bluuebunny/crossref_metadata_2025 huggingface dataset:
A Modified Chief Complaint-Based Cardiac Triage Strategy for Reducing Delays in the Management of Patients With ST-Elevation Myocardial Infarction
Authors: Su Hung-Yuan , Tsai Jen-Long , Hsu Yin-Chou , Lee Kuo-Hsin , Chang Chao-Sheng , Sun Cheuk-Kwan , Wang Yu-Han , Hsu Chih-Wei
Published: November 2020

Background: This study aimed at investigating the efficacy of utilizing a modified cardiac triage strategy at the emergency department for timely detection of ST-elevation myocardial infarction (STEMI).Methods: A chief complaint-based “cardiac triage” protocol comprising (1) raising alert among medical staff with bedside triage tags, and (2) immediate bedside electrocardiography (ECG) after focused history-taking was implemented at the emergency department of a single tertiary referral center since December 2018. All patients diagnosed with STEMI visiting the emergency department (ED) between November 2017 and January 2020 were retrospectively reviewed to investigate the effectiveness of the strategy by comparing the primary [i.e., door-to-ECG (DTE) time and achievement rate of DTE time<10 minutes] and secondary [i.e., door-to-balloon (DTB) time and achievement rate of DTB time<90 minutes] outcomes among STEMI patients before (pre-intervention) and after (post-intervention) strategy implementation.Results: Analysis of a total of 117 ED patients with STEMI (pre-intervention group, n=57; post-intervention group, n=60) showed significant overall improvements in median DTE time from 5 to 4 minutes (p=0.02), achievement rate of DTE time<10 minutes from 45% to 57% (p=0.01), median DTB time from 81 to 70 minutes (p<0.01). Significant trends were also noted in achievement rates for DTE and DTB times (p=0.01 and p=0.006, respectively) after strategy implementation. The incidence of DTE time>10 minutes for those with initially underestimated disease severity was also reduced from 90% to 10% (p<0.01).Conclusions: A chief complaint-based “cardiac triage” strategy successfully improved the quality of emergency care for STEMI patients through reducing delays in diagnosis and treatment.
Postural Synergy-Based Exoskeleton Reproducing Natural Human Movements to Improve Upper Limb Motor Control after Stroke
Authors: He Chang , Xiong Cai-Hua , Chen Ze-Jian , Fan Wei , Huang Xiao-Lin
Published: November 2020

Background: Upper limb exoskeletons have drawn significant attention in neurorehabilitation because of anthropomorphic mechanical structure analogous to human anatomy. Whereas, the training movements are typically underorganized because most exoskeletons only control the movement of the hand in space, without considering rehabilitation of joint motion, particularly inter-joint postural synergy. The purposes of this study were to explore the application of a postural synergy-based exoskeleton (Armule) reproducing natural human movements for robot-assisted neurorehabilitation and to preliminarily assess its effect on patients' upper limb motor control after stroke. Methods: We developed a novel upper limb exoskeleton based on the concept of postural synergy, which provided five degrees of freedom (DOF) , natural human movements of the upper limb. Eight participants with hemiplegia due to a first-ever, unilateral stroke were recruited and included. They participated in exoskeleton therapy sessions 45 minutes/day, 5 days/week for 4 weeks, with passive/active training under anthropomorphic trajectories and postures. The primary outcome was the Fugl-Meyer Assessment for Upper Extremities (FMA-UE). The secondary outcomes were the Action Research Arm Test(ARAT), modified Barthel Index (mBI) , and exoskeleton kinematic as well as interaction force metrics: motion smoothness in the joint space, postural synergy error, interaction force smoothness, and the intent response rate. Results: After the 4-weeks intervention, all subjects showed significant improvements in the following clinical measures: the FMA-UE ( p =0.02), the ARAT ( p =0.003), and the mBI score ( p <0.001). Besides, all subjects showed significant improvements in motion smoothness ( p =0.004), postural synergy error ( p =0.014), interaction force smoothness ( p =0.004), and the intent response rate ( p =0.008). Conclusions: The subjects were well adapted to our device that assisted in completing functional movements with natural human movement characteristics. The results of the preliminary clinical intervention indicate that the Armule exoskeleton improves individuals’ motor control and activities of daily living (ADL) function after stroke, which might be associated with kinematic and interaction force optimization and postural synergy modification during functional tasks. Clinical trial registration: ChiCTR, ChiCTR1900026656; Date of registration: October 17, 2019. http://www.chictr.org.cn/showproj.aspx?proj=44420
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

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

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: The ABC-7* Study on Heart Disease. (*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

