bluuebunny/crossref_metadata_2025_split huggingface dataset:
Postoperative Radiotherapy Improved Survival in pT1-2N1 Oral and&nbsp;Oropharyngeal Cancer Without Adequate Neck Dissection ​
Authors: Yang Ching-Chieh , Kang Bor-Hwang , Liu Wen-Shan , Yin Chun-Hao , Lee Ching-Chih 
Published: September 2020

Abstract
Background: To assess the benefit of postoperative radiotherapy in patients with pT1-2N1M0 oral and oropharyngeal cancer by the quality of neck dissection.Methods: In the Surveillance, Epidemiology, and End Results database, pT1-2N1M0 oral and oropharyngeal cancer patients treated by primary tumor resection and neck dissection with or without radiotherapy were enrolled between 2004 and 2015. Univariate and multivariate analysis were used to explore the effect of adjuvant radiotherapy on 5-year overall survival (OS) and disease-specific survival(DSS).Results: Of the 1,765 patients identified, 1,108 (62.8%) had oral cancer, 1,141 (64.6%) were men, and 1,067 (60.5%) underwent adjuvant radiotherapy. After adjusting for confounding factors, postoperative radiotherapy reduced the adjusted hazard ratio (aHR) of 5-year OS to 0.64 (95% confidence interval[CI], 0.49-0.84) in those with <18 lymph nodes removed, but not in those with 19-24 lymph nodes removed (aHR, 0.78 ; 95% CI, 0.73-1.13), and in those with >25 lymph nodes removed (aHR, 0.96; 95% CI, 0.75-1.24). For 5-year DSS, similar effect was observed. The adjusted hazard ratio was 0.66 (95% confidence interval, 0.45-0.97) in those with <18 lymph nodes. The protective effect was not seen in those with 18-24 lymph nodes (aHR, 1.07; 95% CI 0.59-1.96), and in those with >25 lymph nodes (aHR, 1.12; 95% CI, 0.81-1.56). Sensitivity testing also showed a robust protective effect of postoperative radiotherapy in patients with <18 lymph nodes removed.Conclusion: Radiotherapy significantly improved survival in patients with pT1-2N1M0 oral and oropharyngeal cancer without adequate neck dissection.
Identification of Novel Alternative Splicing Events Associated with Tumorigenesis, Protein Modification, and Immune Microenvironment in Early-Onset Gastric Cancer
Authors: Zhang Jian , Goel Ajay , Zhu Lin 
Published: September 2020

Abstract
Background: Alternative splicing (AS), e.g. tandem alternative polyadenylation (TAPA), has emerged as major post-transcriptional modification events in human disease. However, the roles of AS and TAPA in early-onset gastric cancer (EOGC) have not been revealed.Methods: The global AS profiles of 80 EOGC patients were analyzed. The EOGC-specific AS events (ESASs) were identified in both EOGC and adjacent non-tumor tissues. Functional enrichment analysis, Splicing network, Alternative Polyadenylation (APA) core factor network, and cell abundancy analysis were performed. Furthermore, the landscapes of AS events in the varied subtypes of EOGC patients were evaluated. Results: Overall, 66,075 AS events and 267 ESASs were identified in EOGC. Furthermore, 4809 genes and 6152 gene isoforms were found to be aberrantly expressed in EOGC. The Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway analyses showed that significant pathway alterations might exist in these AS events, genes, and gene isoforms. Moreover, the Protein-protein interaction (PPI) network analysis revealed that UBC, NEK2, EPHB2, and DCTN1 genes were the hub genes in the AS events in EOGC. The immune cell infiltration analysis indicated a correlation between the AS events and the cancer immune microenvironment. The distribution of AS events in varied EOGC subtypes, protein phosphorylation and glycosylation was uneven. Conclusion: The study highlighted the vital roles of AS in EOGC, including modulating the specific protein modification and reshaping the cancer immune microenvironment, and yielded new insights into the diagnosis of EOGC as well as cancer treatment.
Synthesis of DOTA-Pyridine Chelates for 64Cu Coordination and Radiolabeling of αMSH Peptide
Authors: Yang Hua , Gao Feng , McNeil Brooke , Zhang Chengcheng , Zeisler Stefan , Kumlin Joel , Zeisler Jutta , Bénard François , Ramogida Caterina , Schaffer Paul , Yuan Zheliang 
Published: September 2020

