bluuebunny/crossref_metadata_2025_split huggingface dataset:
Knockdown of Son, a mouse homologue of the ZTTK syndrome gene, causes neuronal migration defects and dendritic spine dysgenesis
Authors: Ueda Masashi , Matsuki Tohru , Fukada Masahide , Eda Shima , Toya Akie , Iio Akio , Tabata Hidenori , Nakayama Atsuo 
Published: March 2020

Abstract
Zhu-Tokita-Takenouchi-Kim (ZTTK) syndrome, a rare congenital anomaly syndrome characterized by intellectual disability, brain malformation, facial dysmorphism, musculoskeletal abnormalities, and some visceral malformations is caused by de novo heterozygous mutations of the SON gene. The nuclear protein SON is involved in gene transcription and RNA splicing; however, the roles of SON in neural development remain undetermined. We investigated the effects of Son knockdown on neural development in mice and found that Son knockdown in neural progenitors resulted in defective migration during corticogenesis and reduced spine density on mature cortical neurons. The induction of human wild-type SON expression rescued these neural abnormalities, confirming that the abnormalities were caused by SON insufficiency. We also applied truncated SON proteins encoded by disease-associated mutant SON genes for rescue experiments and found that a truncated SON protein encoded by the most prevalent SON mutant found in ZTTK syndrome rescued the neural abnormalities while another much shorter mutant SON protein did not. These data indicate that SON insufficiency causes neuronal migration defects and dendritic spine dysgenesis, which seem neuropathological bases of the neural symptoms of ZTTK syndrome. In addition, the results strongly suggest that the neural abnormalities in ZTTK syndrome are caused by SON haploinsufficiency independent of the types of mutation that results in functional or dysfunctional proteins.
Seafloor observatory capable of automatically adjusting attitude and maintaining the fixed position for observation
Authors: Tian Wen-Jie , Deng Lu-Ke , Qi Zhan-feng , Zhai Jing-Sheng , Shen Zi-Qian , Yang Guang 
Published: March 2020

Abstract
Seafloor observatory are becoming more and more important in multidisciplinary observations of the seabed, but real-time, long-term and fixed locations observation are still difficult to achieve. This paper describes a new technology that divides the seafloor observatory into three modules: mobile docker, scientific instrument cabin and in-situ gravity station and uses buoys or photoelectric composite cables to meet the above three requirements. After design and manufacture, the workflow of the seafloor observatory was simulated through a pool test. The handling performance of the mobile docker, the reliability of the docking between the three modules and the performance of the in-situ gravity station to adjust its attitude were proved. It has been preliminarily proved that this seafloor observatory has application value.
Direct and indirect costs of cluster headache: a prospective analysis in a tertiary level headache centre
Authors: Negro Andrea , Sciattella Paolo , Spuntarelli Valerio , Martelletti Paolo , Mennini Francesco Saverio 
Published: March 2020

Abstract
Background: Cluster headache (CH) is the most frequent trigemino-autonomic cephalgia. CH can manifest as episodic (ECH) or chronic cluster headache (CCH) causing significant burden of disease and requiring attack therapy and prophylactic treatment. The few data available on the economic burden of CH come from retrospective studies based on questionnaires, population surveys and medical insurance claims database. Although all these studies showed an important economic burden, they provided different estimates depending on variability of CH awareness and management, healthcare systems, available therapies and use of treatments according to different guidelines.Methods: This prospective study aimed to quantify the total direct and indirect cost of ECH and CCH over a cluster period, both for the patient and for the National Health System (NHS), using data from subjects who consecutively attended an Italian tertiary headache centre between January 1, 2018 and December 31, 2018.Results: A total 109 patients (89 ECH, 19 CCH) were included. Mean attack frequency was 2.3±1.4 per day. Mean total cost of a CH bout was €4,398 per patient and total cost of CCH was 5.4 times higher than ECH (€13,350 vs. €2,487, p < 0.001). Direct costs represented the 72.1% of total cost and were covered for the 94.8% by the NHS. The costs for any item of expense were higher for CCH than for ECH (p < 0.001). Mean indirect costs for a CH bout were €1,226 per patient and were higher for CCH compared to ECH (€3.538 vs. €732), but the difference was not significant. Days with reduced productive capacity impacted for the 64.6% of the total indirect costs. The analysis of the impact CH on work showed that 27%% of patients felt that CH had limited their career, 40% had changed their work pattern, 20% had changed their place of employment and 10% had lost a job due to the disease.Conclusion: Our results provide a valuable estimate of the direct and indirect costs of ECH and CCH in the specific setting of a tertiary headache centre and confirm the high economic impact of CH on both the NHS and patients.
β2-AR Activation promotes cleavage and nuclear translocation of Her2 and metastatic potential of cancer cells
Authors: Liu Dan , Xu Xiyue , Liu Shuci , Zhao Xuan , Tang Anqun , Zha Li , Ma Wen , Zheng Junnian , Shi Ming 
Published: March 2020

