bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Impact of Genomic Diversity From Early to Advanced Hepatocellular Carcinoma
Authors: Nault Jean‐Charles , Martin Yoann , Caruso Stefano , Hirsch Théo Z. , Bayard Quentin , Calderaro Julien , Charpy Cecile , Copie‐Bergman Christiane , Ziol Marianne , Bioulac‐Sage Paulette , Couchy Gabrielle , Blanc Jean‐Frédéric , Nahon Pierre , Amaddeo Giuliana , Ganne‐Carrie Nathalie , Morcrette Guillaume , Chiche Laurence , Duvoux Christophe , Faivre Sandrine , Laurent Alexis , Imbeaud Sandrine , Rebouissou Sandra , Llovet Josep M. , Seror Olivier , Letouzé Eric , Zucman‐Rossi Jessica 
Published: June 2019

To date, genomic analyses of hepatocellular carcinoma (HCC) have been limited to early stages obtained from liver resection. We aim to describe the genomic profiling of HCC from early to advanced stages. We analyzed 801 HCC from 720 patients (410 resections, 137 transplantations, 122 percutaneous ablations, and 52 noncurative) for 190 gene expressions and for 31 gene mutations. Forty‐one advanced HCC and 156 whole exome of Barcelona Clinic Liver Cancer (BCLC) 0/A were analyzed by whole‐exome sequencing. Genomic profiling was correlated with tumor stages, clinical features, and survival. Our cohort included patients classified in BCLC stage 0 (9.4%), A (59.5%), B (16.2%), and C (14.9%). Among the overall 801 HCC, the most frequently mutated genes were telomerase reverse transcriptase (TERT) (58.1%), catenin beta 1 (CTNNB1) (30.7%), tumor protein 53 (TP53; 18.7%), AT‐rich interaction domain 1A (ARID1A) (13%), albumin (11.4%), apolipoprotein B (APOB) (9.4%), and AXIN1 (9.2%). Advanced‐stage HCC (BCLC B/C) showed higher frequencies of splicing factor 3b subunit 1 (SF3B1) (P = 0.0003), TP53 (P = 0.0006), and RB Transcriptional Corepressor 1 mutations (P = 0.03). G1‐G6 transcriptomic classification and the molecular prognostic 5‐gene score showed different distributions according to the stage of the disease and the type of treatment with an enrichment of G3 (P < 0.0001), poor prognostic score (P < 0.0001), and increased proliferation and dedifferentiation at the transcriptomic level in advanced HCC. The 5‐gene score predicted survival in patients treated by resection (P < 0.0001) and ablation (P = 0.01) and in advanced HCC (P = 0.04). Twenty‐two percent of advanced HCC harbored potentially druggable genetic alterations, and MET amplification was associated with complete tumor response in patients with advanced HCC treated by a specific MET inhibitor. Conclusion: Genomic analysis across the different stages of HCC revealed the mechanisms of tumor progression and helped to identify biomarkers of response to targeted therapies.
Hippocampal BDNF regulates a shift from flexible, goal‐directed to habit memory system function following cocaine abstinence
Authors: Harvey Eric , Blurton‐Jones Matthew , Kennedy Pamela J. 
Published: June 2019

ABSTRACTThe transition from recreational drug use to addiction involves pathological learning processes that support a persistent shift from flexible, goal‐directed to habit behavioral control. Here, we examined the molecular mechanisms supporting altered function in hippocampal (HPC) and dorsolateral striatum (DLS) memory systems following abstinence from repeated cocaine. After 3 weeks of cocaine abstinence (experimenter‐ or self‐administered), we tested new behavioral learning in male rats using a dual‐solution maze task, which provides an unbiased approach to assess HPC‐ versus DLS‐dependent learning strategies. Dorsal hippocampus (dHPC) and DLS brain tissues were collected after memory testing to identify transcriptional adaptations associated with cocaine‐induced shifts in behavioral learning. Our results demonstrate that following prolonged cocaine abstinence rats show a bias toward the use of an inflexible, habit memory system (DLS) in lieu of a more flexible, easily updated memory system involving the HPC. This memory system bias was associated with upregulation and downregulation of brain‐derived neurotrophic factor (BDNF) gene expression and transcriptionally permissive histone acetylation (acetylated histone H3, AcH3) in the DLS and dHPC, respectively. Using viral‐mediated gene transfer, we overexpressed BDNF in the dHPC during cocaine abstinence and new maze learning. This manipulation restored HPC‐dependent behavioral control. These findings provide a system‐level understanding of altered plasticity and behavioral learning following cocaine abstinence and inform mechanisms mediating the organization of learning and memory more broadly.
Implementation of policies and practices to increase physical activity among children attending centre‐based childcare: A cross‐sectional study
Authors: Razak Lubna A. , Jones Jannah , Clinton‐McHarg Tara , Wolfenden Luke , Lecathelinais Christophe , Morgan Philip J. , Wiggers John H. , Tursan D'Espaignet Edouard , Grady Alice , Yoong Sze Lin 
Published: June 2019

