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1. Metformin Reduces Blood Glucose in Treatment-Naive Type 2 Diabetes by Altering the Gut Microbiome

Author

Daqiang He, Xianjun Wang, Anbing Liu, Xianfeng Zhang, Hui Han, Lizhen Ma, Yuhong Zhan, Xiaodan Fu, and Haiyan Qiu

Subjects
Blood Glucose, Klebsiella, endocrine system diseases, Klebsiella pneumoniae, Endocrinology, Diabetes and Metabolism, Physiology, Type 2 diabetes, Gut flora, Spearman's rank correlation coefficient, Endocrinology, RNA, Ribosomal, 16S, Internal Medicine, Humans, Medicine, Glycated Hemoglobin, biology, business.industry, digestive, oral, and skin physiology, nutritional and metabolic diseases, General Medicine, biology.organism_classification, medicine.disease, Metformin, Gut microbiome, Gastrointestinal Microbiome, Glucose, Diabetes Mellitus, Type 2, business, medicine.drug, Megamonas
Abstract

Background To investigate the causality between metformin and gut microbiome in the treatment of type 2 diabetes (T2D). Methods This study was conducted on individuals with newly diagnosed and treatment-naive T2D. We used 16s rRNA sequencing to understand the effect of metformin on the composition and diversity of the gut microbiota. We also compared the differences in relative abundances of gut microbiome at the genus level in treatment-naive T2D patients before and after metformin treatment for 2 months and used Spearman rank correlation coefficient analysis of genus abundance in relation to blood glucose and related factors. Results Metformin significantly reduced blood glucose and levels of the related factors in treatment-naive individuals with T2D after 2 months of treatment. 16s rRNA sequencing showed that metformin treatment altered the composition and diversity of the gut microbiome. Differences in relative abundances at the genus level among groups revealed that Megamonas and Klebsiella in T2D groups were significantly higher compared with those in the control group. Treatment with metformin caused a significant reduction in the abundances of Megamonas and Klebsiella. Spearman rank correlation coefficient analysis showed a significant positive correlation between Megamonas and blood glucose, HbA1c, GSP, and ALT. In Klebsiella, a significant positive correlation between HbA1c and ALT was found. Conclusions Metformin reduces blood glucose in T2D by interaction with different gut bacteria, possibly Megamonas and Klebsiella pneumoniae.

Published
2022

2. Value of pneumococcal vaccination in controlling the development of antimicrobial resistance (AMR): Case study using DREAMR in Ethiopia

Author

A. P. Stringer, Gauri G. Rao, Hui-Han Chen, Sachiko Ozawa, and Tadesse Eguale

Subjects
medicine.drug_class, Cost-Benefit Analysis, Antibiotics, Pneumococcal Infections, Pneumococcal conjugate vaccine, Pneumococcal Vaccines, Antibiotic resistance, Environmental health, Drug Resistance, Bacterial, medicine, Global health, Humans, Vaccines, Conjugate, General Veterinary, General Immunology and Microbiology, business.industry, Vaccination, Public Health, Environmental and Occupational Health, Infant, Amoxicillin, Anti-Bacterial Agents, Infectious Diseases, Immunization, Ceftriaxone, Molecular Medicine, Ethiopia, business, medicine.drug
Abstract

Background Antimicrobial resistance (AMR) poses an imminent threat to global health security. Pneumococcal vaccination reduces disease incidence, prevents antibiotic use, and decreases antibiotic-resistant infections. However, the benefit of vaccination in reducing AMR has been poorly quantified to date. Methods We developed an agent-based model, DREAMR (Dynamic Representation of the Economics of AMR) to evaluate the economic value of childhood immunization with the pneumococcal conjugate vaccine (PCV) in mitigating the development of AMR. Our model incorporates vaccination coverage, disease incidence, care seeking, and antibiotic use. Accumulation of AMR is simulated based on antibiotic exposure through pharmacokinetics and resulting pharmacodynamics. The model was applied to Ethiopia. Results Introduction of PCV vaccination has helped slow the development of AMR by 14.77% for amoxicillin and 0.59% for ceftriaxone in Ethiopia since 2011. In addition to the benefit of reduction in disease incidence, PCV vaccination has averted approximately 718,100 antibiotic treatment failures and 9,520 AMR-related deaths (27.8% reduction) in Ethiopia between 2011 and 2017, resulting in savings of $32.7 million. Maintaining current PCV immunization coverage will contribute an additional $7.67 million in annual AMR cost savings over five years compared to no vaccination scenario, which could increase to $11.43 million by increasing PCV coverage to 85% by 2022. Conclusions This study is the first to demonstrate the broader economic value of pneumococcal vaccination in controlling the development of AMR in Africa. Vaccination not only saves lives by preventing illnesses, but also benefits society by reducing antibiotic utilization and treatment failures due to AMR.

Published
2021

3. High Expression of PKM2 Was Associated with the Poor Prognosis of Acute Leukemia

Author

Luo-jia Wang, Bao-fang Zhu, Yunxiu Huang, Hui Han, Lin-mu Chen, Weijia Wang, and Jin-ye Xie

Subjects
medicine.medical_specialty, Acute leukemia, Receiver operating characteristic, business.industry, Incidence (epidemiology), breakpoint cluster region, Myeloid leukemia, acute lymphoblastic leukemia, acute myeloid leukemia, Gastroenterology, Oncology, hemic and lymphatic diseases, Internal medicine, Genotype, medicine, Clinical significance, acute leukemia, pyruvate kinase M2, business, Survival analysis, Original Research
Abstract

Purpose To explore the clinical significance of plasma pyruvate kinase M2 (PKM2) in assessing the incidence and prognosis of acute leukemia. Methods Plasma samples from 56 acute myeloid leukemia (AML) patients, 40 acute lymphoblastic leukemia (ALL) patients, and 66 plasma samples from healthy individuals were collected. The level of plasma PKM2 was detected by enzyme-linked immunosorbent assay. The clinical significance of PKM2 in acute leukemia was assessed by analyzing receiver operating characteristic and survival curves. Results The plasma levels of PKM2 in AML or ALL patients were significantly higher than those in healthy individuals, respectively. PKM2 can be used as a potential diagnostic index with the AUC of 0.827 for AML and 0.837 for ALL. The level of plasma PKM2 in ALL patients with a BCR/ABL-positive genotype was significantly higher than that in patients with a BCR/ABL-negative genotype (p

Published
2021

5. Deep Learning-Based Wavelet Threshold Function Optimization on Noise Reduction in Ultrasound Images

Author

Zhuxiang Shen, Hui Han, and Wei Li

Subjects
Article Subject, Mean squared error, business.industry, Noise (signal processing), Computer science, Noise reduction, Wavelet transform, Speckle noise, Image processing, Pattern recognition, Convolutional neural network, Computer Science Applications, QA76.75-76.765, Wavelet, Computer Science::Computer Vision and Pattern Recognition, Computer software, Artificial intelligence, business, Software
Abstract

To explore the utilization of the convolutional neural network (CNN) and wavelet transform in ultrasonic image denoising and the influence of the optimized wavelet threshold function (WTF) algorithm on image denoising, in this exploration, first, the imaging principle of ultrasound images is studied. Due to the limitation of the principle of ultrasound imaging, the inherent speckle noise will seriously affect the quality of ultrasound images. The denoising principle of the WTF based on the wavelet transform is analyzed. Based on the traditional threshold function algorithm, the optimized WTF algorithm is proposed and applied to the simulation experiment of ultrasound images. By comparing quantitatively and qualitatively with the traditional threshold function algorithm, the advantages of the optimized WTF algorithm are analyzed. The results suggest that the image is denoised by the optimized WTF. The mean square error (MSE), peak signal-to-noise ratio (PSNR), and structural similarity index measurement (SSIM) of the images are 20.796 dB, 34.294 dB, and 0.672 dB, respectively. The denoising effect is better than the traditional threshold function. It can denoise the image to the maximum extent without losing the image information. In addition, in this exploration, the optimized function is applied to the actual medical image processing, and the ultrasound images of arteries and kidneys are denoised separately. It is found that the quality of the denoised image is better than that of the original image, and the extraction of effective information is more accurate. In summary, the optimized WTF algorithm can not only remove a lot of noise but also obtain better visual effect. It has important value in assisting doctors in disease diagnosis, so it can be widely applied in clinics.

Published
2021

6. A New Time-Window Prediction Model For Traumatic Hemorrhagic Shock Based on Interpretable Machine Learning

Author

Li Tanshi, Hongxin Wang, Wei Chen, Guo Xin, Zhaohong Wang, Jing Li, Yuzhuo Zhao, Xiucheng Li, Cong Feng, Lijing Jia, Zijian Wei, Zheyuan Yu, Jiaming Wang, Heng Zhang, Hui Han, Shuxiao Pan, Xueyan Li, and Ruiqi Jia

Subjects
Male, systolic blood pressure, Computer science, the Medical Information Mart for Intensive Care III, 95% confidence interval, Critical Care and Intensive Care Medicine, computer.software_genre, Clinical Science Aspects, AUPRC, DBP, Machine Learning, Time windows, HR, heart rate, Interpretability, electronic medical record, RESP, prediction window, AUROC, LOS, TEMP, EMR, IQR, area under the receiver operating characteristic curve, blood pressure, Middle Aged, base excess, PaCO2, partial pressure of carbon dioxide, shock index, 95% CI, Shapley additive explanation, Hct, area under the precision-recall curve, SHAP, platelets, Emergency Medicine, Female, Algorithms, PLAGH-ERD, partial pressure of oxygen, Adult, TCO2, interquartile range, hematocrit, mean blood pressure, total carbon dioxide, BE, the PLA General Hospital Emergency Rescue Database, PLT, WBC, Shock, Hemorrhagic, Machine learning, traumatic hemorrhagic shock, BP, THS, length of stay, MBP, Humans, respiration rate, SI, SBP, Aged, Lac, lactate, Vital Signs, business.industry, Hb, diastolic blood pressure, temperature, PaO2, hemoglobin, Logistic Models, Hemorrhagic shock, Artificial intelligence, time series, MIMIC III, Blood Gas Analysis, business, computer, white blood cell count
Abstract

Early warning prediction of traumatic hemorrhagic shock (THS) can greatly reduce patient mortality and morbidity. We aimed to develop and validate models with different stepped feature sets to predict THS in advance. From the PLA General Hospital Emergency Rescue Database and Medical Information Mart for Intensive Care III, we identified 604 and 1,614 patients, respectively. Two popular machine learning algorithms (i.e., extreme gradient boosting [XGBoost] and logistic regression) were applied. The area under the receiver operating characteristic curve (AUROC) was used to evaluate the performance of the models. By analyzing the feature importance based on XGBoost, we found that features in vital signs (VS), routine blood (RB), and blood gas analysis (BG) were the most relevant to THS (0.292, 0.249, and 0.225, respectively). Thus, the stepped relationships existing in them were revealed. Furthermore, the three stepped feature sets (i.e., VS, VS + RB, and VS + RB + sBG) were passed to the two machine learning algorithms to predict THS in the subsequent T hours (where T = 3, 2, 1, or 0.5), respectively. Results showed that the XGBoost model performance was significantly better than the logistic regression. The model using vital signs alone achieved good performance at the half-hour time window (AUROC = 0.935), and the performance was increased when laboratory results were added, especially when the time window was 1 h (AUROC = 0.950 and 0.968, respectively). These good-performing interpretable models demonstrated acceptable generalization ability in external validation, which could flexibly and rollingly predict THS T hours (where T = 0.5, 1) prior to clinical recognition. A prospective study is necessary to determine the clinical utility of the proposed THS prediction models.

Published
2021

7. Assessment of intramyocardial hemorrhage with dark-blood T2*-weighted cardiovascular magnetic resonance

Author

Xinheng Zhang, John Butler, Hsin-Jung Yang, Xingmin Guan, Hui Han, Mengsu Zeng, Frank S. Prato, Yinyin Chen, Rohan Dharmakumar, Jane Sykes, and Daoyuan Ren

Subjects
Magnetic Resonance Spectroscopy, genetic structures, Dark-blood T2, Myocardial Infarction, 030204 cardiovascular system & hematology, Cardiorespiratory Medicine and Haematology, Cardiovascular, 030218 nuclear medicine & medical imaging, 0302 clinical medicine, Myocardial infarction, screening and diagnosis, Radiological and Ultrasound Technology, medicine.diagnostic_test, Magnetic Resonance Imaging, Detection, Nuclear Medicine & Medical Imaging, Intramyocardial hemorrhage, Cardiology, cardiovascular system, Bright-blood T2, Biomedical Imaging, Cardiology and Cardiovascular Medicine, T2 weighted, 4.2 Evaluation of markers and technologies, circulatory and respiratory physiology, medicine.medical_specialty, T2*MRI, Hemorrhage, T2* MRI, 03 medical and health sciences, Dogs, Predictive Value of Tests, Internal medicine, medicine, Animals, Humans, Diseases of the circulatory (Cardiovascular) system, Radiology, Nuclear Medicine and imaging, cardiovascular diseases, Reference standards, Angiology, business.industry, Research, Myocardium, Magnetic resonance imaging, medicine.disease, 4.1 Discovery and preclinical testing of markers and technologies, RC666-701, Dark blood, sense organs, business
Abstract

Background Intramyocardial hemorrhage (IMH) within myocardial infarction (MI) is associated with major adverse cardiovascular events. Bright-blood T2*-based cardiovascular magnetic resonance (CMR) has emerged as the reference standard for non-invasive IMH detection. Despite this, the dark-blood T2*-based CMR is becoming interchangeably used with bright-blood T2*-weighted CMR in both clinical and preclinical settings for IMH detection. To date however, the relative merits of dark-blood T2*-weighted with respect to bright-blood T2*-weighted CMR for IMH characterization has not been studied. We investigated the diagnostic capacity of dark-blood T2*-weighted CMR against bright-blood T2*-weighted CMR for IMH characterization in clinical and preclinical settings. Materials and methods Hemorrhagic MI patients (n = 20) and canines (n = 11) were imaged in the acute and chronic phases at 1.5 and 3 T with dark- and bright-blood T2*-weighted CMR. Imaging characteristics (Relative signal-to-noise (SNR), Relative contrast-to-noise (CNR), IMH Extent) and diagnostic performance (sensitivity, specificity, accuracy, area-under-the-curve, and inter-observer variability) of dark-blood T2*-weighted CMR for IMH characterization were assessed relative to bright-blood T2*-weighted CMR. Results At both clinical and preclinical settings, compared to bright-blood T2*-weighted CMR, dark-blood T2*-weighted images had significantly lower SNR, CNR and reduced IMH extent (all p p Conclusion While IMH can be visible on dark-blood T2*-weighted CMR, the overall conspicuity of IMH is significantly reduced compared to that observed in bright-blood T2*-weighted images, across infarct age in clinical and preclinical settings at 1.5 and 3 T. Hence, bright-blood T2*-weighted CMR would be preferable for clinical use since dark-blood T2*-weighted CMR carries the potential to misclassify hemorrhagic MIs as non-hemorrhagic MIs.

Published
2021

8. Promoting, seeking, and reaching vaccination services: A systematic review of costs to immunization programs, beneficiaries, and caregivers

Author

Colleen R. Higgins, Taiwo Abimbola, Patrick T. Wedlock, Sarah Wood Pallas, Tatenda T. Yemeke, Aaron S. Wallace, Sarah M. Bartsch, Bruce Y. Lee, Hui Han Chen, Sachiko Ozawa, and Elizabeth A. Mitgang

Subjects
Vaccination Coverage, Population, Psychological intervention, Scopus, 03 medical and health sciences, 0302 clinical medicine, 030225 pediatrics, Environmental health, Humans, Medicine, 030212 general & internal medicine, education, Productivity, health care economics and organizations, education.field_of_study, General Veterinary, General Immunology and Microbiology, Immunization Programs, business.industry, Vaccination, Public Health, Environmental and Occupational Health, Infectious Diseases, Caregivers, Immunization, Vaccination coverage, Molecular Medicine, business, Know-how
Abstract

Introduction Understanding the costs to increase vaccination demand among under-vaccinated populations, as well as costs incurred by beneficiaries and caregivers for reaching vaccination sites, is essential to improving vaccination coverage. However, there have not been systematic analyses documenting such costs for beneficiaries and caregivers seeking vaccination. Methods We searched PubMed, Scopus, and the Immunization Delivery Cost Catalogue (IDCC) in 2019 for the costs for beneficiaries and caregivers to 1) seek and know how to access vaccination (i.e., costs to immunization programs for social mobilization and interventions to increase vaccination demand), 2) take time off from work, chores, or school for vaccination (i.e., productivity costs), and 3) travel to vaccination sites. We assessed if these costs were specific to populations that faced other non-cost barriers, based on a framework for defining hard-to-reach and hard-to-vaccinate populations for vaccination. Results We found 57 studies describing information, education, and communication (IEC) costs, social mobilization costs, and the costs of interventions to increase vaccination demand, with mean costs per dose at $0.41 (standard deviation (SD) $0.83), $18.86 (SD $50.65) and $28.23 (SD $76.09) in low-, middle-, and high-income countries, respectively. Five studies described productivity losses incurred by beneficiaries and caregivers seeking vaccination ($38.33 per person; SD $14.72; n = 3). We identified six studies on travel costs incurred by beneficiaries and caregivers attending vaccination sites ($11.25 per person; SD $9.54; n = 4). Two studies reported social mobilization costs per dose specific to hard-to-reach populations, which were 2–3.5 times higher than costs for the general population. Eight studies described barriers to vaccination among hard-to-reach populations. Conclusion Social mobilization/IEC costs are well-characterized, but evidence is limited on costs incurred by beneficiaries and caregivers getting to vaccination sites. Understanding the potential incremental costs for populations facing barriers to reach vaccination sites is essential to improving vaccine program financing and planning.

Published
2021

9. Systematic review of the costs for vaccinators to reach vaccination sites: Incremental costs of reaching hard-to-reach populations

Author

Colleen R. Higgins, Taiwo Abimbola, Bruce Y. Lee, Elizabeth A. Mitgang, Sachiko Ozawa, Hui-Han Chen, Tatenda T. Yemeke, Sarah Wood Pallas, Sarah M. Bartsch, Aaron S. Wallace, and Patrick T. Wedlock

Subjects
Marginal cost, Motivation, Vaccines, General Veterinary, General Immunology and Microbiology, Immunization Programs, business.industry, Vaccination, Public Health, Environmental and Occupational Health, Beneficiary, Immunization (finance), Infectious Diseases, Incentive, Environmental health, Humans, Molecular Medicine, Medicine, Incremental costs, business, Activity-based costing, health care economics and organizations, Average cost
Abstract

Introduction Economic evidence on how much it may cost for vaccinators to reach populations is important to plan vaccination programs. Moreover, knowing the incremental costs to reach populations that have traditionally been undervaccinated, especially those hard-to-reach who are facing supply-side barriers to vaccination, is essential to expanding immunization coverage to these populations. Methods We conducted a systematic review to identify estimates of costs associated with getting vaccinators to all vaccination sites. We searched PubMed and the Immunization Delivery Cost Catalogue (IDCC) in 2019 for the following costs to vaccinators: (1) training costs; (2) labor costs, per diems, and incentives; (3) identification of vaccine beneficiary location; and (4) travel costs. We assessed if any of these costs were specific to populations that are hard-to-reach for vaccination, based on a framework for examining supply-side barriers to vaccination. Results We found 19 studies describing average vaccinator training costs at $0.67/person vaccinated or targeted (SD $0.94) and $0.10/dose delivered (SD $0.07). The average cost for vaccinator labor and incentive costs across 29 studies was $2.15/dose (SD $2.08). We identified 13 studies describing intervention costs for a vaccinator to know the location of a beneficiary, with an average cost of $19.69/person (SD $26.65), and six studies describing vaccinator travel costs, with an average cost of $0.07/dose (SD $0.03). Only eight of these studies described hard-to-reach populations for vaccination; two studies examined incremental costs per dose to reach hard-to-reach populations, which were 1.3–2 times higher than the regular costs. The incremental cost to train vaccinators was $0.02/dose, and incremental labor costs for targeting hard-to-reach populations were $0.16–$1.17/dose. Conclusion Additional comparative costing studies are needed to understand the potential differential costs for vaccinators reaching the vaccination sites that serve hard-to-reach populations. This will help immunization program planners and decision-makers better allocate resources to extend vaccination programs.

