Author: "D. Watson" / Publisher: oxford university press - Searchworks@Jio Institute Digital Library Search Results

110 results on '"D. Watson"'

1. Integration host factor bends and bridges DNA in a multiplicity of binding modes with varying specificity

Author: Victor Velasco-Berrelleza, Mark C. Leake, Samuel B. Yoshua, Jamieson A. L. Howard, Agnes Noy, and George D. Watson
Subjects: DNA, Bacterial, Integration Host Factors, AcademicSubjects/SCI00010, Biology, Genome Integrity, Repair and Replication, Molecular Dynamics Simulation, medicine.disease_cause, 010402 general chemistry, Microscopy, Atomic Force, 01 natural sciences, 03 medical and health sciences, chemistry.chemical_compound, Molecular dynamics, Transcription (biology), DNA Packaging, Genetics, medicine, Escherichia coli, Gene, 030304 developmental biology, Host factor, Physics, 0303 health sciences, Single Molecule Imaging, 0104 chemical sciences, Nucleoprotein, DNA-Binding Proteins, Nucleoproteins, chemistry, Prokaryotic DNA replication, Biophysics, bacteria, Nucleic Acid Conformation, Recombination, DNA
Abstract: Nucleoid-associated proteins (NAPs) are crucial in organizing prokaryotic DNA and regulating genes. Vital to these activities are complex nucleoprotein structures, however, how these form remains unclear. Integration host factor (IHF) is an Escherichia coli NAP that creates very sharp bends in DNA at sequences relevant to several functions including transcription and recombination, and is also responsible for general DNA compaction when bound non-specifically. We show that IHF–DNA structural multimodality is more elaborate than previously thought, and provide insights into how this drives mechanical switching towards strongly bent DNA. Using single-molecule atomic force microscopy and atomic molecular dynamics simulations we find three binding modes in roughly equal proportions: “associated” (73° of DNA bend), “half-wrapped” (107°) and “fully-wrapped” (147°), only the latter occurring with sequence specificity. We show IHF bridges two DNA double helices through non-specific recognition that gives IHF a stoichiometry greater than one and enables DNA mesh assembly. We observe that IHF-DNA structural multiplicity is driven through non-specific electrostatic interactions that we anticipate to be a general NAP feature for physical organization of chromosomes.
Published: 2021

2. Postnatal Effects of Gestational and Lactational Gavage Exposure to Boric Acid in the Developing Sprague Dawley Rat

Author: Johnathan Furr, B Collins, Keith R. Shockley, Helen Cunny, Charles D. Hébert, AtLee T. D. Watson, Lori Smith, Lutfiya Miller-Pinsler, Kristin Aillon, Vicki Sutherland, Guanhua Xie, Trey Vinke, Suramya Waidyanatha, and Barry S. McIntyre
Subjects: Male, Offspring, Developmental and Reproductive Toxicology, Developmental toxicity, Physiology, 010501 environmental sciences, Toxicology, 01 natural sciences, Boric acid, Dietary Exposure, Rats, Sprague-Dawley, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Boric Acids, medicine, Animals, Lactation, 030212 general & internal medicine, 0105 earth and related environmental sciences, Pregnancy, Reference dose, business.industry, Reproduction, Organ Size, medicine.disease, Rats, chemistry, Animals, Newborn, Gestation, Female, Animal studies, medicine.symptom, business, Weight gain
Abstract: Human exposure to boron occurs primarily through diet and drinking water sources. Animal studies have found that reduced fetal weight following gestational exposure to boron (as boric acid) is the most sensitive toxicological effect. However, recent studies suggest that newborns in areas with elevated boron in drinking water may receive levels of exposure that exceed the U.S. EPA oral reference dose for B. Currently, there are no data to inform a boron risk assessment accounting for this developmental window. To address this knowledge gap, the National Toxicology Program evaluated developmental toxicity following pre- and postnatal boron exposure. Time-mated female Sprague Dawley (Hsd: Sprague Dawley SD) rats were administered 0–20 mg B/kg/day (as boric acid) via gavage from gestation day 6 to 21; offspring were dosed via gavage at the same respective dose level from postnatal day (PND) 1 to 28. There were no dose-related effects on dam bodyweight, bodyweight gain, or feed consumption. Clinical findings were limited to low incidences of umbilical hernia in the 20 mg B/kg pups which resolved by study completion. Pup plasma boron concentrations increased in dose-proportional manner and were similar between PND 4 and PND 28. Postnatal weight gain was significantly reduced at 20 mg B/kg, with male and female pups weighing 23% less than the controls on PND 28. These findings demonstrate that postnatal growth in the Sprague Dawley rat is sensitive to boron exposure and highlights the importance of evaluating the potential toxicity of agents with known human exposures during early life stages.
Published: 2020

3. Multigenerational analysis of sex-specific phenotypic differences at midgestation caused by abnormal folate metabolism

Author: Georgina E T Blake, Joanna Rakoczy, Nisha Padmanabhan, Erica D. Watson, Monika Kondratowicz, Katerina Menelaou, Blake, Gina [0000-0002-6485-799X], Watson, Erica [0000-0003-4496-2271], and Apollo - University of Cambridge Repository
Subjects: 0301 basic medicine, intrauterine growth restriction, placenta, Folate Metabolism, Health, Toxicology and Mutagenesis, MTRR, 03 medical and health sciences, folic acid, 0302 clinical medicine, Transgenerational epigenetics, Genetics, Molecular Biology, Genetics (clinical), 2. Zero hunger, Congenital malformations, Sex specific, Genealogy, Joint research, 030104 developmental biology, Folic acid, sexual dimorphism, transgenerational epigenetic inheritance, developmental phenotypes, Psychology, 030217 neurology & neurosurgery, congenital malformations, Research Article
Abstract: The exposure to adverse environmental conditions (e.g. poor nutrition) may lead to increased disease risk in an individual and their descendants. In some cases, the results may be sexually dimorphic. A range of phenotypes has been associated with deficiency in or defective metabolism of the vitamin folate. However, the molecular mechanism linking folate metabolism to development is still not well defined nor is it clear whether phenotypes are sex-specific. The enzyme methionine synthase reductase (MTRR) is required for the progression of folate metabolism and the utilization of methyl groups from the folate cycle. Previously, we showed that the hypomorphic Mtrrgt mutation in mice results in metabolic disruption, epigenetic instability, and a wide spectrum of developmental phenotypes (e.g. growth defects, congenital malformations) at midgestation that appear in subsequent wild-type generations. This transgenerational effect only occurs through the maternal lineage. Here, we explore whether the phenotypes that result from either intrinsic or ancestral Mtrr deficiency are sexually dimorphic. We found that no sexual dimorphism is apparent in either situation when the phenotypes were broadly or specifically defined. However, when we focused on the group of phenotypically normal conceptuses derived from maternal grandparental Mtrr deficiency, we observed an apparent increase in placental efficiency in each subsequent generation leading to F4 generation female embryos that weigh more than controls. These data suggest that ancestral abnormal folate metabolism may lead to male grandprogeny that are less able to adapt or female grandprogeny that are programmed to become more sensitive to folate availability in subsequent generations.
Published: 2017

4. Effects of switching between anti-TNF therapies on HAQ response in patients who do not respond to their first anti-TNF drug

Author: Kath D. Watson, Deborah P M Symmons, Kimme I. Hyrich, Mark Lunt, and William G Dixon
Subjects: Male, medicine.medical_specialty, Arthritis, Treatment response, Antibodies, Monoclonal, Humanized, Severity of Illness Index, Receptors, Tumor Necrosis Factor, Etanercept, Arthritis, Rheumatoid, Clinical, Disability Evaluation, Rheumatology, Disease-modifying anti-rheumatic drugs, Internal medicine, Immunopathology, Severity of illness, medicine, Adalimumab, Anti-tumour necrosis factor therapy, Humans, Pharmacology (medical), Registries, Treatment Failure, Rheumatoid arthritis, Aged, Disability, business.industry, Tumor Necrosis Factor-alpha, Antibodies, Monoclonal, Middle Aged, medicine.disease, Infliximab, Treatment Outcome, Antirheumatic Agents, Immunoglobulin G, Switching, Physical therapy, Female, business, medicine.drug, Follow-Up Studies
Abstract: Objectives. Small studies have shown an improvement in disease activity in patients with RA who have switched between anti-TNF therapies for reasons of inefficacy. However, it is not clear whether switching improves longer term outcomes, such as disability. This analysis compares changes in HAQ scores 1 yr following lack of response to a first anti-TNF based on subsequent treatment during that year. Methods. Analysis was limited to RA patients with inefficacy to a first anti-TNF based on (i) clinician opinion and/or (ii) disease activity score in 28 joints and had an HAQ measured at time of non-response and 12 months later. Patients were classified into three groups based on treatment during the next 12 months: (i) continued anti-TNF despite non-response; (ii) stopped anti-TNF with no further biologics; and (iii) switched to a second anti-TNF. Mean improvement in HAQ was compared among the groups using multivariable linear regression models. Results. As of July 2006, 868 patients met the inclusion for this analysis. Four hundred and seventy-nine patients stopped anti-TNF of whom 331 switched to a second anti-TNF. Three hundred and eighty-nine continued treatment. Patients who continued and those who switched had improvements in HAQ over the 12 months, unlike patients who discontinued all biologic therapy. The best improvement was seen in those who switched [adjusted mean improvement in HAQ 0.15 (95% CI 0.26, 0.05)]. Conclusion. There is a significant improvement in HAQ in patients who switch to a second anti-TNF, providing an effective next choice of therapy for some patients who fail to respond to their first anti-TNF.
Published: 2008

5. Climate Change and Agriculture

Author: Derrill D. Watson
Subjects: Poverty, Natural resource economics, Political economy of climate change, Sustainability, Economics, Climate change, Climate change and agriculture, Agricultural productivity, Agricultural economics
Abstract: Complementarities between improving agricultural production, adapting to climate change, and reducing poverty are likely to increase with climate change. Thus, the worse you believe the effects of climate change will be, the more valuable it will be to invest in sustainable agriculture and poverty reduction. Agriculture will better support climate goals to the extent that externalities are internalized by market participants through a set of policies termed full-costing. Even though global full-costing may be out of reach for technical, practical, and political reasons, this chapter illustrates that numerous options exist to bring agricultural policies closer to socially optimal values.
Published: 2014
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6. Cory, Sir George Edward (1862–1935), chemist and historian

Author: K. D. Watson
Published: 2004
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7. Cruickshank, William (d. 1810/11), military surgeon and chemist

Author: K. D. Watson
Published: 2004
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8. Johnson, Robert (1676?–03 May 1735), governor of South Carolina

Author: Alan D. Watson
Published: 2000
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9. The surgical safety checklist and patient outcomes after surgery