Abstract
Background : 64Cu is one of the few radioisotopes that can be used for both imaging and therapy, enabling theranostics with identical chemical composition. Development of stable chelators is essential to harness the potential of this isotope, challenged by the presence of endogenous copper chelators. Pyridyl type chelators show good coordination ability with copper, prompting the present study of a series of chelates DOTA-xPy (x=1-4) that sequentially substitute carboxyl moieties with pyridyl moieties on a DOTA backbone. Results: We found that the presence of pyridyl groups significantly increases 64 Cu labeling yield, with DOTA-2Py, -3Py and -4Py quantitatively complexing 64 Cu at room temperature within 5 min (10 -4 M). [ 64 Cu]Cu-DOTA-xPy (x=2-4) exhibited good stability in human serum up to 24 hours. When challenged with 1000 eq. of NOTA, no transmetallation was observed for all three 64 Cu complexes. DOTA-xPy (x=1-3) were conjugated to a cyclized α-melanocyte-stimulating hormone (αMSH) peptide by using one of the pendant carboxyl groups as a bifunctional handle. [ 64 Cu]Cu-DOTA-xPy-αMSH retained good serum stability (>96% in 24 hours) and showed high binding affinity (Ki=2.1-3.7 nM) towards the melanocortin 1 receptor. Conclusion : DOTA-xPy (x=1-3) are promising chelators for 64 Cu. Further in vivo evaluation is necessary to assess the full potential of these chelators as a tool to enable further theranostic radiopharmaceutical development.
A Solitary Giant Neurofibroma of Inguinal Region——A Case Report
Authors: Zhou Haiying , Lu Hui 
Published: September 2020

Abstract
BackgroundNeurofibroma is a rare nerve sheath tumor of neuroectodermal origin, especially the huge and isolated neurofibroma located in the inguinal region. To our knowledge, no such case has previously been reported.Case presentationWe report a case of 34-year-old male patient with a 4-year history of progressive enlargement of the medial root mass in his left thigh with sitting and standing disorders along with pain. The tumor was completely removed by operation, and pathological diagnosis showed neurofibroma. There was no obvious neurologic defect after surgery, and no recurrence tendency was found in the follow-up of 2 years.ConclusionsFor a large solitary mass with slow growth and no malignant clinical manifestations for a long time, clinicians can not rule out the hypothetical diagnosis of neurofibroma, even though its growth site is very rare, such as this case of a huge tumor located in the groin. For neurogenic tumors, early operation should be performed, and the prognosis of patients after tumor resection is excellent.
Identification of MEG8-miR378d-SOBP Axis as a Novel Regulatory Network and Associated With Immune Infiltrates in Ovarian Carcinoma by Integrated Bioinformatics Analysis
Authors: Lei Jian , He Zhen-Yu , Wang Jun , Hu Min , Zhou Ping , Lian Chen-Lu , Hua Li , Wu San-Gang , Zhou Juan 
Published: September 2020

Abstract
BackgroundTo investigate the potential molecular mechanism of ovarian cancer (OC) evolution and immunological correlation using the integrated bioinformatics analysis.MethodsData from the Gene Expression Omnibus (GEO) was used to gain differentially expressed genes (DEGs). Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway analysis were completed by utilizing the Database for Annotation, Visualization, and Integrated Discovery (DAVID). After multiple validation via The Cancer Genome Atlas (TCGA), Gene Expression Profiling Interactive Analysis 2 (GEPIA 2), the Human Protein Atlas (HPA) and Kaplan-Meier (KM) plotter, immune logical relationships of the key gene SOBP were evaluated based on Tumor Immune Estimation Resource (TIMER), and Gene Set Enrichment Analysis (GSEA) software. Finally, the lncRNAs-miRNAs-mRNAs sub-network was predicted by starBase, Targetscan, miRBD, and LncBase, individually. Correlation of expression and prognosis for mRNAs, miRNAs and lncRNAs were confirmed by TCGA, GEPIA 2, starBase, and KM.ResultsA total of 192 shared DEGs were discovered from the four data sets, including 125 upregulated and 67 downregulated genes. Functional enrichment analysis presented that they were mainly enriched in cartilage development, pathway in PI3K-Akt signaling pathway. Lower expression of SOBP was the independent prognostic factor for inferior prognosis in OC patients. Intriguingly, downregulated SOBP enhanced the infiltration levels of B cells, CD8+ T cells, Macrophage, Neutrophil and Dendritic cells. GSEA also disclosed low SOBP showed significantly association with the activation of various immune-related pathways. Finally, we firstly reported that MEG8-miR378d-SOBP axis was linked to development and prognosis of ovarian cancer through regulating cytokines pathway.Conclusions Our study establishes a novel MEG8-miR378d-SOBP axis in the development and prognosis of OC, and the triple sub-network probably affects the progression of ovarian tumor by regulating cytokines pathway.
CT radiomics facilitates more accurate diagnosis of COVID-19 pneumonia: compared with CO-RADS
Authors: Liu Huanhuan , Ren Hua , Wu Zengbin , Xu He , Zhang Shuhai , Li Jinning , Hou Liang , Chi Runmin , Zheng Hui , Chen Yanhong , Duan Shaofeng , Li Huimin , Xie Zongyu , Wang Dengbin 
Published: September 2020

