bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Nesfatin-1 and Wnt /β-Catenin Pathway on OGCs in PCOS
Authors: Ding Peihui , Ai Ding-Ding , Lao Kai-Xue , Huang Ying , Zhang Yan , Li Qing-Chun , Wang Yan-Lin 
Published: November 2020

Abstract
Background Polycystic ovary syndrome is a complex disease related to the endocrine and metabolism. Its specific cause and pathogenesis have not been clear. Nesfatin-1 could not only regulate energy balance and glucose metabolism, but also affect the reproductive system. The Wnt/β-catenin signaling pathway affects follicle development, ovulation, corpus luteum formation, and steroid hormone production. Results Here, we studied the roles of nesfatin-1 and Wnt/β-catenin signaling pathway in the pathogenesis of polycystic ovary syndrome. Firstly, the human primary ovarian granulosa cells in vitro was cultured. The results showed that the apoptosis rate of ovarian granulosa cells in polycystic ovary syndrome patients was significantly higher than that of granular cells in normal people. Moreover, nesfatin-1 and Wnt/β-catenin pathway inhibitor IWR-1could inhibit the expressions of ovarian granulosa cells apoptosis genes and promote their proliferation, as well as nesfatin-1 affected the expressions of foxo3a and its downstream factors. Then, an in vitro culture system for ovarian granulosa cells (OGCs) was established by employing a rat model. The results are the same with those mentioned above. Conclusion This strongly proves that the nesfatin-1 participates in regulating the apoptosis and proliferation of granulosa cells by the Wnt/β-catenin pathway. According to the role of nesfatin-1 and IWR in polycystic ovary syndrome, nesfatin-1 and Wnt/β-catenin pathway can provide a guideline for the diagnosis and treatment of Polycystic ovary syndrome (PCOS).
A Retrospective Study of Noninvasive Prenatal Testing for Chromosome Aneuploidies and Sub-Chromosomal Copy Number Variations in 24359 Single Pregnancies
Authors: Liu Yuefang , Cheng Longfei , Peng Yuan , Liang Zhe , Qiong Pan 
Published: November 2020

Abstract
Background: With the development of whole-genome sequencing, small sub-chromosomal deletions and duplications could be found by non-invasive prenatal testing(NIPT). This study aimed to review the efficiency of NIPT as a screening test for aneuploidies and sub-chromosomal copy number variations (CNVs) in 24359 single pregnancies.Methods: A total of 24359 single pregnancies with different clinical indications were retrospectively analyzed. The positive predictive value （PPV）of chromosome aneuploidies and subchromosomal CNVs were analyzed. Pathogenicity of abnormal NIPT results were assessed according to American College of Medical Genetics and Genomics(ACMG). Results: A total of 442 pregnancies (442/24359,1.9%) were with abnormal NIPT results. PPV for trisomy 21(T21), trisomy 18 (T18), trisomy 13 (T13), and sex chromosome aneuploidies (SCAs) was 84.8%, 54.2%, 11.1% an 40.5% respectively. The PPV for sub-chromosomal CNVs was 59.0% (46/78). The PPV for CNVs ≤5 Mb was 68.9% (31/45), for CNVs within 5-10 Mb was 83.3%(5/6) and for CNVs ≥10 Mb was 37.1% (10/27) respectively. The clinical information, prenatal diagnosis results and follow-up results of 46 true positive cases, 6 cases with sub-chromosomal CNVs inconsistent with NIPT and 1 false negative case were also described in detail.Conclusions: Our data have potential significance in demonstrating the significance of NIPT not only for common whole chromosome aneuploidies but also for sub-chromosomal CNVs. Besides, the clinical information, prenatal diagnosis results and follow-up results of 52 cases with sub-chromosomal CNVs and 1 false negative case would provide important guidance for genetic counseling.
Risk of Malignancy Long After Acute Coronary Syndrome in Selected Urban and Rural Areas and Comparison With Smoking Risk:&nbsp;The ABC-7* Study on Heart Disease.&nbsp;(*ABC is An Acronym for Adria, Bassano, Conegliano, and Padova Hospitals)
Authors: Berton Giuseppe , Mahmoud Heba Talat , Palmieri Rosa , Cavuto Fiorella , Cordiano Rocco , Lorenzon Elisabetta , Bagato Francesco 
Published: November 2020