Author: T.E.F. Abbott, T. Ahmad, M.K. Phull, A.J. Fowler, R. Hewson, B.M. Biccard, M.S. Chew, M. Gillies, R.M. Pearse, Rupert M. Pearse, Scott Beattie, Pierre-Alain Clavien, Nicolas Demartines, Lee A. Fleisher, Mike Grocott, James Haddow, Andreas Hoeft, Peter Holt, Rui Moreno, Naomi Pritchard, Andrew Rhodes, Duminda Wijeysundera, Matt Wilson, Tahania Ahmed, Kirsty Everingham, Russell Hewson, Marta Januszewska, Mandeep-Kaur Phull, Richard Halliwell, Mark Shulman, Paul Myles, Werner Schmid, Michael Hiesmayr, Patrick Wouters, Stefan de Hert, Suzana Lobo, Xiangming Fang, Lars Rasmussen, Emmanuel Futier, Matthieu Biais, Aurélien Venara, Karem Slim, Michael Sander, Despoina Koulenti, Kostoula Arvaniti, Mathew Chan, Atul Kulkarni, Susilo Chandra, Aida Tantri, Emad Geddoa, Muntadhar Abbas, Giorgio Della Rocca, Datin Sivasakthi, Marzida Mansor, Pastor Luna, Arthur Bouwman, Wolfgang Buhre, Vanessa Beavis, Douglas Campbell, Tim Short, Tunde Osinaike, Ricardo Matos, Ioana Grigoras, Mikhail Kirov, Denis Protsenko, Bruce Biccard, Cesar Aldecoa, Michelle Chew, Christoph Hofer, Martin Hubner, James Ditai, Tamas Szakmany, Lee Fleisher, Marissa Ferguson, Michael MacMahon, Ritchie Cherian, Helen Currow, Kathirgamanathan Kanathiban, David Gillespie, Edward Pathmanathan, Katherine Phillips, Jenifer Reynolds, Joanne Rowley, Jeanene Douglas, Ross Kerridge, Sameer Garg, Michael Bennett, Megha Jain, David Alcock, Nico Terblanche, Rochelle Cotter, Kate Leslie, Marcelle Stewart, Nicolette Zingerle, Antony Clyde, Oliver Hambidge, Adam Rehak, Sharon Cotterell, Wilson Binh Quan Huynh, Timothy McCulloch, Erez Ben-Menachem, Thomas Egan, Jennifer Cope, Paul Fellinger, Markus Haisjackl, Simone Haselberger, Caroline Holaubek, Paul Lichtenegger, Florian Scherz, Franz Hoffer, Veronika Cakova, Andreas Eichwalder, Norbert Fischbach, Reinhold Klug, Elisabeth Schneider, Martin Vesely, Reinhart Wickenhauser, Karl Gernot Grubmueller, Marion Leitgeb, Friedrich Lang, Nancy Toro, Marlene Bauer, Friedrich Laengle, Claudia Haberl, Thomas Mayrhofer, Christoph Trybus, Christian Buerkle, Karin Forstner, Reinhard Germann, Harald Rinoesl, Elke Schindler, Ernst Trampitsch, Gerhard Bogner, Daniel Dankl, Martin Duenser, Gerhard Fritsch, Ilse Gradwohl-Matis, Andreas Hartmann, Thomas Hoelzenbein, Tarkan Jaeger, Franz Landauer, Gregor Lindl, Michael Lux, Johannes Steindl, Ottokar Stundner, Christian Szabo, Jawad Bidgoli, Hans Verdoodt, Patrice Forget, David Kahn, Fernande Lois, Mona Momeni, Caroline Prégardien, Audrey Pospiech, Arnaud Steyaert, Laurent Veevaete, Dirk De Kegel, Karen De Jongh, Luc Foubert, Carine Smitz, Marcel Vercauteren, Jan Poelaert, Veerle Van Mossevelde, Jacques Abeloos, Stefaan Bouchez, Marc Coppens, Luc De Baerdemaeker, Isabel Deblaere, Ann De Bruyne, Kristine Fonck, Bjorn Heyse, Tom Jacobs, Koen Lapage, Anneliese Moerman, Martine Neckebroek, Aliaksandra Parashchanka, Nathalie Roels, Nancy Van Den Eynde, Michael Vandenheuvel, JurgenVan Limmen, Ann Vanluchene, Caroline Vanpeteghem, Piet Wyffels, Christel Huygens, Punitha Vandenbempt, Marc Van de Velde, Dimitri Dylst, Bruno Janssen, Evelien Schreurs, Fábia Berganton Aleixo, Keulle Candido, Hugo Dias Batista, Mario Guimarães, Jaqueline Guizeline, João Hoffmann, Francisco Ricardo Marques Lobo, Vinícius Nascimento, Katia Nishiyama, Lucas Pazetto, Daniela Souza, Rodrigo Souza Rodrigues, Ana Maria Vilela dos Santos, Jaquelline Jardim, Luiz Marcelo Sá Malbouisson, Joao Silva, Paulo do Nascimento Junior, Thalissa Hermínia Baio, Gabriel Isaac Pereira de Castro, Henri Roger Watanabe Oliveira, Cristina Prata Amendola, Gutemberg Cardoso, Daniela Ortega, Ana Flavia Brotto, Mirella Cristine De Oliveira, Álvaro Réa-Neto, Fernando Dias, Maria Eduarda Travi, Luiza Zerman, Pedro Azambuja, Marcos Freitas Knibel, Antonio Martins, William Almeida, Calim Neder Neto, Maria Angela Tardelli, Eliana Caser, Marcio Machado, Crisitiano Aguzzoli, Sérgio Baldisserotto, Fernanda Beck Tabajara, Fernanda Bettega, La Hore Correa Rodrigues Júnior, Julia de Gasperi, Lais Faina, Marcos Farias Nolasco, Bruna Ferreira da Costa Fischer, Mariana Fosch de Campos Ferreira, Cristina Hartmann, Marta Kliemann, Gustavo Luis Hubert Ribeiro, Julia Merladete Fraga, Thiago Motta Netto, Laura Valduga Pozza, Paulo Rafael Wendling, Caroline Azevedo, Juliana Garcia, Marcel Lopes, Bernardo Maia, Paula Maselli, Ralph Melo, Weslley Mendes, Matheus Neves, Jacqueline Ney, Claudio Piras, Christopher Applewhaite, Adrienne Carr, Lorraine Chow, Kaylene Duttchen, Julena Foglia, Michael Greene, Ashley Hinther, Kendra Houston, Thomas Jared McCormick, Jennifer Mikhayel, Sam Montasser, Alex Ragan, Andrew Suen, Adrianna Woolsey, Hai Chuan Yu, Duane Funk, Stephen Kowalski, Regina Legaspi, Heather McDonald, Faisal Siddiqui, Jeremy Pridham, Bernadette Rowe, Sonia Sampson, Barton Thiessen, Geoff Zbitnew, Andre Bernard, Ronald George, Philip Jones, Rita Moor, Naveed Siddiqui, Alexandra Wolfer, Diem Tran, Denyse Winch, Gary Dobson, Thomas McCormick, Osama Montasser, Richard Hall, Leyla Baghirzada, Gerard Curley, Si Yuan Dai, Gregory Hare, Esther Lee, Uma Shastri, Albert Tsui, Anmol Yagnik, Danielle Alvares, Stephen Choi, Heather Dwyer, Kathrina Flores, Colin McCartney, Priya Somascanthan, Jo Carroll, Janneth Pazmino-Canizares, Noam Ami, Vincent Chan, Anahi Perlas, Ruth Argue, Yang Huang, Katie Lavis, Kelly Mayson, Ying Cao, Hong Gao, Tingju Hu, Jie Lv, Jian Yang, Yang Yang, Yi Zhong, Jing Zhou, Xiaohua Zou, Miao He, Xiaoying Li, Dihuan Luo, Haiying Wang, Tian Yu, Liyong Chen, Lijun Wang, Yunfei Cai, Zhongming Cao, Yanling Li, Jiaxin Lian, Haiyun Sun, Sheng Wang, Zhipeng Wang, Kenru Wang, Yi Zhu, Xindan Du, Hao Fan, Yunbin Fu, Lixia Huang, Yanming Huang, Haifang Hwan, Hong Luo, Pi-Sheng Qu, Fan Tao, Zhen Wang, Guoxiang Wang, Shun Wang, Yan Zhang, Xiaolin Zhang, Chao Chen, Weixing Wang, Zhengyuan Liu, Lihua Fan, Jing Tang, Yijun Chen, Yongjie Chen, Yangyang Han, Changshun Huang, Guojin Liang, Jing Shen, Jun Wang, Qiuhong Yang, Jungang Zhen, Haidong Zhou, Junping Chen, Zhang Chen, Xiaoyu Li, Bo Meng, Haiwang Ye, Xiaoyan Zhang, Yanbing Bi, Jianqiao Cao, Fengying Guo, Hong Lin, Yang Liu, Meng Lv, Pengcai Shi, Xiumei Song, Chuanyu Sun, Yongtao Sun, Yuelan Wang, Shenhui Wang, Min Zhang, Rong Chen, Jiabao Hou, Yan Leng, Qing-tao Meng, Li Qian, Zi-ying Shen, Zhong-yuan Xia, Rui Xue, Yuan Zhang, Bo Zhao, Xian-jin Zhou, Qiang Chen, Huinan Guo, Yongqing Guo, Yuehong Qi, Zhi Wang, Jianfeng Wei, Weiwei Zhang, Lina Zheng, Qi Bao, Yaqiu Chen, Yijiao Chen, Yue Fei, Nianqiang Hu, Xuming Hu, Min Lei, Xiaoqin Li, Xiaocui Lv, Fangfang Miao, Lingling Ouyang, Lu Qian, Conyu Shen, Yu Sun, Yuting Wang, Dong Wang, Chao Wu, Liyuan Xu, Jiaqi Yuan, Lina Zhang, Huan Zhang, Yapping Zhang, Jinning Zhao, Chong Zhao, Lei Zhao, Tianzhao Zheng, Dachun Zhou, Haiyan Zhou, Ce Zhou, Kaizhi Lu, Ting Zhao, Changlin He, Hong Chen, Shasha Chen, Baoli Cheng, Jie He, Lin Jin, Caixia Li, Hui Li, Yuanming Pan, Yugang Shi, Xiao Hong Wen, Shuijing Wu, Guohao Xie, Kai Zhang, Bing Zhao, Xianfu Lu, Feifei Chen, Qisheng Liang, Xuewu Lin, Yunzhi Ling, Gang Liu, Jing Tao, Lu Yang, Jialong Zhou, Fumei Chen, Zhonggui Cheng, Hanying Dai, Yunlin Feng, Benchao Hou, Haixia Gong, Chun hua Hu, Haijin Huang, Jian Huang, Zhangjie Jiang, Mengyuan Li, Jiamei Lin, Mei Liu, Weicheng Liu, Zhen Liu, Zhiyi Liu, Foquan Luo, Longxian Ma, Jia Min, Xiaoyun Shi, Zhiping Song, Xianwen Wan, Yingfen Xiong, Lin Xu, Shuangjia Yang, Qin Zhang, Hongyan Zhang, Huaigen Zhang, Xuekang Zhang, Lili Zhao, Weihong Zhao, Weilu Zhao, Xiaoping Zhu, Yun Bai, Linbi Chen, Sijia Chen, Qinxue Dai, Wujun Geng, Kunyuan Han, Xin He, Luping Huang, Binbin Ji, Danyun Jia, Shenhui Jin, Qianjun Li, Dongdong Liang, Shan Luo, Lulu Lwang, Yunchang Mo, Yuanyuan Pan, Xinyu Qi, Meizi Qian, Jinling Qin, Yelong Ren, Yiyi Shi, Junlu Wang, Junkai Wang, Leilei Wang, Junjie Xie, Yixiu Yan, Yurui Yao, Mingxiao Zhang, Jiashi Zhao, Xiuxiu Zhuang, Yanqiu Ai, Fang Du, Long He, Ledan Huang, Zhisong Li, Huijuan Li, Yetong Li, Liwei Li, Su Meng, Yazhuo Yuan, Enman Zhang, Jie Zhang, Shuna Zhao, Zhenrong Ji, Ling Pei, Li Wang, Chen Chen, Beibei Dong, Jing Li, Ziqiang Miao, Hongying Mu, Chao Qin, Lin Su, Zhiting Wen, Keliang Xie, Yonghao Yu, Fang Yuan, Xianwen Hu, Ye Zhang, Wangpin Xiao, Zhipeng Zhu, Qingqing Dai, Kaiwen Fu, Rong Hu, Xiaolan Hu, Song Huang, Yaqi Li, Yingping Liang, Shuchun Yu, Zheng Guo, Yan Jing, Na Tang, Jie Wu, Dajiang Yuan, Ruilin Zhang, Xiaoying Zhao, Yuhong Li, Hui-Ping Bai, Chun-Xiao Liu, Fei-Fei Liu, Wei Ren, Xiu-Li Wang, Guan-Jie Xu, Na Hu, Bo Li, Yangwen Ou, Yongzhong Tang, Shanglong Yao, Shihai Zhang, Cui-Cui Kong, Bei Liu, Tianlong Wang, Wei Xiao, Bo Lu, Yanfei Xia, Jiali Zhou, Fang Cai, Pushan Chen, Shuangfei Hu, Hongfa Wang, Qiong Xu, Liu Hu, Liang Jing, Bin Li, Qiang Liu, Yuejiang Liu, Xinjian Lu, Zhen Dan Peng, Xiaodong Qiu, Quan Ren, Youliang Tong, Jin Wang, Yazhou Wen, Qiong Wu, Jiangyan Xia, Jue Xie, Xiapei Xiong, Shixia Xu, Tianqin Yang, Hui Ye, Ning Yin, Jing Yuan, Qiuting Zeng, Baoling Zhang, Kang Zheng, Jing Cang, Shiyu Chen, Yu Fan, Shuying Fu, Xiaodong Ge, Baolei Guo, Wenhui Huang, Linghui Jiang, Xinmei Jiang, Yi Liu, Yan Pan, Yun Ren, Qi Shan, Jiaxing Wang, Fei Wang, Chi Wu, Xiaoguang Zhang, Ida Cecilie Christiansen, Simon Nørgaard Granum, Bodil Steen Rasmussen, Morten Daugaard, Rajiv Gambhir, Birgitte Brandsborg, Guðný Erla Steingrímsdóttir, Peter Jensen-Gadegaard, Karsten Skovgaard Olsen, Hanna Siegel, Katrine Zwicky Eskildsen, Mona Ring Gätke, Ida Wibrandt, Simon Bisgaard Heintzelmann, Kai Henrik Wiborg Lange, Rune Sarauw Lundsgaard, Louise Amstrup-Hansen, Claus Hovendal, Michael Larsen, Mette Lenstrup, Tina Kobborg, Jens Rolighed Larsen, Anette Barbre Pedersen, Søren Hübertz Smith, Rebecca Monett Oestervig, Arash Afshari, Cheme Andersen, Kim Ekelund, Erik Lilja Secher, Helene Beloeil, Sigismond Lasocki, Alexandre Ouattara, Marlene Sineus, Serge Molliex, Marie Lim Legouge, Florent Wallet, Antoine Tesniere, Christophe Gaudin, Paul Lehur, Emma Forsans, Stéphane de Rudnicki, Valerie Serra Maudet, Didier Mutter, Ghassan Sojod, Mehdi Ouaissi, Jean-Marc Regimbeau, Jacques Desbordes, Nicolas Comptaer, Diae el Manser, Sabine Ethgen, Gilles Lebuffe, Patrick Auer, Christine Härtl, Maria Deja, Kirill Legashov, Susanne Sonnemann, Carola Wiegand-Loehnert, Elke Falk, Marit Habicher, Stefan Angermair, Beatrix Laetsch, Katrin Schmidt, Christian Von Heymann, Axel Ramminger, Florian Jelschen, Svenja Pabel, Andreas Weyland, Elke Czeslick, Jochen Gille, Michael Malcharek, Armin Sablotzki, Katharina Lueke, Peter Wetzel, Joerg Weimann, Franz-Peter Lenhart, Florian Reichle, Frederike Schirmer, Michael Hüppe, Karl Klotz, Carla Nau, Julika Schön, Thomas Mencke, Christina Wasmund, Carla Bankewitz, Georg Baumgarten, Andreas Fleischer, Vera Guttenthaler, Yvonne Hack, Katharina Kirchgaessner, Olja Männer, Marlen Schurig-Urbaniak, Rafael Struck, Rebekka van Zyl, Maria Wittmann, Ulrich Goebel, Sarah Harris, Siegfried Veit, Evangelia Andreadaki, Flora Souri, Ioannis Katsiadramis, Anthi Skoufi, Maria Vasileiou, Eleni Aimoniotou- Georgiou, Anastasios Katsourakis, Fotini Veroniki, Glyceria Vlachogianni, Konstantina Petra, Dimitra Chlorou, Eirini Oloktsidou, Vasileios Ourailoglou, Konstantinos Papapostolou, Georgia Tsaousi, Panagoula Daikou, Georgia Dedemadi, Ioannis Kalaitzopoulos, Christos Loumpias, Sotirios Bristogiannis, Nikolaos Dafnios, Georgios Gkiokas, Elissaios Kontis, Dimitra Kozompoli, Aspasia Papailia, Theodosios Theodosopoulos, Christol Bizios, Anastasia Koutsikou, Aleaxandra Moustaka, Ioannis Plaitakis, Apostolos Armaganidis, Theodora Christodoulopoulou, Mihail Lignos, Maria Theodorakopoulou, Andreas Asimakos, Eleni Ischaki, Angeliki Tsagkaraki, Spyros Zakynthinos, Eleni Antoniadou, Ioannis Koutelidakis, Dimitrios Lathyris, Irene Pozidou, Nikolaos Voloudakis, Maria Dalamagka, Gkonezou Elena, Christos Chronis, Dimitra Manolakaki, Dimitris Mosxogiannidis, Tatiana Slepova, Isaia-sissy Tsakiridou, Claire Lampiri, Anastasia Vachlioti, Christos Panagiotakis, Dimitrios Sfyras, Fotios Tsimpoukas, Athanasia Tsirogianni, Elena Axioti, Andreas Filippopoulos, Elli Kalliafa, George Kassavetis, Petros Katralis, Ioannis Komnos, Georgios Pilichos, Ifigenia Ravani, Antonis Totis, Eymorfia Apagaki, Andromachi Efthymiadi, Nikolaos Kampagiannis, Theoniki Paraforou, Agoritsa Tsioka, Georgios Georgiou, Aristeidis Vakalos, Aggeliki Bairaktari, Efthimios Charitos, George Markou, Panagiota Niforopoulou, Nikolaos Papakonstantinou, Evdoxia Tsigou, Archontoula Xifara, Menelaos Zoulamoglou, Panagiota Gkioni, Stylianos Karatzas, Aikaterini Kyparissi, Efstratios Mainas, Ioannis Papapanagiotou, Theonymfi Papavasilopoulou, George Fragandreas, Eleni Georgopoulou, Eleni Katsika, Kyriakos Psarras, Eirini Synekidou, Maria Verroiotou, Evangelia Vetsiou, Donika Zaimi, Athina Anagnou, Konstantinos Apostolou, Theodora Melissopoulou, Theophilos Rozenberg, Christos Tsigris, Georgios Boutsikos, Vasileios Kalles, Nikolaos Kotsalas, Christina Lavdaiou, Fotini Paikou, Georgia-Laura Panagou, Anna Spring, Ioannis Botis, Maria Drimala, Georgios Georgakakis, Ellada Kiourtzieva, Panagiota Ntouma, Apostolos Prionas, Kyriakos Xouplidis, Eleftheria Dalampini, Chrysavgi Giannaki, Christina Iasonidou, Orestis Ioannidis, Athina Lavrentieva, Athena Lavrentieva, George Papageorgiou, Maria Kokkinoy, Maria Stafylaraki, Stylianos Gaitanakis, Periclis Karydakis, Josef Paltoglou, Panagiotis Ponireas, Panagiotis Chaloulis, Athanasios Provatidis, Anisoglou Sousana, Varvara Vanessa Gardikou, Maria Konstantivelli, Olga Lataniotou, Elisavet Lisari, Maria Margaroni, Konstantinos Stamatiou, Edouardos Nikolaidis, Ioannis Pnevmatikos, Eleni Sertaridou, Alexandros Andreou, Eleni Arkalaki, Elias Athanasakis, Fotini Chaniotaki, Chatzimichali Aikaterini Chatzimichali, Maria Christofaki, Despina Dermitzaki, Klara Fiorentza, Georgios Frantzeskos, Elisavet Geromarkaki, Kalliopi Kafkalaki, Marina Kalogridaki, Konstyllia Karydi, Sofia Kokkini, Georgios Kougentakis, Tatiana Lefaki, Emmanouhl Lilitsis, Aikaterini Makatounaki, Polychronis Malliotakis, Dimosthenis Michelakis, Maria Neonaki, Vasileia Nyktari, Iliana Palikyra, Eleftherios Papadakis, Alexandra Papaioannou, Konstantinos Sfakianakis, Maria Sgouraki, Xenia Souvatzis, Anastasia Spartinou, Nefeli Stefanidou, Paulina Syrogianni, Georgia Tsagkaraki, Elena Arnaoutoglou, Christina Arnaoutoglou, Christina Bali, Vasilios Bouris, Rodamanthos Doumos, Konstantia-Paraskevi Gkini, Clio Kapaktsi, Vasilios Koulouras, Arian Lena, Dimitra Lepida, Evangelos Michos, Dimitrios Papadopoulos, Minas Paschopoulos, Vaia Aliki Rompou, Ioanna Siouti, Stavros Tsampalas, Ourania Ververidou, Georgios Zilis, Alexandra Charlalampidoy, Gregory Christodoulidis, Andreas Flossos, Konstantinos Stamoulis, Matthew Chan, Man Shing Caleb Tsang, Man Shing Tsang, Man Ling Lai, Chi Pang Yip, Hey Man Heymans Chan, Bassanio Law, Wing Sze Li, Hiu Man Chu, Emily Gar Yee Koo, Chi Cheong Joe Lam, Ka Ho Cheng, Tracy Lam, Susanna Chu, Wing yan Lam, Kin Wai Kevin Wong, Dilys Kwok, Ching Yue Janice Hung, Wai Kit Jacky Chan, Wing Lam Wong, Chun Kwong Eric Chung, Shu Kai Ma, Shuchi Kaushik, Bhagyesh Shah, Dhiren Shah, 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Akerman, Philip Antill, Lynsey Bourner, Sarah Buckley, Gail Castle, Rob Charles, Christopher Eggleston, Rebecca Foster, Satwant Gill, Kate Lindley, Mohamed Lklouk, Tracey Lowery, Oliver Martin, David Milne, Patrick O'Connor, Andrew Ratcliffe, Alastair Rose, Annie Smith, Sandeep Varma, Jackie Ward, Helena Barcraft-Barnes, Julie Camsooksai, Carolyn Colvin, Henrik Reschreiter, Lee Tbaily, Nicola Venner, Caroline Hamilton, Lewis Kelly, Piroska Toth-Tarsoly, Kerry Dodsworth, Denise Foord, Paul Gordon, Elizabeth Hawes, Nikki Lamb, Johanna Mouland, Jeremy Nightingale, Steve Rose, Joe Schrieber, Khalid Al'Amri, Hafiz Aladin, Mohammed Asif Arshad, James Barraclough, Conor Bentley, Colin Bergin, Ronald Carrera, Aisling Clarkson, Michelle Collins, Lauren Cooper, Samuel Denham, Ewen Griffiths, Peter Ip, Somasundaram Jeyanthan, Kavita Joory, Satwant Kaur, Paul Marriott, Natalie Mitchell, Sukumar Nagaiah, Annette Nilsson, Nilesh Parekh, Martin Pope, Joseph Seager, Hosam Serag, Alifia Tameem, Anna 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Queen Mary University of London (QMUL), Royal Free Hospital [London, UK], NHS Foundation Trust [London], The Royal Marsden, University of Cape Town, Linköping university hospital, University of Edinburgh, Abbott, T E F, Ahmad, T, Phull, M K, Fowler, A J, Hewson, R, Biccard, B M, Chew, M S, Gillies, M, Pearse RM, Beattie S, Clavien PA, Demartines N, Fleisher LA, Grocott M, Haddow J, Hoeft A, Holt P, Moreno R, Pritchard N, Rhodes A, Wijeysundera D, Wilson M, Ahmed T, Everingham K, Hewson R, Januszewska M, Phull MK, Halliwell R, Shulman M, Myles P, Schmid W, Hiesmayr M, Wouters P, de Hert S, Lobo S, Fang X, Rasmussen L, Futier E, Biais M, Venara A, Slim K, Sander M, Koulenti D, Arvaniti K, Chan M, Kulkarni A, Chandra S, Tantri A, Geddoa E, Abbas M, Della Rocca G, Sivasakthi D, Mansor M, Luna P, Bouwman A, Buhre W, Beavis V, Campbell D, Short T, Osinaike T, Matos R, Grigoras I, Kirov M, Protsenko D, Biccard B, Aldecoa C, Chew M, Hofer C, Hubner M, Ditai J, Szakmany T, Fleisher L, Ferguson 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Poelaert J, Van Mossevelde V, Abeloos J, Bouchez S, Coppens M, De Baerdemaeker L, Deblaere I, De Bruyne A, Fonck K, Heyse B, Jacobs T, Lapage K, Moerman A, Neckebroek M, Parashchanka A, Roels N, Van Den Eynde N, Vandenheuvel M, Limmen J, Vanluchene A, Vanpeteghem C, Wyffels P, Huygens C, Vandenbempt P, Van de Velde M, Dylst D, Janssen B, Schreurs E, Aleixo FB, Candido K, Batista HD, Guimarães M, Guizeline J, Hoffmann J, Lobo FRM, Nascimento V, Nishiyama K, Pazetto L, Souza D, Rodrigues RS, Vilela Dos Santos AM, Jardim J, Sá Malbouisson LM, Silva J, Nascimento Junior PD, Baio TH, Pereira de Castro GI, Watanabe Oliveira HR, Amendola CP, Cardoso G, Ortega D, Brotto AF, De Oliveira MC, Réa-Neto Á, Dias F, Travi ME, Zerman L, Azambuja P, Knibel MF, Martins A, Almeida W, Neto CN, Tardelli MA, Caser E, Machado M, Aguzzoli C, Baldisserotto S, Tabajara FB, Bettega F, Rodrigues Júnior HC, de Gasperi J, Faina L, Nolasco MF, Ferreira da Costa Fischer B, Fosch de Campos Ferreira M, Hartmann C, Kliemann M, Hubert Ribeiro GL, Fraga JM, Netto TM, Pozza LV, Wendling PR, Azevedo C, Garcia J, Lopes M, Maia B, Maselli P, Melo R, Mendes W, Neves M, Ney J, Piras C, Applewhaite C, Carr A, Chow L, Duttchen K, Foglia J, Greene M, Hinther A, Houston K, McCormick TJ, Mikhayel J, Montasser S, Ragan A, Suen A, Woolsey A, Yu HC, Funk D, Kowalski S, Legaspi R, McDonald H, Siddiqui F, Pridham J, Rowe B, Sampson S, Thiessen B, Zbitnew G, Bernard A, George R, Jones P, Moor R, Siddiqui N, Wolfer A, Tran D, Winch D, Dobson G, McCormick T, Montasser O, Hall R, Baghirzada L, Curley G, Dai SY, Hare G, Lee E, Shastri U, Tsui A, Yagnik A, Alvares D, Choi S, Dwyer H, Flores K, McCartney C, Somascanthan P, Carroll J, Pazmino-Canizares J, Wolfer A, Ami N, Chan V, Perlas A, Argue R, Huang Y, Lavis K, Mayson K, Cao Y, Gao H, Hu T, Lv J, Yang J, Yang Y, Zhong Y, Zhou J, Zou X, He M, Li X, Luo D, Wang H, Yu T, Chen L, Wang L, Cai Y, Cao Z, Li Y, Lian J, Sun H, Wang S, Wang Z, Wang K, Zhu Y, Du X, Fan H, Fu Y, Huang L, Huang Y, Hwan H, Luo H, Qu PS, Tao F, Wang Z, Wang G, Wang S, Zhang Y, Zhang X, Chen C, Wang W, Liu Z, Fan L, Tang J, Chen Y, Chen Y, Han Y, Huang C, Liang G, Shen J, Wang J, Yang Q, Zhen J, Zhou H, Chen J, Chen Z, Li X, Meng B, Ye H, Zhang X, Bi Y, Cao J, Guo F, Lin H, Liu Y, Lv M, Shi P, Song X, Sun C, Sun Y, Wang Y, Wang S, Zhang M, Chen R, Hou J, Leng Y, Meng QT, Qian L, Shen ZY, Xia ZY, Xue R, Zhang Y, Zhao B, Zhou XJ, Chen Q, Guo H, Guo Y, Qi Y, Wang Z, Wei J, Zhang W, Zheng L, Bao Q, Chen Y, Chen Y, Fei Y, Hu N, Hu X, Lei M, Li X, Lv X, Miao F, Ouyang L, Qian L, Shen C, Sun Y, Wang Y, Wang D, Wu C, Xu L, Yuan J, Zhang L, Zhang H, Zhang Y, Zhao J, Zhao C, Zhao L, Zheng T, Zhou D, Zhou H, Zhou C, Lu K, Zhao T, He C, Chen H, Chen S, Cheng B, He J, Jin L, Li C, Li H, Pan Y, Shi Y, Wen XH, Wu S, Xie G, Zhang K, Zhao B, Lu X, Chen F, Liang Q, Lin X, Ling Y, Liu G, Tao J, Yang L, Zhou J, Chen F, Cheng Z, Dai H, Feng Y, Hou B, Gong H, Hu CH, Huang H, Huang J, Jiang Z, Li M, Lin J, Liu M, Liu W, Liu Z, Liu Z, Luo F, Ma L, Min J, Shi X, Song Z, Wan X, Xiong Y, Xu L, Yang S, Zhang Q, Zhang H, Zhang H, Zhang X, Zhao L, Zhao W, Zhao W, Zhu X, Bai Y, Chen L, Chen S, Dai Q, Geng W, Han K, He X, Huang L, Ji B, Jia D, Jin S, Li Q, Liang D, Luo S, Lwang L, Mo Y, Pan Y, Qi X, Qian M, Qin J, Ren Y, Shi Y, Wang J, Wang J, Wang L, Xie J, Yan Y, Yao Y, Zhang M, Zhao J, Zhuang X, Ai Y, Du F, He L, Huang L, Li Z, Li H, Li Y, Li L, Meng S, Yuan Y, Zhang E, Zhang J, Zhao S, Ji Z, Pei L, Wang L, Chen C, Dong B, Li J, Miao Z, Mu H, Qin C, Su L, Wen Z, Xie K, Yu Y, Yuan F, Hu X, Zhang Y, Xiao W, Zhu Z, Dai Q, Fu K, Hu R, Hu X, Huang S, Li Y, Liang Y, Yu S, Guo Z, Jing Y, Tang N, Wu J, Yuan D, Zhang R, Zhao X, Li Y, Bai HP, Liu CX, Liu FF, Ren W, Wang XL, Xu GJ, Hu N, Li B, Ou Y, Tang Y, Yao S, Zhang S, Kong CC, Liu B, Wang T, Xiao W, Lu B, Xia Y, Zhou J, Cai F, Chen P, Hu S, Wang H, Xu Q, Hu L, Jing L, Li B, Liu Q, Liu Y, Lu X, Peng ZD, Qiu X, Ren Q, Tong Y, Wang J, Wen Y, Wu Q, Xia J, Xie J, Xiong X, Xu S, Yang T, Ye H, Yin N, Yuan J, Zeng Q, Zhang B, Zheng K, Cang J, Chen S, Fan Y, Fu S, Ge X, Guo B, Huang W, Jiang L, Jiang X, Liu Y, Pan Y, Ren Y, Shan Q, Wang J, Wang F, Wu C, Zhang X, Christiansen IC, Granum SN, Rasmussen BS, Daugaard M, Gambhir R, Brandsborg B, Steingrímsdóttir GE, Jensen-Gadegaard P, Olsen KS, Siegel H, Eskildsen KZ, Gätke MR, Wibrandt I, Heintzelmann SB, Wiborg Lange KH, Lundsgaard RS, Amstrup-Hansen L, Hovendal C, Larsen M, Lenstrup M, Kobborg T, Larsen JR, Pedersen AB, Smith SH, Oestervig RM, Afshari A, Andersen C, Ekelund K, Secher EL, Beloeil H, Lasocki S, Ouattara A, Sineus M, Molliex S, Legouge ML, Wallet F, Tesniere A, Gaudin C, Lehur P, Forsans E, de Rudnicki S, Maudet VS, Mutter D, Sojod G, Ouaissi M, Regimbeau JM, Desbordes J, Comptaer N, Manser DE, Ethgen S, Lebuffe G, Auer P, Härtl C, Deja M, Legashov K, Sonnemann S, Wiegand-Loehnert C, Falk E, Habicher M, Angermair S, Laetsch B, Schmidt K, Von Heymann C, Ramminger A, Jelschen F, Pabel S, Weyland A, Czeslick E, Gille J, Malcharek M, Sablotzki A, Lueke K, Wetzel P, Weimann J, Lenhart FP, Reichle F, Schirmer F, Hüppe M, Klotz K, Nau C, Schön J, Mencke T, Wasmund C, Bankewitz C, Baumgarten G, Fleischer A, Guttenthaler V, Hack Y, Kirchgaessner K, Männer O, Schurig-Urbaniak M, Struck R, van Zyl R, Wittmann M, Goebel U, Harris S, Veit S, Andreadaki E, Souri F, Katsiadramis I, Skoufi A, Vasileiou M, Aimoniotou-Georgiou E, Katsourakis A, Veroniki F, Vlachogianni G, Petra K, Chlorou D, Oloktsidou E, Ourailoglou V, Papapostolou K, Tsaousi G, Daikou P, Dedemadi G, Kalaitzopoulos I, Loumpias C, Bristogiannis S, Dafnios N, Gkiokas G, Kontis E, Kozompoli D, Papailia A, Theodosopoulos T, Bizios C, Koutsikou A, Moustaka A, Plaitakis I, Armaganidis A, Christodoulopoulou T, Lignos M, Theodorakopoulou M, Asimakos A, Ischaki E, Tsagkaraki A, Zakynthinos S, Antoniadou E, Koutelidakis I, Lathyris D, Pozidou I, Voloudakis N, Dalamagka M, Elena G, Chronis C, Manolakaki D, 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Craw N, Craw S, Pitt-Kerby T, Rowland-Axe R, Spurdle K, McDonald A, Simon D, Sinha V, Smith T, Banner-Goodspeed V, Boone M, Campbell K, Lu F, Scannell J, Sobol J, Balajonda N, Clemmons K, Conde C, Elgasim M, Funk B, Hall R, Hopkins T, Olaleye O, Omer O, Pender M, Porto A, Stevens A, Waweru P, Yeh E, Bodansky D, Evans A, Kleopoulos S, Maril R, Mathney E, Sanchez A, Tinuoye E, Bateman B, Eng K, Jiang N, Ladha K, Needleman J, Chen LL, Lane R, Robinowitz D, Ghushe N, Irshad M, O'Connor J, Patel S, Takemoto S, Wallace A, Mazzeffi M, Rock P, Wallace K, Zhu X, Chua P, Mattera M, Sharar R, Thilen S, Treggiari M, Morgan A, Sofjan I, Subramaniam K, Avidan M, Maybrier H, Muench M, Wildes T., Université de Lille, CHU Lille, Queen Mary University of London [QMUL], Graduate School, Medical Microbiology and Infection Prevention, Clinical Immunology and Rheumatology, 01 Internal and external specialisms, ACS - Heart failure & arrhythmias, AGEM - Endocrinology, metabolism and nutrition, APH - Quality of Care, ACS - Diabetes & metabolism, AII - Amsterdam institute for Infection and Immunity, ACS - Microcirculation, Pearse, R M, International Surgical Outcomes Study (ISO), Group, Zangrillo, A, Landoni, G, Beretta, L., International Surgical Outcomes Study (ISOS) group, Pearse, R.M., Beattie, S., Clavien, P.A., Demartines, N., Fleisher, L.A., Grocott, M., Haddow, J., Hoeft, A., Holt, P., Moreno, R., Pritchard, N., Rhodes, A., Wijeysundera, D., Wilson, M., Ahmed, T., Everingham, K., Hewson, R., Januszewska, M., Phull, M.K., Halliwell, R., Shulman, M., Myles, P., Schmid, W., Hiesmayr, M., Wouters, P., de Hert, S., Lobo, S., Fang, X., Rasmussen, L., Futier, E., Biais, M., Venara, A., Slim, K., Sander, M., Koulenti, D., Arvaniti, K., Chan, M., Kulkarni, A., Chandra, S., Tantri, A., Geddoa, E., Abbas, M., Della Rocca, G., Sivasakthi, D., Mansor, M., Luna, P., Bouwman, A., Buhre, W., Beavis, V., Campbell, D., Short, T., Osinaike, T., Matos, R., Grigoras, I., Kirov, M., Protsenko, D., Biccard, B., Aldecoa, C., Chew, M., Hofer, C., Hubner, M., Ditai, J., Szakmany, T., Fleisher, L., Ferguson, M., MacMahon, M., Cherian, R., Currow, H., Kanathiban, K., Gillespie, D., Pathmanathan, E., Phillips, K., Reynolds, J., Rowley, J., Douglas, J., Kerridge, R., Garg, S., Bennett, M., Jain, M., Alcock, D., Terblanche, N., Cotter, R., Leslie, K., Stewart, M., Zingerle, N., Clyde, A., Hambidge, O., Rehak, A., Cotterell, S., Huynh, WBQ, McCulloch, T., Ben-Menachem, E., Egan, T., Cope, J., Fellinger, P., Haisjackl, M., Haselberger, S., Holaubek, C., Lichtenegger, P., Scherz, F., Hoffer, F., Cakova, V., Eichwalder, A., Fischbach, N., Klug, R., Schneider, E., Vesely, M., Wickenhauser, R., Grubmueller, K.G., Leitgeb, M., Lang, F., Toro, N., Bauer, M., Laengle, F., Haberl, C., Mayrhofer, T., Trybus, C., Buerkle, C., Forstner, K., Germann, R., Rinoesl, H., Schindler, E., Trampitsch, E., Bogner, G., Dankl, D., Duenser, M., Fritsch, G., Gradwohl-Matis, I., Hartmann, A., Hoelzenbein, T., Jaeger, T., Landauer, F., Lindl, G., Lux, M., Steindl, J., Stundner, O., Szabo, C., Bidgoli, J., Verdoodt, H., Forget, P., Kahn, D., Lois, F., Momeni, M., Prégardien, C., Pospiech, A., Steyaert, A., Veevaete, L., De Kegel, D., De Jongh, K., Foubert, L., Smitz, C., Vercauteren, M., Poelaert, J., Van Mossevelde, V., Abeloos, J., Bouchez, S., Coppens, M., De Baerdemaeker, L., Deblaere, I., De Bruyne, A., Fonck, K., Heyse, B., Jacobs, T., Lapage, K., Moerman, A., Neckebroek, M., Parashchanka, A., Roels, N., Van Den Eynde, N., Vandenheuvel, M., Limmen, J., Vanluchene, A., Vanpeteghem, C., Wyffels, P., Huygens, C., Vandenbempt, P., Van de Velde, M., Dylst, D., Janssen, B., Schreurs, E., Aleixo, F.B., Candido, K., Batista, H.D., Guimarães, M., Guizeline, J., Hoffmann, J., Lobo, FRM, Nascimento, V., Nishiyama, K., Pazetto, L., Souza, D., Rodrigues, R.S., Vilela Dos Santos, A.M., Jardim, J., Sá Malbouisson, L.M., Silva, J., Nascimento Junior, P.D., Baio, T.H., Pereira de Castro, G.I., Watanabe Oliveira, H.R., Amendola, C.P., Cardoso, G., Ortega, D., Brotto, A.F., De Oliveira, M.C., Réa-Neto, Á., Dias, F., Travi, M.E., Zerman, L., Azambuja, P., Knibel, M.F., Martins, A., Almeida, W., Neto, C.N., Tardelli, M.A., Caser, E., Machado, M., Aguzzoli, C., Baldisserotto, S., Tabajara, F.B., Bettega, F., Rodrigues Júnior, H.C., de Gasperi, J., Faina, L., Nolasco, M.F., Ferreira da Costa Fischer, B., Fosch de Campos Ferreira, M., Hartmann, C., Kliemann, M., Hubert Ribeiro, G.L., Fraga, J.M., Netto, T.M., Pozza, L.V., Wendling, P.R., Azevedo, C., Garcia, J., Lopes, M., Maia, B., Maselli, P., Melo, R., Mendes, W., Neves, M., Ney, J., Piras, C., Applewhaite, C., Carr, A., Chow, L., Duttchen, K., Foglia, J., Greene, M., Hinther, A., Houston, K., McCormick, T.J., Mikhayel, J., Montasser, S., Ragan, A., Suen, A., Woolsey, A., Yu, H.C., Funk, D., Kowalski, S., Legaspi, R., McDonald, H., Siddiqui, F., Pridham, J., Rowe, B., Sampson, S., Thiessen, B., Zbitnew, G., Bernard, A., George, R., Jones, P., Moor, R., Siddiqui, N., Wolfer, A., Tran, D., Winch, D., Dobson, G., McCormick, T., Montasser, O., Hall, R., Baghirzada, L., Curley, G., Dai, S.Y., Hare, G., Lee, E., Shastri, U., Tsui, A., Yagnik, A., Alvares, D., Choi, S., Dwyer, H., Flores, K., McCartney, C., Somascanthan, P., Carroll, J., Pazmino-Canizares, J., Ami, N., Chan, V., Perlas, A., Argue, R., Huang, Y., Lavis, K., Mayson, K., Cao, Y., Gao, H., Hu, T., Lv, J., Yang, J., Yang, Y., Zhong, Y., Zhou, J., Zou, X., He, M., Li, X., Luo, D., Wang, H., Yu, T., Chen, L., Wang, L., Cai, Y., Cao, Z., Li, Y., Lian, J., Sun, H., Wang, S., Wang, Z., Wang, K., Zhu, Y., Du, X., Fan, H., Fu, Y., Huang, L., Hwan, H., Luo, H., Qu, P.S., Tao, F., Wang, G., Zhang, Y., Zhang, X., Chen, C., Wang, W., Liu, Z., Fan, L., Tang, J., Chen, Y., Han, Y., Huang, C., Liang, G., Shen, J., Wang, J., Yang, Q., Zhen, J., Zhou, H., Chen, J., Chen, Z., Meng, B., Ye, H., Bi, Y., Cao, J., Guo, F., Lin, H., Liu, Y., Lv, M., Shi, P., Song, X., Sun, C., Sun, Y., Wang, Y., Zhang, M., Chen, R., Hou, J., Leng, Y., Meng, Q.T., Qian, L., Shen, Z.Y., Xia, Z.Y., Xue, R., Zhao, B., Zhou, X.J., Chen, Q., Guo, H., Guo, Y., Qi, Y., Wei, J., Zhang, W., Zheng, L., Bao, Q., Fei, Y., Hu, N., Hu, X., Lei, M., Lv, X., Miao, F., Ouyang, L., Shen, C., Wang, D., Wu, C., Xu, L., Yuan, J., Zhang, L., Zhang, H., Zhao, J., Zhao, C., Zhao, L., Zheng, T., Zhou, D., Zhou, C., Lu, K., Zhao, T., He, C., Chen, H., Chen, S., Cheng, B., He, J., Jin, L., Li, C., Li, H., Pan, Y., Shi, Y., Wen, X.H., Wu, S., Xie, G., Zhang, K., Lu, X., Chen, F., Liang, Q., Lin, X., Ling, Y., Liu, G., Tao, J., Yang, L., Cheng, Z., Dai, H., Feng, Y., Hou, B., Gong, H., Hu, C.H., Huang, H., Huang, J., Jiang, Z., Li, M., Lin, J., Liu, M., Liu, W., Luo, F., Ma, L., Min, J., Shi, X., Song, Z., Wan, X., Xiong, Y., Yang, S., Zhang, Q., Zhao, W., Zhu, X., Bai, Y., Dai, Q., Geng, W., Han, K., He, X., Ji, B., Jia, D., Jin, S., Li, Q., Liang, D., Luo, S., Lwang, L., Mo, Y., Qi, X., Qian, M., Qin, J., Ren, Y., Xie, J., Yan, Y., Yao, Y., Zhuang, X., Ai, Y., Du, F., He, L., Li, Z., Li, L., Meng, S., Yuan, Y., Zhang, E., Zhang, J., Zhao, S., Ji, Z., Pei, L., Dong, B., Li, J., Miao, Z., Mu, H., Qin, C., Su, L., Wen, Z., Xie, K., Yu, Y., Yuan, F., Xiao, W., Zhu, Z., Fu, K., Hu, R., Huang, S., Liang, Y., Yu, S., Guo, Z., Jing, Y., Tang, N., Wu, J., Yuan, D., Zhang, R., Zhao, X., Bai, H.P., Liu, C.X., Liu, F.F., Ren, W., Wang, X.L., Xu, G.J., Li, B., Ou, Y., Tang, Y., Yao, S., Zhang, S., Kong, C.C., Liu, B., Wang, T., Lu, B., Xia, Y., Cai, F., Chen, P., Hu, S., Xu, Q., Hu, L., Jing, L., Liu, Q., Peng, Z.D., Qiu, X., Ren, Q., Tong, Y., Wen, Y., Wu, Q., Xia, J., Xiong, X., Xu, S., Yang, T., Yin, N., Zeng, Q., Zhang, B., Zheng, K., Cang, J., Fan, Y., Fu, S., Ge, X., Guo, B., Huang, W., Jiang, L., Jiang, X., Shan, Q., Wang, F., Christiansen, I.C., Granum, S.N., Rasmussen, B.S., Daugaard, M., Gambhir, R., Brandsborg, B., Steingrímsdóttir, G.E., Jensen-Gadegaard, P., Olsen, K.S., Siegel, H., Eskildsen, K.Z., Gätke, M.R., Wibrandt, I., Heintzelmann, S.B., Wiborg Lange, K.H., Lundsgaard, R.S., Amstrup-Hansen, L., Hovendal, C., Larsen, M., Lenstrup, M., Kobborg, T., Larsen, J.R., Pedersen, A.B., Smith, S.H., Oestervig, R.M., Afshari, A., Andersen, C., Ekelund, K., Secher, E.L., Beloeil, H., Lasocki, S., Ouattara, A., Sineus, M., Molliex, S., Legouge, M.L., Wallet, F., Tesniere, A., Gaudin, C., Lehur, P., Forsans, E., de Rudnicki, S., Maudet, V.S., Mutter, D., Sojod, G., Ouaissi, M., Regimbeau, J.M., Desbordes, J., Comptaer, N., Manser, D.E., Ethgen, S., Lebuffe, G., Auer, P., Härtl, C., Deja, M., Legashov, K., Sonnemann, S., Wiegand-Loehnert, C., Falk, E., Habicher, M., Angermair, S., Laetsch, B., Schmidt, K., Von Heymann, C., Ramminger, A., Jelschen, F., Pabel, S., Weyland, A., Czeslick, E., Gille, J., Malcharek, M., Sablotzki, A., Lueke, K., Wetzel, P., Weimann, J., Lenhart, F.P., Reichle, F., Schirmer, F., Hüppe, M., Klotz, K., Nau, C., Schön, J., Mencke, T., Wasmund, C., Bankewitz, C., Baumgarten, G., Fleischer, A., Guttenthaler, V., Hack, Y., Kirchgaessner, K., Männer, O., Schurig-Urbaniak, M., Struck, R., van Zyl, R., Wittmann, M., Goebel, U., Harris, S., Veit, S., Andreadaki, E., Souri, F., Katsiadramis, I., Skoufi, A., Vasileiou, M., Aimoniotou-Georgiou, E., Katsourakis, A., Veroniki, F., Vlachogianni, G., Petra, K., Chlorou, D., Oloktsidou, E., Ourailoglou, V., Papapostolou, K., Tsaousi, G., Daikou, P., Dedemadi, G., Kalaitzopoulos, I., Loumpias, C., Bristogiannis, S., Dafnios, N., Gkiokas, G., Kontis, E., Kozompoli, D., Papailia, A., Theodosopoulos, T., Bizios, C., Koutsikou, A., Moustaka, A., Plaitakis, I., Armaganidis, A., Christodoulopoulou, T., Lignos, M., Theodorakopoulou, M., Asimakos, A., Ischaki, E., Tsagkaraki, A., Zakynthinos, S., Antoniadou, E., Koutelidakis, I., Lathyris, D., Pozidou, I., Voloudakis, N., Dalamagka, M., Elena, G., Chronis, C., Manolakaki, D., Mosxogiannidis, D., Slepova, T., Tsakiridou, I.S., Lampiri, C., Vachlioti, A., Panagiotakis, C., Sfyras, D., Tsimpoukas, F., Tsirogianni, A., Axioti, E., Filippopoulos, A., Kalliafa, E., Kassavetis, G., Katralis, P., Komnos, I., Pilichos, G., Ravani, I., Totis, A., Apagaki, E., Efthymiadi, A., Kampagiannis, N., Paraforou, T., Tsioka, A., Georgiou, G., Vakalos, A., Bairaktari, A., Charitos, E., Markou, G., Niforopoulou, P., Papakonstantinou, N., Tsigou, E., Xifara, A., Zoulamoglou, M., Gkioni, P., Karatzas, S., Kyparissi, A., Mainas, E., Papapanagiotou, I., Papavasilopoulou, T., Fragandreas, G., Georgopoulou, E., Katsika, E., Psarras, K., Synekidou, E., Verroiotou, M., Vetsiou, E., Zaimi, D., Anagnou, A., Apostolou, K., Melissopoulou, T., Rozenberg, T., Tsigris, C., Boutsikos, G., Kalles, V., Kotsalas, N., Lavdaiou, C., Paikou, F., Panagou, G.L., Spring, A., Botis, I., Drimala, M., Georgakakis, G., Kiourtzieva, E., Ntouma, P., Prionas, A., Xouplidis, K., Dalampini, E., Giannaki, C., Iasonidou, C., Ioannidis, O., Lavrentieva, A., Papageorgiou, G., Kokkinoy, M., Stafylaraki, M., Gaitanakis, S., Karydakis, P., Paltoglou, J., Ponireas, P., Chaloulis, P., Provatidis, A., Sousana, A., Gardikou, V.V., Konstantivelli, M., Lataniotou, O., Lisari, E., Margaroni, M., Stamatiou, K., Nikolaidis, E., Pnevmatikos, I., Sertaridou, E., Andreou, A., Arkalaki, E., Athanasakis, E., Chaniotaki, F., Chatzimichali, C.A., Christofaki, M., Dermitzaki, D., Fiorentza, K., Frantzeskos, G., Geromarkaki, E., Kafkalaki, K., Kalogridaki, M., Karydi, K., Kokkini, S., Kougentakis, G., Lefaki, T., Lilitsis, E., Makatounaki, A., Malliotakis, P., Michelakis, D., Neonaki, M., Nyktari, V., Palikyra, I., Papadakis, E., Papaioannou, A., Sfakianakis, K., Sgouraki, M., Souvatzis, X., Spartinou, A., Stefanidou, N., Syrogianni, P., Tsagkaraki, G., Arnaoutoglou, E., Arnaoutoglou, C., Bali, C., Bouris, V., Doumos, R., Gkini, K.P., Kapaktsi, C., Koulouras, V., Lena, A., Lepida, D., Michos, E., Papadopoulos, D., Paschopoulos, M., Rompou, V.A., Siouti, I., Tsampalas, S., Ververidou, O., Zilis, G., Charlalampidoy, A., Christodoulidis, G., Flossos, A., Stamoulis, K., Tsang, MSC, Tsang, M.S., Lai, M.L., Yip, C.P., Heymans Chan, H.M., Law, B., Li, W.S., Chu, H.M., Koo, EGY, Lam, CCJ, Cheng, K.H., Lam, T., Chu, S., Lam, W.Y., Wong, KWK, Kwok, D., Hung, CYJ, Chan, WKJ, Wong, W.L., Chung, CKE, Ma, S.K., Kaushik, S., Shah, B., Shah, D., Shah, S., Ar, P., Muthuchellappan, R., Agarwal, V., Divatia, J., Mishra, S., Nimje, G., Pande, S., Savarkar, S., Shrivastava, A., Thomas, M., Yegnaram, S., Hidayatullah, R., Puar, N., Niman, S., Indra, I., Hamzah, Z., Yuliana, A., Abidin, U.N., Dursin, A.N., Kurnia, A., Susanti, A., Handayani, D., Alit, M.A., Arya, A., Senapathi, TGA, Utara, U.H., Wid, W.M., Wima, S., Wir, W.M., Jehosua, B., Kaunang, J., Lantang, E.Y., Najoan, R., Waworuntu, N., Awad, H., Fuad, A., Geddoa, B., Khalaf, A.R., Al Hussaini, S., Albaj, S., Kenber, M., Bettinelli, A., Spadaro, S., AlbertoVolta, C., Giancarlo, L., Sottosanti, V., Copetti, E., Spagnesi, L., Toretti, I., Alloj, C., Cardellino, S., Carmino, L., Costanzo, E., Fanfani, L.C., Novelli, M.T., Roasio, A., Bellandi, M., Bignami, E., Bocchino, S., Cabrini, L., Corti, D., Landoni, G., Meroni, R., Moizo, E., Monti, G., Pintaudi, M., Plumari, V.P., Taddeo, D., Testa, V., Winterton, D., Zangrillo, A., Cloro, L.M., Colangelo, C., Colangelo, A., Rotunno, G., Paludi, M.A., Maria, C.P., Pata, A., Parrini, V., Gatta, A., Nastasi, M., Tinti, C., Baroselli, A., Arrigo, M., Benevento, A., Bottini, C., Cannavo', M., Gastaldi, C., Marchesi, A., Pascazio, A., Pata, F., Pozzi, E., Premoli, A., Tessera, G., Boschi, L., D'Andrea, R., Ghignone, F., Poggioli, G., Sibilio, A., Taffurelli, M., Ugolini, G., Ab Majid, M.A., Ab Rahman, R., Joseph, J., Pathan, F., Sybil Shah, M.H., Yap, H.L., Cheah, S., Chin, I.I., Looi, J.K., Tan, S.C., Visvalingam, S., Kwok, F.Y., Lee, C.K., Tan, T.S., Wong, S.M., Abdullah, N.H., Liew, C.F., Luxuman, L., Mohd Zin, N.H., Norddin, M.F., Raja Alias, R.L., Wong, J.Y., Yong, J., Bin Mustapha, M.T., Chan, W.K., Dzulkipli, N., Kuan, P.X., Lee, Y.C., Alias, A., Guok, E.C., Jee, C.C., Ramon, B.R., Wong, C.W., Abd Ghafar, FNI, Aziz, F.Z., Hussain, N., Lee, H.S., Sukawi, I., Woon, Y.L., Abd Hadi, H.Z., Ahmad Azam, U.A., Alias, A.H., Kesut, S.A., Lee, J.M., Ooi, D.V., Sulaiman, H.A., Lih, TAT, Veerakumaran, J., Rojas, E., Resendiz, GEA, Zapata, DDM, López, JCJA, Flores, AAA, Amador, JCB, Avila, EJD, Aquino, LPG, Rodriguez, R.L., Landa, M.T., Urias, E., Hollmann, M., Hulst, A., Benedikt Preckel, O.K., Gemert, A.K., Buise, M., Tolenaar, N., Weber, E., de Fretes, J., Houweling, P., Ormskerk, P., Van Bommel, J., Lance, M., Smit-Fun, V., van Zundert, T., Baas, P., de Boer, H.D., Sprakel, J., Elferink-Vonk, R., Noordzij, P., van Zeggeren, L., Brand, B., Spanjersberg, R., Bokkel-Andela, J.T., Numan, S., van Klei, W., van Zaane, B., Boer, C., van Duivenvoorde, Y., Hering, J.P., van Rossum, S., Zonneveldt, H., Hoare, S., Santa, S., Ali, M., Allen, S.J., Bell, R., Choi, H.D., Drake, M., Farrell, H., Hayes, K., Higgie, K., Holmes, K., Jenkins, N., Kim, C.J., Kim, S., Law, K.C., McAllister, D., Park, K., Pedersen, K., Pfeifer, L., Pozaroszczyk, A., Salmond, T., Steynor, M., Tan, M., Waymouth, E., Ab Rahman, A.S., Armstrong, J., Dudson, R., Nilakant, J., Richard, S., Virdi, P., Dixon, L., Donohue, R., Farrow, M., Kennedy, R., Marissa, H., McKellow, M., Nicola, D., Pascoe, R., Roberts, S.J., Rowell, G., Sumner, M., Templer, P., Chandrasekharan, S., Fulton, G., Jammer, I., More, R., Wilson, L., Chang, Y.H., Foley, J., Fowler, C., Panckhurst, J., Sara, R., Stapelberg, F., Cherrett, V., Ganter, D.L., McCann, L., Gilmour, F., Lumsden, R., Moores, M., Olliff, S., Sardareva, E., Tai, J., Wikner, M., Wong, C., Chaddock, M., Czepanski, C., McKendry, P., Polakovic, D., Polakovich, D., Robert, A., Belda, M.T., Norton, T., Alherz, F., Barneto, L., Ramirez, A., Sayeed, A., Smith, N., Bennett, C., McQuoid, S., Jansen, T.L., Nico, Z., Scott, J., Freschini, D., Freschini, A., 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S., Batchelor, N., Boxall, L., Broomby, R., Deen, T., Hellewell, A., Helliwell, L., Hutchings, M., Hutchins, D., Keenan, S., Mackie, D., Potter, A., Smith, F., Stone, L., Thorpe, K., Wassall, R., Woodgate, A., Baillie, S., Campbell, T., James, S., King, C., Marques de Araujo, D., Martin, D., Morkane, C., Neely, J., Rajendram, R., Burton, M., James, K., Keevil, E., Minik, O., Morgan, J., Musgrave, A., Rajanna, H., Roberts, T., Adamson, M., Jumbe, S., Kendall, J., Muthuswamy, M.B., Cruikshanks, A., Wrench, I., Zeidan, L., Ardern, D., Harris, B., Hellstrom, J., Martin, J., Thomas, R., Varsani, N., Brown, C.W., Docherty, P., Gillies, M., McGregor, E., Usher, H., Craig, J., Ahmad, T., Bodger, P., Creary, T., Fowler, A., Ijuo, E., Jones, T., Kantsedikas, I., Lahiri, S., McLean, A.L., Niebrzegowska, E., Phull, M., Wickboldt, N., Baldwin, J., Doyle, D., Mcmullan, S., Oladapo, M., Owen, T., Williams, A., Gregory, P., Husain, T., Kirk-Bayley, J., Mathers, E., Montague, L., Harper, M., Jack, J., Ridley, C., Avis, J., Cook, T., Dali-Kemmery, L., Kerslake, I., Lambourne, V., Pearson, A., Boyd, C., Callaghan, M., Lawson, C., McCrossan, R., Nesbitt, V., O'connor, L., Sinclair, R., Farid, N., Morgese, C., Bhatia, K., Karmarkar, S., Ahmed, J., Branagan, G., Hutton, M., Swain, A., Brookes, J., Cornell, J., Dolan, R., Hulme, J., Jansen van Vuuren, A., Jowitt, T., Kalashetty, G., Lloyd, F., Patel, K., Sherwood, N., Brown, L., Chandler, B., Deighton, K., Emma, T., Haunch, K., Cheeseman, M., Dent, K., Gray, C., Hood, M., Jones, D., Juj, J., Rao, R., Walker, T., Al Anizi, M., Cheah, C., Cheing, Y., Coutinho, F., Gondo, P., Hadebe, B., Hove, M.O., Khader, A., Krishnachetty, B., Rhodes, K., Sokhi, J., Baker, K.A., Bertram, W., Looseley, A., Mouton, R., Hanna, G., Arnold, G., Arya, S., Balfoussia, D., Baxter, L., Harris, J., Jones, C., Knaggs, A., Markar, S., Perera, A., Scott, A., Shida, A., Sirha, R., Wright, S., Frost, V., Andrews, E., Arrandale, L., Barrett, S., Cifra, E., Cooper, M., 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N., Parsons, T., Piper, R., Prakash, R., Ramesh, B., Rasip, S., Reading, J., Rela, M., Reyes, A., Stephens, R., Rooms, M., Shah, K., Simons, H., Solanki, S., Spowart, E., Stevens, A., Waggett, H., Yassaee, A., Kennedy, A., Scott, S., Somanath, S., Berg, A., Hernandez, M., Nanda, R., Tank, G., Wilson, N., Wilson, D., Al-Soudaine, Y., Baldwin, M., Cornish, J., Davies, Z., Davies, L., Edwards, M., Frewer, N., Gallard, S., Glasbey, J., Harries, R., Hopkins, L., Kim, T., Koompirochana, V., Lawson, S., Lewis, M., Makzal, Z., Scourfield, S., Ahmad, Y., Bates, S., Blackwell, C., Bryant, H., Collins, H., Coulter, S., Cruickshank, R., Daniel, S., Daubeny, T., Golder, K., Hawkins, L., Helen, B., Hinxman, H., Levett, D., Salmon, K., Seaward, L., Skinner, B., Tyrell, B., Wadams, B., Walsgrove, J., Dickson, J., Constantin, K., Karen, M., O'Brien, P., O'Donohoe, L., Payne, H., Sundayi, S., Walker, E., Brooke, J., Cardy, J., Humphreys, S., Kessack, L., Kubitzek, C., Kumar, S., Cotterill, D., Hodzovic, E., Hosdurga, G., Miles, E., Saunders, G., Campbell, M., Chan, P., Jemmett, K., Raj, A., Naik, A., Oshowo, A., Ramamoorthy, R., Shah, N., Sylvan, A., Blyth, K., Burtenshaw, A., Freeman, D., Johnson, E., Lo, P., Martin, T., Plunkett, E., Wollaston, J., Allison, J., Carroll, C., Craw, N., Craw, S., Pitt-Kerby, T., Rowland-Axe, R., Spurdle, K., McDonald, A., Simon, D., Sinha, V., Banner-Goodspeed, V., Boone, M., Campbell, K., Lu, F., Scannell, J., Sobol, J., Balajonda, N., Clemmons, K., Conde, C., Elgasim, M., Funk, B., Hopkins, T., Olaleye, O., Omer, O., Pender, M., Porto, A., Waweru, P., Yeh, E., Bodansky, D., Evans, A., Kleopoulos, S., Maril, R., Mathney, E., Sanchez, A., Tinuoye, E., Bateman, B., Eng, K., Jiang, N., Ladha, K., Needleman, J., Chen, L.L., Lane, R., Robinowitz, D., Ghushe, N., Irshad, M., O'Connor, J., Patel, S., Takemoto, S., Wallace, A., Mazzeffi, M., Rock, P., Wallace, K., Chua, P., Mattera, M., Sharar, R., Thilen, S., Treggiari, M., Morgan, A., Sofjan, I., Subramaniam, K., Avidan, M., Maybrier, H., Muench, M., and Wildes, T.
Subjects: Male, Postoperative Complications/epidemiology, Hospital mortality, [SDV]Life Sciences [q-bio], surgery, Postoperative Complications, 0302 clinical medicine, cohort studies, 030202 anesthesiology, patient safety, 030212 general & internal medicine, Postoperative Period, Medicine(all), Middle Aged, Checklist, 3. Good health, Treatment Outcome, operative/mortality, Elective Surgical Procedures, Surgical Procedures, Operative, Meta-analysis, Cohort, Cohort studies, Female, Elective Surgical Procedure, postoperative care/methods, postoperative care/statistics and numerical data, surgical procedures, Anesthesiology and Pain Medicine, Cohort study, Adult, medicine.medical_specialty, Evidence-based medicine, NO, 03 medical and health sciences, Patient safety, medicine, postoperative care/method, Humans, Elective Surgical Procedures/standards, Aged, Cohort Studies, Evidence-Based Medicine, Hospital Mortality, Patient Safety, Postoperative Complications/mortality, Postoperative Complications/prevention & control, Surgical Procedures, Operative/methods, business.industry, Odds ratio, Surgery, Observational study, business, cohort studie
Abstract: BACKGROUND: The surgical safety checklist is widely used to improve the quality of perioperative care. However, clinicians continue to debate the clinical effectiveness of this tool.METHODS: Prospective analysis of data from the International Surgical Outcomes Study (ISOS), an international observational study of elective in-patient surgery, accompanied by a systematic review and meta-analysis of published literature. The exposure was surgical safety checklist use. The primary outcome was in-hospital mortality and the secondary outcome was postoperative complications. In the ISOS cohort, a multivariable multi-level generalized linear model was used to test associations. To further contextualise these findings, we included the results from the ISOS cohort in a meta-analysis. Results are reported as odds ratios (OR) with 95% confidence intervals.RESULTS: We included 44 814 patients from 497 hospitals in 27 countries in the ISOS analysis. There were 40 245 (89.8%) patients exposed to the checklist, whilst 7508 (16.8%) sustained ≥1 postoperative complications and 207 (0.5%) died before hospital discharge. Checklist exposure was associated with reduced mortality [odds ratio (OR) 0.49 (0.32-0.77); PCONCLUSIONS: Patients exposed to a surgical safety checklist experience better postoperative outcomes, but this could simply reflect wider quality of care in hospitals where checklist use is routine.
Published: 2018
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10. Single-dose human papillomavirus vaccination: an update.

