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53. Carboxypeptidase-B activation peptide, a marker of pancreatic acinar injury, but notl-selectin, a marker of neutrophil activation, predicts severity of acute pancreatitis.

Author

Hilal, Moh'd Abu, Tsiang Ung, C., Westlake, Sarah, and Johnson, Colin D.

Subjects
*MEDICAL research, *PANCREATITIS, *NEUTROPHILS, *PEPTIDES, *CARBOXYPEPTIDASES, *BIOMARKERS
Abstract

Background: Severity prediction is difficult early in the course of acute pancreatitis. Markers of pancreatic injury, or inflammatory activation are candidate markers of severity. The aim of the present study was to assess predictive abilities of carboxypeptidase-B activation peptide (CAPAP-B) and solublel-selectin (sL-selectin) using samples collected on admission to hospital. Methods: Patients with acute pancreatitis and disease (acute abdomen) and normal controls were studied. Samples were collected at admission and daily for 5 days. There were significant differences between mild and severe pancreatitis in urinary and plasma CAPAP-B on admission, C-reactive protein on day 3 and acute physiology and chronic health evaluation (APACHE)-II scores. Prediction of severity with CAPAP-B on admission was as good as with APACHE-II score after 48 h. Carboxypeptidase-B activation peptide was not raised in disease controls. By contrast, sL-selectin was lowered in all cases of acute pancreatitis, and in disease controls. There was no difference between mild and severe pancreatitis. Conclusion: Urinary CAPAP-B, a marker of acinar injury, can be used to predict severity of acute pancreatitis at the time of admission to hospital, but sL-selectin has no value in this regard. The extent of acinar injury may be a more important early marker of severity than markers of inflammatory activation. [ABSTRACT FROM AUTHOR]

Published
2007
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57. In silico prediction of pregnane X receptor activators by machine learning approaches.

Author

Ung, C Y, Li, H, Yap, C W, and Chen, Y Z

Abstract

Pregnane X receptor (PXR) regulates drug metabolism and is involved in drug-drug interactions. Prediction of PXR activators is important for evaluating drug metabolism and toxicity. Computational pharmacophore and quantitative structure-activity relationship models have been developed for predicting PXR activators. Because of the structural diversity of PXR activators, more efforts are needed for exploring methods applicable to a broader spectrum of compounds. We explored three machine learning methods (MLMs) for predicting PXR activators, which were trained and tested by using significantly higher number of compounds, 128 PXR activators (98 human) and 77 PXR non-activators, than those of previous studies. The recursive feature-selection method was used to select molecular descriptors relevant to PXR activator prediction, which are consistent with conclusions from other computational and structural studies. In a 10-fold cross-validation test, our MLM systems correctly predicted 81.2 to 84.0% of PXR activators, 80.8 to 85.0% of hPXR activators, 61.2 to 70.3% of PXR nonactivators, and 67.7 to 73.6% of hPXR nonactivators. Our systems also correctly predicted 73.3 to 86.7% of 15 newly published hPXR activators. MLMs seem to be useful for predicting PXR activators and for providing clues to physicochemical features of PXR activation.

Published
2007
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58. Effect of Selection of Molecular Descriptors on the Prediction of Blood−Brain Barrier Penetrating and Nonpenetrating Agents by Statistical Learning Methods

Author

Li, H., Yap, C. W., Ung, C. Y., Xue, Y., Cao, Z. W., and Chen, Y. Z.

Abstract

The ability or inability of a drug to penetrate into the brain is a key consideration in drug design. Drugs for treating central nervous system (CNS) disorders need to be able to penetrate the blood−brain barrier (BBB). BBB nonpenetration is desirable for non-CNS-targeting drugs to minimize potential CNS-related side effects. Computational methods have been employed for the prediction of BBB-penetrating (BBB+) and -nonpenetrating (BBB−) agents at impressive accuracies of 75~92% and 60~80%, respectively. However, the majority of these studies give a substantially lower BBB− accuracy, and thus overall accuracy, than the BBB+ accuracy. This work examined whether proper selection of molecular descriptors can improve both the BBB− and the overall accuracies of statistical learning methods. The methods tested include logistic regression, linear discriminate analysis, k nearest neighbor, C4.5 decision tree, probabilistic neural network, and support vector machine. Molecular descriptors were selected by using a feature selection method, recursive feature elimination (RFE). Results by using 415 BBB+ and BBB− agents show that RFE substantially improves both the BBB− and the overall accuracy for all of the methods studied. This suggests that statistical learning methods combined with proper feature selection is potentially useful for facilitating a more balanced and improved prediction of BBB+ and BBB− agents.

Published
2005

68. 欧洲基线系列香料标志物的皮肤接触测试:2016年更新.

Author

Ung, C. Y., White, J. M. L., White, I. R., Banerjee, P., and McFadden, J. P.

Abstract

Summary: 香料接触性过敏症是引起湿疹的过敏性皮肤反应的普通原因。接触性过敏症可因皮肤长期反复暴露在过敏原中引起。香料接触性过敏症会通过皮肤接触测试进行诊断(将已知过敏原敷于皮肤上以评估反应)。欧盟规定化妆品应将暴露限制在已知过敏原中。此外,欧盟还规定含有任何26种已知单个香料过敏原的化妆品必须进行标注,以帮助消费者避开其过敏的过敏原。在英国的大部分皮肤科中,医生会通过对以下4种筛查标志物的皮肤接触测试来诊断香料接触性过敏症,而非对所有26种单个香料过敏原一一进行测试:混合香料I、混合香料II、秘鲁香和羟基异己基3‐环已基甲醛。在本研究中,作者审查了2084个湿疹患者记录,这些患者有的对所有单个香料过敏原都进行了皮肤接触测试,而有的仅对香料过敏原筛查标志物进行了测试,从而找出仅通过测试筛查标志物检测出实际香料接触性过敏症的比例。他们发现,仅对筛查标志物进行皮肤接触测试检测出40.8%的实际香料接触性过敏症患者(通过额外测试单个香料过敏原而确诊患有香料过敏症的患者)。他们还发现,大部分香料接触性过敏症患者并不清楚他们接触香料后会加重皮肤反应。作者总结道,目前使用的筛查标志物并不足以诊断香料接触性过敏症。 [ABSTRACT FROM AUTHOR]

Published
2018
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74. Machine learning approaches for predicting compounds that interact with therapeutic and ADMET related proteins.

Author

Li, H., Yap, C. W., Ung, C. Y., Xue, Y., Li, Z. R., Han, L. Y., Lin, H. H., and Chen, Y. Z.

