bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pathways of nurses in Long-term care hospitals: Seeking work-life balance
Authors: Kim Samsook , Lee Ga Eon , Bowers Barbara , Jo Yeonjae 
Published: May 2020

Abstract
Background

This study explores the pathways of nurses in LTCHs and its underlying conditions in Korea. Nursing shortage in long-term care setting has been a worldwide concern. Although the factors of staying or leaving of nurses in long term care hospitals (LTCHs) have been reported, few studies have examined the trajectory and conditions of nurses staying in and leaving LTCHs.
Methods

A qualitative study design with a grounded theory approach was conducted. Data were collected in one to one interviews. Purposive and theoretical sampling led to the inclusion of 17 registered nurses with diverse characteristics from 14 LTCHs in a metropolitan city in South Korea. Individual, in-depth interviews were conducted. Data collection and analysis coincided. Data were analyzed using open and focused coding, constant comparison, theoretical sampling and memoing, and this enabled the construction of a substantive theory.
Results

Seeking work-life balance was the core category of nurses’ pathway. Consequences of nurses’ pathway were categorized into three groups: thriving, surviving, and leaving. Thriving nurses in LTCHs found meaning in their work, fostered good relationships, and saw opportunities for growth. Surviving nurses in LTCHs were enduring their jobs in LTCHs, having a work-life balance, and supportive nursing leader. Leaving group nurses wished to leave LTCHs due to lack of professional growth, unappealing work, continuing conflict, and social stigma. However, compensation, work system, and interpersonal relationships were the common moving conditions for all three groups.
Conclusions

This study provided the trajectory and conditions of nurses to enter, stay, move, or leave at LTCHs. Understanding the pathways for staying or leaving can be used as a strategy for successful retention of registered nurses in LTCHs.
The Nanomaterial-Induced Bystander Effects Reprogrammed Macrophage Immune Function
Authors: Yuan Peng , Ban Zhan , Hu Xiangang , Zhou Qixing 
Published: May 2020

Abstract
Background: In the case of most popularly engineered nanomaterials (e.g., transition-metal dichalcogenide (TMDCs) nanosheets), direct exposure toxicities are investigated extensively to understand the effect on specific cells and organs; however, there has been limited focus on their potential bystander effects. Bystander effects in biological systems are the responses shown by nontargeted neighboring cells or tissues, and critical to the bio-nano interface interactions. In addition to direct effects, bystander effects also determine the design, applications and safety of nanomaterials, although the related information of bystander effects remain largely unknown.Results: A coculture system of A549 and THP-1 was established to mimic the lung microenvironment to study the bystander effects of WS2 nanosheets (representative TMDCs nanosheets) on microenvironment macrophages during the inhalation exposure or the nanomaterial biomedical application in the lung. Lung cells exposed to WS2 nanosheet resulted in an increase in reactive oxygen species and the depolarization of mitochondrial membrane potential in neighboring macrophages. Bystander exposure also induced macrophage polarization toward the anti-inflammatory M2 phenotype, which is adverse to disease therapy. Metabolomics showed that WS2 nanosheets disturbed the energy metabolism and amino acid metabolism of macrophages, consistent with the metabolic characteristics of M2 macrophages. Nitric oxide-transforming growth factor-β1 played an important mediator in the bystander effects. Importantly, WS2 nanosheet bystander exposure affected macrophage phagocytosis and migration and altered the macrophage immune response to environmental endotoxin.Conclusion: This study demonstrated that WS2 exposed lung cells would elicit bystander effects on surrounding macrophage cells, which weaken the immune response of surrounding macrophage cells. This study improves the current understanding of bio-nano interactions and highlights the importance of bystander effects and neighboring cell responses, allowing us to use the maximum benefits of nanomaterials while limiting their adverse bystander effects.
Identification of key miRNA and hub genes in lung adenocarcinoma by bioinformatics and functional analysis
Authors: Zhu Jiayao , Zhang Yan , Lu Jingjing , Wang Le , Zhu Xiaoren , Lu Yimin , Chen Minbin 
Published: May 2020