Author: Kreimer AR, Watson-Jones D, Kim JJ, and Dull P
Subjects: Humans, Female, Vaccination methods, Adolescent, Cost-Benefit Analysis, Immunization Schedule, Vaccine Efficacy, Human Papillomavirus Viruses, Papillomavirus Vaccines administration & dosage, Papillomavirus Infections prevention & control, Uterine Cervical Neoplasms prevention & control, Uterine Cervical Neoplasms virology
Abstract: Human papillomavirus (HPV) vaccines received regulatory approval and were recommended for use in young girls nearly 2 decades ago. Uptake is mostly high in resource-rich settings. In resource-limited settings, where the burden of cervical cancer is disproportionately high, access to and uptake of HPV vaccines are nowhere near satisfactory, despite evidence that HPV vaccination is highly cost-effective and a significant value-for-money investment. The discovery that only a single dose of the HPV vaccines may be needed to confer adequate protection may make equitable access to HPV vaccines possible. Indeed, the recent World Health Organization recommendation allowing for 1 or 2 doses is already gaining traction. This monograph aims to update the state of the science related to single-dose HPV vaccine protection and includes both primary data and modeling efforts that address key gaps in the knowledge regarding 1) durability of protection of a single dose of the HPV vaccine, 2) single-dose HPV vaccine effectiveness in both high-income and low-income settings, 3) implementation of single-dose HPV vaccination, and 4) how to accelerate control of cervical cancer by integrating a 1-time screen for cervical disease. The content published in this monograph will continue to advance the science of HPV vaccination and will be vital as new countries make informed decisions about how best to use this remarkable vaccine., (Published by Oxford University Press 2024.)
Published: 2024
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11. Immunogenicity and Vaccine Shedding After 1 or 2 Doses of rVSVΔG-ZEBOV-GP Ebola Vaccine (ERVEBO®): Results From a Phase 2, Randomized, Placebo-controlled Trial in Children and Adults.