Abstract
Background Increased cancer risk has been reported in patients with acute coronary syndrome (ACS). Objectives To investigate geographic differences in risk malignancy long after ACS. Methods We enrolled 586 ACS patients admitted to hospitals in three provinces in the Veneto region of Italy in this prospective study. Patient's residency was classified into three urban and three nearby rural areas. Results All (except for 3) patients completed the follow-up (22 years or death) and 54% were living in rural areas. Sixteen patients had pre-existing malignancy, and 106 developed the disease during follow-up. Cancer prevalence was 17% and 24% (p=0.05) and incidence of malignancy was 16 and 21/1000 person-years for urban and rural areas, respectively. In unadjusted logistic regression analysis, cancer risk increased from urban to rural areas (odds ratio [OR] 3.4;95% confidence interval [CI] 1.7-7.1; p=0.001), with little change from north to south provinces (OR 1.5;95% CI 1.0-2.2; p=0.06). Yet, we found a strong positive interaction between urban-rural areas and provinces (OR 2.1;95% CI 1.2-3.5; p=0.003). These results kept true in the fully adjusted model. Unadjusted Cox regression analysis revealed increasing hazards ratios (HRs) for malignancy onset from urban to rural areas (HR 3.0;95% CI 1.5-6.2; p=0.02), but not among provinces (HR 1.3;95% CI 1.0-2.0; p=0.14). Also, we found a strong positive interaction between geographic areas (HR 2.1;95% CI 1.3-3.5; p=0.002), even with a fully adjusted model. Conclusion The results in unselected real-world patients demonstrate a significant geographic difference in malignancy risk in ACS patients, with the highest risk in the north-rural area.
Egr2 Upregulation Induced Mitochondrial Iron Overload Implicating in Cognitive Deficits after Sevoflurane Administration
Authors: Zhang Piao , Chen Yeru , Zhang Shuxia , Fang Man , Lin Xianyi , Liu Tieshuai , Zhou Youfa , Yu Xin , Chen Gang 
Published: November 2020

Abstract
Background: Sevoflurane inhalation initiated cognitive deficits implicated in mitochondrial dysfunction, synaptogenesis impairment and neuroinflammation. Egr2 plays a crucial role in maintaining cognitive function. Therefore, we attempted to clarify the potential correlation regarding Egr2 expression and cognitive deficits induced by sevoflurane administration. Methods: Animals received sevoflurane anesthesia, and the behavioral tests including Morris water maze, novel object recognition test and trace fear conditioning were performed. Then, the Golgi-Cox staining and Nissl staining were employed to detect the effect of sevoflurane inhalation in hippocampal neurons. Meanwhile, bioinformatics analysis was implemented, and western blot (WB) and bisulfite sequencing PCR (BSP) technique were utilized to validate this hypothesis. Moreover, the level of lipid peroxidation, mitochondrial membrane potential, morphology and membrane permeability, and cytoplasm calcium levels were investigated after Egr2 interference by using JC-1 probe, MitoTracker staining, Mitochondrial permeability transition pore (mPTP) assay, and Fluo calcium indicators, respectively. Additionally, Prussian blue staining was used to evaluate the iron content.Results: The behavioral tests indicated that the cognitive function was significantly attenuated after sevoflurane administration. The Golgi-Cox staining displayed that the dendritic length, density and nodes were significantly reduced, and the typical neuropathological changes including neuron loss, nucleus shrinkaged and disappearance of Nissl bodies were observed by Nissl staining. Moreover, bioinformatics analysis showed that the Egr2 expression was significantly upregulated, and WB and BSP confirmed this result. Additionally, the results suggested that sevoflurane administration elevated the cytoplasm calcium levels, reduced the mitochondrial membrane potential and triggered the opening of mPTP. Prussian blue staining showed that the iron deposition was apparently increased. However, Egr2 level downregulation partly reversed these above changes.Conclusion: These findings demonstrated that sevoflurane administration elicited mitochondrial dysfunction and iron dyshomeostasis, and eventually resulted in cognitive impairments, whereas suppressing Egr2 expression partly improved this pathological process.
Short Survival-Related Genes Harbor EMT Processes and Dendritic Cell Infiltration in Glioblastoma
Authors: Yang Zhenkun , Zhang Bo , Zhang Zhenhao , Wang Jingjing , Hu Yaling , Pu Zhening , Yin Ying , Zou Jian 
Published: November 2020