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

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

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

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

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

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

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

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.
Integrated analysis of the proteome and transcriptome in human ischemic cardiomyopathy
Authors: Zhang Kai , Qin Xianyu , Wu Min , Wen Pengju , Wu Yueheng , Zhuang Jian
Published: November 2020

Background: Ischemic cardiomyopathy (ICM) is the primary cause of heart failure, which leads to an unacceptable rate of mortality and morbidity. The molecular mechanisms involved in ICM remains incompletely understood. This study aimed to investigate the molecular mechanisms of ICM by integrated proteome and transcriptome analyses.Methods and Results: Data independent acquisition (DIA) mass spectrometry and RNA-seq technologies were performed in left ventricular species from 5 ICM patients and 5 unused non-failing donors. A total of 546 differentially expressed proteins (DEPs) and 1080 mRNAs (DEGs) were identified in ICM compared with control, which were mainly involved in inflammatory/immune response, response to stress (such as hypoxia and reactive oxidative species), oxidative stress, and ECM (extracellular matrix) organization. Moreover, though the low correlation between transcriptome and proteome, 41 key genes were identified, which showed the same expression directions at mRNA and protein levels. Among them, HSP90AA1 occupied a central position in the PPI network. Furthermore, a differentially expressed lncRNA-mRNA-protein network was constructed, which consisted of 13, 11, and 11 differentially expressed lncRNAs, mRNAs, and proteins, respectively, and the expression of this network were validated by qRT-PCR.Conclusion: This identified some key genes and a lncRNA-mRNA-protein regulatory network involved in ICM, which should provide a framework for an in-depth interrogation into the complex molecular mechanisms of ICM.
Identification of a novel metabolism‑related prognostic signature in hepatocellular carcinoma through bioinformatics analysis and validation through experimental studies
Authors: Wang Zhihao , Embaye Kidane Siele , Yang Qing , Qin Lingzhi Qin , Zhang Chao , Liu Liwei , Zhan Xiaoqian , Zhang Fengdi , Wang Xi , Qin Shenghui
Published: November 2020

BackgroundGiven that metabolic reprogramming has been recognized as an essential hallmark of cancer cells, this study sought to investigate the potential prognostic values of metabolism-related genes(MRGs) for hepatocellular carcinoma (HCC) diagnosis and treatment.MethodsThe metabolism-related genes sequencing data of HCC samples with clinical information were obtained from the International Cancer Genome Consortium(ICGC) and The Cancer Genome Atlas (TCGA). The differentially expressed MRGs were identified by Wilcoxon rank sum test. Then, univariate Cox regression analysis were performed to identify metabolism-related DEGs that related to overall survival(OS) . A novel metabolism-related prognostic signature was developed using the least absolute shrinkage and selection operator (Lasso) and multivariate Cox regression analyses . Furthermore, the signature was validated in the TCGA dataset. Finally, the expression levels of hub genes were validated in cell lines by Western blotting (WB) and quantitative real-timePCR (qRT-PCR).ResultsA total of 178 differentially expressed MRGs were detected between the ICGA dataset and the TCGA dataset. We found that 17 MRGs were most significantly associated with OS by using the univariate Cox proportional hazards regression analysis in HCC. Then, the Lasso and multivariate Cox regression analyses were applied to construct the novel metabolism-relevant prognostic signature, which consisted of six MRGs. The prognostic value of this prognostic model was further successfully validated in the TCGA dataset. Further analysis indicated that this signature could be an independent prognostic indicator after adjusting to other clinical factors. Six MRGs (FLVCR1, MOGAT2, SLC5A11, RRM2, COX7B2, and SCN4A) showed high prognostic performance in predicting HCC outcomes. Finally, hub genes were chosen for validation and the expression of FLVCR1, SLC5A11, and RRM2 were significantly increased in human hepatocellular carcinoma cell lines when compared to normal human hepatic cell line, which were in agreement with the results of differential expression analysis.ConclusionsIn summary, our data provided evidence that the metabolism-based signature could serve as a reliable prognostic and predictive tool for overall survival in patients with HCC.
Prognostic value of immune-related genes and comparative analysis of immune cell infiltration in lung adenocarcinoma of different genders
Authors: Fan Tao , Li Chunxiang , He Jie
Published: November 2020

Background

Lung adenocarcinoma (LUAD) is one of the most important subtypes of lung cancer. Compared with male LUAD patients, female patients have a higher incidence, but better long-term survival rate, with unknown reasons. In this study, we aimed to explore the effect of gender on immune cell infiltration of LUAD tumor microenvironment (TME), and tried to clarify the reasons for the different clinical characteristics of male and female LUAD patients, by conducting a comparative analysis of the TME in female and male LUAD patients.
Methods