Abstract
Background: lung adenocarcinoma is the main subtype of lung cancer and the most fatal malignant disease in the world. However, the pathogenesis of lung adenocarcinoma has not been fully elucidated.Methods: Three LUAD-associated datesets (GSE118370, GSE43767 and GSE74190) were downloaded from the Gene Expression Omnibus (GEO) datebase and the differentially expressed miRNAs (DEMs) and genes (DEGs) were screened by GEO2R. The prediction of target gene of differentially expressed miRNA were used miRWALK. Metascape was used to enrich the overlapped genes of DEGs and target genes. Then, the protein-protein interaction(PPI) and DEMs-DEGs regulatory network were created via String datebase and Cytoscape. Finally, overall survival analysis was established via the Kaplan–Meier curve and look for the possible prognostic biomarkers.Result: In this study, 433 differential genes were identified. There were 267 genes overlapped with the target gene of Dems, and eight hub genes (CDH1, CDH5, CAV1, MMP9, PECAM1, CD24, ENG, MME) were screened out. There were 85 different miRNAs in total, among which 16 miRNA target genes intersect with DEGs, 12 miRNAs with the highest interaction were screened out, and survival analysis of miRNA and hub genes was carried out.Conclusion: we found that miRNA-940, miRNA-125a-3p, miRNA-140-3p, miRNA-542-5p, CDH1, CDH5, CAV1, MMP9, PECAM1 may be related to the development of LUAD.
Apoptotic resistance,cell cycle dysregulation and autophagy activation contribute to arsenic carcinogenesis
Authors: Zhou Youyou , Wang Xiaolong , Lu Yonghong , Wang Yanfu , Zhong Weiming , Pei Guangde , Gao Mingyang 
Published: May 2020

Abstract
Background: Arsenic is a common environmental pollutant, chronic arsenic exposure causes multiple cancers including skin cancer. However, the underlying mechanisms of arsenic-driven skin carcinogenesis remains unclear. Methods: HaCaT cells were exposed to a low level of arsenic (100nM) for 28 weeks. Then, xenograft mouse model and H&E staining were used to test their ability of tumors formation. The effect of arsenic on apoptosis demonstrated by TUNEL assay. XIAP and cIAP1 were determined by immunocytochemistry. MMP9, p16, Cyclin D1, CDK4 and Rb were detected by Real-time PCR. The protein expression level of Cyclin D1 was detected by Western blot . The formation of autophagosome was examined by a transmission electron microscope. Results: After HaCaT cells were chronic exposed to arsenic for 28 weeks, malignant transformation occurred as evidenced by the formation of highly aggressive squamous cell carcinoma after inoculation into nude mice. In addition to increased secretion of MMP9, apoptotic resistance generalized and members of the inhibitor of apoptosis (IAP), including XIAP and cIAP1, were significantly elevated in arsenic-transformed cells (termed AS-TM). Furthermore, p16, Cyclin D1, CDK4, and Rb were significantly increased in AS-TM. The protein expression level of Cyclin D1 in AS-TM cells was significantly higher than that in control. More interesting, arsenic was found to induce autophagy after chronic arsenic exposure, heightened autophagosome release was observed in AS-TM. Conclusion: Apoptotic resistance, cell cycle dysregulation and activation of autophagy are the underlying mechanisms of arsenic-driven skin carcinogenesis, which provide new insight on the pathogenesis of arsenic-induced skin cancer.
Genetic variations within the CCR5 promoter region among elite and viremic controllers in Uganda
Authors: NYIRO BRIAN , Amanya Bright Sharon , Nabatanzi Rose , Bayiyana Alice , Kalazane Linda Igumba , Waswa Francis , Nabulime Eva , Karara Daniel , Kayongo Alex , Nankya Immaculate , Kabali Joel , Kateete David Patrick , Sande Obondo James 
Published: May 2020