Published
2021

10. Outcome of acute hypoxaemic respiratory failure: insights from the LUNG SAFE Study

Author

Pham, Tài, Pesenti, Antonio, Bellani, Giacomo, Rubenfeld, Gordon, Fan, Eddy, Bugedo, Guillermo, Lorente, José Angel, Fernandes, Antero do Vale, Van Haren, Frank, Bruhn, Alejandro, Rios, Fernando, Esteban, Andres, Gattinoni, Luciano, Larsson, Anders, McAuley, Daniel F., Ranieri, Marco, Thompson, B. Taylor, Wrigge, Hermann, Brochard, Laurent J., Laffey, John G, Antonio Pesenti, John G Laffey, Laurent Brochard, Andres Esteban, Luciano Gattinoni, Frank van Haren, Anders Larsson, Daniel F McAuley, Marco Ranieri, Gordon Rubenfeld, B Taylor Thompson, Hermann Wrigge, Arthur S Slutsky, Giacomo Bellani, Tài Pham, Eddy Fan, Fernando Rios, Thierry Sottiaux, Pieter Depuydt, Fredy S Lora, Luciano Cesar Azevedo, Guillermo Bugedo, Haibo Qiu, Marcos Gonzalez, Juan Silesky, Vladimir Cerny, Jonas Nielsen, Manuel Jibaja, Dimitrios Matamis, Jorge Luis Ranero, Pravin Amin, S M Hashemian, Kevin Clarkson, Kiyoyasu Kurahashi, Asisclo Villagomez, Amine Ali Zeggwagh, Leo M Heunks, Jon Henrik Laake, Jose Emmanuel Palo, Antero do Vale Fernandes, Dorel Sandesc, Yaasen Arabi, Vesna Bumbasierevic, Nicolas Nin, Jose A Lorente, Lise Piquilloud, Fekri Abroug, Lia McNamee, Javier Hurtado, Ed Bajwa, Gabriel Démpaire, Hektor Sula, Lordian Nunci, Alma Cani, Alan Zazu, Christian Dellera, Carolina S Insaurralde, Risso V Alejandro, Julio Daldin, Mauricio Vinzio, Ruben O Fernandez, Luis P Cardonnet, Lisandro R Bettini, Mariano Carboni Bisso, Emilio M Osman, Mariano G Setten, Pablo Lovazzano, Javier Alvarez, Veronica Villar, Norberto C Pozo, Nicolas Grubissich, Gustavo A Plotnikow, Daniela N Vasquez, Santiago Ilutovich, Norberto Tiribelli, Ariel Chena, Carlos A Pellegrini, María G Saenz, Elisa Estenssoro, Matias Brizuela, Hernan Gianinetto, Pablo E Gomez, Valeria I Cerrato, Marco G Bezzi, Silvina A Borello, Flavia A Loiacono, Adriana M Fernandez, Serena Knowles, Claire Reynolds, Deborah M Inskip, Jennene J Miller, Jing Kong, Christina Whitehead, Shailesh Bihari, Aylin Seven, Amanda Krstevski, Helen J Rodgers, Rebecca T Millar, Toni E McKenna, Irene M Bailey, Gabrielle C Hanlon, Anders Aneman, Joan M Lynch, Raman Azad, John Neal, Paul W Woods, Brigit L Roberts, Mark R Kol, Helen S Wong, Katharina C Riss, Thomas Staudinger, Xavier Wittebole, Caroline Berghe, Pierre A Bulpa, Alain M Dive, Rik Verstraete, Herve Lebbinck, Joris Vermassen, Philippe Meersseman, Helga Ceunen, Jonas I Rosa, Daniel O Beraldo, Claudio Piras, Adenilton M Rampinelli, Antonio P Nassar Jr, Sergio Mataloun, Marcelo Moock, Marlus M Thompson, Claudio H Gonçalves, Ana Carolina P Antônio, Aline Ascoli, Rodrigo S Biondi, Danielle C Fontenele, Danielle Nobrega, Vanessa M Sales, Ahmad Yazid Bin Hj Abul Wahab, Maizatul Ismail, Suresh Shindhe, John Laffey, Francois Beloncle, Kyle G Davies, Rob Cirone, Venika Manoharan, Mehvish Ismail, Ewan C Goligher, Mandeep Jassal, Erin Nishikawa, Areej Javeed, Gerard Curley, Nuttapol Rittayamai, Matteo Parotto, Niall D Ferguson, Sangeeta Mehta, Jenny Knoll, Antoine Pronovost, Sergio Canestrini, Alejandro R Bruhn, Patricio H Garcia, Felipe A Aliaga, Pamela A Farías, Jacob S Yumha, Claudia A Ortiz, Javier E Salas, Alejandro A Saez, Luis D Vega, Eduardo F Labarca, Felipe T Martinez, Nicolás G Carreño, Pilar Lora, Haitao Liu, Ling Liu, Rui Tang, Xiaoming Luo, Youzhong An, Huiying Zhao, Yan Gao, Zhe Zhai, Zheng L Ye, Wei Wang, Wenwen Li, Qingdong Li, Ruiqiang Zheng, Wenkui Yu, Juanhong Shen, Xinyu Li, Tao Yu, Weihua Lu, Ya Q Wu, Xiao B Huang, Zhenyang He, Yuanhua Lu, Hui Han, Fan Zhang, Renhua Sun, Hua X Wang, Shu H Qin, Bao H Zhu, Jun Zhao, Jian Liu, Bin Li, Jing L Liu, Fa C Zhou, Qiong J Li, Xing Y Zhang, Zhou Li-Xin, Qiang Xin-Hua, Liangyan Jiang, Yuan N Gao, Xian Y Zhao, Yuan Y Li, Xiao L Li, Chunting Wang, Qingchun Yao, Rongguo Yu, Kai Chen, Huanzhang Shao, Bingyu Qin, Qing Q Huang, Wei H Zhu, Ai Y Hang, Ma X Hua, Yimin Li, Yonghao Xu, Yu D Di, Long L Ling, Tie H Qin, Shou H Wang, Junping Qin, Yi Han, Suming Zhou, Monica P Vargas, Juan I Silesky Jimenez, Manuel A González Rojas, Jaime E SolisQuesada, Christian M Ramirez-Alfaro, Jan Máca, Peter Sklienka, Jakob Gjedsted, Aage Christiansen, Boris G Villamagua, Iguel Llano, Philippe Burtin, Gautier Buzancais, Pascal Beuret, Nicolas Pelletier, Satar Mortaza, Alain Mercat, Jonathan Chelly, Sébastien Jochmans, Nicolas Terzi, Cédric Daubin, Guillaume Carteaux, Nicolas de Prost, Jean-Daniel Chiche, Fabrice Daviaud, Muriel Fartoukh, Guillaume Barberet, Jerome Biehler, Jean Dellamonica, Denis Doyen, Jean-Michel Arnal, Anais Briquet, Sami Hraiech, Laurent Papazian, Arnaud Follin, Damien Roux, Jonathan Messika, Evangelos Kalaitzis, Laurence Dangers, Alain Combes, Siu-Ming Au, Gaetan Béduneau, Dorothée Carpentier, Elie H Zogheib, Herve Dupont, Sylvie Ricome, Francesco L Santoli, Sebastien L Besset, Philippe Michel, Bruno Gelée, Pierre-Eric Danin, Bernard Goubaux, Philippe J Crova, Nga T Phan, Frantz Berkelmans, Julio C Badie, Romain Tapponnier, Josette Gally, Samy Khebbeb, Jean-Etienne Herbrecht, Francis Schneider, PierreLouis M Declercq, Jean-Philippe Rigaud, Jacques Duranteau, Anatole Harrois, Russell Chabanne, Julien Marin, Charlene Bigot, Sandrine Thibault, Mohammed Ghazi, Messabi Boukhazna, Salem Ould Zein, Jack R Richecoeur, Daniele M Combaux, Fabien Grelon, Charlene Le Moal, Elise P Sauvadet, Adrien Robine, Virginie Lemiale, Danielle Reuter, Martin Dres, Alexandre Demoule, Dany Goldgran-Toledano, Loredana Baboi, Claude Guérin, Ralph Lohner, Jens Kraßler, Susanne Schäfer, Kai D Zacharowski, Patrick Meybohm, Andreas W Reske, Philipp Simon, HansBernd F Hopf, Michael Schuetz, Thomas Baltus, Metaxia N Papanikolaou, Theonymfi G Papavasilopoulou, Giannis A Zacharas, Vasilis Ourailogloy, Eleni K Mouloudi, Eleni V Massa, Eva O Nagy, Electra E Stamou, Ellada V Kiourtzieva, Marina A Oikonomou, Luis E Avila, Cesar A Cortez, Johanna E Citalán, Sameer A Jog, Safal D Sable, Bhagyesh Shah, Mohan Gurjar, Arvind K Baronia, Mohammedfaruk Memon, Radhakrishnan Muthuchellappan, Venkatapura J Ramesh, Anitha Shenoy, Ramesh Unnikrishnan, Subhal B Dixit, Rachana V Rhayakar, Nagarajan Ramakrishnan, Vallish K Bhardwaj, Heera L Mahto, Sudha V Sagar, Vijayanand Palaniswamy, Deeban Ganesan, Seyed Mohammadreza Hashemian, Hamidreza Jamaati, Farshad Heidari, Edel A Meaney, Alistair Nichol, Karl M Knapman, Donall O'Croinin, Eimhin S Dunne, Dorothy M Breen, Kevin P Clarkson, Rola F Jaafar, Rory Dwyer, Fahd Amir, Olaitan O Ajetunmobi, Aogan C O'Muircheartaigh, Colin S Black, Nuala Treanor, Daniel V Collins, Wahid Altaf, Gianluca Zani, Maurizio Fusari, Savino Spadaro, Carlo A Volta, Romano Graziani, Barbara Brunettini, Salvatore Palmese, Paolo Formenti, Michele Umbrello, Andrea Lombardo, Elisabetta Pecci, Marco Botteri, Monica Savioli, Alessandro Protti, Alessia Mattei, Lorenzo Schiavoni, Andrea Tinnirello, Manuel Todeschini, Antonino Giarratano, Andrea Cortegiani, Massimo M Antonelli, Luca M Montini, Paolo Casalena, Sergio Scafetti, Giovanna Panarello, Giovanna Occhipinti, Nicolò Patroniti, Matteo Pozzi, Roberto R Biscione, Michela M Poli, Ferdinando Raimondi, Daniela Albiero, Giulia Crapelli, Eduardo Beck, Vincenzo Pota, Vincenzo Schiavone, Alexandre Molin, Fabio Tarantino, Giacomo Monti, Elena Frati, Lucia Mirabella, Gilda Cinnella, Tommaso Fossali, Riccardo Colombo, Pierpaolo Terragni, Ilaria Pattarino, Francesco Mojoli, Antonio Braschi, Erika E Borotto, Andrea N Cracchiolo, Daniela M Palma, Francesco Raponi, Giuseppe Foti, Ettore R Vascotto, Andrea Coppadoro, Luca Brazzi, Leda Floris, Giorgio A Iotti, Aaron Venti, Osamu Yamaguchi, Shunsuke Takagi, Hiroki N Maeyama, Eizo Watanabe, Yoshihiro Yamaji, Kazuyoshi Shimizu, Kyoko Shiozaki, Satoru Futami, Sekine Ryosuke, Koji Saito, Yoshinobu Kameyama, Keiko Ueno, Masayo Izawa, Nao Okuda, Hiroyuki Suzuki, Tomofumi Harasawa, Michitaka Nasu, Tadaaki Takada, Fumihito Ito, Shin Nunomiya, Kansuke Koyama, Toshikazu Abe, Kohkichi Andoh, Kohei Kusumoto, Akira Hirata, Akihiro Takaba, Hiroyasu Kimura, Shuhei Matsumoto, Ushio Higashijima, Hiroyuki Honda, Nobumasa Aoki, Hiroshi Imai, Yasuaki Ogino, Ichiko Mizuguchi, Kazuya Ichikado, Kenichi Nitta, Katsunori Mochizuki, Tomoaki Hashida, Hiroyuki Tanaka, Tomoyuki Nakamura, Daisuke Niimi, Takeshi Ueda, Yozo Kashiwa, Akinori Uchiyama, Olegs Sabelnikovs, Peteris Oss, Youssef Haddad, Kong Y Liew, Silvio A Ñamendys-Silva, Yves D Jarquin-Badiola, Luis A Sanchez-Hurtado, Saira S Gomez-Flores, Maria C Marin, Asisclo J Villagomez, Jordana S Lemus, Jonathan M Fierro, Mavy Ramirez Cervantes, Francisco Javier Flores Mejia, Dulce Dector, Alejandro Rojas, Daniel R Gonzalez, Claudia R Estrella, Jorge R Sanchez-Medina, Alvaro Ramirez-Gutierrez, Fernando G George, Janet S Aguirre, Juan A Buensuseso, Manuel Poblano, Tarek Dendane, Hicham Balkhi, Mina Elkhayari, Nacer Samkaoui, Hanane Ezzouine, Abdellatif Benslama, Mourad Amor, Wajdi Maazouzi, Nedim Cimic, Oliver Beck, Monique M Bruns, Jeroen A Schouten, Myra Rinia, Monique Raaijmakers, Hellen M van Wezel, Serge J Heines, Ulrich Strauch, Marc P Buise, Fabienne D Simonis, Marcus J Schultz, Jennifer C Goodson, Troy S Browne, Leanlove Navarra, Anna Hunt, Robyn A Hutchison, Mathew B Bailey, Lynette Newby, Colin McArthur, Michael Kalkoff, Alex Mcleod, Jonathan Casement, Danielle J Hacking, Finn H Andersen, Merete S Dolva, Jon H Laake, Andreas Barratt-Due, Kim Andre L Noremark, Eldar Søreide, Brit Å Sjøbø, Anne B Guttormsen, Hector H Leon Yoshido, Ronald Zumaran Aguilar, Fredy A Montes Oscanoa, Alain U Alisasis, Joanne B Robles, Rossini Abbie B Pasanting-Lim, Beatriz C Tan, Pawel Andruszkiewicz, Karina Jakubowska, Cristina M Coxo, António M Alvarez, Bruno S Oliveira, Gustavo M Montanha, Nelson C Barros, Carlos S Pereira, António M Messias, Jorge M Monteiro, Ana M Araujo, Nuno T Catorze, Susan M Marum, Maria J Bouw, Rui M Gomes, Vania A Brito, Silvia Castro, Joana M Estilita, Filipa M Barros, Isabel M Serra, Aurelia M Martinho, Dana R Tomescu, Alexandra Marcu, Ovidiu H Bedreag, Marius Papurica, Dan E Corneci, Silvius Ioan Negoita, Evgeny Grigoriev, Alexey I Gritsan, Andrey A Gazenkampf, Ghaleb Almekhlafi, Mohamad M Albarrak, Ghanem M Mustafa, Khalid A Maghrabi, Nawal Salahuddin, Tharwat M Aisa, Ahmed S Al Jabbary, Edgardo Tabhan, Yaseen M Arabi, Olivia A Trinidad, Hasan M Al Dorzi, Edgardo E Tabhan, Vesna Bumbasirevic, Bojan Jovanovic, Stefan Bolon, Oliver Smith, Jordi Mancebo, Hernan Aguirre-Bermeo, Juan C Lopez-Delgado, Francisco Esteve, Gemma Rialp, Catalina Forteza, Candelaria De Haro, Antonio Artigas, Guillermo M Albaiceta, Sara De Cima-Iglesias, Leticia Seoane-Quiroga, Alexandra Ceniceros-Barros, Antonio L RuizAguilar, Luis M Claraco-Vega, Juan Alfonso Soler, Maria Del Carmen Lorente, Cecilia Hermosa, Federico Gordo, Miryam PrietoGonzález, Juan B López-Messa, Manuel P Perez, Cesar P Perez, Raquel Montoiro Allue, Ferran RocheCampo, Marcos Ibañez-Santacruz, Susana TempranoSusana, Maria C Pintado, Raul De Pablo, Pilar Ricart Aroa Gómez, Silvia Rodriguez Ruiz, Silvia Iglesias Moles, Mª Teresa Jurado, Alfons Arizmendi, Enrique A Piacentini, Nieves Franco, Teresa Honrubia, Meisy Perez Cheng, Elena Perez Losada, Javier Blanco, Luis J Yuste, Cecilia Carbayo-Gorriz, Francisca G Cazorla-Barranquero, Javier G Alonso, Rosa S Alda, Ángela Algaba, Gonzalo Navarro, Enrique Cereijo, Esther Diaz-Rodriguez, Diego Pastor Marcos, Laura Alvarez Montero, Luis Herrera Para, Roberto Jimenez Sanchez, Miguel Angel Blasco Navalpotro, Ricardo Diaz Abad, Raquel Montiel González, Dácil Parrilla Toribio, Alejandro G Castro, Maria Jose D Artiga, Oscar Penuelas, Tomas P Roser, Moreno F Olga, Elena Gallego Curto, Rocío Manzano Sánchez, Vallverdu P Imma, Garcia M Elisabet, Laura Claverias, Monica Magret, Ana M Pellicer, Lucia L Rodriguez, Jesús Sánchez-Ballesteros, Ángela González-Salamanca, Antonio G Jimenez, Francisco P Huerta, Juan Carlos J Sotillo Diaz, Esther Bermejo Lopez, David D Llinares Moya, Alec A Tallet Alfonso, Palazon Sanchez Eugenio Luis, Palazon Sanchez Cesar, Sánchez I Rafael, Corcoles G Virgilio, Noelia N Recio, Christian C Rylander, Bernhard Holzgraefe, Lars M Broman, Joanna Wessbergh, Linnea Persson, Fredrik Schiöler, Hans Kedelv, Anna Oscarsson Tibblin, Henrik Appelberg, Lars Hedlund, Johan Helleberg, Karin E Eriksson, Rita Glietsch, Niklas Larsson, Ingela Nygren, Silvia L Nunes, Anna-Karin Morin, Thomas Kander, Anne Adolfsson, Hervé O Zender, Corinne Leemann-Refondini, Souheil Elatrous, Slaheddine Bouchoucha, Imed Chouchene, Islem Ouanes, Asma Ben Souissi, Salma Kamoun, Oktay Demirkiran, Mustafa Aker, Emre Erbabacan, Ilkay Ceylan, Nermin Kelebek Girgin, Menekse Ozcelik, Necmettin Ünal, Basak Ceyda Meco, Onat O Akyol, Suleyman S Derman, Barry Kennedy, Ken Parhar, Latha Srinivasa, Danny McAuley, Phil Hopkins, Clare Mellis, Vivek Kakar, Dan Hadfield, Andre Vercueil, Kaushik Bhowmick, Sally K Humphreys, Andrew Ferguson, Raymond Mckee, Ashok S Raj, Danielle A Fawkes, Philip Watt, Linda Twohey, Rajeev R Jha, Matthew Thomas, Alex Morton, Varsha Kadaba, Mark J Smith, Anil P Hormis, Santhana G Kannan, Miriam Namih, Henrik Reschreiter, Julie Camsooksai, Alek Kumar, Szabolcs Rugonfalvi, Christopher Nutt, Orla Oneill, Colette Seasman, Ged Dempsey, Christopher J Scott, Helen E Ellis, Stuart Mckechnie, Paula J Hutton, Nora N Di Tomasso, Michela N Vitale, Ruth O Griffin, Michael N Dean, Julius H Cranshaw, Emma L Willett, Nicholas Ioannou, Sarah Gillis, Peter Csabi, Rosaleen Macfadyen, Heidi Dawson, Pieter D Preez, Alexandra J Williams, Owen Boyd, Laura Ortiz-Ruiz de Gordoa, Jon Bramall, Sophie Symmonds, Simon K Chau, Tim Wenham, Tamas Szakmany, Piroska Toth-Tarsoly, Katie H McCalman, Peter Alexander, Lorraine Stephenson, Thomas Collyer, Rhiannon Chapman, Raphael Cooper, Russell M Allan, Malcolm Sim, David W Wrathall, Donald A Irvine, Kim S Zantua, John C Adams, Andrew J Burtenshaw, Gareth P Sellors, Ingeborg D Welters, Karen E Williams, Robert J Hessell, Matthew G Oldroyd, Ceri E Battle, Suresh Pillai, Istvan Kajtor, Mageswaran Sivashanmugavel, Sinead C Okane, Adrian Donnelly, Aniko D Frigyik, Jon P Careless, Martin M May, Richard Stewart, T John Trinder, Samantha J Hagan, Jade M Cole, Caroline C MacFie, Anna T Dowling, Nicolás Nin, Edgardo Nuñez, Gustavo Pittini, Ruben Rodriguez, María C Imperio, Cristina Santos, Ana G França, Alejandro Ebeid, Alberto Deicas, Carolina Serra, Aditya Uppalapati, Ghassan Kamel, Valerie M Banner-Goodspeed, Jeremy R Beitler, Satyanarayana Reddy Mukkera, Shreedhar Kulkarni, John O Shinn Iii, Dina Gomaa, Christopher Tainter, Jarone Lee, Tomaz MesarJarone Lee, Dale J Yeatts, Jessica Warren, Michael J Lanspa, Russel R Miller, Colin K Grissom, Samuel M Brown, Philippe R Bauer, Ryan J Gosselin, Barrett T Kitch, Jason E Cohen, Scott H Beegle, Shazia Choudry, Renaud M Gueret, Aiman Tulaimat, William Stigler, Hitesh Batra, Nidhi G Huff, Keith D Lamb, Trevor W Oetting, Nicholas M Mohr, Claine Judy, Shigeki Saito, Fayez M Kheir, Fayez Kheir, Adam B Schlichting, Angela Delsing, Daniel R Crouch, Mary Elmasri, Dina Ismail, Kyle R Dreyer, Thomas C Blakeman, Rebecca M Baro, Carolina Quintana Grijalba, Peter C Hou, Raghu Seethala, Imo Aisiku, Galen Henderson, Gyorgy Frendl, Sen-Kuang Hou, Robert L Owens, Ashley Schomer, Pham, Tài, Pesenti, Antonio, Bellani, Giacomo, Rubenfeld, Gordon, Fan, Eddy, Bugedo, Guillermo, Lorente, José Angel, Fernandes, Antero do Vale, Van Haren, Frank, Bruhn, Alejandro, Rios, Fernando, Esteban, Andre, Gattinoni, Luciano, Larsson, Ander, McAuley, Daniel F., Ranieri, Marco, Thompson, B. Taylor, Wrigge, Hermann, Brochard, Laurent J., Laffey, John G, Antonio Pesenti, John G Laffey, Laurent Brochard, Andres Esteban, Luciano Gattinoni, Frank van Haren, Anders Larsson, Daniel F McAuley, Marco Ranieri, Gordon Rubenfeld, B Taylor Thompson, Hermann Wrigge, Arthur S Slutsky, John G Laffey, Giacomo Bellani, Tài Pham, Eddy Fan, Fernando Rios, Frank van Haren, Thierry Sottiaux, Pieter Depuydt, Fredy S Lora, Luciano Cesar Azevedo, Eddy Fan, Guillermo Bugedo, Haibo Qiu, Marcos Gonzalez, Juan Silesky, Vladimir Cerny, Jonas Nielsen, Manuel Jibaja, Tài Pham, Hermann Wrigge, Dimitrios Matamis, Jorge Luis Ranero, Pravin Amin, S M Hashemian, Kevin Clarkson, Giacomo Bellani, Kiyoyasu Kurahashi, Asisclo Villagomez, Amine Ali Zeggwagh, Leo M Heunks, Jon Henrik Laake, Jose Emmanuel Palo, Antero do Vale Fernandes, Dorel Sandesc, Yaasen Arabi, Vesna Bumbasierevic, Nicolas Nin, Jose A Lorente, Anders Larsson, Lise Piquilloud, Fekri Abroug, Daniel F McAuley, Lia McNamee, Javier Hurtado, Ed Bajwa, Gabriel Démpaire, Hektor Sula, Lordian Nunci, Alma Cani, Alan Zazu, Christian Dellera, Carolina S Insaurralde, Risso V Alejandro, Julio Daldin, Mauricio Vinzio, Ruben O Fernandez, Luis P Cardonnet, Lisandro R Bettini, Mariano Carboni Bisso, Emilio M Osman, Mariano G Setten, Pablo Lovazzano, Javier Alvarez, Veronica Villar, Norberto C Pozo, Nicolas Grubissich, Gustavo A Plotnikow, Daniela N Vasquez, Santiago Ilutovich, Norberto Tiribelli, Ariel Chena, Carlos A Pellegrini, María G Saenz, Elisa Estenssoro, Matias Brizuela, Hernan Gianinetto, Pablo E Gomez, Valeria I Cerrato, Marco G Bezzi, Silvina A Borello, Flavia A Loiacono, Adriana M Fernandez, Serena Knowles, Claire Reynolds, Deborah M Inskip, Jennene J Miller, Jing Kong, Christina Whitehead, Shailesh Bihari, Aylin Seven, Amanda Krstevski, Helen J Rodgers, Rebecca T Millar, Toni E McKenna, Irene M Bailey, Gabrielle C Hanlon, Anders Aneman, Joan M Lynch, Raman Azad, John Neal, Paul W Woods, Brigit L Roberts, Mark R Kol, Helen S Wong, Katharina C Riss, Thomas Staudinger, Xavier Wittebole, Caroline Berghe, Pierre A Bulpa, Alain M Dive, Rik Verstraete, Herve Lebbinck, Pieter Depuydt, Joris Vermassen, Philippe Meersseman, Helga Ceunen, Jonas I Rosa, Daniel O Beraldo, Claudio Piras, Adenilton M Rampinelli, Antonio P Nassar Jr, Sergio Mataloun, Marcelo Moock, Marlus M Thompson, Claudio H Gonçalves, Ana Carolina P Antônio, Aline Ascoli, Rodrigo S Biondi, Danielle C Fontenele, Danielle Nobrega, Vanessa M Sales, Ahmad Yazid Bin Hj Abul Wahab, Maizatul Ismail, Suresh Shindhe, John Laffey, Francois Beloncle, Kyle G Davies, Rob Cirone, Venika Manoharan, Mehvish Ismail, Ewan C Goligher, Mandeep Jassal, Erin Nishikawa, Areej Javeed, Gerard Curley, Nuttapol Rittayamai, Matteo Parotto, Niall D Ferguson, Sangeeta Mehta, Jenny Knoll, Antoine Pronovost, Sergio Canestrini, Alejandro R Bruhn, Patricio H Garcia, Felipe A Aliaga, Pamela A Farías, Jacob S Yumha, Claudia A Ortiz, Javier E Salas, Alejandro A Saez, Luis D Vega, Eduardo F Labarca, Felipe T Martinez, Nicolás G Carreño, Pilar Lora, Haitao Liu, Haibo Qiu, Ling Liu, Rui Tang, Xiaoming Luo, Youzhong An, Huiying Zhao, Yan Gao, Zhe Zhai, Zheng L Ye, Wei Wang, Wenwen Li, Qingdong Li, Ruiqiang Zheng, Wenkui Yu, Juanhong Shen, Xinyu Li, Tao Yu, Weihua Lu, Ya Q Wu, Xiao B Huang, Zhenyang He, Yuanhua Lu, Hui Han, Fan Zhang, Renhua Sun, Hua X Wang, Shu H Qin, Bao H Zhu, Jun Zhao, Jian Liu, Bin Li, Jing L Liu, Fa C Zhou, Qiong J Li, Xing Y Zhang, Zhou Li-Xin, Qiang Xin-Hua, Liangyan Jiang, Yuan N Gao, Xian Y Zhao, Yuan Y Li, Xiao L Li, Chunting Wang, Qingchun Yao, Rongguo Yu, Kai Chen, Huanzhang Shao, Bingyu Qin, Qing Q Huang, Wei H Zhu, Ai Y Hang, Ma X Hua, Yimin Li, Yonghao Xu, Yu D Di, Long L Ling, Tie H Qin, Shou H Wang, Junping Qin, Yi Han, Suming Zhou, Monica P Vargas, Juan I Silesky Jimenez, Manuel A González Rojas, Jaime E SolisQuesada, Christian M Ramirez-Alfaro, Jan Máca, Peter Sklienka, Jakob Gjedsted, Aage Christiansen, Jonas Nielsen, Boris G Villamagua, Iguel Llano, Philippe Burtin, Gautier Buzancais, Pascal Beuret, Nicolas Pelletier, Satar Mortaza, Alain Mercat, Jonathan Chelly, Sébastien Jochmans, Nicolas Terzi, Cédric Daubin, Guillaume Carteaux, Nicolas de Prost, Jean-Daniel Chiche, Fabrice Daviaud, Tài Pham, Muriel Fartoukh, Guillaume