We calculated immune and stromal scores of LUAD patients samples from The Cancer Genome Atlas (TCGA) database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were conducted to reveal biological processes of intersecting genes. Cox regression analysis and protein-protein interaction (PPI) network analysis were conducted to screen immune-related prognostic genes in female (CCR2, LCP2, and PTPRC) and male (BTK and CCR2) patients. Kaplan-Meier survival analysis was used to evaluate prognostic value of identified genes. Mann-Whitney test was used to compare various indicators of male patients and female patients. The main result was subsequently validated in 420 cases from GSE72094.
Results

304 and 368 intersecting genes were identified in female and male patients respectively. The immune score is ranged from − 943.17 to 3229.35 among female patients with LUAD and from − 541.75 to 3441.78 among male patients with LUAD. The stromal score is ranged from − 1790.23 to 2097.27 among female patients and from − 1786.94 to 1722.70 among male patients. The immune and stromal scores of women were higher than those of men (P < 0.05). CCR2, LCP2 and PTPRC were identified as the most important immune-related prognostic genes in women. BTK and CCR2 were identified as the most important immune-related prognostic genes in men. Female patients had a higher proportion of memory B cells than that of male patients, while the percentage of T cells CD4 naïve and resting NK cells was lower in female patients (P < 0.05).
Conclusions

This study compared the differences in TIICs in the TME of male and female LUAD patients, and identified prognosis-related genes for patients of different genders.
Overexpressed WDR3 Induces the Activation of Hippo Pathway by Interacting with GATA4 in Pancreatic Cancer
Authors: Su Wenjie , Zhu Shikai , Chen Kai , Yang Hongji , Tian Mingwu , Fu Qiang , Shi Ganggang , Feng Shijian , Ren Dianyun , Jin Xin , Yang Chong
Published: November 2020

Background: WD repeat domain 3 (WDR3) is involved in a variety of cellular processes including gene regulation, cell cycle progression, signal transduction and apoptosis. However, the biological role of WDR3 in pancreatic cancer and the associated mechanism remains unclear. We seek to explore the immune-independent functions and relevant mechanism for WDR3 in pancreatic cancer.Methods: The GEPIA web tool was searched, and IHC assays were conducted to determine the mRNA and protein expression levels of WDR3 in pancreatic cancer patients. MTS, colony formation, and transwell assays were conducted to determine the biological role of WDR3 in human cancer. Western blot analysis, RT-qPCR, and immunohistochemistry were used to detect the expression of specific genes. An immunoprecipitation assay was used to explore protein-protein interactions.Results: Our study proved that overexpressed WDR3 was correlated with poor survival in pancreatic cancer and that WDR3 silencing significantly inhibited the proliferation, invasion and tumor growth of pancreatic cancer. Furthermore, WDR3 activated the Hippo signaling pathway by inducing yes association protein 1 (YAP1) expression, and the combination of WDR3 silencing and administration of the YAP1 inhibitor TED-347 had a synergistic inhibitory effect on the progression of pancreatic cancer. Finally, the upregulation of YAP1 expression induced by WDR3 was dependent on an interaction with GATA binding protein 4 (GATA4), the transcription factor of YAP1, in pancreatic cancer cells.Conclusions: We identified a novel mechanism by which WDR3 plays a critical role in promoting pancreatic cancer progression by activating the Hippo signaling pathway through an interaction with GATA4. Therefore, WDR3 is potentially a therapeutic target for pancreatic cancer treatment.
Gut Microbiome of the Amazon Master of the Grasses Harbors Unprecedented Enzymatic Strategies for Plant Glycans Breakdown
Authors: Cabral Lucelia , Persinoti Gabriela F , Paixao Douglas A , Martins Marcele P , Chinaglia Mariana , Domingues Mariane N , Morais Mariana AB , Sforca Mauricio L , Pirolla Renan A. S. , Generoso Wesley C , Santos Clelton A , Maciel Lucas F , terrapon Nicolas , Lombard Vincent , Henrissat Bernard , Murakami Mario
Published: November 2020

