bluuebunny/crossref_metadata_2025_split huggingface dataset:
Equity impacts of interventions to increase physical activity among older adults: a quantitative health impact assessment
Authors: Schönbach Johanna-Katharina , Bolte Gabriele , Czwikla Gesa , Manz Kristin , Mensing Monika , Muellmann Saskia , Voelcker-Rehage Claudia , Lhachimi Stefan K. 
Published: August 2020

AbstractBackgroundBehavioural interventions may increase social inequalities in health. This study aimed to project the equity impact of physical activity interventions that have differential effectiveness across education groups on the long-term health inequalities by education and gender among older adults in Germany.MethodsWe created six intervention scenarios targeting the elderly population: Scenarios #1–#4 applied realistic intervention effects that varied by education (low, medium high). Under scenario #5, all older adults adapted the physical activity pattern of those with a high education. Under scenario #6, all increased their physical activity level to the recommended 300 min weekly. The number of incident ischemic heart disease, stroke and diabetes cases as well as deaths from all causes under each of these six intervention scenarios was simulated for males and females over a 10-year projection period using the DYNAMO-HIA tool. Results were compared against a reference-scenario with unchanged physical activity.ResultsUnder scenarios #1–#4, approximately 3589–5829 incident disease cases and 6248–10,320 deaths could be avoided among males over a 10-year projection period, as well as 4381–7163 disease cases and 6914–12,605 deaths among females. The highest reduction for males would be achieved under scenario #4, under which the intervention is most effective for those with a high education level. Scenario #4 realizes 2.7 and 2.4% of the prevented disease cases and deaths observed under scenario #6, while increasing inequalities between education groups. In females, the highest reduction would be achieved under scenario #3, under which the intervention is most effective amongst those with low levels of education. This scenario realizes 2.7 and 2.9% of the prevented disease cases and deaths under scenario #6, while decreasing inequalities between education groups. Under scenario #5, approximately 31,687 incident disease cases and 59,068 deaths could be prevented among males over a 10-year projection period, as well as 59,173 incident disease cases and 121,689 deaths among females. This translates to 14.4 and 22.2% of the prevented diseases cases among males and females under scenario #6, and 13.7 and 27.7% of the prevented deaths under scenario #6.ConclusionsThis study shows how the overall population health impact varies depending on how the intervention-induced physical activity change differs across education groups. For decision-makers, both the assessment of health impacts overall as well as within a population is relevant as interventions with the greatest population health gain might be accompanied by an unintended increase in health inequalities.
How do short sleepers use extra waking hours? A compositional analysis of 24-h time-use patterns among children and adolescents
Authors: Gába Aleš , Dygrýn Jan , Štefelová Nikola , Rubín Lukáš , Hron Karel , Jakubec Lukáš , Pedišić Željko 
Published: August 2020

AbstractBackgroundTo examine compositional associations between short sleep duration and sedentary behavior (SB), light physical activity (LPA) and moderate-to-vigorous physical activity (MVPA) among children and adolescents.MethodsMulti-day 24-h data on sleep, SB, LPA and MVPA were collected using accelerometers among 343 children (8–13 years old) and 316 adolescents (14–18 years old). Children and adolescents with sleep duration of < 9 and < 8 h, respectively, were classified as short sleepers. Robust compositional regression analysis was used to examine the associations between short sleep duration and the waking-time composition.ResultsSeventy-one percent of children and 75.3% of adolescents were classified as short sleepers. In children, being a short sleeper was associated with higher SB by 95 min/day (p < 0.001) and lower MVPA by 16 min/day (p = 0.002). Specifically, it was associated with a higher amount of time spent in long sedentary bouts (βilr1 = 0.46, 95% confidence interval [CI] = 0.29 to 0.62) and lower amounts of time spent in sporadic SB (βilr1 = − 0.17, 95% CI = –0.24 to − 0.10), sporadic LPA (βilr1 = − 0.09, 95% CI = –0.14 to − 0.04) and sporadic MVPA (βilr1 = − 0.17, 95% CI = –0.25 to − 0.10,p < 0.001 for all), relative to the remaining behaviours. In adolescents, being a short sleeper was associated with a higher amount of time spent in SB by 67 min/day (p = 0.001) and lower LPA by 2 min/day (p = 0.035). Specifically, it was associated with more time spent in sedentary bouts of 1–9 min (βilr1 = 0.08, 95% CI = 0.02 to 0.14,p = 0.007) and 10–29 min (βilr1 = 0.10, 95% CI = 0.02 to 0.18,p = 0.015), relative to the remaining behaviours.ConclusionsAmong children and adolescents, short sleep duration seems to be highly prevalent and associated with less healthy waking time. Public health interventions and strategies to tackle the high prevalence of short sleep duration among children and adolescents are warranted.
Prognostic significance of plasma IL-2 and sIL-2Rα in patients with first-ever ischaemic stroke
Authors: Zhao Haiping , Li Fangfang , Huang Yuyou , Zhang Sijia , Li Lingzhi , Yang Zhenhong , Wang Rongliang , Tao Zhen , Han Ziping , Fan Junfen , Zheng Yangmin , Ma Qingfeng , Luo Yumin 
Published: August 2020

