bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brain Connectivity and Behaviour in Post-Concussion Syndrome: A Scoping Review Protocol
Authors: Gumus Melisa , Santos Alexandra , Tartaglia Maria Carmela 
Published: May 2020

Abstract
Background

About 10-15% of patients experience persistent symptoms 3-months post-concussion, referred to as Post-Concussion Syndrome (PCS). There are no biomarkers for detecting this condition, but advanced neuroimaging tools such as Diffusion Tensor/Weighted Imaging (DTI/DWI) or functional MRI (fMRI) can detect subtle changes in the integrity of white matter tracts or brain activity, respectively.

Methods

This study protocol presents search strategies for a scoping review that provides an overview of the studies that assessed both alterations of structural and/or functional connectivity and cognitive/neuropsychiatric outcomes in PCS.

Discussion

A better understanding of the brain-behaviour relationships in PCS can lead to improved diagnosis of this condition. Scoping Review Protocol Registration: osf.io/sqt7d
The benefits of smoking cessation on survival in cancer patients by integrative analysis of multi-omics data
Authors: Yang Sheng , Liu Tong , Liang Geyu 
Published: May 2020

Abstract
Background: Few studies have examined the association between smoking cessation at the time of diagnosis and overall survival among cancer patients. We aimed to assess the benefits of quitting smoking on prognosis.Methods: We obtained cohorts of smoking-related cancer patients from the Cancer Genome Atlas (TCGA) database. Hazard ratios (HR) with 95% confidence intervals (CIs) were calculated to evaluate smoking behavior at cancer diagnosis (reformed smokers vs. current smokers) in association with overall survival using age and multivariate-adjusted Cox regressions analysis. Comprehensive analysis of multi-component data was carried out to determine the genetic and epigenetic landscape differences and their effects on the differential expression genes (DEGs) between reformed smokers and current smokers. The smoking signature was constructed using univariate Cox regression and LASSO-Cox regression model.Results: According to the multivariate-adjusted Cox regressions analysis, quitting smoking was the independent protective factor for overall survival in lung squamous cell carcinoma (LUSC) (HR=0.67, 95%CI=0.48-0.94). A total of 85 key DEGs were found to be affected by different modes of genetic and epigenetic regulation, which might represent key drivers in smokers. At last, we provided the smoking signature which could predict prognosis with high power (HR=1.70, 95% CI=1.19-2.43, AUC= 0.65, 0.67 and 0.70 for 2, 3 and 5-year survival, respectively). The smoking signature was also applicable in other smoking-related cancers, including bladder urothelial carcinoma (HR=1.70, 95% CI=1.01-2.88), cervical carcinoma (HR=5.69, 95% CI=1.37-23.69), head and neck squamous cell carcinoma (HR=1.97, 95% CI=1.41-2.76), lung adenocarcinoma (HR=1.73, 95% CI=1.16-2.57), and pancreatic adenocarcinoma (HR=4.28, 95% CI=1.47-12.47).Conclusions: The present study demonstrated that quitting smoking at diagnosis decreased risk of death in cancer patients. We also provided the smoking signature to evaluate the true effect of smoking, suggesting that smoking cessation could be a part of cancer treatment to improve the survival rate of cancer patients.
Overexpression of sperm associated antigen 5 promotes cell growth, metastasis, and adriamycin resistance in esophageal squamous cell carcinoma via activating PI3K/AKT signaling pathway
Authors: Yan Yan , Zhang Fang bin , Yi Qiao li , Zhou Kun 
Published: May 2020

