ruins solved the boundary problem of the width and length of the Shahe ancient bridge, evaluated the exact age of Shahe ancient bridge, provided the important materials for the research on ancient bridges, river embankments and other ruins, and also provided the important clues for the traffic and layout around Chang'an during the Qin and Han Dynasties of Chinese history.
Effect of Early Life Exposure of Polystyrene Microplastics on Behavior and DNA Methylation in Later Life Stage of Zebrafish
Authors: Im Jeongeun , Eom Hyun-Jung , Choi Jinhee 
Published: November 2021

Abstract
Microplastic contamination has received increasing attention in recent years, and concern regarding the toxicity of microplastics to the environment and humans has increased. In this study, we investigated the neurodevelopmental toxicity of polystyrene microplastics (PSMPs) in the zebrafish Danio rerio under different exposure scenario. We investigated the effect of early life exposure to PSMPs on responses later in life, under different exposure scenarios. Zebrafish were exposed to PSMPs during embrionic stage, then allowed the fish to recover. The neurodevelopmental toxic responses were investigated using fish behavior and behavior-related gene expression. Early life exposure to PSMPs did not alter fish behavior at the early stage, however, it led to hyperactivity later life-stage. Generally, oxidative stress (i.e. sod2 and nrf2a) and nervous system (i.e. slc6a4b, npy and nrbf2)-related gene expression increased in all PSMPs-exposed fish. DNA hypomethylation was observed in fish challenged for a second time using the same PSMPs. Taken together, the current results imply that PSMPs have neurodevelopmental toxic potential when introduced early in life.
Sensory nerves directly promote osteoclastogenesis by secreting Cyp40
Authors: Pei Guo-Xian , Yang Liu , Li Junqin , Liu Bin , Wu Hao , Zhang Shuaishuai , Liang Zhuowen , Guo Shuo , Xiao Guozhi , Wang Ling , Xu Jing , Jiang Huijie , Cheng Pengzhen , Song Yue , Lei Xing , Wang Jimeng , Li Donglin , Gao Yi , Liu Yang , Wang Di , Zhan Nazhi 
Published: November 2021

Abstract
BackgroundGiven the afferent functions, sensors have been found exerting efferent influences and directly alter organ physiology. Sensory nerves have been found critical in osteoclasts and bone resorption. However, the direct evidence of whether sensory nerve efferent influences osteoclast, remains lacking. MethodsWe treated mice with resiniferatoxin (RTX) or complete Freund’s adjuvant (CFA) to induce sensory hypersensitivity. Bone histomorphometry including micro-ct, three-point bending assay, von kossa staining, calcein double labeling, toluidine blue staining, and trap staining were performed to monitor bone quality and bone cells. Multiple virus vectors were applied to trace signals between sensory nerves and osteoclasts. Sensory neurons (SN) and osteoclasts were cocultured to study the effects and mechanisms of the sensory nerves on osteoclasts in vitro. Isobaric tag for relative and absolute quantitation (iTRAQ) was used to identify secreted proteins in the sensory nerve. ResultsHere, we found sensory hypersensitivity significantly increased osteoclast bone resorption; SN directly promote osteoclastogenesis in vitro; and abundant sensory efferent signals transported into osteoclasts. Then our screening identified a novel neuropeptide Peptidyl-prolyl cis-trans isomerase D (Cyp40), is the reverse signal from the sensory nerve and plays a critical role for osteoclastogenesis, via aryl hydrocarbon receptor (AhR)-Ras/Raf-pErk-NFATc1 pathway. The efferent signals from sensory nerves tend to involves in the rapid feedback process: vast majority of sensory efferent signals (87.28%) present in fast-twitch myofibers. ConclusionThis study revealed a novel mechanism of sensory nerves on osteoclasts: the direct promotion of osteoclastogenesis by the Cyp40. This mechanism may represent a direct, and quick response of sensory nerves to the changes in bone. Targeting the Cyp40 could therefore be a strategy to promote bone repair at the early stage of bone injury.