Abstract
Background: Glioblastoma is an aggressive primary tumour with the lowest survival time among brain tumours. Tumour-infiltrating immune cells (TIICs) are involved in tumour progression and determine the prognosis, while the association of immune cell infiltration with glioblastoma is rarely unknown. This study aimed to screen survival-related (SR) genes and major biological processes through bioinformatic analysis and to identify the relationship between SR genes and TIICs.Methods:SR genes were screened by comparing the long-term (>36 months) and short-term (<12 months) survivors in the database GSE53733. Gene set enrichment analysis (GSEA) was applied to compare the differences in biological processes between long-term survivors and short-term survivors. The SR genes were identified using the limma package of R. Gene Ontology (GO) analysis was conducted through Metascape. The protein-protein interaction (PPI) network of the SR genes was established through the Search Tool for the Retrieval of Interacting Genes (STRING) website and further analysed by the Molecular Complex Detection (MCODE) algorithm. UALCAN and GlioVis were employed to analyse the expression levels and prognostic value of hub genes. The correlation of hub genes with immune cell filtration was estimated by the Tumor Immune Estimation Resource (TIMER). The gene-drug interaction network was constructed using the Comparative Toxicogenomics Database (CTD).Results: The functions of the detected genes were mainly enriched in epithelial mesenchymal transition (EMT) and oxidative phosphorylation. Of the detected genes, a total of 220 SR genes were identified, including 78 upregulated genes and 142 downregulated genes in long-term survivors. The upregulated genes were mainly related to neuron projection morphogenesis, extracellular matrix, and cation channel activity. The downregulated genes were mainly related to extracellular matrix organization and angiogenesis. The PPI network for SR genes was constructed with 65 edges and 195 nodes, and two significant modules were selected. The results indicated that COL1A2, COL6A2, COL8A1, and COL8A2 were hub SR genes. In addition, they were correlated with immune cell infiltration, especially dendritic cell infiltration.Conclusions: These results revealed that collagens accounted for the progression and prognosis of glioblastoma. In addition, DC infiltration is a risk factor for glioblastoma patients. The expression of collagen protein COL6A2 was significantly correlated with the DC infiltration level and poor prognosis. Further, potential drugs that affect the function of COL6A2 could improve the outcomes of glioblastoma.
Differential Efficacy of TNF Inhibitors With or Without the Immunoglobulin Fc Portion in Rheumatoid Arthritis - The ANSWER Cohort Study
Authors: Nakayama Yoichi , Hashimoto Motomu , Murakami Kosaku , Murata Koichi , Tanaka Masao , Ito Hiromu , Yamamoto Wataru , Ebina Kosuke , Hata Kenichiro , Hiramatsu Yuri , Katayama Masaki , Son Yonsu , Amuro Hideki , Akashi Kengo , Onishi Akira , Hara Ryota , Yamamoto Keiichi , Ohmura Koichiro , Matsuda Shuichi 
Published: November 2020

Abstract
Background: Rheumatoid factor (RF) binds to the Fc portion of immunoglobulin and can bind to the Fc portion of anti-TNF monoclonal antibodies (TNFi), attenuating their clinical efficacy. We tried to determine whether the therapeutic efficacy is different between TNFi with or without the immunoglobulin Fc portion in rheumatoid arthritis (RA) patients depending upon the RF titres.Methods: RA patients treated with TNFi were enrolled from an observational multi-centre registry in Japan. TNFi treatments were divided into two groups based on the structural characteristics between TNFi with Fc (infliximab, adalimumab, golimumab, etanercept) and TNFi without Fc (certolizumab-pegol). Patients were classified into 4 groups according to RF titre quartiles. The sequential disease activity score in 28 joints using erythrocyte sedimentation rate (DAS28-ESR) were compared by the Mann-Whitney U test between TNFi with and without the immunoglobulin Fc portion in each RF titre group.Results: A total of 705 RA patients were included and classified into four groups according to quartiles of baseline RF titres (RF1; RF 0-15.0 IU/mL, RF2; 15.0-55.0, RF3; 55.0-166, RF4; 166-7555). In RF4, RA patients treated with TNFi without Fc had a significantly lower DAS28-ESR than those treated with TNFi with Fc (3.2 (2.3-4.2) vs. 2.7 (2.0-3.0)) (median, IQR) after 12 months of follow-up, while there were no significant differences in RF1, RF2, and RF3.Conclusion: TNFi without Fc (certolizumab-pegol) may be more efficacious than TNFi with Fc in RA patients with high RF titres.
Comparative Effectiveness and Safety of 32 Pharmacological Interventions Recommended by Guidelines for COVID-19: A Systematic Review and Network Meta-Analysis Combining 66 Trials
Authors: Wu Shanshan , Zhou Qingxin , Zeng Xueyang , Zhang Jingxue , Yang Zhirong , Yang Qingqing , Zhang Zilu , Chen Yahong , Sun Feng , Zhan Siyan 
Published: November 2020