Abstract
Background: Esophageal cancer (ESCC) is one of the most common malignant tumors in the digestive system. This study aims to explore the effects of sperm associated antigen 5 (SPAG5) on cell growth, metastasis, and azithromycin resistance in esophagus cancer and its molecular mechanism.Methods: The DEGs were obtained from GSE92396, GSE17351, and GSE9982 datasets about ESCC. The PPI network was constructed using the STRING database and was visualized using Cytoscape software. The cytohubba plug-in of Cytoscape software was used to identify the hub genes of the PPI network. The DEGs were used to perform GO and KEGG pathway enrichment analysis using the DAVID database. Statistical analysis was performed to test the clinical and prognostic significance of SPAG5. Cell viability, proliferation, apoptosis, migration, and invasion were detected using CCK-8, colony formation, flow cytometry, transwell and scratch-wound assays. The expression of related genes was detected by qRT-PCR, western blot and IHC assays. The oncogenicity of SPAG5 in ESCC cells was determined using the nude mouse transplantation tumor experiment.Results: Ninety-three overlapping genes from the DEGs were used to construct the PPI network, and mainly enriched in BP, CC, and MF terms. COX regression analysis of OS showed that SPAG5 expression and pN category were correlated with OS. Univariate and multivariate analyses showed that SPAG5 was an independent prognostic factor for OS in ESCC. The ROC curve analysis showed the AUC of SPAG5 was 0.74. Multiple logistic regression showed that SPAG5 were subsequently identified as an independent risk factor associated with OS. SPAG5 overexpression was detected in ESCC tissues and cell lines, and improved cell proliferation. SPAG5 knockdown reduced cell growth and metastasis and promoted its apoptosis. The functions of SPAG5 overexpression promoting ESCC cell growth and affecting cleaved caspase-3, Ki67, VEGF, and MMP-2/-9 expression were reversed by PI3K/AKT inhibitor. SPAG5 overexpression enhanced resistance to ADM in EC9706 and Eca109 cells and it was closely related to the activation of PI3K/AKT signaling pathway.Conclusion: The overexpression of SPAG5 was an independent good prognostic factor and promoted the proliferation, invasion, migration, and ADM resistance, and inhibited the apoptosis via activating PI3K/AKT signaling pathway in ESCC.
Drug-drug interactions associated with adverse clinical outcomes and abnormal laboratory findings in patients with malaria
Authors: Noor Sidra , Ismail Mohammad , Khadim Faiza 
Published: May 2020

Abstract
Background: Hospitalized patients with malaria often present with comorbidities or associated complications for which a variety of drugs are prescribed. Multiple drug therapy often leads to drug-drug interactions (DDIs). Therefore, we investigated the prevalence, levels, risk factors, clinical relevance, and monitoring parameters/management guidelines of potential DDIs (pDDIs) among inpatients with malaria.
Methods: A retrospective cohort study was carried out at multiple hospital settings. A total of 398 patients’ profiles were evaluated for pDDIs using the Micromedex Drug-Reax ® . Odds ratios were calculated to identify the strength of association between presence of DDIs and potential risk factors via logistic regression analysis. Further, the clinical relevance of frequent pDDIs was investigated.
Results: Of 398 patients, pDDIs were observed in 37.2% patients, while major-pDDIs in 19.3% patients. Total 325 interaction were found, of which 45.5% were of major- and 34.5% moderate-severity. Patients with the most common pDDIs were found with signs/symptoms and abnormalities in laboratory findings representing nephrotoxicity, hepatotoxicity, QT interval prolongation, and reduced therapeutic efficacy . The adverse events were more common in patients prescribed with the higher doses of interacting drugs. Multivariate regression analysis showed statistically significant association of pDDIs with 5-6 prescribed medicines (p=0.01), >6 prescribed medicines (p<0.001), >5 days of hospital stay (p=0.03), and diabetes mellitus (p=0.04).
Conclusions: PDDIs are commonly observed in patients with malaria. Healthcare professional’s knowledge about the most common pDDIs could help in preventing pDDIs and their associated negative effects. Pertinent clinical parameters, such as laboratory findings and signs/symptoms need to be checked, particularly in patients with polypharmacy, longer hospital stay, and diabetes mellitus.
Healthcare disparities in cardio oncology: patients receive same level of surveillance regardless of race at a safety net hospital
Authors: Chen Crystal , Dalsania Raj , Hamad Eman A 
Published: May 2020

