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2. Low-carbon optimal operation strategy of multi-park integrated energy system considering multi-energy sharing trading mechanism and asymmetric Nash bargaining

Author

Wen-wei Zhang, Wei-qing Wang, Xiao-chao Fan, Shan He, Hai-yun Wang, Jia-hui Wu, and Rui-jing Shi

Subjects
Asymmetric Nash bargaining, Improved ladder-type carbon trading mechanism, Multi-park integrated energy system, Multi-energy sharing trading mechanism, The interaction between supply and demand, Electrical engineering. Electronics. Nuclear engineering, TK1-9971
Abstract

In the current energy transactions of multi-park integrated energy system (M-PIES), aiming at the problems that the interaction between the supply side and the demand side is not fully considered, the sharing potential of multiple energy sources is not fully tapped, the benefit distribution mechanism considering the contribution of the load aggregator (LA) is lacking, and with the all-round development of the carbon trading market (CTM), the existing ladder-type carbon trading (LCT) mechanism has insufficient capacity to limit CO2 discharges of M-PIES, etc., this paper puts forward a low-carbon optimal operation strategy of M-PIES considering the multi-energy sharing trading mechanism (MSTM) and asymmetric Nash bargaining (ANB). Firstly, the interaction between supply and demand (IS&D) is fully considered, and the benefit maximization model of PIES operator-LA multi-agent alliance considering MSTM and improved ladder-type carbon trading mechanism (ILCTM) is established by using Nash negotiation theory (NNT). Then, according to the different bargaining capabilities of each agent, a profit distribution model based on ANB is proposed, and it is solved by alternating direction method of multipliers (ADMM). Finally, through the comparison of different cases, it is proved that the proposed method can further reduce CO2 discharges of M-PIES, improve the benefits of each agent and alliance, and realize the fair and reasonable distribution of energy sharing (ES) benefits.

Published
2023
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3. CD20highCD138low tumor-infiltrating lymphocytes predominantly related to cytokine‒cytokine receptor interactions are associated with favorable outcomes in neuroblastoma patients

Author

Liang-Jun Qin, Hui Xu, Li-Ping Li, Shu-Hua Li, Shuo-Yu Xu, Kai Chen, Tianyou Yang, Feng-Hua Wang, Liandong Zuo, Liang Zeng, and Hai-Yun Wang

Subjects
Neuroblastoma, B-cell CD20, Plasma cell CD138, Prognosis, cytokine‒cytokine receptor interactions, Science (General), Q1-390, Social sciences (General), H1-99
Abstract

Recent advances have revealed that the role of the immune system is prominent in the antitumor response. In the present study, it is aimed to provide an expression profile of tumor-infiltrating lymphocytes (TILs), including mature B cells, plasma cells, and their clinical relevance in neuroblastoma. The expression of CD20 and CD138 was analyzed in the Cangelosi786 dataset (n = 769) as a training dataset and in our cohort (n = 120) as a validation cohort. CD20 high expression was positively associated with favorable overall survival (OS) and event-free survival (EFS) (OS: P

Published
2024
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4. Clinical significance of genetic profiling based on different anatomic sites in patients with mucosal melanoma who received or did not receive immune checkpoint inhibitors

Author

Hai-Yun Wang, Ye Liu, Ling Deng, Kuntai Jiang, Xin-Hua Yang, Xiao-Yan Wu, Kai-Hua Guo, and Fang Wang

Subjects
Mucosal melanoma, Clinical significance, Primary site, Prognosis, Genetic alterations, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282, Cytology, QH573-671
Abstract

Abstract Background To date, data on the efficacy of targeted therapies for mucosal melanoma (MM) are limited. In this study, we analyzed genetic alterations according to the primary site of origin, which could provide clues for targeted therapy for MM. Methods We conducted a retrospective cohort study of 112 patients with MM. Targeted sequencing was performed to analyze genetic aberrations. Kaplan–Meier analysis was conducted with the log-rank test to compare the significance among subgroups. Results In total, 112 patients with MM were included according to the anatomic sites: 38 (33.9%) in the head and neck, 22 (19.6%) in the genitourinary tract, 21 (18.8%) in the anorectum, 19 (17.0%) in the esophagus, 10 (8.9%) in the uvea, and 2 (1.8%) in the small bowel. The most significantly mutated genes included BRAF (17%), KIT (15%), RAS (15%), TP53 (13%), NF1 (12%), SF3B1 (11%), GNA11 (7%), GNAQ (5%), and FBXW7 (4%). A large number of chromosomal structural variants was found. The anatomic sites of esophagus and small bowel were independent risk factors for progression-free survival (PFS, hazard ratio [HR] 4.78, 95% confidence interval [CI] 2.42–9.45, P

Published
2023
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8. Cross-cohort analysis identified an immune checkpoint-based signature to predict the clinical outcomes of neuroblastoma

Author

Hui Xu, Lei Miao, Na Liu, Fang Wang, Feng-Hua Wang, Ran Wang, Sha Fu, Ling Deng, Ying-Qing Li, Shuo-Yu Xu, Kai Chen, Liang Zeng, Le Li, Shu-Hua Li, Liang-Jun Qin, and Hai-Yun Wang

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Background Neuroblastoma (NB) places a substantial health burden on families worldwide. This study aimed to develop an immune checkpoint-based signature (ICS) based on the expression of immune checkpoints to better assess patient survival risk and potentially guide patient selection for immunotherapy of NB.Methods Immunohistochemistry integrated with digital pathology was used to determine the expression levels of 9 immune checkpoints in 212 tumor tissues used as the discovery set. The GSE85047 dataset (n=272) was used as a validation set in this study. In the discovery set, the ICS was constructed using a random forest algorithm and confirmed in the validation set to predict overall survival (OS) and event-free survival (EFS). Kaplan-Meier curves with a log-rank test were drawn to compare the survival differences. A receiver operating characteristic (ROC) curve was applied to calculate the area under the curve (AUC).Results Seven immune checkpoints, including PD-L1, B7-H3, IDO1, VISTA, T-cell immunoglobulin and mucin domain containing-3 (TIM-3), inducible costimulatory molecule (ICOS) and costimulatory molecule 40 (OX40), were identified as abnormally expressed in NB in the discovery set. OX40, B7-H3, ICOS and TIM-3 were eventually selected for the ICS model in the discovery set, and 89 patients with high risk had an inferior OS (HR 15.91, 95% CI 8.87 to 28.55, p

Published
2023
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11. Phosphoserine phosphatase as a prognostic biomarker in patients with gastric cancer and its potential association with immune cells

Author

Ma-Yan Huang, Xiao-Yun Liu, Qiong Shao, Xu Zhang, Lei Miao, Xiao-Yan Wu, Yu-Xia Xu, Fang Wang, Hai-Yun Wang, Liang Zeng, and Ling Deng

Subjects
PSPH, Metabolic genes, Poor prognosis, Immune score, Gastric cancer, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Abstract Background Because of dismal prognosis in gastric cancer, identifying relevant prognostic factors is necessary. Phosphoserine phosphatase (PSPH) exhibits different expression patterns in many cancers and has been reported to affect the prognosis of patients with cancer. In this study, we examined the prognostic role of metabolic gene PSPH in gastric cancer based on the TCGA dataset and our hospital–based cohort cases. Methods We collected and analysed RNA-seq data of Pan-cancer and gastric cancer in the TCGA dataset and PSPH expression data obtained from immunohistochemical analysis of 243 patients with gastric cancer from Sun Yat-sen University cancer center. Further, Kaplan–Meier survival analysis and Cox analysis were used to assess the effect of PSPH on prognosis. The ESTIMATE and Cibersort algorithms were used to elucidate the relationship between PSPH and the abundance of immune cells using the TCGA dataset. Results We observed that PSPH expression displayed considerably high in gastric cancer and it was significantly associated with inferior prognosis (P = 0.043). Surprisingly, there was a significant relationship between lower immune scores and high expression of PSPH (P

Published
2022
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12. Risk model based on minichromosome maintenance 2 using objective assessment for predicting survival of neuroblastoma

Author

Liang Zeng, Xiao-Yun Liu, Lei Miao, Kai Chen, Hui Xu, Liang-Jun Qin, Meng Li, Kai Liu, Jiahao Feng, and Hai-Yun Wang

Subjects
Clinical finding, Association analysis, Cancer, Science
Abstract

Summary: Aberrant minichromosome maintenance (MCM) expression is associated with tumorigenesis. Here, we performed immunohistochemistry integrated with digital pathology to identify MCM2/5/6 expression in 130 neuroblastoma patients. A risk score was established using least absolute shrinkage and selection operator that predicts outcomes according to MCM2 expression, age, and the International Neuroblastoma Staging System in the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) dataset (n = 150), where the patients with high risk had significantly worse prognosis that was validated in a hospital-based cohort (n = 130). After multivariable adjustment, the risk model remained an independent factor for survival in the TARGET cohort (overall survival [OS]: hazard ratio [HR] 2.3, 95% confidence interval [CI] 1.4–4.0; event-free survival [EFS]: HR 1.8, 95% CI 1.1–3.1) and for OS in the validation cohort (HR 8.3, 95% CI 1.6–44.5). The ESTIMATE indicates that the risk model is negatively correlated with low ESTIMATE and stromal scores. These findings show the additive nature of this score, fostering its future implementation with new prognostic variables.

Published
2023
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13. PTBP2-Mediated Alternative Splicing of IRF9 Controls Tumor-Associated Monocyte/Macrophage Chemotaxis and Repolarization in Neuroblastoma Progression

Author

Jue Tang, Jing He, Huiqin Guo, Huiran Lin, Meng Li, Tianyou Yang, Hai-Yun Wang, Di Li, Jiabin Liu, Le Li, Huimin Xia, Zhenjian Zhuo, and Lei Miao

Subjects
Science
Abstract

The recurrence and metastasis of children with mediastinal neuroblastoma (NB) are also occurred after surgery, chemotherapy, or radiotherapy. Strategies targeting the tumor microenvironment have been reported to improve survival; however, thorough investigations of monocytes and tumor-associated macrophages (Mϕs) with specialized functions in NB are still lacking. Our data first demonstrated polypyrimidine tract binding protein 2 (PTBP2) as a possible identifier in patients with mediastinal NB screened by proteomic profiling and that PTBP2 predicted good outcomes. Functional studies revealed that PTBP2 in NB cells induced the chemotactic activity and repolarization of tumor-associated monocytes and Mϕs, which, in turn, inhibited NB growth and dissemination. Mechanistically, PTBP2 prevents interferon regulatory factor 9 alternative splicing and upregulates signal transducers and activators of transcription 1 to stimulate C-C motif chemokine ligand 5 (CCL5) and interferon-stimulated gene factor-dependent type I interferon secretion, to induce monocyte/Mϕs chemotaxis, and to sustain monocytes in a proinflammatory phenotype. Our study defined a critical event of PTBP2-induced monocytes/Mϕs in NB progression and revealed that RNA splicing occurred by PTBP2 benefits immune compartmentalization between NB cells and monocytes. This work revealed the pathological and biological role of PTBP2 in NB development and indicates that PTBP2-induced RNA splicing benefits immune compartmentalization and predicted a favorable prognosis in mediastinal NB.

Published
2023
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14. Plasma Epstein-Barr virus DNA and risk of nasopharyngeal carcinoma in a prospective seropositive population

Author

Wen-Jie Chen, Wen-Na Xu, Hai-Yun Wang, Xiao-Xia Chen, Xue-Qi Li, Shang-Hang Xie, Dong-Feng Lin, and Su-Mei Cao

Subjects
Nasopharyngeal carcinoma, Plasma EBV DNA, Risk prediction, Population screening, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Objective Plasma Epstein-Barr virus (EBV) DNA is considered a biomarker for nasopharyngeal carcinoma (NPC). However, its long-term role in NPC development is unclear. Materials and methods A total of 1363 participants seropositive for EBV VCA-IgA and EBNA1-IgA in a community-based NPC screening program in southern China were tested for plasma EBV DNA levels by real-time qPCR between 2008 and 2015. New NPC cases were confirmed by active follow-up approach and linkage to local cancer registry through the end of 2016. Cox proportional hazards regression analysis was performed to calculate the hazard ratios (HRs) for NPC risk with plasma EBV DNA. Results Thirty patients were newly diagnosed during a median 7.5 years follow-up. NPC incidence increased with the plasma EBV DNA load ranging from 281.46 to 10,074.47 per 100,000 person-years in participants with undetectable and ≥ 1000 copies/ml levels; the corresponding cumulative incidence rates were 1.73 and 50%. Furthermore, plasma EBV DNA loads conferred an independent risk for NPC development after adjustment for other risk factors, with HRs of 7.63 for > 3–999 copies/ml and 39.79 for ≥1000 copies/ml. However, the HRs decreased gradually after excluding NPC cases detected in the first 2 to 3 years and became statistically nonsignificant by excluding cases detected during the first 4 years. Conclusion Elevated plasma EBV DNA can predict NPC risk over 3 years. Monitoring plasma EBV DNA can be used as a complementary approach to EBV serological antibody-based screening for NPC.