BackgroundPlant biomass is a promising feedstock to replace fossil-based products including fuels, chemicals and materials. However, the high resistance of plant biomass to either physicochemical or biological deconstruction has been hampering its broad industrial utilization and, consequently, the transition to a sustainable bioeconomy. The gut system from herbivores are formidable bioreactors in nature for lignocellulose breakdown and the diverse ecological niches where herbivores are found have led to the rise of a myriad of molecular strategies to cope with the sheer complexity of plant polysaccharides. This study illuminates how the unexplored microbiota of the largest living rodent, capybara, found in Pantanal wetlands and the Amazon basin, can efficiently depolymerize and utilize lignocellulosic biomass. ResultsHere, we have elucidated the gut microbial structure and composition of the semiaquatic herbivorous capybara through multi-omics approaches. Metabolic reconstruction of this microbiota showed that cellulose degradation is chiefly performed by Fibrobacter bacteria, whereas hemicelluloses and pectins are processed by a broad arsenal of Carbohydrate-Active enZymes (CAZymes) organized in polysaccharide utilization loci (PULs) identified in multiple metagenome-assembled genomes from the phylum Bacteroidetes. Furthermore, metabolomics analysis showed short chain fatty acids as major fermentation products, which are key markers of digestion performance of plant polysaccharides. Exploring the genomic dark matter of this gut microbial community, two novel CAZymes families were unveiled including a glycoside hydrolase family of β-galactosidases and a carbohydrate-binding module family involved in xylan binding that establishes an unprecedented three-dimensional fold among associated modules to CAZymes. ConclusionsOur results unveil how the capybara gut microbiota orchestrates the depolymerization and utilization of dietary plant polysaccharides, representing an untapped reservoir of new and intricate enzymatic strategies to overcome the recalcitrance of plant polysaccharides, a central challenge toward a circular and sustainable economy.
Vairimorpha Ceranae Alters Honey Bee Microbiota Composition and Sustain the Survival of Adult Honey Bees
Authors: Zhang Yakun , Su Meiling , Wang Lon , Huang Shaokang , Su Songkun , HUANG WEI-FONE
Published: November 2020

Background: Vairimorpha (Nosema) ceranae is the most common eukaryotic gut pathogen in honey bees, Apis mellifera. Infection is typically chronic but may result in mortality. Additional factors may be involved in mortality, including the honey bee gut microbiota. Previous studies of V. ceranae and gut microbiota identified positive associations between core bacteria and V. ceranae infection. These possibly synergistic or mutualistic associations are often disregarded because some core bacteria act as probiotic symbionts. Methods: To clarify the effects caused by the positive associations, we added isomaltooligosaccharide (IMO), a prebiotic also found in honey, to alter the interactions between V. ceranae and gut bacteria. Mortality and sugar consumption of the caged bees were monitored. Infection intensities and gut bacteria were examed after 12 days post inoculation, the plateau phase of infection. The gut bacteria were evaluated using both qPCR and 16S rDNA sequencing.Results: We confirmed that V. ceranae infections alone significantly enhance several core bacterial populations, including Bifidobacterium spp., Snodgrassella alvi, and Gilliamella apicola in the honey bee hindgut microbiota. Moreover, the qPCR results suggested that V. ceranae infected bees had significantly higher bacterial microbiota populations. In addition to the enhanced core bacteria, Commensalibacter and Bartonella were significantly increased in the fecal microbiome. Infected bees fed IMO had significantly higher V. ceranae spore counts but lower mortality; however, infected bees fed IMO did not have significant changes in gut bacteria populations compared to those fed only sucrose, but feeding IMO further reduced the fecal microbiome alpha-diversity. Conclusions: The microbiota alterations caused by infection were similar to the microbiota differences found between summer bees and winter bees, the latter of which have longer lifespans, and feeding IMO increased this similarity. Our results indicated that the interactions between gut bacteria and V. ceranae not only enhanced both the pathogen and bacteria populations but also sustained the host survival. This mutualistic interaction potentially enhances disease transmission and avoids social immune responses of the honey bee hosts.
Development of a Rapid, Efficient, Intelligent and Cost-Saving Tool to Diagnose Pasteurella Multocida by Using Whole Genome Sequence and Genotypes of Pasteurella Multocida From Different Hosts
Authors: Peng Zhong , Liu Junyang , Liang Wan , Wang Fei , Wang Li , Hua Lin , Wang Xiangru , Tan Chen , Zhou Rui , Chen Huanchun , Wilson Brenda A. , Wang Jia , Wu Bin
Published: November 2020