Abstract
Background: The importance of the C-C chemokine receptor type 5 (CCR5) in HIV infection and disease progression was recognized with the discovery of the ∆32 allele. Individuals homozygous for this mutation lack functional CCR5, and are almost completely resistant to HIV infection while heterozygous individuals display decreased cell surface CCR5, which slows disease progression. However, this mutation is rare in Africa. Genetic variations within the CCR5 promoter region have been associated with regulation of CCR5 gene expression and could attempt to explain the different disease progression statues seen within Uganda. However, the distribution and impact of these variations are not known within this setting where this population exists. A study done in Rakai, reported a prevalence of LTNPs as 9.1% and another study done by Alex Kayondo in 2018, reported a prevalence of 0.26% of HIV controllers in an Urban HIV ambulatory center in Kampala, Uganda. Reasons for their intrinsic resistance to HIV are not fully understood. We hypothesized that variations in the CCR5 promoter gene could affect CCR5 expression thus impacting on the clinical course of HIV. In this study, we determined the median CCR5 expression by CD4 + T cells and the CCR5 promoter genetic variations that could be associated with delayed progression to HIV/AIDS seen among this study group.Results: There was significant reduction in CCR5 densities on CD4 + T cells among elite and viremic controllers compared to non-controllers. CCR5 Promoter polymorphism − 2459 G/G was highly prevalent among Elite and Viremic Controllers and it is associated with delayed progression to AIDS while − 2459 A/A and − 2132C/T were high prevalent among NCs and they are associated with rapid progression to AIDS.Conclusion: The reduction in CCR5 densities and percentage CCR5 + CD4 + T cells could explain the delayed progression to AIDS among these individuals. The reduction could be accounted for by the mutation 2459 G/G reported in the CCR5 promoter region.
Curcumin suppresses oxidative stress via regulation of ROS/NF-κB signaling pathway to protect retinal vascular endothelial cell in diabetic retinopathy
Authors: Huang Jiang , Yi Quanyong , Chen Yao , Li Yi , Xu Guoxu , Zhang Ji , Niu Tongtong , You Yuhong , Zou Weijie , Qian Sicheng , Luo Weifeng 
Published: May 2020

Abstract
Background: Diabetic retinopathy (DR) is one of the most serious complications of diabetes mellitus and a leading blindness disease in the world. The retinal vascular endothelial cells can be damaged by oxidative stress even in the early stage of diabetic retinopathy. NF-κB is a key transcription factor in cell apoptosis and oxidative stress. Curcumin can relieve oxidative stress induced by high glucose. This study aimed to investigate the effect of curcumin on the rat retinal vascular endothelial cells (RRVECs) in DR and to deduce the possible molecular mechanism. Methods: The cultured RRVECs were identified by both of vWF and CD31 expression.The RRVECs were divided into four groups: the normal control group, the osmolarity control group, the high glucose group and the curcumin treatment group (High glucose +Curcumin). We observed the different morphological changes in the groups by transmission electron microscopy. Oxidative stress was detected by flow cytometry. The Activation of ROS/NF-κB signal pathway was detected by electrophoretic Mobility Shift Assay (EMSA), immunohistochemistry and western-blot; the apoptosis of RRVECs was tested by flow cytometry. Results: We found that curcumin reduced the reactive oxygen species (ROS) and relieved the apoptosis in RRVECs exposed to the high glucose by flow cytometry. We detected that the increased activity of NF-κB and phosphorylated NF-κB in RRVECs induced by high glucose concentration was significantly suppressed by curcumin. Furthermore, based on the assay quantifying the level of apoptosis-related proteins, including bcl-2 and bax, we illustrated that curcumin could decrease the apoptosis of RRVECs induced by high glucose concentration. Conclusion: We concluded that ROS/NF-κB signaling pathway played an important role in the progress of DR and curcumin could suppress the oxidative stress via regulation of NF-κB signal to protect the RRVECs in DR.
Neutrophil to Lymphocyte Ratio is Increased and Associated with Left Ventricular Diastolic Function in Newly Diagnosed Essential Hypertension Children.
Authors: Hou Miao , Cao Lei , Ding Yueyue , Chen Ye , Wang Bo , Shen Jie , Zhou Wanping , Huang Jie , Xu Qiuqin , Lv Haitao , Sun Ling 
Published: May 2020