Published
2021
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15. Phosphoserine phosphatase as an indicator for survival through potentially influencing the infiltration levels of immune cells in neuroblastoma

Author

Liang Zeng, Xiao-Yun Liu, Kai Chen, Liang-Jun Qin, Feng-Hua Wang, Lei Miao, Le Li, and Hai-Yun Wang

Subjects
neuroblastoma, PSPH, growth and metastasis, immune cell, prognosis, Biology (General), QH301-705.5
Abstract

Introduction: Metabolic deregulation, a hallmark of cancer, fuels cancer cell growth and metastasis. Phosphoserine phosphatase (PSPH), an enzyme of the serine metabolism pathway, has been shown to affect patients’ prognosis in many cancers but its significance in neuroblastoma remains unknown. Here, we show that the functional role and potential mechanism of PSPH and it is correlated with survival of neuroblastoma patients.Patients and Methods: The TARGET dataset (n = 151) and our hospital-based cases (n = 55) were used for assessing the expression level of PSPH associated with survival in neuroblastoma patients, respectively. Then, in vitro experiments were performed to define the role of PSPH in neuroblastoma. The ESTIMATE and TIMER algorithms were utilized to examine the correlation between PSPH expression level and abundance of immune cells. Further, Kaplan-Meier survival analysis was performed to evaluate the effect of both PSPH and immune cells on patients’ prognosis.Results: High expression of PSPH was significantly associated with unfavorable overall survival (OS) and event-free survival (EFS) in both the TARGET dataset and our hospital-based cases, and was an independent predictor of OS (hazard ratio, 2.00; 95% confidence intervals, 1.21–3.30, p = 0.0067). In vitro experiments showed that high expression of PSPH significantly promoted cell growth and metastasis. Further, the ESTIMATE result suggested that high expression level of PSPH was negatively associated with low stromal and ESTIMATE score. Specifically, high PSPH expression was found to be negatively associated with CD8+ T cell, macrophages and neutrophils, which negatively affected survival of neuroblastoma patients (p < 0.0001, p = 0.0005, and p = 0.0004, respectively).Conclusion: These findings suggested that PSPH expression could be a promising indicator for prognosis and immunotherapy in neuroblastoma patients by potentially influencing infiltration levels of immune cells.

Published
2022
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16. Clinical Significance of a CD3/CD8-Based Immunoscore in Neuroblastoma Patients Using Digital Pathology

Author

Liang Zeng, Shu-Hua Li, Shuo-Yu Xu, Kai Chen, Liang-Jun Qin, Xiao-Yun Liu, Fang Wang, Sha Fu, Ling Deng, Feng-Hua Wang, Lei Miao, Le Li, Na Liu, Ran Wang, and Hai-Yun Wang

Subjects
neuroblastoma, prognosis, immunology, digital pathology, CD3/CD8 T cells, Immunologic diseases. Allergy, RC581-607
Abstract

BackgroundInfiltrating immune cells have been reported as prognostic markers in many cancer types. We aimed to evaluate the prognostic role of tumor-infiltrating lymphocytes, namely CD3+ T cells, CD8+ cytotoxic T cells and memory T cells (CD45RO+), in neuroblastoma.Patients and MethodsImmunohistochemistry was used to determine the expression of CD3, CD8 and CD45RO in the tumor samples of 244 neuroblastoma patients. We then used digital pathology to calculate the densities of these markers and derived an immunoscore based on such densities.ResultsDensities of CD3+ and CD8+ T cells in tumor were positively associated with the overall survival (OS) and event-free survival (EFS), whereas density of CD45RO+ T cells in tumor was negatively associated with OS but not EFS. An immunoscore with low density of CD3 and CD8 (CD3-CD8-) was indictive of a greater risk of death (hazard ratio 6.39, 95% confidence interval 3.09-13.20) and any event (i.e., relapse at any site, progressive disease, second malignancy, or death) (hazard ratio 4.65, 95% confidence interval 2.73-7.93). Multivariable analysis revealed that the CD3-CD8- immunoscore was an independent prognostic indicator for OS, even after adjusting for other known prognostic indicators.ConclusionsThe new immunoscore based on digital pathology evaluated densities of tumor-infiltrating CD3+ and CD8+ T cells contributes to the prediction of prognosis in neuroblastoma patients.

Published
2022
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17. Effects of minimally invasive surgery combined with specialized pain management nursing care on postoperativepain improvement and life quality after spinal injury.

Author

Na Zhong, Hai-yun Wang, Qiong Wei, Hui Li, Na Zhang, and Jian-xue Hao

Subjects
*MINIMALLY invasive procedures, *PAIN management, *SPINAL injuries, *QUALITY of life, *SURGICAL complications, *PERIOPERATIVE care, *HOME nursing
Abstract

Objective: To determine the impacts to research the impacts of pain's Specialized Pain Management Nursing Care in the perioperative period on pain symptoms and life quality of patients experiencing minimally invasive surgery for spinal injury. Method: Eighty patients with a spinal injury who underwent minimally invasive surgery in the Department of Orthopedics of Baoding No.1 Hospital from January 2018 to December 2021 were retrospectively analyzed. They were split into two groups following different nursing methods (n=40 each group). Specialized Pain Management Nursing Care were given to patients in the observation group. Those in the control group were given treated with routine care. Their pain score and nursing effect were compared, after which their quality of life, daily living ability and complication rate compared and analyzed. Results: The pain degree in the control group was considerably more than that in the observation group in the 1st postoperative period. The pain degree, which decreased in both groups, slumped more significantly in the observation group on the 2nd and 3rd postoperative days. The postoperative hospital stays and pain duration in the observation group were shorter than those in the control group (P<0.05), and the nursing effect was significantly better than that in the control group (P<0.05). After postoperative nursing intervention. Conclusion: Minimally invasive surgery integrated with the Specialized Pain Management Nursing Care can remarkably ameliorate pain after spinal injury surgery, reducing complications' incidence, and improving the life quality for patients. [ABSTRACT FROM AUTHOR]

Published
2024
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18. Prognostic implications of a molecular classifier derived from whole‐exome sequencing in nasopharyngeal carcinoma

Author

Hai‐Yun Wang, Fugen Li, Na Liu, Xiao‐Yun Liu, Xin‐Hua Yang, Yun‐Miao Guo, Jin‐Xin Bei, Yi‐Xin Zeng, and Jian‐Yong Shao

Subjects
copy number variants, indels, molecular classifier, nasopharyngeal carcinoma, single‐nucleotide variants, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract The aim of this study was to use whole‐exome sequencing to derive a molecular classifier for nasopharyngeal carcinoma (NPC) and evaluate its clinical performance. We performed whole‐exome sequencing on 82 primary NPC tumors from Sun Yat‐sen University Cancer Center (Guangzhou cohort) to obtain somatic single‐nucleotide variants, indels, and copy number variants. A novel molecular classifier was then developed and validated in another NPC cohort (Hong Kong cohort, n = 99). Survival analysis was estimated by the Kaplan‐Meier method and compared using the log‐rank test. Cox proportional hazards model was adopted for univariate and multivariate analyses. We identified three prominent NPC genetic subtypes: RAS/PI3K/AKT (based on RAS, AKT1, and PIK3CA mutations), cell‐cycle (based on CDKN2A/CDKN2B deletions, and CDKN1B and CCND1 amplifications), and unclassified (based on dominant mutations in epigenetic regulators, such as KMT2C/2D, or the Notch signaling pathway, such as NOTCH1/2). These subtypes differed in survival analysis, with good, intermediate, and poor progression‐free survival in the unclassified, cell‐cycle, and RAS/PI3K/AKT subgroups, respectively, among the Guangzhou, Hong Kong, and combined cohorts (n = 82, P = 0.0342; n = 99, P = 0.0372; and n = 181, P = 0.0023; log‐rank test). We have uncovered genetic subtypes of NPC with distinct mutations and/or copy number changes, reflecting discrete paths of NPC tumorigenesis and providing a roadmap for developing new prognostic biomarkers and targeted therapies.

Published
2019
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19. Identification of genetic alterations associated with primary resistance to EGFR-TKIs in advanced non-small-cell lung cancer patients with EGFR sensitive mutations

Author

Fang Wang, Xia-Yao Diao, Xiao Zhang, Qiong Shao, Yan-Fen Feng, Xin An, and Hai-Yun Wang

Subjects
Epidermal growth factor receptor, Tyrosine kinase inhibitors, Resistance, Non-small-cell lung cancer, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Identification of activated epidermal growth factor receptor (EGFR) mutations and application of EGFR-tyrosine kinase inhibitors (EGFR-TKIs) have greatly changed the therapeutic strategies of non-small-cell lung cancer (NSCLC). However, the long-term efficacy of EGFR-TKI therapy is limited due to the development of drug resistance. The aim of this study was to investigate the correlation between the aberrant alterations of 8 driver genes and the primary resistance to EGFR-TKIs in advanced NSCLC patients with activated EGFR mutations. Methods We retrospectively reviewed the clinical data from 416 patients with stage III/IV or recurrent NSCLC who received an initial EGFR-TKI treatment, from April 2004 and March 2011, at the Sun Yat-sen University Cancer Center. Several genetic alterations associated with the efficacy of EGFR-TKIs, including the alterations in BIM, ALK, KRAS, PIK3CA, PTEN, MET, IGF1R, and ROS1, were detected by the routine clinical technologies. The progression-free survival (PFS) and overall survival (OS) were compared between different groups using Kaplan–Meier survival analysis with the log-rank test. A Cox regression model was used to estimate multivariable-adjusted hazard ratios (HRs) and their 95% confidence intervals (95% CIs) associated with the PFS and OS. Results Among the investigated patients, 169 NSCLC patients harbored EGFR-sensitive mutations. EGFR-mutant patients having PTEN deletion had a shorter PFS and OS than those with intact PTEN (P = 0.003 for PFS, and P = 0.034 for OS). In the combined molecular analysis of EGFR signaling pathway and resistance genes, we found that EGFR-mutant patients coexisted with aberrant alterations in EGFR signaling pathway and those having resistant genes had a statistically poorer PFS than those without such alterations (P

Published
2019
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20. FABP4 deactivates NF‐κB‐IL1α pathway by ubiquitinating ATPB in tumor‐associated macrophages and promotes neuroblastoma progression

Author

Lei Miao, Zhenjian Zhuo, Jue Tang, Xiaomei Huang, Jiabin Liu, Hai‐Yun Wang, Huimin Xia, and Jing He

Subjects
FABP4, neuroblastoma, tumor environment, tumor‐associated macrophages, Medicine (General), R5-920
Abstract

Abstract Neuroblastoma (NB) is the most common and deadliest pediatric solid tumor. Targeting and reactivating tumor‐associated macrophages (TAMs) is necessary for reversing immune suppressive state and stimulating immune defense to exert tumoricidal function. However, studies on the function and regulation of TAMs in NB progression are still limited. Fatty acid binding protein 4 (FABP4) in TAMs was correlated with advanced clinical stages and unfavorable histology of NB. FABP4‐mediated macrophages increased migration, invasion, and tumor growth of NB cells. Mechanically, FABP4 could directly bind to ATPB to accelerate ATPB ubiquitination in macrophages. The consequently decreased ATP levels could deactivate NF‐κB/RelA‐IL1α pathway, which subsequently results in macrophages reprogrammed to an anti‐inflammatory phenotype. We also demonstrated that FABP4‐enhanced migration and invasion were significantly suppressed by IL1α blocking antibody. Furthermore, circulating FABP4 was also associated with the clinical stages of NB. Our findings suggest that FABP4‐mediated macrophages may promote proliferation and migration phenotypes in NB cells through deactivating NF‐κB‐IL1α pathway by ubiquitinating ATPB. This study reveals the pathologic and biologic role of FABP4‐mediated macrophages in NB development and exhibits a novel application of targeting FABP4 in macrophages for NB treatment.

Published
2021
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22. A new prognostic histopathologic classification of nasopharyngeal carcinoma

Author

Hai-Yun Wang, Yih-Leong Chang, Ka-Fai To, Jacqueline S. G. Hwang, Hai-Qiang Mai, Yan-Fen Feng, Ellen T. Chang, Chen-Ping Wang, Michael Koon Ming Kam, Shie-Lee Cheah, Ming Lee, Li Gao, Hui-Zhong Zhang, Jie-Hua He, Hao Jiang, Pei-Qing Ma, Xiao-Dong Zhu, Liang Zeng, Chun-Yan Chen, Gang Chen, Ma-Yan Huang, Sha Fu, Qiong Shao, An-Jia Han, Hai-Gang Li, Chun-Kui Shao, Pei-Yu Huang, Chao-Nan Qian, Tai-Xiang Lu, Jin-Tian Li, Weimin Ye, Ingemar Ernberg, Ho Keung Ng, Joseph T. S. Wee, Yi-Xin Zeng, Hans-Olov Adami, Anthony T. C. Chan, and Jian-Yong Shao

Subjects
Nasopharyngeal carcinoma, Pathologic classification, Prognosis, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background The current World Health Organization (WHO) classification of nasopharyngeal carcinoma (NPC) conveys little prognostic information. This study aimed to propose an NPC histopathologic classification that can potentially be used to predict prognosis and treatment response. Methods We initially developed a histopathologic classification based on the morphologic traits and cell differentiation of tumors of 2716 NPC patients who were identified at Sun Yat-sen University Cancer Center (SYSUCC) (training cohort). Then, the proposed classification was applied to 1702 patients (retrospective validation cohort) from hospitals outside SYSUCC and 1613 patients (prospective validation cohort) from SYSUCC. The efficacy of radiochemotherapy and radiotherapy modalities was compared between the proposed subtypes. We used Cox proportional hazards models to estimate hazard ratios (HRs) with 95% confidence intervals (CI) for overall survival (OS). Results The 5-year OS rates for all NPC patients who were diagnosed with epithelial carcinoma (EC; 3708 patients), mixed sarcomatoid-epithelial carcinoma (MSEC; 1247 patients), sarcomatoid carcinoma (SC; 823 patients), and squamous cell carcinoma (SCC; 253 patients) were 79.4%, 70.5%, 59.6%, and 42.6%, respectively (P