Barberet, Jerome Biehler, Jean Dellamonica, Denis Doyen, Jean-Michel Arnal, Anais Briquet, Sami Hraiech, Laurent Papazian, Arnaud Follin, Damien Roux, Jonathan Messika, Evangelos Kalaitzis, Laurence Dangers, Alain Combes, Siu-Ming Au, Gaetan Béduneau, Dorothée Carpentier, Elie H Zogheib, Herve Dupont, Sylvie Ricome, Francesco L Santoli, Sebastien L Besset, Philippe Michel, Bruno Gelée, Pierre-Eric Danin, Bernard Goubaux, Philippe J Crova, Nga T Phan, Frantz Berkelmans, Julio C Badie, Romain Tapponnier, Josette Gally, Samy Khebbeb, Jean-Etienne Herbrecht, Francis Schneider, PierreLouis M Declercq, Jean-Philippe Rigaud, Jacques Duranteau, Anatole Harrois, Russell Chabanne, Julien Marin, Charlene Bigot, Sandrine Thibault, Mohammed Ghazi, Messabi Boukhazna, Salem Ould Zein, Jack R Richecoeur, Daniele M Combaux, Fabien Grelon, Charlene Le Moal, Elise P Sauvadet, Adrien Robine, Virginie Lemiale, Danielle Reuter, Martin Dres, Alexandre Demoule, Dany Goldgran-Toledano, Loredana Baboi, Claude Guérin, Ralph Lohner, Jens Kraßler, Susanne Schäfer, Kai D Zacharowski, Patrick Meybohm, Andreas W Reske, Philipp Simon, HansBernd F Hopf, Michael Schuetz, Thomas Baltus, Metaxia N Papanikolaou, Theonymfi G Papavasilopoulou, Giannis A Zacharas, Vasilis Ourailogloy, Eleni K Mouloudi, Eleni V Massa, Eva O Nagy, Electra E Stamou, Ellada V Kiourtzieva, Marina A Oikonomou, Luis E Avila, Cesar A Cortez, Johanna E Citalán, Sameer A Jog, Safal D Sable, Bhagyesh Shah, Mohan Gurjar, Arvind K Baronia, Mohammedfaruk Memon, Radhakrishnan Muthuchellappan, Venkatapura J Ramesh, Anitha Shenoy, Ramesh Unnikrishnan, Subhal B Dixit, Rachana V Rhayakar, Nagarajan Ramakrishnan, Vallish K Bhardwaj, Heera L Mahto, Sudha V Sagar, Vijayanand Palaniswamy, Deeban Ganesan, Seyed Mohammadreza Hashemian, Hamidreza Jamaati, Farshad Heidari, Edel A Meaney, Alistair Nichol, Karl M Knapman, Donall O'Croinin, Eimhin S Dunne, Dorothy M Breen, Kevin P Clarkson, Rola F Jaafar, Rory Dwyer, Fahd Amir, Olaitan O Ajetunmobi, Aogan C O'Muircheartaigh, Colin S Black, Nuala Treanor, Daniel V Collins, Wahid Altaf, Gianluca Zani, Maurizio Fusari, Savino Spadaro, Carlo A Volta, Romano Graziani, Barbara Brunettini, Salvatore Palmese, Paolo Formenti, Michele Umbrello, Andrea Lombardo, Elisabetta Pecci, Marco Botteri, Monica Savioli, Alessandro Protti, Alessia Mattei, Lorenzo Schiavoni, Andrea Tinnirello, Manuel Todeschini, Antonino Giarratano, Andrea Cortegiani, Massimo M Antonelli, Luca M Montini, Paolo Casalena, Sergio Scafetti, Giovanna Panarello, Giovanna Occhipinti, Nicolò Patroniti, Matteo Pozzi, Roberto R Biscione, Michela M Poli, Ferdinando Raimondi, Daniela Albiero, Giulia Crapelli, Eduardo Beck, Vincenzo Pota, Vincenzo Schiavone, Alexandre Molin, Fabio Tarantino, Giacomo Monti, Elena Frati, Lucia Mirabella, Gilda Cinnella, Tommaso Fossali, Riccardo Colombo, Pierpaolo Terragni, Ilaria Pattarino, Francesco Mojoli, Antonio Braschi, Erika E Borotto, Andrea N Cracchiolo, Daniela M Palma, Francesco Raponi, Giuseppe Foti, Ettore R Vascotto, Andrea Coppadoro, Luca Brazzi, Leda Floris, Giorgio A Iotti, Aaron Venti, Osamu Yamaguchi, Shunsuke Takagi, Hiroki N Maeyama, Eizo Watanabe, Yoshihiro Yamaji, Kazuyoshi Shimizu, Kyoko Shiozaki, Satoru Futami, Sekine Ryosuke, Koji Saito, Yoshinobu Kameyama, Keiko Ueno, Masayo Izawa, Nao Okuda, Hiroyuki Suzuki, Tomofumi Harasawa, Michitaka Nasu, Tadaaki Takada, Fumihito Ito, Shin Nunomiya, Kansuke Koyama, Toshikazu Abe, Kohkichi Andoh, Kohei Kusumoto, Akira Hirata, Akihiro Takaba, Hiroyasu Kimura, Shuhei Matsumoto, Ushio Higashijima, Hiroyuki Honda, Nobumasa Aoki, Hiroshi Imai, Yasuaki Ogino, Ichiko Mizuguchi, Kazuya Ichikado, Kenichi Nitta, Katsunori Mochizuki, Tomoaki Hashida, Hiroyuki Tanaka, Tomoyuki Nakamura, Daisuke Niimi, Takeshi Ueda, Yozo Kashiwa, Akinori Uchiyama, Olegs Sabelnikovs, Peteris Oss, Youssef Haddad, Kong Y Liew, Silvio A Ñamendys-Silva, Yves D Jarquin-Badiola, Luis A Sanchez-Hurtado, Saira S Gomez-Flores, Maria C Marin, Asisclo J Villagomez, Jordana S Lemus, Jonathan M Fierro, Mavy Ramirez Cervantes, Francisco Javier Flores Mejia, Dulce Dector, Alejandro Rojas, Daniel R Gonzalez, Claudia R Estrella, Jorge R Sanchez-Medina, Alvaro Ramirez-Gutierrez, Fernando G George, Janet S Aguirre, Juan A Buensuseso, Manuel Poblano, Juan A Buensuseso, Manuel Poblano, Tarek Dendane, Amine Ali Zeggwagh, Hicham Balkhi, Mina Elkhayari, Nacer Samkaoui, Hanane Ezzouine, Abdellatif Benslama, Mourad Amor, Wajdi Maazouzi, Nedim Cimic, Oliver Beck, Monique M Bruns, Jeroen A Schouten, Myra Rinia, Monique Raaijmakers, Leo M Heunks, Hellen M van Wezel, Serge J Heines, Ulrich Strauch, Marc P Buise, Fabienne D Simonis, Marcus J Schultz, Jennifer C Goodson, Troy S Browne, Leanlove Navarra, Anna Hunt, Robyn A Hutchison, Mathew B Bailey, Lynette Newby, Colin McArthur, Michael Kalkoff, Alex Mcleod, Jonathan Casement, Danielle J Hacking, Finn H Andersen, Merete S Dolva, Jon H Laake, Andreas Barratt-Due, Kim Andre L Noremark, Eldar Søreide, Brit Å Sjøbø, Anne B Guttormsen, Hector H Leon Yoshido, Ronald Zumaran Aguilar, Fredy A Montes Oscanoa, Alain U Alisasis, Joanne B Robles, Rossini Abbie B Pasanting-Lim, Beatriz C Tan, Pawel Andruszkiewicz, Karina Jakubowska, Cristina M Coxo, António M Alvarez, Bruno S Oliveira, Gustavo M Montanha, Nelson C Barros, Carlos S Pereira, António M Messias, Jorge M Monteiro, Ana M Araujo, Nuno T Catorze, Susan M Marum, Maria J Bouw, Rui M Gomes, Vania A Brito, Silvia Castro, Joana M Estilita, Filipa M Barros, Isabel M Serra, Aurelia M Martinho, Dana R Tomescu, Alexandra Marcu, Ovidiu H Bedreag, Marius Papurica, Dan E Corneci, Silvius Ioan Negoita, Evgeny Grigoriev, Alexey I Gritsan, Andrey A Gazenkampf, Ghaleb Almekhlafi, Mohamad M Albarrak, Ghanem M Mustafa, Khalid A Maghrabi, Nawal Salahuddin, Tharwat M Aisa, Ahmed S Al Jabbary, Edgardo Tabhan, Yaseen M Arabi, Yaseen M Arabi, Olivia A Trinidad, Hasan M Al Dorzi, Edgardo E Tabhan, Vesna Bumbasirevic, Bojan Jovanovic, Stefan Bolon, Oliver Smith, Jordi Mancebo, Hernan Aguirre-Bermeo, Juan C Lopez-Delgado, Francisco Esteve, Gemma Rialp, Catalina Forteza, Candelaria De Haro, Antonio Artigas, Guillermo M Albaiceta, Sara De Cima-Iglesias, Leticia Seoane-Quiroga, Alexandra Ceniceros-Barros, Antonio L RuizAguilar, Luis M Claraco-Vega, Juan Alfonso Soler, Maria Del Carmen Lorente, Cecilia Hermosa, Federico Gordo, Miryam PrietoGonzález, Juan B López-Messa, Manuel P Perez, Cesar P Perez, Raquel Montoiro Allue, Ferran RocheCampo, Marcos Ibañez-Santacruz, Susana TempranoSusana, Maria C Pintado, Raul De Pablo, Pilar Ricart Aroa Gómez, Silvia Rodriguez Ruiz, Silvia Iglesias Moles, Mª Teresa Jurado, Alfons Arizmendi, Enrique A Piacentini, Nieves Franco, Teresa Honrubia, Meisy Perez Cheng, Elena Perez Losada, Javier Blanco, Luis J Yuste, Cecilia Carbayo-Gorriz, Francisca G Cazorla-Barranquero, Javier G Alonso, Rosa S Alda, Ángela Algaba, Gonzalo Navarro, Enrique Cereijo, Esther Diaz-Rodriguez, Diego Pastor Marcos, Laura Alvarez Montero, Luis Herrera Para, Roberto Jimenez Sanchez, Miguel Angel Blasco Navalpotro, Ricardo Diaz Abad, Raquel Montiel González, Dácil Parrilla Toribio, Alejandro G Castro, Maria Jose D Artiga, Oscar Penuelas, Tomas P Roser, Moreno F Olga, Elena Gallego Curto, Rocío Manzano Sánchez, Vallverdu P Imma, Garcia M Elisabet, Laura Claverias, Monica Magret, Ana M Pellicer, Lucia L Rodriguez, Jesús Sánchez-Ballesteros, Ángela González-Salamanca, Antonio G Jimenez, Francisco P Huerta, Juan Carlos J Sotillo Diaz, Esther Bermejo Lopez, David D Llinares Moya, Alec A Tallet Alfonso, Palazon Sanchez Eugenio Luis, Palazon Sanchez Cesar, Sánchez I Rafael, Corcoles G Virgilio, Noelia N Recio, Christian C Rylander, Bernhard Holzgraefe, Lars M Broman, Joanna Wessbergh, Linnea Persson, Fredrik Schiöler, Hans Kedelv, Anna Oscarsson Tibblin, Henrik Appelberg, Lars Hedlund, Johan Helleberg, Karin E Eriksson, Rita Glietsch, Niklas Larsson, Ingela Nygren, Silvia L Nunes, Anna-Karin Morin, Thomas Kander, Anne Adolfsson, Lise Piquilloud, Hervé O Zender, Corinne Leemann-Refondini, Souheil Elatrous, Slaheddine Bouchoucha, Imed Chouchene, Islem Ouanes, Asma Ben Souissi, Salma Kamoun, Oktay Demirkiran, Mustafa Aker, Emre Erbabacan, Ilkay Ceylan, Nermin Kelebek Girgin, Menekse Ozcelik, Necmettin Ünal, Basak Ceyda Meco, Onat O Akyol, Suleyman S Derman, Barry Kennedy, Ken Parhar, Latha Srinivasa, Lia McNamee, Danny McAuley, Phil Hopkins, Clare Mellis, Vivek Kakar, Dan Hadfield, Andre Vercueil, Kaushik Bhowmick, Sally K Humphreys, Andrew Ferguson, Raymond Mckee, Ashok S Raj, Danielle A Fawkes, Philip Watt, Linda Twohey, Rajeev R Jha, Matthew Thomas, Alex Morton, Varsha Kadaba, Mark J Smith, Anil P Hormis, Santhana G Kannan, Miriam Namih, Henrik Reschreiter, Julie Camsooksai, Alek Kumar, Szabolcs Rugonfalvi, Christopher Nutt, Orla Oneill, Colette Seasman, Ged Dempsey, Christopher J Scott, Helen E Ellis, Stuart Mckechnie, Paula J Hutton, Nora N Di Tomasso, Michela N Vitale, Ruth O Griffin, Michael N Dean, Julius H Cranshaw, Emma L Willett, Nicholas Ioannou, Sarah Gillis, Peter Csabi, Rosaleen Macfadyen, Heidi Dawson, Pieter D Preez, Alexandra J Williams, Owen Boyd, Laura Ortiz-Ruiz de Gordoa, Jon Bramall, Sophie Symmonds, Simon K Chau, Tim Wenham, Tamas Szakmany, Piroska Toth-Tarsoly, Katie H McCalman, Peter Alexander, Lorraine Stephenson, Thomas Collyer, Rhiannon Chapman, Raphael Cooper, Russell M Allan, Malcolm Sim, David W Wrathall, Donald A Irvine, Kim S Zantua, John C Adams, Andrew J Burtenshaw, Gareth P Sellors, Ingeborg D Welters, Karen E Williams, Robert J Hessell, Matthew G Oldroyd, Ceri E Battle, Suresh Pillai, Istvan Kajtor, Mageswaran Sivashanmugavel, Sinead C Okane, Adrian Donnelly, Aniko D Frigyik, Jon P Careless, Martin M May, Richard Stewart, T John Trinder, Samantha J Hagan, Jade M Cole, Caroline C MacFie, Anna T Dowling, Javier Hurtado, Nicolás Nin, Javier Hurtado, Edgardo Nuñez, Gustavo Pittini, Ruben Rodriguez, María C Imperio, Cristina Santos, Ana G França, Alejandro Ebeid, Alberto Deicas, Carolina Serra, Aditya Uppalapati, Ghassan Kamel, Valerie M Banner-Goodspeed, Jeremy R Beitler, Satyanarayana Reddy Mukkera, Shreedhar Kulkarni, John O Shinn Iii, Dina Gomaa, Christopher Tainter, Jarone Lee, Tomaz MesarJarone Lee, Dale J Yeatts, Jessica Warren, Michael J Lanspa, Russel R Miller, Colin K Grissom, Samuel M Brown, Philippe R Bauer, Ryan J Gosselin, Barrett T Kitch, Jason E Cohen, Scott H Beegle, Shazia Choudry, Renaud M Gueret, Aiman Tulaimat, William Stigler, Hitesh Batra, Nidhi G Huff, Keith D Lamb, Trevor W Oetting, Nicholas M Mohr, Claine Judy, Shigeki Saito, Fayez M Kheir, Fayez Kheir, Adam B Schlichting, Angela Delsing, Daniel R Crouch, Mary Elmasri, Daniel R Crouch, Dina Ismail, Kyle R Dreyer, Thomas C Blakeman, Dina Gomaa, Rebecca M Baro, Carolina Quintana Grijalba, Peter C Hou, Raghu Seethala, Imo Aisiku, Galen Henderson, Gyorgy Frendl, Sen-Kuang Hou, Robert L Owens, Ashley Schomer, Intensive Care Medicine, ACS - Diabetes & metabolism, ACS - Pulmonary hypertension & thrombosis, ACS - Microcirculation, Pham, T, Pesenti, A, Bellani, G, Rubenfeld, G, Fan, E, Bugedo, G, Lorente, J, Fernandes, A, Van Haren, F, Bruhn, A, Rios, F, Esteban, A, Gattinoni, L, Larsson, A, Mcauley, D, Ranieri, M, Thompson, B, Wrigge, H, Brochard, L, Laffey, J, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), St. Michael's Hospital, University of Toronto, Groupe de recherche clinique CARMAS, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Università degli Studi di Milano [Milano] (UNIMI), University of Milan, San Gerardo Hospital, Sunnybrook Health Sciences Center, Mount Sinai Hospital [Toronto, Canada] (MSH), Pontificia Universidad Católica de Chile (UC), University Hospital of Getafe, CIBER Enfermedades Respiratorias (CIBERES), Universidad Europea de Madrid, Hospital Garcia de Orta (EPE), Canberra Hospital, Medical School [Australian National University - ANU], Australian National University (ANU), University of Canberra, Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES), University of Göttingen - Georg-August-Universität Göttingen, Uppsala University, Queen's University [Belfast] (QUB), Royal Victoria Hospital, McGill University Health Center [Montreal] (MUHC), Università degli Studi di Bologna, Massachusetts General Hospital [Boston], University Hospital Leipzig, Department of Anaesthesiology, Intensive Care and Emergency Medicine, Pain Therapy, Bergmannstrost Hospital Halle, 06112, Halle, National University of Ireland [Galway] (NUI Galway), Bayer GlaxoSmithKline, GSK Baxter International Boehringer Ingelheim Wellcome Trust, WT National Institute for Health Research, NIHR Queen's University Belfast, QUB Medical Research Council Canada, MRC European Society of Intensive Care Medicine, ESICM, Support statement: This work was supported by the European Society of Intensive Care Medicine. Funding information for this article has been deposited with the Crossref Funder Registry., Conflict of interest: T. Pham has nothing to disclose. A. Pesenti reports personal fees from Maquet, Novalung/Xenios, Baxter, Gilead and Boehringer Ingelheim, outside the submitted work. G. Bellani reports grants and personal fees from Draeger Medical, personal fees from Getinge, Hamilton, GE Healthcare, Dimar SRL, Intersurgical and Flowmeter SPA, outside the submitted work. G. Rubenfeld has nothing to disclose. E. Fan reports personal fees from ALung Technologies, Getinge and MC3 Cardiopulmonary, grants, personal fees and non-financial support from Fresenius Medical Care, outside the submitted work. G. Bugedo has nothing to disclose. J.A. Lorente has nothing to disclose. A.D. V. Fernandes has nothing to disclose. F. Van Haren has nothing to disclose. A. Bruhn has nothing to disclose. F. Rios has nothing to disclose. A. Esteban has nothing to disclose. L. Gattinoni has nothing to disclose. A. Larsson reports grants from the Swedish Heart and Lung Foundation, during the conduct of the study. D.F. McAuley reports personal fees from consultancy for GlaxoSmithKline, Boehringer Ingelheim and Bayer, outside the submitted work, in addition, his institution has received funds from grants from the UK NIHR, Wellcome Trust, Innovate UK, NI HSC R&D Division, NI Chest Heart and Stroke, and MRC, is one of four named inventors on a patent US8962032 covering the use of sialic acid-bearing nanoparticles as anti-inflammatory agents issued to his institution, The Queen’s University of Belfast (http://www.google.com/patents/US8962032), and is a Director of Research for the Intensive Care Society and NIHR EME Programme Director. M. Ranieri has nothing to disclose. B.T. Thompson reports personal fees from Bayer, Thetis and Novartis, outside the submitted work. H. Wrigge reports personal fees for consultancy from Dräger Medical, personal fees for advisory board work from Liberate Medical, grants and personal fees for lectures from InfectoPharm, personal fees for lectures from MSD and GE, outside the submitted work. L.J. Brochard reports grants from Medtronic Covidien, grants and non-financial support from Fisher Paykel, non-financial support from Air Liquide, Sentec and Philips, other (patent) from General Electric, outside the submitted work. J.G. Laffey reports grants and personal fees from Baxter, grants and non-financial support from Aerogen and Factor Biosciences, outside the submitted work., LUNG SAFE Investigators and the European Society of Intensive Care Medicine Trials Group: Antonio Pesenti, John G Laffey, Laurent Brochard, Andres Esteban, Luciano Gattinoni, Frank van Haren, Anders Larsson, Daniel F McAuley, Marco Ranieri, Gordon Rubenfeld, B Taylor Thompson, Hermann Wrigge, Arthur S Slutsky, John G Laffey, Giacomo Bellani, Tài Pham, Eddy Fan, Fernando Rios, Frank van Haren, Thierry Sottiaux, Pieter Depuydt, Fredy S Lora, Luciano Cesar Azevedo, Eddy Fan, Guillermo Bugedo, Haibo Qiu, Marcos Gonzalez, Juan Silesky, Vladimir Cerny, Jonas Nielsen, Manuel Jibaja, Tài Pham, Hermann Wrigge, Dimitrios Matamis, Jorge Luis Ranero, Pravin Amin, S M Hashemian, Kevin Clarkson, Giacomo Bellani, Kiyoyasu Kurahashi, Asisclo Villagomez, Amine Ali Zeggwagh, Leo M Heunks, Jon Henrik Laake, Jose Emmanuel Palo, Antero do Vale Fernandes, Dorel Sandesc, Yaasen Arabi, Vesna Bumbasierevic, Nicolas Nin, Jose A Lorente, Anders Larsson, Lise Piquilloud, Fekri Abroug, Daniel F McAuley, Lia McNamee, Javier Hurtado, Ed Bajwa, Gabriel Démpaire, Hektor Sula, Lordian Nunci, Alma Cani, Alan Zazu, Christian Dellera, Carolina S Insaurralde, Risso V Alejandro, Julio Daldin, Mauricio Vinzio, Ruben O Fernandez, Luis P Cardonnet, Lisandro R Bettini, Mariano Carboni Bisso, Emilio M Osman, Mariano G Setten, Pablo Lovazzano, Javier Alvarez, Veronica Villar, Norberto C Pozo, Nicolas Grubissich, Gustavo A Plotnikow, Daniela N Vasquez, Santiago Ilutovich, Norberto Tiribelli, Ariel Chena, Carlos A Pellegrini, María G Saenz, Elisa Estenssoro, Matias Brizuela, Hernan Gianinetto, Pablo E Gomez, Valeria I Cerrato, Marco G Bezzi, Silvina A Borello, Flavia A Loiacono, Adriana M Fernandez, Serena Knowles, Claire Reynolds, Deborah M Inskip, Jennene J Miller, Jing Kong, Christina Whitehead, Shailesh Bihari, Aylin Seven, Amanda Krstevski, Helen J 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Kaushik Bhowmick, Sally K Humphreys, Andrew Ferguson, Raymond Mckee, Ashok S Raj, Danielle A Fawkes, Philip Watt, Linda Twohey, Rajeev R Jha, Matthew Thomas, Alex Morton, Varsha Kadaba, Mark J Smith, Anil P Hormis, Santhana G Kannan, Miriam Namih, Henrik Reschreiter, Julie Camsooksai, Alek Kumar, Szabolcs Rugonfalvi, Christopher Nutt, Orla Oneill, Colette Seasman, Ged Dempsey, Christopher J Scott, Helen E Ellis, Stuart Mckechnie, Paula J Hutton, Nora N Di Tomasso, Michela N Vitale, Ruth O Griffin, Michael N Dean, Julius H Cranshaw, Emma L Willett, Nicholas Ioannou, Sarah Gillis, Peter Csabi, Rosaleen Macfadyen, Heidi Dawson, Pieter D Preez, Alexandra J Williams, Owen Boyd, Laura Ortiz-Ruiz de Gordoa, Jon Bramall, Sophie Symmonds, Simon K Chau, Tim Wenham, Tamas Szakmany, Piroska Toth-Tarsoly, Katie H McCalman, Peter Alexander, Lorraine Stephenson, Thomas Collyer, Rhiannon Chapman, Raphael Cooper, Russell M Allan, Malcolm Sim, David W Wrathall, Donald A Irvine, Kim S Zantua, John C Adams, Andrew J Burtenshaw, Gareth P Sellors, Ingeborg D Welters, Karen E Williams, Robert J Hessell, Matthew G Oldroyd, Ceri E Battle, Suresh Pillai, Istvan Kajtor, Mageswaran Sivashanmugavel, Sinead C Okane, Adrian Donnelly, Aniko D Frigyik, Jon P Careless, Martin M May, Richard Stewart, T John Trinder, Samantha J Hagan, Jade M Cole, Caroline C MacFie, Anna T Dowling, Javier Hurtado, Nicolás Nin, Javier Hurtado, Edgardo Nuñez, Gustavo Pittini, Ruben Rodriguez, María C Imperio, Cristina Santos, Ana G França, Alejandro Ebeid, Alberto Deicas, Carolina Serra, Aditya Uppalapati, Ghassan Kamel, Valerie M Banner-Goodspeed, Jeremy R Beitler, Satyanarayana Reddy Mukkera, Shreedhar Kulkarni, John O Shinn Iii, Dina Gomaa, Christopher Tainter, Jarone Lee, Tomaz MesarJarone Lee, Dale J Yeatts, Jessica Warren, Michael J Lanspa, Russel R Miller, Colin K Grissom, Samuel M Brown, Philippe R Bauer, Ryan J Gosselin, Barrett T Kitch, Jason E Cohen, Scott H Beegle, Shazia Choudry, Renaud M Gueret, Aiman Tulaimat, William Stigler, Hitesh Batra, Nidhi G Huff, Keith D Lamb, Trevor W Oetting, Nicholas M Mohr, Claine Judy, Shigeki Saito, Fayez M Kheir, Fayez Kheir, Adam B Schlichting, Angela Delsing, Daniel R Crouch, Mary Elmasri, Daniel R Crouch, Dina Ismail, Kyle R Dreyer, Thomas C Blakeman, Dina Gomaa, Rebecca M Baro, Carolina Quintana Grijalba, Peter C Hou, Raghu Seethala, Imo Aisiku, Galen Henderson, Gyorgy Frendl, Sen-Kuang Hou, Robert L Owens, Ashley Schomer, UCL - SSS/IREC/MEDA - Pôle de médecine aiguë, UCL - (MGD) Services des soins intensifs, and UCL - (SLuc) Service de soins intensifs