Abstract
Background The prolonged hypersecretion of catecholamine induced by chronic stress may correlate with various steps of malignant progression of cancer and β2-AR overexpressed in certain cancer cells may translate the signals from neuroendocrine system to malignant signals by interacting with oncoproteins such as Her2. Crosstalk of the cell signaling pathways mediated by β2-AR and Her2 may promote a stronger or more sustained biological response. However, the molecular mechanisms underlying cross-communication between β2-AR and Her2 mediated signaling pathways are not fully understood. Methods In this study, the effects of adrenergic signaling on Her2 cleavage were evaluated by various assays, such as western blot, immunofluorescence and immunohistochemistry. In order to reveal the mechanism about Her2 cleavage triggered by β2-AR activation, the molecular and pharmacological means were employed. By using in vitro and in vivo assay, the influences of the crosstalk between β2-AR and Her2 on the bio-behaviors of tumor cells were demonstrated. Results Our data demonstrate that catecholamine stimulation activates the expression and proteolytic activity of ADAM10 by modulating the expression of miR-199a-5p and SIRT1 and also confirm that catecholamine induction triggers the activities of γ-secretase, leading to shedding of Her2 ECD by ADAM10 and subsequent intramembranous cleavage of Her2 ICD by presenilin-dependent γ-secretase, nuclear translocation of Her2 ICD and enhanced transcription of tumor metastasis-associated gene COX-2 . Chronic stimulation of catecholamine strongly promotes the invasive activities of cancer cells in vitro and spontaneous tumor lung metastasis in mice. Furthermore, the nuclear localization of Her2 was significantly correlated with overexpression of β2-AR in human breast cancer tissues. Conclusion This study illustrates that adrenergic signaling activation triggers Her2 cleavage, resulting in enhanced invasive and metastasis activities of cancer cells. Our data also reveal that an unknown mechanism by which the regulated intramembrane proteolysis (RIP) initiated by β2-AR activation controls a novel Her2-mediated signaling transduction under physiological and pathological conditions.
Influence of publication year, add-on design, and geographical region on the progression of Alzheimer’s disease: a modeling analysis of literature aggregate data
Authors: zhang ningyuan , Zheng Xijun , Liu Hongxia , Zheng Qingshan , Li Lujin 
Published: March 2020