Published
2016
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25. Pan-cancer Analysis of Tumor Mutational Burden and Homologous Recombination DNA Damage Repair Using Targeted Next-Generation Sequencing

Author

Yan-Fen Feng, Ling Deng, Hai-Yun Wang, Ying-Qing Li, Tao Tang, Fang Wang, Ya-Kang Long, Xin-Hua Yang, Xiao Zhang, Yuan He, and Xu Zhang

Subjects
Adult, Male, 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, medicine.medical_treatment, Pan-cancer, DNA sequencing, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Neoplasms, Internal medicine, Biomarkers, Tumor, medicine, Carcinoma, Humans, General, Homologous Recombination, Aged, Retrospective Studies, Pan cancer, business.industry, High-Throughput Nucleotide Sequencing, Cancer, Immunotherapy, Homologous recombination DNA damage repair, Middle Aged, Prognosis, DNA Damage Repair, medicine.disease, Tumor mutational burden, Tumor Burden, Gene Expression Regulation, Neoplastic, Survival Rate, 030104 developmental biology, 030220 oncology & carcinogenesis, Mutation, Biomarker (medicine), Original Article, Female, Homologous recombination, business, DNA Damage, Follow-Up Studies
Abstract

Purpose Current variability in methods for tumor mutational burden (TMB) estimation and reporting demonstrates the urgent need for a homogeneous TMB assessment approach. Here, we compared TMB distributions in different cancer types using two customized targeted panels commonly used in clinical practice. Materials and Methods TMB spectra of 295- and 1021-gene panels in multiple cancer types were compared using targeted next-generation sequencing (NGS). The TMB distributions across a diverse cohort of 2,332 cancer cases were then investigated for their associations with clinical features. Treatment response data were collected for 222 patients who received immune-checkpoint inhibitors (ICIs) and their homologous recombination DNA damage repair (HR-DDR) and programmed death-ligand 1 (PD-L1) expression were additionally assessed and compared with the TMB and response rate. Results The median TMB between gene panels was similar despite a wide range in TMB values. The highest TMB was 8 and 10 in patients with squamous cell carcinoma and esophageal carcinoma according to the classification of histopathology and cancer types, respectively. Twenty-three out of 103 patients (22.3%) were HR-DDR‒positive and could benefit from ICI therapy; out of those 23 patients, seven patients had high TMB (p=0.004). Additionally, PD-L1 expression was not associated with TMB or treatment response among patients receiving ICIs. Conclusion Targeted NGS assays demonstrated the ability to evaluate TMB in pan-cancer samples as a tool to predict response to ICIs. In addition, TMB integrated with HR-DDR‒positive status could be a significant biomarker for predicting ICI response in patients.

Published
2021
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26. GhADF6‐mediated actin reorganization is associated with defence against Verticillium dahliae infection in cotton

Author

Ruihui Zhang, Lei Su, Yuan-Bao Li, Yong-Duo Sun, Hai-Yun Wang, Gui-Xian Xia, and Zhong Mengmeng

Subjects
actin cytoskeleton, Soil Science, Plant Science, macromolecular substances, Biology, Verticillium, cotton, Ascomycota, Gene Expression Regulation, Plant, actin depolymerizing factor, Gene silencing, Verticillium dahliae, Molecular Biology, Pathogen, Gene, Actin, Disease Resistance, Plant Diseases, Plant Proteins, Gossypium, Original Articles, biology.organism_classification, Actin cytoskeleton, In vitro, Actins, Cell biology, Actin Depolymerizing Factors, Actin depolymerizing factor, Original Article, Agronomy and Crop Science
Abstract

Several studies have revealed that actin depolymerizing factors (ADFs) participate in plant defence responses; however, the functional mechanisms appear intricate and need further exploration. In this study, we identified an ADF6 gene in upland cotton (designated as GhADF6) that is evidently involved in cotton's response to the fungal pathogen Verticillium dahliae. GhADF6 binds to actin filaments and possesses actin severing and depolymerizing activities in vitro and in vivo. When cotton root (the site of the fungus invasion) was inoculated with the pathogen, the expression of GhADF6 was markedly down‐regulated in the epidermal cells. By virus‐induced gene silencing analysis, the down‐regulation of GhADF6 expression rendered the cotton plants tolerant to V. dahliae infection. Accordingly, the abundance of actin filaments and bundles in the root cells was significantly higher than that in the control plant, which phenocopied that of the V. dahliae‐challenged wild‐type cotton plant. Altogether, our results provide evidence that an increase in filament actin (F‐actin) abundance as well as dynamic actin remodelling are required for plant defence against the invading pathogen, which are likely to be fulfilled by the coordinated expressional regulation of the actin‐binding proteins, including ADF., An increase in filament actin abundance achieved via silencing the expression of GhADF6 is associated with host defence against Verticillium dahliae infection in cotton.

Published
2021

35. Leptin decreases Th17/Treg ratio to facilitate neuroblastoma via inhibiting long-chain fatty acid catabolism in tumor cells

Author

Meng Li, Di Li, Hai-Yun Wang, Weixin Zhang, Zhenjian Zhuo, Huiqin Guo, Jiabin Liu, Yue Zhuo, Jue Tang, Jing He, and Lei Miao

Subjects
Neuroblastoma, long-chain fatty acid, leptin, T cell differentiation, tumor microenvironment, Immunologic diseases. Allergy, RC581-607, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

The exploration of therapeutic targets in neuroblastoma (NB), which needs more attempts, can benefit patients with high-risk NB. Based on metabolomic and transcriptomic data in mediastinal NB tissues, we found that the content of long-chain acylcarnitine (LCAC) was increased and positively associated with leptin expression in advanced NB. Leptin over-expression forced naïve CD4+ T cells to differentiate into Treg cells instead of Th17 cells, which benefited from NB cell proliferation, migration, and drug resistance. Mechanically, leptin in NB cells blunted the activity of carnitine palmitoyltransferase 2 (CPT2), the key enzyme for LCAC catabolism, by inhibiting sirtuin 3-mediated CPT2 deacetylation, which depresses oxidative phosphorylation (OXPHOS) for energy supply and increases lactic acid (LA) production from glycolysis to modulate CD4+ T cell differentiation. These findings highlight that excess leptin contributes to lipid metabolism dysfunction in NB cells and subsequently misdirects CD4+ T cell differentiation in tumor micro-environment (TME), indicating that targeting leptin could be a therapeutic strategy for retarding NB progression.

Published
2025
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36. In Situ Shear-Wave Velocity Assessment at the Delaney Park Downhole Array, Anchorage, Alaska

Author

Hai‐Yun Wang and Wei‐Ping Jiang

Subjects
In situ, Geophysics, 010504 meteorology & atmospheric sciences, Shear (geology), Wave velocity, 010502 geochemistry & geophysics, 01 natural sciences, Geology, Seismology, 0105 earth and related environmental sciences
Abstract

The shear-wave velocity (VS) in soil is an important parameter to characterize dynamic soil properties. The Delaney Park downhole array was deployed in 2003 without measuring the shear- and compression-wave velocity (VS and VP) profiles. Thornley et al. (2019) measured the VS and VP profiles using the downhole method after the sensor was removed from the 61 m borehole with casing in the array. However, the waves propagating along the casing wall may have a great influence on the recognition of the first arrival of waves propagating in the soil. Using horizontal and vertical components of weak-motion data of eight local earthquakes recorded by the array, in situ VS and VP profiles were assessed by the seismic interferometry based on deconvolution, respectively. The results are as follows. The VS and VP profiles computed by this study and measured by Thornley et al. (2019) are in relatively good agreement at a depth of 10–45 m and at a depth of 30–45 m, respectively, and in very poor agreement at other depths. The average VS profiles computed by this study are more consistent with the derived VS from the standard penetration test data at the site with slower near-surface velocities relative to the downhole logging analysis. There are strong anisotropy in the strata below 45 m and weak anisotropy with various degrees at various depths in the strata above 45 m.

Published
2020
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37. Expression of Human Leukocyte Antigen G is associated with Prognosis in Nasopharyngeal Carcinoma

Author

Man-Bo Cai, Hui-Qiong Han, Jin-Xin Bei, Chao-Chun Liu, Jin-Ju Lei, Qian Cui, Qi-Sheng Feng, Hai-Yun Wang, Jia-Xing Zhang, Yi Liang, Li-Zhen Chen, Tie-Bang Kang, Jian-Yong Shao, Yi-Xin Zeng

Subjects
Biology (General), QH301-705.5
Abstract

Human leukocyte antigen G (HLA-G) has multiple immune regulatory functions including the induction of immune tolerance in malignancies. The roles of HLA-G have not been investigated in nasopharyngeal carcinoma (NPC). This study is aimed to evaluate the role of HLA-G as prognostic factor for NPC patients as well as its role in the immune regulation. Western assays showed high HLA-G expression in NPC cell lines, but low in the immortalized nasopharyngeal epithelial cell line NP69. HLA-G protein was further detected in 79.2% of 552 NPC specimens with immunohistochemistry (IHC), but not in normal nasopharyngeal epithelium tissue. Moreover, high expression of HLA-G predicted poor survival of NPC patients and positively correlated with tumor N classification and recurrence or metastasis. Multivariate analysis indicated that HLA-G was an independent and unfavorable prognostic factor. Furthermore, the presence of CD68+macrophages and IL-10 were also examined, which are two prognostic markers of NPC and important factors for regulating immune surveillance. The correlations of HLA-G with these two immune factors were revealed in NPC tissues. Taken together, our results suggest that HLA-G is an independent biomarker for NPC prognosis, and HLA-G might contribute to NPC progression, which might jointly regulate immune surveillance in NPC together with macrophages and IL-10.

Published
2012

39. scCNC: a method based on capsule network for clustering scRNA-seq data

Author

Hai-Yun Wang, Jian-Ping Zhao, Chun-Hou Zheng, and Yan-Sen Su

Subjects
Statistics and Probability, Computational Mathematics, Computational Theory and Mathematics, Sequence Analysis, RNA, Gene Expression Profiling, Cluster Analysis, Single-Cell Analysis, Molecular Biology, Biochemistry, Software, Computer Science Applications
Abstract

Motivation A large number of studies have shown that clustering is a crucial step in scRNA-seq analysis. Most existing methods are based on unsupervised learning without the prior exploitation of any domain knowledge, which does not utilize available gold-standard labels. When confronted by the high dimensionality and general dropout events of scRNA-seq data, purely unsupervised clustering methods may not produce biologically interpretable clusters, which complicate cell type assignment. Results In this article, we propose a semi-supervised clustering method based on a capsule network named scCNC that integrates domain knowledge into the clustering step. Significantly, we also propose a Semi-supervised Greedy Iterative Training method used to train the whole network. Experiments on some real scRNA-seq datasets show that scCNC can significantly improve clustering performance and facilitate downstream analyses. Availability and implementation The source code of scCNC is freely available at https://github.com/WHY-17/scCNC. Supplementary information Supplementary data are available at Bioinformatics online.

Published
2021

43. Prevalence of NRAS Mutation, PD-L1 Expression and Amplification, and Overall Survival Analysis in 36 Primary Vaginal Melanomas

Author

Hai-Yun Wang, Fang Wang, Xin-Hua Yang, Yan-Fen Feng, Xiao-Yan Wu, Ya-Kang Long, and Xiao Zhang

Subjects
Proto-Oncogene Proteins B-raf, Primary vaginal melanoma, 0301 basic medicine, Neuroblastoma RAS viral oncogene homolog, Oncology, Cancer Research, medicine.medical_specialty, NRAS, Malignancy, B7-H1 Antigen, GTP Phosphohydrolases, 03 medical and health sciences, symbols.namesake, 0302 clinical medicine, Internal medicine, Prevalence, medicine, Humans, Telomerase reverse transcriptase, PD‐L1 expression, Melanoma, In Situ Hybridization, Fluorescence, Sanger sequencing, Predictive marker, GNA11, medicine.diagnostic_test, business.industry, Membrane Proteins, Gynecologic Oncology, medicine.disease, Survival Analysis, 030104 developmental biology, Ooncogenic mutations, 030220 oncology & carcinogenesis, Mutation, symbols, Female, business, GNAQ, Fluorescence in situ hybridization
Abstract

Background Primary vaginal melanomas are uncommon and aggressive tumors with poor prognosis, and the development of new targeted therapies is essential. This study aimed to identify the molecular markers occurring in these patients and potentially improve treatment strategies. Materials and Methods The clinicopathological characteristics of 36 patients with primary vaginal melanomas were reviewed. Oncogenic mutations in BRAF, KIT, NRAS, GNAQ and GNA11 and the promoter region of telomerase reverse transcriptase (TERT) were investigated using the Sanger sequencing. The expression and copy number of programmed death‐ligand 1 (PD‐L1) were also assessed. Results Mutations in NRAS, KIT, and TERT promoter were identified in 13.9% (5/36), 2.9% (1/34), and 5.6% (2/36) of the primary vaginal melanomas, respectively. PD‐L1 expression and amplification were observed in 27.8% (10/36) and 5.6% (2/36) of cases, respectively. PD‐L1 positive expression and/or amplification was associated with older patients (p = .008). Patients who had NRAS mutations had a poorer overall survival compared with those with a wild‐type NRAS (33.5 vs. 14.0 months; hazard ratio [HR], 3.09; 95% CI, 1.08–8.83). Strikingly, two patients with/without PD‐L1 expression receiving immune checkpoint inhibitors had a satisfying outcome. Multivariate analysis demonstrated that >10 mitoses per mm2 (HR, 2.96; 95% CI, 1.03–8.51) was an independent prognostic factor. Conclusions NRAS mutations and PD‐L1 expression were most prevalent in our cohort of primary vaginal melanomas and can be potentially considered as therapeutic targets. Implications for Practice This study used the Sanger sequencing, immunohistochemistry, and fluorescence in situ hybridization methods to detect common genetic mutations and PD‐L1 expression and copy number in 36 primary vaginal melanomas. NRAS mutations and PD‐L1 expression were the most prevalent, but KIT and TERT mutations occurred at a lower occurrence in this rare malignancy. Two patients receiving immune checkpoint inhibitors had a satisfying outcome, signifying that the PD‐L1 expression and amplification can be a possible predictive marker of clinical response. This study highlights the possible prospects of biomarkers that can be used for patient selection in clinical trials involving treatments with novel targeted therapies based on these molecular aberrations., Little is known about the molecular characteristics of primary vaginal melanoma. This article reports on the molecular markers of this rare and aggressive disease, focusing on improvements in treatment strategies.

