bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of an endoplasmic reticulum stress‐related signature to evaluate immune features and predict prognosis in glioma
Authors: Zhang Qing , Guan Gefei , Cheng Peng , Cheng Wen , Yang Lianhe , Wu Anhua 
Published: February 2021

AbstractEndoplasmic reticulum (ER) stress has considerable impact on cell growth, proliferation, metastasis, invasion, angiogenesis and chemoradiotherapy resistance in various cancers. However, the effect of ER stress on the outcomes of glioma patients remains unclear. In this study, we established an ER stress risk model based on The Cancer Genome Atlas (TCGA) glioma data set to reflect immune characteristics and predict the prognosis of glioma patients. Survival analysis indicated that there were significant differences in the overall survival (OS) of glioma patients with different ER stress‐related risk scores. Moreover, the ER stress‐related risk signature, which was markedly associated with the clinicopathological properties of glioma patients, could serve as an independent prognostic indicator. Functional enrichment analysis revealed that the risk model correlated with immune and inflammation responses, as well as biosynthesis and degradation. In addition, the ER stress‐related risk model indicated an immunosuppressive microenvironment. In conclusion, we present an ER stress risk model that is an independent prognostic factor and indicates the general immune characteristics in the glioma microenvironment.
FXR‐mediated epigenetic regulation of GLP‐1R expression contributes to enhanced incretin effect in diabetes after RYGB
Authors: Kong Xiangchen , Feng Linxian , Yan Dan , Li Bingfeng , Yang Yanhui , Ma Xiaosong 
Published: February 2021

AbstractIn this study, we investigated how Roux‐en‐Y gastric bypass (RYGB) enhances glucagon‐like peptide 1 (GLP‐1) response in GK rats and explored the potential link between RYGB‐stimulated BAs/FXR signalling and GLP‐1R‐linked signalling in β‐cells, a key pathway that regulates glucose‐stimulated insulin secretion (GSIS). Here we show that RYGB restores GLP‐1R expression in GK rat islets. This involves increased total BAs as well as chenodeoxycholic acid (CDCA), leading to FXR activation, increasing FXR binding to the promoter of Glp‐1r and enhancing occupancy of histone acetyltransferase steroid receptor coactivator‐1 (SRC1), thus increasing histone H3 acetylation at the promoter. These coordinated events bring about increased GLP‐1R expression, resulting in greater GLP‐1 response in β‐cells. Moreover, ablation of FXR suppressed the stimulatory effects of GLP‐1. Thus, this study unravels the crucial role of the BAs/FXR/SRC1 axis‐controlled GLP‐1R expression in β‐cells, which results in enhanced incretin effect and normalized blood glucose of GK rats after RYGB.
Lenvatinib prevents liver fibrosis by inhibiting hepatic stellate cell activation and sinusoidal capillarization in experimental liver fibrosis
Authors: Ogawa Hiroyuki , Kaji Kosuke , Nishimura Norihisa , Takagi Hirotetsu , Ishida Koji , Takaya Hiroaki , Kawaratani Hideto , Moriya Kei , Namisaki Tadashi , Akahane Takemi , Yoshiji Hitoshi 
Published: February 2021

AbstractMolecular targeted agents are pharmacologically used to treat liver fibrosis and have gained increased attention. The present study examined the preventive effect of lenvatinib on experimental liver fibrosis and sinusoidal capillarization as well as the in vitro phenotypes of hepatic stellate cells. LX‐2, a human stellate cell line, was used for in vitro studies. In vivo liver fibrosis was induced in F344 rats using carbon tetrachloride by intraperitoneal injection for 8 weeks, and oral administration of lenvatinib was started two weeks after initial injection of carbon tetrachloride. Lenvatinib restrained proliferation and promoted apoptosis of LX‐2 with suppressed phosphorylation of extracellular signal‐regulated kinase 1/2 and AKT. It also down‐regulated COL1A1, ACTA2 and TGFB1 expressions by inhibiting the transforming growth factor‐β1/Smad2/3 pathway. Treatment with lenvatinib also suppressed platelet‐derived growth factor‐BB‐stimulated proliferation, chemotaxis and vascular endothelial growth factor‐A production, as well as basic fibroblast growth factor‐induced LX‐2 proliferation. In vivo study showed that lenvatinib attenuated liver fibrosis development with reduction in activated hepatic stellate cells and mRNA expression of profibrogenic markers. Intrahepatic neovascularization was ameliorated with reduced hepatic expressions of Vegf1, Vegf2 and Vegfa in lenvatinib‐treated rats. Collectively, these results suggest the potential use of lenvatinib as a novel therapeutic strategy for liver fibrosis.
AS602801 sensitizes glioma cells to temozolomide and vincristine by blocking gap junction communication between glioma cells and astrocytes
Authors: Zhang Shuai , Gong Yong , Wang Hongxin , Li Zhongfan , Huang Yunfeng , Fu Xing , Xiang Peng , Fan TianYu 
Published: February 2021