Abstract
Background Our objective was to develop a disease progression model for cognitive decline in Alzheimer’s disease (AD) and to determine whether disease progression of AD is related to the year of publication, add-on trial design, and geographical regions. Methods Placebo-controlled randomized AD clinical trials were systemically searched in public databases. Longitudinal placebo response (mean change from baseline in the cognitive subscale of the Alzheimer’s Disease Assessment Scale [ADAS-cog]) and the corresponding demographic information were extracted to establish a disease progression model. Covariate screening and subgroup analyses were performed to identify potential factors affecting the disease progression rate. Results A total of 142 publications (148 trials) were included in this model-based meta-analysis. The typical disease progression rate was 5.82 points per year. The baseline ADAS-cog score was included in the final model using an inverse-U type function. Age was found to be negatively correlated with disease progression rate. After correcting the baseline ADAS-cog score and the age effect, no significant difference in disease progression rate was found between trials published before and after 2008, and between trials using add-on design and those that did not use add-on design. However, a significant difference was found among different trial regions. Trials in East Asian countries showed the slowest decline rate and the largest placebo effect. Conclusions Our model successfully quantified AD disease progression by integrating baseline ADAS-cog score and age as important predictors. These factors and geographic location should be considered when optimizing future trial designs and conducting indirect comparisons of clinical outcomes.
Associations between eating behaviors and muscle strength among Chinese adults: A population-based cross-sectional study
Authors: Ding Liang , Zhang Wenbo , Sun Xijun , Wang Yongxiang , Chen Shulei 
Published: March 2020

Abstract
Background: Poor eating behaviors are associated with imbalances in energy and food intake, which may directly or indirectly contribute to muscle strength loss. This study aimed to investigate the association between eating behaviors and muscle strength in Chinese adults. Methods: We designed a cross-sectional study of 2,036 Chinese individuals aged 25–68 years, conducted in 2017. Eating behaviors, including breakfast consumption, snacking after dinner, and eating rate, were assessed using a self-administered questionnaire. Muscle strength was determined by grip strength and assessed using a digital grip dynamometer. Results: After final adjustments for confounding factors, grip strength was measured as 35.2 (95% confidence interval [CI]: 34.6–35.8), 36.0 (95%CI: 35.6–36.4), and 36.9 (95%CI: 36.6–37.2) for those who skipped, occasionally ate, and regularly ate breakfast, respectively (p for trend < 0.001). Those who always, sometimes, and seldom snacked after dinner, respectively (p for trend <0.001), reported the following grip strength: 34.6 (95%CI: 33.9–35.2), 36.2 (95%CI: 35.8–36.6), and 36.8 (95%CI: 36.5–37.2). Significant associations were not found between eating rate and grip strength. Conclusions: Present study showed that higher frequency of breakfast consumption and lower frequency of snacking after dinner were associated with better muscle strength in Chinese adults. Therefore, eating behaviors may be involved in muscle function.
Personal values in adolescence and their associations with metabolic biomarkers in adulthood: a population-based study in Japan
Authors: Sasaki Natsu , Watanabe Kazuhiro , Kawakami Norito 
Published: March 2020

Abstract
Background: Personal values, which are formed in early life, can have an impact on the health outcome later in life. Objective: The aim of this study is to investigate the relationship between personal values in adolescence and bio-indicators related to metabolic syndrome (MetS) in adulthood.Participant and Methods: The longitudinal data was used from the Japanese Study on Stratification, Health, Income, and Neighborhood (J-SHINE) in 2012 and 2017. Personal values in adolescence were retrospectively obtained in 2017 from a self-reporting questionnaire, composed of value priorities and commitment to the values. Venous samples were collected in 2012 for low and high-density lipoprotein (LDL, HDL) cholesterol and hemoglobin A1c (HbA1c). Body mass index (BMI), waist circumference and systolic and diastolic blood pressure (SBP, DBP) were also measured. The associations of each variable were examined by partial correlation analysis. In addition, multiple linear regression analysis was conducted to examine overall associations between personal values and the sum of standardized scores (Z-score) of the biomarkers as a proxy of MetS. Furthermore, cluster analysis was conducted to identify groups of the participants who have some specific values and to examine their associations with the Z-score. Results: The total population (n=668) included 261 men and 407 women. Among men, the personal value priority of “Having influence on society” was associated with high HDL cholesterol (partial r=0.13, p=0.032) and “Cherishing familiar people” with low waist circumference (r=-0.129, p=0.049), low SBP, and high DBP (r=-0.135, p=0.039; r=0.134, p=0.041). In women, “Not bothering others” was associated with high SBP and low DBP (r=0.125, p=0.015; r=-0.123, p=0.017). "Economically succeeding" were associated with worse outcome (β=0.162, p=0.042). In the cluster analysis, both in men and women, the cluster which had highest openness to change value; “Having and keeping a belief”, “Exploring what you were interested in” and “Actively challenging” with the highest commitment showed worst proxy outcomes although there were no significant differences.Conclusions: Although some significant associations were found between personal values in adolescence and MetS-related markers in adulthood, overall associations were not strong. Culturally prevailing values were likely to be associated with a good outcome of metabolic health.
Validation of the parent version of the Strengths and Difficulties Questionnaire (SDQ) to screen child and adolescent mental health problems in Mongolia
Authors: Aoki Ai , Ganchimeg Togoobaatar , Naranbaatar Nyam , Khishigsuren Zuunnast , Gundegmaa Lkagvasuren , Bat-Erdene Shagdar , Munkhbaatar Bolorchimeg , Mori Rintaro , Kikuchi Akihito , Soya Hideaki , Kasai Kiyoto , Takehara Kenji 
Published: March 2020