Published
2019
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44. The Percentage of Anaplastic Lymphoma Kinase-Positive Tumor Cells Has Clinical Implications for Patients with Non-Small Cell Lung Cancer

Author

Jian Yong Shao, Li-Yue Sun, Yuan He, Rui Gong, Qiong Shao, Fei Xu, Zi Chen Zhang, Hai-Yun Wang, and Xiao-Yun Liu

Subjects
Male, Lung Neoplasms, Tumor cells, Cancer Survivors, Risk Factors, Carcinoma, Non-Small-Cell Lung, hemic and lymphatic diseases, medicine, Humans, Anaplastic lymphoma kinase, Anaplastic Lymphoma Kinase, In patient, Lung cancer, In Situ Hybridization, Fluorescence, Genetics (clinical), medicine.diagnostic_test, business.industry, General Medicine, Middle Aged, Prognosis, medicine.disease, Survival Analysis, respiratory tract diseases, Cancer research, Female, Non small cell, business, Anaplastic Lymphoma Kinase Positive, Fluorescence in situ hybridization
Abstract

Objectives: Anaplastic lymphoma kinase (ALK) is one of the leading therapeutic targets in patients with non-small cell lung cancer (NSCLC). However, the clinical importance that the percentage of A...

Published
2019
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45. Clinical genetic features and related survival implications in patients with surgically resected large-cell lung cancer

Author

Fang Wang, Xiao-Yan Wu, Xin An, Qiong Shao, Hai-Yun Wang, Yan-Fen Feng, and Jia-Bin Lu

Subjects
0301 basic medicine, Oncology, Mutation, medicine.medical_specialty, Lung, biology, business.industry, Large cell lung cancer, medicine.disease, medicine.disease_cause, 03 medical and health sciences, Exon, 030104 developmental biology, 0302 clinical medicine, medicine.anatomical_structure, 030220 oncology & carcinogenesis, PD-L1, Internal medicine, biology.protein, ROS1, Medicine, KRAS, business, Lung cancer
Abstract

Background: Large-cell lung carcinomas (LCLCs) were reclassified by the World Health Organization 2015 criteria. and remain fairly unknown at the molecular level and targeted-therapeutic options. Methods: Data of 184 lung cancer patients were retrieved from clinical records, of which 54 were found to be pathologically diagnosed as LCLC. The genetic alterations EGFR/KRAS/BRAF mutations, MET copy number, and exon 14 mutation, ALK and ROS1 rearrangements, and PDL1 expression were investigated using clinical technologies. The relationship between clinicopathologic and genetic features was analyzed, and the Kaplan–Meier method with log-rank test was used for analyzing patient survival. Results: Major events, including EGFR, KRAS, and BRAF mutations and MET copy-number gain, were found in 5.6%, 16.7%, 1.9%, and 18.5% in LCLC, respectively. No ALK or ROS1 translocation was detected. PDL1 expression in tumor cells and in tumor-infiltrating lymphocytes was observed in 24 (44.4%) and 16 (29.6%) patients. Kaplan–Meier analysis showed that patients with a KRAS mutation had ower 5-year overall survival than those with wild-type KRAS (25.4% vs 47.8%, P=0.028) and that patients with negative PDL1 stained in tumor cells but positive for tumor-infiltrating lymphocytes had significantly favorable overall survival compared to those with solitary and positive PDL1 stained in tumor cells (62.5% vs 20.6%, P=0.044). Conclusion: KRAS mutations and PDL1 expression can predict patient survival and be potential target options in LCLC.

Published
2019
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46. Mutation spectrum of germline cancer susceptibility genes among unselected Chinese colorectal cancer patients

Author

Li-Yue Sun, Da-Dong Zhang, Xin-Hua Yang, Xin-Kai Cao, Lingheng Kong, Bin Li, Zu-Lu Ye, Yuan He, Rui Gong, Hai-Yun Wang, Jian Yong Shao, Yu Hong Li, Rui-Hua Xu, and Xiao-Yun Liu

Subjects
0301 basic medicine, Oncology, Mutation rate, medicine.medical_specialty, business.industry, Cancer, Microsatellite instability, medicine.disease, MLH1, Lynch syndrome, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Germline mutation, 030220 oncology & carcinogenesis, Internal medicine, Mutation (genetic algorithm), medicine, Missense mutation, business
Abstract

Background: Genetic factors play an important role in colorectal cancer (CRC) risk, yet the prevalence and spectrum of germline cancer susceptibility gene mutations among unselected Chinese CRC patients is largely undetermined. Methods: We performed next-generation sequencing with a 73-genes panel and analyzed the prevalence and spectrum of germline mutations in 618 unselected Chinese CRC patients. We classified all identified germline alterations for pathogenicity and calculated the frequencies of pathogenic mutations. Clinical characteristics were assessed by age and mutation status. Protein expressions and interactions of MLH1 missense variants were evaluated by western blot and co- immunoprecipitation. Results: Overall, 112 (18.1%) of 618 unselected Chinese CRC patients were found to carry at least one pathogenic or likely pathogenic variant (totaling 97 variants), including 70 (11.3%) Lynch syndrome (LS) mutation carriers and 42 (6.8%) non-LS mutation carriers. LS mutation carriers were significantly younger at CRC diagnosis and were more likely to have right-sided, poorly differentiated, early stage, high-frequency microsatellite instability (MSI-H) or dMMR CRC and a family history of cancer compared with noncarriers. Non-LS mutation carriers were more likely to be proficient mismatch repair (pMMR) than noncarriers (p=0.039). We found four clinical variables (gender, tumor histological stage, cancer stage and mutation status) that showed significant differences between patients younger and older than 50 years old. Higher mutation rates were found in patients under 50 years old (p=0.017). Thirty-three novel variants were discovered and evaluated as pathogenic mutations by our study. Conclusion: Given the high frequency and wide spectrum of mutations, genetic testing with a multigene panel should be considered for all Chinese CRC patients under 50 years old and is also needed to determine whether a gene is associated with CRC susceptibility and to promote clinical translation.

Published
2019
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47. Prognostic implications of a molecular classifier derived from whole‐exome sequencing in nasopharyngeal carcinoma

Author

Na Liu, Xin-Hua Yang, Jin-Xin Bei, Hai‐Yun Wang, Xiao-Yun Liu, Jian Yong Shao, Yun-Miao Guo, Yi Xin Zeng, and Fugen Li

Subjects
0301 basic medicine, Oncology, Male, Cancer Research, Kaplan-Meier Estimate, medicine.disease_cause, 0302 clinical medicine, CDKN2A, CDKN2B, Copy-number variation, Exome sequencing, Original Research, Aged, 80 and over, Nasopharyngeal Carcinoma, single‐nucleotide variants, Middle Aged, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Prognosis, Cell Transformation, Neoplastic, 030220 oncology & carcinogenesis, Female, Signal Transduction, Adult, medicine.medical_specialty, DNA Copy Number Variations, Biology, lcsh:RC254-282, Polymorphism, Single Nucleotide, 03 medical and health sciences, Young Adult, Internal medicine, Chromosomal Instability, Exome Sequencing, medicine, Biomarkers, Tumor, Humans, Radiology, Nuclear Medicine and imaging, molecular classifier, Survival analysis, Aged, Neoplasm Staging, Proportional hazards model, Gene Expression Profiling, Clinical Cancer Research, Computational Biology, medicine.disease, 030104 developmental biology, Nasopharyngeal carcinoma, Mutation, indels, Carcinogenesis, copy number variants
Abstract

The aim of this study was to use whole‐exome sequencing to derive a molecular classifier for nasopharyngeal carcinoma (NPC) and evaluate its clinical performance. We performed whole‐exome sequencing on 82 primary NPC tumors from Sun Yat‐sen University Cancer Center (Guangzhou cohort) to obtain somatic single‐nucleotide variants, indels, and copy number variants. A novel molecular classifier was then developed and validated in another NPC cohort (Hong Kong cohort, n = 99). Survival analysis was estimated by the Kaplan‐Meier method and compared using the log‐rank test. Cox proportional hazards model was adopted for univariate and multivariate analyses. We identified three prominent NPC genetic subtypes: RAS/PI3K/AKT (based on RAS, AKT1, and PIK3CA mutations), cell‐cycle (based on CDKN2A/CDKN2B deletions, and CDKN1B and CCND1 amplifications), and unclassified (based on dominant mutations in epigenetic regulators, such as KMT2C/2D, or the Notch signaling pathway, such as NOTCH1/2). These subtypes differed in survival analysis, with good, intermediate, and poor progression‐free survival in the unclassified, cell‐cycle, and RAS/PI3K/AKT subgroups, respectively, among the Guangzhou, Hong Kong, and combined cohorts (n = 82, P = 0.0342; n = 99, P = 0.0372; and n = 181, P = 0.0023; log‐rank test). We have uncovered genetic subtypes of NPC with distinct mutations and/or copy number changes, reflecting discrete paths of NPC tumorigenesis and providing a roadmap for developing new prognostic biomarkers and targeted therapies.