Subjects
Pulmonary and Respiratory Medicine, ARDS, Unidades de cuidados intensivos, [SDV]Life Sciences [q-bio], medicine.medical_treatment, mechanical ventilation, NO, law.invention, 03 medical and health sciences, Tratamiento médico, 0302 clinical medicine, law, Settore MED/41 - ANESTESIOLOGIA, Insuficiencia respiratoria, Medicine, Humans, 030212 general & internal medicine, Prospective Studies, Prospective cohort study, Lung, Mechanical ventilation, Respiratory Distress Syndrome, business.industry, Respiration, Incidence (epidemiology), medicine.disease, Intensive care unit, Respiration, Artificial, 3. Good health, Intensive Care Units, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], medicine.anatomical_structure, 030228 respiratory system, Respiratory failure, Heart failure, Anesthesia, Artificial, ards, business, Respiratory Insufficiency, Enfermedad
Abstract

BackgroundCurrent incidence and outcome of patients with acute hypoxaemic respiratory failure requiring mechanical ventilation in the intensive care unit (ICU) are unknown, especially for patients not meeting criteria for acute respiratory distress syndrome (ARDS).MethodsAn international, multicentre, prospective cohort study of patients presenting with hypoxaemia early in the course of mechanical ventilation, conducted during four consecutive weeks in the winter of 2014 in 459 ICUs from 50 countries (LUNG SAFE). Patients were enrolled with arterial oxygen tension/inspiratory oxygen fraction ratio ≤300 mmHg, new pulmonary infiltrates and need for mechanical ventilation with a positive end-expiratory pressure of ≥5 cmH2O. ICU prevalence, causes of hypoxaemia, hospital survival and factors associated with hospital mortality were measured. Patients with unilateral versus bilateral opacities were compared.Findings12 906 critically ill patients received mechanical ventilation and 34.9% with hypoxaemia and new infiltrates were enrolled, separated into ARDS (69.0%), unilateral infiltrate (22.7%) and congestive heart failure (CHF; 8.2%). The global hospital mortality was 38.6%. CHF patients had a mortality comparable to ARDS (44.1% versus 40.4%). Patients with unilateral-infiltrate had lower unadjusted mortality, but similar adjusted mortality compared to those with ARDS. The number of quadrants on chest imaging was associated with an increased risk of death. There was no difference in mortality comparing patients with unilateral-infiltrate and ARDS with only two quadrants involved.InterpretationMore than one-third of patients receiving mechanical ventilation have hypoxaemia and new infiltrates with a hospital mortality of 38.6%. Survival is dependent on the degree of pulmonary involvement whether or not ARDS criteria are reached.

Published
2021

12. Metastasis-directed stereotactic body radiotherapy for oligometastatic renal cell carcinoma: extent of tumor burden eradicated by radiotherapy

Author

Yang Liu, Zhiling Zhang, Wen Long, Liru He, Hui Han, Lixin Mai, Sijuan Huang, Pei Dong, Fangjian Zhou, and Zitong Zhang

Subjects
Nephrology, Adult, medicine.medical_specialty, Adolescent, Urology, medicine.medical_treatment, 030232 urology & nephrology, Radiosurgery, Metastasis, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Renal cell carcinoma, Internal medicine, medicine, Carcinoma, Humans, Carcinoma, Renal Cell, Aged, Retrospective Studies, Aged, 80 and over, Stereotactic techniques, business.industry, Proportional hazards model, Middle Aged, medicine.disease, Nephrectomy, Kidney Neoplasms, renal cell, Tumor Burden, Radiation therapy, Treatment Outcome, 030220 oncology & carcinogenesis, Original Article, Radiology, business
Abstract

Purpose We aimed to explore whether complete eradication of tumor burden with stereotactic body radiotherapy (SBRT) would affect the outcomes of oligometastatic renal cell carcinoma (RCC). Materials and methods Patients diagnosed with extracranial oligometastatic RCC (no more than five metastases) between 2007 and 2019 were reviewed. Those without nephrectomy were excluded. SBRT to all, some and no lesions were defined as complete, incomplete, and no SBRT. Progression-free survival (PFS) and cancer-specific survival (CSS) were analyzed using Kaplan–Meier method, Cox regression model and the Fine and Gray method. Result A total of 101 patients were included, 51.5% of whom had p = 0.043) and CSS (not reached vs. 55.3 months; p = 0.012) compared with the no or incomplete SBRT group. In multivariate analysis, ECOG 0–1 (HR 0.389, 95% CI 0.167–0.906, p = 0.029) and complete SBRT were prognostic factors for CSS (HR 0.307, 95% CI 0.108–0.876, p = 0.027). Complete SBRT was associated with improved CSS in the subgroups of patients with age Conclusion Complete eradication of tumor burden with SBRT was associated with better survival in patients with oligometastatic RCC. The recommendation of SBRT to all lesions should be individualized.

Published
2021

13. Evaluation of amide proton transfer-weighted imaging for endometrial carcinoma histological features: a comparative study with diffusion kurtosis imaging

Author

Zhun Huang, Wei Wei, Fengmin Shao, Hui Han, Kaiyu Wang, Xuejia Wang, Jing Sun, Meiyun Wang, Yan Bai, Jie Shang, Nan Meng, Dongming Han, and Zhen Yang

Subjects
medicine.medical_specialty, Amide proton, Independent predictor, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Carcinoma, medicine, Humans, Endometrioid adenocarcinoma, Radiology, Nuclear Medicine and imaging, Magnetization transfer, Diffusion Kurtosis Imaging, business.industry, Reproducibility of Results, General Medicine, medicine.disease, Clinical type, Amides, Endometrial Neoplasms, Diffusion Magnetic Resonance Imaging, Diffusion Tensor Imaging, 030220 oncology & carcinogenesis, Female, Histological grades, Radiology, Protons, business, Nuclear medicine
Abstract

To investigate whether amide proton transfer-weighted imaging (APTWI) and diffusion kurtosis imaging (DKI) can be used to evaluate endometrial carcinoma (EC) in terms of clinical type, histological grade, subtype, and Ki-67 index. Eighty-eight patients with EC underwent pelvic DKI and APTWI. The non-Gaussian diffusion coefficient (Dapp), apparent kurtosis coefficient (Kapp), and magnetization transfer ratio asymmetry (MTRasym (3.5 ppm)) were calculated and compared based on the clinical type (type I, II), histological grade (high- and low-grade), and subtype (endometrioid adenocarcinoma (EA) and non-EA). Correlation coefficients were calculated for each parameter with histological grades and the Ki-67 index. The MTRasym (3.5 ppm) and Kapp values were higher in the type II group and high-grade group than in the type I and low-grade groups, respectively, while the Dapp values were lower in the type I and low-grade groups, respectively (all p < 0.05). The Kapp value was higher in the EA group than in the non-EA group (p = 0.022). The Kapp value was the only independent predictor for the histological grade of EA and the clinical type of EC. The AUC (DKI) was higher than the AUC (APTWI) in the identification of type I and II EC and high- and low-grade EA (Z = 2.042, 2.013, p = 0.041, 0.044), while in the identification of EA and non-EA, only the difference in Kapp was statistically significant. Moreover, the Kapp and MTRasym (3.5 ppm) values and Dapp values correlated positively and negatively, respectively, with histological grade (r = 0.759, 0.555, 0.624, and 0.462, all p < 0.05) and Ki-67 index (r = −0.704, −0.507, all p < 0.05). Both DKI- and APTWI-related parameters have potential as imaging markers in estimating the histological features of EC, while DKI shows better performance than APTWI in this study. • DKI and APTWI can be used to preliminarily evaluate the histological characteristics of endometrial carcinoma (EC). • The Kapp was the only independent predictor for the histological grade of EA and the clinical type of EC. • The Kapp, MTRasym (3.5 ppm), and Dapp correlated positively and negatively, respectively, with histological grade and Ki-67 index.

Published
2021

14. Stability mechanism recognition and failure risk assessment on a high slope by synthesizing different analysis methods

Author

Feifei Gan, Liuyang Li, Changqing Qi, Ruoqi Li, Wentao Zhang, and Hui Han

Subjects
021110 strategic, defence & security studies, Atmospheric Science, geography, Hydrogeology, geography.geographical_feature_category, business.product_category, Plateau, 010504 meteorology & atmospheric sciences, Bedrock, 0211 other engineering and technologies, 02 engineering and technology, Slip (materials science), Classification of discontinuities, 01 natural sciences, Wedge (mechanical device), Tectonics, Earth and Planetary Sciences (miscellaneous), Geotechnical engineering, business, Rock mass classification, Geology, 0105 earth and related environmental sciences, Water Science and Technology
Abstract

The studied slope is located in the middle reach of the Yalong River in the eastern margin of Qinghai-Tibet Plateau in Southwest China. A large hydropower station is planning to be built near the slope. Understanding the stability mechanism of the slope is important for dam site design. Under a combination of tectonic activity, unloading and weathering, the bedrock mass was fractured. On the basis of field investigation, the GSI classification system and Barton criterion were introduced to determine the strength of the rock mass. The kinematic, limit equilibrium and discontinuum modeling methods were carried out to comprehensively understand the stability of the slope. The kinematic analyses show that only wedge mode is possible for large rock mass failure. However, limit equilibrium analyses show that both wedge failure and circular slip are not expected for rock mass. The slope rock mass is now in the surface rebalance stage. The potentially unstable part is the covering deposit. The 40 million m3 surface deposit is now nearly in a limit equilibrium state. The possibility of failure reaches 41%. Mitigation measures must be put into effect on the deposit to assure the stability of the slope. The results indicated that the failure mechanism of the slope was not controlled by the discontinuities in the rock mass at present but depended on the stability of the surface deposit.

Published
2021

15. Ocular surface disease associated with immune checkpoint inhibitor therapy

Author

Jennifer Park, Sandeep Jain, Royce B. Park, and Hui Han

Subjects
medicine.medical_specialty, Drug-Related Side Effects and Adverse Reactions, Eye Diseases, genetic structures, medicine.medical_treatment, Ocular rosacea, Disease, Eye, Keratitis, 03 medical and health sciences, 0302 clinical medicine, Cancer immunotherapy, medicine, Humans, Adverse effect, Immune Checkpoint Inhibitors, business.industry, Immunotherapy, medicine.disease, Dermatology, eye diseases, Clinical trial, Ophthalmology, 030220 oncology & carcinogenesis, 030221 ophthalmology & optometry, sense organs, business, Uveitis
Abstract

Immune-related adverse events (irAEs) is a term used to describe the various toxicities associated with immune checkpoint inhibitor (ICI) use. As this class of cancer immunotherapy grows, the diversity of documented irAEs also continues to expand. Ocular toxicities secondary to ICI use are relatively rare, with dry eye and uveitis as the most frequently reported ocular side effects. This article specifically investigates the relationship between ocular surface disease and ICI therapy through a review of the existing literature. Dry eye disease (DED), conjunctivitis, and keratitis were the most commonly reported irAEs affecting the ocular surface across the 29 studies reviewed. Keratoplasty graft rejection was also described in two case reports. Our review of eight clinical trials found the incidence of DED, the most common ocular surface irAE, to range from 1 to 4%. Nearly all cases of ocular surface irAEs were graded as mild or moderate in severity and were often self-limited or controlled with conservative treatment. Duration of checkpoint inhibitor use prior to onset of ocular surface side effects varied widely, ranging from days to months. Ocular surface toxicities associated with checkpoint immunotherapy appear to be under-reported and under-investigated. Further work remains to be done to investigate the full breadth of ocular surface pathologies and the molecular mechanisms by which these toxicities occur.

Published
2021

16. Ocular surface disease in psoriatic patients in a developing country

Author

Yihui Goh, Tsung Fei Khang, Tajunisah Iqbal, Fariz Yahya, Sujaya Singh, Zhenli Kwan, and Winn Hui Han

Subjects
medicine.medical_specialty, genetic structures, Meibomian gland, Psoriatic arthritis, Psoriasis, medicine, Humans, Developing Countries, Ocular surface disease, business.industry, Meibomian Glands, Odds ratio, medicine.disease, Control subjects, Dermatology, eye diseases, Ophthalmology, medicine.anatomical_structure, Case-Control Studies, Tears, Eyelid Diseases, Dry Eye Syndromes, sense organs, Eyelid, business, Ocular surface
Abstract

To evaluate ocular surface changes among patients with psoriasis in Malaysia, a developing country in Southeast Asia. An interdisciplinary case–control study (60 psoriasis patients and 40 control subjects) to look at the differences in ocular surface manifestations between patients with psoriasis and a group of age-, gender- and ethnicity-matched healthy controls. One hundred and twenty eyes of 60 patients with psoriasis and 80 eyes of 40 healthy controls without psoriasis were included in the study. Mild-to-moderate psoriasis was found in 42 patients (70%), while 18 patients (30%) had severe psoriasis. Psoriatic arthritis was found in 19 patients (32%). Of the 60 psoriatic patients, the prevalence of ocular involvement was 65% (39/60), in which 32% (19/60) had dry eyes, 27% (16/60) had lid margin abnormalities, 33% (20/60) had cataract, and one had history of anterior uveitis. Compared to controls, ocular surface of psoriatic patients showed more eyelid margin abnormalities, higher meibomian gland loss and lower tear film break-up time. The estimated odds ratio for dry eyes in the psoriasis group was 2.2 (95% CI: 0.8–6.9). Ocular surface disorders encompassing eyelid margin abnormalities, meibomian gland loss and tear dysfunction occur at an earlier and higher rate among psoriatic patients.

Published
2021

17. Effects of combination treatment with cilnidipine and telmisartan on hypertension, cardiovascular injury, and high blood glucose

Author

Keun-Woo Jang, Joo-Hui Han, Do-Hyung Lee, Miji Lee, Chang-Seon Myung, and Jun-Hwan Jo

Subjects
Combination therapy, business.industry, Insulin tolerance test, Pharmaceutical Science, 02 engineering and technology, Cilnidipine, Pharmacology, 010402 general chemistry, 021001 nanoscience & nanotechnology, medicine.disease, 01 natural sciences, Angiotensin II, 0104 chemical sciences, Blood pressure, medicine, Cardiovascular Injury, Metabolic syndrome, Telmisartan, 0210 nano-technology, business, Pharmacology, Toxicology and Pharmaceutics (miscellaneous), medicine.drug
Abstract

Polypharmacy is an important strategy for managing high blood pressure (BP). Combination treatment with a Ca2+ channel blocker (CCB) and an angiotensin II type 1 receptor blocker (ARB) can be used for this purpose. If combination therapy had additional beneficial effects such as protection against cardiovascular injury and regulation of blood glucose, it would be an effective tool for managing metabolic syndrome. Thus, this study investigated the effects of combination treatment with the CCB cilnidipine and the ARB telmisartan on hypertension, cardiovascular injury, and hyperglycemia. A telemetry system was used to measure BP and heart rate (HR) in spontaneous hypertensive rats (SHRs). The effectiveness of combination therapy in protecting against cardiovascular injury was examined using a myocardial ischemia/reperfusion (MI/R) system in SHRs and a cuff-placement-induced neointima hyperplasia model in C57BL/6 mice. An oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were also performed in obese diabetic mice. Combination treatment with a fixed (human equivalent) dose of cilnidipine and telmisartan can effectively lower BP without reflex tachycardia. This combination therapy may also induce cardioprotective effects by increasing the expression of endothelial nitric oxide synthase (eNOS) and vasoprotective effects by inhibiting DNA synthesis in cuff-induced vascular injury. In addition, it may also attenuate high blood glucose levels. The results of this study suggest that combination treatment with cilnidipine and telmisartan can be used as an effective strategy for the treatment of hypertension and related complications.

Published
2021

18. Prognostic significance of regional lymphadenectomy in T1b gallbladder cancer: Results from 24 hospitals in China

Author

Wan Yee Lau, Bo Yang, Xiaoqing Jiang, Zhe-Wei Fei, Chong Jin, Ya-Wei Hua, Chang-Jun Liu, Xi Zhang, Yongsheng Li, Hong Cao, Hong-Yu Cai, Bei Sun, Kun-Hua Wang, Yijun Shu, Chao-Liu Dai, Jian-Feng Gu, Ying-Bin Liu, Yunfu Cui, Jun Liu, Yang Li, Linhui Zheng, Jing-Yu Cao, Xue-Yi Dang, Ziyu Shao, Yi Wang, Bing Li, Zai-Yang Zhang, Tai Ren, Xiangsong Wu, Hui-Han Jin, Maolan Li, Xu'an Wang, Runfa Bao, Wenguang Wu, Chang Liu, Chun-Fu Zhu, and Ye-Ben Qian

Subjects
medicine.medical_specialty, Staging, business.industry, medicine.medical_treatment, General surgery, Observational Study, Lymphadenectomy, medicine.disease, Gallbladder cancer, Prognosis, Surgery, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, medicine, Hepatectomy, 030211 gastroenterology & hepatology, business
Abstract

BACKGROUND Whether regional lymphadenectomy (RL) should be routinely performed in patients with T1b gallbladder cancer (GBC) remains a subject of debate. AIM To investigate whether RL can improve the prognosis of patients with T1b GBC. METHODS We studied a multicenter cohort of patients with T1b GBC who underwent surgery between 2008 and 2016 at 24 hospitals in 13 provinces in China. The log-rank test and Cox proportional hazards model were used to compare the overall survival (OS) of patients who underwent cholecystectomy (Ch) + RL and those who underwent Ch only. To investigate whether combined hepatectomy (Hep) improved OS in T1b patients, we studied patients who underwent Ch + RL to compare the OS of patients who underwent combined Hep and patients who did not. RESULTS Of the 121 patients (aged 61.9 ± 10.1 years), 77 (63.6%) underwent Ch + RL, and 44 (36.4%) underwent Ch only. Seven (9.1%) patients in the Ch + RL group had lymph node metastasis. The 5-year OS rate was significantly higher in the Ch + RL group than in the Ch group (76.3% vs 56.8%, P = 0.036). Multivariate analysis showed that Ch + RL was significantly associated with improved OS (hazard ratio: 0.51; 95% confidence interval: 0.26-0.99). Among the 77 patients who underwent Ch + RL, no survival improvement was found in patients who underwent combined Hep (5-year OS rate: 79.5% for combined Hep and 76.1% for no Hep; P = 0.50). CONCLUSION T1b GBC patients who underwent Ch + RL had a better prognosis than those who underwent Ch. Hep + Ch showed no improvement in prognosis in T1b GBC patients. Although recommended by both the National Comprehensive Cancer Network and Chinese Medical Association guidelines, RL was only performed in 63.6% of T1b GBC patients. Routine Ch + RL should be advised in T1b GBC.

Published
2021

19. Protective Effects of Anti-depressants against the Subsequent Development of Psoriasis in Patients with Major Depressive Disorder: a Cohort Study

Author

Yi-Hsien Chen, Jui-Hu Shih, Hui-Han Kao, Li Ting Kao, Chin-Bin Yeh, Ya-Mei Tzeng, and I-Hsun Li

Subjects
medicine.medical_specialty, Population, Taiwan, Lower risk, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Psoriasis, Internal medicine, medicine, Humans, education, Retrospective Studies, Depressive Disorder, Major, education.field_of_study, Proportional hazards model, business.industry, Hazard ratio, medicine.disease, 030227 psychiatry, Psychiatry and Mental health, Clinical Psychology, Major depressive disorder, Antidepressant, business, Selective Serotonin Reuptake Inhibitors, 030217 neurology & neurosurgery, Cohort study
Abstract

Background : Inflammation may mediate the relationship between major depressive disorder (MDD) and psoriasis. However, it is unclear whether anti-depressants can decrease the subsequent risk of psoriasis among MDD patients. This study investigated the effects of anti-depressants on the subsequent risk of psoriasis in MDD patients. Methods : This was a population-based cohort study in Taiwan. 58,454 MDD patients who had received anti-depressants and 6,034 MDD patients who did not receive anti-depressants were included. Each patient was tracked for 5 years to confirm a diagnosis of psoriasis following the index date. Cox proportional hazards models were performed to estimate the hazard ratio (HR) for psoriasis. Results : In this study, after using time-dependent Cox regression with both inverse probability of treatment weighting (IPTW) and adjustment for confounders, anti-depressant users had a significantly lower risk of psoriasis than the nonusers (IPTW-adjusted HR [aHR] = 0.69). Additionally, most types and dosages of anti-depressants tended to protect against psoriasis. Selective serotonin reuptake inhibitor use (IPTW-aHR = 0.67) and low-dose anti-depressant use (IPTW-aHR = 0.66) had significant protective effects even after IPTW and adjustment for confounders. Limitations : This study had no information about over-the-counter medications. Conclusions : This study revealed the protective effects of anti-depressants on psoriasis risk in patients with MDD. Antidepressant users had significantly lower risk of psoriasis than the nonusers. Further analyses indicated that the usage of SSRIs and low antidepressant dosage could statistically decrease risk of psoriasis.

