bluuebunny/crossref_metadata_2025_split huggingface dataset:
A network embedding model for pathogenic genes prediction by multi-path random walking on heterogeneous network
Authors: Xu Bo , Liu Yu , Yu Shuo , Wang Lei , Dong Jie , Lin Hongfei , Yang Zhihao , Wang Jian , Xia Feng 
Published: December 2019

Abstract
Background
Prediction of pathogenic genes is crucial for disease prevention, diagnosis, and treatment. But traditional genetic localization methods are often technique-difficulty and time-consuming. With the development of computer science, computational biology has gradually become one of the main methods for finding candidate pathogenic genes.

Methods
We propose a pathogenic genes prediction method based on network embedding which is called Multipath2vec. Firstly, we construct an heterogeneous network which is called GP−network. It is constructed based on three kinds of relationships between genes and phenotypes, including correlations between phenotypes, interactions between genes and known gene-phenotype pairs. Then in order to embedding the network better, we design the multi-path to guide random walk in GP−network. The multi-path includes multiple paths between genes and phenotypes which can capture complex structural information of heterogeneous network. Finally, we use the learned vector representation of each phenotype and protein to calculate the similarities and rank according to the similarities between candidate genes and the target phenotype.

Results
We implemented Multipath2vec and four baseline approaches (i.e., CATAPULT, PRINCE, Deepwalk and Metapath2vec) on many-genes gene-phenotype data, single-gene gene-phenotype data and whole gene-phenotype data. Experimental results show that Multipath2vec outperformed the state-of-the-art baselines in pathogenic genes prediction task.

Conclusions
We propose Multipath2vec that can be utilized to predict pathogenic genes and experimental results show the higher accuracy of pathogenic genes prediction.
CDK1 and CCNB1 as potential diagnostic markers of rhabdomyosarcoma: validation following bioinformatics analysis
Authors: Li Qianru , Zhang Liang , Jiang Jinfang , Zhang Yangyang , Wang Xiaomeng , Zhang Qiaochu , Wang Yang , Liu Chunxia , Li Feng 
Published: December 2019

Abstract
Background
Rhabdomyosarcoma (RMS), a common soft-tissue malignancy in pediatrics, presents high invasiveness and mortality. However, besides known changes in the PAX3/7-FOXO1 fusion gene in alveolar RMS, the molecular mechanisms of the disease remain incompletely understood. The purpose of the study is to recognize potential biomarkers related with RMS and analyse their molecular mechanism, diagnosis and prognostic significance.

Methods
The Gene Expression Omnibus was used to search the RMS and normal striated muscle data sets. Differentially expressed genes (DEGs) were filtered using R software. The DAVID has become accustomed to performing functional annotations and pathway analysis on DEGs.
The protein interaction was constructed and further processed by the STRING tool and Cytoscape software. Kaplan–Meier was used to estimate the effect of hub genes on the ending of sarcoma sufferers, and the expression of these genes in RMS was proved by real-time polymerase chain reaction (RT-PCR). Finally, the expression of CDK1 and CCNB1 in RMS was validated by immunohistochemistry (IHC).

Results
A total of 1932 DEGs were obtained, amongst which 1505 were up-regulated and 427were down-regulated. Up-regulated genes were largely enriched in the cell cycle, ECM-receptor interaction, PI3K/Akt and p53 pathways, whilst down-regulated genes were primarily enriched in the muscle contraction process. CDK1, CCNB1, CDC20, CCNB2, AURKB, MAD2L1, HIST2H2BE, CENPE, KIF2C and PCNA were identified as hub genes by Cytoscape analyses. Survival analysis showed that, except for HIST2H2BE, the other hub genes were highly expressed and related to poor prognosis in sarcoma. RT-PCR validation showed that CDK1, CCNB1, CDC20, CENPE and HIST2H2BE were significantly differential expression in RMS compared to the normal control. IHC revealed that the expression of CDK1 (28/32, 87.5%) and CCNB1 (26/32, 81.25%) were notably higher in RMS than normal controls (1/9, 11.1%; 0/9, 0%). Moreover, the CCNB1 was associated with the age and location of the patient’s onset.