Published
2019

48. Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Author

Labeau, Sonia O, Afonso, Elsa, Benbenishty, Julie, Blackwood, Bronagh, Boulanger, Carole, Brett, Stephen J, Calvino-Gunther, Silvia, Chaboyer, Wendy, Coyer, Fiona, Deschepper, Mieke, François, Guy, Honore, Patrick M, Jankovic, Radmilo, Khanna, Ashish K, Llaurado-Serra, Mireia, Lin, Frances, Rose, Louise, Rubulotta, Francesca, Saager, Leif, Williams, Ged, Blot, Stijn I, Dritan, Muzha, Antoni Margarit Ribas, Fernando, Lipovesty, Cecilia, Loudet, Fiona, Coyer, Philipp, Eller, Nafseen, Mostafa, Patrick, M Honoré, Vanesa Mercado Telleria, Jasmina, Smajic, Paula Cristina Nogueira, Khalid Mahmood Khan Nafees, Romuald, Hentchoya, Louise, Rose, Javiera, Soledad, Frances, Lin, Yenny, Cardenas, Amylkar Garay Reyes, Alan, Sustic, Meropi, Mpouzika, Tamas, Vymazal, Hanne Irene Jensen, Hernan, Aguirre-Bermeo, Liivi, Maddison, Maija, Valta, Silvia, Calvino-Gunther, Frank, Bloos, Faustina Excel Adipa, Vasilios, Koulouras, Judy, Enamorado, Zsuzsann, Ágoston, Hrönn, Birgisdóttir, Amit, Gupta, Mohan, Gurjar, Bram, Kilapong, Seyed Mohammadreza Hashemian, Ignacio, Martin-Loeches, Julie, Benbenishty, Andrea, Cortegiani, Kelly, Fletcher, Yoshiro, Hayashi, Wangari, Waweru-Siika, Khalid, Abidi, Sang-Min, Lee, Burhan, Hadri, Mihails, Dolgusevs, Fayez François Abillama, Tomas, Jovaisa, Cyril, Thix, Muhammed, Elhadi, Basri Mat Nor, Shanti, Ratnam, Mohd Zulfakar Mazlan, Sundaresan, Maiyalagan, Luis, Sánchez-Hurtado, Adrian, Belii, Mendsaikhan, Naranpurev, Prabha, Gautam, Dylan De Lange, Rachael, Parke, Rose Ekama Ilesanmi, Mirjana, Shosholcheva, Antonija, Petosic, Ranveig, Lind, Madiha Hashmi Ffarcsi, Javier, Bogarin, Aaron Mark Hernandez, Malgorzata, Mikaszewska-Sokolewicz, Bruno, Sousa, Dana, Tomescu, Dorel, Sandesc, Theogene, Twagirumugabe, Vitaly, Gusarov, Maie, Ebaid, Radmilo, Jankovic, Gari, Slobodianiuk, Andrea, Martonova, Rihard, Knafelj, Mervyn, Mer, Emilio, Maseda, Bernardo, Panka, Joerg, C Schefold, Eva, Joelsson-Alm, Konlawij, Trongtrakul, Lorna, Merritt-Charles, Lamia Ouanes Besbes, Yalım, Dikmen, Lesia, Zgrzheblovska, Mark, Fielding, Francesca, Rubulotta, Ashish, K Khanna, Leif, Saager, Ingrid von der Osten, Alban, Greca, Alma, Cani, Nordian, Xhindi, Genci, Hyska, Antonio Margarit Ribas, Susana, Pinto, Paulo, Alves, Romina, Esposito, Emanuel, Valgolio, John Thomas Sanchez Minope, Antonio, Abdala, Maria, Ayala, Silvina, Bravo, Ana, Bantar, Patricia, Delgado, Gustavo, Badariotti, Fernando, Lipovestky, Ana, Diaz, Pablo, Saul, Mariano, Setten, Alejandra, Aucapina, Ysica, Acosta, Victor, Gonzalez, Luis, Camputaro, Fernando, Baccaro, Robert, Villa, Marcela, Mastantuono, Emiliano, Dean, Oscar Fernández Rostello, Patricia, Brizuela, Julio Ricardo Bartoli, Matias, Guereschi, Cristian, Quiroga, Sofia, Putruele, Paula, Villegas, Veronica, Curilen, Ruben, Fernandez, Mariangeles Gabriela Nocheretti, Rosana Gabriela Escalante, Cecilia Inés Loudet, Silvia, Fernandez, Ana Laura Gonzalez, Gustavo Andres Alvarez, Federico, Iglesias, Silvia, Chaparro, Graciela, Zakalik, Gonzalo, Pagella, Matías, Baini, Pierina Arias Campos, Ignacio, Sabbag, Armando, Schmukler, Imelda Perdomo Fonseca, Gonzalo Martín Alvarez, Mario, Ramirez, Fernando, Tapia, Carlos Alejandro Bascary, Graciela Del Valle Gimenez, Fernando Pablo Bertoletti, Esteban, Milioto, Pablo Julio Maldonaldo Bonsignore, Maria Alejandra Fernandez, Julie, Smith, Tim, Chimunda, Lorraine, Thompson, Teena, Maguire, Wendy, Chaboyer, Stacey, Watts, Marion, Mitchell, Madeleine, Powell, India, Lye, Leanne, Parsons, Nerilee, Baker, Claire, Reynolds, Amy, Thompson, Kristy, Masters, Kellie, Sosnowski, Lynette, Morrison, Gavin, D Leslie, Ramanathan, Lakshmanan, Alexis, Tabah, Wendy, Brown, Sharon, McDowell-Skaines, Andrea, Mclucas, Chris, Smith, Mandy, Tallot, Sarah, Jones, Michelle, Barakat-Johnson, Thomas, Leong, Rand, Butcher, Kerrie, Martin, Philipp, Douschan, Dirk von Lewinski, René, Schmutz, Uta, Kolussi, Fatema, Salman, Zainab, Ateya, Koen De Decker, Niels Van Regenmortel, Anita, Jans, Patricia, Wijnands, Stefano, Coremans, Patrick, M Honore, David De Bels, Tanja, Depuydt, Caroline, Paillet, Luc-Marie, Jacquet, Walter, Swinnen, Francis, Hannes, Matthia, Mergeay, Stijn Van de Velde, Silvie, Allaert, Pieter, Hoste, Christophe, Borin, Sandrine, Balon, Vincent, Fraipont, Patrick, Biston, Nicolas De Schryver, Thierry, Dugernier, Ilse Van Cotthem, Angelica Olivetto de Almeida, Silvia Angelica Jorge, Delmiro, Becker, Raysa Cristina Schmidt, Evellyn, Oliveira, Aline, Ramalho, Eliane, Mazocoli, Audrey, Fioretti, Elaine, Barros, Leticia, Serpa, Suzana, Bianchini, Ticiane, Campanili, Taís, Pantaleao, Paulo Carlos Garcia, Ana Lucia Vitti Ronchini, Rayanne, Santos, Nurulhuda Binti, A Manap, Sean, Bagshaw, Dominic, Carney, Jon, Davidow, Ella, Rokosh, Andréa Maria Laizner, Samantha, Smith, Megan, Mcquirter, Betty Star Kampayana, René, Favre, Martin, Sills, Julie, Dallaire, Cathy, Becker, Sherissa, Microys, Bonnie, Bowes, Jennifer, Lajeunesse, Rishi, Ghosh, Jacqueline, Baptiste-Savoie, Rose, Raizman, Gabriel, Suen, Noushin, Taghavi, Orla, Smith, Clare, Fielding, Julieta, Canales, Pia, Molina, Javiera, Chaparro, Maria Idalia Sepulveda, Matias Jesús Flamm Zamorano, Pamela, Rocha, Ximena, Villanueva, Paola, Araya, Meneses, Dayan, Fernando, Avalos, Xiaohan, Li, Liu, Yu, Xinxia, Li, Xiaoyan, Chen, Zhixia, Jiang, Jing, Yang, Jingfang, Chen, Lei, Yang, Kefang, Wang, Jie, Gao, Xiuhua, Fang, Ronghua, Zhao, Xinhua, Xia, Hongmei, Liu, Jing, Li, Haiyan, Wang, Gen, Meng, Yanhong, Di, Damei, Wang, Rong Hua Zhao, Li Ping Hu, Peipei, Xu, Qing Feng Jiao, Hai Yun Wang, Chun Jie Xia, Yan, Liu, Mei, Ye, Yan, Wan, Wenmei, Wang, Yajun, Ding, Aiua, Ren, Yan, Gao, Qi, Li, Guifang, Du, Yanling, Shen, Yanming, Ding, Ning, Li, Cui, Yuan, Lei, Tan, Qiang, Lin, Hailing, Guo, Howe, Yan, Xiao, Xu, Wei, Zhang, Jinxian, Liang, Libing, Zhang, Eryun, Tian, Qian, Zhao, Lin, Insu, Jingwen, Dong, Yanmei, Gu, Ying, Liu, Lina, Zhao, Wei, Wang, Hongmei, Qiao, Lili, Tuo, Mengmeng, Lv, Jin Yu Zhu, Jifen, Zhu, Ying, Wei, Man, Liu, Yin, He, Jiyin, Cheng, Jin, Liu, Jia, Na, Dongfang, Wei, Qing, Li, Xiaoying, Wu, Huan, Duan, Dongliang, Lin, Qiong, Liang, Xiaofang, Luo, Yunfeng, Xiong, Rong Fen Huang, Jing, Fu, Tao, Zan, Man, Ye, Zeya, Shi, Yanfei, Long, Yang, Lei, Xiaodi, Liu, Chen, Yumei, Lingling, Wang, Yali, Zhang, Yan, Xu, Cheng, Wang, Zhijuan, Chengxia, Sun, Jinhui, Song, Yingli, Wang, Xiumei, Liu, Yupeng, Liu, Yuxia, Yuan, Qingping, Huang, Fengling, Yang, Yun, Wu, Xianping, Luo, Xiaowu, Bai, Hong, Zheng, Min, Song, Yue, Sun, Zhangshuangzi, Li, Feifei, Luo, Miao, Liu, Li Chuntang Li, Xinjian, Li, Guiping, Zhang, Lina, Xiao, Tingting, Yu, Guangyuan, Gao, Wei, Wei, Fanglan, Wang, Ting, Han, Tingting, Li, Zeng, Qi, Jing Mei Zeng, Yan, Long, Fuqun, Pan, Jing, Wang, Guoxue, He, Haiyan, Chen, Feifei, Zhang, Chao, Yu, Gao, Chunhua, Xiuying, Yao, Dongmei, Bai, Liu, Lu, Xuelian, Xu, Yan, Wang, Xuejuan, Liang, Zhang, Na, Aizhi, Zhang, Xiaochun, Hu, Hui, Zhang, Ruixia, Wang, Poon Shing Tak, Sung Wai Ho, Qun Xia Jiang, Xinran, Ding, Liu, Hong, Limei, Miao, Zhaoxia, Feng, Liping, Huang, Juan, Wu, Yuping, Wang, Jiye, Guo, Baoke, Zhang, Chaoqun, Ma, Han, Yu, Congcong, Liu, Min, Ding, Linlin, Luan, Jing, Zheng, Shanshan, Lv, Shumin, Jiang, Wenzhen, Cao, Xiujuan, Xue, Guangyan, Liu, Xiyan, Wei, Youru, Jiang, Zhiru, Yao, Gao, Li, Jinhua, Li, Wenwen, Zhao, Mei, Jiang, Junping, Hao, Jing, Zhang, Caiju, Song, Feifei, Chen, Shuhui, Wang, Lili, Hu, Deyan, Cao, Jianhong, Wan, Xiaomin, Wang, Hongyan, Shao, Zhenxia, Zhang, Xia, Cui, Jingyu, Liu, Lijuan, Zhao, Xingguo, Li, Limei, Fan, Ling, Zhang, Min, Yu, Biyan, Li, Chunxia, Li, Ling, Liu, Xuelian, Liu, Wenmin, Chen, Yan, Li, Zhang, Zhigang, Yuchen, Wu, Chenghau, Mu, Guoyan, Zhu, Fan, Yang, Qi, Bo, Ling, Li, Meili, Chen, Jing Hua Jiang, Hai, Yin, Xuelian, Pang, Yue Ying Gong, Shunzhu, Yang, Xiaoli, Yan, Xianhong, Zheng, Dehong, Lei, Lei, Lei, Yinhua, Guo, Lihong, Liu, Jing, Yu, Wei, Sun, Aiping, Bi, Weiwei, Li, Yang, Wu, Ji, Li, Dongshu, Ni, Zijing, Wu, Bing, Song, Qin, Fei, Yang, Xiaoyan, Qiong, Ran, Xixi, Li, Xueping, Jiao, Hua, Ji, Sun, Zhiping, Hong, Ma, Jianhong, Mu, Yanhua, Hao, Yin, Li, Ying, Wang, Caihong, Hui, Wenjie, Ju, Yuxia, Huo, Yuxia, Wang, Lei, Chen, Yan, Yan, Qingli, Zhao, Hongjuan, Chen, Guijun, Bao, Ying, Cao, Hong, Li, Hong, Zhang, Ying, Zhang, Lina, Xu, Jia, Guixiang, Ying, Li, Hui Min Zhao, Xia, Huang, Zhaoxing, Dai, Yanman, Jian, Hongsu, Zhang, Zhixia, Tian, Zu Qing Cao, Miao, Li, Yang, Liu, Fei, Ouyang, Fuying, Ma, Wangyan, Jin, Liuyan, Ge, Shifen, Wu, Weilian, Yuan, Tianfei, Chen, Guanxiu, Shi, Zhihong, Chen, Kewei, Liu, Xue, Lin, Yuemen, Ly, Sun, Lijuan, Xiao Fang Tian, Shuo, Wang, Zhangxia, Feng, Xiaozhe, Liu, Yunchun, Dong, Jundi, Zhang, Nie, Bocui, Guoxian, Wang, Yingjuan, Zhao, Xiaojun, Wu, Qiao, Yang, Rongjun Ling Hu, Xue Qin Li, Zhu Jun Yu, Yanlan, Yao, Xiaoqiong, Deng, Yan, Xiao, Yan, Xie, Yanping, Yang, Huai, Yang, Yuming, Zhou, Zhuqing, Li, Min, Xiao, Yongxia, Yang, Yani, Tian, Luz Marina Silva Gama, 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Guillén, Josep Trenado Alvarez, Mercedes Del Cotillo, Jesus Emilio Barrueco-Francioni, Belen Burgos Conde, Maria Pilar Sogues Blanco, Maria Luisa Blasco, Ana Isabel Clement, Clara, Hurtado, Luz Coronado Sanz, David, Perez-Torres, Estefanía, Prol-Silva, Jorge, Pereira, Iván Areán González, Anastasio Espejo Cano, Cesar Rodriguez Nuñez, Inmaculada Lorenzo Fernadez, Alejandra Azahara Marguello Fernandez, Rosa Del Bosque Diez, Badiola, Hilario, Begoña, Zalba-Etayo, Ana, Pascual-Bielsa, Preveen, Banwarie, Dick, Nahar, Alisha van Axel, Naraindath, N Boedjawan, Erika Backlund Jansson, Ann-Sofie, Malvemyr, Lotta, Johansson, Ulla, Sandberg, Catarina, Tingsvik, Gunilla, Mattsson, Gun, Löf, Martin, Spångfors, Mona, Ringdal, Sebastian, Geijer, Lotti, Orvelius, Mia, Hylen, Caroline, Lagerhäll, Eva, Åkerman, Viveca Hamback Hellkvist, Ulrica, Mickelsson, Ewa, Wahlbom, Ing-Marie, Larsson, Ewa, Wallin, Filippo, Boroli, Solenne, Ory, Margaret Lynn Jong, Alexander, Dullenkopf, Martin, Lang, Yvan, Fleury, Marianne, Maus, Nawfel, Ben-Hamouda, Anne, Fishman, Mei Yu Hsu, Shu Chuan Chang, Konlawij, Trongtratul, Chaiwut, Sawawiboon, Sunthiti, Morakul, Bodin, Khwannimit, Keevan, Singh, Dale, Ventour, Dianne, Figaro-Barclay, Sasha, Sankar-Maharaj, Mhamed Sami Mebazaa, Salma, Kamoun, Souheil, Elatrous, Lamia, Besbes, Fekri, Abroug, Walid, Naija, Youssef Zied Elhechmi, Walid, Sellami, Zied, Hajjej, Takoua, Merhabene, Imen, Talik, Ozlem Ozkan Kuscu, Ozcengiz, Dilek, Avşar, Zerman, Hayriye Cankar Dal, Sema, Turan, Semih, Aydemir, Hakan, Yilmaz, Duygu Kayar Calili, Seval, İzdes, Melike, Cengiz, Ayça, Gümüş, Banu, Taşdemir, Ali, Kağnıcı, Mustafa, Ay, Serap Avcı Ay, Gulbahar, Caliskan, Turkay, Akbas, Abidin Oner Balbay, Serdar, Efe, Volkan, Inal, Gülseren, Elay, Pınar, Karabacak, Boğaç, Özserezli, Evren, Şentürk, Oktay, Demirkiran, Suha, Bozbay, Elif, Erdogan, Mustafa, Akker, Nebia, Peker, Asu, Ozgultekin, Sibel Ocak Serin, Can, Turan, Gulsah, Karaoren, Senay, Goksu, Sait, Karakurt, Huseyin, Arikan, Fethi, Gül, İsmail, Cinel, Iskender, Kara, Hasan Nabi Undar, Yesim Serife Bayraktar, Jale Bengi Çelik, Murat Emre Tokur, Demet Tok Aydin, İsmail, Yildiz, Beysim, Özcan, Başar, Erdivanli, Ahmet, Eroglu, Devrim, Akdağ, Nurdan, Ünlü, Adonis, Dungca, Ashwaq, Ali, Bindu, Thankamma, Paul Eric Reyes, Sini, John, Ajitha, Rajendran, Fatima Kasem El Ahmad, Kathleen Ann Smiley, Susanna, Hojden, Mia Thorning Miller, Vishnu Das Sasidharan Nair, Maria Gracia San Antonio, Khaled Al Qawasmeh, Sabah Abu Shawish, Hilary, Twiggs, Ines, Rosado, Volodymyr, Babych, Faye, Morren, Charlotte, Young, Nicola, Vaughan-Jones, Stephanie, Harris, Karen, Burns, Carmel, Georgiev, Rosina, Shayamano, Ian, Kerslake, Peter, Creber, Ana, Vochin, Catherine, O'Brien, Paul, Caddell, Samantha, Hagan, Mandy, Hughes, Tomasz, Torlinski, James, Sherwin, Santhana, Kannan, Amber, Markham, Richard, Lebon, Jason, Cupitt, Julius, Cranshaw, Nigel, White, Victoria, Marriott, Wendy, Milner, Casiano Barrera Groba, Joao, Azoia, Petra, Polgarova, Shaly, George, Ritoo, Kapoor, Ceri, Lynch, Nathalie, Fox, Karen, Cranmer, Natalie, Fox, Thomas, Llewellym, Kelly, Matthews, Louise, Maltby, Jowena, Ibao, Karen, Boulton, Rachel, Jarman, Karen, Baxter, Ashok Sundai Raj, Arif, Moghal, Joanne, White, Suzanne, Barrowcliffe, Mark, Pulletz, Vaarisan, Ganeshalingam, Rosaleen, Baruah, Carole, Boulanger, Helen, Baker, Justin, Woods, Poe Poe Ei, Vongayi, Ogbeide, Paul, Hayden, Jennifer, Hughes, Madhu, Balasubramanian, Armorel, Salberg, Rajnish, Saha, Dagmar, Holmquist, Claire, Derbyshire, Neil, Smith, Elizabeth, Stones, Jane, Ademokun, Monica, Popescu, Maria Schofield Legorburo, Samantha, North, Carole, Brett, Helen, Jaundoo, Jayne, Craig, Simon, Whiteley, Clare, Howcroft, Liz, Wilby, Peter, Delve, David, Shaw, Karen, Williams, Ingeborg, D Welters, Jane, Mcmullen, Stephen, Brett, Leah, Flores, Treiza, Trueman-Dawkins, Mae, Templeton, John, Adams, Catherine, Smith, John, Prowle, Heather, Byers, Andrea, Mcdonnell, Bernd Oliver Rose, Rosie, Reece-Anthony, Luis, Mendes, Marcela, Vizcaychipi, Rhian, Bull, Grace, Lacaden, Eleanor, Santiago, Carlos Castro Delgado, Sarah, Farnell-Ward, Elaine, Thorpe, Justine, Somerville, Anne, Williams, Donna, Cummings, Helen, Derrick, Sarah, Brumwell, Claire, Randell, Nicola, Mccann, Emma, Aves, Gillian, Berry, Tamas, Szakmany, Una, Gunter, Paul, Pulak, Nikki, Sarkar, Kerry, Wright, Vitor, Gomes, Jones, Jo, Ruth, Palfrey, Julie, Camsooksai, Abby, Lewis, Antony, Eneas, Ascanio, Tridente, Louise, Barr, Beverley, Thomas, Emma, Parkin, Daniel, Horner, Christian, Frey, Suzanne, Bench, Rachel, Baumber, Phil, Broadhurst, Matthew, Jackson, Lynne, Williams, Michele, Clark, Jonathan, Paddle, Sarah, Bean, Sarah, Buckley, Christopher, Palfreeman, Sophie, Liu, Nicola, Allison, Ben, Attwood, Penny, Parsons, Victoria, Houghton, Sarah Jane Turner, David, Higgins, Egidija, Bielskute, Nicola, Horrigan, Reni, Jacob, Karen, Habgood, Ahmed, Zaki, Amy, Collins, Jenny, Lord, Charalice, Ramiro, Agnieszka, 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European Society of Intensive Care Medicine (ESICM) Trials Group Collaborators, Muzha, D., Ribas, A.M., Lipovesty, F., Loudet, C., Coyer, F., Eller, P., Mostafa, N., Honoré, P.M., Telleria, V.M., Smajic, J., Nogueira, P.C., Nafees, KMK, Hentchoya, R., Rose, L., Soledad, J., Lin, F., Cardenas, Y., Reyes, A.G., Sustic, A., Mpouzika, M., Vymazal, T., Jensen, H.I., Aguirre-Bermeo, H., Maddison, L., Valta, M., Calvino-Gunther, S., Bloos, F., Adipa, F.E., Koulouras, V., Enamorado, J., Ágoston, Z., Birgisdóttir, H., Gupta, A., Gurjar, M., Kilapong, B., Hashemian, S.M., Martin-Loeches, I., Benbenishty, J., Cortegiani, A., Fletcher, K., Hayashi, Y., Waweru-Siika, W., Abidi, K., Lee, S.M., Hadri, B., Dolgusevs, M., Abillama, F.F., Jovaisa, T., Thix, C., Elhadi, M., Nor, B.M., Ratnam, S., Mazlan, M.Z., Maiyalagan, S., Sánchez-Hurtado, L., Belii, A., Naranpurev, M., Gautam, P., De Lange, D., Parke, R., Ilesanmi, R.E., Shosholcheva, M., Petosic, A., Lind, R., Ffarcsi, M.H., Bogarin, J., Hernandez, 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A.S., Goller, S., Afonso, E., Larina, E., Labeau, Sonia O. 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X.L., Chen W., Li Y., Zhigang Z., Yuchen W., Mu C., Zhu G., Bo Q., Li L., Chen M., Jiang J.H., Yin H., Pang X., Gong Y.Y., Yang S., Yan X., Zheng X., Lei D.H., Lei L., Guo Y., Yu J., Sun W., Bi A.P., Li W., Ni D., Wu Z., Song B., Fei Q., Xiaoyan Y., Ran Q., Xixi L., Jiao X., Ji H., Zhiping S., Hong M., Jianhong M., Hao Y., Yin L., Hui C., Ju W., Huo Y., Chen L., Yan Y., Bao G., Cao Y., Xu L., Guixiang J., Zhao H.M., Huang X., Dai Z., Jian Y., Tian Z., Cao Z.Q., Li M., Ouyang F., Ma F., Jin W., Ge L., Wu S.F., Yuan W., Chen T., Shi G., Chen Z., Liu K., Lin X., Yuemen L., Lijuan S., Tian X.F., Feng Z.X., Liu X.Z., Dong Y., Bocui N., Jiang Z.X., Wang G.X., Zhao Y., Yang Q., Hu R.L., Li X.Q., Yu Z.J., Yao Y., Deng X., Xiao Y., Xie Y., Yang Y., Yang H., Zhou Y., Li Z., Xiao M., Yang Y.X., Tian Y., Gama L.M.S., Hernandez J.S., Caicedo N., Marin J., Ochoa M.-E., Gomez M., Rojas-Suarez J., Gonzalez J., Reyes A.J.G., Chapeta E., Orozco E., Filipovic-Grcic I., Vukovic A., Pecenkovic S., Suput 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M.A., Mentec H., Plantefeve G., Besch G., Pili-Floury S., Ledochowski S., Deserts M.D., Giacardi C., Daubin C., Massard A., Le Guen Y., Blanc A., Mandaroux S., Gunther S.C., Avogadro P., Radavidson A., Turc J., Jochmans S., Quintard H., Boyer L., Bruel C., Philippart F., Montravers P., Atchade E., Flessel N., Chinardet B., Soulisse L., Pillard C., Ngo D., Bongiorno B., Heitzler N., Souppart V., Gautheret N., Timsit J.-F., Essardy F., Fartoukh M., Mehay D., Etourneau F., Farkas J.-C., Beuret P., Preda G., De Montmollin E., Castelain V., Jaschinski U., Rothenfusser M., Kindgen-Milles D., Dimski T., Fiedler C., Heinicke T., Meybohm P., Schulze T., Bota M., Pelz S., Odenthal T., Christ M., Bosl K., Chovas A., Stehr S., Simon P., Grotheer S., Schuppel S., Schaller S., Albrecht L., Stubner A., Graeser S., Kolbe N., Lausch M., Diers A., Guenther U., Riessen R., Roller M., Osei I.P., Kusi-Appiah A.-C., Yakubu Y.H., Guadi-Gosh B., Dragoumanis C., Christofis C., Kazakos N., Bastani S., Martinos C., Bekos V., Papanikolaou M., Papavasilopoulou T., Efthymiou A., Chantziara V., Kyriakoudi A., Kakaras N., Diakaki C., Flevari A., Nikolaou C., Katerina K., Avramopoulou L., Tsikritsaki K., Gkiokas G., Pantiora E., Katsenos C., Patsiou E.