Published
2021

20. Corpora Cavernos invasion vs. Corpus Spongiosum invasion in Penile Cancer: A systematic review and meta-analysis

Author

Jiun Hung Geng, Wayne Lam, Antonio Augusto Ornellas, Fangjian Zhou, Zaishang Li, Xueying Li, Yabing Cao, and Hui Han

Subjects
medicine.medical_specialty, 030232 urology & nephrology, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Medicine, Penile cancer, Stage (cooking), lymph node metastasis, business.industry, Hazard ratio, Cancer, Odds ratio, medicine.disease, penile cancer, stage, Confidence interval, meta-analysis, Oncology, Corpus Spongiosum, 030220 oncology & carcinogenesis, Meta-analysis, prognosis, business, Research Paper
Abstract

Objective: Changes were made in the 8th edition of the American Joint Committee on Cancer (AJCC) staging system according to cavernosum invasion for penile squamous cell carcinoma. This study aimed to determine the difference of prognostic validity between corpora cavernosa (CC) invasion and corpus spongiosum (CS) invasion. Methods: In this study, we searched PubMed, Cochrane CENTRAL, and Embase to select English-language articles until July 15, 2020. Pooled analyses of hazard ratios (HRs) and odds ratios (ORs) were performed. Results: Eleven studies including 3692 cases were included in the final ananlysis (1431 cases with CC and 1360 cases with CS). According to the anatomical structure, the pooled results demonstrated that patients with CC invasion had a similar rate of LNM to those with CS invasion (OR 1.34, 95% confidence interval (CI) 0.97-1.86; P=0.076). However, patients with CC invasion had a higher rate of lymph node metastasis (LNM) than those with CS invasion according to the 8th edition tumor stage (OR 1.58, 95% CI 1.14-2.21; P

Published
2021

21. Major depressive disorder increased risk of psoriasis: A propensity score matched cohort study

Author

Wei-Ming Wang, I-Hsun Li, Chin-Bin Yeh, Hui-Han Kao, Li Ting Kao, and Yi-Hsien Chen

Subjects
Male, medicine.medical_specialty, Population, Taiwan, behavioral disciplines and activities, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Psoriasis, mental disorders, medicine, Humans, Prospective Studies, Risk factor, Propensity Score, education, Depressive Disorder, Major, education.field_of_study, business.industry, Incidence, Hazard ratio, medicine.disease, 030227 psychiatry, Psychiatry and Mental health, Clinical Psychology, Cohort, Propensity score matching, Major depressive disorder, business, 030217 neurology & neurosurgery, Cohort study
Abstract

Background Reports showed that elevated proinflammatory cytokines, as detected in patients with psoriasis, was noted in individuals with major depressive disorder (MDD). Therefore, this study aimed to clarify the association of MDD and prospective incidence of psoriasis in human using a nationwide study. Method This population-based cohort study used the data from the Taiwan National Health Insurance system. 64,486 patients were defined as MDD cohort and 64,486 propensity score matched subjects without MDD were identified as comparison cohort. Each patient was independently tracked for a 5-year study period to assure them for a psoriasis diagnosis after the index date. Stratified Cox proportional hazard models were used to calculate the hazard ratio (HRs) for 5-year psoriasis risk. Results After adjustments, the HR of psoriasis for MDD patients was 1.32 compared with subjects without MDD. The stratified analyses present that MDD patients had approximately 1.30-fold significantly higher risk of psoriasis than comparison subjects in most subgroups. Furthermore, compared with the matched subjects without MDD, the adjusted HRs of psoriasis in the 2-, 3-, 4- and 5-year study periods were 1.33, 1.32, 1.33 and 1.32, respectively. Limitations Several patients with MDD or psoriasis might not include in this study, because of using a medical claims database. Conclusions This study provides population-based evidence that MDD is an independent risk factor of developing psoriasis, with an increased risk in the male sex. Additional investigations verifying our findings and exploring possible pathological mechanisms would be of great interest and value to the psychiatric field.

Published
2021

22. Lymph Node Mapping in Patients with Penile Cancer Undergoing Pelvic Lymph Node Dissection

Author

Zhiming Wu, Hui Han, Zike Qin, Zhiyong Li, Dong Chen, Yanjun Wang, Zaishang Li, Yunlin Ye, Yonghong Li, Zhuowei Liu, Fangjian Zhou, Yue Chen, and Kai Yao

Subjects
Male, medicine.medical_specialty, Urology, Penile Neoplasm, 030232 urology & nephrology, Dissection (medical), Lymph node metastasis, Disease-Free Survival, Pelvis, 03 medical and health sciences, 0302 clinical medicine, Humans, Medicine, Penile cancer, In patient, Penile Neoplasms, Lymph node, Neoplasm Staging, Retrospective Studies, Lymph node mapping, business.industry, Middle Aged, medicine.disease, Survival Analysis, body regions, medicine.anatomical_structure, Lymphatic Metastasis, Lymph Node Excision, Lymph Nodes, Radiology, Neoplasm Recurrence, Local, business, Follow-Up Studies
Abstract

A map of pelvic lymph node metastasis in patients with penile cancer helps to clarify the pattern of pelvic spread and define the reasonable limits of dissection, and it has not been established. We aim to provide an accurate map of lymph node metastasis in patients with penile cancer and determine the reasonable extent of pelvic lymph node dissection.We enrolled patients with penile cancer undergoing pelvic lymph node dissection (128) at our institution from 1999 to 2018. The numbers of removed lymph nodes and positive lymph nodes at 10 distinct regions were recorded. The chi-square and Fisher exact tests were used.The median number of pelvic lymph nodes retrieved was 18 (IQR 10-30), with the majority being from the external iliac package (43.0%) and obturator package (31.9%). Pelvic lymph node metastasis was present in 57/128 (44.5%) patients. The median number of positive pelvic lymph nodes removed was 2 (IQR 1-4), with the majority being from the external iliac package (50.0%) and obturator package (36.6%). Advanced T-stage was related to higher risk of pelvic lymph node metastasis, which was present in 30.3%, 44.2%, 59.0% and 58.3% of patients with pT1, pT2, pT3 and pT4, respectively. Notably, 2 patients had crossover metastasis from 1 inguinal region to the contralateral pelvic region.We present a detailed map of pelvic lymph node metastasis in patients with penile carcinoma. The external iliac and obturator packages appear to be most commonly involved. Optimal pelvic lymph node dissection may extend to the common iliac artery, including common iliac, external iliac, internal iliac and obturator lymph nodes. Extranodal extension in inguinal nodes may not be as important as previously thought.

Published
2021

23. miR-30c-5p inhibits glioma proliferation and invasion via targeting Bcl2

Author

Hui Han, Liqun Yuan, Tan Zhang, Shihai Liu, and Liang Xu

Subjects
Cancer Research, Bcl2, Oncology, business.industry, Glioma, Cancer research, medicine, Radiology, Nuclear Medicine and imaging, Original Article, medicine.disease, business, miRNA
Abstract

Background Glioma is a highly malignant brain tumor, characterized by the poor prognosis and high recurrence rates. Previous studies have confirmed that miRNA-30c-5p is closely associated with tumor cell biological properties. The present study explored the biological role of miR-30c-5p in human glioma malignant behavior and underlying mechanisms. Methods Levels of miR-30c-5p were detected in glioma tissues and adjacent normal tissues. Two glioma cell lines including U87 and U251 were transfected with miR-30c-5p mimic or inhibitors. Cell proliferation was evaluated by MTT assay and colony formation assay. Cell apoptosis and invasive potential of glioma cells were assessed by flow cytometry and transwell assays, respectively. Luciferase reporter assay was performed to validate the target gene of miR-30c-5p. Results Levels of miR-30c-5p were dramatically decreased in glioma tissues as compared to the adjacent normal tissues. Upregulation of miR-30c-5p significantly suppressed cell growth and colony formation, and induced apoptosis in glioma cells. In contrast, inhibition of miR-30c-5p promoted the proliferation and inhibited apoptosis in tumor cells. Furthermore, miR-30c-5p strongly suppresses the invasion of glioma cells. Western blot showed that Bcl-2 was significantly decreased following treatment with miR-30c-5p mimics and increased after miR-30c-5p inhibitor treatment. Moreover, luciferase reporter assays indicated that transfection of miR-30c-5p led to a marked reduction of luciferase activity, but had no effect on Bcl-2 3'-UTR mutated fragment. Mechanically, miR-30c-5p promoted the activation of caspase 3 and caspase 9 in glioma cells. Furthermore, miR-30c-5p promoted apoptosis and inhibited colony formation and migration, and knockdown of Bcl2 further increased the number of apoptotic cells and suppressed colony formation and migration of glioma cells. By contrast, miR-30c-5p inhibitors decreased apoptosis and increased colony formation and migration, and restored Bcl2 expression further suppressed glioma cell apoptosis and enhanced colony formation and migration. Conclusions These results demonstrated that miR-30c-5p regulated growth, apoptosis and migration in glioma cells by targeting Bcl2, suggesting that miR-30c-5p might serve as a novel target for glioma therapy.

Published
2021

26. The introduction of treatment and the cultural adaptability of western psychotherapies for eating disorders in China

Author

Lei Guo, Hui Han, Lian Gu, and Jue Chen

Subjects
China, 050103 clinical psychology, Psychotherapist, medicine.medical_treatment, Behavioral therapy, Support group, law.invention, Feeding and Eating Disorders, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, Behavior Therapy, law, medicine, Humans, 0501 psychology and cognitive sciences, Cultural Characteristics, Cognitive Behavioral Therapy, business.industry, 05 social sciences, Treatment method, medicine.disease, 030227 psychiatry, Psychotherapy, Cognitive behavioral therapy, Psychiatry and Mental health, Eating disorders, Psychotherapy, Group, Family Therapy, business
Abstract

In the past 40 years, the prevalence of eating disorders (ED) in China has shown an increasing trend, leading to an urgent need to develop efficient treatment modes and methods. Since the beginning of the new century, the diagnosis, treatment, and research of ED in China have been under development. This article gives an introduction and commentary on the treatment modes, treatment methods and their applications in ED in China. There are two main treatment forms for ED until now, that is, inpatient treatment and outpatient treatment. Inpatient treatment is recommended as the first choice. Since 2008, clinical psychotherapies such as cognitive behavioral therapy (CBT), dialectical behavioral therapy (DBT), and family-based treatment (FBT), which are effective for pathological symptoms of ED, have been introduced into China and developed clinically. Group CBT and group DBT for patients with ED and group FBT for caregivers might be the most efficient psychotherapy in China nowadays. A multi-family FBT support group could be developed as the basic treatment of ED patients. Although these new types of psychotherapy have observed effectiveness in clinical application, the Randomized Controlled Trials (RCT) are rare and need to be developed.

Published
2020

28. Relationship Between the Sizes of Blood Vessel and Selected Stent

Author

Hui-Han Lin

Subjects
medicine.medical_specialty, medicine.anatomical_structure, business.industry, medicine.medical_treatment, medicine, General Earth and Planetary Sciences, Stent, Radiology, business, General Environmental Science, Blood vessel
Published
2020

29. Mechanisms of resistance to immune checkpoint inhibitors and strategies to reverse drug resistance in lung cancer

Author

Fang-Fei Qian, Bao-Hui Han, and Pei-Fang Wei

Subjects
Lung Neoplasms, Population, Antigen presentation, Resistance, Drug Resistance, lcsh:Medicine, Drug resistance, B7-H1 Antigen, 03 medical and health sciences, Immune checkpoint inhibitors, 0302 clinical medicine, Antigen, Tumor Microenvironment, Medicine, Humans, CTLA-4 Antigen, Combination therapy, Lung cancer, education, Review Articles, Tumor microenvironment, education.field_of_study, biology, business.industry, lcsh:R, General Medicine, Precision medicine, medicine.disease, 030220 oncology & carcinogenesis, Cancer research, biology.protein, Mechanism, Immunotherapy, Antibody, business, 030217 neurology & neurosurgery
Abstract

In recent years, the research of immune checkpoint inhibitors has made a great breakthrough in lung cancer treatment. Currently, a variety of immune checkpoint inhibitors have been applied into clinical practice, including antibodies targeting the programmed cell death-1, programmed cell death-ligand 1, and cytotoxic T-lymphocyte antigen 4, and so on. However, not all patients can benefit from the treatment. Abnormal antigen presentation, functional gene mutation, tumor microenvironment, and other factors can lead to primary or secondary resistance. In this paper, we reviewed the molecular mechanism of immune checkpoint inhibitor resistance and various combination strategies to overcome resistance, in order to expand the beneficial population and enable precision medicine.

Published
2020

30. Bmi1 Severs as a Potential Tumor-Initiating Cell Marker and Therapeutic Target in Esophageal Squamous Cell Carcinoma

Author

Yong Bao, Jianwen Chen, Hui Han, Liang Peng, Wenjing Liao, Maosheng Cheng, Xiaochen Wang, Kang Li, Demeng Chen, Zhi Chen, Ganping Wang, and Fangfang Chen

Subjects
Cisplatin, Article Subject, biology, business.industry, Cell, Therapeutic effect, macromolecular substances, Cell Biology, biology.organism_classification, Tumor initiating cell, RC31-1245, Esophageal squamous cell carcinoma, digestive system diseases, medicine.anatomical_structure, BMI1, Lineage tracing, Murine leukemia virus, medicine, Cancer research, business, Internal medicine, neoplasms, Molecular Biology, Research Article, medicine.drug
Abstract

Esophageal squamous cell carcinoma (ESCC) is a frequent malignant tumor with low 5-year overall survival. Targeting ESCC tumor-initiating cells (TICs) may provide a new research avenue to achieve better therapeutic effects of ESCC. However, the identity and characteristics of ESCC TICs remain poorly understood. Through genetic lineage tracing approach, we found that a group of Moloney murine leukemia virus insertion site 1- (Bmi1-) expressing cell populations present in the invasive front of the esophageal epithelium, providing a continuous flow of tumor cells for ESCC. Subsequently, we found that ablation of Bmi1+ cells from mice with ESCC led to inhibition of tumor growth. In addition, our results demonstrated that PTC-209, an inhibitor of Bmi1, was able to inhibit ESCC progression when combined with cisplatin. In summary, our data suggest that Bmi1+ cells serve as TICs in ESCC.

Published
2020

31. Comparison of Body-Image Dissatisfaction Among Chinese Children and Adolescents at Different Pubertal Development Stages

Author

Rongying Yao, Yifei Zhang, Lili Sun, Xuesen Wu, Lu Wu, Lianguo Fu, Ting Li, Huaiquan Gao, and Hui Han

Subjects
Psychiatry and Mental health, Breast development, Secondary sex characteristic, business.industry, Negative body image, Menarche, Medicine, Sex organ, Self perception, business, General Psychology, Demography
Abstract

Background Body-image dissatisfaction among children and adolescent has become increasingly serious, and may be the result of staged differences in the puberty-development process. The aim of this study was to compare differences in body-image dissatisfaction among children and adolescents at different pubertal stages. Methods A total of 574 students aged 8-15 years were recruited from two nine-year schools via stratified cluster sampling, their secondary sex characteristics and external genital development examined, and body-image cognition surveyed using the teenage body-image annoyance questionnaire. This questionnaire covers body-shape, gender, sexual organ, and appearance dissatisfaction. Lower scores indicate a more negative body image. Results Total, gender, and appearance-dissatisfaction scores in girls were significantly lower than in boys (P

Published
2020

32. miR‐448‐3p alleviates diabetic vascular dysfunction by inhibiting endothelial–mesenchymal transition through DPP‐4 dysregulation

Author

Yang Sun, Guo-Ying Guan, Ying-Ying Xu, Ya-Mei Dai, Hui Han, Ru-Xin Pan, Tao Song, Lu-Lu Zhang, Nan Wei, and Chao Zhao

Subjects
0301 basic medicine, medicine.medical_specialty, Epithelial-Mesenchymal Transition, Physiology, Dipeptidyl Peptidase 4, Clinical Biochemistry, Cell, SMAD, Diabetes Mellitus, Experimental, 03 medical and health sciences, 0302 clinical medicine, Downregulation and upregulation, Internal medicine, Diabetes mellitus, Diabetes Mellitus, medicine, Animals, Humans, Endothelial dysfunction, Dipeptidyl peptidase-4, business.industry, Endothelial Cells, Cell Biology, Transfection, medicine.disease, Streptozotocin, Rats, MicroRNAs, 030104 developmental biology, Endocrinology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, business, Diabetic Angiopathies, medicine.drug
Abstract

Diabetes mellitus (DM) often causes vascular endothelial damage and alters vascular microRNA (miR) expression. miR-448-3p has been reported to be involved in the development of DM, but whether miR-448-3p regulates diabetic vascular endothelial dysfunction remains unclear. To investigate the molecular mechanism of diabetic vascular endothelial dysfunction and the role of miR-448-3p therein, Sprague-Dawley rats were injected with streptozotocin (STZ) to establish diabetic animal model and the rat aortic endothelial cells were treated with high glucose to establish diabetic cell model. For the treatment group, after the induction of diabetes, the miR-448-3p levels in vivo and in vitro were upregulated by adeno-associated virus serotype 2 (AAV2)-miR-448-3p injection and miR-448-3p mimic transfection, respectively. Our results showed that AAV2-miR-448-3p injection alleviated the body weight loss and blood glucose level elevation induced by STZ injection. The miR-448-3p level was significantly decreased and the dipeptidyl peptidase-4 (DPP-4) messenger RNA level was increased in diabetic animal and cell models, which was reversed by miR-448-3p treatment. Moreover, the diabetic rats exhibited endothelial damage and endothelial-mesenchymal transition (EndMT), while AAV2-miR-448-3p injection relieved those situations. In vitro experiments demonstrated that miR-448-3p overexpression in endothelial cells alleviated endothelial damage by inhibiting EndMT through blocking the transforming growth factor-β/Smad pathway. We further proved that miR-448-3p negatively regulated DPP-4 by binding to its 3'-untranslated region, and DPP-4 overexpression reversed the effect of miR-448-3p overexpression on EndMT. Overall, we conclude that miR-448-3p overexpression inhibits EndMT via targeting DPP-4 and further ameliorates diabetic vascular endothelial dysfunction, indicating that miR-448-3p may serve as a promising therapeutic target for diabetic endothelial dysfunction.

Published
2020

33. Self-reported generalised pruritus among community-dwelling older adults in Malaysia

Author

Winn Hui Han, Zhenli Kwan, Maw Pin Tan, Adrian Sze Wai Yong, Shahrul Bahyah Kamaruzzaman, Ai-Vyrn Chin, Shin Shen Yong, Chin Chwen Ch'ng, and Leng Leng Tan

Subjects
medicine.medical_specialty, medicine.medical_treatment, Population, Comorbidity, Dermatology, lcsh:Geriatrics, Geriatrics medicine, Pittsburgh Sleep Quality Index, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Quality of life, Internal medicine, medicine, Humans, 030212 general & internal medicine, education, skin and connective tissue diseases, Depression (differential diagnoses), Aged, Generalised pruritus, education.field_of_study, Rehabilitation, integumentary system, business.industry, Pruritus, Malaysia, Sleep quality, medicine.disease, body regions, lcsh:RC952-954.6, Cross-Sectional Studies, Quality of Life, Anxiety, Independent Living, Self Report, Geriatrics and Gerontology, medicine.symptom, business, Psychosocial, Research Article
Abstract

BackgroundThe ageing skin is more susceptible to pruritic dermatoses, which are associated with adverse psychosocial effects and reduced quality of life among older adults. This cross-sectional study aimed to identify the burden of pruritus and factors associated with its presence and severity among older adults recruited to the Malaysian Elders Longitudinal Research study.MethodsSeven hundred seventy individuals aged 55 years (lower age limit) and above were interviewed as to whether they experienced pruritus during the preceding week and the locations involved if present. The association between generalised pruritus, sleep quality, and major systemic risk factors were explored.Results5.97% of respondents reported generalised pruritus. Generalised pruritus was associated with poorer sleep quality, with Pittsburgh Sleep Quality Index score above 6. Mean haemoglobin level was lower in subjects with generalised pruritus (13.14 g/dL) but there was no significant difference in the frequency of generalised pruritus and severe generalized pruritus between subjects with clinically defined anaemia. Also, there were no significant associations between other major systemic risk factors and generalised pruritus in this population-based study. There was no association between generalised pruritus with depression, anxiety or stress.ConclusionThe negative effect of pruritus on sleep quality suggests a possible deleterious effect of pruritus on health and quality of life. Further prospective research on the longer-term effects of pruritus on health status is now warranted.(222 words)

Published
2020

34. A Novel Indicator of Children’s Lipid Accumulation Product Associated with Impaired Fasting Glucose in Chinese Children and Adolescents

Author

Bangxuan Wang, Yongting Yuan, Li Zhang, Lianguo Fu, Yehuan Sun, Hui Han, Rongying Yao, Lili Sun, and Hong Xie

Subjects
Pharmacology, medicine.medical_specialty, Waist, Receiver operating characteristic, business.industry, nutritional and metabolic diseases, 030209 endocrinology & metabolism, 030204 cardiovascular system & hematology, medicine.disease, Impaired fasting glucose, Logistic regression, Abdominal Skinfold Thickness, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, Metabolic syndrome, business, Lipid Accumulation Product
Abstract

Background Diabetes is one of the most prevalent noncommunicable diseases worldwide. Children's lipid accumulation product (CLAP) is a novel indicator to show children's lipid accumulation and is effectively associated with metabolic syndrome among children and adolescents. The aim of the present study was to explore an association between CLAP and impaired fasting glucose (IFG) in Chinese children and adolescents. Methods A total of 683 children and adolescents aged 8-15 years were recruited using the stratified cluster sampling method in this cross-sectional study and were measured for body height, weight, waist circumference (WC), abdominal skinfold thickness (AST), triglycerides (TG), fasting plasma glucose, dietary behaviors and physical activities. A logistic regression model and receiver operating characteristic (ROC) curve were used to compare the effects of CLAP for predicting IFG. Results The prevalence of IFG in children and adolescents was 13.8%: 16.9% in boys and 10.1% in girls (P

Published
2020

35. Radiotherapy plus chemotherapy versus chemotherapy alone in penile cancer patients with extracapsular nodal extension after inguinal lymph node surgery: a multi-institutional study

Author

Fangjian Zhou, Zike Qin, Zhuowei Liu, Peng Chen, Zaishang Li, Xiang Li, Ornellas Antonio Augusto, Xueying Li, Yonghong Li, Hui Han, and Bin Wang

Subjects
Nephrology, Chemotherapy, medicine.medical_specialty, business.industry, Proportional hazards model, Urology, medicine.medical_treatment, Penile Neoplasm, 030232 urology & nephrology, medicine.disease, Surgery, Radiation therapy, 03 medical and health sciences, 0302 clinical medicine, Interquartile range, 030220 oncology & carcinogenesis, Internal medicine, Adjuvant therapy, Medicine, Penile cancer, business
Abstract

Because there is a lack of evidence, it is not generally recommended to use adjuvant radiotherapy plus chemotherapy to treat lymph node disease in penile cancer. The aim of this study was to determine the benefit of using adjuvant radiotherapy after inguinal surgery for penile cancer. Multi-institutional data were obtained from a total of nine centers from April 2003 to April 2015 and retrospectively analyzed. pN3 patients with an extracapsular nodal extension who received adjuvant therapy after inguinal surgery were included. Cancer-specific survival (CSS) was estimated using the Kaplan–Meier method. The multivariate analysis was performed using a Cox proportional hazards model. A total of 93 pN3 patients met the inclusion criteria. During the study period, 32 (34.4%) and 61 (65.6%) of these patients received adjuvant radiotherapy plus chemotherapy (AR + AC) or adjuvant chemotherapy alone (AC). The median CSS in all patients was 12.0 months (interquartile range [IQR] 7.5–16.5). The Kaplan–Meier estimated 3-year CSS rate was significantly longer in the AR + AC group (28.5%) than the AC group (16.2%) (p = 0.036). AC + AR was associated with an improvement in CSS by 7.7 months (17.7 [IQR 3.8–31.6] vs. 10.0 [IQR 6.6–13.4] months). In the Cox regression analysis, AR + AC was an independent predictor of CSS [model a: HR 0.486 (95% CI 0.258–0.916), model b: HR 0.527 (95% CI 0.286–0.972)]. In conclusions, AR + AC was associated with improved CCS in patients with penile cancer who displayed an extracapsular nodal extension after inguinal surgery. This hypothesis requires further confirmation.