Conclusions
These results show that these hub genes, especially CDK1 and CCNB1, may be potential diagnostic biomarkers for RMS and provide a new perspective for the pathogenesis of RMS.
Neurally adjusted ventilatory assist mitigates ventilator-induced diaphragm injury in rabbits
Authors: Shimatani Tatsutoshi , Shime Nobuaki , Nakamura Tomohiko , Ohshimo Shinichiro , Hotz Justin , Khemani Robinder G. 
Published: December 2019

Abstract
Background
Ventilator-induced diaphragmatic dysfunction is a serious complication associated with higher ICU mortality, prolonged mechanical ventilation, and unsuccessful withdrawal from mechanical ventilation. Although neurally adjusted ventilatory assist (NAVA) could be associated with lower patient-ventilator asynchrony compared with conventional ventilation, its effects on diaphragmatic dysfunction have not yet been well elucidated.

Methods
Twenty Japanese white rabbits were randomly divided into four groups, (1) no ventilation, (2) controlled mechanical ventilation (CMV) with continuous neuromuscular blockade, (3) NAVA, and (4) pressure support ventilation (PSV). Ventilated rabbits had lung injury induced, and mechanical ventilation was continued for 12 h. Respiratory waveforms were continuously recorded, and the asynchronous events measured. Subsequently, the animals were euthanized, and diaphragm and lung tissue were removed, and stained with Hematoxylin-Eosin to evaluate the extent of lung injury. The myofiber cross-sectional area of the diaphragm was evaluated under the adenosine triphosphatase staining, sarcomere disruptions by electron microscopy, apoptotic cell numbers by the TUNEL method, and quantitative analysis of Caspase-3 mRNA expression by real-time polymerase chain reaction.

Results
Physiological index, respiratory parameters, and histologic lung injury were not significantly different among the CMV, NAVA, and PSV. NAVA had lower asynchronous events than PSV (median [interquartile range], NAVA, 1.1 [0–2.2], PSV, 6.8 [3.8–10.0], p = 0.023). No differences were seen in the cross-sectional areas of myofibers between NAVA and PSV, but those of Type 1, 2A, and 2B fibers were lower in CMV compared with NAVA. The area fraction of sarcomere disruptions was lower in NAVA than PSV (NAVA vs PSV; 1.6 [1.5–2.8] vs 3.6 [2.7–4.3], p < 0.001). The proportion of apoptotic cells was lower in NAVA group than in PSV (NAVA vs PSV; 3.5 [2.5–6.4] vs 12.1 [8.9–18.1], p < 0.001). There was a tendency in the decreased expression levels of Caspase-3 mRNA in NAVA groups. Asynchrony Index was a mediator in the relationship between NAVA and sarcomere disruptions.

Conclusions
Preservation of spontaneous breathing using either PSV or NAVA can preserve the cross sectional area of the diaphragm to prevent atrophy. However, NAVA may be superior to PSV in preventing sarcomere injury and apoptosis of myofibrotic cells of the diaphragm, and this effect may be mediated by patient-ventilator asynchrony.
RETRACTED ARTICLE: Degradation of long non-coding RNA-CIR decelerates proliferation, invasion and migration, but promotes apoptosis of osteosarcoma cells
Authors: Liu Shiwei , Li Jingchao , Kang Liang , Tian Yueyang , Xue Yuan 
Published: December 2019

Abstract
Background
Over the years, long non-coding RNAs (lncRNAs) have been clarified in malignancies, this research was focused on the role of lncRNA cartilage injury-related (lncRNA-CIR) in osteosarcoma cells.

Methods
LncRNA-CIR expression in osteosarcoma tissues and cells, and adjacent normal tissues and normal osteoblasts was determined, then the relations between lncRNA-CIR expression and the clinicopathological features, and between lncRNA-CIR expression and the prognosis of osteosarcoma patients were analyzed. Moreover, the MG63 and 143B cells were treated with silenced or overexpressed lncRNA-CIR, and then the proliferation, invasion, migration and apoptosis of the cells were evaluated by gain- and loss-of-function approaches. The tumor growth, and proliferation and apoptosis of osteosarcoma cells in vivo were observed by subcutaneous tumorigenesis in nude mice.

Results
We have found that lncRNA-CIR was up-regulated in osteosarcoma tissues and cells, which was respectively relative to adjacent normal tissues and normal osteoblasts. The expression of lncRNA-CIR was evidently correlated with disease stages, distant metastasis and differentiation of osteosarcoma patients, and the high expression of lncRNA-CIR indicated a poor prognosis. Furthermore, the reduction of lncRNA-CIR could restrict proliferation, invasion and migration, but promote apoptosis of osteosarcoma cells in vitro. Meanwhile, inhibited lncRNA-CIR also restrained tumor growth and osteosarcoma cell proliferation, whereas accelerated apoptosis of osteosarcoma cells in vivo.