Subjects
*PHARMACODYNAMICS, *BIOCHEMISTRY, *PROTEIN kinases, *SEX hormones, *THERAPEUTICS, *CYTOCHROME P-450, *METALLOENZYMES
Abstract

Computational methods for predicting compounds of specific pharmacodynamic and ADMET (absorption, distribution, metabolism, excretion and toxicity) property are useful for facilitating drug discovery and evaluation. Recently, machine learning methods such as neural networks and support vector machines have been explored for predicting inhibitors, antagonists, blockers, agonists, activators and substrates of proteins related to specific therapeutic and ADMET property. These methods are particularly useful for compounds of diverse structures to complement QSAR methods, and for cases of unavailable receptor 3D structure to complement structure-based methods. A number of studies have demonstrated the potential of these methods for predicting such compounds as substrates of P-glycoprotein and cytochrome P450 CYP isoenzymes, inhibitors of protein kinases and CYP isoenzymes, and agonists of serotonin receptor and estrogen receptor. This article is intended to review the strategies, current progresses and underlying difficulties in using machine learning methods for predicting these protein binders and as potential virtual screening tools. Algorithms for proper representation of the structural and physicochemical properties of compounds are also evaluated. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 96: 2838–2860, 2007 [ABSTRACT FROM AUTHOR]

Published
2007
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75. Dual targeting of the epigenome via FACT complex and histone deacetylase is a potent treatment strategy for DIPG

Author

Swapna Joshi, Murray D. Norris, Sandy Simon, Orazio Vittorio, Sylvie Shen, Andrei V. Gudkov, Ornella Tolhurst, Anahid Ehteda, Caitlin Ung, Jourdin R. C. Rouaen, Ruby Pandher, Aaminah Khan, Michelle Haber, Elisha Hayden, Laura Franshaw, Rebecca Lehmann, Chelsea Mayoh, Yujie Tang, Katerina Gurova, David S. Ziegler, Maria Tsoli, Federico M. Giorgi, Anjana Gopalakrishnan, Jie Liu, Chi Nam Ignatius Pang, Anne Kankean, Peter Trebilcock, Ehteda A., Simon S., Franshaw L., Giorgi F.M., Liu J., Joshi S., Rouaen J.R.C., Pang C.N.I., Pandher R., Mayoh C., Tang Y., Khan A., Ung C., Tolhurst O., Kankean A., Hayden E., Lehmann R., Shen S., Gopalakrishnan A., Trebilcock P., Gurova K., Gudkov A.V., Norris M.D., Haber M., Vittorio O., Tsoli M., and Ziegler D.S.

Subjects
0301 basic medicine, xenograft model, Cell Cycle Proteins, Retinoblastoma Protein, Epigenesis, Genetic, Histones, Epigenome, Mice, chemistry.chemical_compound, 0302 clinical medicine, facilitates chromatin transcription complex, HDAC, Panobinostat, Brain Stem Neoplasms, Biology (General), Child, EZH2, Histone deacetylase inhibitor, High Mobility Group Proteins, Acetylation, Drug Synergism, Chromatin, pediatric cancer, DNA-Binding Proteins, DIPG, Transcriptional Elongation Factors, Neuroglia, Signal Transduction, medicine.drug_class, QH301-705.5, Primary Cell Culture, Carbazoles, Antineoplastic Agents, Methylation, General Biochemistry, Genetics and Molecular Biology, Chromatin remodeling, 03 medical and health sciences, H3K27M, Cell Line, Tumor, medicine, Animals, Humans, anticancer therapy, Histone H3 acetylation, Diffuse Intrinsic Pontine Glioma, brainstem glioma, Survival Analysis, Xenograft Model Antitumor Assays, Pediatric cancer, 030104 developmental biology, chemistry, E2F1, Cancer research, Histone deacetylase, Tumor Suppressor Protein p53, E2F1 Transcription Factor, 030217 neurology & neurosurgery, Transcription Factors
Abstract

Summary: Diffuse intrinsic pontine glioma (DIPG) is an aggressive and incurable childhood brain tumor for which new treatments are needed. CBL0137 is an anti-cancer compound developed from quinacrine that targets facilitates chromatin transcription (FACT), a chromatin remodeling complex involved in transcription, replication, and DNA repair. We show that CBL0137 displays profound cytotoxic activity against a panel of patient-derived DIPG cultures by restoring tumor suppressor TP53 and Rb activity. Moreover, in an orthotopic model of DIPG, treatment with CBL0137 significantly extends animal survival. The FACT subunit SPT16 is found to directly interact with H3.3K27M, and treatment with CBL0137 restores both histone H3 acetylation and trimethylation. Combined treatment of CBL0137 with the histone deacetylase inhibitor panobinostat leads to inhibition of the Rb/E2F1 pathway and induction of apoptosis. The combination of CBL0137 and panobinostat significantly prolongs the survival of mice bearing DIPG orthografts, suggesting a potential treatment strategy for DIPG.