AbstractPrevious studies showed that the chemotherapeutic effect of temozolomide (TMZ) and vincristine (VCR) against glioma might be blunted by the co‐culture with astrocytes, and connexin‐43 (CX43) was thought to play a vital role in the communication between glioma cells and astrocytes. In this study, we aimed to investigate the combined chemotherapeutic effect of AS602801 and TMZ/ VCR in glioma cells both. Dye transfer assay was used to evaluate the gap junction activity between U251 cells and astrocytes. Western blot and immunohistochemistry were carried out to analyse the expression of p‐JNK, CX43 and CASP‐3 proteins treated under different conditions. AS602801 significantly suppressed the gap junction activity between U251 cells and astrocytes. The expression of p‐JNK and CX43 was remarkably inhibited by AS602801. TMZ/VCR‐induced apoptosis of glioma cells was effectively enhanced by AS602801 treatment. Accordingly, the inhibitory role of TMZ/VCR in the expression of p‐JNK, CX43 and CASP‐3 in glioma cells was notably restored by AS602801. Furthermore, in a glioma cell xenograft, AS602801 showed an apparent capability to enhance TMZ/VCR‐induced tumour cell apoptosis through altering the expression of p‐JNK, CX43 and CASP‐3. The findings of this study demonstrated that the co‐culture of glioma cells with astrocytes blunted the tumour killing effect of TMZ and VCR. AS602801 down‐regulated CX43 expression by inhibiting JNK. And AS602801 also sensitized glioma cells to TMZ/VCR by blocking the gap junction communication between glioma cells and astrocytes via down‐regulating CX43, indicating its potential role as a novel adjuvant chemotherapeutic agent in the treatment of glioma.
MARCH5 restores endothelial cell function against ischaemic/hypoxia injury via Akt/eNOS pathway
Authors: Lei Wenhua , Li Junli , Li Changming , Chen Li , Huang Fangyang , Xiao Dan , Zhang Jialiang , Zhao Jiahao , Li Guoyong , Qu Tianyi , Zhou Hao , Liao Yanbiao , Chen Mao 
Published: February 2021

AbstractMARCH5 is a critical regulator of mitochondrial dynamics, apoptosis and mitophagy. However, its role in cardiovascular system remains poorly understood. This study aimed to investigate the role of MARCH5 in endothelial cell (ECs) injury and the involvement of the Akt/eNOS signalling pathway in this process. Rat models of myocardial infarction (MI) and human cardiac microvascular endothelial cells (HCMECs) exposed to hypoxia (1% O2) were used in this study. MARCH5 expression was significantly reduced in ECs of MI hearts and ECs exposed to hypoxia. Hypoxia inhibited the proliferation, migration and tube formation of ECs, and these effects were aggravated by knockdown of MARCH5 but antagonized by overexpressed MARCH5. Overexpression of MARCH5 increased nitric oxide (NO) content, p‐eNOS and p‐Akt, while MARCH5 knockdown exerted the opposite effects. The protective effects mediated by MARCH5 overexpression on ECs could be inhibited by eNOS inhibitor L‐NAME and Akt inhibitor LY294002. In conclusion, these results indicated that MARCH5 acts as a protective factor in ischaemia/hypoxia‐induced ECs injury partially through Akt/eNOS pathway.
Metformin attenuates post‐epidural fibrosis by inhibiting the TGF‐β1/Smad3 and HMGB1/TLR4 signaling pathways
Authors: Song Zeyuan , Wu Tao , Sun Jinpeng , Wang Haoran , Hua Feng , Nicolas Yap San Min , KC Rupesh , Chen Kun , Jin Zhen , Liu Jun , Zhang Mingshun 
Published: February 2021