Published
2020

36. The effects of combined treatment of losartan and ramipril on hypertension and related complications

Author

Miji Lee, Joo-Hui Han, Hyun-Soo Park, Keun-Woo Jang, Do-Hyung Lee, Sang-Hyuk Jung, and Chang-Seon Myung

Subjects
Ramipril, Neointima, Mean arterial pressure, medicine.medical_specialty, Combination therapy, Ischemia, Pharmaceutical Science, 02 engineering and technology, 010402 general chemistry, 01 natural sciences, Internal medicine, medicine, cardiovascular diseases, Myocardial infarction, Pharmacology, Toxicology and Pharmaceutics (miscellaneous), business.industry, 021001 nanoscience & nanotechnology, medicine.disease, 0104 chemical sciences, Blood pressure, Losartan, cardiovascular system, Cardiology, 0210 nano-technology, business, medicine.drug
Abstract

Polypharmacy has been an important strategy for the management of hypertension. The aim of this study was to investigate the effect of combined treatment of losartan with ramipril on hypertension, myocardial infarction and vascular remodeling in disease animal models. In 8-telemetered spontaneous hypertensive rats (SHRs) orally treated with various doses of drugs or vehicle by cross-over protocol, systolic blood pressure (SBP), mean arterial pressure (MAP) and heart rate (HR) were measured. The infarct size was measured in rats subjected to 30 min occlusion of the left anterior descending coronary artery (LAD) followed by 150 min reperfusion in myocardial ischemia/reperfusion (MI/R) rats injected drugs or vehicle once through femoral vein 15 min before inducing ischemia. The neointima formation and DNA synthesis in intima and media layer of the blood vessels were measured in cuff-induced vascular injury mice orally treated with drugs for 2 weeks. As compared with single treatment, the combination therapy of both drugs significantly decreased SBP and MAP without significant reflex tachycardia. The combined treatment of both drugs significantly increased the expression of endothelial nitric oxide synthase (eNOS) in coronary arterial tissues including area at occlusion. The combination therapy significantly decreased the thickness of vascular media layer and the number of bromodeoxyuridine (BrdU)-positive cells in both intima and media. The present data suggest that the combination therapy with fixed doses of losartan and ramipril may exert greater BP-lowering effects with protection against myocardial infarction and vascular remodeling.

Published
2020

37. 3–D Numerical study for the film thickness distribution of n–pentane falling film flow around the curved egg–shaped tube bundle

Author

Hui Han, Shaowei Wang, Chongzheng Sun, and Yuxing Li

Subjects
Materials science, business.industry, 020209 energy, General Chemical Engineering, Flow (psychology), 02 engineering and technology, General Chemistry, 021001 nanoscience & nanotechnology, Pentane, chemistry.chemical_compound, chemistry, Natural gas, Heat transfer, Heat exchanger, 0202 electrical engineering, electronic engineering, information engineering, Fluid dynamics, Tube (fluid conveyance), Composite material, 0210 nano-technology, business, Falling (sensation)
Abstract

Shell-side falling film flow is extremely important for the heat transfer performance of spiral wound heat exchangers used in liquefied process of natural gas. In this paper, 3-D simulations using hydrocarbon (n-pentane) as the testing fluid are conducted to study the fluid flow characteristic of heat exchanger with curved egg-shaped tube. The effects of different Re numbers (Re) and longitudinal inter-tube spacing (S) on the inter-tube flow modes and the distribution of film thickness (δ) with Re varying from 327 to 2944 are investigated. The axial and circumferential distribution of δ is analyzed qualitatively and quantitatively. The results show that when Re is relatively small (327 and 736), the effect of S on average value of δ (δa) is negligible. When Re is relatively large (1472 and 2944), the increase of S would thicken δ on tube lower perimeter. When Re increased from 327 to 2944, δa firstly increases and then decreases as the increase of Re and the ratio (Lb) of the axial length of basin zone to the axial measurement range increases from 52% to 76%. In addition, δ of basin zone is almost always much lower (59.23% thinner when Re = 2944) than the classic prediction results of equal-perimeter circular tube.

Published
2020

38. Up‐regulation of indoleamine 2,3‐dioxygenase 1 (IDO1) expression and catalytic activity is associated with immunosuppression and poor prognosis in penile squamous cell carcinoma patients

Author

Zai Shang Li, Zi Ke Qin, Yun Lin Ye, Yong Hong Li, Chuang Zhong Deng, Zhuo Wei Liu, Jie Ping Chen, Sheng Jie Guo, Kang bo Huang, Qiang Hua Zhou, Hui Han, Ting Yu Liu, Jia bin Lu, Fang Jian Zhou, Ran yi Liu, and Kai Yao

Subjects
0301 basic medicine, Male, Cancer Research, cytotoxic T‐lymphocyte‐associated protein 4, medicine.medical_treatment, B7-H1 Antigen, programmed death‐ligand 1, chemistry.chemical_compound, 0302 clinical medicine, Medicine, Cytotoxic T cell, Interferon gamma, CTLA-4 Antigen, Indoleamine 2,3-dioxygenase, Kynurenine, Aged, 80 and over, immunosuppression, Tryptophan, Immunosuppression, programmed cell death protein 1, Middle Aged, Prognosis, interferon‐gamma, Up-Regulation, Survival Rate, Oncology, 030220 oncology & carcinogenesis, Lymphatic Metastasis, Carcinoma, Squamous Cell, Original Article, medicine.drug, Adult, indoleamine 2,3‐dioxygenase 1, Andrology, 03 medical and health sciences, Young Adult, Immune system, Cell Line, Tumor, Biomarkers, Tumor, Immune Tolerance, Penile cancer, Humans, Indoleamine-Pyrrole 2,3,-Dioxygenase, Penile Neoplasms, Aged, business.industry, tumor‐infiltrating immune cells, Original Articles, medicine.disease, penile cancer, 030104 developmental biology, chemistry, Cancer cell, kynurenine/tryptophan ratio, business
Abstract

Background Indoleamine 2,3‐dioxygenase 1 (IDO1) and tryptophan (Trp) catabolism have been demonstrated to play an important role in tumor immunosuppression. This study examined the expression and catalytic activity of IDO1 in penile squamous cell carcinoma (PSCC) and explored their clinical significance. Methods IDO1 expression level, serum concentrations of Trp and kynurenine (Kyn) were examined in 114 PSCC patients by immunohistonchemistry and solid‐phase extraction‐liquid chromatography‐tandem mass spectrometry. The survival was analyzed using Kaplan‐Meier method and the log‐rank test. Hazard ratio of death was analyzed via univariate and multivariate Cox regression. Immune cell types were defined by principal component analysis. The correlativity was assessed by Pearson's correlation analysis. Results The expression level of IDO1 in PSCC cells was positively correlated with serum Kyn concentration and Kyn/Trp radio (KTR; both P

Published
2020

39. Generation of Bright-Dark Soliton Pairs in Mode-Locked Fiber Laser Based on Molybdenum Diselenide

Author

Dongxin Liu, Hui-Hui Han, and Xiaofa Wang

Subjects
Molybdenum diselenide, Materials science, General Computer Science, Field (physics), business.industry, General Engineering, Physics::Optics, Saturable absorption, Soliton (optics), Chemical vapor deposition, mode-locked fiber laser, Amplitude modulation, chemistry.chemical_compound, Mode locked fiber laser, bright-dark soliton pairs, chemistry, Fiber ring laser, Optoelectronics, General Materials Science, lcsh:Electrical engineering. Electronics. Nuclear engineering, business, lcsh:TK1-9971
Abstract

In this article, molybdenum diselenide (MoSe2) was fabricated by chemical vapor deposition (CVD) with a modulation depth of about 7.3% and nonsaturable loss of about 30.6%. Bright-dark soliton pairs have been obtained in a thulium-holmium-doped fiber ring laser based on MoSe2 as a saturable absorber (SA) for the first time, to the best of our knowledge. The results not only prove that MoSe2 can be used as an excellent saturable absorber in the field of ultra-fast optics, but also provide a certain reference value for the future research on bright-dark soliton pairs based on two-dimensional materials.

Published
2020

40. Two-Week Prevalence of Disease Among the Rural Elderly — 6 Provinces, China, 2018−2019

Author

Tong Xu and Hui Han

Subjects
medicine.medical_specialty, Population ageing, business.industry, Public health, Ethnic group, MEDLINE, Prevalence, Disease, Preplanned Studies, Environmental health, medicine, General Agricultural and Biological Sciences, business, China, Elderly health
Abstract

What is already known about this topic? As population aging becomes serious in China, the elderly health problems stand out prominently. The 2-week prevalence of the elderly is rising year by year, but it has been rarely studied for the rural seniors in the central and western China. What is added by this report? The 2-week prevalence rate of rural elderly in the central and western China is 28.5%, and it varies among different ethnic groups. The top prevalence is chronic diseases, and the severity of diseases is higher in female and high age group (80-year-old and over) people. What are the implications for public health practice? Considering the health status, health awareness and ethnic differences of the elderly in the central and western China, medical and health resources should be rationally allocated to prevent and treat chronic diseases and support differentiated health services. This is of great significance for the development of health service plan.

Published
2020

41. Towards a data science platform for improving SME collaboration through Industry 4.0 technologies

Author

Silvana Trimi, Hui Han, and Publica

Subjects
Standardization, Industry 4.0, business.industry, Computer science, media_common.quotation_subject, Big data, Digital transformation, Data science, Adaptability, Order (business), Management of Technology and Innovation, Small and medium-sized enterprises, Business and International Management, Resilience (network), business, Applied Psychology, media_common
Abstract

Industry 4.0 (I4.0) is about realizing digital transformation by linking machines to plants, fleets, and humans through sensors and control elements in order to create smart networks, smart factories, smart manufacturing, and smart value chains. By leveraging I4.0 technologies, a small and medium enterprise (SME) can increase its organizational agility, adaptability, and resilience to cope with today's competitive environment by becoming a valuable and innovative partner in the power dynamics with its large buyer counterparts. However, SMEs face technology, trust, and big data challenges when they adopt I4.0 technologies. This study provides new solutions for SMEs to overcome these three challenges in implementing I4.0. Specifically, the paper proposes the following: (1) a roadmap for the application of I4.0 technologies to enhance the collaboration capabilities of SMEs; (2) a structure for I4.0 standardization to develop and sustain trust among partners; and (3) an improved data science platform for systematizing big data to extract critical information for collaboration solutions for SMEs. Additionally, the solutions are evaluated based on an application case of a Greek SME, demonstrating their potentials for practical implementation.

Published
2022

42. Relationship between exterior environment and quality characteristics of the traditional Gochujang produced in 2018 by eight regions in Korea

Author

Young-Eun Song, Na-Young Gil, Heui-Yun Kang, Seung-Yeon Baek, Ha-Yeon Lee, Myeong-Hui Han, So-Young Kim, Sunkyung Lee, Hyang-Sik Yoon, Hyeon-Young Kim, Jeong Lee, Soo-Hwan Yeo, and Jung-A Ryu

Subjects
business.industry, media_common.quotation_subject, Environmental resource management, Environmental science, Quality (business), business, Quality characteristics, Food Science, media_common
Abstract

The objective of this study was to investigate the quality and environment properties of traditional Gochujang produced by 56 rural farms in 8 regions of Korea for evaluating the relationship between the components and environmental factors. Based on the regional means at the initiatory and after fermentation, the ranges of moisture content, salinity, pH, and acidity of Gochujang were determined to be from 46.87±7.09% to 43.80±7.17%, from 7.52±2.21% to 8.53±2.57%, from 5.01±0.30 to 4.63±0.34, and from 1.13±0.50% to 1.43±0.58%, respectively. The mean contents of reducing sugar and amino-type nitrogen were from 16.46±7.63% to 20.48±7.57% and from 140.06±78.00 mg% to 198.68±87.11 mg%, respectively. Hunter color values (L, a, and b) of Gochujang were from 26.16±9.27 to 22.49±9.02, from 21.87±6.31 to 20.14±7.58, and from 19.43±11.94 to 19.18±12.06, respectively. Total aerobic number was increased from 6.50±1.29 log CFU/g to 8.15±0.88 log CFU/g, while the fungal number was steadily decreased after fermentation. Next generation sequencing analysis to investigate the microbial communities revealed that the dominant bacteria in Gochujang belong to the phyla of Firmicutes and Cyanobacteria. Similarly, Aspergillus spp. of the phylum Ascomycota was the predominant fungi in traditional Gochujang. Finally, according to principle component analysis of the relationship between the quality and environmental properties of Gochujang, the contents of amino-type nitrogen, salinity, titratable acidity, and reducing sugar had strong correlations with exterior humidity. These results also suggest that the quality of traditional soybean sauces can be controlled by exterior environmental change.

Published
2019

43. A Novel Classifier Design Algorithm Based on Gray Relation Theory

Author

Yulong Ying, Jingchao Li, Hui Han, and Xiang Chen

Subjects
010302 applied physics, Computer science, business.industry, 020208 electrical & electronic engineering, General Engineering, Pattern recognition, 02 engineering and technology, 01 natural sciences, 0103 physical sciences, 0202 electrical engineering, electronic engineering, information engineering, Artificial intelligence, business, Theory of relations, Gray (horse), Classifier (UML)
Abstract

Background: With the technical development of counter-reconnaissance and antijamming, communication system becomes more and more complex, and therefore, the recognition of communication signal becomes a challenging task according to recent patents. In order to achieve successful recognition and classification of radiation source signal under variant SNR environment, the design and selection of classifier are one of the key points. Methods: Gray relation theory can solve the learning problem with a small number of samples and its algorithm is simple and can solve the issue of generality versus accuracy, which is very suitable for dealing with fuzzy mathematical problems. However, the selection of distinguishing coefficient has a direct effect on the recognition results by gray relation classifier. For conventional gray relation classifier, the distinguishing coefficient is usually set as a fixed value of 0.5, and for different types of signals, its recognition rate varies. Aiming at this issue, an improved adaptive gray relation classifier algorithm is proposed in the paper. Results: The simulation results show that the recognition rate can still reach more than 87% even at the SNR of 10dB. Conclusion: The proposed methods can improve the anti-jamming capability of the classifier, which can be widely used in the fields of electronic reconnaissance, fault diagnosis and image processing.

Published
2019

44. Slice encoding for the reduction of outflow signal artifacts in cine balanced SSFP imaging

Author

Vahid Ghodrati, Fadil Ali, Peng Hu, Mark Bydder, Hui Han, Ashley Prosper, Chang Gao, J. Paul Finn, Da Wang, and Kim-Lien Nguyen

Subjects
Computer science, Biomedical Engineering, Signal, Imaging phantom, Phantoms, 030218 nuclear medicine & medical imaging, Imaging, Reduction (complexity), Breath Holding, 03 medical and health sciences, 0302 clinical medicine, Computer-Assisted, Encoding (memory), Humans, Radiology, Nuclear Medicine and imaging, bSSFP, out-of-slice, Image Interpretation, Balanced ssfp, business.industry, slice encoding, Nonparametric statistics, Pattern recognition, Single breath, signal profile, Magnetic Resonance Imaging, Nuclear Medicine & Medical Imaging, Cine, Biomedical Imaging, Outflow, Artificial intelligence, business, Artifacts, cardiac cine, 030217 neurology & neurosurgery
Abstract

PURPOSE Standard balanced SSFP (bSSFP) cine MRI often suffers from blood outflow artifacts. We propose a method that spatially encodes these outflowing spins to reduce their effects in the intended slice. METHODS Bloch simulations were performed to characterize through-plane flow and to investigate how the use of phase encoding along the slice select's direction ("slice encoding") could alleviate its issues. Phantom scans and in vivo cines were acquired on a 3T system, comparing the standard 2D acquisition to the proposed slice-encoding method. Nineteen healthy volunteers were recruited for short-axis and horizontal long-axis oriented scans. An expert radiologist evaluated each slice-encoded/standard cine pairs in a rank comparison test and graded their quality on a 1-5 scale. The grades were used for a nonparametric paired evaluation for independent samples with a null hypothesis that there was no statistical difference between the two quality-grade distributions for α = 0.05 significance. RESULTS Bloch simulation results demonstrated this technique's feasibility, showing a fully resolved slice profile given a sufficient number of slice encodes. These results were confirmed with the phantom experiments. Each in vivo slice-encoded cine had a higher quality than its corresponding standard acquisition. The nonparametric paired evaluation came to 0.01 significance, encouraging us to reject the null hypothesis and conclude that slice-encoding effectively works in reducing outflow effects. CONCLUSION The slice-encoding balanced SSFP technique is helpful in mitigating outflow effects and is achievable within a single breath hold, being a useful alternative for cases in which the flow artifacts are significant.

Published
2021

45. MP14-18 NEOADJUVANT COMBINATION OF PAZOPANIB OR AXITINIB AND PD-1-ACTIVATED DC-CIK CELLS IMMUNOTHERAPY MAY FACILITATE SURGERY IN PATIENTS WITH RENAL CELL CARCINOMA

Author

Pei Dong, Chunping Yu, Longbin Xiong, Ya Ding, Fangjian Zhou, Hui Han, Zeshen Wu, Shengjie Guo, Desheng Weng, Huiming Liu, Lijuan Jiang, Yulu Peng, Zhiling Zhang, Jianchuan Xia, and Kang Ning

Subjects
Oncology, medicine.medical_specialty, business.industry, Urology, medicine.medical_treatment, Immunotherapy, medicine.disease, Axitinib, Pazopanib, Renal cell carcinoma, Internal medicine, medicine, In patient, business, medicine.drug
Published
2021

46. Deep Inguinal Lymph Node Metastases Can Predict Pelvic Lymph Node Metastases and Prognosis in Penile Squamous Cell Carcinoma

Author

Zhenyu Yang, Xingliang Tan, Yanjun Wang, Yuantao Zou, Dong Chen, Zhiming Wu, Zhuowei Liu, Yonghong Li, Zike Qin, Hui Han, Fangjian Zhou, and Kai Yao

Subjects
Cancer Research, medicine.medical_specialty, Proportional hazards model, business.industry, Deep inguinal lymph node, Penile Neoplasm, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, lymph node dissection, staging, Logistic regression, medicine.disease, Metastasis, Log-rank test, Dissection, neoplasm metastasis, medicine.anatomical_structure, Oncology, penile neoplasms, medicine, Radiology, prognosis, business, Lymph node, RC254-282, Original Research
Abstract

ObjectivesTo evaluate the relationship between deep inguinal lymph node metastasis (ILNM) and pelvic lymph node metastasis (PLNM) and explore the prognostic value of deep ILNM in penile squamous cell carcinoma (PSCC).Materials and MethodsThe records of 189 patients with ILNM treated for PSCC were analysed retrospectively. Logistic regression models were used to test for predictors of PLNM. Cox regression was performed in univariable and multivariable analyses of cancer-specific survival (CSS). CSS was compared using Kaplan-Meier analyses and log rank tests.ResultsPLNM were observed in 53 cases (28.0%). According to logistic regression models, only deep ILNM (OR 9.72, pvs not reached, pvs not reached, pConclusionsDeep ILNM is the most accurate factor for predicting PLNM in PSCC according to our data. We recommend that patients with deep ILNM should be referred for pelvic lymph node dissection. Involvement of deep ILNs indicates poor prognosis. We propose that patients with metastases of deep ILNs may be staged as pN3.

Published
2021

47. Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome: Insights from the LUNG SAFE study