AbstractIssue addressedSupporting centre‐based childcare services to create physical activity (PA) environments is a recommended strategy to improve child PA. This study aimed to describe the implementation of PA policies and practices by these services, and to examine the associations with service characteristics.MethodsNominated supervisors of childcare services (n = 309) in the Hunter New England region, New South Wales, Australia, completed a telephone interview. Using previously validated measures, the interview assessed the implementation of evidence‐based practices shown to be associated with child PA. This includes: (a) provision of active play opportunities, (b) portable play equipment availability, (c) delivery of daily fundamental movement skills, (d) having at least 50% of staff trained in promoting child PA the past 5 years and (e) having written PA and small screen recreation policies.ResultsAlthough 98% (95% CI 96, 99) of childcare services provided active play opportunities for at least 25% of their daily opening hours, only 8% (95% CI 5, 11) of services fully implemented all policies and practices; with no service characteristic associated with full implementation. Long day care service had twice the odds of having a written PA policy (OR 2.0, 95% CI 0.7, 5.8), compared to preschools (adjusted for service size, socio‐economic disadvantage and geographical location).ConclusionsImprovements could be made to childcare services’ operations to support the promotion of child PA.So what?To ensure the benefits to child health, childcare services require support to implement a number of PA promoting policies and practices that are known to improve child PA.
Performance analysis of spiral and serpentine tube solar collector with carbon nanotube nanofluids under natural flow method
Authors: Kabeel Abd Elnaby , El‐Agouz El‐Sayed , Prakash Nakka , Prasad Chandran , Sathyamurthy Ravishankar , Manokar Athikesavan Muthu 
Published: June 2019

AbstractThis study communicates the performance analysis of spiral and serpentine tube solar collector with carbon nanotube nanofluids under natural flow method. Experiments were carried out at three different mass flow rates namely 3, 5, and 7 kg/hour while the concentration of nanoparticles was varied from 0.05% and 0.1%, respectively. Experiments were carried out under the same condition of ambient parameters for validation. Results show that the maximum exit water temperature was found to be about 75°C with a maximum concentration of 0.1% under a minimum flow rate of 3 kg/hour during the peak intensity. Similarly, the improvement in temperature of the water is found to be 6% under peak intensity and decreased to about 4.3% and 4.2% for the flow rates of 5 and 7 kg/hour, respectively
The allergic phenotype during the first 10 years of life in a prospective cohort
Authors: Björkander Sophia , Hallberg Jenny , Persson Jan‐Olov , Lilja Gunnar , Nilsson Caroline , Sverremark‐Ekström Eva 
Published: June 2019

AbstractBackgroundHeredity and environmental parameters jointly affect allergy development. Here, we used a Swedish prospective cohort to study the influence of heredity and factors usually associated with allergic disease and the development of allergic manifestations in combination with immunoglobulin E (IgE) sensitization at four different time points until 10 years of age.MethodsParents‐to‐be were characterized concerning allergy and their children (n = 281) were divided based on allergic heredity and followed from birth and clinically examined for IgE‐associated allergic symptoms until 10 years of age. The relation between allergy and early‐life parameters was analyzed by logistic regression. Group‐wise comparisons were made by nonparametrical tests.ResultsEarly life eczema and/or asthma in combination with IgE sensitization, was a strong indicator of allergy at a later time point. Further, the early occurrence of multiple allergic symptoms among IgE‐sensitized children predisposed for a more complex allergic phenotype at later ages, independently of allergic heredity. At 10 years of age, allergic children had higher fractional exhaled nitrogen oxide (FeNO) levels, regardless of asthma, and FeNO levels were also influenced by heredity. Birth season was strongly associated with allergy development, but only in children with two allergic parents.ConclusionAllergic eczema/asthma in early life, being born during the autumn/winter, having multiple allergic symptoms and two allergic parents were all strong predictors for having allergic diseases at 5 and 10 years of age. However, the allergic march seems to be independent of heredity, as IgE‐mediated allergies follow the same trajectories in children with and without allergic heredity.
Water‐insoluble amorphous silk fibroin scaffolds from aqueous solutions
Authors: Fan Zhihai , Xiao Liying , Lu Guozhong , Ding Zhaozhao , Lu Qiang 
Published: June 2019