AbstractExcessive post‐epidural fibrosis is a common cause of recurrent back pain after spinal surgery. Though various treatment methods have been conducted, the safe and effective drug for alleviating post‐epidural fibrosis remains largely unknown. Metformin, a medicine used in the treatment of type 2 diabetes, has been noted to relieve fibrosis in various organs. In the present study, we aimed to explore the roles and mechanisms of metformin in scar formation in a mouse model of laminectomy. Post‐epidural fibrosis developed in a mouse model of laminectomy by spinous process and the T12‐L2 vertebral plate with a rongeur. With the administration of metformin, post‐epidural fibrosis was reduced, accompanied with decreased collagen and fibronectin in the scar tissues. Mechanistically, metformin decreased fibronectin and collagen deposition in fibroblast cells, and this effect was dependent on the HMGB1/TLR4 and TGF‐β1/Smad3 signalling pathways. In addition, metformin influenced the metabolomics of the fibroblast cells. Taken together, our study suggests that metformin may be a potential option to mitigate epidural fibrosis after laminectomy.
Cytoglobin promotes sensitivity to ferroptosis by regulating p53‐YAP1 axis in colon cancer cells
Authors: Ye Shazhou , Xu Mingjun , Zhu Tingwei , Chen Jiayi , Shi Shanping , Jiang Haizhong , Zheng Qingfang , Liao Qi , Ding Xiaoyun , Xi Yang 
Published: February 2021

AbstractFerroptosis is an iron‐dependent mode of non‐apoptotic cell death characterized by accumulation of lipid reactive oxygen species (ROS). As a regulator of ROS, cytoglobin (CYGB) plays an important role in oxygen homeostasis and acts as a tumour suppressor. However, the mechanism by which CYGB regulates cell death is largely unknown. Here, we show that CYGB overexpression increased ROS accumulation and disrupted mitochondrial function as determined by the oxygen consumption rate and membrane potential. Importantly, ferroptotic features with accumulated lipid ROS and malondialdehyde were observed in CYGB‐overexpressing colorectal cancer cells. Moreover, CYGB significantly increased the sensitivity of cancer cells to RSL3‐ and erastin‐induced ferroptotic cell death. Mechanically, both YAP1 and p53 were significantly increased based on the RNA sequencing. The knock‐down of YAP1 alleviated production of lipid ROS and sensitivity to ferroptosis in CYGB overexpressed cells. Furthermore, YAP1 was identified to be inhibited by p53 knock‐down. Finally, high expression level of CYGB had the close correlation with key genes YAP1 and ACSL4 in ferroptosis pathway in colon cancer based on analysis from TCGA data. Collectively, our results demonstrated a novel tumour suppressor role of CYGB through p53‐YAP1 axis in regulating ferroptosis and suggested a potential therapeutic approach for colon cancer.
Survival in hospice patients with dementia: the effect of home hospice and nurse visits
Authors: Luth Elizabeth A. , Russell David J. , Xu Jiehui Cici , Lauder Bonnie , Ryvicker Miriam B. , Dignam Ritchell R. , Baughn Rosemary , Bowles Kathryn H. , Prigerson Holly G. 
Published: February 2021

AbstractBackgroundHospice patients with dementia are at increased risk for live discharge and long lengths of stay (>180 days), causing patient and family caregiver stress and burden. The location and timing of clinician visits are important factors influencing whether someone dies as expected, in hospice, or experiences a live discharge or long length of stay.ObjectiveExamine how home hospice and nurse visit frequency relate to dying in hospice within the Medicare‐intended 6‐month period.DesignRetrospective cohort study.SettingNon‐profit hospice agency.ParticipantsThree thousand eight hundred and thirty seven patients with dementia who received hospice services from 2013 to 2017.MethodsMultivariable survival analyses examined the effects of receiving home hospice (vs. nursing home) and timing of nurse visits on death within 6 months of hospice enrollment, compared to live discharge or long length of stay. Models adjust for relevant demographic and clinical factors.ResultsThirty‐nine percent (39%) of patients experienced live discharge or long length of stay. Home hospice patients were more likely to experience live discharge or long length of stays (HR for death: 0.77, 95%CI: 0.69–0.86, p < 0.001). Frequency of nurse visits was inversely associated with live discharge and long lengths of stay (HR for death: 2.87, 95%CI: 2.47–3.33, p < 0.001).ConclusionNearly 40% of patients with dementia in our study experienced live discharge or a long length of stay. Additional research is needed to understand why home hospice may result in live discharge or a long length of stay for patients with dementia. Nurse visits were associated with death, suggesting their responsiveness to deteriorating patient health. Hospice guidelines may need to permit longer stays so community‐dwelling patients with dementia, a growing segment of hospice patients, can remain continuously enrolled in hospice and avoid burden and costs associated with live discharge.
Fiscal Consolidation and Public Wages
Authors: CHANG JUIN‐JEN , LIN HSIEH‐YU , TRAUM NORA , YANG SHU‐CHUN S. 
Published: February 2021