Abstract
Aim Hypertension is associated with cardiac structural and functional changes, including left ventricular hypertrophy (LVH), LV systolic dysfunction, and diastolic dysfunction. Neutrophil to lymphocyte ratio (NLR) is a novel inflammatory biomarker associated with cardiovascular diseases. The current study aimed to evaluate NLR in children with newly diagnosed essential hypertension and its relationship between blood pressure and cardiac changes. Methods and subjects 44 children with newly diagnosed essential hypertension and 43 healthy children were included. Clinical characteristics, blood cell counts and biochemical parameters were collected. LVH was assessed by calculation of LV mass index (LVMI), and LV systolic function was evaluated by measuring LV ejection fraction and fractional shortening. LV diastolic function was primarily assessed with E/E’ ratio by doppler and echocardiography. Results The hypertension children had significantly higher LVMI and E/E’ ratio compared to the controls, whereas there was no difference in LV systolic function between two groups. The NLR was significantly higher in the hypertension group than the control group. Moreover, NLR and it was positively correlated with SBP and DBP levels in the hypertension group. Additionally, a significantly positive correlation between NLR and E/E’ ratio was found in the hypertension group. However, NLR was not related to LVH and LV systolic function indicators in hypertension children.Conclusion The higher NLR may be a potential indicator of increased risk for the development of hypertension in children. Moreover, NLR may help to assess the presence of LV diastolic dysfunction in hypertension children.
Identification of a prognostic long non-coding RNA signature in breast cancer
Authors: Lan Gaochen , Yu Xiaoling , Zhao Yanna , Lan Jinjian , Li Wan , Gao Ruilan 
Published: May 2020

Abstract
Background: Breast cancer is the most common malignant disease among women. At present, more and more attention has been paid to long non-coding RNAs (lncRNAs) in the field of breast cancer research. We aimed to investigate the expression profiles of lncRNAs and construct a prognostic lncRNA for predicting the overall survival (OS) of breast cancer.Methods: The expression profiles of lncRNAs and clinical data with breast cancer were obtained from The Cancer Genome Atlas (TCGA). Differentially expressed lncRNAs were screened out by R package (limma). The survival probability was estimated by the Kaplan‑Meier Test. The Cox Regression Model was performed for univariate and multivariate analysis. The risk score (RS) was established on the basis of the lncRNAs’ expression level (exp) multiplied regression coefficient (β) from the multivariate cox regression analysis with the following formula: RS=exp a1 * β a1 + exp a2 * β a2 +……+ exp an * β an. Functional enrichment analysis was performed by Metascape.Results: A total of 3404 differentially expressed lncRNAs were identified. Among them, CYTOR, MIR4458HG and MAPT-AS1 were significantly associated with the survival of breast cancer. Finally, The RS could predict OS of breast cancer (RS=exp CYTOR * β CYTOR + exp MIR4458HG * β MIR4458HG + exp MAPT-AS1 * β MAPT-AS1). Moreover, it was confirmed that the three-lncRNA signature could be an independent prognostic biomarker for breast cancer (HR=3.040, P=0.000).Conclusions: This study established a three-lncRNA signature, which might be a novel prognostic biomarker for breast cancer.
Escherichia coli Nissle 1917 secreting functional interleukin 2 targets tumours and enhances the immune response to suppress tumours
Authors: Lu Binghua , Yang Huijun , Liu Fei , Sun Yunjun , He Haocheng , Ding Xuezhi , Hu Shengbiao , xia liqiu 
Published: May 2020

Abstract
Escherichia coli Nissle 1917 (EcN) is non-pathogenic probiotic bacteria. Previous studies have indicated that EcN can accumulate and proliferate selectively in solid tumours in BALB/c mouse models. In this study, EcN was engineered to express human interleukin 2 (hIL-2), which is known to enhance immune responses to tumours by activating a variety of immune cells. IL-2 expressed by EcN was proven to activate PBMCs in vitro. Compared to control EcN, intraperitoneally injected EcN expressing hIL-2 (EcN(hIL-2)) was selectively distributed in the tumour microenvironment and inhibited the growth of CT26 tumours in a tumour-bearing mouse model. Antitumour activity was achieved without toxicity to key normal organs and tissues, such as liver, spleen and kidneys. The antitumour mechanism was associated with the infiltration of inflammatory cells, such as T cells, neutrophils and macrophages. These findings provide evidence that the combination of tumour-targeting EcN bacteria and delivery of the immunostimulatory factor IL-2 can be exploited as a promising tumour immunotherapy.
Inflammatory factors are associated with early neurological deterioration in acute ischemic stroke patients receiving endovascular therapy-The AISRNA study
Authors: Deng Qi-Wen , Huang Shi , Li Shuo , Zhai Qian , Zhang Qing , Wang Zhen-Jie , Chen Wen-Xia , Shi Hong-Chao , Zhou Feng , Sun Hui-Ling , Lu Min , Zhou Jun-Shan 
Published: May 2020