AbstractBackgroundAn imbalance between circulating neuroprotective and neurotoxic T cell subsets leads to poor prognosis in acute ischaemic stroke (AIS). Preclinical studies have indicated that the soluble form of the interleukin-2 receptor α (sIL-2Rα)-IL-2 complex regulates T cell differentiation. However, the association between sIL-2Rα levels and AIS remains unclear.MethodsA total of 201 first-ever AIS patients within 24 h after stroke onset and 76 control subjects were recruited. The National Institutes of Health Stroke Scale (NIHSS) score and 3-month functional outcome (modified Rankin Scale [mRS] score) at admission were assessed. Plasma sIL-2Rα and IL-2 levels at admission were measured. Prognostic significance was identified by using univariate and multivariate logistic regression analyses.ResultsPatients with poor functional outcomes at 3 months had significantly higher levels of sIL-2Rα and lower levels of IL-2 than patients with good outcomes. Moreover, sIL-2Rα levels showed a strong positive correlation with NIHSS and mRS scores (p< 0.0001), whereas IL-2 levels were negatively correlated with mRS scores (p< 0.01). Univariate analyses showed that higher sIL-2Rα and IL-2 levels were associated with an increased and reduced risk of unfavourable outcomes, respectively. After adjusting for confounding variables, the sIL-2Rα level remained independently associated with an increased risk of an unfavourable outcome, and adding sIL-2Rα levels to the conventional risk factor model significantly improved risk reclassification (net reclassification improvement 17.56%,p= 0.003; integrated discrimination improvement 5.78%,p =0.0003).ConclusionssIL-2Rα levels represent a novel, independent prognostic marker that can improve the currently used risk stratification of AIS patients. Our findings also highlight that elevated plasma sIL-2Rα and IL-2 levels manifested opposite correlations with functional outcome, underlining the importance of IL-2/IL-2R autocrine loops in AIS.
Early leucine programming on protein utilization and mTOR signaling by DNA methylation in zebrafish (Danio rerio)
Authors: Zhu Qiang-Sheng , Wang Jie , He Shan , Liang Xu-Fang , Xie Shuang , Xiao Qian-Qian 
Published: August 2020

AbstractBackgroundEarly nutritional programming affects a series of metabolism, growth and development in mammals. Fish also exhibit the developmental plasticity by early nutritional programming. However, little is known about the effect of early amino acid programming on growth and metabolism.MethodsIn the present study, zebrafish (Danio rerio) was used as the experimental animal to study whether early leucine stimulation can programmatically affect the mechanistic target of rapamycin (mTOR) signaling pathway, growth and metabolism in the later life, and to undercover the mechanism of epigenetic regulation. Zebrafish larvas at 3 days post hatching (dph) were raised with 1.0% leucine from 3 to 13 dph during the critical developmental stage, then back to normal water for 70 days (83 dph).ResultsThe growth performance and crude protein content of zebrafish in the early leucine programming group were increased, and consistent with the activation of the mTOR signaling pathway and the high expression of genes involved in the metabolism of amino acid and glycolipid. Furthermore, we compared the DNA methylation profiles between the control and leucine-stimulated zebrafish, and found that the methylation levels of CG-differentially methylated regions (DMGs) and CHH-DMGs of genes involved in mTOR signaling pathway were different between the two groups. With quantitative PCR analysis, the decreased methylation levels of CG type of Growth factor receptor-bound protein 10 (Grb10), eukaryotic translation initiation factor 4E (eIF4E) andmTORgenes of mTOR signaling pathway in the leucine programming group, might contribute to the enhanced gene expression.ConclusionsThe early leucine programming could improve the protein synthesis and growth, which might be attributed to the methylation of genes in mTOR pathway and the expression of genes involved in protein synthesis and glycolipid metabolism in zebrafish. These results could be beneficial for better understanding of the epigenetic regulatory mechanism of early nutritional programming.
Particulate matters increase epithelial-mesenchymal transition and lung fibrosis through the ETS-1/NF-κB-dependent pathway in lung epithelial cells
Authors: Chen Yu-Chen , Chuang Tzu-Yi , Liu Chen-Wei , Liu Chi-Wei , Lee Tzu-Lin , Lai Tsai-Chun , Chen Yuh-Lien 
Published: August 2020