-C., Alexandropoulou P., Koutsodimitropoulos I., Farmakis E., Nestora K., Chatzis M., Kondili E., Soundoulounaki S., Mousafiri O., Lepida D., Liarmakopoulou A., Papathanakos G., Oikonomou M., Ioannides P., Papadopoulos D., Staikos I., Stafylaraki M., Raitsiou B., Mandis K., Ravani I., Kourelea S., Efthimiou A., Thoma G., Bakas A., Psarulis K., Anisoglou S., Papageorgiou E., Michailidou E., Tholioti T., Lavrentieva A., Sourla E., Spyropoulou A., Pantelas N., Stalika K.M.M., Georgakas I., Karathanou A., Tsikriki S., Dimoula A., Kanakaki S., Vakalos A., Pagioulas K., Enamorado J.E., Nardai G., Hawchar F., Blondal A., Rygvadottir B., Jonasdottir R.J., Shah B., Kaushik S., Tripathy S., Singh M., Agarwal S., Gupta M., Ahmad M., Mangal K., Bhargava V., Kushare V., Jha S., Bhakhtiani L., Kamal M., Baronia A., Susanti A., Lestari M.I., Zulkifli Z., Baskoro W., Zand F., Zarei F., Mahmoodpoor A., Heidari F., Jafaraghaee F., O'Shea A., O'Shea F., O'Donnell C., Craig G., Fitzpatrick G., Dunne L., Hastings J., Marsh B., Cody C., Campbell E., Doyle D., Pacturanan M., Sheehan C., Carey A., Carter C., Mulvey R., Finn D.O.C.R., Motherway C., Walsh A., Kehoe J., Delossantos S., Lalor J., O'Nuallain S., Behan H., McPherson S., Corcoran A., Gordon P., Rooney G., Levy D., Azencot M., Gurevich V., Lavy A., Bendelari V., Marconi R., Barone A., Gatti C., Giampaoletti A., Borgognoni C., Ghioldi D.M., Raimondo A., Castiglione G., Bruno A.V., Rubulotta G., Mo A., Corso A., Girianni S., Bruni A., Garofalo E., Maggiore S.M., Di Risio A., Calamai I., Spina R., Spadaro S., Volta C.A., Cotoia A., Mirabella L., Maulicino L., Abregal G., Donvito M., D'Ambrosio P., Binda F., Adamina I., Galazzi A., Negro A., Vaschetto R., Capuzzi F., Boschetto M., Stivanello L., Bonaccorso L., Megna C., Iozzo P., Rizzo A., Scire G., Taibi M.R., Tranello F.P., Manzo A., Traina L., Pastore B., Quaini A., Giusti G.D., Montaldi G., Piergentili F., Mancini F., Casaioli S., Uccelli F., Guarracino F., Onelli A., Di Gravio V., Cossu M., Matrona O., Rocco M., Alampi D., Dellafiore F., Ranalli F., Bossolasco M., Brizio E., Migliorino P., Cortellazi P., Rosati M., D'Ambrosio F., Quagliotto C., Roman-Pognuz E., Peratoner A., De Rosa S., Martin M.A., De Sanctis F., Ciorba P., Toppin P., Harding-Goldson H., Taito S., Shime N., Yamamoto R., Kanda F., Hirao A., Egi M., Noguchi A., Hashimoto S., Aya U., Sakuramoto H., Ohuchi A., Kataoka J., Maruyama K., Nakayama I., Nishime Y., Fujimoto K., Takahashi K., Tsujimoto M., Shimizu M., Tole E., Correia M.C., Kim J.H., Park S., Kim K.C., Baek J., Bae J.-M., Park S.Y., Park T.S., Lee H.B., Park J., Yeon-Joo L., Young-Jae C., Jeon K., Kim S.C., Lee J., Chee H.K., Huh J.W., Sim Y.S., Kim J., Chang Y., Ahn J.-J., Kang B.J., Lee W.-Y., Lee S.J., Baftiu N., Krastins I., Stiban S., Feghaly M.E., Gharios E., Merheb M., Benlamin M., Khaled A., Belkhair W.A., Tabib M., Ashour F., Elhadi A., Tababa O.W.E., Khaled T., Alkhumsi S.I.R., Alshrif A.I., Aboufray A.A., Alabuzidi A., Triki A.R., Elgammudi M., Zahra H.B., Soula E., Al-Alawi M.M.S., Ahmed H., Ghula M.A.A., Vosylius S., Mouton L., Rastegar T., Sertznig C., Martin G., Theisen C., Ferretti C., Gils F., Gallion M., Zainudin A., Bahrin L.K.K., Deva S.R., Rahim A.H.A., Wahab S., Hassan W.N.W., Ismail W.N.W., Ali M.N., Khoo T.M., Samat N.M., Tong J.M.G., Adib N.A.N., Nor M.B.M., Ismail N., Sulaiman S.R., Foong K.W., Alias A., Hua N.P., Zermeno J.M., Blanco D., Duran K., Nava C.L.L., Nandyelly S.J.R., Sanchez-Hurtado L.A., Tejeda-Huezo B., Del Moral Armengol M., Nava L.P.A., Herrera J.G., de Anda G.F.V., Gallegos-Perez H., Hernandez-Sanchez N., Hernandez-Ponce L., Gorordo-Delsol L., Hernandez-Romero M., Gomez S., Molinar F., Namendys-Silva S.A., Romero-Gonzalez J.P., Gonzalez D., Landaverde A., Sosa M.A., Navarro B., de Molina Serrano J.I.R., Iburrigarro S.R., Ibarra A., Aguirre J., Martinez-Gonzalez M., Padilla N.R.C., Pineda A.A.V., Villafuerte M.V.E., Herrera M.O.G., Baasanjav B., Hachimi A., Elkhayari M., Dendane T., Subedi N.B., Pathak S.D., Manandhar M., Van Gulik L., Van Den Brink M., Van Vliet P., Gerretsen B., Van Den Berg L., De Haan M., Tuinstra B., Kuijpers P., Reijntjens J., Vermeijden J.W., Rinket M., Vanroest M., Reidinga A., Loef B., Dieperink W., Onrust M., Dormans T., Bormans L., Koopmans M., Gerritsen R.T., Van Den Elst A., Evers M., Oiting O., Wilting R., Ramaker B., van der Kuil M., Fijen J.-W., Haas L., De Lange D., Haringman J., Newby L., Gilder E., Hacking D., Dagooc R., Song R., Waibel H., Dawn F., Rapley J., Chadwick L., Chapman C., Crone P., Albrett J., Marko P., Goodson J., Browne T., Whitticase R., Davidson C., Judd H., Owens D., Onyeka T., Ugwu I., Ilesanmi R., Adejumo P.O., Owojuyigbe A., Adenekan A., Uba S., Chime C., Jibrin D., Sankey B.J., Adekola O., Olanipekun S., Shosolcheva M., Gievski V., Kartalov A., Naumovski F., Kuzmanovska B., Trposak A., Bogoevska-Miteva Z., Rosalia R., Olsen B.F., Sjobo B., Jensen K.D., Sykehus D., Johansen B.F., Straede E., Johansen E., Finnstrom I.J., Toellefsen A., Ostenjo H., Bjorgen H., Bratsberg B., Kristoffersen E., Skorstad E.M., Hansen S., Vullum S., Lunde G.A., Arntsen W., Lund M., Akselsen G.R., Monstad K.R., Stenset A., Haugom H., Monsen B., Hogvall L., Trudvang S., Galaaen B., Malmin S.K., Andersen M.H., Hargott R.F., Andersen Y., Steffenak E., Nyhus M., Meland B., Hashmi M., Rivas N., Maidana E., de Jesus Ortiz A., Cabral D.M.B., Simi M., Aponte C., Rivas J.C., Gill S., Garcia A., Alvarenga G., Cespedes L., Perez H., Moreira M.L., Canete F., Gonzalez R., Monges N., Coman M., Pederzani M., Franco N., Aganon F., Martinez R., Noblezada-Uy D., Ellazar C.G., Cerezo F.D., Palo J.E., Aperocho C.A.J., Isanan M., Tubacka M., Jasiewicz P., Czuczwar M., Borys M., Gutysz-Wojnicka A., Glinka L., Gawda R., Bilawicz J., Cabrita P., Vieira J., Figueiredo M.F., Pinheiro C.M., Antunes N., Pedro L., Ferreira F., Parente I., Varela M., Fernandes F., Martins C., Viveiros A., Cavaco R., Rita C.S., Dias S., Feranandes A.M., Silva P., Nunes C., Cabral J., Pires F., Ferreira H., Santos J., Pinto V.M.V., Bispo B.M., Ferreira A., Molinos E., Lafuente E., Gregorio R., Costa H., Lima A., Ferreira S., Seromenho V., Luis E., Valerio I., Cesar H., Tavares A., Alsheikhly A.S., Mahmood S., Guran C.T., Moise A., Filipescu D.C., Luchian M., Popescu M., Scutariu M.A., Petrisor C., Hagau N., Grigoras I., Patrichi T., Gusarev V., Pivkina A., Kulakov V., Ignatenko O., Kovaleva J., Zhivotneva T., Zhedaeva M., Matiushkov N., Ershova O., Egorova N., Khoronenko V., Baskakov D., Sergeev D., Piradov M., Grishina L., Magomedov M., Zuev E., Gorokhovatsky U., Leonova A., Fadeeva L., Belskiy V., Galishevskiy D., Zubareva N., Tribulev M., Zueva O., Kiselev A., Kamenshchikov N., Tokareva E., Petrushin M., Starchenko I., Nshimyumuremyi I., Muhizi J., Buregeya E., Nzarora J., Assiri A., Ebaid M.S., Almekhlafi G., Mandourah Y., Velickovic J., Velickovic D., Jovanovic B., Hadzibegovic A., Stefanovic B., Misic V., Bumbasirevic V., Rajkovic M., Stojanovic M., Gavrilovic S., Stanojevic M., Yaghi A., Turcan A., Firment P., Rabarova D., Lancaricova D., Vlaovic J., Groznik M., Lukic M., Perme J., Sostaric M., Umek N., Mirkovic T., Dolenc S., Fister M., Zorko N., Markota A., Yeni N.P., Jali P., Schmollgruber S., Syed M.R., Parag N., Wise R., Galiana M., Navarro J.A., De Pablo A.M., Albert P., Martinez P., Mendiara Y., Garcia B., Llinas A.A., Riveiro M., Gallart E., Riera A., Sanz M., Salo S., Lajara M.A.G., Nieto M.V., Garcia R., Pena J.M.G., Gorgolas M.C., Isasi M.A., Sierra R., Gordo F., Conejo I., Salva-Costa V., Garzon-Tovar C., Lospitao S., Gutierrez P., Girona M., Adamuz J., Olivares P.G., de Ceballos J.P.G., Tirado C., De Wit I., Polo A.B.C., del Mar Diaz Salcedo M., Ripolles-Melchor J., Martinez-Hurtado E., Alvarez J.D., Arcas M.L.B., Gonzalez J.I.T., de la Ventana A.B.S., Calleja P.L.-A., Alvarez R.G., Zamora P.S., Guerrero A.O., Cosano R., Perez-Vacas J., Campos-Perez M., Barreiro E.M., Sanchez L.C., Diaz M.G., Jimenez R., Del Rio Cabajo L., Muriel D.S., Alonso H.F., Fernandez A.W., Pinan I.S., Albaiceta G.M., Fernandez M.C.I., Abos F.J.S., Monedero P., Chueca R.M., Aguirre L.G., Manosa S.C., Luque C.P., Calpe N., Losilla M.R., Fores M.T., Farre O., Fernandez O., del Rosario Villar Redondo M., Arteta Arteta D.S., Sanchez M.A.H., Espinosa C.P., Reyes L.M., Domenech L.C., Guillen C.V., Alvarez J.T., del Cotillo M., Barrueco-Francioni J.E., Conde B.B., Blanco M.P.S., Blasco M.L., Clement A.I., Hurtado C., Sanz L.C., Perez-Torres D., Prol-Silva E., Pereira J., Gonzalez I.A., Cano A.E., Nunez C.R., Fernadez I.L., Fernandez A.A.M., Del Bosque Diez R., Hilario B., Zalba-Etayo B., Pascual-Bielsa A., Banwarie P., Nahar D., van Axel A., Boedjawan N.N., Jansson E.B., Malvemyr A.-S., Johansson L., Sandberg U., Tingsvik C., Mattsson G., Lof G., Spangfors M., Ringdal M., Geijer S., Orvelius L., Hylen M., Lagerhall C., Akerman E., Hellkvist V.H., Mickelsson U., Wahlbom E., Larsson I.-M., Wallin E., Boroli F., Ory S., Jong M.L., Dullenkopf A., Lang M., Fleury Y., Maus M., Ben-Hamouda N., Fishman A., Hsu M.Y., Chang S.C., Trongtratul K., Sawawiboon C., Morakul S., Khwannimit B., Singh K., Ventour D., Figaro-Barclay D., Sankar-Maharaj S., Mebazaa M.S., Kamoun S., Elatrous S., Besbes L., Abroug F., Naija W., Elhechmi Y.Z., Sellami W., Hajjej Z., Merhabene T., Talik I., Kuscu O.O., Dilek O., Zerman A., Dal H.C., Turan S., Aydemir S., Yilmaz H., Calili D.K., Izdes S., Cengiz M., Gumus A., Tasdemir B., Kagnici A., Ay M., Ay S.A., Caliskan G., Akbas T., Balbay A.O., Efe S., Inal V., Elay G., Karabacak P., Ozserezli B., Senturk E., Demirkiran O., Bozbay S., Erdogan E., Akker M., Peker N., Ozgultekin A., Serin S.O., Turan C., Karaoren G., Goksu S., Karakurt S., Arikan H., Gul F., Cinel I., Kara I., Undar H.N., Bayraktar Y.S., Celik J.B., Tokur M.E., Aydin D.T., Yildiz I., Ozcan B., Erdivanli B., Eroglu A., Akdag D., Unlu N., Dungca A., Ali A., Thankamma B., Reyes P.E., John S., Rajendran A., Ahmad F.K.E., Smiley K.A., Hojden S., Miller M.T., Das Sasidharan Nair V., Antonio M.G.S., Qawasmeh K.A., Shawish S.A., Twiggs H., Rosado I., Babych V., Morren F., Young C., Vaughan-Jones N., Harris S., Burns K., Georgiev C., Shayamano R., Kerslake I., Creber P., Vochin A., O'Brien C., Caddell P., Hagan S., Hughes M., Torlinski T., Sherwin J., Kannan S., Markham A., Lebon R., Cupitt J., Cranshaw J., White N., Marriott V., Milner W., Groba C.B., Azoia J., Polgarova P., George S., Kapoor R., Lynch C., Fox N., Cranmer K., Llewellym T., Matthews K., Maltby L., Ibao J., Boulton K., Jarman R., Baxter K., Raj A.S., Moghal A., White J., Barrowcliffe S., Pulletz M., Ganeshalingam V., Baruah R., Baker H., Woods J., Ei P.P., Ogbeide V., Hayden P., Hughes J., Balasubramanian M., Salberg A., Saha R., Holmquist D., Derbyshire C., Smith N., Stones E., Ademokun J., Legorburo M.S., North S., Brett C., Jaundoo H., Craig J., Whiteley S., Howcroft C., Wilby L., Delve P., Shaw D., Williams K., Welters I.D., McMullen J., Brett S., Flores L., Trueman-Dawkins T., Templeton M., Adams J., Prowle J., Byers H., McDonnell A., Rose B.O., Reece-Anthony R., Mendes L., Vizcaychipi M., Bull R., Lacaden G., Santiago E., Delgado C.C., Farnell-Ward S., Thorpe E., Somerville J., Williams A., Cummings D., Derrick H., Brumwell S., Randell C., McCann N., Aves E., Berry G., Szakmany T., Gunter U., Pulak P., Sarkar N., Wright K., Gomes V., Jones J., Palfrey R., Camsooksai J., Lewis A., Eneas A., Tridente A., Barr L., Thomas B., Parkin E., Horner D., Frey C., Bench S., Baumber R., Broadhurst P., Jackson M., Williams L., Clark M., Paddle J., Bean S., Buckley S., Palfreeman C., Liu S., Allison N., Attwood B., Parsons P., Houghton V., Turner S.J., Higgins D., Bielskute E., Horrigan N., Jacob R., Habgood K., Zaki A., Collins A., Lord J., Ramiro C., Kubisz-Pudelko A., Kotze M., Williams H., Iovenko I., Tsarev A., Briva A., Mendez G., Napolitano L., Teig M., Rodriguez G.E., Ben-Jacob T., Potestio C., Eng T., Mahanes D., Khanna A., Duggal A., Nananmori M., Lois M., Karamchandani K., Bealer C., Barefield C., Terry D., Fivecoat P., Idowu O., Cata J., Clesi T., Peterson J., Hatton K., Dhaliwal J., Mueller D., Tao J., Eltorai A.S., Pastores S.M., Remor N., Salazar J., Barkas D., Joffe A., Barnes C., Sona C., Schallom M., Short J., Lorenzo J., Von Der Osten I., Borkowska M., Demarre L., Pleitinckx V., Xing C., Debue A.-S., Goller S., Larina E., Labeau, S. O., Blackwood, B., Brett, S. J., Deschepper, M., Francois, G., Honore, P. M., Khanna, A. K., Williams, G., Blot, S. I., Ribas, A. M., Telleria, V. M., Nogueira, P. C., Nafees, K. M. K., Reyes, A. G., Jensen, H. I., Adipa, F. E., Agoston, Z., Hashemian, S. M., Lee, S. -M., Abillama, F. F., Nor, B. M., Mazlan, M. Z., Sanchez-Hurtado, L., De lange, D., Ilesanmi, R. E., Ffarcsi, M. H., Hernandez, A. M., Schefold, J. C., Besbes, L. O., Minope, J. T. S., Rostello, O. F., Bartoli, J. R., Nocheretti, M. G., Escalante, R. G., Loudet, C. I., Gonzalez, A. L., Alvarez, G. A., Campos, P. A., Fonseca, I. P., Alvarez, G. M., Bascary, C. A., del Valle Gimenez, G., Bertoletti, F. P., Bonsignore, P. J. M., Fernandez, M. A., Leslie, G. D., Mclucas, A., Jacquet, L. -M., de Almeida, A. O., Jorge, S. A., Schmidt, R. C., Garcia, P. C., Ronchini, A. L. V., Manap, N. B. A., Laizner, A. M., Mcquirter, M., Kampayana, B. S., Sepulveda, M. I., Zamorano, M. J. F., Zhao, R. H., Hu, L. P., Jiao, Q. F., Wang, H. Y., Xia, C. J., Insu, L., Zhu, J. Y., Zhu, J. F., Huang, R. F., Wang, L. L., Song, J. H., Liu, X. M., Li, Z. S., Li, L. C., Zeng, J. M., Hu, X. C., Wang, R. X., Tak, P. S., Ho, S. W., Jiang, Q. X., Huang, L. P., Liu, X. L., Jiang, J. H., Gong, Y. Y., Lei, D. H., Bi, A. P., Zhao, H. M., Cao, Z. Q., Wu, S. F., Tian, X. F., Feng, Z. X., Liu, X. Z., Jiang, Z. X., Wang, G. X., Hu, R. L., Li, X. Q., Yu, Z. J., Yang, Y. X., Gama, L. M. S., Hernandez, J. S., Ochoa, M. -E., Reyes, A. J. G., Filipovic-Grcic, I., Vukovic, A., Pecenkovic, S., Suput, A., Radivojevic, R. C., Culjak, H., Adam, V. N., Pedersen, K. R., Kjaergard, I. E., Kodal, A. M., Hansen, T. C. B., Pedersen, A. S. B., Thomsen, T. D., Frandsen, T. M., Bliksted, I. A., Tamayo, L. M., Tutillo, D. R. M., Hurtado, C. V., Garcia, M. F., Kutimets, M., Lofqvist, C., Sakki, J. -K., Valta, M. A., Plantefeve, G., Deserts, M. D., Gunther, S. C., Timsit, J. -F., Farkas, J. -C., Bosl, K., Schuppel, S., Stubner, A., Osei, I. P., Kusi-Appiah, A. -C., Yakubu, Y. H., Patsiou, E. -C., Stalika, K. M. M., Enamorado, J. E., Jonasdottir, R. J., Lestari, M. I., Finn, D. O. C. R., Mcpherson, S., Ghioldi, D. M., Bruno, A. V., Maggiore, S. M., Volta, C. A., Taibi, M. R., Tranello, F. P., Giusti, G. D., Martin, M. A., Correia, M. C., Kim, J. H., Kim, K. C., Bae, J. -M., Park, S. Y., Park, T. S., Lee, H. B., Kim, S. C., Chee, H. K., Huh, J. W., Sim, Y. S., Ahn, J. -J., Kang, B. J., Lee, W. -Y., Lee, S. J., Feghaly, M. E., Belkhair, W. A., Tababa, O. W. E., Alkhumsi, S. I. R., Alshrif, A. I., Aboufray, A. A., Triki, A. R., Zahra, H. B., Al-Alawi, M. M. S., Ghula, M. A. A., Bahrin, L. K. K., Deva, S. R., Rahim, A. H. A., Hassan, W. N. W., Ismail, W. N. W., Ali, M. N., Khoo, T. M., Samat, N. M., Tong, J. M. G., Adib, N. A. N., Nor, M. B. M., Sulaiman, S. R., Foong, K. W., Hua, N. P., Zermeno, J. M., Nava, C. L. L., Nandyelly, S. J. R., Sanchez-Hurtado, L. A., Nava, L. P. A., Herrera, J. G., de Anda, G. F. V., Namendys-Silva, S. A., Romero-Gonzalez, J. P., Sosa, M. A., de Molina Serrano, J. I. R., Iburrigarro, S. R., Padilla, N. R. C., Pineda, A. A. V., Villafuerte, M. V. E., Herrera, M. O. G., Subedi, N. B., Pathak, S. D., Vermeijden, J. W., Gerritsen, R. T., Fijen, J. -W., Adejumo, P. O., Sankey, B. J., Olsen, B. F., Jensen, K. D., Johansen, B. F., Finnstrom, I. J., Skorstad, E. M., Lunde, G. A., Akselsen, G. R., Monstad, K. R., Hogvall, L., Malmin, S. K., Andersen, M. H., Hargott, R. F., de Jesus Ortiz, A., Cabral, D. M. B., Rivas, J. C., Moreira, M. L., Ellazar, C. G., Cerezo, F. D., Palo, J. E., Aperocho, C. A. J., Figueiredo, M. F., Pinheiro, C. M., Rita, C. S., Feranandes, A. M., Pinto, V. M. V., Bispo, B. M., Lima, A., Alsheikhly, A. S., Guran, C. T., Filipescu, D. C., Scutariu, M. A., Ebaid, M. S., Velickovic, D., Rajkovic, M., Stanojevic, M., Turcan, A., Lancaricova, D., Yeni, N. P., Syed, M. R., Navarro, J. A., De Pablo, A. M., Llinas, A. A., Lajara, M. A. G., Nieto, M. V., Pena, J. M. G., Gorgolas, M. C., Isasi, M. A., Salva-Costa, V., Garzon-Tovar, C., Olivares, P. G., de Ceballos, J. P. G., Polo, A. B. C., del Mar Diaz Salcedo, M., Alvarez, J. D., Arcas, M. L. B., Gonzalez, J. I. T., de la Ventana, A. B. S., Calleja, P. L. -A., Alvarez, R. G., Zamora, P. S., Guerrero, A. O., Barreiro, E. M., Sanchez, L. C., Diaz, M. G., Muriel, D. S., Alonso, H. F., Fernandez, A. W., Pinan, I. S., Albaiceta, G. M., Fernandez, M. C. I., Abos, F. J. S., Chueca, R. M., Aguirre, L. G., Manosa, S. C., Luque, C. P., Losilla, M. R., Fores, M. T., del Rosario Villar Redondo, M., Arteta Arteta, D. S., Sanchez, M. A. H., Espinosa, C. P., Reyes, L. M., Domenech, L. C., Guillen, C. V., Alvarez, J. T., del Cotillo, M., Barrueco-Francioni, J. E., Conde, B. B., Blanco, M. P. S., Blasco, M. L., Clement, A. I., Sanz, L. C., Gonzalez, I. A., Cano, A. E., Nunez, C. R., Fernadez, I. L., Fernandez, A. A. M., Boedjawan, N. N., Jansson, E. B., Malvemyr, A. -S., Lof, G., Spangfors, M., Lagerhall, C., Akerman, E., Hellkvist, V. H., Larsson, I. -M., Jong, M. L., Hsu, M. Y., Chang, S. C., Mebazaa, M. S., Elhechmi, Y. Z., Kuscu, O. O., Dal, H. C., Calili, D. K., Izdes, S., Gumus, A., Tasdemir, B., Kagnici, A., Ay, S. A., Balbay, A. O., Ozserezli, B., Senturk, E., Serin, S. O., Gul, F., Cinel, I., Undar, H. N., Bayraktar, Y. S., Celik, J. B., Tokur, M. E., Aydin, D. T., Yildiz, I., Ozcan, B., Akdag, D., Unlu, N., Reyes, P. E., Ahmad, F. K. E., Smiley, K. A., Miller, M. T., Antonio, M. G. S., Qawasmeh, K. A., Shawish, S. A., Groba, C. B., Raj, A. S., Ei, P. P., Legorburo, M. S., Welters, I. D., Mcmullen, J., Mcdonnell, A., Rose, B. O., Delgado, C. C., Mccann, N., Turner, S. J., Rodriguez, G. E., Eltorai, A. S., Pastores, S. M., Demarre, L., and Debue, A. -S.