Author

Madotto F, Rezoagli E, Pham T, Schmidt M, McNicholas B, Protti A, Panwar R, Bellani G, Fan E, van Haren F, Brochard L, Laffey JG, Antonio Pesenti, John G Laffey, Laurent Brochard, Andres Esteban, Luciano Gattinoni, Frank van Haren, Anders Larsson, Daniel F McAuley, Marco Ranieri, Gordon Rubenfeld, B Taylor Thompson, Hermann Wrigge, Arthur S Slutsky, Fernando Rios, T Sottiaux, P Depuydt, Fredy S Lora, Luciano Cesar Azevedo, Eddy Fan, Guillermo Bugedo, Haibo Qiu, Marcos Gonzalez, Juan Silesky, Vladimir Cerny, Jonas Nielsen, Manuel Jibaja, Tài Pham, Dimitrios Matamis, Jorge Luis Ranero, Pravin Amin, S M Hashemian, Kevin Clarkson, Giacomo Bellani, Kiyoyasu Kurahashi, Asisclo Villagomez, Amine Ali Zeggwagh, Leo M Heunks, Jon Henrik Laake, Jose Emmanuel Palo, Antero do Vale Fernandes, Dorel Sandesc, Yaasen Arabi, Vesna Bumbasierevic, Nicolas Nin, Jose A Lorente, Lise Piquilloud, Fekri Abroug, Lia McNamee, Javier Hurtado, Ed Bajwa, Gabriel Démpaire, Uhc Mother Theresa, Hektor Sula, Lordian Nunci, Alma Cani, Villa Maria, Alan Zazu, Christian Dellera, Carolina S Insaurralde, Risso V Alejandro, Julio Daldin, Mauricio Vinzio, Ruben O Fernandez, Luis P Cardonnet, Lisandro R Bettini, Mariano Carboni Bisso, Emilio M Osman, Mariano G Setten, Pablo Lovazzano, Javier Alvarez, Veronica Villar, Norberto C Pozo, Nicolas Grubissich, Gustavo A Plotnikow, Daniela N Vasquez, Santiago Ilutovich, Norberto Tiribelli, Ariel Chena, Carlos A Pellegrini, María G Saenz, Elisa Estenssoro, Matias Brizuela, Hernan Gianinetto, Pablo E Gomez, Valeria I Cerrato, Marco G Bezzi, Silvina A Borello, Flavia A Loiacono, Adriana M Fernandez, Serena Knowles, Claire Reynolds, Deborah M Inskip, Jennene J Miller, Jing Kong, Christina Whitehead, Shailesh Bihari, Aylin Seven, Amanda Krstevski, Helen J Rodgers, Rebecca T Millar, Toni E Mckenna, Irene M Bailey, Gabrielle C Hanlon, Anders Aneman, Joan M Lynch, Raman Azad, John Neal, Paul W Woods, Brigit L Roberts, Mark R Kol, Helen S Wong, Katharina C Riss, Thomas Staudinger, Xavier Wittebole, Caroline Berghe, Pierre A Bulpa, Alain M Dive, Rik Verstraete, Herve Lebbinck, Pieter Depuydt, Joris Vermassen, Philippe Meersseman, Helga Ceunen, Jonas I Rosa, Daniel O Beraldo, Claudio Piras, Adenilton M Rampinelli, Antonio P Nassar Jr, Sergio Mataloun, Marcelo Moock, Marlus M Thompson, Claudio H Gonçalves, Ana Carolina P Antônio, Aline Ascoli, Rodrigo S Biondi, Danielle C Fontenele, Danielle Nobrega, Vanessa M Sales, Suresh Shindhe, Dk Maizatul Aiman B Pg Hj Ismail, John Laffey, Francois Beloncle, Kyle G Davies, Rob Cirone, Venika Manoharan, Mehvish Ismail, Ewan C Goligher, Mandeep Jassal, Erin Nishikawa, Areej Javeed, Gerard Curley, Nuttapol Rittayamai, Matteo Parotto, Niall D Ferguson, Sangeeta Mehta, Jenny Knoll, Antoine Pronovost, Sergio Canestrini, Alejandro R Bruhn, Patricio H Garcia, Felipe A Aliaga, Pamela A Farías, Jacob S Yumha, Claudia A Ortiz, Javier E Salas, Alejandro A Saez, Luis D Vega, Eduardo F Labarca, Felipe T Martinez, Nicolás G Carreño, Pilar Lora, Haitao Liu, Ling Liu, Rui Tang, Xiaoming Luo, Youzhong An, Huiying Zhao, Yan Gao, Zhe Zhai, Zheng L Ye, Wei Wang, Wenwen Li, Qingdong Li, Ruiqiang Zheng, Wenkui Yu, Juanhong Shen, Xinyu Li, Tao Yu, Weihua Lu, Ya Q Wu, Xiao B Huang, Zhenyang He, Yuanhua Lu, Hui Han, Fan Zhang, Renhua Sun, Hua X Wang, Shu H Qin, Bao H Zhu, Jun Zhao, Jian Liu, Bin Li, Jing L Liu, Fa C Zhou, Qiong J Li, Xing Y Zhang, Zhou Li-Xin, Qiang Xin-Hua, Liangyan Jiang, Yuan N Gao, Xian Y Zhao, Yuan Y Li, Xiao L Li, Chunting Wang, Qingchun Yao, Rongguo Yu, Kai Chen, Huanzhang Shao, Bingyu Qin, Qing Q Huang, Wei H Zhu, Ai Y Hang, Ma X Hua, Yimin Li, Yonghao Xu, Yu D Di, Long L Ling, Tie H Qin, Shou H Wang, Junping Qin, Yi Han, Suming Zhou, Monica P Vargas, Juan I Silesky Jimenez, Manuel A González Rojas, Jaime E Solis-Quesada, Christian M Ramirez-Alfaro, Jan Máca, Peter Sklienka, Jakob Gjedsted, Aage Christiansen, Boris G Villamagua, Miguel Llano, Philippe Burtin, Gautier Buzancais, Pascal Beuret, Nicolas Pelletier, Satar Mortaza, Alain Mercat, Jonathan Chelly, Sébastien Jochmans, Nicolas Terzi, Cédric Daubin, Guillaume Carteaux, Nicolas de Prost, Jean-Daniel Chiche, Fabrice Daviaud, Tai Pham, Muriel Fartoukh, Guillaume Barberet, Jerome Biehler, Jean Dellamonica, Denis Doyen, Jean-Michel Arnal, Anais Briquet, Sami Hraiech, Laurent Papazian, Arnaud Follin, Damien Roux, Jonathan Messika, Evangelos Kalaitzis, Laurence Dangers, Alain Combes, Siu-Ming Au, Gaetan Béduneau, Dorothée Carpentier, Elie H Zogheib, Herve Dupont, Sylvie Ricome, Francesco L Santoli, Sebastien L Besset, Philippe Michel, Bruno Gelée, Pierre-Eric Danin, Bernard Goubaux, Philippe J Crova, Nga T Phan, Frantz Berkelmans, Julio C Badie, Romain Tapponnier, Josette Gally, Samy Khebbeb, Jean-Etienne Herbrecht, Francis Schneider, Pierre-Louis M Declercq, Jean-Philippe Rigaud, Jacques Duranteau, Anatole Harrois, Russell Chabanne, Julien Marin, Charlene Bigot, Sandrine Thibault, Mohammed Ghazi, Messabi Boukhazna, Salem Ould Zein, Jack R Richecoeur, Daniele M Combaux, Fabien Grelon, Charlene Le Moal, Elise P Sauvadet, Adrien Robine, Virginie Lemiale, Danielle Reuter, Martin Dres, Alexandre Demoule, Dany Goldgran-Toledano, Loredana Baboi, Claude Guérin, Ralph Lohner, Jens Kraßler, Susanne Schäfer, Kai D Zacharowski, Patrick Meybohm, Andreas W Reske, Philipp Simon, Hans-Bernd F Hopf, Michael Schuetz, Thomas Baltus, Metaxia N Papanikolaou, Theonymfi G Papavasilopoulou, Giannis A Zacharas, Vasilis Ourailogloy, Eleni K Mouloudi, Eleni V Massa, Eva O Nagy, Electra E Stamou, Ellada V Kiourtzieva, Marina A Oikonomou, Luis E Avila, Cesar A Cortez, Johanna E Citalán, Sameer A Jog, Safal D Sable, Bhagyesh Shah, Mohan Gurjar, Arvind K Baronia, Mohammedfaruk Memon, Radhakrishnan Muthuchellappan, Venkatapura J Ramesh, Anitha Shenoy, Ramesh Unnikrishnan, Subhal B Dixit, Rachana V Rhayakar, Nagarajan Ramakrishnan, Vallish K Bhardwaj, Heera L Mahto, Sudha V Sagar, Vijayanand Palaniswamy, Deeban Ganesan, Seyed Mohammadreza Hashemian, Hamidreza Jamaati, Farshad Heidari, Edel A Meaney, Alistair Nichol, Karl M Knapman, Donall O'Croinin, Eimhin S Dunne, Dorothy M Breen, Kevin P Clarkson, Rola F Jaafar, Rory Dwyer, Fahd Amir, Olaitan O Ajetunmobi, Aogan C O'Muircheartaigh, Colin S Black, Nuala Treanor, Daniel V Collins, Wahid Altaf, Gianluca Zani, Maurizio Fusari, Savino Spadaro, Carlo A Volta, Romano Graziani, Barbara Brunettini, Salvatore Palmese, Paolo Formenti, Michele Umbrello, Andrea Lombardo, Elisabetta Pecci, Marco Botteri, Monica Savioli, Alessandro Protti, Alessia Mattei, Lorenzo Schiavoni, Andrea Tinnirello, Manuel Todeschini, Antonino Giarratano, Andrea Cortegiani, Sara Sher, Anna Rossi, Massimo M Antonelli, Luca M Montini, Paolo Casalena, Sergio Scafetti, Giovanna Panarello, Giovanna Occhipinti, Nicolò Patroniti, Matteo Pozzi, Roberto R Biscione, Michela M Poli, Ferdinando Raimondi, Daniela Albiero, Giulia Crapelli, Eduardo Beck, Vincenzo Pota, Vincenzo Schiavone, Alexandre Molin, Fabio Tarantino, Giacomo Monti, Elena Frati, Lucia Mirabella, Gilda Cinnella, Tommaso Fossali, Riccardo Colombo, Pierpaolo Terragni Ilaria Pattarino, Francesco Mojoli, Antonio Braschi, Erika E Borotto, Andrea N Cracchiolo, Daniela M Palma, Francesco Raponi, Giuseppe Foti, Ettore R Vascotto, Andrea Coppadoro, Luca Brazzi, Leda Floris, Giorgio A Iotti, Aaron Venti, Osamu Yamaguchi, Shunsuke Takagi, Hiroki N Maeyama, Eizo Watanabe, Yoshihiro Yamaji, Kazuyoshi Shimizu, Kyoko Shiozaki, Satoru Futami, Sekine Ryosuke, Koji Saito, Yoshinobu Kameyama, Keiko Ueno, Masayo Izawa, Nao Okuda, Hiroyuki Suzuki, Tomofumi Harasawa, Michitaka Nasu, Tadaaki Takada, Fumihito Ito, Shin-Nunomiya Kansuke-Koyama, Toshikazu Abe, Kohkichi Andoh, Kohei Kusumoto, Akira Hirata, Akihiro Takaba, Hiroyasu Kimura, Shuhei Matsumoto, Ushio Higashijima, Hiroyuki Honda, Nobumasa Aoki, Hiroshi Imai, Yasuaki Ogino, Ichiko Mizuguchi, Kazuya Ichikado, Kenichi Nitta, Katsunori Mochizuki, Tomoaki Hashida, Hiroyuki Tanaka, Tomoyuki Nakamura, Daisuke Niimi, Takeshi Ueda, Yozo Kashiwa, Akinori Uchiyama, Olegs Sabelnikovs, Peteris Oss, Youssef Haddad, Kong Y Liew, Silvio A Ñamendys-Silva, Yves D Jarquin-Badiola, Luis A Sanchez-Hurtado, Saira S Gomez-Flores, Maria C Marin, Asisclo J Villagomez, Jordana S Lemus, Jonathan M Fierro, Mavy Ramirez Cervantes, Francisco Javier Flores Mejia, Dulce Dector, Dulce M Dector, Daniel R Gonzalez, Claudia R Estrella, Jorge R Sanchez-Medina, Alvaro Ramirez-Gutierrez, Fernando G George, Janet S Aguirre, Juan A Buensuseso, Manuel Poblano, Tarek Dendane, Hicham Balkhi, Mina Elkhayari, Nacer Samkaoui, Hanane Ezzouine, Abdellatif Benslama Mourad Amor, Wajdi Maazouzi, Nedim Cimic, Oliver Beck, Monique M Bruns, Jeroen A Schouten, Myra-Rinia, Monique Raaijmakers, Hellen M Van Wezel, Serge J Heines, Ulrich Strauch, Marc P Buise, Fabienne D Simonis, Marcus J Schultz, Jennifer C Goodson, Troy S Browne, Leanlove Navarra, Anna Hunt, Robyn A Hutchison, Mathew B Bailey, Lynette Newby, Colin Mcarthur, Michael Kalkoff, Alex Mcleod, Jonathan Casement, Danielle J Hacking, Finn H Andersen, Merete S Dolva, Jon H Laake, Andreas Barratt-Due, Kim Andre L Noremark, Eldar Søreide, Brit Å Sjøbø, Anne B Guttormsen, Hector H Leon Yoshido, Ronald Zumaran Aguilar, Fredy A Montes Oscanoa, Alain U Alisasis, Joanne B Robles, Rossini Abbie B Pasanting-Lim, Beatriz C Tan, Pawel Andruszkiewicz, Karina Jakubowska, Cristina M Coxo, António M Alvarez, Bruno S Oliveira, Gustavo M Montanha, Nelson C Barros, Carlos S Pereira, António M Messias, Jorge M Monteiro, Ana M Araujo, Nuno T Catorze, Susan M Marum, Maria J Bouw, Rui M Gomes, Vania A Brito, Silvia Castro, Joana M Estilita, Filipa M Barros, Isabel M Serra, Aurelia M Martinho, Dana R Tomescu, Alexandra Marcu, Ovidiu H Bedreag, Marius Papurica, Dan E Corneci, Silvius Ioan Negoita, Evgeny Grigoriev, Alexey I Gritsan, Andrey A Gazenkampf, Ghaleb Almekhlafi, Mohamad M Albarrak, Ghanem M Mustafa, Khalid A Maghrabi, Nawal Salahuddin, Tharwat M Aisa, Ahmed S Al Jabbary, Edgardo Tabhan, Yaseen M Arabi, Olivia A Trinidad, Hasan M Al Dorzi, Edgardo E Tabhan, Stefan Bolon, Oliver Smith, Jordi Mancebo, Hernan Aguirre-Bermeo, Juan C Lopez-Delgado, Francisco Esteve, Gemma Rialp, Catalina Forteza, Candelaria De Haro, Antonio Artigas, Guillermo M Albaiceta, Sara De Cima-Iglesias, Leticia Seoane-Quiroga, Alexandra Ceniceros-Barros, Antonio L Ruiz-Aguilar, Luis M Claraco-Vega, Juan Alfonso Soler, Maria Del Carmen Lorente, Cecilia Hermosa, Federico Gordo, Miryam-Prieto-González, Juan B López-Messa, Manuel P Perez, Cesar P Perez, Raquel Montoiro Allue, Ferran Roche-Campo, Marcos Ibañez-Santacruz, Susana-Temprano, Maria C Pintado, Raul De Pablo, Pilar Ricart Aroa Gómez, Silvia Rodriguez Ruiz, Silvia Iglesias Moles, Mª Teresa Jurado, Alfons Arizmendi, Enrique A Piacentini, Nieves Franco, Teresa Honrubia, Meisy Perez Cheng, Elena Perez Losada, Javier-Blanco, Luis J Yuste, Cecilia Carbayo-Gorriz, Francisca G Cazorla-Barranquero, Javier G Alonso, Rosa S Alda, Ángela Algaba, Gonzalo Navarro, Enrique Cereijo, Esther Diaz-Rodriguez, Diego Pastor Marcos, Laura Alvarez Montero, Luis Herrera Para, Roberto Jimenez Sanchez, Miguel Angel Blasco Navalpotro, Ricardo Diaz Abad, Raquel Montiel Gonz Á Lez, D Á Cil Parrilla Toribio, Alejandro G Castro, Maria Jose D Artiga, Oscar Penuelas, Tomas P Roser, Moreno F Olga, Elena Gallego Curto, Rocío Manzano Sánchez, Vallverdu P Imma, Garcia M Elisabet, Laura Claverias, Monica Magret, Ana M Pellicer, Lucia L Rodriguez, Jesús Sánchez-Ballesteros, Ángela González-Salamanca, Antonio G Jimenez, Francisco P Huerta, Juan Carlos J Sotillo Diaz, Esther Bermejo Lopez, David D Llinares Moya, Alec A Tallet Alfonso, Palazon Sanchez Eugenio Luis, Palazon Sanchez Cesar, Sánchez I Rafael, Corcoles G Virgilio, Noelia N Recio, Richard O Adamsson, Christian C Rylander, Bernhard Holzgraefe, Lars M Broman, Joanna Wessbergh, Linnea Persson, Fredrik Schiöler, Hans Kedelv, Anna Oscarsson Tibblin, Henrik Appelberg, Lars Hedlund, Johan Helleberg, Karin E Eriksson, Rita Glietsch, Niklas Larsson, Ingela Nygren, Silvia L Nunes, Anna-Karin Morin, Thomas Kander, Anne Adolfsson, Hervé O Zender, Corinne Leemann-Refondini, Souheil Elatrous, Slaheddine Bouchoucha, Imed Chouchene, Islem Ouanes, Asma Ben Souissi, Salma Kamoun, Oktay Demirkiran, Mustafa Aker, Emre Erbabacan, Ilkay Ceylan, Nermin Kelebek Girgin, Menekse Ozcelik, Necmettin Ünal, Basak Ceyda Meco, Onat O Akyol, Suleyman S Derman, Barry Kennedy, Ken Parhar, Latha Srinivasa, Danny McAuley, Phil Hopkins, Clare Mellis, Vivek Kakar, Dan Hadfield, Andre Vercueil, Kaushik Bhowmick, Sally K Humphreys, Andrew Ferguson, Raymond Mckee, Ashok S Raj, Danielle A Fawkes, Philip Watt, Linda Twohey, Rajeev R JhaMatthew Thomas, Alex Morton, Varsha Kadaba, Mark J Smith, Anil P Hormis, Santhana G Kannan, Miriam Namih, Henrik Reschreiter, Julie Camsooksai, Alek Kumar, Szabolcs Rugonfalvi, Christopher Nutt, Orla O'Neill, Colette Seasman, Ged Dempsey, Christopher J Scott, Helen E Ellis, Stuart Mckechnie, Paula J Hutton, Nora N Di Tomasso, Michela N Vitale, Ruth O Griffin, Michael N Dean, Julius H Cranshaw, Emma L Willett, Nicholas Ioannou, Sarah Gillis, Peter Csabi, Rosaleen Macfadyen, Heidi Dawson, Pieter D Preez, Alexandra J Williams, Owen Boyd, Laura Ortiz-Ruiz De Gordoa, Jon Bramall, Sophie Symmonds, Simon K Chau, Tim Wenham, Tamas Szakmany, Piroska Toth-Tarsoly, Katie H McCalman, Peter Alexander, Lorraine Stephenson, Thomas Collyer, Rhiannon Chapman, Raphael Cooper, Russell M Allan, Malcolm Sim, David W Wrathall, Donald A Irvine, Kim S Zantua, John C Adams, Andrew J Burtenshaw, Gareth P Sellors, Ingeborg D Welters, Karen E Williams, Robert J Hessell, Matthew G Oldroyd, Ceri E Battle, Suresh Pillai, Istvan Kajtor, Mageswaran Sivashanmugavel, Sinead C O'Kane, Adrian Donnelly, Aniko D Frigyik, Jon P Careless, Martin M May, Richard Stewart, T John Trinder, Samantha J Hagan, Matt P Wise, Jade M Cole, Caroline C MacFie, Anna T Dowling, Nicolás Nin, Edgardo Nuñez, Gustavo Pittini, Ruben Rodriguez, María C Imperio, Cristina Santos, Ana G França, Alejandro Ebeid, Alberto Deicas, Carolina Serra, Aditya Uppalapati, Ghassan Kamel, Valerie M Banner-Goodspeed, Jeremy R Beitler, Satyanarayana Reddy Mukkera, Shreedhar Kulkarni, Jarone Lee, Tomaz Mesar, John O Shinn 3rd, Dina Gomaa, Christopher Tainter, Dale J Yeatts, Jessica Warren, Michael J Lanspa, Russel R Miller, Colin K Grissom, LUNG SAFE Investigators and the ESICM Trials Group, Samuel M Brown, Philippe R Bauer, Ryan J Gosselin, Barrett T Kitch, Jason E Cohen, Scott H Beegle, Renaud M Gueret, Aiman Tulaimat, Shazia Choudry, William Stigler, Hitesh Batra, Nidhi G Huff, Keith D Lamb, Trevor W Oetting, Nicholas M Mohr, Claine Judy, Shigeki Saito, Fayez M Kheir, Fayez Kheir, Adam B Schlichting, Angela Delsing, Daniel R Crouch, Mary Elmasri, Dina Ismail, Kyle R Dreyer, Thomas C Blakeman, Rebecca M Baron, Carolina Quintana Grijalba, Peter C Hou, Raghu Seethala, Imo Aisiku, Galen Henderson, Gyorgy Frendl, Sen-Kuang Hou, Robert L Owens, Ashley Schomer, Vesna Bumbasirevic, Bojan Jovanovic, Maja Surbatovic, Milic Veljovic, Madotto, F., Rezoagli, E., Pham, T., Schmidt, M., Mcnicholas, B., Protti, A., Panwar, R., Bellani, G., Fan, E., Van Haren, F., Brochard, L., Laffey, J. G., Pesenti, A., Esteban, A., Gattinoni, L., Larsson, A., Mcauley, D. F., Ranieri, M., Rubenfeld, G., Thompson, B. T., Wrigge, H., Slutsky, A. S., Rios, F., Sottiaux, T., Depuydt, P., Lora, F. S., Azevedo, L. C., Bugedo, G., Qiu, H., Gonzalez, M., Silesky, J., Cerny, V., Nielsen, J., Jibaja, M., Matamis, D., Ranero, J. L., Amin, P., Hashemian, S. M., Clarkson, K., Kurahashi, K., Villagomez, A., Zeggwagh, A. A., Heunks, L. M., Laake, J. H., Palo, J. E., Do Vale Fernandes, A., Sandesc, D., Arabi, Y., Bumbasierevic, V., Nin, N., Lorente, J. A., Piquilloud, L., Abroug, F., Mcnamee, L., Hurtado, J., Bajwa, E., Dempaire, G., Theresa, U. M., Sula, H., Nunci, L., Cani, A., Maria, V., Zazu, A., Dellera, C., Insaurralde, C. S., Alejandro, R. V., Daldin, J., Vinzio, M., Fernandez, R. O., Cardonnet, L. P., Bettini, L. R., Bisso, M. C., Osman, E. M., Setten, M. G., Lovazzano, P., Alvarez, J., Villar, V., Pozo, N. C., Grubissich, N., Plotnikow, G. A., Vasquez, D. N., Ilutovich, S., Tiribelli, N., Chena, A., Pellegrini, C. A., Saenz, M. G., Estenssoro, E., Brizuela, M., Gianinetto, H., Gomez, P. E., Cerrato, V. I., Bezzi, M. G., Borello, S. A., Loiacono, F. A., Fernandez, A. M., Knowles, S., Reynolds, C., Inskip, D. M., Miller, J. J., Kong, J., Whitehead, C., Bihari, S., Seven, A., Krstevski, A., Rodgers, H. J., Millar, R. T., Mckenna, T. E., Bailey, I. M., Hanlon, G. C., Aneman, A., Lynch, J. M., Azad, R., Neal, J., Woods, P. W., Roberts, B. L., Kol, M. R., Wong, H. S., Riss, K. C., Staudinger, T., Wittebole, X., Berghe, C., Bulpa, P. A., Dive, A. M., Verstraete, R., Lebbinck, H., Vermassen, J., Meersseman, P., Ceunen, H., Rosa, J. I., Beraldo, D. O., Piras, C., Rampinelli, A. M., Nassar, A. P., Mataloun, S., Moock, M., Thompson, M. M., Goncalves, C. H., Antonio, A. C. P., Ascoli, A., Biondi, R. S., Fontenele, D. C., Nobrega, D., Sales, V. M., Shindhe, S., Pg Hj Ismail, D. M. A. B., Laffey, J., Beloncle, F., Davies, K. G., Cirone, R., Manoharan, V., Ismail, M., Goligher, E. C., Jassal, M., Nishikawa, E., Javeed, A., Curley, G., Rittayamai, N., Parotto, M., Ferguson, N. D., Mehta, S., Knoll, J., Pronovost, A., Canestrini, S., Bruhn, A. R., Garcia, P. H., Aliaga, F. A., Farias, P. A., Yumha, J. S., Ortiz, C. A., Salas, J. E., Saez, A. A., Vega, L. D., Labarca, E. F., Martinez, F. T., Carreno, N. G., Lora, P., Liu, H., Liu, L., Tang, R., Luo, X., An, Y., Zhao, H., Gao, Y., Zhai, Z., Ye, Z. L., Wang, W., Li, W., Li, Q., Zheng, R., Yu, W., Shen, J., Li, X., Yu, T., Lu, W., Wu, Y. Q., Huang, X. B., He, Z., Lu, Y., Han, H., Zhang, F., Sun, R., Wang, H. X., Qin, S. H., Zhu, B. H., Zhao, J., Liu, J., Li, B., Liu, J. L., Zhou, F. C., Li, Q. J., Zhang, X. Y., Li-Xin, Z., Xin-Hua, Q., Jiang, L., Gao, Y. N., Zhao, X. Y., Li, Y. Y., Li, X. L., Wang, C., Yao, Q., Yu, R., Chen, K., Shao, H., Qin, B., Huang, Q. Q., Zhu, W. H., Hang, A. Y., Hua, M. X., Li, Y., Xu, Y., Di, Y. D., Ling, L. L., Qin, T. H., Wang, S. H., Qin, J., Han, Y., Zhou, S., Vargas, M. P., Silesky Jimenez, J. I., Gonzalez Rojas, M. A., Solis-Quesada, J. E., Ramirez-Alfaro, C. M., Maca, J., Sklienka, P., Gjedsted, J., Christiansen, A., Villamagua, B. G., Llano, M., Burtin, P., Buzancais, G., Beuret, P., Pelletier, N., Mortaza, S., Mercat, A., Chelly, J., Jochmans, S., Terzi, N., Daubin, C., Carteaux, G., De Prost, N., Chiche, J. -D., Daviaud, F., Fartoukh, M., Barberet, G., Biehler, J., Dellamonica, J., Doyen, D., Arnal, J. -M., Briquet, A., Hraiech, S., Papazian, L., Follin, A., Roux, D., Messika, J., Kalaitzis, E., Dangers, L., Combes, A., Au, S. -M., Beduneau, G., Carpentier, D., Zogheib, E. H., Dupont, H., Ricome, S., Santoli, F. L., Besset, S. L., Michel, P., Gelee, B., Danin, P. -E., Goubaux, B., Crova, P. J., Phan, N. T., Berkelmans, F., Badie, J. C., Tapponnier, R., Gally, J., Khebbeb, S., Herbrecht, J. -E., Schneider, F., Declercq, P. -L. 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A., Nichol, A., Knapman, K. M., O'Croinin, D., Dunne, E. S., Breen, D. M., Clarkson, K. P., Jaafar, R. F., Dwyer, R., Amir, F., Ajetunmobi, O. O., O'Muircheartaigh, A. C., Black, C. S., Treanor, N., Collins, D. V., Altaf, W., Zani, G., Fusari, M., Spadaro, S., Volta, C. A., Graziani, R., Brunettini, B., Palmese, S., Formenti, P., Umbrello, M., Lombardo, A., Pecci, E., Botteri, M., Savioli, M., Mattei, A., Schiavoni, L., Tinnirello, A., Todeschini, M., Giarratano, A., Cortegiani, A., Sher, S., Rossi, A., Antonelli, M. M., Montini, L. M., Casalena, P., Scafetti, S., Panarello, G., Occhipinti, G., Patroniti, N., Pozzi, M., Biscione, R. R., Poli, M. M., Raimondi, F., Albiero, D., Crapelli, G., Beck, E., Pota, V., Schiavone, V., Molin, A., Tarantino, F., Monti, G., Frati, E., Mirabella, L., Cinnella, G., Fossali, T., Colombo, R., Pattarino, P. T. I., Mojoli, F., Braschi, A., Borotto, E. E., Cracchiolo, A. N., Palma, D. M., Raponi, F., Foti, G., Vascotto, E. 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A., Poblano, M., Dendane, T., Balkhi, H., Elkhayari, M., Samkaoui, N., Ezzouine, H., Amor, A. B. M., Maazouzi, W., Cimic, N., Beck, O., Bruns, M. M., Schouten, J. A., Myra-Rinia, Van Wezel, H. M., Heines, S. J., Strauch, U., Buise, M. P., Simonis, F. D., Schultz, M. J., Goodson, J. C., Browne, T. S., Raaijmakers, M., Hunt, A., Hutchison, R. A., Bailey, M. B., Newby, L., Mcarthur, C., Kalkoff, M., Mcleod, A., Casement, J., Hacking, D. J., Andersen, F. H., Dolva, M. S., Barratt-Due, A., Noremark, K. A. L., Soreide, E., Sjobo, B. A., Guttormsen, A. B., Leon Yoshido, H. H., Aguilar, R. Z., Montes Oscanoa, F. A., Alisasis, A. U., Robles, J. B., Pasanting-Lim, R. A. B., Tan, B. C., Andruszkiewicz, P., Jakubowska, K., Coxo, C. M., Alvarez, A. M., Oliveira, B. S., Montanha, G. M., Barros, N. C., Pereira, C. S., Messias, A. M., Monteiro, J. M., Araujo, A. M., Catorze, N. T., Marum, S. M., Bouw, M. J., Gomes, R. M., Brito, V. A., Castro, S., Estilita, J. M., Barros, F. M., Serra, I. 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O., Leemann-Refondini, C., Elatrous, S., Bouchoucha, S., Chouchene, I., Ouanes, I., Souissi, A. B., Kamoun, S., Demirkiran, O., Aker, M., Erbabacan, E., Ceylan, I., Girgin, N. K., Ozcelik, M., Unal, N., Meco, B. C., Akyol, O. O., Derman, S. S., Kennedy, B., Parhar, K., Srinivasa, L., Hopkins, P., Mellis, C., Kakar, V., Hadfield, D., Vercueil, A., Bhowmick, K., Humphreys, S. K., Ferguson, A., Mckee, R., Raj, A. S., Fawkes, D. A., Watt, P., Twohey, L., Jhamatthew Thomas, R. R., Morton, A., Kadaba, V., Smith, M. J., Hormis, A. P., Kannan, S. G., Namih, M., Reschreiter, H., Camsooksai, J., Kumar, A., Rugonfalvi, S., Nutt, C., O'Neill, O., Seasman, C., Dempsey, G., Scott, C. J., Ellis, H. E., Mckechnie, S., Hutton, P. J., Di Tomasso, N. N., Vitale, M. N., Griffin, R. O., Dean, M. N., Cranshaw, J. H., Willett, E. L., Ioannou, N., Gillis, S., Csabi, P., Macfadyen, R., Dawson, H., Preez, P. D., Williams, A. J., Boyd, O., De Gordoa, L. O. -R., Bramall, J., Symmonds, S., Chau, S. K., Wenham, T., Szakmany, T., Toth-Tarsoly, P., Mccalman, K. H., Alexander, P., Stephenson, L., Collyer, T., Chapman, R., Cooper, R., Allan, R. M., Sim, M., Wrathall, D. W., Irvine, D. A., Zantua, K. S., Adams, J. C., Burtenshaw, A. J., Sellors, G. P., Welters, I. D., Williams, K. E., Hessell, R. J., Oldroyd, M. G., Battle, C. E., Pillai, S., Kajtor, I., Sivashanmugavel, M., O'Kane, S. C., Donnelly, A., Frigyik, A. D., Careless, J. P., May, M. M., Stewart, R., Trinder, T. J., Hagan, S. J., Wise, M. P., Cole, J. M., Macfie, C. C., Dowling, A. T., Nunez, E., Pittini, G., Rodriguez, R., Imperio, M. C., Santos, C., Franca, A. G., Ebeid, A., Deicas, A., Serra, C., Uppalapati, A., Kamel, G., Banner-Goodspeed, V. M., Beitler, J. R., Mukkera, S. R., Kulkarni, S., Lee, J., Mesar, T., Shinn, J. O., Gomaa, D., Tainter, C., Yeatts, D. J., Warren, J., Lanspa, M. J., Miller, R. R., Grissom, C. K., Brown, S. M., Bauer, P. R., Gosselin, R. J., Kitch, B. T., Cohen, J. E., Beegle, S. H., Gueret, R. M., Tulaimat, A., Choudry, S., Stigler, W., Batra, H., Huff, N. G., Lamb, K. D., Oetting, T. W., Mohr, N. M., Judy, C., Saito, S., Kheir, F. M., Kheir, F., Schlichting, A. B., Delsing, A., Crouch, D. R., Elmasri, M., Ismail, D., Dreyer, K. R., Blakeman, T. C., Baron, R. M., Grijalba, C. Q., Hou, P. C., Seethala, R., Aisiku, I., Henderson, G., Frendl, G., Hou, S. -K., Owens, R. L., Schomer, A., Bumbasirevic, V., Jovanovic, B., Surbatovic, M., Veljovic, M., UCL - SSS/IREC/MEDA - Pôle de médecine aiguë, UCL - (MGD) Services des soins intensifs, UCL - (SLuc) Service de soins intensifs, Graduate School, Intensive Care Medicine, ACS - Heart failure & arrhythmias, ACS - Diabetes & metabolism, ACS - Pulmonary hypertension & thrombosis, ACS - Microcirculation, Madotto, F, Rezoagli, E, Pham, T, Schmidt, M, Mcnicholas, B, Protti, A, Panwar, R, Bellani, G, Fan, E, Van Haren, F, Brochard, L, Laffey, J, Pesenti, A, Esteban, A, Gattinoni, L, Larsson, A, Mcauley, D, Ranieri, M, Rubenfeld, G, Thompson, B, Wrigge, H, Slutsky, A, Rios, F, Sottiaux, T, Depuydt, P, Lora, F, Azevedo, L, Bugedo, G, Qiu, H, Gonzalez, M, Silesky, J, Cerny, V, Nielsen, J, Jibaja, M, Matamis, D, Ranero, J, Amin, P, Hashemian, S, Clarkson, K, Kurahashi, K, Villagomez, A, Zeggwagh, A, Heunks, L, Laake, J, Palo, J, Do Vale Fernandes, A, Sandesc, D, Arabi, Y, Bumbasierevic, V, Nin, N, Lorente, J, Piquilloud, L, Abroug, F, Mcnamee, L, Hurtado, J, Bajwa, E, Dempaire, G, Theresa, U, Sula, H, Nunci, L, Cani, A, Maria, V, Zazu, A, Dellera, C, Insaurralde, C, Alejandro, R, Daldin, J, Vinzio, M, Fernandez, R, Cardonnet, L, Bettini, L, Bisso, M, Osman, E, Setten, M, Lovazzano, P, Alvarez, J, Villar, V, Pozo, N, Grubissich, N, Plotnikow, G, Vasquez, D, Ilutovich, S, Tiribelli, N, Chena, A, Pellegrini, C, Saenz, M, Estenssoro, E, Brizuela, M, Gianinetto, H, Gomez, P, Cerrato, V, Bezzi, M, Borello, S, Loiacono, F, Fernandez, A, Knowles, S, Reynolds, C, Inskip, D, Miller, J, Kong, J, Whitehead, C, Bihari, S, Seven, A, Krstevski, A, Rodgers, H, Millar, R, Mckenna, T, Bailey, I, Hanlon, G, Aneman, A, Lynch, J, Azad, R, Neal, J, Woods, P, Roberts, B, Kol, M, Wong, H, Riss, K, Staudinger, T, Wittebole, X, Berghe, C, Bulpa, P, Dive, A, Verstraete, R, Lebbinck, H, Vermassen, J, Meersseman, P, Ceunen, H, Rosa, J, Beraldo, D, Piras, C, Rampinelli, A, Nassar, A, Mataloun, S, Moock, M, Thompson, M, Goncalves, C, Antonio, A, Ascoli, A, Biondi, R, Fontenele, D, Nobrega, D, Sales, V, Shindhe, S, Pg Hj Ismail, D, Beloncle, F, Davies, K, Cirone, R, Manoharan, V, Ismail, M, Goligher, E, Jassal, M, Nishikawa, E, Javeed, A, Curley, G, Rittayamai, N, Parotto, M, Ferguson, N, Mehta, S, Knoll, J, Pronovost, A, Canestrini, S, Bruhn, A, Garcia, P, Aliaga, F, Farias, P, Yumha, J, Ortiz, C, Salas, J, Saez, A, Vega, L, Labarca, E, Martinez, F, Carreno, N, Lora, P, Liu, H, Liu, L, Tang, R, Luo, X, An, Y, Zhao, H, Gao, Y, Zhai, Z, Ye, Z, Wang, W, Li, W, Li, Q, Zheng, R, Yu, W, Shen, J, Li, X, Yu, T, Lu, W, Wu, Y, Huang, X, He, Z, Lu, Y, Han, H, Zhang, F, Sun, R, Wang, H, Qin, S, Zhu, B, Zhao, J, Liu, J, Li, B, Zhou, F, Zhang, X, Li-Xin, Z, Xin-Hua, Q, Jiang, L, Zhao, X, Li, Y, Wang, C, Yao, Q, Yu, R, Chen, K, Shao, H, Qin, B, Huang, Q, Zhu, W, Hang, A, Hua, M, Xu, Y, Di, Y, Ling, L, Qin, T, Wang, S, Qin, J, Han, Y, Zhou, S, Vargas, M, Silesky Jimenez, J, Gonzalez Rojas, M, Solis-Quesada, J, Ramirez-Alfaro, C, Maca, J, Sklienka, P, Gjedsted, J, Christiansen, A, Villamagua, B, Llano, M, Burtin, P, Buzancais, G, Beuret, P, Pelletier, N, Mortaza, S, Mercat, A, Chelly, J, Jochmans, S, Terzi, N, Daubin, C, Carteaux, G, De Prost, N, Chiche, J, Daviaud, F, Fartoukh, M, Barberet, G, Biehler, J, Dellamonica, J, Doyen, D, Arnal, J, Briquet, A, Hraiech, S, Papazian, L, Follin, A, Roux, D, Messika, J, Kalaitzis, E, Dangers, L, Combes, A, Au, S, Beduneau, G, Carpentier, D, Zogheib, E, Dupont, H, Ricome, S, Santoli, F, Besset, S, Michel, P, Gelee, B, Danin, P, Goubaux, B, Crova, P, Phan, N, Berkelmans, F, Badie, J, Tapponnier, R, Gally, J, Khebbeb, S, Herbrecht, J, Schneider, F, Declercq, P, Rigaud, J, Duranteau, J, Harrois, A, Chabanne, R, Marin, J, Bigot, C, Thibault, S, Ghazi, M, Boukhazna, M, Zein, S, Richecoeur, J, Combaux, D, Grelon, F, Le Moal, C, Sauvadet, E, Robine, A, Lemiale, V, Reuter, D, Dres, M, Demoule, A, Goldgran-Toledano, D, Baboi, L, Guerin, C, Lohner, R, Krassler, J, 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Claraco-Vega, Juan Alfonso Soler, Maria Del Carmen Lorente, Cecilia Hermosa, Federico Gordo, Miryam-Prieto-González, Juan B López-Messa, Manuel P Perez, Cesar P Perez, Raquel Montoiro Allue, Ferran Roche-Campo, Marcos Ibañez-Santacruz, Susana-Temprano, Maria C Pintado, Raul De Pablo, Pilar Ricart Aroa Gómez, Silvia Rodriguez Ruiz, Silvia Iglesias Moles, Mª Teresa Jurado, Alfons Arizmendi, Enrique A Piacentini, Nieves Franco, Teresa Honrubia, Meisy Perez Cheng, Elena Perez Losada, Javier-Blanco, Luis J Yuste, Cecilia Carbayo-Gorriz, Francisca G Cazorla-Barranquero, Javier G Alonso, Rosa S Alda, Ángela Algaba, Gonzalo Navarro, Enrique Cereijo, Esther Diaz-Rodriguez, Diego Pastor Marcos, Laura Alvarez Montero, Luis Herrera Para, Roberto Jimenez Sanchez, Miguel Angel Blasco Navalpotro, Ricardo Diaz Abad, Raquel Montiel Gonz Á Lez, D Á Cil Parrilla Toribio, Alejandro G Castro, Maria Jose D Artiga, Oscar Penuelas, Tomas P Roser, Moreno F Olga, Elena Gallego Curto, Rocío Manzano Sánchez, Vallverdu P Imma, Garcia M Elisabet, Laura Claverias, Monica Magret, Ana M Pellicer, Lucia L Rodriguez, Jesús Sánchez-Ballesteros, Ángela González-Salamanca, Antonio G Jimenez, Francisco P Huerta, Juan Carlos J Sotillo Diaz, Esther Bermejo Lopez, David D Llinares Moya, Alec A Tallet Alfonso, Palazon Sanchez Eugenio Luis, Palazon Sanchez Cesar, Sánchez I Rafael, Corcoles G Virgilio, Noelia N Recio, Richard O Adamsson, Christian C Rylander, Bernhard Holzgraefe, Lars M Broman, Joanna Wessbergh, Linnea Persson, Fredrik Schiöler, Hans Kedelv, Anna Oscarsson Tibblin, Henrik Appelberg, Lars Hedlund, Johan Helleberg, Karin E Eriksson, Rita Glietsch, Niklas Larsson, Ingela Nygren, Silvia L Nunes, Anna-Karin Morin, Thomas Kander, Anne Adolfsson, Hervé O Zender, Corinne Leemann-Refondini, Souheil Elatrous, Slaheddine Bouchoucha, Imed Chouchene, Islem Ouanes, Asma Ben Souissi, Salma Kamoun, Oktay Demirkiran, Mustafa Aker, Emre Erbabacan, Ilkay Ceylan, Nermin Kelebek Girgin, Menekse Ozcelik, Necmettin Ünal, Basak Ceyda Meco, Onat O Akyol, Suleyman S Derman, Barry Kennedy, Ken Parhar, Latha Srinivasa, Danny McAuley, Phil Hopkins, Clare Mellis, Vivek Kakar, Dan Hadfield, Andre Vercueil, Kaushik Bhowmick, Sally K Humphreys, Andrew Ferguson, Raymond Mckee, Ashok S Raj, Danielle A Fawkes, Philip Watt, Linda Twohey, Rajeev R JhaMatthew Thomas, Alex Morton, Varsha Kadaba, Mark J Smith, Anil P Hormis, Santhana G Kannan, Miriam Namih, Henrik Reschreiter, Julie Camsooksai, Alek Kumar, Szabolcs Rugonfalvi, Christopher Nutt, Orla O'Neill, Colette Seasman, Ged Dempsey, Christopher J Scott, Helen E Ellis, Stuart Mckechnie, Paula J Hutton, Nora N Di Tomasso, Michela N Vitale, Ruth O Griffin, Michael N Dean, Julius H Cranshaw, Emma L Willett, Nicholas Ioannou, Sarah Gillis, Peter Csabi, Rosaleen Macfadyen, Heidi Dawson, Pieter D Preez, Alexandra J Williams, Owen Boyd, Laura Ortiz-Ruiz De Gordoa, Jon Bramall, Sophie Symmonds, Simon K Chau, Tim Wenham, Tamas Szakmany, Piroska Toth-Tarsoly, Katie H McCalman, Peter Alexander, Lorraine Stephenson, Thomas Collyer, Rhiannon Chapman, Raphael Cooper, Russell M Allan, Malcolm Sim, David W Wrathall, Donald A Irvine, Kim S Zantua, John C Adams, Andrew J Burtenshaw, Gareth P Sellors, Ingeborg D Welters, Karen E Williams, Robert J Hessell, Matthew G Oldroyd, Ceri E Battle, Suresh Pillai, Istvan Kajtor, Mageswaran Sivashanmugavel, Sinead C O'Kane, Adrian Donnelly, Aniko D Frigyik, Jon P Careless, Martin M May, Richard Stewart, T John Trinder, Samantha J Hagan, Matt P Wise, Jade M Cole, Caroline C MacFie, Anna T Dowling, Nicolás Nin, Edgardo Nuñez, Gustavo Pittini, Ruben Rodriguez, María C Imperio, Cristina Santos, Ana G França, Alejandro Ebeid, Alberto Deicas, Carolina Serra, Aditya Uppalapati, Ghassan Kamel, Valerie M Banner-Goodspeed, Jeremy R Beitler, Satyanarayana Reddy Mukkera, Shreedhar Kulkarni, Jarone Lee, Tomaz Mesar, John O Shinn 3rd, Dina Gomaa, Christopher Tainter, Dale J Yeatts, Jessica Warren, Michael J Lanspa, Russel R Miller, Colin K Grissom, Madotto F, Rezoagli E, Pham T, Schmidt M, McNicholas B, Protti A, Panwar R, Bellani G, Fan E, van Haren F, Brochard L, Laffey JG, and LUNG SAFE Investigators and the ESICM Trials Group, Samuel M Brown, Philippe R Bauer, Ryan J Gosselin, Barrett T Kitch, Jason E Cohen, Scott H Beegle, Renaud M Gueret, Aiman Tulaimat, Shazia Choudry, William Stigler, Hitesh Batra, Nidhi G Huff, Keith D Lamb, Trevor W Oetting, Nicholas M Mohr, Claine Judy, Shigeki Saito, Fayez M Kheir, Fayez Kheir, Adam B Schlichting, Angela Delsing, Daniel R Crouch, Mary Elmasri, Dina Ismail, Kyle R Dreyer, Thomas C Blakeman, Rebecca M Baron, Carolina Quintana Grijalba, Peter C Hou, Raghu Seethala, Imo Aisiku, Galen Henderson, Gyorgy Frendl, Sen-Kuang Hou, Robert L Owens, Ashley Schomer, Vesna Bumbasirevic, Bojan Jovanovic, Maja Surbatovic, Milic Veljovic