Abstract
Background
Particulate matters (PMs) in ambient air pollution are closely related to the incidence of respiratory diseases and decreased lung function. Our previous report demonstrated that PMs-induced oxidative stress increased the expression of proinflammatory intracellular adhesion molecule-1 (ICAM-1) through the IL-6/AKT/STAT3/NF-κB pathway in A549 cells. However, the role of O-PMs in epithelial-mesenchymal transition (EMT) development and pulmonary fibrosis and the related mechanisms have not been determined. The aim of this study was to investigate the effects of O-PMs on the pathogenesis of EMT and pulmonary fibrosis as well as the expression of ETS-1 and NF-κB p65, in vitro and in vivo.

Results
O-PMs treatment induced EMT development, fibronectin expression, and cell migration. O-PMs affected the expression of the EMT-related transcription factors NF-κB p65 and ETS-1. Interference with NF-κB p65 significantly decreased O-PMs-induced fibronectin expression. In addition, O-PMs affected the expression of fibronectin, E-cadherin, and vimentin through modulating ETS-1 expression. ATN-161, an antagonist of integrin α5β1, decreased the expression of fibronectin and ETS-1 and EMT development. EMT development and the expression of fibronectin and ETS-1 were increased in the lung tissue of mice after exposure to PMs for 7 and 14 days. There was a significant correlation between fibronectin and ETS-1 expression in human pulmonary fibrosis tissue.

Conclusion
O-PMs can induce EMT and fibronectin expression through the activation of transcription factors ETS-1 and NF-κB in A549 cells. PMs can induce EMT development and the expression of fibronectin and ETS-1 in mouse lung tissues. These findings suggest that the ETS-1 pathway could be a novel and alternative mechanism for EMT development and pulmonary fibrosis.
Missed radiation therapy sessions in first three weeks predict distant metastasis and less favorable outcomes in surgically treated patients with oral cavity squamous cell carcinoma
Authors: Chiang Yin-Yin , Chou Yung-Chih , Chang Kai-Ping , Liao Chun-Ta , Wu Yao-Yu , Yap Wing-Keen , Pai Ping-Ching , Chang Joseph Tung-Chieh , Lin Chien-Yu , Fan Kang-Hsing , Huang Bing-Shen , Hung Tsung-Min , Tsang Ngan-Ming 
Published: August 2020

AbstractBackgroundWe sought to investigate the prognostic impact of missed RT sessions in patients who had undergone surgery for oral cavity squamous cell carcinoma (OCSCC).MethodsThe study sample consisted of 905 patients with surgically treated OCSCC who fulfilled criteria of RT course ≤8 weeks. The study participants were divided into three groups based on the characteristics of missed RT, as follows: 1) early missed RT, 2) late missed RT, and 3) RT as scheduled.ResultsThe 5-year overall survival (OS) rates in the early missed RT, late missed RT, and RT as scheduled groups were 53.0, 58.1, and 64.5%, respectively (p = 0.046). In multivariate analysis, early missed RT was independently associated with both OS (hazard ratio (HR) = 1.486; 95% confidence interval (CI): 1.122–1.966;p = 0.006) and the occurrence of distant metastasis (HR = 1.644; 95% CI: 1.047–2.583;p = 0.031).ConclusionEarly missed RT was independently associated with a higher occurrence of distant metastasis and less favorable OS in patients who had undergone surgery for OCSCC.
Clinical impact of Hypofractionated carbon ion radiotherapy on locally advanced hepatocellular carcinoma
Authors: Shiba Shintaro , Shibuya Kei , Okamoto Masahiko , Okazaki Shohei , Komatsu Shuichiro , Kubota Yoshiki , Nakano Takashi , Ohno Tatsuya 
Published: August 2020