Abstract
BackgroundChild and adolescent mental health problems are urgent health issues in low- and middle-income countries (LMICs). To promote mental health services for child and adolescent mental problems, simple validated screening tools are helpful. In Mongolia, the Strengths and Difficulties Questionnaire (SDQ), an internationally used child and adolescent mental health screening tool for children aged 4 to 17, was translated but not yet validated. To use the questionnaire for surveillance, research, and clinical purpose, validation is necessary.MethodsA community sample and a clinical sample were used. The discriminating ability of the parental version of the SDQ was examined using Receiver Operating Characteristics (ROC) analysis on the SDQ total difficulties score. The area under the ROC curve was used as a measure. Cut-off score was determined by normative banding that categorizes children with the highest 10% score range as abnormal and the second highest 10% score as borderline following the original method; this cut-off score was compared with the cut-off score candidates with good balance between sensitivity and specificity using ROC analysis.ResultsWe included 2301 children in the community sample, and 429 children in the clinical sample. Mean age was 9.7 years (SD 0.4) among the community sample and 10.4 years (SD 3.8) among the clinical sample. A total of 88.8% of the community sample and 98.8% of the clinical sample answered the SDQ. Using ROC analysis, the area under the curve was 0.82 (95% confident interval 0.80-0.85), which meant moderate discriminating ability. The mean total difficulties score was 12.9 (SD 4.8) among the community sample and 20.4 (SD 6.2) among the clinical sample. Using normative banding, the cut-off score between normal and borderline was 16/17 and between borderline and abnormal was 19/20. Sensitivity was 71.9% and 53.8% and specificity was 78.5% and 90.5% for cut-off scores of 16/17 and 19/20, respectively. The cut-off score candidates by ROC analysis was 16/17 and 17/18.ConclusionsThe parental version of the SDQ had moderate discriminating ability in Mongolia. For the screening of mental health problems among community children, cut-off score of 16/17 is recommended.
Correlates of relationship issues among youth: Findings from a large scale youth mental health promotion program in India
Authors: Banandur Pradeep , Kalpana Gopalan , Pai Shikha G , Arelingaiah Mutharaju , Velu Sathya R , Garady Lavanya , Koujageri Jyoti M , Sajjanar Sateesh L , Ramesh M S , K Srinivas , Gururaj Gopalakrishna 
Published: March 2020

Abstract
Background : Relationships and mental health have a bidirectional effect. The effect of relationships on mental health is stronger than vice versa. We analyzed two-year case records of 8595 beneficiaries aged 15-35 years attending youth guidance centres (Yuva Spandana Kendras) in Karnataka, India to understand factors affecting relationship issues. Methods : Multivariate logistic regression was performed with any beneficiary reporting having a relationship issue as outcome. Results : Occupation, marital status, health and lifestyle issues, personality issues, safety issues, gender, sex, & sexuality issues, suicidality, alcohol, and different emotions experienced,had significant association with relationship issues. Investing in health promotion interventions focusing on these precursors of relationship issues amongst youth seems strategic. Conclusion : Our findings have implications for other states in India and other low-middle-income countries like India.
Development and validation of the isothermal recombinase polymerase amplification assays for rapid detection of Mycoplasma ovipneumoniae
Authors: Wang Jinfeng , Li Ruiwen , Sun Xiaoxia , Liu Libing , Hao Xuepiao , Wang Jianchang , Yuan Wanzhe 
Published: March 2020