Abstract
Background: Cardiotoxicity remains a dreaded complication for patients undergoing chemotherapy with human epidermal growth factor (HER)-2 receptor antagonists and anthracyclines. Though many studies have looked at racial disparities in heart failure patients, minimal data is present for the cardio-oncology population. Methods: We queried the echocardiogram database at a safety net hospital, defined by a high proportion of patients with Medicaid or no insurance, for patients who received HER2 receptor antagonists and/or anthracyclines from January 2016 to December 2018. Patient demographics, clinical characteristics, and treatment outcomes were collected. Based on US census data in 2019, home ZIP codes were used to group patients into quartiles based on median annual household income. The primary end point studied was referral rate to cardiology for patients undergoing chemotherapy. Results: We identified 151 patients who had echocardiograms and also underwent treatment with HER2 receptor antagonists and/or anthracyclines, of which 70 (46.4%) were referred to the cardio-oncology program at our institution. Basic demographics were similar, but white patients were more likely to live in ZIP codes with higher income quartiles (p<0.00001). Comparing between racial groups, there was no statistical difference in the percentage of patients that had a reduction in ejection fraction (EF) (p=0.78). There was no statistical difference between racial groups in the number of cardiology or oncology appointments attended, number of appointments cancelled, or average number of echocardiograms received. A logistic regression model was created using race, age, gender, insurance, income quartile by home ZIP code, cardiomyopathy risk factors (hypertension, hyperlipidemia, diabetes mellitus, smoking, family history, age >65), cancer type, cancer stage, and chemotherapy. This model found that there was an increased referral rate among patients from higher income quartiles (p=0.004), patients with a history of hypertension (p=0.0001), and patients with breast cancer (p=0.04). Conclusions: The results of this study suggest that patients of our cardio-oncology population at a safety net hospital receive the same level of surveillance and treatment, and develop drop in ejection fraction at similar rates regardless of their race. However, patients that reside in ZIP codes associated with higher income quartiles do trend towards increased referrals.
Dexmedetomidine alleviates pulmonary edema through epithelial sodium channel (ENaC) via the PI3K/Akt/Nedd4-2 pathway in LPS- induced acute lung injury
Authors: Jiang Yuanxu , Xu jing , Huang Qiang , Yang Wenjie , Xia Mingzhu , Zhang Xueping 
Published: May 2020

Abstract
Background: Pulmonary edema is a hallmark in acute lung injury(ALI). Researchers have also revealed that dexmedetomidine (Dex) alleviate pulmonary edema following ALI, but the mechanism is unclear.The alveolar epithelial sodium channel (ENaC)-mediated alveolar fluid clearance (AFC) plays an important role in reducing pulmonary edema. In this study, we attempted to investigate the effect of Dex on ENaC in modulating AFC and its mechanism.
Methods: LipopolysacchAride (LPS) was used to induce ALI in rat and alveolar epithelial cell injury in A549 cell. The rats were randomly allotted into the following groups: control, LPS, LPS+Dex, LPS+Dex+LY294002 (n = 6 per group). In vitro, cells (1×10 6 cells/cm 2 ) were subcultured in six-well plates, then cells were allotted into the following groups: control, LPS, LPS+Dex, LPS+Dex+LY294002.
Results: In vivo, Dex markedly reduced pulmonary edema induced by LPS through promoting AFC.Moreover, Dex prevented LPS-induced downregulation of α-, β- and γ-ENaC expression. In A549 cells stimulated with LPS, Dex attanuated LPS-mediated cell injury and the downregulation of α-, β- and γ-ENaC expression. Howere, all of which was blocked by PI3K inhibitor LY294002,suggesting that the protective role of Dex is PI3K dependent. Additionaly, Dex increases the expression of phosphorylated Akt and reduces the expression of Need4-2 in vivo and vitro, while the LY294002 reverses the effect of Dex, indicating that Dex activates the PI3K/Akt/Nedd4-2 signaling pathway.
C onclusio ns: Dex alleviates pulmonary edema by promoting AFC, and the mechanism is partly related to up-regulation of ENaC expression via PI3K/Akt/Nedd4-2 signaling pathway.
Teladorsagia Circumcincta Beta Tubulin: The Presence of the E198L Polymorphism on Its Own is Associated with Benzimidazole Resistance
Authors: Valladares María Martínez , Valderas-García Elora , Gandasegui Javier , Skuce Philip , Morrison Alison , de Agüero Verónica Castilla Gómez , Cambra-Pellejà Maria , Balaña-Fouce Rafael , Vázquez Francisco A. Rojo 
Published: May 2020