Published
2021

76. Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Author

Zeineb, Zian, Brown, Peter, Tan, Aik-Choon, El-Esawi, Mohamed A., Liehr, Thomas, Blanck, Oliver, Gladue, Douglas P., Almeida, Gabriel M. F., Cernava, Tomislav, Sorzano, Carlos O., Yeung, Andy W. K., Engel, Michael S., Chandrasekaran, Arun Richard, Muth, Thilo, Staege, Martin S., Daulatabad, Swapna V., Widera, Darius, Zhang, Junpeng, Meule, Adrian, Honjo, Ken, Pourret, Olivier, Yin, Cong-Cong, Zhang, Zhongheng, Cascella, Marco, Flegel, Willy A., Goodyear, Carl S., Raaij, Mark J. van, Bukowy-Bieryllo, Zuzanna, Campana, Luca G., Kurniawan, Nicholas A., Lalaouna, David, Hüttner, Felix J., Ammerman, Brooke A., Ehret, Felix, Cobine, Paul A., Tan, Ene-Choo, Han, Hyemin, Xia, Wenfeng, McCrum, Christopher, Dings, Ruud P. M., Marinello, Francesco, Nilsson, Henrik, Nixon, Brett, Voskarides, Konstantinos, Yang, Long, Costa, Vincent D., Bengtsson-Palme, Johan, Bradshaw, William, Grimm, Dominik G., Kumar, Nitin, Martis, Elvis, Prieto, Daniel, Sabnis, Sandeep C., Amer, Said E. D. R., Liew, Alan W. C., Perco, Paul, Rahimi, Farid, Riva, Giuseppe, Zhang, Chongxing, Devkota, Hari P., Ogami, Koichi, Basharat, Zarrin, Fierz, Walter, Siebers, Robert, Tan, Kok-Hian, Boehme, Karen A., Brenneisen, Peter, Brown, James A. L., Dalrymple, Brian P., Harvey, David J., Ng, Grace, Werten, Sebastiaan, Bleackley, Mark, Dai, Zhanwu, Dhariwal, Raman, Gelfer, Yael, Hartmann, Marcus D., Miotla, Pawel, Tamaian, Radu, Govender, Pragashnie, Gurney-Champion, Oliver J., Kauppila, Joonas H., Zhang, Xiaolei, Echeverría, Natalia, Subhash, Santhilal, Sallmon, Hannes, Tofani, Marco, Bae, Taeok, Bosch, Oliver, Cuív, Páraic O., Danchin, Antoine, Diouf, Barthelemy, Eerola, Tuomas, Evangelou, Evangelos, Filipp, Fabian V., Klump, Hannes, Kurgan, Lukasz, Smith, Simon S., Terrier, Olivier, Tuttle, Neil, Ascher, David B., Janga, Sarath C., Schulte, Leon N., Becker, Daniel, Browngardt, Christopher, Bush, Stephen J., Gaullier, Guillaume, Ide, Kazuki, Meseko, Clement, Werner, Gijsbert D. A., Zaucha, Jan, Al-Farha, Abd A., Greenwald, Noah F., Popoola, Segun I., Rahman, Md Shaifur, Xu, Jialin, Yang, Sunny Y., Hiroi, Noboru, Alper, Ozgul M., Baker, Chris I., Bitzer, Michael, Chacko, George, Debrabant, Birgit, Dixon, Ray, Forano, Evelyne, Gilliham, Matthew, Kelly, Sarah, Klempnauer, Karl-Heinz, Lidbury, Brett A., Lin, Michael Z., Lynch, Iseult, Ma, Wujun, Maibach, Edward W., Mather, Diane E., Nandakumar, Kutty S., Ohgami, Robert S., Parchi, Piero, Tressoldi, Patrizio, Xue, Yu, Armitage, Charles, Barraud, Pierre, Chatzitheochari, Stella, Coelho, Luis P., Diao, Jiajie, Doxey, Andrew C., Hu, Pingzhao, Kaiser, Stefan, Mitchell, Kate M., Salama, Mohamed F., Shabalin, Ivan G., Song, Haijun, Stevanovic, Dejan, Yadollahpour, Ali, Zeng, Erliang, Zinke, Katharina, Alimba, C. G., Beyene, Tariku J., Cao, Zehong, Chan, Sherwin S., Gatchell, Michael, Kleppe, Andreas, Piotrowski, Marcin, Torga, Gonzalo, Woldesemayat, Adugna A., Cosacak, Mehmet I., Haston, Scott, Ross, Stephanie A., Williams, Richard, Wong, Alvin, Abramowitz, Matthew K., Effiong, Andem, Lee, Senhong, Abid, Muhammad Bilal, Agarabi, Cyrus, Alaux, Cedric, Albrecht, Dirk R., Atkins, Gerald J., Beck, Charles R., Bonvin, A. M. J. J., Bourke, Emer, Brand, Thomas, Braun, Ralf J., Bull, James A., Cardoso, Pedro, Carter, Dee, Delahay, Robin M., Ducommun, Bernard, Duijf, Pascal H. G., Epp, Trevor, Eskelinen, Eeva-Liisa, Fallah, Mazyar, Farber, Debora B., Fernandez-Triana, Jose, Feyerabend, Frank, Florio, Tullio, Friebe, Michael, Furuta, Saori, Gabrielsen, Mads, Gruber, Jens, Grybos, Malgorzata, Han, Qian, Heinrich, Michael, Helanterä, Heikki, Huber, Michael, Jeltsch, Albert, Jiang, Fan, Josse, Claire, Jurman, Giuseppe, Kamiya, Haruyuki, Keersmaecker, Kim de, Kristiansson, Erik, Leeuw, Frank-Erik de, Li, Jiuyong, Liang, Shide, Lopez-Escamez, Jose A., Lopez-Ruiz, Francisco J., Marchbank, Kevin J., Marschalek, Rolf, Martín, Carmen S., Miele, Adriana E., Montagutelli, Xavier, Morcillo, Esteban, Nicoletti, Rosario, Niehof, Monika, O’Toole, Ronan, Ohtomo, Toshihiko, Oster, Henrik, Palma, Jose-Alberto, Paterson, Russell, Peifer, Mark, Portilla, Maribel, Portillo, M. C., Pritchard, Antonia L., Pusch, Stefan, Raghava, Gajendra P. S., Roberts, Nicola J., Ross, Kehinde, Schuele, Birgitt, Sergeant, Kjell, Shen, Jun, Stella, Alessandro, Sukocheva, Olga, Uversky, Vladimir N., Vanneste, Sven, Villet, Martin H., Viveiros, Miguel, Vorholt, Julia A., Weinstock, Christof, Yamato, Masayuki, Zabetakis, Ioannis, Zhao, Xin, Ziegler, Andreas, Aizat, Wan M., Atlas, Lauren, Bridges, Kristina M., Chakraborty, Sayan, Deschodt, Mieke, Domingues, Helena S., Esfahlani, Shabnam S., Falk, Sebastian, Guisado, J. L., Kane, Nolan C., Kueberuwa, Gray, Lau, Colleen L., Liang, Dai, Liu, Enwu, Luu, Andreas M., Ma, Chuang, Ma, Lisong, Moyer, Robert, Norris, Adam D., Panthee, Suresh, Parsons, Jerod R., Peng, Yousong, Pinto, Inês Mendes, Reschke, Cristina R., Sillanpää, Elina, Stewart, Christopher J., Uhle, Florian, Yang, Hui, Zhou, Kai, Zhu, Shu, Ashry, Mohamed, Bergsland, Niels, Berthold, Maximilian, Chen, Chang-Er, Colella, Vito, Cuypers, Maarten, Eskew, Evan A., Fan, Xiao, Gajda, Maksymilian, Gonzálezlez-Prendes, Rayner, Goodin, Amie, Graham, Emily B., Groen, Ewout