Subjects
Male, Original, medicine.medical_treatment, artificial, Critical Care and Intensive Care Medicine, Medical and Health Sciences, Pressure ulcer, law.invention, Decubitus epidemiology, ICU, Morbidity, Mortality, Outcome, Pressure injury, Risk factors, Adult, Aged, Hospital Mortality, Humans, Patient Discharge, Prevalence, Risk Factors, Intensive Care Units, Respiration, Artificial, 0302 clinical medicine, decubitus epidemiology, pressure injury, pressure ulcer, outcome, risk factors, morbidity, mortality, law, Medicine and Health Sciences, adults, Medicine, Simplified Acute Physiology Score, icu, ziekenhuissterfte, Immunodeficiency, intensive care, European Society of Intensive Care Medicine (ESICM) Trials Group Collaborators, mannen, volwassenen, COST, Intensive care unit, STATE, ULCERS, Underweight, medicine.symptom, Life Sciences & Biomedicine, Human, medicine.medical_specialty, risicofactoren, Decubitus epidemiology, ICU, Pressure injury, Pressure ulcer, Outcome, Risk factors, Morbidity, Mortality, pressure injuries, Intensive Care Unit, prevalentie, NO, 1117 Public Health and Health Services, DecubICUs Study Team, 03 medical and health sciences, Critical Care Medicine, Anesthesiology, General & Internal Medicine, Health Sciences, ouderen, Mechanical ventilation, Science & Technology, business.industry, decubitus, Risk Factor, 030208 emergency & critical care medicine, 1103 Clinical Sciences, Odds ratio, medicine.disease, Emergency & Critical Care Medicine, Confidence interval, 030228 respiratory system, Emergency medicine, kunstmatige ademhaling, RISK-FACTORS, business, respiration
Abstract