Abstract
Background: To evaluate comparative efficacy and safety of pharmacological interventions in patients with coronavirus disease 2019. Methods: Medline, Embase, the Cochrane Library and clinicaltrials.gov were searched for randomized controlled trials (RCTs) in patients infected with SARS-COV-2/SARS-COV. Random-effects network meta-analysis within Bayesian framework was performed, followed by Grading of Recommendations Assessment, Development and Evaluation (GRADE) system assessing quality of evidence. The primary outcome of interest includes mortality, cure, viral negative conversion (VNC) and overall adverse events (OAE). Odds ratio (OR) with 95% confidence interval (CI) was calculated as the measure of effect size.Results: 66 RCTs with 19,095 patients were included, involving standard care (SOC), 8 different antiviral agents, 6 different antibiotics, high and low dose chloroquine (CQ_HD, CQ_LD), traditional Chinese medicine (TCM), corticosteroids and other treatments. Compared with SOC, significant reduction of mortality was observed for TCM (OR=0.34, 95%CI: 0.20-0.56, moderate quality) and corticosteroids (OR=0.84, 0.75-0.96, low quality) with improved cure rate (OR=2.16, 1.60-2.91, low quality for TCM; OR=1.17, 1.05-1.30, low quality for corticosteroids). However, increased risk of mortality was found for CQ_HD versus SOC (OR=3.20, 1.18-8.73, low quality). TCM was associated with decreased risk of OAE (OR=0.52, 0.38-0.70, very low quality) but CQ_HD (OR=2.51, 1.20-5.24) and IFN (OR=2.69, 1.02-7.08) versus SOC with very low quality) were associated with an increased risk. Conclusions: Corticosteroids and TCM may reduce mortality and increase cure rate with no increased risk of OAEs compared with standard care. CQ_HD might increase the risk of mortality. CQ, IFN and other antiviral agents could increase the risk of OAEs. The current evidence is generally uncertain with low quality and further high-quality trials are needed.
Prevalence, Features and Workplace Factors Associated With Burnout Amongst Intensivists in Australia and New Zealand
Authors: Mair Shona , Mair Shona , Crowe Liz , Crowe Liz , Nicholls Mark , Nicholls Mark , Senthuran Siva , Senthuran Siva , Gibbons Kristen , Gibbons Kristen , Jones Daryl , Jones Daryl 
Published: November 2020

Abstract
BackgroundBurnout has been reported to be common amongst intensive care physicians and can be associated with staff absenteeism, drug and alcohol abuse, and suboptimal patient care. We aimed to investigate the prevalence and features of self-reported burnout amongst intensivists working in Australia and New Zealand (ANZ); and to evaluate workplace stressors associated with increased risk of self-reported burnout.MethodsElectronic survey amongst registered intensivists in Australia and New Zealand. Burnout and professional quality of life were measured using the Professional Quality of Life Scale 5 (ProQOL-5). Socio-organisational factors were defined a-priori and assessed using a five-point Likert scale. Thematic analysis was conducted on an open-ended question on workplace stressors. Associations between the ProQOL burnout subscale and demographic characteristics were investigated using analysis of variance or Kruskal-Wallis. Results261 of 921 estimated intensivists responded (response rate: 28.3%). Overall, few participants (0.8%) demonstrated high scores (>75th centile) for burnout, and 70.9% of participants scored in the average range for burnout. Of note, 98.1% of participants scored in the average to high range for compassion satisfaction. No association was found between gender, age, or years of practice with the level of burnout or compassion satisfaction. Seven themes emerged regarding intensivists’ most stressful aspects of work: (1) interpersonal interactions and workplace relationships (25.5%); (2) workload and its impact (24.9%); (3) resources and capacity (16.3%); (4) health systems leadership and bureaucracy (16.1%); (5) end-of-life issues and moral distress (8.4%); (6) clinical management (4.9%); and (7) job security and future uncertainty (1.3%). ConclusionFewer ANZ intensivists experienced burnout than has previously been reported. Many self-reported work stressors do not relate to clinical work, but instead potentially modifiable factors related to interpersonal interactions with other colleagues and, more importantly, hospital administrators.
Analysis of The Demand for Older Adult Care Services and Related Influencing Factors Among Older Adults Living Alone in China
Authors: Zeng Yanbing , Lin Chenxi , Fang Ya 
Published: November 2020