Author: Lee AW, Liu K, Lhomme E, Blie J, McCullough J, Onorato MT, Connor L, Simon JK, Dubey S, VanRheenen S, Deutsch J, Owens A, Morgan A, Welebob C, Hyatt D, Nair S, Hamzé B, Guindo O, Sow SO, Beavogui AH, Leigh B, Samai M, Akoo P, Serry-Bangura A, Fleck S, Secka F, Lowe B, Watson-Jones D, Roy C, Hensley LE, Kieh M, and Coller BG
Subjects: Adult, Child, Humans, Antibodies, Viral, Viral Envelope Proteins, Vaccines, Synthetic, Vaccination methods, Vaccines, Attenuated, Immunogenicity, Vaccine, Hemorrhagic Fever, Ebola, Ebola Vaccines, Ebolavirus
Abstract: Background: The rVSVΔG-ZEBOV-GP vaccine (ERVEBO®) is a single-dose, live-attenuated, recombinant vesicular stomatitis virus vaccine indicated for the prevention of Ebola virus disease (EVD) caused by Zaire ebolavirus in individuals 12 months of age and older., Methods: The Partnership for Research on Ebola VACcination (PREVAC) is a multicenter, phase 2, randomized, double-blind, placebo-controlled trial of 3 vaccine strategies in healthy children (ages 1-17) and adults, with projected 5 years of follow-up (NCT02876328). Using validated assays (GP-ELISA and PRNT), we measured antibody responses after 1-dose rVSVΔG-ZEBOV-GP, 2-dose rVSVΔG-ZEBOV-GP (given on Day 0 and Day 56), or placebo. Furthermore, we quantified vaccine virus shedding in a subset of children's saliva using RT-PCR., Results: In total, 819 children and 783 adults were randomized to receive rVSVΔG-ZEBOV-GP (1 or 2 doses) or placebo. A single dose of rVSVΔG-ZEBOV-GP increased antibody responses by Day 28 that were sustained through Month 12. A second dose of rVSVΔG-ZEBOV-GP given on Day 56 transiently boosted antibody concentrations. In vaccinated children, GP-ELISA titers were superior to placebo and non-inferior to vaccinated adults. Vaccine virus shedding was observed in 31.7% of children, peaking by Day 7, with no shedding observed after Day 28 post-dose 1 or any time post-dose 2., Conclusions: A single dose of rVSVΔG-ZEBOV-GP induced robust antibody responses in children that was non-inferior to the responses induced in vaccinated adults. Vaccine virus shedding in children was time-limited and only observed after the first dose. Overall, these data support the use of rVSVΔG-ZEBOV-GP for the prevention of EVD in at-risk children. Clinical Trials Registration. The study is registered at ClinicalTrials.gov (NCT02876328), the Pan African Clinical Trials Registry (PACTR201712002760250), and the European Clinical Trials Register (EudraCT number: 2017-001798-18)., Competing Interests: Potential conflicts of interest. K. L., M. T. O., L. C., S. D., S. V., A. O., C. W., D .H., S. N., and B.-A. C. G. are employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ USA, who may own stock and/or hold stock options in Merck & Co., Inc., Rahway, NJ, USA. A. W. L., J. K. S., J. D., and A. M. were employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA and may own/have owned stock and/or hold/held stock options in Merck & Co., Inc., Rahway, NJ, USA at the time the study was conducted. E. L., B. H., and C. R. report provision of vaccines from Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA to the academic sponsors for the PREVAC trial, but no funding directly to themselves or their institution. J. M. reports provision of sample collection kits for the study sites, provision and support of lab software, technical support and supervision of lab activities, and lab data management. S. O. S. reports payments from Leidos to his institution. P. A. reports support for attending meetings and/or travel including Air tickets and accommodations for attending study related meetings during the conduct of the study. D. W.-J reports funding from Innovative Medicines Initiative 2 Joint Undertaking, additionally D. W.-J. reports funding and donations of an HPV vaccine (Gardasil®) from Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA for another unrelated study. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
Published: 2024
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12. A high-resolution haplotype-resolved Reference panel constructed from the China Kadoorie Biobank Study.