J. N., Gutiérrez-Sacristán, Alba, Habes, Mohamad, Heffler, Enrico, Higginbottom, Daniel B., Janzen, Thijs, Jayaraman, Jayakumar, Jibb, Lindsay A., Jongen, Stefan, Kinyanjui, Timothy, Koleva-Kolarova, Rositsa G., Li, Zhixiu, Liu, Yu-Peng, Lund, Bjarte A., Lussier, Alexandre A., Ma, Liping, Mier, Pablo, Moore, Matthew D., Nagler, Katja, Orme, Mark W., Pearson, James A., Prajapati, Anilkumar S., Saito, Yu, Tröder, Simon E., Uchendu, Florence, Verloh, Niklas, Voutchkova, Denitza D., Abu-Zaid, Ahmed, Bakkach, Joaira, Baumert, Philipp, Dono, Marcos, Hanson, Jack, Herbelet, Sandrine, Hobbs, Emma, Kulkarni, Ameya, Kumar, Narendra, Liu, Siqi, Loft, Nikolai D., Reddan, Tristan, Senghore, Thomas, Vindin, Howard, Xu, Haotian, Bannon, Ross, Chen, Branson, Cheung, Johnny T. K., Cooper, Jeffrey, Esnakula, Ashwini K., Feghali, Karine A., Ghelardi, Emilia, Gnasso, Agostino, Horbar, Jeffrey, Lai, Hei M., Li, Jian, Ma, Lan, Ma, Ruiyan, Pan, Zihang, Peres, Marco A., Pranata, Raymond, Seow, Esmond, Sydes, Matthew, Testoni, Ines, Westermair, Anna L., Yang, Yongliang, Afnan, Masoud, Albiol, Joan, Albuquerque, Lucia G., Amiya, Eisuke, Amorim, Rogerio M., An, Qianli, Andersen, Stig U., Aplin, John D., Argyropoulos, Christos, Asmann, Yan W., Assaeed, Abdulaziz M., Atanasov, Atanas G., Atchison, David A., Avery, Simon V., Avillach, Paul, Baade, Peter D., Backman, Lars, Badie, Christophe, Baldi, Alfonso, Ball, Elizabeth, Bardot, Olivier, Barnett, Adrian G., Basner, Mathias, Batra, Jyotsna, Bazanova, O. M., Beale, Andrew, Beddoe, Travis, Bell, Melanie L., Berezikov, Eugene, Berners-Price, Sue, Bernhardt, Peter, Berry, Edward, Bessa, Theolis B., Billington, Craig, Birch, John, Blakely, Randy D., Blaskovich, Mark A. T., Blum, Robert, Boelaert, Marleen, Bogdanos, Dimitrios, Bosch, Carles, Bourgoin, Thierry, Bouvard, Daniel, Boykin, Laura M., Bradley, Graeme, Braun, Daniel, Brownlie, Jeremy, Brühl, Albert, Burt, Austin, Butler, Lisa M., Byrareddy, Siddappa N., Byrne, Hugh J., Cabantous, Stephanie, Calatayud, Sara, Candal, Eva, Carlson, Kimberly, Casillas, Sònia, Castelvetro, Valter, Caswell, Patrick T., Cavalli, Giacomo, Cerovsky, Vaclav, Chagoyen, Monica, Chen, Chang-Shi, Chen, Dong F., Chen, Hao, Chen, Hui, Chen, Jui-Tung, Chen, Yinglong, Cheng, Changxiu, Cheng, Jianlin, Chinapaw, Mai, Chinopoulos, Christos, Cho, William C. S., Chong, Lillian, Chowdhury, Debashish, Chwalibog, Andre, Ciresi, A., Cockcroft, Shamshad, Conesa, Ana, Cook, Penny A., Cooper, David N., Coqueret, Olivier, Corea, Enoka M., Costa, Elisio, Coupland, Carol, Crawford, Stephanie Y., Cruz, Aparecido D., Cui, Huijuan, Cui, Qiang, Culver, David C., D’Angiulli, Amedeo, Dahms, Tanya E. S., Daigle, France, Dalgleish, Raymond, Danielsen, Håvard E., Darras, Sébastien, Davidson, Sean M., Day, David A., Degirmenci, Volkan, Demaison, Luc, Devriendt, Koenraad, Ding, Jiandong, Dogan, Yunus, Dong, X. C., Donner, Claudio F., Dressick, Walter, Drevon, Christian A., Duan, Huiling, Ducho, Christian, Dumaz, Nicolas, Dwarakanath, Bilikere S., Ebell, Mark H., Eisenhardt, Steffen, Elkum, Naser, Engel, Nadja, Erickson, Timothy B., Fairhead, Michael, Faville, Marty J., Fejzo, Marlena S., Festa, Fernanda, Feteira, Antonio, Flood-Page, Patrick, Forsayeth, John, Fox, Simon A., Franks, Steven J., Frentiu, Francesca D., Frilander, Mikko J., Fu, Xinmiao, Fujita, Satoshi, Galea, Ian, Galluzzi, Luca, Gani, Federica, Ganpule, Arvind P., García-Alix, Antonio, Gedye, Kristene, Giordano, Maurizio, Giunta, Cecilia, Gleeson, Paul A., Goarant, Cyrille, Gong, Haipeng, Gora, Diop, Gough, Michael J., Goyal, Ravinder, Graham, Kathryn E., Grande-Pérez, Ana, Graves, Patricia M., Greidanus, Harm, Grice, Darren, Grunau, Christoph, Gumulya, Yosephine, Guo, Yabin, Gurevich, Vsevolod V., Gusev, Oleg, Hacker, Elke, Hage, Steffen R., Hagen, Guy, Hahn, Steven, Haller, Dagmar M., Hammerschmidt, Sven, Han, Jianwei, Han, Renzhi, Handfield, Martin, Hapuarachchi, Hapuarachchige C., Harder, Timm, Hardingham, Jennifer E., Heck, Michelle, Heers, Marcel, Hew, Khe F., Higuchi, Yohei, Hilaire, Cynthia St, Hilton, Rachel, Hodzic, Enisa, Hone, Andrew, Hongoh, Yuichi, Hu, Guoku, Huber, Heinz P., Hueso, Luis E., Huirne, Judith, Hurt, Lisa, Idborg, Helena, Ikeo, Kazuho, Ingley, Evan, Jakeman, Philip M., Jensen, Arne, Jia, Hong, Jia, Husen, Jia, Shuqin, Jiang, Jianping, Jiang, Xingyu, Jin, Yi, Jo, Daehyun, Johnson, Andrew M., Johnston, Marie, Jonscher, Karen R., Jorens, Philippe G., Jorgensen, Jens O. L., Joubert, Johan W., Jung, Sin-Ho, Junior, Antonio M., Kahan, Thomas, Kamboj, Sunjeev K., Kang, Yong-Kook, Karamanos, Yannis, Karp, Natasha A., Kelly, Ryan, Kenna, Ralph, Kennedy, Jonathan, Kersten, Birgit, Khalaf, Roy A., Khalid, Javaria M., Khatlani, T., Khider, Tarig, Kijanka, Gregor S., King, Sarah R. B., Kluz, Tomasz, Knox, Paul, Kobayashi, Tatsuya, Koch, Karl-Wilhelm, Kohonen-Corish, Maija R. J., Kong, Xiangpeng, Konkle-Parker, Deborah, Korpela, Kalevi M., Kostrikis, Leondios G., Kraiczy, Peter, Kratz, Harald, Krause, Günter, Krebsbach, Paul H., Kristensen, Søren R., Kumari, Prerna, Kunimatsu, Akira, Kurdak, Hatice, Kwon, Young D., Lachat, Carl, Lagisz, Malgorzata, Laky, Brenda, Lammerding, Jan, Lange, Matthias, Larrosa, Mar, Laslett, Andrew L., LeClair, Elizabeth E., Lee, Kyung-Woo, Lee, Ming-Yih, Lee, Moon-Soo, Li, Genyuan, Li, Jiansheng, Lieb, Klaus, Lim, Yau