Conclusion
We have found in this study that the inhibited lncRNA-CIR could decelerate proliferation, invasion and migration, but accelerate apoptosis of osteosarcoma cells, which may provide a novel target for osteosarcoma treatment.
Adherence to low carbohydrate diet and prevalence of psychological disorders in adults
Authors: Ebrahimpour-Koujan Soraiya , Keshteli Ammar Hassanzadeh , Afshar Hamid , Esmaillzadeh Ahmad , Adibi Peyman 
Published: December 2019

Abstract
Background
Although individual macronutrients were studied in relation to mental health, no information exist about the association between adherence to low carbohydrate diet and psychological disorders. This study was conducted to investigate the association between adherence to a low carbohydrate diet and prevalence of psychological disorders among Iranian adults.

Methods
In this cross-sectional study on 3362 adult men and women, dietary intakes were examined by the use of a validated semi-quantitative food frequency questionnaire. Low carbohydrate diet (LCD) score was computed for each participant based on deciles of percentages of energy from macronutrients. Then the scores of carbohydrate, protein and fat intake for each participant were summed up to achieve the overall LCD score, which ranged from 3 (highest carbohydrate intake and lowest fat and protein intakes) to 30 (lowest carbohydrate intake and highest fat and protein intakes). Anxiety, depression, and psychological distress were assessed by validated Iranian versions of the Hospital Anxiety and Depression Scale and General Health Questionnaire-12.

Results
Prevalence of depression, anxiety and psychological distress in the whole population were 28.0, 13.3 and 22.6%, respectively. No significant differences were observed in the distribution of depression, anxiety and psychological distress across different quartiles of LCD score. After controlling for potential confounders, no significant association was seen between LCD score and prevalence of depression (OR for the highest vs. the lowest quartile of LCD score: (1.15; 95% CI: 0.93, 1.39). Consumption of LCD was not also associated with increased risk of anxiety (0.82; 95% CI: 0.59, 1.14) and psychological distress (0.92; 95% CI: 0.72, 1.16). These associations did not alter when the analyses were done stratified by gender or BMI status.

Conclusion
Adherence to the low carbohydrate diet, which contains high amount of fat and proteins but low amounts of carbohydrates, was not associated with increased odds of psychological disorders including depression, anxiety and psychological distress. Given the cross-sectional nature of the study which cannot reflect causal relationships, longitudinal studies, focusing on types of macronutrients, are required to clarify this association.
Study on the biomechanical responses of the loaded bone in macroscale and mesoscale by multiscale poroelastic FE analysis
Authors: Yu WeiLun , Wu XiaoGang , Cen HaiPeng , Guo Yuan , Li ChaoXin , Wang YanQin , Qin YiXian , Chen WeiYi 
Published: December 2019

Abstract
Background
Bone is a hierarchically structured composite material, and different hierarchical levels exhibit diverse material properties and functions. The stress and strain distribution and fluid flow in bone play an important role in the realization of mechanotransduction and bone remodeling.

Methods
To investigate the mechanotransduction and fluid behaviors in loaded bone, a multiscale method was developed. Based on poroelastic theory, we established the theoretical and FE model of a segment bone to provide basis for researching more complex bone model. The COMSOL Multiphysics software was used to establish different scales of bone models, and the properties of mechanical and fluid behaviors in each scale were investigated.

Results
FE results correlated very well with analytical in macroscopic scale, and the results for the mesoscopic models were about less than 2% different compared to that in the macro–mesoscale models, verifying the correctness of the modeling. In macro–mesoscale, results demonstrated that variations in fluid pressure (FP), fluid velocity (FV), von Mises stress (VMS), and maximum principal strain (MPS) in the position of endosteum, periosteum, osteon, and interstitial bone and these variations can be considerable (up to 10, 8, 4 and 3.5 times difference in maximum FP, FV, VMS, and MPS between the highest and the lowest regions, respectively). With the changing of Young’s modulus (E) in each osteon lamella, the strain and stress concentration occurred in different positions and given rise to microscale spatial variations in the fluid pressure field. The heterogeneous distribution of lacunar–canalicular permeability (klcp) in each osteon lamella had various influence on the FP and FV, but had little effect on VMS and MPS.