Abstract
Background: The number of older adults living alone in China is rising sharply and their care needs have become an increasing public health concern. This study aimed to explore the anticipated living arrangements and demand for home and community-based care services (HCBS) of older adults living alone and examine the related influencing factors.Methods: The data of 2217 participants living alone were extracted from the 2018 Chinese Longitudinal Health Longevity Survey (CLHLS). A chi-square test was used to examine the differences in older adult care services between respondents with different characteristics. Using the Andersen model as the analysis framework, multinomial and binary logistic regressions were used to analyze the influencing factors of anticipated living arrangements and HCBS, respectively. Results: 75.4% of the respondents hoped to maintain living alone when considering the future. Those who were older, had more children, income source was family members, always felt lonely and isolated and had limitation in activities of daily living (ADL) were inclined to choose the arrangement of “co-residence with children”. Childless and loneliness had significant impact on older adults’ willingness to live in institution. There were significant differences between urban and rural areas for provision of HCBS and the demand exceeds supply in all service types. Those who were younger, lived in urban areas, farmers, income source was family members, had poor economic status, had access to social services, with higher sense of loneliness and chronic diseases tend to show anticipated demands for various HCBS.Conclusions: The demand for older adult care services were affected by predisposing, enabling and need variables. There is a need for an overall improvement of the community care system to create a supportive environment for older adults living alone.
Fear of Falling is More Important Than Previous Falls in Terms of Limiting Activities: A Longitudinal Study
Authors: Liu Minhui , Hou Tianxue , Li Yuxiao , Sun Xiaocao , Szanton Sarah L. , Clemson Lindy , Davidson Patricia M. 
Published: November 2020

Abstract
Background: Fear of falling and previous falls are both risk factors that affect daily activities of older adults. However, it remains unclear whether they independently limit daily activities accounting for each other. This study aims to examine whether previous falls and fear of falling independently predict limited daily activities among older adults.Methods: We used the data from Round 1 to Round 5 of the National Health and Aging Trends Study. We included a total of 866 community-dwelling participants who provided data on previous falls, fear of falling and limited activities from Round 1 to Round 5 and had no limited daily activities at Round 1 in this study. Previous falls and fear of falling were ascertained by asking participants whether they had fallen in the past year and whether they had worried about falling in the last month. Limited daily activities included any difficulties with mobility (e.g., going outside), self-care (e.g., eating), and household activities (e.g., laundering). Generalized estimation equation models were used to examine whether previous falls and fear of falling independently predicted development of limited daily activities adjusting covariates.Results: Participants were mainly between 65 and 79 years old (83%), male (57%), and non-Hispanic White (79%). Among participants who fell in Round 1, 13.2%-27.6%, 29.0%-52.0%, and 18.4%-32.9% developed limitations in mobility, self-care, household activities during Round 2 to Round 4, respectively. Among those who had fear of falling in Round 1, 22.5%-41.3%, 30.0%-55.0%, and 18.8%-36.3% developed limitations in mobility, self-care, and household activities during Round 2 to Round 4, respectively. Fear of falling independently predicted limitations in mobility (Incidence rate ratio [IRR]: 1.86, 95% CI: 1.50, 2.31), self-care (IRR: 1.32, 95% CI: 1.11, 1.62) and household activities (IRR: 1.34, 95% CI: 1.11, 1.62) after adjusting for previous falls and covariates. Previous falls only independently predicted limitations in mobility (IRR: 1.30, 1.08, 1.56) and household activities (IRR: 1.27, 95% CI: 1.05, 1.54) after adjusting fear of falling and covariates. Conclusions: While recognizing the risk factor of previous falls, fear of falling can be a more critical factor to intervene to reduce limited daily activities.