Y., Lindsey, Merry L., Line, Paul-Dag, Liu, Dengcai, Liu, Fengbin, Liu, Haiyan, Liu, Hongde, Lloyd, Vett K., Lo, Te-Wen, Locci, Emanuela, Loidl, Josef, Lorenzen, Johan, Lorkowski, Stefan, Lovell, Nigel H., Lu, Hua, Lu, Wei, Lu, Zhiyong, Luengo, Gustavo S., Lundh, Lars-Gunnar, Lysy, Philippe A., Mabb, Angela, Mack, Heather G., Mackey, David A., Mahdavi, S. R., Maher, Pamela, Maher, Toby, Maity, Sankar N., Malgrange, Brigitte, Mamoulakis, Charalampos, Mangoni, Arduino A., Manke, Thomas, Manstead, Antony S. R., Mantalaris, Athanasios, Marsal, Jan, Marschall, Hanns-Ulrich, Martin, Francis L., Martinez-Raga, Jose, Martinez-Salas, Encarnacion, Mathieu, Daniel, Matsui, Yoichi, Maza, Elie, McCutcheon, James E., McKay, Gareth J., McMillan, Brian, McMillan, Nigel, Meads, Catherine, Medina, Loreta, Merrick, B. Alex, Metzger, Dennis W., Meunier, Frederic A., Michaelis, Martin, Micheau, Olivier, Mihara, Hisaaki, Mintz, Eric M., Mizukami, Takuo, Moalic, Yann, Mohapatra, D. P., Monteiro, Antonia, Montes, Matthieu, Moran, John V., Morozov, Sergey Y., Mort, Matthew, Murai, Noriyuki, Murphy, Denis J., Murphy, Susan K., Murray, Shauna A., Naganawa, Shinji, Nammi, Srinivas, Nasios, Grigorios, Natoli, Roman M., Nguyen, Frederique, Nicol, Christine, Nieuwerburgh, Filip van, Nilsen, Erlend B., Nobile, Clarissa J., O’Mahony, Margaret, Ohlsson, Sophie, Olatunbosun, Oluremi, Olofsson, Per, Ortiz, Alberto, Ostrikov, Kostya, Otto, Siegmar, Outeiro, Tiago F., Ouyang, Songying, Paganoni, Sabrina, Page, Andrew, Palm, Christoph, Paradies, Yin, Parsons, Michael H., Parsons, Nick, Pascal, Pigny, Paul, Elisabeth, Peckham, Michelle, Pedemonte, Nicoletta, Pellizzon, Michael A., Petrelli, M., Pichugin, Alexander, Pinto, Carlos J. 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A., Williams, Brendan A., Workman, Alan D., Xiang, Tingxiu, Xie, Li-Xin, Xu, Jun, Xu, Taosheng, Yang, Chongjun, Yoon, Jihoon G., Yuan, Christina M., Zaritsky, Arno, Zhang, Yao, Zhao, Haochen, Zuckerman, Hannah, Lyu, Ran, Pullan, Wayne, Zhou, Yaoqi, Gobet, Angélique, Sadoine, Margaux L., Ontwikkelingspsychologie (Psychologie, FMG), British Lung Foundation, Brown, P, Zhou, Y, Tan, A, El-Esawi, M, Liehr, T, Blanck, O, Gladue, D, Almeida, G, Cernava, T, Sorzano, C, Yeung, A, Engel, M, Chandrasekaran, A, Muth, T, Staege, M, Daulatabad, S, Widera, D, Zhang, J, Meule, A, Honjo, K, Pourret, O, Yin, C, Zhang, Z, Cascella, M, Flegel, W, Goodyear, C, van Raaij, M, Bukowy-Bieryllo, Z, Campana, L, Kurniawan, N, Lalaouna, D, Huttner, F, Ammerman, B, Ehret, F, Cobine, P, Tan, E, Han, H, Xia, W, Mccrum, C, Dings, R, Marinello, F, Nilsson, H, Nixon, B, Voskarides, K, Yang, L, Costa, V, Bengtsson-Palme, J, Bradshaw, W, Grimm, D, Kumar, N, Martis, E, Prieto, D, Sabnis, S, Amer, S, Liew, A, Perco, P, 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Mechanisms, Pediatric surgery, APH - Methodology, ACS - Atherosclerosis & ischemic syndromes, RELISH Consortium [Member of the MPIB: Lucas Molleman], Kostrikis, Leondios G. 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Bessa, TB, Blakely, RD, Blaskovich, MAT, Boykin, LM, Butler, LM, Byrareddy, SN, Byrne, HJ, Caswell, PT, Chen, CS, Chen, DF, Chen, JT, Chen, YL, Cheng, CX, Cheng, JL, Cho, WCS, Cook, PA, Cooper, DN, Corea, EM, Crawford, SY, Cruz, AD, Cui, HJ, Culver, DC, Dahms, TES, Danielsen, HE, Davidson, SM, Day, DA, Dong, XC, Donner, CF, Drevon, CA, Duan, HL, Dwarakanath, BS, Ebell, MH, Erickson, TB, Faville, MJ, Fejzo, MS, Fox, SA, Franks, SJ, Frentiu, FD, Frilander, MJ, Fu, XM, Ganpule, AP, Gleeson, PA, Gong, HP, Gough, MJ, Graham, KE, Graves, PM, Guo, YB, Gurevich, VV, Hage, SR, Haller, DM, Han, JW, Hapuarachchi, HC, Hardingham, JE, Hew, KF, St Hilaire, C, Hu, GK, Huber, HP, Hueso, LE, Jakeman, PM, Jia, HS, Jia, SQ, Jiang, JP, Jiang, XY, Johnson, AM, Jonscher, KR, Jorens, PG, Jorgensen, JOL, Joubert, JW, Jung, SH, Junior, AM, Kamboj, SK, Kang, YK, Karp, NA, Khalaf, RA, Khalid, JM, Kijanka, GS, King, SRB, Koch, KW, Kohonen-Corish, MRJ, Korpela, KM, Kostrikis, LG, Krebsbach, PH, Kristensen, SR, 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del Tredici, AL, Udo, EE, Vandenbroucke, RE, Veiga, FH, Vesk, PA, Victor, VM, Vohl, MC, Voolstra, CR, Walsh, LJ, Wang, AY, Wen, JC, White, EP, Wojan, TR, Wong, BM, Wu, TW, Xiao, XS, Xu, JW, Xu, JP, Yang, EC, Yang, SQ, Ye, YZ, Ye, ZQ, Yuan, GC, Yuh, CH, Zhang, YK, Zhang, YS, Zhang, ZY, Aanei, CM, Atack, JM, Biedermann, PHW, den Bos, W, Boudreau, SA, Bramoweth, AD, Cao, ZX, Cheng, SQ, Chung, HJ, Chavez-Fumagalli, MA, Costa, BM, Dean, LT, Denzel, MS, Dlamini, SV, Dudley, KJ, Emmrich, JV, Eustace, AJ, Falter-Wagner, CM, Gao, JZ, Gill, MR, Grundle, DS, Ikonomopoulou, MP, Johnson, DM, Kaye, LK, Khan, MM, Kim, YM, Kish, JK, Kugler, JM, Lauschke, VM, Li, BL, Lim, CJ, Liu, XD, Lu, JJ, McGarrigle, CA, Mondal, SR, Van de Mortel, T, Moss, WN, Moultos, OA, Neumann, PA, Nie, JY, Nie, YJ, Oldenmenger, WH, Ou, JH, Pearce, SP, Pelleri, MC, Pereira, JL, Pinto, KA, Podolsky, IM, Qi, DC, Qi, XS, Raikou, VD, Rotge, JY, Rowe, AD, Schuon, RA, Smout, MJ, Song, CJ, Srivastava, RK, Tai, CNP, Tao, WY, Tian, CF, 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Univ Calif Irvine, Univ Hosp Leuven, Chongqing Med Univ, Childrens Hosp Kings Daughters, China Three Gorges Univ, and Xiangtan Univ