Abstract
Background: This study aimed to explore several peripheral blood-based markers related to inflammatory response in a total of 85 patients with acute ischemic stroke (AIS) caused by large artery occlusion in the anterior circulation receiving endovascular therapy (EVT) from the AISRNA study regarding the association between inflammatory factors and early neurological deterioration (END), and investigated whether their time course correlated with END after EVT.Methods: We collected baseline characteristics of 85 AIS patients participating in an observational acute stroke cohort: the AISRNA study. The following inflammatory factors were measured in these participants: interleukin-2 [IL-2], IL-4, IL-6, IL-10, tumor necrosis factor-α [TNF-α], and interferon-γ [IFN-γ]. The National Institute of Health Stroke Scale score increase of ≥4 within 24 hours after EVT defined as END.Results: IL-6 and IL-10 were higher in patients with END compared to those with non-END (P<0.01), and they were also associated with risk factors of END after EVT. Furthermore, we found that the area under curves (AUCs) of IL-6 and IL-10 for predicting END were 0.791 (0.689-0.871), and 0.564 (0.452-0.671), respectively. Adjusting for age, sex, and atrial fibrillation, the odds ratios (ORs; 95% confidence interval) for incident END for IL-6 and IL-10 were 1.83 (1.08-6.36) and 1.15 (1.02-1.30), respectively. Additionally, we found significant changes over time in the expression levels of IL-4, IL-6, and IL-10 in patients undergoing END compared with non-END (P<0.05).Conclusions: IL-6 and IL-10 levels on admission are significantly associated with END after EVT, and time course of IL-4, IL-6, and IL-10 is correlated with stroke progression. Further study of molecular mechanisms on peripheral immunomodulation in AIS would be helpful.Trial registration: ClinicalTrials.gov NCT04175691. Registered November 21, 2019.
A novel prognostic index model constructed with five autophagy-related genes may be a potential prognostic biomarker and therapeutic target in liver hepatocellular carcinoma
Authors: Zhu Qingqing , Wang Jia , Liu Menghan , Zhang Qiujing , Shen Miaomiao , Xie Chao , Zhang Jianjun , Fu Shuai , Han Congcong , Song Bao , Wang Fuxia , Liu Zining , Liu Jie 
Published: May 2020

Abstract
Background Early diagnosis and effective treatment of liver hepatocellular carcinoma (LIHC) are keys to improving the prognosis of patients. Increasing evidences clarify that autophagy-related genes (ARGs) make great differences to the generation and progression of LIHC, and may serve as prognostic biomarkers for LIHC. Methods We randomly divided the LIHC patients in The Cancer Genome Atlas (TCGA) into the training and testing group. Next, use the training group to perform univariate Cox, LASSO and multivariate Cox analysis to construct our prognostic index (PI) model for LIHC; use the testing group and the whole TCGA set to make internal validations; use the International Cancer Genome Consortium to make external validations; and use the whole TCGA, GSE14520 and Oncomine to exam the expression patterns of the five ARGs. Then, we performed the ROC curve as well as univariate and multivariate analysis to evaluate the independent prognostic prediction power of the PI model, and made nomograms to estimate 1,3,5-year survival rate of LIHC patients. Besides, we conducted functional enrichment analyses of differentially expressed ARGs with GO, KEGG and GSEA, and made drug sensitivity analysis for the PI model via the GDSC database. Results A novel PI model which was composed of five key ARGs ( ATG9A , EIF2S1 , GRID1 , SAR1A and SQSTM1 ) succeeded to be constructed. All the internal and external validations testified that the PI model could well distinguish high-risk patients from low-risk ones, with AUC values > 0.60. Further comparison analysis showed that the PI model was no less than some common prognostic factors. People can estimate the 1,3,5-year survival rate of individual LIHC patient with the nomograms. Additionally, we obtained 62 differentially expressed ARGs and studied the potential mechanisms or pathways. Furthermore, we also found some potential targeted drugs associated to the five ARGs for LIHC patients. Conclusions The novel five-ARGs PI model has great potential to serve as a diagnostic or prognostic biomarker and therapeutic target in LIHC, which may guide future clinical applications to some extent and improve the outcome of LIHC patients.