Abstract
Background: Benzimidazole resistance is associated with isotype-1 β-tubulin gene F200Y, E198A and F167Y SNPs. In this study, the recently described polymorphism E198L was reported and analysed in Teladorsagia circumcincta.Methods: The benzimidazole phenotypic resistance was measured by the Faecal Egg Count Reduction Test (FECRT) and the Egg Hatch Test (EHT) using a discriminating dose in 39 sheep flocks. Around 1,000 larvae collected before and after treatment were used for DNA extraction. The resistant species identified in all flocks was T. circumcincta . The resistance alleles frequencies were measured for F200Y and E198A. A 371 bp fragment of the isotype-1 β-tubulin gene was analysed, including the three codons of interest, and a new pyrosequencing assay was designed for testing E198L. Results: The percentage of resistant flocks was 32% by FECRT or 26% by EHT, however F200Y and E198A SNPs were absent in T. circumcincta . The amplification a 371 bp fragment confirmed the absence of F167Y and F200Y in 6 resistant flocks. Regarding codon 198, all samples after treatment carried a leucine (CTA). A pyrosequencing assay analysed the allele frequencies for the first two bases at codon 198 independently, G/C and A/T. The correlation between C and T frequencies was almost 1 (r = 0.929; p = 0.000) and the mean value of both was calculated to measure the leucine frequency; this value ranged between 10.4 and 80.7% before treatment, and from 82.3 to 92.8% after treatment. Very high and similar correlations were reported between the genotypic variables (C frequency, T frequency or mean of both frequencies) and phenotypic resistance (r > 0.720; p = 0.000), although negatively associated with the FECRT and positively with the EHT. According to multivariate linear regression analysis, the T frequency was the most significant variable influencing the phenotypic resistance (FECRT or EHT; p = 0.000). In the EHT, 67.1% of the phenotypic variability is associated with the T frequency but in the FECRT only 33.4%; therefore, the EHT using a DD seems to detect the genotypic resistance more accurately than the FECRT. Conclusions: The E198L polymorphism can confer BZ resistance on its own in T. circumcincta .
Integrated analysis of the functions of RNA binding proteins in clear cell renal cell carcinoma
Authors: Hua Xiaoliang , Chen Juan , Ge Shengdong , Xiao Haibing , Zhang Li , Liang Chaozhao 
Published: May 2020

Abstract
Background: RNA binding proteins (RBPs) dysregulation is involved in the process es of various tumor. However, the roles of RBPs in clear cell renal cell carcinoma (ccRCC) remain poorly understand. Systematic exploration of the roles of RBPs in ccRCC may provide new insights for the treatments of ccRCC. Methods: Expression data of RBPs was obtained from The Cancer Genome Atlas database. The roles of RBPs in ccRCC were systematically investigated using consensus clustering methods. Differentially expressed RBPs between normal and tumor tissues were obtained. Protein-protein interaction (PPI) network was constructed using “STRING” software. The expression levels of hub genes were validated in The Human Protein Atlas (HPA) database and receiver operating characteristic (ROC) curves were used to evaluate diagnostic value . Univariate and Lasso Cox regression and Kaplan–Meier curves were used to screen the most useful prognostic genes. Multivariate Cox regression was performed to construct a risk score model. The efficiency of the model was evaluated using time-dependent ROC and Kaplan–Meier curves, and validated in E-MTAB-3267 set. Results: Two clusters were identified based on the expression similarity of RBPs, and the cluster 2 was closely correlated with the malignancy of ccRCC. Several oncogenic pathways, including epithelial mesenchymal transition, G2M checkpoint, KRAS signaling and IL6 JAK STAT3 signaling were enriched in cluster 2. In addition, we obtained 115 differently expressed RBPs in ccRCC, comprising 71 up-regulated and 44 down-regulated ones. Ten hub RBPs with good diagnostic value were obtained from PPI network and validated in HPA database. Ten RBPs were identified as survival-related genes and used to construct a risk score model. The model could be used to stratify patients with different prognosis. We found high-risk patients tended to be advanced stage, high grade, high pathological T staging and could be an independent risk factor for overall survival of ccRCC patients. Conclusions: We identified ten RBPs with diagnostic value, which might be the potential diagnostic biomarkers for ccRCC. A risk score model was established to stratify patients and could be used as a complementation for clinical factors to guide clinical practice in the future.
The Natural Course of Hereditary Angioedema in a Chinese Cohort
Authors: Cao Yang , Liu Shuang , Zhi Yuxiang 
Published: May 2020

Abstract
Background: Hereditary angioedema (HAE) is a rare disease with potential life-threatening risks. Until now, few studies have focused on the natural course of HAE, which is essential for practitioners and patients to predict disease progression and avoid possible risk factors. Objectives: Describe the natural course of HAE and explore possible risk factors, providing new clues for guiding clinical prevention and treatment. Methods: A web-based survey was conducted in 103 Chinese patients with type 1 HAE. Disease progression under therapy-free conditions was collected at different age stages. The demographic characteristics, lifestyles, disease severity and family history were also provided by each participant. Results: Among 103 patients, 14 (13.6%) had their first HAE attack before ten years old and 51 (49.5%) between 10 and 19. The disease worsened in 83.3% of the patients in their twenties. The proportion of patients with symptoms alleviated increased after the age of 30 years old, but the disease maintained relatively severe in most cases before 50. The participants also reported 233 members shared similar symptoms of angioedema in their family and 30 had died of laryngeal edema with the median death age of 46 years old. The disease severity was not observed to be affected significantly by gender, BMI, alcohol or smoking. Conclusions: We summarized HAE progression patterns in therapy-free conditions, showing the natural course of disease development along with aging. Long-term prophylaxis and symptomatic treatment are recommended for all HAE patients, especially young and middle-aged and might be adjusted depending on the disease progression.
Exploring the happiness and sense of purpose associated with older peoples' activities using ecological momentary analysis: an observational study
Authors: Hancock Karen Elizabeth , Downward Paul , Sherar Lauren 
Published: May 2020