AbstractA New Keynesian model with government production, public compensation, and unemployment is fit to U.S. data to study the effects of public wage reductions. Estimation implies reductions in public wages and government goods purchases have similar effects on total output, and the fiscal balance, yet the former can raise private output slightly, while the latter does not. Exogenous public wage reductions decrease private wages. Model counterfactuals show that sufficiently rigid nominal private wages can reverse the private wage response, as the rigidity dampens the labor reallocation effect from the public to private sector that exerts downward pressure on private wages.
Sociolinguistics of pathologized speech: A case of deaf and hard‐of‐hearing speakers of Taiwan Mandarin
Authors: Wan Tsung‐Lun Alan 
Published: February 2021

AbstractSpeakers of pathologized speech have not received much attention from sociolinguists. This article explores the stylistic practices of deaf and hard‐of‐hearing (DHH) people who demonstrate pathologized variants. This article adopts minimal pair reading and story reading to elicit various stylistic practices, as part of a larger project that aims to describe and empower DHH speech. Results show that DHH speakers who have experiences of medicalization are also the ones who consider learning the speech of hearing people necessary. A portion of these speakers embody their ideological stance—converging towards hearing speech—in the minimal pair reading.
Comparison of gluteus medius muscle activity in Haflinger and Noriker horses with polysaccharide storage myopathy
Authors: Zsoldos Rebeka Roza , Khayatzadeh Negar , Soelkner Johann , Schroeder Ulrike , Hahn Caroline , Licka Theresia Franziska 
Published: February 2021

AbstractType 1 polysaccharide storage myopathy caused by genetic mutation in the glycogen synthase 1 gene is present in many breeds including the Noriker and Haflinger horses. In humans, EMG has already been used to document changes in the muscle activity patterns of patients affected by human glycogen storage disorders. Therefore, the aim of the present study was to describe gluteus muscle activity with surface electromyography (sEMG) in Haflinger and Noriker horses with known GYS1 mutation status during walk and trot. Thirty‐two horses (11 Haflinger and 21 Noriker horses) with homozygous non‐affected (GG), heterozygous affected (GA) and homozygous affected (AA) status of GYS1 mutation without overt clinical signs of any myopathy were selected for the current study. Using surface electromyography gluteus medius muscle activity at walk and at trot was measured, and muscle activity was described in relation to the maximum observed value at the same sensor and the same gait. In order to further describe the signals in detail comprising both frequencies and amplitudes, the crossings through the baseline and the 25, 50 and 75 percentile lines were determined. The result of the relative muscle activity did not show a consistent difference between affected and non‐affected horses. Genetically affected (GA and AA) horses showed significantly less density of muscle activity for both gaits and horse breeds except for the crossings per second at the baseline and 75 percentile at walk in the Haflinger horses and 75 percentile at trot in the Noriker horses. The medians of all calculated density values were significantly lower in the GA Haflingers compared to the GG Haflingers (p = 0.012) and also in the AA Norikers compared to the GG Norikers (p = 0.011). Results indicate that the GYS1 mutation reduces the number of functional muscle fibres detected by sEMG measurements even in the absence of overt clinical signs.
Drivers of European bat population change: a review reveals evidence gaps
Authors: Browning Ella , Barlow Kate E. , Burns Fiona , Hawkins Charlotte , Boughey Katherine 
Published: February 2021

Abstract

Bat populations are thought to have suffered significant declines in the past century throughout Europe. Fortunately, there are some signs of recovery; for instance, of the 11 species monitored in the UK, population trends of five are increasing. The drivers of past losses and recent trends are unclear; identifying them will enable targeted conservation strategies to support further recovery.