Abstract
Background

Mycoplasmal pneumonia is an important infectious disease that threatens sheep and goat production worldwide, and Mycoplasma ovipneumoniae is one of major etiological agent causing mycoplasmal pneumonia. It is an urgent need to develop a rapid and accurate method to detect M. ovipneumoniae . Recombinase polymerase amplification (RPA) is an isothermal nucleic acid amplification technique, and RPA-based diagnostic assays have been described for the detection of different types of pathogens.

Results

The RPA assays using real-time fluorescence detection (real-time RPA) and lateral flow strip detection (LFS RPA) were developed to detect M. ovipneumoniae targeting a conserved region of the 16SrRNA gene. Real-time RPA was performed in a portable florescence scanner at 39 °C for 20 min. LFS RPA was performed in a portable metal bath incubator at 39 °C for 15 min, and the amplicons were visualized with the naked eyes within 5 min on the lateral flow strip. Both assays were highly specific for M. ovipneumoniae , as there were no cross-reactions with other pathogens tested, especially the M. capricolum subsp. capripneumoniae . The limit of detection of LFS RPA assay was 1.0×10 1 copies per reaction using a recombinant plasmid containing target gene as template, which is 10 times higher than the limit of detection of the real-time RPA and real-time PCR assays. The RPA assays were further validated on 46 clinical sheep nasal swab and fresh lung samples, and M. ovipneumoniae DNA was detected in 17 samples in the RPA assays and 19 samples in the real-time PCR assay. The real-time RPA and LFS RPA showed diagnostic specificity of 100%, diagnostic sensitivity of 89.47%, and a kappa coefficient of 0.909.

Conclusions

The developed real-time RPA and LFS RPA assays provide the attractive and promising tools for rapid, convenient and reliable detection of M. ovipneumoniae , especially in resource-limited settings.
Integrated miRNA-mRNA expression profiles revealing key molecules in ovarian cancer based on bioinformatics analysis
Authors: Li Chao , Zhu Xiaodan , Zhang Linghua , Ou Miaoling , Hong Zhantong 
Published: March 2020

Abstract
Background: Ovarian cancer was one of the leading causes of death in gynecological malignancies, of which molecular mechanism hadn’t been elucidated clearly yet. Our research aimed to reveal the potential key molecular and biological processes of ovarian cancer by means of bioinformatics.Methods: The microarray sets of miRNA and mRNA expression profiles were downloaded from the GEO database. The target prediction was performed on the differentially expressed miRNAs identified and the overlapped differentially expressed genes (DEGs) were obtained combined with miRNA and mRNA datasets. The regulatory network of miRNA-gene was further constructed by cytoscape software. The overlapped DEGs in the network were analyzed to explore the biological processes involved by enrichment analysis. The molecular protein-protein interaction (PPI) network was used to identify key genes among the DEGs.Results: A total of 167 overlapped DEGs were identified. The miRNA-gene network analysis found that miR-29c-3p, miR-1271-5p, and miR-133b, existed the most extensive targeting relationship with overlapped DEGs, being three key miRNAs of the regulatory network, and played the role of tumor suppressor. The GO enrichment showed that the overlapped DEGs were mainly involved in process named extracellular related organization, embryonic organ development, postsynaptic specialization, collagen trimer and DNA−binding transcription activator et al. The KEGG pathway analysis showed that these DEGs were involved in protein digestion and absorption and relaxin signaling pathway. The PPI network identified 10 key genes, playing the role in promoting tumor.Conclusion: The methodology used and identification of key molecules in our study contributed to understanding the pathogenesis of ovarian cancer and providing new candidate biomarkers for early screening of ovarian cancer.