AbstractBackgroundHepatocellular carcinoma (HCC) involving a major branch of the portal or hepatic vein is in a locally advanced stage and remains difficult to cure. This study aimed to evaluate the clinical effects of carbon ion radiotherapy (C-ion RT) in locally advanced HCC (LAHCC).MethodsThe data of 11 consecutive patients with LAHCC who received C-ion RT were analyzed. The C-ion RT doses of 52.8 Gy (relative biological effectiveness [RBE]) and 60.0 Gy (RBE) were delivered in 4 fractions for standard cases, and the 60.0 Gy dose was delivered in 12 fractions for close-to-gastrointestinal-tract cases. Survival and local control probabilities were calculated using the Kaplan-Meier method.ResultsThe median follow-up duration after C-ion RT was 36.4 months. The median age at the time of registration for C-ion RT was 76 years. The median tumor size was 53 mm. The numbers of treatment-naive and recurrent HCC patients were 1 and 10, respectively. Direct invasion of the major branch of the portal vein, hepatic vein, or both portal and hepatic veins was observed in three, five, and three patients, respectively. The 3-year overall survival, local control, and progression-free survival rates were 64, 78, and 18%, respectively. No patient developed radiation-induced liver diseases or grade 3 or higher toxicities in the acute and late phases.ConclusionsC-ion RT showed favorable clinical outcomes with a high rate of local control and minimal toxicities in LAHCC. Our findings suggest that C-ion RT is a promising multidisciplinary treatment option in LAHCC.
A SNP-mediated lncRNA (LOC146880) and microRNA (miR-539-5p) interaction and its potential impact on the NSCLC risk
Authors: Feng Tienan , Feng Nannan , Zhu Tengteng , Li Qiang , Zhang Qi , Wang Yu , Gao Ming , Zhou Baosen , Yu Herbert , Zheng Min , Qian Biyun 
Published: August 2020

AbstractBackgroundMany cancer-associated single nucleotide polymorphisms (SNPs) are located in the genomic regions of long non-coding RNAs (lncRNAs). Mechanisms of these SNPs in connection to cancer risk are not fully understood.MethodsAssociation of SNP (rs140618127) in lncRNALOC146880with non-small cell lung cancer (NSCLC) was evaluated in a case-control study of 2707 individuals. The mechanism of the SNP’s biologic influence was explored with in vitro and in vivo experiments, including plasmid transfection, siRNA knockdown, flow cytometry assessment, and assays of cell proliferation, migration, invasion, and colony formation.ResultsAssociation analysis showed that A allele of SNP rs140618127 was associated with low risk of NSCLC in the Chinese population. Lab experiments indicated that SNP rs140618127 contained a binding site for miR-539-5p and the binding between miR-539-5p andLOC146880resulted in declined phosphorylation of an oncogene, ENO1. The reduced phosphorylation of ENO1 led to decreased phosphorylation of PI3K and Akt, which is further linked to the decline in cell proliferation and tumor progression.ConclusionThe study demonstrates that SNP rs140618127 in lncRNA loc146880 provides an alternate binding site for microRNA miR-539-5p which affects the phosphorylation of ENO1 and activation of the PI3K and Akt pathway.
TNFAIP8 promotes AML chemoresistance by activating ERK signaling pathway through interaction with Rac1
Authors: Pang Yihua , Zhao Yanan , Wang Yan , Wang Xinlu , Wang Ruiqing , Liu Na , Li Peng , Ji Min , Ye Jingjing , Sun Tao , Li Jingxin , Ma Daoxin , Lu Fei , Ji Chunyan 
Published: August 2020

AbstractBackgroundChemoresistance is emerging as a major barrier to successful treatment in acute myeloid leukemia (AML), and evasion of apoptosis is among the fundamental underlying mechanisms. Therefore, unraveling molecular networks that drive this process constitutes an urgent unmet need. Herein, we aim to characterize the role and molecular mechanism of the tumor necrosis factor ɑ-induced protein 8 (TNFAIP8), a novel anti-apoptotic molecule, in AML chemoresistance.MethodsThe expression levels of TNFAIP8 were assessed in AML patients and cell lines by RT-qPCR and western blots. The transcriptional regulation of TNFAIP8 was analyzed with luciferase reporter assay and ChIP followed by RT-qPCR. Functional experiments were conducted to evaluate the effects of TNFAIP8 on apoptosis, drug sensitivity and proliferation of AML cells. Potential effects of TNFAIP8 on the activation of extracellular signal-regulated kinase (ERK) pathway were detected by western blots. CoIP and P21-activated kinase (PAK) pull-down assay were performed to ascertain the upstream target. The overall effects of TNFAIP8 on AML were examined in murine models.ResultsUpregulated TNFAIP8 expression was first confirmed in human AML patients and cell lines. E74 like ETS transcription factor 1 (ELF1) was then identified to contribute to its aberrant expression. Through manipulating TNFAIP8 expression, we described its role in protecting AML cells from apoptosis induced by chemotherapeutic agents and in promoting drug resistance. Notably, the leukemia-promoting action of TNFAIP8 was mediated by sustaining activity of the ERK signaling pathway, through an interaction with Rac family small GTPase 1 (Rac1). In addition, in vivo experiments confirmed that TNFAIP8 suppression lowered leukemia infiltration and improved survival.ConclusionOur data provide a molecular basis for the role of TNFAIP8 in chemoresistance and progression of AML and highlight the unique function of TNFAIP8 as an attractive therapeutic target.
Long noncoding RNA ZFPM2-AS1 acts as a miRNA sponge and promotes cell invasion through regulation of miR-139/GDF10 in hepatocellular carcinoma
Authors: He Hui , Wang Yawei , Ye Peng , Yi Dehui , Cheng Ying , Tang Haibo , Zhu Zhi , Wang Xun , Jin Shi 
Published: August 2020