Abstract
Background
Limited data was available for rapid and accurate detection of COVID-19 using CT-based machine learning model. This study aimed to investigate the value of chest CT radiomics for diagnosing COVID-19 pneumonia compared with clinical model and COVID-19 reporting and data system (CO-RADS), and develop an open-source diagnostic tool with the constructed radiomics model.
Methods
This study enrolled 115 laboratory-confirmed COVID-19 and 435 non-COVID-19 pneunomia patients (training dataset, n = 379; validation dataset, n = 131; testing dataset, n = 40). Key radiomics features extracted from chest CT images were selected to build a radiomics signature using least absolute shrinkage and selection operator (LASSO) regression. Clinical and clinico-radiomics combined models were constructed. The combined model was further validated in the viral pneumonia cohort, and compared with performance of two radiologists with CO-RADS. The diagnostic performance was assessed by receiver operating characteristics curve (ROC) analysis, calibration curve, and decision curve analysis (DCA).
Results
Eight radiomics features and 5 clinical variables were selected to construct the combined radiomics model, which outperformed the clinical model in diagnosing COVID-19 pneumonia with an area under the ROC (AUC) of 0.98 and good calibration in the validation cohort. The combined model also performed better in distinguishing COVID-19 from other viral pneumonia with an AUC of 0.93 compared with 0.75 (P = 0.03) for clinical model, and 0.69 (P = 0.008) or 0.82 (P = 0.15) for two trained radiologists using CO-RADS. The sensitivity and specificity of the combined model can be achieved to 0.85 and 0.90. The DCA confirmed the clinical utility of the combined model. An easy-to-use open-source diagnostic tool was developed using the combined model.
Conclusions
The combined radiomics model outperformed clinical model and CO-RADS for diagnosing COVID-19 pneumonia, which can facilitate more rapid and accurate detection.
Determinants of Life Expectancy in Most Polluted Countries: Exploring the Effect of Environmental Degradation
Authors: Rahman Mafiz , Rana Rezwanul , Khanam Rasheda 
Published: September 2020

Abstract
Background: Better understanding of the determinants of national life expectancy is crucial for economic development, as healthy nation is a prerequisite for a wealthy nation. Many socioeconomic, nutritional, lifestyle, genetic and environmental factors can influence a nation’s health and longevity. Environmental degradation is one of the critical determinants of life expectancy, which is still under researched as the literature suggests Objectives: This study aims to investigate the determinants of life expectancy in 31 world’s most polluted countries with particular attention on environmental degradation using the World Bank annual data and British Petroleum data over the period of 18 years (2000-2017), Methods: The empirical investigation is based on the model of Preston Curve where panel corrected standard errors (PCSE) and feasible general least square (FGLS) estimates are employed to explore the long run effects. Pairwise Granger causality test is also used to have short run causality among the variables of interest taking into account the cross sectional dependence test and other essential diagnostic tests. Results: The results confirm the existence of Preston Curve, implying the positive effect of economic growth on the life expectancy. Environmental degradation is found as a threat while health expenditure, clean water and improved sanitation affect the life expectancy positively in the sample countries. The causality test results reveal one-way causality from carbon emissions to life expectancy and bidirectional causalities between drinking water and life expectancy, and sanitation and life expectancy. Conclusion: Our results reveal that environmental degradation is a threat for having the improved life expectancy in our sample countries. Based on the results of this study, we recommend that: (1) policy marker of these countries should adopt policies that will reduce carbon emissions and thus will improve public health and productivity; (2) environment-friendly technologies and resources, such as renewable energy, should be used in production process; (3) healthcare expenditure on national budget should be increased; and (4) clean drinking water and basic sanitation facilities must be ensured for all people.
Gender Specificity of Spousal Concordance in the Development of Chronic Disease Among Middle-Aged and Older Chinese Couples: A Prospective Dyadic Analysis
Authors: Liao Jing , Zhang Jing , Xie Jinzhao , Gu Jing 
Published: September 2020

Abstract
Background
This study aimed to explore the gender specificity of spousal concordance in the development of chronic diseases among middle-aged and older Chinese couples.
Methods
Data of 3420 couples (husbands: mean age, 57.5 years, SD = 8.5; wives: mean age, 55.6 years, SD = 8.0) were obtained from the China Health and Retirement Longitudinal Study (CHARLS). Multivariate logistic regression was used to analyze the incidence of chronic disease development over 4 years, conditional on the spousal baseline chronic disease status; and stepwise adjusting for the couples’ sociodemographic characteristics (i.e. age, education, retirement status and household income), and their individual lifestyle (i.e. smoking, drinking, exercise, social participation and (pre-)obesity) all measured at baseline.
Results
The incidence of chronic diseases after 4 years of follow-up was 34.5% in the husbands (727/2110) and 37.2% in the wives (882/2371). Taking the couples’ baseline sociodemographic and lifestyle covariates into account, husbands whose wife had a chronic disease at baseline showed an increased risk of developing a chronic disease over 4 years (ORadjusted=1.37, 95% CI:1.14,1.63), but this risk was not statistically-significant for wives (ORadjusted=1.16, 95%CI:0.97,1.40).
Conclusions
Our study identified gender specificity of spousal concordance in the development of chronic diseases among middle-aged and older- Chinese couples. This finding may contribute to the design of couple-based intervention for disease prevention and management for community-dwelling older adults.
Re-clustering and profiling of digestive system tumors according to microenvironment components
Authors: Wang Yongwei , Guo Sen , Chen Zhihong , Bai Bing , Wang Shuo , Gao Yaxian 
Published: September 2020

Abstract
BackgroundsImmunotherapy has become the most promising therapy in digestive system tumors besides conventional chemotherapy and radiotherapy. However, only a few patients could benefit from this kind of immunotherapy such as immune checkpoint blocking (ICB) treatment. It is urgent to screening and profiling the subgroups of patients with different responsiveness to ICB treatment.MethodsThis study carried out analysis on digestive system tumor patients from the Cancer Genome Atlas (TCGA) cohorts. The analyses were mainly performed by GraphPad Prism 7 and R language.ResultsWe have quantified the microenvironmental components of eight digestive system tumor patients in TCGA cohort and evaluated their clinical value. We re-clustered patients based on the characteristics of the microenvironment composition and divided these patients into 6 clusters. The difference between these 6 clusters were profiled including survival conditions, enriched biological process, genomic mutation and microenvironment traits. We also evaluated the response heterogeneity in ICB cohorts grouping by microenvironmental factors.ConclusionsCluster 3 was the most immune related cluster with high infiltration of non-tumor components and poor survival status, which was also exhibited an inhibitory immune status. High stromal score could represent cluster 3 and indicated a poor response in ICB cohorts.
YAP Manipulates Proliferation Via PTEN/AKT/mTOR-mediated Autophagy in Lung Adenocarcinomas
Authors: Xu Wei , Zhang Mingjiong , Li Yue , Wang Yu , Wang Kai , Chen Qiaoyu , Zhang Runjie , Song Weiwei , Huang Qiqing , Zhao Weihong , Wu Jianqing 
Published: September 2020