AbstractRegenerated silk fibroin (RSF) is emerging as promising biomaterial for regeneration, drug delivery and optical devices, with continued demand for mild, all‐aqueous processes to control microstructure and the performance. Here, temperature control of assembly kinetics was introduced to prepare the water‐insoluble scaffolds from neutral aqueous solutions of RSF protein. Higher temperatures were used to accelerate the assembly rate of the silk fibroin protein chains in aqueous solution and during the lyophilization process, resulting in water‐insoluble scaffold formation. The scaffolds were mainly composed of amorphous states of the silk fibroin chains, endowing softer mechanical properties. These scaffolds also showed nanofibrous structures, improved cell proliferation in vitro and enhanced neovascularization and tissue regeneration in vivo than previously reported silk fibroin scaffolds. These results suggest utility of silk scaffolds in soft tissue regeneration.
Hypermethylation of microRNA‐149 activates SDF‐1/CXCR4 to promote osteogenic differentiation of mesenchymal stem cells
Authors: Li Guangjie , An Jiangdong , Han Xingwen , Zhang Xueliang , Wang Wenjin , Wang Shuanke 
Published: June 2019

AbstractMicroRNAs (miRs) involve in osteogenic differentiation and osteogenic potential of mesenchymal stem cells (MSCs). Accordingly, the present study aimed to further uncover role miR‐149 plays in osteogenic differentiation of MSCs with the involvement of the stromal cell‐derived factor‐1 (SDF‐1)/CXC chemokine receptor‐4 (CXCR4) pathway. Initially, the osteogenic differentiation model was induced. Next, the positive expression of STRO‐1 in periosteum, alkaline phosphatase (ALP) activity, osteocalcin (OCN) protein content, and the calcium deposition in MSCs were determined. MSCs were treated with DNA methyltransferase inhibitor 5‐aza‐CdR, SDF‐1 neutralizing antibody, or CXCR4 antagonist AMD3100 to investigate their roles in osteogenic differentiation; with the expression of CD44, CD90, CD14, and CD45 detected. Furthermore, the levels of SDF‐1 and CXCR4, and the genes related to stemness (Nanog, Oct‐4, and Sox‐2) were measured to explore the effects of miR‐149. The obtained data revealed the upregulation of STRO‐1 in the periosteum. miR‐149 could specifically bind to SDF‐1. Besides, increased miR‐149 methylation, higher ALP activity and OCN content, decreased positive rates of CD44 and CD90, and increased positive rates of CD14 and CD45 were found in osteogenic differentiation of MSCs. Subsequently, 5‐Aza‐CdR treatment reversed the above‐mentioned effects. MSCs were finally treated with SDF‐1 neutralizing antibody or AMD3100 to decrease Nanog, Oct‐4, and Sox‐2 expression. Taken together these results, miR‐149 hypermethylation has the potential to activate the SDF‐1/CXCR4 pathway and further promote osteogenic differentiation of MSCs.
Small GTPase Arf6 regulates diabetes‐induced cholesterol accumulation in podocytes
Authors: Hu Jijia , Yang Qian , Chen Zhaowei , Liang Wei , Feng Jun , Ding Guohua 
Published: June 2019

AbstractPodocyte injury is a critical factor for the initiation and progression of diabetic kidney disease (DKD). However, the underlying mechanisms of podocyte injury in DKD have not been completely elucidated. Studies suggested that intracellular cholesterol accumulation was correlated with podocyte injury, but the cause of podocyte cholesterol disorders in DKD are still unknown. ADP‐ribosylation factor 6 (Arf6) is a small GTPase with pleiotropic effects and has previously been shown to regulate ATP‐binding cassette transporter 1 (ABCA1) recycling, and thus, cholesterol homeostasis. However, Arf6 involvement in cholesterol metabolism in podocytes is scarce. To investigate the role of Arf6 in cholesterol modulation in podocytes, the effect of Arf6 on the regulation of the cholesterol transporter ABCA1 was studied in podocytes in vivo and in vitro. Intracellular cholesterol accumulation was significantly increased in podocytes from streptozotocin‐induced diabetic rats and that hyperglycemia downregulated the expression of Arf6. Arf6 knockdown could cause ABCA1 recycling disorders, and thus, further aggravate cholesterol accumulation in podocytes under high‐glucose (HG) conditions. Our results demonstrate that HG‐induced cholesterol accumulation and cellular injury in podocytes may be related to the recycling disorder of ABCA1 caused by the downexpression of Arf6 in DKD.
Upregulation of lncRNA GAS5 inhibits the growth and metastasis of cervical cancer cells
Authors: Yang Wenwu , Xu Xuexian , Hong Li , Wang Qin , Huang Jinling , Jiang Li 
Published: June 2019