Author: Yu C, Lan X, Tao Y, Guo Y, Sun D, Qian P, Zhou Y, Walters RG, Li L, Zhu Y, Zeng J, Millwood IY, Guo R, Pei P, Yang T, Du H, Yang F, Yang L, Ren F, Chen Y, Chen F, Jiang X, Ye Z, Dai L, Wei X, Xu X, Yang H, Wang J, Chen Z, Zhu H, Lv J, Jin X, and Li L
Subjects: Humans, Haplotypes, Genotype, Genome-Wide Association Study, Polymorphism, Single Nucleotide, China, Biological Specimen Banks, Genome
Abstract: Precision medicine depends on high-accuracy individual-level genotype data. However, the whole-genome sequencing (WGS) is still not suitable for gigantic studies due to budget constraints. It is particularly important to construct highly accurate haplotype reference panel for genotype imputation. In this study, we used 10 000 samples with medium-depth WGS to construct a reference panel that we named the CKB reference panel. By imputing microarray datasets, it showed that the CKB panel outperformed compared panels in terms of both the number of well-imputed variants and imputation accuracy. In addition, we have completed the imputation of 100 706 microarrays with the CKB panel, and the after-imputed data is the hitherto largest whole genome data of the Chinese population. Furthermore, in the GWAS analysis of real phenotype height, the number of tested SNPs tripled and the number of significant SNPs doubled after imputation. Finally, we developed an online server for offering free genotype imputation service based on the CKB reference panel (https://db.cngb.org/imputation/). We believe that the CKB panel is of great value for imputing microarray or low-coverage genotype data of Chinese population, and potentially mixed populations. The imputation-completed 100 706 microarray data are enormous and precious resources of population genetic studies for complex traits and diseases., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)
Published: 2023
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13. Adverse events during short- and long-term exposure to low-dose weekly methotrexate for rheumatic diseases.

Author: Garton M, Teoh YP, and Watson D
Published: 2023
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14. Developmental dynamics of chromatin accessibility during post-implantation development of monkey embryos.

Author: Dai X, Shao H, Sun N, Ci B, Wu J, Liu C, Wu L, Yuan Y, Wei X, Yang H, Liu L, Ji W, Bai B, Shang Z, and Tan T
Subjects: Animals, Macaca fascicularis, Transposases, Chromatin genetics, Transcription Factors
Abstract: Background: Early post-implantation development, especially gastrulation in primates, is accompanied by extensive drastic chromatin reorganization, which remains largely elusive., Results: To delineate the global chromatin landscape and understand the molecular dynamics during this period, a single-cell assay for transposase accessible chromatin sequencing (scATAC-seq) was applied to in vitro cultured cynomolgus monkey (Macaca fascicularis, hereafter referred to as monkey) embryos to investigate the chromatin status. First, we delineated the cis-regulatory interactions and identified the regulatory networks and critical transcription factors involved in the epiblast (EPI), hypoblast, and trophectoderm/trophoblast (TE) lineage specification. Second, we observed that the chromatin opening of some genome regions preceded the gene expression during EPI and trophoblast specification. Third, we identified the opposing roles of FGF and BMP signaling in pluripotency regulation during EPI specification. Finally, we revealed the similarity between EPI and TE in gene expression profiles and demonstrated that PATZ1 and NR2F2 were involved in EPI and trophoblast specification during monkey post-implantation development., Conclusions: Our findings provide a useful resource and insights into dissecting the transcriptional regulatory machinery during primate post-implantation development., (© The Author(s) 2023. Published by Oxford University Press GigaScience.)
Published: 2022
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15. Referral for Imaging in Physical Therapist Practice: Key Recommendations for Successful Implementation.

Author: Keil AP, Hazle C, Maurer A, Kittleson C, Watson D, Young B, Rezac S, Epsley S, and Baranyi B
Subjects: Humans, United States, Curriculum, Diagnostic Imaging, Interdisciplinary Communication, Musculoskeletal Diseases diagnostic imaging, Physical Therapy Modalities education, Referral and Consultation
Abstract: In recent years, the use of diagnostic imaging in physical therapist practice in the United States has gained considerable interest. In several countries around the world and in the US military, patient direct referral for diagnostic imaging has been considered normative practice for decades. US physical therapy program accreditation standards now stipulate that diagnostic imaging content must be included in physical therapist educational curricula. The American Physical Therapy Association has made efforts to pursue practice authority for imaging referral. A recent review of state practice acts and other statutory language concluded that many states have no prohibitions against physical therapists referring for imaging studies. Additionally, physical therapists can now pursue certification as musculoskeletal sonographers. In light of these advances, and with a growing number of physical therapists serving patients who have not yet seen another health care provider, it may be helpful for those who have been actively involved in the use of imaging in physical therapist practice to provide their collective recommendations to serve as a guideline to those interested in incorporating this practice privilege. The purpose of this perspective article is to provide an overview of the key elements necessary for effective implementation of referral for imaging in physical therapist practice while emphasizing the cornerstone of effective communication., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Physical Therapy Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
Published: 2021
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16. Corrigendum to: Participation in local food projects is associated with better psychological well-being: evidence from the East of England.

Author: Bharucha ZP, Weinstein N, Watson D, and Boehm S
Published: 2020
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17. Evaluating Associations Between Nonclinical Cardiovascular Functional Endpoints and Repeat-dose Cardiovascular Toxicity in the Beagle Dog: A Cross-company Initiative.

Author: Milliken P, Aylott M, Edmunds N, Engle S, Ewart L, Fleurance R, Guffroy M, Hargreaves A, Heinz-Taheny K, Kirk S, Leishman D, Leong L, McMahon N, Valentin JP, Watson D, Wallis R, and Clements P
Subjects: Animals, Blood Pressure, Dogs, Drug Evaluation, Preclinical, Electrocardiography, Heart Rate, Hemodynamics, Male, Retrospective Studies, Telemetry, Cardiovascular System drug effects, Dose-Response Relationship, Drug
Abstract: Integrating nonclinical in vitro, in silico, and in vivo datasets holistically can improve hazard characterization and risk assessment. In pharmaceutical development, cardiovascular liabilities are a leading cause of compound attrition. Prior to clinical studies, functional cardiovascular data are generated in single-dose safety pharmacology telemetry studies, with structural pathology data obtained from repeat-dose toxicology studies with limited concurrent functional endpoints, eg, electrocardiogram via jacketed telemetry. Relationships between datasets remain largely undetermined. To address this gap, a cross-pharma collaboration collated functional and structural data from 135 compounds. Retrospective functional data were collected from good laboratory practice conscious dog safety pharmacology studies: effects defined as hemodynamic blood pressure or heart rate changes. Morphologic pathology findings (mainly degeneration, vacuolation, inflammation) from related toxicology studies in the dog (3-91 days repeat-dosing) were reviewed, harmonized, and location categorized: cardiac muscle (myocardium, epicardium, endocardium, unspecified), atrioventricular/aortic valves, blood vessels. The prevalence of cardiovascular histopathology changes was 11.1% of compounds, with 53% recording a functional blood pressure or heart rate change. Correlations were assessed using the Mantel-Haenszel Chi-square trend test, identifying statistically significant associations between cardiac muscle pathology and (1) decreased blood pressure, (2) increased heart rate, and between cardiovascular vessel pathology and increased heart rate. Negative predictive values were high, suggesting few compounds cause repeat-dose cardiovascular structural change in the absence of functional effects in single-dose safety pharmacology studies. Therefore, observed functional changes could prompt moving (sub)chronic toxicology studies forward, to identify cardiovascular liabilities earlier in development, and reduce late-stage attrition., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Published: 2020
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18. Assessment of fecal DNA extraction protocols for metagenomic studies.

Author: Yang F, Sun J, Luo H, Ren H, Zhou H, Lin Y, Han M, Chen B, Liao H, Brix S, Li J, Yang H, Kristiansen K, and Zhong H
Subjects: Biodiversity, Biomarkers, High-Throughput Nucleotide Sequencing, Sequence Analysis, DNA, Feces microbiology, Gastrointestinal Microbiome, Metagenome, Metagenomics methods
Abstract: Background: Shotgun metagenomic sequencing has improved our understanding of the human gut microbiota. Various DNA extraction methods have been compared to find protocols that robustly and most accurately reflect the original microbial community structures. However, these recommendations can be further refined by considering the time and cost demands in dealing with samples from very large human cohorts. Additionally, fungal DNA extraction performance has so far been little investigated., Results: We compared 6 DNA extraction protocols, MagPure Fast Stool DNA KF Kit B, Macherey Nagel™ NucleoSpin™®Soil kit, Zymo Research Quick-DNA™ Fecal/Soil Microbe kit, MOBIO DNeasy PowerSoil kit, the manual non-commercial protocol MetaHIT, and the recently published protocol Q using 1 microbial mock community (MMC) (containing 8 bacterial and 2 fungal strains) and fecal samples. All samples were manually extracted and subjected to shotgun metagenomics sequencing. Extracting DNA revealed high reproducibility within all 6 protocols, but microbial extraction efficiencies varied. The MMC results demonstrated that bead size was a determining factor for fungal and bacterial DNA yields. In human fecal samples, the MagPure bacterial extraction performed as well as the standardized protocol Q but was faster and more cost-effective. Extraction using the PowerSoil protocol resulted in a significantly higher ratio of gram-negative to gram-positive bacteria than other protocols, which might contribute to reported gut microbial differences between healthy adults., Conclusions: We emphasize the importance of bead size selection for bacterial and fungal DNA extraction. More importantly, the performance of the novel protocol MP matched that of the recommended standardized protocol Q but consumed less time, was more cost-effective, and is recommended for further large-scale human gut metagenomic studies., (© The Author(s) 2020. Published by Oxford University Press.)
Published: 2020
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19. A catalog of microbial genes from the bovine rumen unveils a specialized and diverse biomass-degrading environment.

Author: Li J, Zhong H, Ramayo-Caldas Y, Terrapon N, Lombard V, Potocki-Veronese G, Estellé J, Popova M, Yang Z, Zhang H, Li F, Tang S, Yang F, Chen W, Chen B, Li J, Guo J, Martin C, Maguin E, Xu X, Yang H, Wang J, Madsen L, Kristiansen K, Henrissat B, Ehrlich SD, and Morgavi DP
Subjects: Animals, Biomass, Cattle, Diet, Digestion, Drug Resistance, Microbial, Humans, Mice, Swine, Gastrointestinal Microbiome genetics, Metagenome, Metagenomics methods, Microbiota genetics, Rumen microbiology
Abstract: Background: The rumen microbiota provides essential services to its host and, through its role in ruminant production, contributes to human nutrition and food security. A thorough knowledge of the genetic potential of rumen microbes will provide opportunities for improving the sustainability of ruminant production systems. The availability of gene reference catalogs from gut microbiomes has advanced the understanding of the role of the microbiota in health and disease in humans and other mammals. In this work, we established a catalog of reference prokaryote genes from the bovine rumen., Results: Using deep metagenome sequencing we identified 13,825,880 non-redundant prokaryote genes from the bovine rumen. Compared to human, pig, and mouse gut metagenome catalogs, the rumen is larger and richer in functions and microbial species associated with the degradation of plant cell wall material and production of methane. Genes encoding enzymes catalyzing the breakdown of plant polysaccharides showed a particularly high richness that is otherwise impossible to infer from available genomes or shallow metagenomics sequencing. The catalog expands the dataset of carbohydrate-degrading enzymes described in the rumen. Using an independent dataset from a group of 77 cattle fed 4 common dietary regimes, we found that only <0.1% of genes were shared by all animals, which contrast with a large overlap for functions, i.e., 63% for KEGG functions. Different diets induced differences in the relative abundance rather than the presence or absence of genes, which explains the great adaptability of cattle to rapidly adjust to dietary changes., Conclusions: These data bring new insights into functions, carbohydrate-degrading enzymes, and microbes of the rumen to complement the available information on microbial genomes. The catalog is a significant biological resource enabling deeper understanding of phenotypes and biological processes and will be expanded as new data are made available., (© The Author(s) 2020. Published by Oxford University Press.)
Published: 2020
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20. Participation in local food projects is associated with better psychological well-being: evidence from the East of England.

Author: Bharucha ZP, Weinstein N, Watson D, and Böhm S
Subjects: Diet, England, Exercise, Humans, Personal Satisfaction, Psychological Distress
Abstract: Background: Studies suggest that local food may contribute to well-being, but do not use standardized measures, or control groups., Methods: An online survey compared participants of local food initiatives (n = 302) with members of the general population (n = 157) in terms of scores on standardized measures of well-being and distress. Using hierarchical ordinary least squares regression models, we explored the relationship between participation and well-being via four mediators-nature connectedness, psychological need satisfaction, diet and physical activity., Results: Participants scored higher than non-participants on life satisfaction (t(346) = 2.30, P = 0.02, ρr = 0.12) and the WEMWBS scale (t(335) = 2.12, P = 0.04, ρr = 0.10), but differences in psychological distress were insignificant. More actively engaged participants scored higher on positive well-being and longer duration participation was associated with higher life satisfaction and less psychological distress. Finally, we found that participation contributes to psychological need satisfaction, better diet and connection to nature, three known drivers of well-being., Conclusions: Well-being may be a co-benefit of local food initiatives beyond the physical and psychological benefits of growing food. Further research is needed to explore the mediators driving these effects, quantify benefits, and track impacts over time and across different social groups., (© The Author(s) 2019. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Published: 2020
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21. Spectrum: fast density-aware spectral clustering for single and multi-omic data.