AbstractBackgroundEmerging evidence has shown that dysregulated expression of long noncoding RNAs (lncRNAs) is implicated in liver hepatocellular carcinoma (HCC). However, the role and molecular mechanism of differentially expressed lncRNAs in HCC has not been fully explained.MethodsThe expression profiles of lncRNAs in HCC samples were derived from microarrays analysis or downloaded from The Cancer Genome Atlas (TCGA), and their correlation with prognosis and clinical characteristics were further analyzed. Silencing of lncRNA ZFPM2-AS1 was conducted to assess the effect of ZFPM2-AS1 in vitro. The miRcode and Target Scan databases were used to determine the lncRNA-miRNA-mRNA interactions. The biological functions were demonstrated by luciferase reporter assay, western blotting, PCR and rescue experiments.ResultsThe expression level of lncRNA ZFPM2-AS1 was significantly higher in HCC tissues than in adjacent normal tissues, and higher ZFPM2-AS1 was remarkably related to poor survival. Functionally, silencing of lncRNA ZFPM2-AS1 inhibited cell proliferation, migration, invasion and promoted cell apoptosis in vitro. Bioinformatics analysis based on the miRcode and TargetScan databases showed that lncRNA ZFPM2-AS1 regulated GDF10 expression by competitively binding to miR-139. miR-139 and downregulated GDF10 reversed cell phenotypes caused by lncRNA ZFPM2-AS1 by rescue analysis.ConclusionsZFPM2-AS1, an upregulated lncRNA in HCC, was associated with malignant tumor phenotypes and worse patient survival. ZFPM2-AS1 regulated the progression of HCC by acting as a competing endogenous RNA (ceRNA) to competitively bind to miR-139 and regulate GDF10 expression. Our study provides new insight into the posttranscriptional regulation mechanism of lncRNA ZFPM2-AS1 and suggests that ZFPM2-AS1/miR-139/GDF10 may act as a potential therapeutic target and prognostic biomarker for HCC.
Pre-hospital blood transfusion – an ESA survey of European practice
Authors: Thies Karl-Christian , Truhlář Anatolij , Keene Damian , Hinkelbein Jochen , Rützler Kurt , Brazzi Luca , Vivien Benoît 
Published: August 2020

Abstract
Background
Blood products are a lifesaving commodity in the treatment of major trauma.
Although there is little evidence for use of pre-hospital blood products (PHBP) in seriously injured patients, an increasing number of emergency medical services have started using PHBP for treatment of major haemorrhage.
The primary aim of this survey was to establish the degree of prehospital blood product use throughout Europe and discover main indications. The secondary aim was to evaluate opinions about PHBP and also the experience and the personal views of its users.

Methods
The subcommittee for Critical Emergency Medicine of the European Society of Anaesthesiology (ESA) held an online survey of European Helicopter Emergency Services (HEMS) and all French Services d’Aide Médicale Urgente (SAMU) regions. It contained 13 questions both open and multiple-choice about the frequency transfusions are carried out, the PHBP used and the perceived benefit. The survey was distributed to the corresponding HEMS leads in 14 European countries.

Results
In total there were 172 valid responses; overall 48% of all respondents have prehospital access to packed red cells, 22% to fresh plasma and 14% use lyophilised plasma. Besides blood product administration, 94% of all services use tranexamic acid. Sixty five percent of all replies came from French and from German services (37 and 28% respectively). PHBP were mainly used for trauma related emergencies. France has the highest uptake of use of blood products at 89%, whereas the rate in Germany was far lower at 6%.
Fifty five percent of the service leads felt that PHBP are beneficial, and even lifesaving in individual cases despite being needed infrequently.

Conclusions
We found remarkable dissimilarities in practice between the different European countries. Even if there is not an absolute consensus amongst providers on the benefit of PHBP, the majority feel they are beneficial. The difference in practice is possibly related to the perceived lack of evidence on prehospital blood transfusion. We suggest to include the use of PHBP in trauma registries in order to consolidate the existing evidence.