AbstractThis study aims to figure out the methylation of long non‐coding RNA GAS5 promoter in cervical cancer and the mechanism of GAS5 on the progression of cervical cancer cells. The expression of GAS5 and methylation state of GAS5 in cervical cancer tissues and cells were determined. With the aim to to explore the ability of GAS5 in the proliferation, cell cycle progression, apoptosis, invasion, migration as well as the tumor growth, and metastasis in nude mice were determined. The expression of GAS5 was decreased and methylation state of GAS5 was elevated in cervical cancer. Overexpression of GAS5 inhibited proliferation, cell cycle progression, invasion, migration while inducing apoptosis of cervical cancer cells as well as suppressed tumor growth and metastasis in nude mice. Our study demonstrates that abnormal methylation of GAS5 contributes to poor expression of GAS5 in cervical cancer. In addition, upregulation of GAS5 inhibits the cervical cancer development.
The molecular markers of cancer stem cells in head and neck tumors
Authors: Yu Si Si , Cirillo Nicola 
Published: June 2019

AbstractHead and neck cancer (HNC) is the six most common malignancy worldwide leading to more than 350,000 deaths annually. Despite recent advances in treatment modalities for these patients, there has been only a slight improvement of prognosis. As cancer stem cells (CSCs) have been implicated in tumor cell survival, progression, and response to therapy, the identification of this tumor subpopulation would have important therapeutic and prognostic implications. In this structured appraisal of the literature, Embase, PubMed, and Ovid were searched for publications that investigated CSC markers of HNC in humans. The search was conducted under the PRISMA guidelines with clear inclusion and exclusion criteria for articles published in the last two decades. The review process resulted in the identification of some key CSC‐associated molecules such as CD44, ALDH1, CD133, Oct3/4, Nanog, and Sox2, although a single common CSC sorting marker could not be found. These biomarkers were identified in a range of HNCs but the most common one was squamous cell carcinoma (SCC), predominantly oral SCC. Patient cohorts were of variable size (3–195 individuals) and the most common technique used for detection was immunohistochemistry. Some of the molecules were associated with poor prognosis and may be able to inform the choice of appropriate treatment for these patients.
Mst1 deletion reduces hyperglycemia‐mediated vascular dysfunction via attenuating mitochondrial fission and modulating the JNK signaling pathway
Authors: Qin Ruijie , Lin Dong , Zhang Lina , Xiao Fei , Guo Lixin 
Published: June 2019

AbstractDiabetes is a leading cause of microvascular complications, such as nephropathy and retinopathy. Recent studies have proposed that hyperglycemia‐induced endothelial cell dysfunction is modulated by mitochondrial stress. Therefore, our experiment was to detect the upstream mediator of mitochondrial stress in hyperglycemia‐treated endothelial cells with a focus on macrophage‐stimulating 1 (Mst1) and mitochondrial fission. Our data illuminated that hyperglycemia incubation reduced cell viability, as well as increased apoptosis ratio in endothelial cell, and this alteration seemed to be associated with Mst1 upregulation. Inhibition of Mst1 via transfection of Mst1 siRNA into an endothelial cell could sustain cell viability and maintain mitochondrial function. At the molecular levels, endothelial cell death was accompanied with the activation of mitochondrial oxidative stress, mitochondrial apoptosis, and mitochondrial fission. Genetic ablation of Mst1 could reduce mitochondrial oxidative injury, block mitochondrial apoptosis, and repress mitochondrial fission. Besides, we also found Mst1 triggered mitochondrial dysfunction as well as endothelial cell damage through augmenting JNK pathway. Suppression of JNK largely ameliorated the protective actions of Mst1 silencing on hyperglycemia‐treated endothelial cells and sustain mitochondrial function. The present study identifies Mst1 as a primary key mediator for hyperglycemia‐induced mitochondrial damage and endothelial cell dysfunction. Increased Mst1 impairs mitochondrial function and activates endothelial cell death via opening mitochondrial death pathway through JNK.
The prognostic significance of weight loss in chronic obstructive pulmonary disease‐related cachexia: a prospective cohort study
Authors: Kwan Hoi Yee , Maddocks Matthew , Nolan Claire M. , Jones Sarah E. , Patel Suhani , Barker Ruth E. , Kon Samantha S.C. , Polkey Michael I. , Cullinan Paul , Man William D.‐C. 
Published: June 2019