Author: John CR, Watson D, Barnes MR, Pitzalis C, and Lewis MJ
Subjects: Cluster Analysis, Humans, Single-Cell Analysis, Transcriptome, Precision Medicine, Software
Abstract: Motivation: Clustering patient omic data is integral to developing precision medicine because it allows the identification of disease subtypes. A current major challenge is the integration multi-omic data to identify a shared structure and reduce noise. Cluster analysis is also increasingly applied on single-omic data, for example, in single cell RNA-seq analysis for clustering the transcriptomes of individual cells. This technology has clinical implications. Our motivation was therefore to develop a flexible and effective spectral clustering tool for both single and multi-omic data., Results: We present Spectrum, a new spectral clustering method for complex omic data. Spectrum uses a self-tuning density-aware kernel we developed that enhances the similarity between points that share common nearest neighbours. It uses a tensor product graph data integration and diffusion procedure to reduce noise and reveal underlying structures. Spectrum contains a new method for finding the optimal number of clusters (K) involving eigenvector distribution analysis. Spectrum can automatically find K for both Gaussian and non-Gaussian structures. We demonstrate across 21 real expression datasets that Spectrum gives improved runtimes and better clustering results relative to other methods., Availability and Implementation: Spectrum is available as an R software package from CRAN https://cran.r-project.org/web/packages/Spectrum/index.html., Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author(s) 2019. Published by Oxford University Press.)
Published: 2020
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22. PIRD: Pan Immune Repertoire Database.

Author: Zhang W, Wang L, Liu K, Wei X, Yang K, Du W, Wang S, Guo N, Ma C, Luo L, Wu J, Lin L, Yang F, Gao F, Wang X, Li T, Zhang R, Saksena NK, Yang H, Wang J, Fang L, Hou Y, Xu X, and Liu X
Subjects: Antigens, Databases, Factual, Humans, Immunotherapy, High-Throughput Nucleotide Sequencing, Receptors, Antigen, T-Cell genetics
Abstract: Motivation: T and B cell receptors (TCRs and BCRs) play a pivotal role in the adaptive immune system by recognizing an enormous variety of external and internal antigens. Understanding these receptors is critical for exploring the process of immunoreaction and exploiting potential applications in immunotherapy and antibody drug design. Although a large number of samples have had their TCR and BCR repertoires sequenced using high-throughput sequencing in recent years, very few databases have been constructed to store these kinds of data. To resolve this issue, we developed a database., Results: We developed a database, the Pan Immune Repertoire Database (PIRD), located in China National GeneBank (CNGBdb), to collect and store annotated TCR and BCR sequencing data, including from Homo sapiens and other species. In addition to data storage, PIRD also provides functions of data visualization and interactive online analysis. Additionally, a manually curated database of TCRs and BCRs targeting known antigens (TBAdb) was also deposited in PIRD., Availability and Implementation: PIRD can be freely accessed at https://db.cngb.org/pird., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Published: 2020
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23. Epidemiology of Bloodstream Infections in Hospitalized Children in the United States, 2009-2016.

Author: Spaulding AB, Watson D, Dreyfus J, Heaton P, Grapentine S, Bendel-Stenzel E, and Kharbanda AB
Subjects: Adolescent, Child, Child, Preschool, Comorbidity, Cross Infection etiology, Cross Infection history, Female, Geography, Medical, History, 21st Century, Hospitalization statistics & numerical data, Humans, Infant, Male, Public Health Surveillance, Retrospective Studies, Sepsis etiology, Sepsis history, United States epidemiology, Cross Infection epidemiology, Sepsis epidemiology
Abstract: Background: Bloodstream infections (BSIs) cause significant morbidity and mortality in children. Recent pediatric epidemiological data may inform prevention strategies and empiric antimicrobial therapy selection., Methods: We conducted a retrospective cohort study from 2009 through 2016 utilizing demographic and microbiologic data on inpatients aged <19 years using the Premier Healthcare Database. BSIs were positive blood cultures without known contaminants. Hospitalization rate was the number of BSI-positive encounters per 1000 admissions. Community-acquired infections (CAIs) were cultures positive ≤2 days of admission among nonneonates. BSI patients were compared to documented positive BSI patients (non-BSI); differences were analyzed using χ2 test, t test, and Cochran-Armitage test for time trends., Results: Among 1 809 751 encounters from 162 US hospitals, 5340 (0.30%) were BSI positive; CAIs were most common (50%). BSI patients were more often aged 1-5 years and had complex chronic conditions or central lines compared to non-BSI patients. The BSI hospitalization rate declined nonsignificantly over time (3.13 in 2009 to 2.98 in 2016, P = .08). Among pathogens, Escherichia coli (0.80 to 1.26), methicillin-sensitive Staphylococcus aureus (0.83 to 1.98), and group A Streptococcus (0.16 to 0.37) significantly increased for nonneonates, while Streptococcus pneumoniae (1.07 to 0.26) and Enterococcus spp. (0.60 to 0.17) declined. Regional differences were greatest for E. coli and highest in the New England and South Atlantic regions., Conclusions: Trends in pediatric BSI hospitalization rates varied by pathogen and regionally. Overall the BSI hospitalization rate did not significantly decline, indicating a continued need to improve pediatric BSI assessment and prevention., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)
Published: 2019
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24. Development of coupling controlled polymerizations by adapter-ligation in mate-pair sequencing for detection of various genomic variants in one single assay.

Author: Dong Z, Zhao X, Li Q, Yang Z, Xi Y, Alexeev A, Shen H, Wang O, Ruan J, Ren H, Wei H, Qi X, Li J, Zhu X, Zhang Y, Dai P, Kong X, Kirkconnell K, Alferov O, Giles S, Yamtich J, Kermani BG, Dong C, Liu P, Mi Z, Zhang W, Xu X, Drmanac R, Choy KW, and Jiang Y
Subjects: Genetic Predisposition to Disease, Humans, Infertility, Male genetics, Male, Genome-Wide Association Study methods, Genotyping Techniques methods, Polymorphism, Single Nucleotide, Sequence Analysis, DNA methods
Abstract: The diversity of disease presentations warrants one single assay for detection and delineation of various genomic disorders. Herein, we describe a gel-free and biotin-capture-free mate-pair method through coupling Controlled Polymerizations by Adapter-Ligation (CP-AL). We first demonstrated the feasibility and ease-of-use in monitoring DNA nick translation and primer extension by limiting the nucleotide input. By coupling these two controlled polymerizations by a reported non-conventional adapter-ligation reaction 3' branch ligation, we evidenced that CP-AL significantly increased DNA circularization efficiency (by 4-fold) and was applicable for different sequencing methods but at a faction of current cost. Its advantages were further demonstrated by fully elimination of small-insert-contaminated (by 39.3-fold) with a ∼50% increment of physical coverage, and producing uniform genome/exome coverage and the lowest chimeric rate. It achieved single-nucleotide variants detection with sensitivity and specificity up to 97.3 and 99.7%, respectively, compared with data from small-insert libraries. In addition, this method can provide a comprehensive delineation of structural rearrangements, evidenced by a potential diagnosis in a patient with oligo-atheno-terato-spermia. Moreover, it enables accurate mutation identification by integration of genomic variants from different aberration types. Overall, it provides a potential single-integrated solution for detecting various genomic variants, facilitating a genetic diagnosis in human diseases., (© The Author(s) 2019. Published by Oxford University Press on behalf of Kazusa DNA Research Institute.)
Published: 2019
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25. A Rare Deep-Rooting D0 African Y-Chromosomal Haplogroup and Its Implications for the Expansion of Modern Humans Out of Africa.

Author: Haber M, Jones AL, Connell BA, Asan, Arciero E, Yang H, Thomas MG, Xue Y, and Tyler-Smith C
Subjects: Humans, Male, Nigeria, Phylogeny, Polymorphism, Genetic, Chromosomes, Human, Y genetics, Evolution, Molecular, Haplotypes, Human Migration
Abstract: Present-day humans outside Africa descend mainly from a single expansion out ∼50,000-70,000 years ago, but many details of this expansion remain unclear, including the history of the male-specific Y chromosome at this time. Here, we reinvestigate a rare deep-rooting African Y-chromosomal lineage by sequencing the whole genomes of three Nigerian men described in 2003 as carrying haplogroup DE* Y chromosomes, and analyzing them in the context of a calibrated worldwide Y-chromosomal phylogeny. We confirm that these three chromosomes do represent a deep-rooting DE lineage, branching close to the DE bifurcation, but place them on the D branch as an outgroup to all other known D chromosomes, and designate the new lineage D0. We consider three models for the expansion of Y lineages out of Africa ∼50,000-100,000 years ago, incorporating migration back to Africa where necessary to explain present-day Y-lineage distributions. Considering both the Y-chromosomal phylogenetic structure incorporating the D0 lineage, and published evidence for modern humans outside Africa, the most favored model involves an origin of the DE lineage within Africa with D0 and E remaining there, and migration out of the three lineages (C, D, and FT) that now form the vast majority of non-African Y chromosomes. The exit took place 50,300-81,000 years ago (latest date for FT lineage expansion outside Africa - earliest date for the D/D0 lineage split inside Africa), and most likely 50,300-59,400 years ago (considering Neanderthal admixture). This work resolves a long-running debate about Y-chromosomal out-of-Africa/back-to-Africa migrations, and provides insights into the out-of-Africa expansion more generally., (Copyright © Haber et al.)
Published: 2019
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26. Safety and Immunogenicity of a 2-Dose Heterologous Vaccination Regimen With Ad26.ZEBOV and MVA-BN-Filo Ebola Vaccines: 12-Month Data From a Phase 1 Randomized Clinical Trial in Uganda and Tanzania.

Author: Anywaine Z, Whitworth H, Kaleebu P, Praygod G, Shukarev G, Manno D, Kapiga S, Grosskurth H, Kalluvya S, Bockstal V, Anumendem D, Luhn K, Robinson C, Douoguih M, and Watson-Jones D
Subjects: Adolescent, Adult, Antibodies, Neutralizing immunology, Antibodies, Viral immunology, Disease Outbreaks prevention & control, Female, Healthy Volunteers, Hemorrhagic Fever, Ebola virology, Humans, Male, Middle Aged, Tanzania, Uganda, Vaccination adverse effects, Vaccines, DNA, Viral Vaccines adverse effects, Young Adult, Antibody Formation immunology, Ebola Vaccines adverse effects, Ebola Vaccines immunology, Ebolavirus immunology, Hemorrhagic Fever, Ebola immunology, Viral Vaccines immunology
Abstract: Background: Ebola vaccine development was accelerated in response to the 2014 Ebola virus infection outbreak. This phase 1 study (VAC52150EBL1004) assessed safety, tolerability, and immunogenicity of heterologous 2-dose Ad26.ZEBOV, MVA-BN-Filo vaccination regimens in the Lake Victoria Basin of Tanzania and Uganda in mid-level altitude, malaria-endemic settings., Methods: Healthy volunteers aged 18-50 years from Tanzania (n = 25) and Uganda (n = 47) were randomized to receive placebo or active vaccination with Ad26.ZEBOV or MVA-BN-Filo (first vaccination), followed by MVA-BN-Filo or Ad26.ZEBOV (second vaccination) dose 2, respectively, with intervals of 28 or 56 days., Results: Seventy-two adults were randomized to receive vaccine (n = 60) or placebo (n = 12). No vaccine-related serious adverse events were reported. The most frequent solicited local and systemic adverse events were injection site pain (frequency, 70%, 66%, and 42% per dose for MVA-BN-Filo, Ad26.ZEBOV, and placebo, respectively) and headache (57%, 56%, and 46%, respectively). Adverse event patterns were similar among regimens. Twenty-one days after dose 2, 100% of volunteers demonstrated binding antibody responses against Ebola virus glycoprotein, and 87%-100% demonstrated neutralizing antibody responses. Ad26.ZEBOV dose 1 vaccination induced more-robust initial binding antibody and cellular responses than MVA-BN-Filo dose 1 vaccination., Conclusions: Heterologous 2-dose vaccination with Ad26.ZEBOV and MVA-BN-Filo against Ebola virus is well tolerated and immunogenic in healthy volunteers., Clinical Trials Registration: NCT02376400., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.)
Published: 2019
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27. THE AUTHORS REPLY.

Author: Watson D, Spaulding AB, and Dreyfus J
Subjects: Humans, Bacteremia, Cross Infection
Published: 2019
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28. Single-cell transcriptomic landscape of nucleated cells in umbilical cord blood.

Author: Zhao Y, Li X, Zhao W, Wang J, Yu J, Wan Z, Gao K, Yi G, Wang X, Fan B, Wu Q, Chen B, Xie F, Wu J, Zhang W, Chen F, Yang H, Wang J, Xu X, Li B, Liu S, Hou Y, and Liu X
Subjects: Cell Lineage genetics, Cell Proliferation genetics, Erythroblasts pathology, Fetal Blood transplantation, Gene Expression Regulation genetics, Granzymes genetics, High-Throughput Nucleotide Sequencing, Humans, Erythroblasts metabolism, Fetal Blood metabolism, Single-Cell Analysis, Transcriptome genetics
Abstract: Background: For both pediatric and adult patients, umbilical cord blood (UCB) transplant is a therapeutic option for a variety of hematologic diseases, such as blood cancers, myeloproliferative disorders, genetic diseases, and metabolic disorders. However, the level of cellular heterogeneity and diversity of nucleated cells in UCB has not yet been assessed in an unbiased and systemic fashion. In the present study, nucleated cells from UCB were subjected to single-cell RNA sequencing to simultaneously profile the gene expression signatures of thousands of cells, generating a rich resource for further functional studies. Here, we report the transcriptomes of 17,637 UCB cells, covering 12 major cell types, many of which can be further divided into distinct subpopulations., Results: Pseudotemporal ordering of nucleated red blood cells identifies wave-like activation and suppression of transcription regulators, leading to a polarized cellular state, which may reflect nucleated red blood cell maturation. Progenitor cells in UCB also comprise 2 subpopulations with activation of divergent transcription programs, leading to specific cell fate commitment. Detailed profiling of cytotoxic cell populations unveiled granzymes B and K signatures in natural killer and natural killer T-cell types in UCB., Conclusions: Taken together, our data form a comprehensive single-cell transcriptomic landscape that reveals previously unrecognized cell types, pathways, and mechanisms of gene expression regulation. These data may contribute to the efficacy and outcome of UCB transplant, broadening the scope of research and clinical innovations., (© The Author(s) 2019. Published by Oxford University Press.)
Published: 2019
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29. Correction to: Deep whole-genome sequencing of 90 Han Chinese Genomes.

Author: Lan T, Lin H, Zhu W, Tellier LCAM, Yang M, Liu X, Wang J, Wang J, Yang H, Xu X, and Guo X
Published: 2019
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30. Risk-Set Matching to Assess the Impact of Hospital-Acquired Bloodstream Infections.

Author: Watson D, Spaulding AB, and Dreyfus J
Subjects: Catheter-Related Infections economics, Catheter-Related Infections epidemiology, Cross Infection economics, Cross Infection mortality, Hospital Costs statistics & numerical data, Humans, Length of Stay economics, Propensity Score, Proportional Hazards Models, Sepsis economics, Sepsis mortality, Time Factors, Cross Infection epidemiology, Epidemiologic Methods, Sepsis epidemiology
Abstract: Hospital-acquired bloodstream infections have a definite impact on patient encounters and cause increased length of stay, costs, and mortality. However, methods for estimating these effects are potentially biased, especially if the time of infection is not incorporated into the estimation strategy. We focused on matching patient encounters in which a hospital-acquired infection occurred to comparable encounters in which an infection did not occur. This matching strategy is susceptible to a selection bias because inpatients that stay longer in the hospital are more likely to acquire an infection and thus also are more likely to have longer and more costly stays. Instead, we have proposed risk-set matching, which matches infected encounters to similar encounters still at risk for infection at the corresponding time of infection. Matching on the one-dimensional propensity score can create comparable pairs for a large number of characteristics; an analogous propensity score is described for risk-set matching. We have presented dramatically different estimates using these 2 approaches with data from a pediatric cohort from the Premier Healthcare Database, United States, 2009-2016. The results suggest that estimates that did not incorporate time of infection exaggerated the impact of hospital-acquired infections with regard to attributed length of stay and costs.
Published: 2019
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31. CRISPR-C: circularization of genes and chromosome by CRISPR in human cells.

Author: Møller HD, Lin L, Xiang X, Petersen TS, Huang J, Yang L, Kjeldsen E, Jensen UB, Zhang X, Liu X, Xu X, Wang J, Yang H, Church GM, Bolund L, Regenberg B, and Luo Y
Subjects: Base Sequence, Biosensing Techniques, CRISPR-Associated Protein 9 metabolism, Cell Line, Chromosomes, Human, Pair 18 chemistry, Chromosomes, Human, Pair 18 metabolism, DNA End-Joining Repair, DNA, Circular metabolism, Fibroblasts, Fluorescent Dyes chemistry, Fluorescent Dyes metabolism, Genes, Reporter, Genetic Loci, Genetic Vectors chemistry, Genetic Vectors metabolism, Genome, Human, Green Fluorescent Proteins genetics, Green Fluorescent Proteins metabolism, HEK293 Cells, Humans, Luminescent Proteins genetics, Luminescent Proteins metabolism, RNA, Guide, CRISPR-Cas Systems genetics, RNA, Guide, CRISPR-Cas Systems metabolism, CRISPR-Associated Protein 9 genetics, CRISPR-Cas Systems, Clustered Regularly Interspaced Short Palindromic Repeats, DNA, Circular genetics, Gene Editing methods
Abstract: Extrachromosomal circular DNA (eccDNA) and ring chromosomes are genetic alterations found in humans with genetic disorders. However, there is a lack of genetic engineering tools to recapitulate and study the biogenesis of eccDNAs. Here, we created a dual-fluorescence biosensor cassette, which upon the delivery of pairs of CRISPR/Cas9 guide RNAs, CRISPR-C, allows us to study the biogenesis of a specific fluorophore expressing eccDNA in human cells. We show that CRISPR-C can generate functional eccDNA, using the novel eccDNA biosensor system. We further reveal that CRISPR-C also can generate eccDNAs from intergenic and genic loci in human embryonic kidney 293T cells and human mammary fibroblasts. EccDNAs mainly forms by end-joining mediated DNA-repair and we show that CRISPR-C is able to generate endogenous eccDNAs in sizes from a few hundred base pairs and ranging up to 207 kb. Even a 47.4 megabase-sized ring chromosome 18 can be created by CRISPR-C. Our study creates a new territory for CRISPR gene editing and highlights CRISPR-C as a useful tool for studying the cellular impact, persistence and function of eccDNAs.
Published: 2018
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32. Genomic Takeover by Transposable Elements in the Strawberry Poison Frog.