Abstract
Background: Autophagy is a double-edged sword during the initiation or progression of multiple tumors. Hippo pathway core-factor YAP has been proved to be involved in autophagy processes. The present study aimed to identify the mechanism underlying modulation of YAP via PTEN/AKT/mTOR-mediated autophagy in lung adenocarcinomas (LUAD).Methods: Data of LUAD chip GSE43458 was obtained from Gene Expression Omnibus (GEO). RT-qPCR and Western blot were used to assess YAP expression in LUAD cell lines. CCK-8 assay, flow cytometry, xenograft tumor model, immunochemistry and GFP-mRFP-LC3 fusion proteins were utilized to evaluate the effect of YAP on autophagy of LUAD cells in vitro and in vivo. Autophagy inhibitor and rescue experiments were carried out to elucidate the mechanism by which YAP manipulating autophagy in LUAD cells.Results: YAP significantly overexpressed in samples of LUAD patients and related to 5-year survival. YAP manipulates the proliferation and autophagy of A549 and H1299 LUAD cells. YAP induces activation of Akt/mTOR signaling pathway via suppressing PTEN in a Hippo-pathway-dependent manner. 3-Methyladenine impeded autophagy flux and promoted the proliferation in vitro and in vivo.Conclusions: Hippo pathway critical transcriptional coactivators YAP manipulates the proliferation of lung adenocarcinoma, which is regulated by PTEN/AKT/mTOR autophagic signaling.
Associations Between Continuous Glucose Monitoring-derived Metrics and Arterial Stiffness in Patients with Type 2 Diabetes
Authors: Wakasugi Satomi , Mita Tomoya , Katakami Naoto , Okada Yosuke , Yoshii Hidenori , Osonoi Takeshi , Kuribayashi Nobuichi , Taneda Yoshinobu , Kojima Yuichi , Gosho Masahiko , Shimomura Iichiro , Watada Hirotaka 
Published: September 2020

Abstract
Background Previous studies have suggested that high mean glucose levels and various glycemic abnormalities such as glucose fluctuation and hypoglycemia accelerate the progression of atherosclerosis in patients with type 2 diabetes. Although continuous glucose monitoring (CGM) that could evaluate such glycemic abnormalities has been rapidly adopted, the associations between CGM-derived metrics and arterial stiffness are not entirely clear. Methods This is an exploratory analysis of an ongoing prospective, multicenter, 5-year follow-up observational study. Study participants included 445 outpatients with type 2 diabetes who underwent CGM and brachial-ankle pulse wave velocity (baPWV) measurement at baseline. Associations between CGM-derived metrics and baPWV were investigated using multivariate regression models.Results In a linear regression model, all CGM–derived metrics were significantly associated with baPWV, but HbA1c was not. Some CGM–derived metrics related to intra-day glucose variability, hyperglycemia, and hypoglycemia remained significantly associated with baPWV after adjusting for possible atherosclerotic risk factors, including HbA1c. Based on baPWV ≥1,800 cm/s as indicative of high arterial stiffness, multivariate logistic regression found that some CGM-derived metrics related to intra-day glucose variability and hyperglycemia are significantly associated with high arterial stiffness even after adjusting for possible atherosclerotic risk factors, including HbA1c.Conclusions Multiple CGM-derived metrics are significantly associated with baPWV and high arterial stiffness in patients with type 2 diabetes who have no history of apparent cardiovascular disease. These metrics might be useful for identifying patients at high risk of developing cardiovascular disease.This study has been registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN000032325).
Ruxolitinib Might Be an Effective Hormone Reduction and Replacement Drug in Children With Secondary Hemophagocytic Lymphohistiocytosis&nbsp;
Authors: Chi Ying , Liu Rong , Zhou Zhixuan , Shi Xiaodong , Ding Yuchuan , Li Jianguo 
Published: September 2020

Abstract
Background: To analyze the effects of ruxolitinib on children with secondary hemophagocytic lymphohistiocytosis (HLH).Methods: Eleven pediatric patients diagnosed with HLH and treated with ruxolitinib (ruxolitinib group: group R) between November 2017 and August 2018 were retrospectively analyzed. Eleven age-matched pediatric patients with HLH undergoing conventional treatment (control group: group C) were also analyzed.Results: In group R, three patients who did not respond to conventional treatment (dexamethasone and etoposide) were treated with Ruxolitinib and their temperature decreased to normal levels. Four patients had normal temperature after conventional treatment, but they had severe organ involvement, including obvious yellowing of the skin, increased liver enzyme levels and neuropsychiatric symptoms, and they were all ameliorated with ruxolitinib treatment. Four patients were relieved with ruxolitinib therapy alone. In group C, the body temperature of eleven patients all decreased to normal levels after conventional treatment. The body temperature of group R patients decreased to normal levels more rapidly than that of group C patients. The hormone dosage in group R was significantly lower than that in group C. Both groups were followed up for 2–2.5 years. No obvious adverse drug reactions of ruxolitinib were observed during treatment and follow-up.Conclusion: Ruxolitinib might be an effective drug in controlling body temperature and reducing inflammation indicators. It might be a potential replacement for hormone therapy for HLH treatment in children, thereby reducing or avoiding hormone-related adverse reactions.