Subjects
ARDS, medicine.medical_treatment, 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, Hyperoxemia, Hypoxemia, law.invention, 0302 clinical medicine, law, Fraction of inspired oxygen, Oxygen therapy, Prevalence, Medicine, Hypoxia, Acute respiratory distress syndrome, Hyperoxia, Invasive mechanical ventilation, Mortality, Respiratory Distress Syndrome, Hyperbaric Oxygenation, Respiration, lcsh:Medical emergencies. Critical care. Intensive care. First aid, Intensive care unit, Intensive Care Units, Anesthesia, Artificial, medicine.symptom, Human, Artificial ventilation, Intensive Care Unit, NO, 03 medical and health sciences, Intensive care, Settore MED/41 - ANESTESIOLOGIA, Humans, business.industry, Research, Respiratory Distress Syndrome, Adult, lcsh:RC86-88.9, medicine.disease, Respiration, Artificial, respiratory tract diseases, Oxygen, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], 030228 respiratory system, business
Abstract

Background Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55–100 mmHg) patients (P = 0.47). Conclusions Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073

Published
2020

48. Ultra-Homogeneous B0 field for High-Field Body Magnetic Resonance Imaging with Unified Shim-RF Coils

Author

Meiyun Wang, Yibin Xie, Zhaoyang Fan, Waishing Liu, Ghazal Yoosefian, Nan Wang, Richard Handelin, Rohan Dharmakumar, Linda Azab, John Stager, Christodoulou Anthony, Meng Lu, Hyunsuk Shim, Yuheng Huang, Alan C. Kwan, Peng Hu, Debiao Li, Hui Han, Hsin-Jung Yang, and Fardad Michael Serry

Subjects
Optics, Materials science, Field (physics), medicine.diagnostic_test, Homogeneous, business.industry, medicine, Shim (magnetism), Magnetic resonance imaging, High field, business
Abstract

High-field magnetic resonance imaging (MRI, 3.0T and above) offers numerous advantages for imaging the human body over lower-field strengths. However, it suffers from unwanted fast spatially-varying main (B0 ) fields caused by the susceptibility mismatch at the tissue interfaces. When this is combined with the anatomical complexity of the human body, undesirable image artifacts can become damaging as they can compromise potential image contrasts, limit the use of accelerated imaging, and interfere with clinical interpretation. Consequently, these limitations restrict the effective utilization of high-field body MRI and emphasize the need for a major improvement in B0 field homogeneity to take full advantage of the ever increased B0 field. Here we introduce a Unified shim-RF Coil (UNIC) to overcome this existing bottleneck by transcending the conventional low-efficiency, distantly located B0 shim coils. UNIC allows a shim array to be freely allotted and seamlessly integrated into a standard surface RF coil, thus maximizing both the performance of RF receive sensitivity and effective B0 shimming. We demonstrate the capacity of the UNIC approach through detailed characterization of the coil design, prototyping a body coil integrating the UNIC features, and conducting in-vivo imaging of deep organs adjacent to the lung. Our studies provide evidence that UNIC enables homogeneous B0 fields in the liver and the heart, where strong image artifacts are known to occur, and hence facilitate the acquisition of unprecedented image quality in a clinical 3.0T scanner. Further, UNIC’s design is practical as it overcomes one of the most, if not the most, critical limitations of the state-of-the-art high-field MRI with minimal changes to the current MRI hardware architecture. Accordingly, the proposed technique offers opportunities for major advancements in noninvasive imaging of deep organs with high-field imaging in a way it has not been possible thus far.

Published
2021

49. Tensor Data Representation, Privacy Protection and Heterogeneous Computing for Internet of Things: a Survey

Author

Liu Wang, Hui Han, Dengyong Zhang, and Jin Wang

Subjects
Data processing, business.industry, Computer science, Privacy protection, Symmetric multiprocessor system, Computer security, computer.software_genre, External Data Representation, Market research, Parallel processing (DSP implementation), The Internet, Tensor, business, computer
Abstract

The Internet of Things (IoT) is the Internet of everything connected. In the era of rapid development of the IoT, the paper summarizes the current progress of the IoT, and then finds out the high-dimensional tensor data generated by the IoT. However, with the increase of tensor data, the computing speed of the computer will decrease, and there will be corresponding privacy protection and compute problems. Therefore, this paper lists two applications that deal with different IoT scenarios, namely privacy protection, and heterogeneous computing. This paper holds that while processing data in parallel efficiently, protecting the security of data is the key point of the future development trend of the IoT.

Published
2021

50. Intestinal dysbiosis in nonalcoholic fatty liver disease (NAFLD): focusing on the gut-liver axis

Author

Yi Jiang, Yong Zhao, Mebratu Melaku, Hui Han, Bao Yi, Nadia Everaert, Lei Liu, Mengyu Wang, and Hongfu Zhang

Subjects
biology, business.industry, digestive, oral, and skin physiology, Lipid metabolism, Inflammation, General Medicine, Gut flora, Bioinformatics, biology.organism_classification, medicine.disease, digestive system, digestive system diseases, Industrial and Manufacturing Engineering, Pathogenesis, Biliary tract, Fibrosis, Nonalcoholic fatty liver disease, medicine, medicine.symptom, business, Drug metabolism, Food Science
Abstract

Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver disorders in humans, partly because it is closely related to metabolic disorders of the liver with increasing prevalence. NAFLD begins with hepatic lipid accumulation, which may cause inflammation and eventually lead to fibrosis in the liver. Numerous studies have demonstrated the close relationship between gut dysfunction (especially the gut microbiota and its metabolites) and the occurrence and progression of NAFLD. The bidirectional communication between the gut and liver, named the gut-liver axis, is mainly mediated by the metabolites derived from both the liver and gut through the biliary tract, portal vein, and systemic circulation. Herein, we review the effects of the gut-liver axis on the pathogenesis of NAFLD. We also comprehensively describe the potential molecular mechanisms from the perspective of the role of liver-derived metabolites and gut-related components in hepatic metabolism and inflammation and gut health, respectively. The study provides insights into the mechanisms underlying current summarizations that support the intricate interactions between a disordered gut and NAFLD and can provide novel strategies to lessen the prevalence and consequence of NAFLD.

Published
2021

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