Subjects
Technology and Engineering, SCIENTIFIC SEARCH, Expert-curated database, Biokemia, solu- ja molekyylibiologia - Biochemistry, cell and molecular biology, Databases, RElevant LIterature SearcH consortium, Medicine and Health Sciences, Biomedical research, benchmarking, Biology, GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries), Settore MED/42 - IGIENE GENERALE E APPLICATA, database, Computer. Automation, Science & Technology, 0804 Data Format, relisch, Scientific research in health sciences, Mathematics and Statistics, litearture search, relisch , database, biomedical research, Biomedical literature, Original Article, RELISH, Mathematical & Computational Biology, RECOMMENDER-SYSTEMS, Life Sciences & Biomedicine, Mathematics, 0807 Library and Information Studies
Abstract

Made available in DSpace on 2020-12-11T01:57:28Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-10-29 Griffith University Gowonda HPC Cluster Queensland Cyber Infrastructure Foundation Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research. 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Montpellier, CNRS, Inst Human Genet, Montpellier, France Czech Acad Sci, Inst Organ Chem & Biochem, Prague, Czech Republic CSIC, Natl Ctr Biotechnol CNB, Computat Syst Biol Grp, Madrid, Spain Natl Cheng Kung Univ, Dept Biochem & Mol Biol, Tainan, Taiwan Harvard Med Sch, Schepens Eye Res Inst, Ophthalmol, Boston, MA 02115 USA Lanzhou Univ, Hosp 2, Dept Gen Surg, Lanzhou, Gansu, Peoples R China Univ Technol Sydney, Sch Life Sci, Sydney, NSW, Australia JT Chen Clin, Gynecol, Tokyo, Japan Univ Western Australia, Sch Agr & Environm, Perth, WA, Australia Beijing Normal Univ, Fac Geog Sci, Beijing, Peoples R China Univ Missouri, Elect Engn & Comp Sci, Columbia, MO USA Vrije Univ Amsterdam Med Ctr, Amsterdam Publ Hlth Res Inst, Dept Publ & Occupat Hlth, Amsterdam, Netherlands Semmelweis Univ, Med Biochem, Budapest, Hungary Queen Elizabeth Hosp, Dept Clin Oncol, Hong Kong, Peoples R China Univ Pittsburgh, Chem, Pittsburgh, PA USA GB Pant Inst Post Grad Med Educ & Res, Neurol, New Delhi, India Univ Copenhagen, Vet & Anim Sci, Copenhagen, Denmark Univ Palermo, Biomed Dept Internal & Specialist Med DIBIMIS, Sect Endocrinol, Palermo, Italy UCL, NPP, London, England Univ Florida, Microbiol & Cell Sci, Gainesville, FL USA Univ Salford, Sch Hlth Sci, Manchester, Lancs, England Cardiff Univ, Inst Med Genet, Cardiff, S Glam, Wales INSERM, ICO Canc Ctr, Angers, France Univ Colombo, Fac Med, Microbiol, Colombo, Sri Lanka Beijing Univ Chinese Med, Sch Chinese Mat Med, Beijing, Peoples R China Univ Porto, Fac Pharm, Porto, Portugal Univ Nottingham, Div Primary Care, Nottingham, England Univ Illinois, Pharm Syst Outcomes & Policy, Chicago, IL USA Pontificia Univ Catolica Goias, Escola Ciencias Agr & Biol, Goiania, Go, Brazil China Japan Friendship Hosp, Dept Oncol, Beijing, Peoples R China Boston Univ, Chem, Boston, MA 02215 USA Amer Univ, Environm Sci, Washington, DC 20016 USA Carleton Univ, Neurosci, Ottawa, ON, Canada Univ Regina, Chem & Biochem, Regina, SK, Canada Univ Montreal, Microbiolgy, Montreal, PQ, Canada Univ Leicester, Dept Genet & Genome Biol, Leicester, Leics, England Univ Queensland, Sch Agr & Food Sci, Gatton, Qld, Australia CNRS, BIOM, Paris, France UCL, Hatter Cardiovasc Inst, London, England Flinders Univ S Australia, Sci & Engn, Adelaide, SA, Australia Univ Warwick, Engn, Coventry, W Midlands, England Katholieke Univ Leuven, Ctr Human Genet, Leuven, Belgium Fudan Univ, Dept Macromol Sci, Shanghai, Peoples R China Dokuz Eylul Univ, Biol Educ, Izmir, Turkey Indiana Univ Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46202 USA Mondo Med, Pulm Dis, Borgomanero, Italy US Naval, Res Lab, Ctr Bio Mol Sci & Engn, Washington, DC USA Univ Oslo, Inst Basic Med Sci, Dept Nutr, Oslo, Norway Peking Univ, Dept Mech & Engn Sci, Beijing, Peoples R China Saarland Univ, Dept Pharm Pharmaceut & Med Chem, Saarbrucken, Germany INSERM, Natl Inst Hlth & Med Res, Skin Res Inst, Paris, France Shanghai Proton & Heavy Ion Ctr, Res & Dev, Shanghai, Peoples R China Univ Georgia, Epidemiol, Athens, GA 30602 USA Univ Freiburg, Med Ctr, Dept Plast & Hand Surg, Freiburg, Germany Sidra Med, Res, Doha, Qatar Rostock Univ, Med Ctr, Dept Oral Maxillofacial & Plast Surg, Rostock, Germany Harvard Med Sch, Brigham & Womens Hosp, Emergency Med, Boston, MA 02115 USA AgResearch, Forage Sci, Palmerston North, New Zealand Univ Calif Los Angeles, Med, Los Angeles, CA USA Arizona State Univ, Biodesign Inst, Virginia G Piper Ctr Personalized Diagnost, Tempe, AZ USA Sheffield Hallam Univ, Res Inst, Mat & Engn, Sheffield, S Yorkshire, England Aneurin Bevan Univ Healthboard, Resp Med, Newport, Shrops, England Univ Calif San Francisco, Neurol Surg, San Francisco, CA 94143 USA Univ Western Australia, UWA Dent Sch, Perth, WA, Australia Fordham Univ, Biol Sci, Bronx, NY 10458 USA Univ Helsinki, Inst Biotechnol, Helsinki, Finland Fujian Normal Univ, Coll Life Sci, Fuzhou, Fujian, Peoples R China Univ Fukui, Dept Frontier Fiber Technol & Sci, Fukui, Japan Univ Southampton, Fac Med, Clin & Expt Sci, Southampton, Hants, England Univ Urbino, Dept Biomol Sci, Urbino, Italy Osped San Luigi, Allergol Unit, Turin, Italy Muljibhai Patel Urol Hosp, Dept Urol, Nadiad, Gujarat, India Univ Granada, Stratig & Paleontol, Granada, Spain Massey Univ, Sch Vet Sci, Auckland, New Zealand CNR, High Performance Comp & Networking Inst, Naples, Italy Univ Childrens Hosp Zurich, Div Metab, Zurich, Switzerland Univ Childrens Hosp Zurich, Childrens Res Ctr, Zurich, Switzerland Univ Melbourne, Biochem & Mol Biol, Parkville, Vic, Australia Inst Pasteur, Leptospirosis Res & Expertise Unit, Noumea, New Caledonia Tsinghua Univ, Sch Life Sci, Beijing, Peoples R China Cheikh Anta Diop Univ UCAD, Sci Fac, Biol Anim Dept, Dakar, Senegal Providence Portland Med Ctr, Earle A Chiles Res Inst, Portland, OR USA Agr & Agri Food Canada, Lacombe Res & Dev Ctr, Lacombe, AB, Canada Alberta Innovates, Performance Management & Evaluat, Edmonton, AB, Canada Univ Malaga, CSIC, Inst Hortofruticultura Subtrop Mediterranea La Ma, IHSM,UMA, Malaga, Spain James Cook Univ, Coll Publ Hlth Med & Vet Sci, Cairns, Qld, Australia European Commiss, Joint Res Ctr, Ispra, Italy Univ Montpellier, Montpellier, France CSIRO, Floreat, WA, Australia Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Guangzhou, Guangdong, Peoples R China Vanderbilt Univ, Pharmacol, 221 Kirkland Hall, Nashville, TN 37235 USA RIKEN, KFU RIKEN Translat Genom Unit, Yokohama, Kanagawa, Japan Univ Tubingen, Neurobiol Vocal Commun, Tubingen, Germany Univ Colorado, UCCS Ctr Biofrontiers Inst, Colorado Springs, CO 80907 USA Fred Hutchinson Canc Ctr, Div Basic Sci, Seattle, WA USA Univ Geneva, Fac Med, Primary Care Unit, Geneva, Switzerland Ernst Moritz Arndt Univ Greifswald, Dept Mol Genet & Infect Biol, Greifswald, Germany East China Univ Sci & Technol, Dept Fine Chem, Shanghai, Peoples R China Ohio State Univ, Surg, Columbus, OH 43210 USA Oragenics, R&D, Tampa, FL USA Natl Environm Agcy, Environm Hlth Inst, Singapore, Singapore Friedrich Loeffler Inst, Inst Diagnost Virol, Greifswald, Germany Queen Elizabeth Hosp, Oncol, Woodville, SA, Australia USDA, Emerging Pests & Pathogens Res Unit, Ithaca, NY USA Univ Freiburg, Med Ctr, Dept Neurosurg, Epilepsy Ctr, Freiburg, Germany Univ Hong Kong, Fac Educ, Informat & Technol Studies, Hong Kong, Peoples R China Univ Tokyo, Grad Sch Agr & life Sci, Agr & Environm Biol, Tokyo, Japan Univ Pittsburgh, Dept Med, Pittsburgh Heart Lung & Blood Vasc Med Inst, Pittsburgh, PA USA Guys & St Thomas NHS Fdn Trust, Directorate Transplant Renal & Urol, London, England Univ Sarajevo, Clin Ctr, Clin Heart Blood Vessel & Rheumat Dis, Sarajevo, Bosnia & Herceg Univ Kent, Sch Math Stat & Actuarial Sci, Canterbury, Kent, England Tokyo Inst Technol, Dept Life Sci & Technol, Tokyo, Japan Univ Appl Sci Munich, Laser Ctr Dept Appl Sci & Mechatron, Munich, Germany CIC NanoGUNE, Nanodevices, San Sebastian, Spain Vrije Univ Amsterdam Med Ctr, Gynaecol, Amsterdam, Netherlands Cardiff Univ, Med Sch, Div Populat Med, Cardiff, S Glam, Wales Karolinska Inst, Dept Med, Solna, Sweden Natl Inst Genet, Ctr Informat Biol, Mishima, Shizuoka, Japan Murdoch Univ, Harry Perkins Inst Med Res, Perth, WA, Australia Univ Limerick, Phys Educ & Sport Sci, Limerick, Ireland Ruhr Univ Bochum, Campus Clin Gynecol, Univ Str, Bochum, Germany Southwest Med Univ, Sch Publ Hlth, Epidemiol & Biostat, Luzhou, Sichuan, Peoples R China Beijing Canc Hosp, Minist Educ Beijing, Key Lab Carcinogenesis & Translat Res, Ctr Mol Diagnost, Beijing, Peoples R China Chinese Acad Sci, Chengdu Inst Biol, Herpetol Dept, Chengdu, Sichuan, Peoples R China Key Lab Nano Biol Effects & Safety, Beijing, Peoples R China NIBR, PK Sci, Basel, Switzerland Daejeon St Marys Hosp, Pain Ctr, Daejeon, South Korea Univ Western Ontario, Sch Hlth Studies, London, ON, Canada Univ Aberdeen, Hlth Psychol Grp, Aberdeen, Scotland Univ Colorado, Anesthesiol, Anschutz Med Campus, Boulder, CO 80309 USA Univ Antwerp, UZA Antwerp Univ Hosp, Crit 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Res Ctr, Stem Cell & Regenerat Med, Riyadh, Saudi Arabia Univ Bahri, Ind Pulp & Paper, Khartoum, Sudan Univ Queensland, Mater Med Res Inst, Mater Res Inst, Brisbane, Qld, Australia Colorado State Univ, NREL, Ft Collins, CO 80523 USA Rzeszow Univ Hosp, Ob Gyn Dept, Rzeszow, Poland Univ Leeds, Fac Biol Sci, Leeds, W Yorkshire, England Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA Carl von Ossietzky Univ Oldenburg, Neurosci, Oldenburg, Germany UNSW, St George & Sutherland Clin Sch, Microbiome Res Ctr, Sydney, NSW, Australia NYU, Sch Med, Dept Biochem, New York, NY 10016 USA NYU, Sch Med, Dept Mol Pharmacol, New York, NY USA Univ Mississippi, Med Ctr, Med Infect Dis, Jackson, MS 39216 USA Tampere Univ, Fac Social Sci Psychol, Tampere, Finland Univ Cyprus, Dept Biol Sci, Nicosia, Cyprus Goethe Univ, Inst Med Microbiol & Infect Control, Frankfurt, Germany Charite Med Univ Berlin, Inst Radiol, Berlin, Germany Univ Cologne, Univ Hosp Cologne, Internal Med 1, Cologne, Germany Univ Calif Los Angeles, Sch Dent, Sect Periodont, Los Angeles, CA 90024 USA Aalborg Univ Hosp, Dept Clin Biochem, Aalborg, Denmark Manipal Acad Higher Educ, Pharm Practice, Manipal, Karnataka, India Univ Tokyo, Inst Med Sci, Dept Radiol, Tokyo, Japan Cukurova Univ, Family Med, Fac Med, Adana, Turkey Catholic Univ Korea, Coll Med, Dept Humanities & Social Med, Seoul, South Korea Univ Ghent, Food Technol Safety & Hlth, Ghent, Belgium UNSW Sydney, Sch Biol Earth & Environm Sci BEES, Sydney, NSW, Australia St Vincent Shoulder & Sports Clin, Res Unit, Vienna, Austria Cornell Univ, Biomed Engn, Ithaca, NY USA Leibniz Inst Plant Genet & Crop Plant Res IPK, Res Grp Bioinformat & Informat Technol, Gatersleben, Germany Univ Europea Madrid, Sch Doctoral Studies, Madrid, Spain CSIRO Mfg, Biomed Mfg, Melbourne, Vic, Australia Depaul Univ, Biol Sci, Chicago, IL 60604 USA Konkuk Univ, Dept Anim Sci & Technol, Seoul, South Korea Chang Gung Univ, Grad Inst Med Mechatron, Taoyuan, Taiwan Korea Univ, Coll Med, Psychiat, Seoul, South Korea Princeton