We review the evidence linking proposed drivers to impacts on bat populations in Europe, using the results of a previous cross‐taxa semi‐quantitative assessment as a framework. Broadly, the drivers reviewed relate to land‐use practices, climate change, pollution, development and infrastructure, and human disturbance. We highlight where evidence gaps or conflicts present barriers to successful conservation and review emerging opportunities to address these gaps.

We find that the relative importance or impacts of the potential drivers of bat population change are not well understood or quantified, with conflicting evidence in many cases. To close key gaps in the evidence for responses of bat populations to environmental change, future studies should focus on the impacts of climate change, urbanisation, offshore wind turbines, and water pollution, as well as on mitigation measures and the synergistic effects of putative drivers.

To increase available evidence of drivers of bat population change, we propose utilising advances in monitoring tools and statistical methods, together with robust quantitative assessment of conservation interventions to mitigate threats and enable the effective conservation of these protected species.
Data considerations for the success of policy to restrict in‐store food promotions: A commentary from a food industry nutritionist consultation
Authors: Jenneson V. , Morris M. A. 
Published: February 2021

AbstractNew plans to restrict in‐store price and location‐based promotions of less healthy foods and drinks in the UK aimed to encourage healthier choices. With responsibility for implementation likely falling to food retailers, it is important to understand the feasibility of implementation and to ensure policy success. To ensure compliance, retailers will need to assess which products are restricted under the legislation. The large number of products in retailers’ portfolios poses a problem of scale. A recent research case study found the data available to retailers to be insufficient to accurately apply the rules‐based approach set out by the policy proposal. Misclassification would result in some less healthy products being incorrectly promoted and vice versa. Problems with implementation feasibility have the potential to undermine the public health goals of the legislation. Interviews were carried out with nutrition representatives from the UK food retail and manufacturing sector, to understand the real‐world implications of the proposed legislation. Industry nutritionists recommended a review of the use of the UK’s Nutrient Profiling Model as the legislative basis, proposed data‐related solutions to implementation problems and suggested a need for shared retailer‐manufacturer responsibility, given the context of data availability.
Assessment of satellite products for filling rainfall data gaps in the Amazon region
Authors: de Moraes Cordeiro Adria Lorena , Blanco Claudio José Cavalcante 
Published: February 2021

AbstractRainfall data series with adequate quality and length are often incomplete or nonexistent. Thus, filling in rainfall gaps becomes necessary to complete databases. This article proposes the use of satellite products (TRMM—Tropical Rainfall Measuring Mission, CHIRPS—Climate Hazards Group InfraRed Precipitation with Stations and CMORPH—CPC Morphing Technique) to fill gaps in the rainfall historical series. The simple regression method, using satellite rainfall estimates, was tested to fill the missing data from 164 rainfall gauge stations in the Amazon region. Large dispersions were observed between rainfall data, withR2ranging from 0.383 to 0.844, the best results were found in areas with less rainfall. As well, the greatest performance of the products was verified in the dry period, withranddhigher than 0.899 and 0.950, respectively. The product with the best representation in the region was CHIRPS, which had the lowest monthly values of mean absolute error (0.979 mm) and root mean square error (3.656 mm). The results confirm that the satellite estimates satisfactorily represent the seasonal variation of rainfall in the region, despite presenting cases of overestimation and underestimation of data. The higher performance of CHIRPS can be explained by the higher spatial resolution (0.05°), allowing for more accurate weather forecasts. In fact, CHIRPS has the CHPclim model, which adds other factors to the good product performance. These characteristics justify the better performance of the CHIRPS product for filling gaps in daily rainfall data in the Amazon region, favoring the best monthly rainfall estimates for each region state analyzed.Recommendations for Resource ManagersSatellite products have been increasingly used for estimating rainfall data in regions with a low number of installed rainfall gauge stations. Thus, the assessment and selection of these products needs to be elaborated for the best decision making of water resource managers.Rainfall data are important to recognize the occurrence patterns for prediction of the climatic behavior of a region. Sectors such as agriculture and disaster prevention (droughts, floods, erosion of watersheds, and river silting) need knowledge of rainfall for planning, management, and mitigation.Knowledge of rainfall behavior is very important in the Amazon region. In this case, the dry season and temperatures have been increasing due to global climate change. These changes establish conditions for more intense fires, which increases the deforestation of the region.