AbstractBackgroundCachexia is an important extra‐pulmonary manifestation of chronic obstructive pulmonary disease (COPD) presenting as unintentional weight loss and altered body composition. Previous studies have focused on the relative importance of body composition compared with body mass rather than the relative importance of dynamic compared with static measures. We aimed to determine the prevalence of cachexia and pre‐cachexia phenotypes in COPD and examine the associations between cachexia and its component features with all‐cause mortality.MethodsWe enrolled 1755 consecutive outpatients with stable COPD from two London centres between 2012 and 2017, stratified according to European Respiratory Society Task Force defined cachexia [unintentional weight loss >5% and low fat‐free mass index (FFMI)], pre‐cachexia (weight loss >5% but preserved FFMI), or no cachexia. The primary outcome was all‐cause mortality. We calculated hazard ratios (HRs) using Cox proportional hazards regression for cachexia classifications (cachexia, pre‐cachexia, and no cachexia) and component features (weight loss and FFMI) and mortality, adjusting for age, sex, body mass index, and disease‐specific prognostic markers.ResultsThe prevalence of cachexia was 4.6% [95% confidence interval (CI): 3.6–5.6] and pre‐cachexia 1.6% (95% CI: 1.0–2.2). Prevalence was similar across sexes but increased with worsening Global Initiative for Chronic Obstructive Pulmonary Disease spirometric stage and Medical Research Council dyspnoea score (all P < 0.001). There were 313 (17.8%) deaths over a median (interquartile range) follow‐up duration 1089 (547–1704) days. Both cachexia [HR 1.98 (95% CI: 1.31–2.99), P = 0.002] and pre‐cachexia [HR 2.79 (95% CI: 1.48–5.29), P = 0.001] were associated with increased mortality. In multivariable analysis, the unintentional weight loss feature of cachexia was independently associated with mortality [HR 2.16 (95% CI: 1.31–3.08), P < 0.001], whereas low FFMI was not [HR 0.88 (95% CI: 0.64–1.20), P = 0.402]. Sensitivity analyses using body mass index‐specific, age‐specific, and gender‐specific low FFMI values found consistent findings.ConclusionsDespite the low prevalence of cachexia and pre‐cachexia, both confer increased mortality risk in COPD, driven by the unintentional weight loss component. Our data suggest that low FFMI without concurrent weight loss may not confer the poor prognosis as previously reported for this group. Weight loss should be regularly monitored in practice and may represent an important target in COPD management. We propose the incorporation of weight monitoring into national and international COPD guidance.
Free‐standing nitrogen‐doped graphene‐carbon nanofiber composite mats: electrospinning synthesis and application as anode material for lithium‐ion batteries
Authors: Shan Changsheng , Wang Yong , Xie Shuya , Guan Hong‐Yu , Argueta Monica , Yue Yanfeng 
Published: June 2019

AbstractBACKGROUNDGraphene and carbon nanofibers have shown outstanding advantages as anode materials in lithium‐ion batteries (LIBs) because of their prominent electronic conductivity, outstanding flexibility, high theoretical specific capacity, high specific surface, and chemical durability. Free‐standing nanocomposite mats from graphene and carbon nanofibers, without any conductive additive and binder, could improve the weight energy density of the LIBs.RESULTSNitrogen‐doped carbon fiber‐reduced graphene oxide (NCNFs‐rGO) mats are fabricated by high‐temperature thermal treatment of graphene oxide/polyacrylonitrile (PAN‐GO) nanofiber composite mats via a simple electrospinning method. The resultant free‐standing NCNFs‐rGO mats which were systematically characterized by scanning electron microscopy, X‐ray diffraction, Raman spectroscopy, X‐ray photoelectron spectroscopy, and electrochemical properties as an anode for LIBs were also measured. Without any conductive additive and binder, the resultant free‐standing NCNFs‐rGO mats were directly used as an anode material in LIBs.CONCLUSIONThe LIBs with NCNFs‐rGO mats as anodes exhibited a high rate capability and long cycle stability owing to the structural integrity and highly electrical conductivity. © 2019 Society of Chemical Industry