Conclusion
Based on the idealized model presented in this article, the presence of endosteum and periosteum has an important influence on the fluid flow in bone. With the hypothetical parameter values in osteon lamellae, the bone material parameters have effect on the propagation of stress and fluid flow in bone. The model can also incorporate alternative material parameters obtained from different individuals. The suggested method is expected to provide dependable biological information for better understanding the bone mechanotransduction and signal transduction.
m6A mRNA methylation regulates CTNNB1 to promote the proliferation of hepatoblastoma
Authors: Liu Li , Wang Jing , Sun Guifeng , Wu Qiong , Ma Ji , Zhang Xin , Huang Nan , Bian Zhixuan , Gu Song , Xu Min , Yin Minzhi , Sun Fenyong , Pan Qiuhui 
Published: December 2019

Abstract
Background
N6-Methyladenosine (m6A) modification has been implicated in many biological processes. It is important for the regulation of messenger RNA (mRNA) stability, splicing, and translation. However, its role in cancer has not been studied in detail. Here we investigated the biological role and underlying mechanism of m6A modification in hepatoblastoma (HB).

Methods
We used Reverse transcription quantitative real-time PCR (RT-qPCR) and Western blotting to determine the expression of m6A related factors. And we clarified the effects of these factors on HB cells using cell proliferation assay, colony formation, apoptotic assay. Then we investigated of methyltransferase-like 13 (METTL3) and its correlation with clinicopathological features and used xenograft experiment to check METTL3 effect in vivo. m6A-Seq was used to profiled m6A transcriptome-wide in hepatoblastoma tumor tissue and normal tissue. Finally, methylated RNA immunoprecipitation (MeRIP) assay, RNA remaining assay to perform the regulator mechanism of MEETL3 on the target CTNNB1 in HB.

Results
In this research, we discovered that m6A modifications are increased in hepatoblastoma, and METTL3 is the main factor involved with aberrant m6A modification. We also profiled m6A across the whole transcriptome in hepatoblastoma tumor tissues and normal tissues. Our findings suggest that m6A is highly expressed in hepatoblastoma tumors. Also, m6A is enriched not only around the stop codon, but also around the coding sequence (CDS) region. Gene ontology analysis indicates that m6A mRNA methylation contributes significantly to regulate the Wnt/β-catenin pathway. Reduced m6A methylation can lead to a decrease in expression and stability of the CTNNB1.

Conclusion
Overall our findings suggest enhanced m6A mRNA methylation as an oncogenic mechanism in hepatoblastoma, METTL3 is significantly up-regulated in HB and promotes HB development. And identify CTNNB1 as a regulator of METTL3 guided m6A modification in HB.
Effect of atorvastatin treatment on circulating adiponectin: a meta-analysis of randomized controlled trials
Authors: Liu Xiaoyu , Zhang Wei , Zhao Ming , Jia Guowei , Sun Rongguo 
Published: December 2019

Abstract
Background
Influences of atorvastatin on atherosclerosis and glycemic metabolism may be related to its potential impact on circulating adiponectin, an adipocyte that exerts anti-inflammatory, ant-atherosclerotic, and anti-oxidative effects. However, results of previous randomized controlled trials (RCTs) were not consistent. We performed a meta-analysis of RCTs to systematic evaluate the influence of atorvastatin on circulating adiponectin.

Methods
Relevant studies were identified via search of electronic databases of PubMed, Embase, and Cochrane’s Library. A random-effect model was applied to pool the results via incorporating the potential heterogeneity. Predefined meta-regression and subgroup analyses were used to evaluate the influences of study characteristics on the outcome.

Results
Fourteen datasets from ten RCTs including 931 patients were included. Pooled results showed that atorvastatin did not significantly affect circulating adiponectin as compared with controls (weighed mean difference = − 0.27 μg/mL, 95% confidence interval: − 0.89 to 0.35 μg/mL, p = 0.39). Results of univariate meta-regression analyses showed that study characteristics including number of patients, mean age, proportion of male patients, body mass index, dose of atorvastatin, or treatment duration did not significantly affect the outcome (p all > 0.05). Moreover, subgroup analyses showed that atorvastatin did not significantly affect circulating adiponectin in studies stratified according to these study characteristics (p all > 0.05).