Background: Different typing systems including capsular genotyping, lipopolysaccharide (LPS) genotyping, multilocus sequence typing (MLST), and virulence genotyping based on the detection of different virulence factor-encoding gene (VFG) profiles have been applied to characterize Pasteurella multocida strains from different host species. However, these methods require much time and effort in laboratories. Particularly, relying on one of these methods is difficult to address the biology of P. multocida from host species. Recently, we found that assigning P. multocida strains according to the combination of their capsular, LPS, and MLST genotypes (marked as capsular genotype: LPS genotype: MLST genotype) could help address the biological characteristics of P. multocida circulation in multiple hosts. However, it is still lack of a rapid, efficient, intelligent and cost-saving tool to diagnose P. multocida according to this system. Results: We have developed an intelligent genotyping and host tropism prediction tool PmGT for P. multocida strains according to their whole genome sequences by using machine learning and web 2.0 technologies. By using this tool, the capsular genotypes, LPS genotypes, and MLST genotypes as well as the main VFGs of P. multocida isolates in different host species were determined based on whole genome sequences. The results revealed a closer association between the genotypes and pasteurellosis rather than between genotypes and host species. Finally, we also used PmGT to predict the host species of P. multocida strains with the same capsular: lipopolysaccharide: MLST genotypes. Conclusions: With the advent of high-quality, inexpensive DNA sequencing, this platform represents a more efficient and cost-saving tool for P. multocida diagnosis in both epidemiological studies and clinical settings.
Gut Microbiota Dysbiosis in High-Risk Individuals For Rheumatoid Arthritis Triggers Mucosal Immunity Perturbation and Promotes Arthritis in Mice
Authors: Tong Yanli , Tang Huairong , Li Yanhong , Su Lin Chong , Wu Yuxi , Bozec Aline , Zaiss Mario , Qing Pingying , Zhao Hua , Tan Chunyu , Bai Yunqiang , Zhang Qiuping , Chen Anping , Lin Hui , Zhao Yi , Liu Yi , Luo Yubin , Niu Haitao
Published: November 2020

The authors have requested that this preprint be removed from Research Square.
Anticoagulation Contributes to Antimicrobial Treatment of Lemierre Syndrome: A Case Report
Authors: Ge Jie , Zhou Peipei , Yang Yifei , Xu Tianshu , Yang Xu
Published: November 2020

Background: Lemierre syndrome (LS) is characterized by multisystemic infection beginning in the oropharynx, thrombophlebitis of the internal jugular vein and thrombotic extension to the periphery. It is difficult to establish an evidence-based guideline for management of the disease and the use of anticoagulation therapy remains controversial.Case presentation: A 61-year-old man suffered left neck swelling, odynophagia, and dyspnea. He underwent emergency surgery and received intravenous antimicrobial treatment. The primary infection was controlled on hospital day 5. However, he had a sudden increased WBC and decreased SpO on hospital day 6. Further thoracic CT angiography revealed an intraluminal filling defect in the pulmonary artery on hospital day 8. LS was diagnosed and then anticoagulation therapy was initiated. The WBC count maintained its peak value on hospital days 6-8 before anticoagulation therapy was initiated and decreased instantly after initiation.Conclusions: Our case supported the opinion that anticoagulation therapy contributed to the antiinflammatory effect achieved by the LS treatment.
National Surveillance of Stroke Quality of Care and Outcomes by Applying Post-Stratification Survey Weights on the Get With The Guidelines-Stroke Patient Registry
Authors: Ziaeian Boback , Xu Haolin , Matsouaka Roland A. , Xian Ying , Khan Yosef , Schwamm Lee S. , Smith Eric E. , Fonarow Gregg C.
Published: November 2020

Background: The U.S. lacks a stroke surveillance system. This study develops a method to transform an existing registry into a nationally representative database to evaluate acute ischemic stroke care quality.Methods: Two statistical approaches were used to develop post-stratification weights for the Get With The Guidelines-Stroke registry by anchoring population estimates to the National Inpatient Sample. Post-stratification survey weights were estimated using a raking procedure and Bayesian interpolation methods. Weighting methods were adjusted to limit the dispersion of weights and make reasonable epidemiologic estimates of patient characteristics, quality of hospital care, and clinical outcomes. Standardized differences in national estimates were reported between the two post-stratification methods for anchored and non-anchored patient characteristics to evaluate estimation quality. Primary measures evaluated were patient and hospital characteristics, stroke severity, vital and laboratory measures, disposition, and clinical outcomes at discharge. Results: A total of 1,388,296 acute ischemic strokes occurred between 2012 and 2014. Raking and Bayesian estimates of clinical data not recorded in administrative databases were estimated within 5% to 10% of the margins of expected values. Median weights for the raking method were 1.386 and the weights at the 99th percentile were 6.881 with a maximum weight of 30.775. Median Bayesian weights were 1.329 and the 99th percentile weights were 11.201 with a maximum weight of 515.689. Conclusions: Leveraging existing databases with patient registries to develop post-stratification weights is a reliable approach to estimate acute ischemic stroke epidemiology and monitoring for stroke quality of care nationally. These methods may be applied to other diseases or settings to better monitor population health.