Abstract
Background Older people have more leisure time, but many are physically inactive. Momentary feelings of pleasure or happiness and sense of purpose can be sources of intrinsic motivation. This study’s objective was to investigate how the type (sedentary, active) and context (social and environmental) of older peoples’ activities relate to momentary feelings of happiness and purpose. MethodsDetails of activities, contexts and feelings of retired or semi-retired adults (n=67, aged 50-78y) were captured over 7 days using ecological momentary assessment (EMA) via a smart phone app. Participants were prompted on their smart phone six times at random per day, resulting in 2,065 valid prompts. They wore an Actigraph accelerometer on the waist for 7 days to measure physical activity. Happiness and sense of purpose outcome variables were regressed on activities, context and potential confounding variables (e.g. age, gender, physical activity). Regression standard errors were clustered on participants to account for the hierarchically structured data. Interactions between activities and contexts were explored.ResultsParticipants were highly active: 98.5% met physical activity guidelines. Sedentary activities were negatively associated with sense of purpose, especially when indoors. Social sedentary activities (e.g. visiting friends and family) were, however, positively associated with feelings of happiness. Active, social outdoor activities were positively associated with both outcomes. Less sedentary participants experienced higher happiness and sense of purpose during all their activities: each 1 percentage point increase in percentage time sedentary was associated with a reduction of 2.78-points on the happiness scale and 3.34 on the purpose scale (p <0.05). Conclusions Context is important for happiness and purpose, with social and outdoor activities likely to have the widest appeal for older adults. The study needs to be replicated in larger and more representative samples of older adults.
Pathogenic Characteristics of Sputum and Bronchoalveolar Lavage Fluid Samples from Patients with Lower Respiratory Tract Infection
Authors: peng zheng , zhou jin'an , tian lei 
Published: May 2020

Abstract
Background Lower respiratory tract infections(LRIs)were a very common disease, no matter in community acquired infection or hospital acquired infection. Sputum and bronchoalveolar lavage fluid (BALF) were the most important specimens of LRIs. The choice of antibiotics for the treatment of LRIs usually depended on the results of antimicrobial sensitivity of bacteria isolated from sputum and BALF. However, it was rarely reported to compare the pathogens isolated from sputum and BALF and the difference of antimicrobial sensitivity.Methods A retrospective study was conducted to analyze the differences between sputum and BALF samples in pathogen isolation and antimicrobial sensitivity in our hospital.Results In our hospital during 2013–2015 year, the quality evaluation of sputum samples was not conducted before sputum culture, but in 2016–2018 year, the quality evaluation of sputum samples was conducted firstly and only qualified sputum samples were cultured. The results of pathogen culture showed that Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, Staphylococcus aureus and Haemophilus influenzae were the top five pathogens isolated from sputum and BALF. Antimicrobial susceptibility test showed for these five pathogens the susceptibility rates of BALF isolates to most antibiotics were higher than those isolated from sputum. The sensitivity of A. baumannii to common antibiotics was less than 50%. In particular, the detection rate of carbapenem resistant A. baumannii (CR-ABA) in sputum and BALF was higher than 80%. The sensitivity of P. aeruginosa to antibiotics other than ticarcillin/clavulanic acid and minocycline were higher than 50%. The detection rate of carbapenem resistant Klebsiella pneumoniae (CR-KPN) was 10% − 20% in 2013–2015 and 30% − 50% in 2016–2018. The detection rate of MRSA in sputum was higher than 80%, while that in BALF was 65% − 70%. The separation rate of beta-lactamase-negative ampicillin-resistant H. influenzae (BLNAR) was between 0–6%.Conclusions The sensitivity of strains isolated from BALF to commonly used antibiotics was generally higher than that from sputum. MRSA, CR-KPN and A. baumannii were the focus of infection control for LRIs.