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347, Funder: Flemish Society for Critical Care Nurses, Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score < 19, ICU stay > 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat.

Published
2021
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50. Mutational landscape of primary pulmonary salivary gland-type tumors through targeted next-generation sequencing

Author

Yuxia Xu, Xin-Hua Yang, Wen-Wen Hao, Xiao-yan Wu, Ling Deng, Shao-Yan Xi, Liang Zeng, Kai-Hua Guo, Fang Wang, and Hai-Yun Wang

Subjects
Pulmonary and Respiratory Medicine, Cancer Research, Lung Neoplasms, Adenoid cystic carcinoma, medicine.disease_cause, DNA sequencing, Salivary Glands, Minor Histocompatibility Antigens, Phosphatidylinositol 3-Kinases, Mucoepidermoid carcinoma, medicine, Biomarkers, Tumor, Humans, MYB, In Situ Hybridization, Fluorescence, Mutation, Salivary gland, medicine.diagnostic_test, business.industry, High-Throughput Nucleotide Sequencing, Nuclear Proteins, RNA-Binding Proteins, Forkhead Transcription Factors, medicine.disease, Repressor Proteins, medicine.anatomical_structure, Oncology, Cancer research, Immunohistochemistry, Carcinoma, Mucoepidermoid, business, Fluorescence in situ hybridization
Abstract

Primary pulmonary salivary gland-type tumors (PSGTs) mainly comprise of mucoepidermoid carcinoma (MEC) and adenoid cystic carcinoma (ACC), which are rare and molecularly poorly understood. This study aimed to profile the molecular alterations of PSGTs via targeted next-generation sequencing (NGS).Immunohistochemistry was used to screen PSGTs in 32 patients and MAML2 and MYB rearrangements were detected using fluorescence in situ hybridization. 1021-Genepanel of targeted NGS was conducted to profile genomic mutations in all the PSGT patients.Among the 32 patients, 25 had MEC and 7 had ACC. MAML2 and MYB rearrangements were detected in 80.0% (20/25) of the MEC and 71.4% (5/7) of the ACC patients. Among the MEC patients, 10 (40.0%) had ≥1 mutation, and 6 of them had 11 isolated mutations with abundance5%, namely NFE2L2, MYOD1, INPP4B, CCND2, SNTG1, HSPD1, TGFBR1, RBM10, NOTCH4, ASXL1, and PTPRD mutations. The remaining 4 patients had 9 mutations with abundance5%, namely KMT2A, PDCD11, FLT1, BRCA2, APC, SLX4, FOXP1, FGFR1, and HRAS mutations. All the ACC patients had mutations, which were enriched in 5 pathways including the PI3K and NOTCH pathways, chromatin and cytoskeleton remodeling, and DNA damage. These results explain PSGTs harbor distinct driver features of MAML2 or MYB rearrangement, accompanied with wide mutational diversity with very low rate of somatic mutation. Several important pathways, including the NOTCH and PI3K pathways, and chromatin remodeling could be targeted to improve the survival in patients with ACC.

Published
2021

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