Author: Rogers RL, Zhou L, Chu C, Márquez R, Corl A, Linderoth T, Freeborn L, MacManes MD, Xiong Z, Zheng J, Guo C, Xun X, Kronforst MR, Summers K, Wu Y, Yang H, Richards-Zawacki CL, Zhang G, and Nielsen R
Subjects: Animals, Evolution, Molecular, Ion Channels genetics, RNA, Small Interfering, Spliceosomes genetics, Anura genetics, DNA Transposable Elements, Gene Transfer, Horizontal
Abstract: We sequenced the genome of the strawberry poison frog, Oophaga pumilio, at a depth of 127.5× using variable insert size libraries. The total genome size is estimated to be 6.76 Gb, of which 4.76 Gb are from high copy number repetitive elements with low differentiation across copies. These repeats encompass DNA transposons, RNA transposons, and LTR retrotransposons, including at least 0.4 and 1.0 Gb of Mariner/Tc1 and Gypsy elements, respectively. Expression data indicate high levels of gypsy and Mariner/Tc1 expression in ova of O. pumilio compared with Xenopus laevis. We further observe phylogenetic evidence for horizontal transfer (HT) of Mariner elements, possibly between fish and frogs. The elements affected by HT are present in high copy number and are highly expressed, suggesting ongoing proliferation after HT. Our results suggest that the large amphibian genome sizes, at least partially, can be explained by a process of repeated invasion of new transposable elements that are not yet suppressed in the germline. We also find changes in the spliceosome that we hypothesize are related to permissiveness of O. pumilio to increases in intron length due to transposon proliferation. Finally, we identify the complement of ion channels in the first genomic sequenced poison frog and discuss its relation to the evolution of autoresistance to toxins sequestered in the skin.
Published: 2018
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33. Chromosome-level reference genome of the Siamese fighting fish Betta splendens, a model species for the study of aggression.

Author: Fan G, Chan J, Ma K, Yang B, Zhang H, Yang X, Shi C, Chun-Hin Law H, Ren Z, Xu Q, Liu Q, Wang J, Chen W, Shao L, Gonçalves D, Ramos A, Cardoso SD, Guo M, Cai J, Xu X, Wang J, Yang H, Liu X, and Wang Y
Subjects: Aggression physiology, Animals, Fish Proteins classification, Fish Proteins genetics, Fishes physiology, Genomics methods, Models, Animal, Phylogeny, Sequence Analysis, DNA methods, Chromosomes genetics, Fishes genetics, Genome genetics, Genome Size
Abstract: Background: Siamese fighting fish Betta splendens are notorious for their aggressiveness and accordingly have been widely used to study aggression. However, the lack of a reference genome has, to date, limited the understanding of the genetic basis of aggression in this species. Here, we present the first reference genome assembly of the Siamese fighting fish., Findings: Frist, we sequenced and de novo assembled a 465.24-Mb genome for the B. splendens variety Giant, with a weighted average (N50) scaffold size of 949.03 Kb and an N50 contig size of 19.01 Kb, covering 99.93% of the estimated genome size. To obtain a chromosome-level genome assembly, we constructed one Hi-C library and sequenced 75.24 Gb reads using the BGISEQ-500 platform. We anchored approximately 93% of the scaffold sequences into 21 chromosomes and evaluated the quality of our assembly using the high-contact frequency heat map and Benchmarking Universal Single-Copy Orthologs. We also performed comparative chromosome analyses between Oryzias latipes and B. splendens, revealing a chromosome conservation evolution in B. splendens. We predicted 23,981 genes assisted by RNA-sequencing data generated from brain, liver, muscle, and heart tissues of Giant and annotated 15% repetitive sequences in the genome. Additionally, we resequenced five other B. splendens varieties and detected ∼3.4 M single-nucleotide variations and 27,305 insertions and deletions., Conclusions: We provide the first chromosome-level genome for the Siamese fighting fish. The genome will lay a valuable foundation for future research on aggression in B. splendens.
Published: 2018
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34. MetaPGN: a pipeline for construction and graphical visualization of annotated pangenome networks.

Author: Peng Y, Tang S, Wang D, Zhong H, Jia H, Cai X, Zhang Z, Xiao M, Yang H, Wang J, Kristiansen K, Xu X, and Li J
Subjects: Escherichia coli genetics, Genome, Bacterial genetics, Humans, Metagenome genetics, Metagenomics methods, Reproducibility of Results, Software, Computational Biology methods, Gene Regulatory Networks, Genome genetics, Genomics methods
Abstract: Pangenome analyses facilitate the interpretation of genetic diversity and evolutionary history of a taxon. However, there is an urgent and unmet need to develop new tools for advanced pangenome construction and visualization, especially for metagenomic data. Here, we present an integrated pipeline, named MetaPGN, for construction and graphical visualization of pangenome networks from either microbial genomes or metagenomes. Given either isolated genomes or metagenomic assemblies coupled with a reference genome of the targeted taxon, MetaPGN generates a pangenome in a topological network, consisting of genes (nodes) and gene-gene genomic adjacencies (edges) of which biological information can be easily updated and retrieved. MetaPGN also includes a self-developed Cytoscape plugin for layout of and interaction with the resulting pangenome network, providing an intuitive and interactive interface for full exploration of genetic diversity. We demonstrate the utility of MetaPGN by constructing Escherichia coli pangenome networks from five E. coli pathogenic strains and 760 human gut microbiomes,revealing extensive genetic diversity of E. coli within both isolates and gut microbial populations. With the ability to extract and visualize gene contents and gene-gene physical adjacencies of a specific taxon from large-scale metagenomic data, MetaPGN provides advantages in expanding pangenome analysis to uncultured microbial taxa.
Published: 2018
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35. Single-cell RNA-seq reveals dynamic transcriptome profiling in human early neural differentiation.

Author: Shang Z, Chen D, Wang Q, Wang S, Deng Q, Wu L, Liu C, Ding X, Wang S, Zhong J, Zhang D, Cai X, Zhu S, Yang H, Liu L, Fink JL, Chen F, Liu X, Gao Z, and Xu X
Subjects: Biomarkers, Cell Communication genetics, Cell Line, Cellular Reprogramming genetics, Computational Biology methods, Gene Regulatory Networks, Humans, Induced Pluripotent Stem Cells, Neural Stem Cells cytology, Neural Stem Cells metabolism, Cell Differentiation, Gene Expression Profiling, High-Throughput Nucleotide Sequencing, Neurons metabolism, Single-Cell Analysis methods, Transcriptome
Abstract: Background: Investigating cell fate decision and subpopulation specification in the context of the neural lineage is fundamental to understanding neurogenesis and neurodegenerative diseases. The differentiation process of neural-tube-like rosettes in vitro is representative of neural tube structures, which are composed of radially organized, columnar epithelial cells and give rise to functional neural cells. However, the underlying regulatory network of cell fate commitment during early neural differentiation remains elusive., Results: In this study, we investigated the genome-wide transcriptome profile of single cells from six consecutive reprogramming and neural differentiation time points and identified cellular subpopulations present at each differentiation stage. Based on the inferred reconstructed trajectory and the characteristics of subpopulations contributing the most toward commitment to the central nervous system lineage at each stage during differentiation, we identified putative novel transcription factors in regulating neural differentiation. In addition, we dissected the dynamics of chromatin accessibility at the neural differentiation stages and revealed active cis-regulatory elements for transcription factors known to have a key role in neural differentiation as well as for those that we suggest are also involved. Further, communication network analysis demonstrated that cellular interactions most frequently occurred in the embryoid body stage and that each cell subpopulation possessed a distinctive spectrum of ligands and receptors associated with neural differentiation that could reflect the identity of each subpopulation., Conclusions: Our study provides a comprehensive and integrative study of the transcriptomics and epigenetics of human early neural differentiation, which paves the way for a deeper understanding of the regulatory mechanisms driving the differentiation of the neural lineage.
Published: 2018
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36. Enhancing Psychosis-Spectrum Nosology Through an International Data Sharing Initiative.

Author: Docherty AR, Fonseca-Pedrero E, Debbané M, Chan RCK, Linscott RJ, Jonas KG, Cicero DC, Green MJ, Simms LJ, Mason O, Watson D, Ettinger U, Waszczuk M, Rapp A, Grant P, Kotov R, DeYoung CG, Ruggero CJ, Eaton NR, Krueger RF, Patrick C, Hopwood C, O'Neill FA, Zald DH, Conway CC, Adkins DE, Waldman ID, van Os J, Sullivan PF, Anderson JS, Shabalin AA, Sponheim SR, Taylor SF, Grazioplene RG, Bacanu SA, Bigdeli TB, Haenschel C, Malaspina D, Gooding DC, Nicodemus K, Schultze-Lutter F, Barrantes-Vidal N, Mohr C, Carpenter WT, and Cohen AS
Subjects: Humans, Information Dissemination, Intersectoral Collaboration, Datasets as Topic, Models, Theoretical, Psychotic Disorders classification, Schizophrenia classification, Schizotypal Personality Disorder classification
Abstract: The latent structure of schizotypy and psychosis-spectrum symptoms remains poorly understood. Furthermore, molecular genetic substrates are poorly defined, largely due to the substantial resources required to collect rich phenotypic data across diverse populations. Sample sizes of phenotypic studies are often insufficient for advanced structural equation modeling approaches. In the last 50 years, efforts in both psychiatry and psychological science have moved toward (1) a dimensional model of psychopathology (eg, the current Hierarchical Taxonomy of Psychopathology [HiTOP] initiative), (2) an integration of methods and measures across traits and units of analysis (eg, the RDoC initiative), and (3) powerful, impactful study designs maximizing sample size to detect subtle genomic variation relating to complex traits (the Psychiatric Genomics Consortium [PGC]). These movements are important to the future study of the psychosis spectrum, and to resolving heterogeneity with respect to instrument and population. The International Consortium of Schizotypy Research is composed of over 40 laboratories in 12 countries, and to date, members have compiled a body of schizotypy- and psychosis-related phenotype data from more than 30000 individuals. It has become apparent that compiling data into a protected, relational database and crowdsourcing analytic and data science expertise will result in significant enhancement of current research on the structure and biological substrates of the psychosis spectrum. The authors present a data-sharing infrastructure similar to that of the PGC, and a resource-sharing infrastructure similar to that of HiTOP. This report details the rationale and benefits of the phenotypic data collective and presents an open invitation for participation.
Published: 2018
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37. The metagenome of the female upper reproductive tract.

Author: Li F, Chen C, Wei W, Wang Z, Dai J, Hao L, Song L, Zhang X, Zeng L, Du H, Tang H, Liu N, Yang H, Wang J, Madsen L, Brix S, Kristiansen K, Xu X, Li J, Wu R, and Jia H
Subjects: Biodiversity, Computational Biology methods, Female, High-Throughput Nucleotide Sequencing, Humans, Vagina microbiology, Metagenome, Metagenomics methods, Microbiota, Reproductive Tract Infections microbiology
Abstract: Background: The human uterus is traditionally believed to be sterile, while the vaginal microbiota plays an important role in fending off pathogens. Emerging evidence demonstrates the presence of bacteria beyond the vagina. However, a microbiome-wide metagenomic analysis characterizing the diverse microbial communities has been lacking., Results: We performed shotgun-sequencing of 52 samples from the cervical canal and the peritoneal fluid of Chinese women of reproductive age using the Illumina platform. Direct annotation of sequencing reads identified the taxonomy of bacteria, archaea, fungi and viruses, confirming and extending the results from our previous study. We replicated our previous findings in another 24 samples from the vagina, the cervical canal, the uterus and the peritoneal fluid using the BGISEQ-500 platform revealing that microorganisms in the samples from the same individuals were largely shared in the entire reproductive tract. Human sequences made up more than 99% of the 20GB raw data. After filtering, vaginal microorganisms were well covered in the generated reproductive tract gene catalogue, while the more diverse upper reproductive tract microbiota would require greater depth of sequencing and more samples to meet the full coverage scale., Conclusions: We provide novel detailed data on the microbial composition of a largely unchartered body site, the female reproductive tract. Our results indicated the presence of an intra-individual continuum of microorganisms that gradually changed from the vagina to the peritoneal fluid. This study also provides a framework for understanding the implications of the composition and functional potential of the distinct microbial ecosystems of the female reproductive tract in relation to health and disease.
Published: 2018
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38. Establishment of a Macaca fascicularis gut microbiome gene catalog and comparison with the human, pig, and mouse gut microbiomes.

Author: Li X, Liang S, Xia Z, Qu J, Liu H, Liu C, Yang H, Wang J, Madsen L, Hou Y, Li J, Jia H, Kristiansen K, and Xiao L
Subjects: Animals, Humans, Macaca fascicularis, Mice, Swine, Bacteria classification, Bacteria genetics, Gastrointestinal Microbiome genetics, Genes, Bacterial
Abstract: Macaca fascicularis, the cynomolgus macaque, is a widely used model in biomedical research and drug development as its genetics and physiology are close to those of humans. Detailed information on the cynomolgus macaque gut microbiota, the functional interplay between the gut microbiota and host physiology, and possible similarities to humans and other mammalians is very limited. The aim of this study was to construct the first cynomolgus macaque gut microbial gene catalog and compare this catalog to the human, pig, and mouse gut microbial gene catalogs. We performed metagenomic sequencing on fecal samples from 20 cynomolgus macaques and identified 1.9 million non-redundant bacterial genes of which 39.49% and 25.45% are present in the human and pig gut bacterial gene catalogs, respectively, whereas only 0.6% of the genes are present in the mouse gut bacterial gene catalog. By contrast, at the functional levels, more than 76% Kyoto Encyclopedia of Genes and Genomes orthologies are shared between the gut microbiota of all four mammalians. Thirty-two highly abundant bacterial genera could be defined as core genera of these mammalians. We demonstrated significant differences in the composition and functional potential of the gut microbiota as well as in the distribution of predicted bacterial phage sequences in cynomolgus macaques fed either a low-fat/high-fiber diet or a high-fat/low-fiber diet. Interestingly, the gut microbiota of cynomolgus macaques fed the high-fat/low-fiber diet became more similar to the gut microbiota of humans.
Published: 2018
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39. Demographic History and Genetic Adaptation in the Himalayan Region Inferred from Genome-Wide SNP Genotypes of 49 Populations.

Author: Arciero E, Kraaijenbrink T, Asan, Haber M, Mezzavilla M, Ayub Q, Wang W, Pingcuo Z, Yang H, Wang J, Jobling MA, van Driem G, Xue Y, de Knijff P, and Tyler-Smith C
Subjects: Bhutan, Genetic Drift, Humans, Nepal, Phylogeography, Population Dynamics, Tibet, Adaptation, Biological, Altitude, Genome, Human, Polymorphism, Single Nucleotide
Abstract: We genotyped 738 individuals belonging to 49 populations from Nepal, Bhutan, North India, or Tibet at over 500,000 SNPs, and analyzed the genotypes in the context of available worldwide population data in order to investigate the demographic history of the region and the genetic adaptations to the harsh environment. The Himalayan populations resembled other South and East Asians, but in addition displayed their own specific ancestral component and showed strong population structure and genetic drift. We also found evidence for multiple admixture events involving Himalayan populations and South/East Asians between 200 and 2,000 years ago. In comparisons with available ancient genomes, the Himalayans, like other East and South Asian populations, showed similar genetic affinity to Eurasian hunter-gatherers (a 24,000-year-old Upper Palaeolithic Siberian), and the related Bronze Age Yamnaya. The high-altitude Himalayan populations all shared a specific ancestral component, suggesting that genetic adaptation to life at high altitude originated only once in this region and subsequently spread. Combining four approaches to identifying specific positively selected loci, we confirmed that the strongest signals of high-altitude adaptation were located near the Endothelial PAS domain-containing protein 1 and Egl-9 Family Hypoxia Inducible Factor 1 loci, and discovered eight additional robust signals of high-altitude adaptation, five of which have strong biological functional links to such adaptation. In conclusion, the demographic history of Himalayan populations is complex, with strong local differentiation, reflecting both genetic and cultural factors; these populations also display evidence of multiple genetic adaptations to high-altitude environments.
Published: 2018
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40. Population genomic data reveal genes related to important traits of quail.

Author: Wu Y, Zhang Y, Hou Z, Fan G, Pi J, Sun S, Chen J, Liu H, Du X, Shen J, Hu G, Chen W, Pan A, Yin P, Chen X, Pu Y, Zhang H, Liang Z, Jian J, Zhang H, Wu B, Sun J, Chen J, Tao H, Yang T, Xiao H, Yang H, Zheng C, Bai M, Fang X, Burt DW, Wang W, Li Q, Xu X, Li C, Yang H, Wang J, Yang N, Liu X, and Du J
Subjects: Amino Acid Sequence, Animals, Biological Evolution, Chromosomes genetics, Feathers physiology, Genome, Genome-Wide Association Study, Immune System metabolism, Multigene Family, Nucleotides genetics, Phylogeny, Pigmentation genetics, Polymorphism, Single Nucleotide genetics, Selection, Genetic, Sexual Maturation genetics, Species Specificity, Genetics, Population, Genomics methods, Quail genetics, Quantitative Trait, Heritable
Abstract: Background: Japanese quail (Coturnix japonica), a recently domesticated poultry species, is important not only as an agricultural product, but also as a model bird species for genetic research. However, most of the biological questions concerning genomics, phylogenetics, and genetics of some important economic traits have not been answered. It is thus necessary to complete a high-quality genome sequence as well as a series of comparative genomics, evolution, and functional studies., Results: Here, we present a quail genome assembly spanning 1.04 Gb with 86.63% of sequences anchored to 30 chromosomes (28 autosomes and 2 sex chromosomes Z/W). Our genomic data have resolved the long-term debate of phylogeny among Perdicinae (Japanese quail), Meleagridinae (turkey), and Phasianinae (chicken). Comparative genomics and functional genomic data found that four candidate genes involved in early maturation had experienced positive selection, and one of them encodes follicle stimulating hormone beta (FSHβ), which is correlated with different FSHβ levels in quail and chicken. We re-sequenced 31 quails (10 wild, 11 egg-type, and 10 meat-type) and identified 18 and 26 candidate selective sweep regions in the egg-type and meat-type lines, respectively. That only one of them is shared between egg-type and meat-type lines suggests that they were subject to an independent selection. We also detected a haplotype on chromosome Z, which was closely linked with maroon/yellow plumage in quail using population resequencing and a genome-wide association study. This haplotype block will be useful for quail breeding programs., Conclusions: This study provided a high-quality quail reference genome, identified quail-specific genes, and resolved quail phylogeny. We have identified genes related to quail early maturation and a marker for plumage color, which is significant for quail breeding. These results will facilitate biological discovery in quails and help us elucidate the evolutionary processes within the Phasianidae family.
Published: 2018
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41. Congenital hypogonadotropic hypogonadism and constitutional delay of growth and puberty have distinct genetic architectures.