Conclusions
Atorvastatin treatment does not significantly affect circulating adiponectin. Influences of atorvastatin on atherosclerosis and glycemic metabolism are not likely to be mediated by modulation of circulating adiponectin.
The construct validity of the Child Health Utility 9D-DK instrument
Authors: Petersen Karin Dam , Ratcliffe Julie , Chen Gang , Serles Dorthe , Frøsig Christine Stampe , Olesen Anne Vingaard 
Published: December 2019

Abstract
Background
Relative to their application with adults there is currently little information about the application of preference-based health-related quality of life (HRQL) instruments among populations of young people. The Child Health Utility 9D (CHU9D) is a paediatric-specific generic preference-based HRQL instrument, recently translated and linguistically validated into Danish (CHU9D-DK). The purpose of this study was to investigate the construct validity of the CHU9D-DK in a sample of Danish high school students.

Methods
All students attending a Danish High School were invited to participate in a web-based survey in January 2018 (N = 272). The survey included the CHU9D-DK, the young adult version of the Pediatric Quality of Life Inventory™ 4.0 Generic Core Scales (PedsQL), self-reported health status, presence/absence of disability/chronic diseases, life satisfaction, and socio-economic questions. CHU9D-DK utility scores were generated by employing the two scoring algorithms developed from adults in the UK and adolescents in Australia, respectively. Internal consistency, reliability and construct validity of the CHU9D-DK instrument were investigated.

Results
Two hundred and twenty-eight (84%) students consented to participate and completed the survey. The mean ± (standard deviation) values of the CHU9D-DK utilities were 0.84 (0.11) when the UK adult algorithm was applied and 0.70 (0.22), when the Australian adolescent algorithm was applied. The mean PedsQL score was 82.32 (13.14). The CHU9D-DK showed good internal consistency reliability (Cronbach’s alpha = 0.803). Higher levels of health status and life satisfaction were significantly associated with higher CHU9D-DK utility scores regardless of which scoring algorithm was applied (p-values < 0.001). Students living with a disability/chronic disease exhibited significantly lower utility scores relative to their healthy peers (p-values < 0.05). Higher socio-economic status (approximated by financial situation and frequency of family vacations) was also associated with higher utility scores (p-values < 0.005).

Conclusion
The CHU9D-DK demonstrated good psychometric performance overall and shows potential as a valid and reliable instrument for assessing the HRQL of Danish young people.

Trial registration
ClinicalTrials.gov identifier: NCT03391999, Registered 15 October 2017.
Reducing maternal and newborn mortality in Nigeria—a qualitative study of stakeholders’ perceptions about the performance of community health workers and the introduction of community midwifery at primary healthcare level
Authors: Okereke Ekechi , Ishaku Salisu Mohammed , Unumeri Godwin , Mohammed Bello , Ahonsi Babatunde 
Published: December 2019

Abstract
Background
Rural communities in Nigeria account for high maternal and newborn mortality rates in the country. Thus, there is a need for innovative models of service delivery, possibly with greater community engagement. Introducing and strengthening community midwifery practice within the Nigerian primary healthcare system is a clear policy option. The potential of community midwifery to increase the availability of skilled care during pregnancy, at birth and within postpartum periods in the health systems of developing countries has not been fully explored. This study was designed to assess stakeholders’ perceptions about the performance of community health workers and the feasibility of introducing and using community midwifery to address the high maternal and newborn mortality within the Nigerian healthcare system.

Methods
This study was undertaken in two human resources for health (HRH) project focal states (Bauchi and Cross River States) in Nigeria, utilizing a qualitative research design. Interviews were conducted with 44 purposively selected key informants. Key informants were selected based on their knowledge and experience working with different cadres of frontline health workers at primary healthcare level. The qualitative data were audio-recorded, transcribed and then thematically analysed.

Results
Some study participants felt that introducing community midwifery will increase access to maternal and newborn healthcare services, especially in rural communities. Others felt that applying community midwifery at the primary healthcare level may lead to duplication of duties among the health worker cadres, possibly creating disharmony. Some key informants suggested that there should be concerted efforts to train and retrain the existing cadres of community health workers via the effective implementation of the task shifting policy in Nigeria, in addition to possibly revising the existing training curricula, instead of introducing community midwifery.

Conclusion
Applying community midwifery within the Nigerian healthcare system has the potential to increase the availability of skilled care during pregnancy, at birth and within postpartum periods, especially in rural communities. However, there needs to be broader stakeholder engagement, more awareness creation and the careful consideration of modalities for introducing and strengthening community midwifery training and practice within the Nigerian health system as well as within the health systems of other developing countries.