Author: Cassatella D, Howard SR, Acierno JS, Xu C, Papadakis GE, Santoni FA, Dwyer AA, Santini S, Sykiotis GP, Chambion C, Meylan J, Marino L, Favre L, Li J, Liu X, Zhang J, Bouloux PM, Geyter C, Paepe A, Dhillo WS, Ferrara JM, Hauschild M, Lang-Muritano M, Lemke JR, Flück C, Nemeth A, Phan-Hug F, Pignatelli D, Popovic V, Pekic S, Quinton R, Szinnai G, l'Allemand D, Konrad D, Sharif S, Iyidir ÖT, Stevenson BJ, Yang H, Dunkel L, and Pitteloud N
Subjects: Adult, Aged, Cohort Studies, Female, Finland epidemiology, Growth Disorders epidemiology, Humans, Hypogonadism epidemiology, Male, Middle Aged, Mutation genetics, Puberty, Delayed epidemiology, Growth Disorders diagnosis, Growth Disorders genetics, Hypogonadism diagnosis, Hypogonadism genetics, Puberty, Delayed diagnosis, Puberty, Delayed genetics
Abstract: Objective: Congenital hypogonadotropic hypogonadism (CHH) and constitutional delay of growth and puberty (CDGP) represent rare and common forms of GnRH deficiency, respectively. Both CDGP and CHH present with delayed puberty, and the distinction between these two entities during early adolescence is challenging. More than 30 genes have been implicated in CHH, while the genetic basis of CDGP is poorly understood., Design: We characterized and compared the genetic architectures of CHH and CDGP, to test the hypothesis of a shared genetic basis between these disorders., Methods: Exome sequencing data were used to identify rare variants in known genes in CHH ( n = 116), CDGP ( n = 72) and control cohorts ( n = 36 874 ExAC and n = 405 CoLaus)., Results: Mutations in at least one CHH gene were found in 51% of CHH probands, which is significantly higher than in CDGP (7%, P = 7.6 × 10 -11 ) or controls (18%, P = 5.5 × 10 -12 ). Similarly, oligogenicity (defined as mutations in more than one gene) was common in CHH patients (15%) relative to CDGP (1.4%, P = 0.002) and controls (2%, P = 6.4 × 10 -7 )., Conclusions: Our data suggest that CDGP and CHH have distinct genetic profiles, and this finding may facilitate the differential diagnosis in patients presenting with delayed puberty., (© 2018 The authors.)
Published: 2018
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42. 10KP: A phylodiverse genome sequencing plan.

Author: Cheng S, Melkonian M, Smith SA, Brockington S, Archibald JM, Delaux PM, Li FW, Melkonian B, Mavrodiev EV, Sun W, Fu Y, Yang H, Soltis DE, Graham SW, Soltis PS, Liu X, Xu X, and Wong GK
Subjects: Embryophyta genetics, Fungi genetics, Genome, Fungal genetics, Genome, Plant genetics, Molecular Sequence Annotation, Chlorophyta genetics, Genetic Variation, Phylogeny
Abstract: Understanding plant evolution and diversity in a phylogenomic context is an enormous challenge due, in part, to limited availability of genome-scale data across phylodiverse species. The 10KP (10,000 Plants) Genome Sequencing Project will sequence and characterize representative genomes from every major clade of embryophytes, green algae, and protists (excluding fungi) within the next 5 years. By implementing and continuously improving leading-edge sequencing technologies and bioinformatics tools, 10KP will catalogue the genome content of plant and protist diversity and make these data freely available as an enduring foundation for future scientific discoveries and applications. 10KP is structured as an international consortium, open to the global community, including botanical gardens, plant research institutes, universities, and private industry. Our immediate goal is to establish a policy framework for this endeavor, the principles of which are outlined here.
Published: 2018
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43. Assessment of the cPAS-based BGISEQ-500 platform for metagenomic sequencing.

Author: Fang C, Zhong H, Lin Y, Chen B, Han M, Ren H, Lu H, Luber JM, Xia M, Li W, Stein S, Xu X, Zhang W, Drmanac R, Wang J, Yang H, Hammarström L, Kostic AD, Kristiansen K, and Li J
Subjects: Bacteria classification, Computational Biology, Feces microbiology, High-Throughput Nucleotide Sequencing methods, Humans, Bacteria genetics, Gastrointestinal Microbiome genetics, Metagenomics methods, Sequence Analysis, DNA methods
Abstract: Background: More extensive use of metagenomic shotgun sequencing in microbiome research relies on the development of high-throughput, cost-effective sequencing. Here we present a comprehensive evaluation of the performance of the new high-throughput sequencing platform BGISEQ-500 for metagenomic shotgun sequencing and compare its performance with that of 2 Illumina platforms., Findings: Using fecal samples from 20 healthy individuals, we evaluated the intra-platform reproducibility for metagenomic sequencing on the BGISEQ-500 platform in a setup comprising 8 library replicates and 8 sequencing replicates. Cross-platform consistency was evaluated by comparing 20 pairwise replicates on the BGISEQ-500 platform vs the Illumina HiSeq 2000 platform and the Illumina HiSeq 4000 platform. In addition, we compared the performance of the 2 Illumina platforms against each other. By a newly developed overall accuracy quality control method, an average of 82.45 million high-quality reads (96.06% of raw reads) per sample, with 90.56% of bases scoring Q30 and above, was obtained using the BGISEQ-500 platform. Quantitative analyses revealed extremely high reproducibility between BGISEQ-500 intra-platform replicates. Cross-platform replicates differed slightly more than intra-platform replicates, yet a high consistency was observed. Only a low percentage (2.02%-3.25%) of genes exhibited significant differences in relative abundance comparing the BGISEQ-500 and HiSeq platforms, with a bias toward genes with higher GC content being enriched on the HiSeq platforms., Conclusions: Our study provides the first set of performance metrics for human gut metagenomic sequencing data using BGISEQ-500. The high accuracy and technical reproducibility confirm the applicability of the new platform for metagenomic studies, though caution is still warranted when combining metagenomic data from different platforms.
Published: 2018
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44. Genetic Architecture and Selection of Chinese Cattle Revealed by Whole Genome Resequencing.

Author: Mei C, Wang H, Liao Q, Wang L, Cheng G, Wang H, Zhao C, Zhao S, Song J, Guang X, Liu GE, Li A, Wu X, Wang C, Fang X, Zhao X, Smith SB, Yang W, Tian W, Gui L, Zhang Y, Hill RA, Jiang Z, Xin Y, Jia C, Sun X, Wang S, Yang H, Wang J, Zhu W, and Zan L
Abstract: The bovine genetic resources in China are diverse, but their value and potential are yet to be discovered. To determine the genetic diversity and population structure of Chinese cattle, we analyzed the whole genomes of 46 cattle from six phenotypically and geographically representative Chinese cattle breeds, together with 18 Red Angus cattle genomes, 11 Japanese black cattle genomes and taurine and indicine genomes available from previous studies. Our results showed that Chinese cattle originated from hybridization between Bos taurus and Bos indicus. Moreover, we found that the level of genetic variation in Chinese cattle depends upon the degree of indicine content. We also discovered many potential selective sweep regions associated with domestication related to breed-specific characteristics, with selective sweep regions including genes associated with coat color (ERCC2, MC1R, ZBTB17, and MAP2K1), dairy traits (NCAPG, MAPK7, FST, ITFG1, SETMAR, PAG1, CSN3, and RPL37A), and meat production/quality traits (such as BBS2, R3HDM1, IGFBP2, IGFBP5, MYH9, MYH4, and MC5R). These findings substantially expand the catalogue of genetic variants in cattle and reveal new insights into the evolutionary history and domestication traits of Chinese cattle., (© The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)
Published: 2018
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45. Genome-wide determination of on-target and off-target characteristics for RNA-guided DNA methylation by dCas9 methyltransferases.

Author: Lin L, Liu Y, Xu F, Huang J, Daugaard TF, Petersen TS, Hansen B, Ye L, Zhou Q, Fang F, Yang L, Li S, Fløe L, Jensen KT, Shrock E, Chen F, Yang H, Wang J, Liu X, Xu X, Bolund L, Nielsen AL, and Luo Y
Subjects: CRISPR-Cas Systems genetics, CpG Islands genetics, HEK293 Cells, Humans, Methyltransferases genetics, DNA Methylation genetics, Genome genetics, RNA, Guide, CRISPR-Cas Systems genetics
Abstract: Background: Fusion of DNA methyltransferase domains to the nuclease-deficient clustered regularly interspaced short palindromic repeat (CRISPR) associated protein 9 (dCas9) has been used for epigenome editing, but the specificities of these dCas9 methyltransferases have not been fully investigated., Findings: We generated CRISPR-guided DNA methyltransferases by fusing the catalytic domain of DNMT3A or DNMT3B to the C terminus of the dCas9 protein from Streptococcus pyogenes and validated its on-target and global off-target characteristics. Using targeted quantitative bisulfite pyrosequencing, we prove that dCas9-BFP-DNMT3A and dCas9-BFP-DNMT3B can efficiently methylate the CpG dinucleotides flanking its target sites at different genomic loci (uPA and TGFBR3) in human embryonic kidney cells (HEK293T). Furthermore, we conducted whole genome bisulfite sequencing (WGBS) to address the specificity of our dCas9 methyltransferases. WGBS revealed that although dCas9-BFP-DNMT3A and dCas9-BFP-DNMT3B did not cause global methylation changes, a substantial number (more than 1000) of the off-target differentially methylated regions (DMRs) were identified. The off-target DMRs, which were hypermethylated in cells expressing dCas9 methyltransferase and guide RNAs, were predominantly found in promoter regions, 5΄ untranslated regions, CpG islands, and DNase I hypersensitivity sites, whereas unexpected hypomethylated off-target DMRs were significantly enriched in repeated sequences. Through chromatin immunoprecipitation with massive parallel DNA sequencing analysis, we further revealed that these off-target DMRs were weakly correlated with dCas9 off-target binding sites. Using quantitative polymerase chain reaction, RNA sequencing, and fluorescence reporter cells, we also found that dCas9-BFP-DNMT3A and dCas9-BFP-DNMT3B can mediate transient inhibition of gene expression, which might be caused by dCas9-mediated de novo DNA methylation as well as interference with transcription., Conclusion: Our results prove that dCas9 methyltransferases cause efficient RNA-guided methylation of specific endogenous CpGs. However, there is significant off-target methylation indicating that further improvements of the specificity of CRISPR-dCas9 based DNA methylation modifiers are required.
Published: 2018
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46. BS-virus-finder: virus integration calling using bisulfite sequencing data.

Author: Gao S, Hu X, Xu F, Gao C, Xiong K, Zhao X, Chen H, Zhao S, Wang M, Fu D, Zhao X, Bai J, Mao L, Li B, Wu S, Wang J, Li S, Yang H, Bolund L, and Pedersen CNS
Subjects: Base Pairing, Base Sequence, Cell Line, Tumor, DNA Methylation, Epigenesis, Genetic, Hepatocytes metabolism, Hepatocytes pathology, High-Throughput Nucleotide Sequencing, Humans, Sensitivity and Specificity, Sulfites chemistry, Whole Genome Sequencing, DNA, Viral genetics, Genome, Human, Hepatitis B virus genetics, Hepatocytes virology, Software, Virus Integration
Abstract: Background: DNA methylation plays a key role in the regulation of gene expression and carcinogenesis. Bisulfite sequencing studies mainly focus on calling single nucleotide polymorphism, different methylation region, and find allele-specific DNA methylation. Until now, only a few software tools have focused on virus integration using bisulfite sequencing data., Findings: We have developed a new and easy-to-use software tool, named BS-virus-finder (BSVF, RRID:SCR_015727), to detect viral integration breakpoints in whole human genomes. The tool is hosted at https://github.com/BGI-SZ/BSVF., Conclusions: BS-virus-finder demonstrates high sensitivity and specificity. It is useful in epigenetic studies and to reveal the relationship between viral integration and DNA methylation. BS-virus-finder is the first software tool to detect virus integration loci by using bisulfite sequencing data., (© The Authors 2017. Published by Oxford University Press.)
Published: 2018
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47. SOAPnuke: a MapReduce acceleration-supported software for integrated quality control and preprocessing of high-throughput sequencing data.

Author: Chen Y, Chen Y, Shi C, Huang Z, Zhang Y, Li S, Li Y, Ye J, Yu C, Li Z, Zhang X, Wang J, Yang H, Fang L, and Chen Q
Subjects: Algorithms, Benchmarking, Computational Biology, Humans, RNA, Small Untranslated metabolism, Time Factors, Workflow, High-Throughput Nucleotide Sequencing statistics & numerical data, Metagenome, Quality Control, RNA, Small Untranslated genetics, Software
Abstract: Quality control (QC) and preprocessing are essential steps for sequencing data analysis to ensure the accuracy of results. However, existing tools cannot provide a satisfying solution with integrated comprehensive functions, proper architectures, and highly scalable acceleration. In this article, we demonstrate SOAPnuke as a tool with abundant functions for a "QC-Preprocess-QC" workflow and MapReduce acceleration framework. Four modules with different preprocessing functions are designed for processing datasets from genomic, small RNA, Digital Gene Expression, and metagenomic experiments, respectively. As a workflow-like tool, SOAPnuke centralizes processing functions into 1 executable and predefines their order to avoid the necessity of reformatting different files when switching tools. Furthermore, the MapReduce framework enables large scalability to distribute all the processing works to an entire compute cluster.We conducted a benchmarking where SOAPnuke and other tools are used to preprocess a ∼30× NA12878 dataset published by GIAB. The standalone operation of SOAPnuke struck a balance between resource occupancy and performance. When accelerated on 16 working nodes with MapReduce, SOAPnuke achieved ∼5.7 times the fastest speed of other tools., (© The Author(s) 2017. Published by Oxford University Press.)
Published: 2018
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48. Taxonomic structure and functional association of foxtail millet root microbiome.

Author: Jin T, Wang Y, Huang Y, Xu J, Zhang P, Wang N, Liu X, Chu H, Liu G, Jiang H, Li Y, Xu J, Kristiansen K, Xiao L, Zhang Y, Zhang G, Du G, Zhang H, Zou H, Zhang H, Jie Z, Liang S, Jia H, Wan J, Lin D, Li J, Fan G, Yang H, Wang J, Bai Y, and Xu X
Subjects: Bacteria classification, Bacteria genetics, DNA Barcoding, Taxonomic, Genome, Bacterial, RNA, Ribosomal, 16S genetics, Microbiota, Millets microbiology, Rhizome microbiology
Abstract: The root microbes play pivotal roles in plant productivity, nutrient uptakes, and disease resistance. The root microbial community structure has been extensively investigated by 16S/18S/ITS amplicons and metagenomic sequencing in crops and model plants. However, the functional associations between root microbes and host plant growth are poorly understood. This work investigates the root bacterial community of foxtail millet (Setaria italica) and its potential effects on host plant productivity. We determined the bacterial composition of 2882 samples from foxtail millet rhizoplane, rhizosphere and corresponding bulk soils from 2 well-separated geographic locations by 16S rRNA gene amplicon sequencing. We identified 16 109 operational taxonomic units (OTUs), and defined 187 OTUs as shared rhizoplane core OTUs. The β-diversity analysis revealed that microhabitat was the major factor shaping foxtail millet root bacterial community, followed by geographic locations. Large-scale association analysis identified the potential beneficial bacteria correlated with plant high productivity. Besides, the functional prediction revealed specific pathways enriched in foxtail millet rhizoplane bacterial community. We systematically described the root bacterial community structure of foxtail millet and found its core rhizoplane bacterial members. Our results demonstrated that host plants enrich specific bacteria and functions in the rhizoplane. The potentially beneficial bacteria may serve as a valuable knowledge foundation for bio-fertilizer development in agriculture., (© The Author 2017. Published by Oxford University Press.)
Published: 2017
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49. The P2X7 receptor antagonist Brilliant Blue G reduces serum human interferon-γ in a humanized mouse model of graft-versus-host disease.

Author: Geraghty NJ, Belfiore L, Ly D, Adhikary SR, Fuller SJ, Varikatt W, Sanderson-Smith ML, Sluyter V, Alexander SI, Sluyter R, and Watson D
Subjects: Animals, Apoptosis drug effects, CD4-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes immunology, Cell Movement drug effects, Cells, Cultured, Disease Models, Animal, Graft vs Host Disease immunology, Humans, Interleukin Receptor Common gamma Subunit genetics, Mice, Mice, Inbred NOD, Mice, Knockout, Mice, SCID, Receptors, Purinergic P2X7 metabolism, Transplantation, Homologous, CD4-Positive T-Lymphocytes drug effects, CD8-Positive T-Lymphocytes drug effects, Graft vs Host Disease drug therapy, Hematopoietic Stem Cell Transplantation, Interferon-gamma blood, Purinergic P2X Receptor Antagonists therapeutic use, Rosaniline Dyes therapeutic use
Abstract: Graft-versus-host disease (GVHD) remains a major problem after allogeneic haematopoietic stem cell transplantation, a curative therapy for haematological malignancies. Previous studies have demonstrated a role for the adenosine triphosphate (ATP)-gated P2X7 receptor channel in allogeneic mouse models of GVHD. In this study, injection of human peripheral blood mononuclear cells (PBMCs) into immunodeficient non-obese diabetic-severe combined immunodeficiency-interleukin (NOD-SCID-IL)-2Rγ null (NSG) mice established a humanized mouse model of GVHD. This model was used to study the effect of P2X7 blockade in this disease. From five weeks post-PBMC injection, humanized mice exhibited clinical signs and histopathology characteristic of GVHD. The P2X7 antagonist, Brilliant Blue G (BBG), blocked ATP-induced cation uptake into both murine and human cells in vitro. Injection of BBG (50 mg/kg) into NSG mice did not affect engraftment of human leucocytes (predominantly T cells), or the clinical score and survival of mice. In contrast, BBG injection reduced circulating human interferon (IFN)-γ significantly, which was produced by human CD4 + and CD8 + T cells. BBG also reduced human T cell infiltration and apoptosis in target organs of GVHD. In conclusion, the P2X7 antagonist BBG reduced circulating IFN-γ in a humanized mouse model of GVHD supporting a potential role for P2X7 to alter the pathology of this disease in humans., (© 2017 British Society for Immunology.)
Published: 2017
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50. Development and characterization of a synthetic DNA, NUversa, to be used as a standard in quantitative polymerase chain reactions for molecular pneumococcal serotyping.

Author: Sakai F, Sonaty G, Watson D, Klugman KP, and Vidal JE
Subjects: DNA, Bacterial chemical synthesis, DNA, Bacterial chemistry, Genome, Bacterial, Humans, Limit of Detection, Molecular Diagnostic Techniques standards, Pneumococcal Infections immunology, Pneumococcal Infections microbiology, Sensitivity and Specificity, Serogroup, Serotyping standards, Streptococcus pneumoniae genetics, Streptococcus pneumoniae immunology, DNA, Bacterial standards, Molecular Diagnostic Techniques methods, Pneumococcal Infections diagnosis, Real-Time Polymerase Chain Reaction, Serotyping methods, Streptococcus pneumoniae classification
Abstract: Identification of Streptococcus pneumoniae and its more than 90 serotypes is routinely conducted by culture and Quellung reactions. Quantitative polymerase chain reactions (qPCRs) have been developed for molecular detection, including a pan-pneumococcus lytA assay, and assays targeting 79 serotypes. Reactions require genomic DNA from every target to prepare standards, which can be time consuming. In this study, we have developed a synthetic DNA molecule as a surrogate for genomic DNA and present new single-plex qPCR reactions to increase molecular detection to 94 pneumococcal serotypes. Specificity of these new reactions was confirmed with a limit of detection between 2 and 20 genome equivalents/reaction. A synthetic DNA (NUversa, ∼8.2 kb) was then engineered to contain all available qPCR targets for serotyping and lytA. NUversa was cloned into pUC57-Amp-modified to generate pNUversa (∼10.2 kb). Standards prepared from pNUversa and NUversa were compared against standards made out of genomic DNA. Linearity [NUversa (R2 > 0.982); pNUversa (R2 > 0.991)] and efficiency of qPCR reactions were similar to those utilizing chromosomal DNA (R2 > 0.981). Quantification with plasmid pNUversa was affected, however, whereas quantification with synthetic NUversa was comparable to that of genomic DNA. Therefore, NUversa may be utilized as DNA standard in single-plex assays of the currently known 94 pneumococcal serotypes., (© FEMS 2017.)
Published: 2017
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