Univ, Chem, Princeton, NJ 08544 USA Henan Univ Chinese Med, Henan Key Lab Chinese Med Resp Dis, Zhengzhou, Henan, Peoples R China Univ Med Ctr Mainz, Dept Psychiat & Psychotherapy, Mainz, Germany Monash Univ Malaysia, Sch Sci, Selangor, Malaysia Univ Mississippi, Med Ctr, Physiol & Biophys, Jackson, MS 39216 USA Univ Oslo, Dept Transplantat Med, Oslo, Norway Sichuan Agr Univ, Triticeae Res Inst, Yaan, Sichuan, Peoples R China Guangzhou Univ Chinese Med, Gastroenterol, Guangzhou, Guangdong, Peoples R China Southeast Univ, Sch Biol Sci & Med Engn, Suzhou, Jiangsu, Peoples R China Mt Allison Univ, Biol, Sackville, NB, Canada Ithaca Coll, Biol, Ithaca, NY 14850 USA Univ Cagliari, Dept Med Sci & Publ Hlth, Monserrato, Italy Univ Vienna, Chromosome Biol, Vienna, Austria Univ Zurich, Nephrol, Zurich, Switzerland Friedrich Schiller Univ, Inst Nutr Sci, Jena, Germany UNSW Sydney, Grad Sch Biomed Engn, Sydney, NSW, Australia Tulane Univ, Sch Med, Biochem & Mol Biol, 1430 Tulane Ave, New Orleans, LA 70112 USA NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA NIH, NCBI, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA LOreal Res & Innovat, Aulnay Sous Bois, France Lund Univ, Dept Psychol, Malmo, Sweden Catholic Univ Louvain, Inst Rech Expt & Clin, Brussels, Belgium Georgia State Univ, Neurosci Inst, Atlanta, GA 30303 USA Univ Melbourne, Ophthalmol, Surg, Parkville, Vic, Australia Univ Western Australia, Ctr Ophthalmol & Visual Sci, Perth, WA, Australia Iran Univ Med Sci, Med Phys, Fac Med, Tehran, Iran Salk Inst Biol Studies, Cellular Neurobiol, La Jolla, CA USA Imperial Coll London, Fibrosis Res Grp, London, England Univ Texas MD Anderson Canc Ctr, Genitourinary Med Oncol, Houston, TX 77030 USA Univ Liege, GIGA Neurosci, Liege, Belgium Univ Crete, Sch Med, Urol, Iraklion, Greece Flinders Univ S Australia, Flinders Med Ctr, Dept Clin Pharmacol, Adelaide, SA, Australia Max Planck Inst Immunobiol & Epigenet, Bioinformat, Breisgau, Germany Cardiff Univ, Sch Psychol, Cardiff, S Glam, Wales Imperial Coll London, Chem Engn, London, England Lund Univ, Skane Univ Hosp, Clin Sci, Malmo, Sweden Sahlgrens Acad, Inst Clin Sci, Dept Mol & Clin Med, Gothenburg, Sweden Univ Cent Lancashire, Sch Pharm & Biomed Sci, Preston, Lancs, England Hosp Univ Doctor Peset, Psychiat & Clin Psychol, Valencia, Spain Ctr Biol Mol Severo Ochoa, Genome Dynam & Funct, Madrid, Spain Unvivers Hosp Lille, Dept Intens Care, Lille, France Kansai Med Univ, Surg, Osaka, Japan Univ Toulouse, Inst Natl Polytech Toulouse, Ecole Natl Super Agron Toulouse, Lab Genom & Biotechnol Fruit, Toulouse, France UiT Arctic Univ Norway, Inst Psychol, Tromsto, Norway Queens Univ, Ctr Publ Hlth, Belfast, Antrim, North Ireland Univ Manchester, Ctr Primary Care & Hlth Serv Res, Manchester, Lancs, England Griffith Univ, Menzies Hlth Inst, Gold Coast, Qld, Australia Anglia Ruskin Univ, FHSCE, Cambridge, England Univ Lleida, Dept Expt Med, Lleida, Spain NIEHS, Biomol Screening Branch, Div Natl Toxicol Program, POB 12233, Res Triangle Pk, NC 27709 USA Albany Med Coll, Immunol & Microbial Dis, Albany, NY 12208 USA Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia Univ Kent, Sch Biosci, Canterbury, Kent, England Univ Bourgogne Franche Comte, INSERM, LNC, UMR 1231, Besancon, France Ritsumeikan Univ, Coll Life Sci, Dept Biotechnol, Shiga, Japan Kent State Univ, Biol Sci, Kent, OH 44242 USA Natl Inst Infect Dis, Dept Safety Res Blood & Biol Prod, Tokyo, Japan European Inst Marine Studies, Lab Microbiol Extreme Environm, Plouzane, France Univ Iowa, Dept Pharmacol, Roy J & Lucille A Carver Coll Med, Iowa City, IA 52242 USA Natl Univ Singapore, Biol Sci, Singapore, Singapore Conservatoire Natl Arts & Metiers, Lab GBA, EA4627, Paris, France Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA Lomonosov Moscow State Univ, Belozersky Inst Physicochem Biol, Moscow, Russia Jikei Univ, Sch Med, Dept Mol Biol, Tokyo, Japan Univ South Wales, Genom & Computat Biol, Treforest, Wales Duke Univ, Med Ctr, Obstet & Gynecol, Durham, NC USA Univ Technol Sydney, Climate Change Cluster, Sydney, NSW, Australia Nagoya Univ, Grad Sch Med, Dept Radiol, Nagoya, Aichi, Japan Western Sydney Univ, Sch Sci & Hlth, Sydney, NSW, Australia TEI Epirus, Dept Speech & Language Therapy, Ioannina, Greece Indiana Univ Purdue Univ, Orthopaed Surg, Indianapolis, IN 46202 USA Oniris, Vet Pathol, Nantes, France Royal Vet Coll, Pathobiol & Populat Sci, Hatfield, Herts, England Univ Ghent, Lab Pharmaceut Biotechnol, Ghent, Belgium Norwegian Inst Nat Res, Terr Ecol, Trondheim, Norway Univ Calif Merced, Mol & Cell Biol, Merced, CA USA Univ Dublin, Trinity Coll Dublin, Sch Engn, Ctr Transport Res, Dublin, Ireland Lund Univ, Inst Clin Sci, Nephrol, Malmo, Sweden Univ Birmingham, Mech Engn, Birmingham, W Midlands, England Lund Univ, Inst Clin Sci, OB GYN, Lund, Sweden Fdn Jimenez Diaz Hosp, Nephrol & Hypertens, Madrid, Spain Queensland Univ Technol, Sch Chem Phys & Mech Engn, Brisbane, Qld, Australia Otto von Guericke Univ, Psychol, Magdeburg, Germany Univ Med Ctr Gottingen, Dept Expt Neurodegenerat, Gottingen, Germany Harvard Med Sch, Spaulding Rehabil Hosp, Phys Med & Rehabil, Boston, MA 02115 USA Quadram Inst Biosci, Sci Operat, Norwich, Norfolk, England Ostbayer Tech Hsch Regensburg OTH Regensburg, Regensburg Med Image Comp ReMIC, Regensburg, Germany Deakin Univ, Fac Arts & Educ, Melbourne, Vic, Australia Univ Warwick, Warwick Med Sch, Coventry, W Midlands, England INSERM, Natl Inst Hlth & Med Res, Biochem & Mol Biol, Paris, France Univ Liege, Tax Inst, Liege, Belgium Univ Leeds, Sch Mol & Cellular Biol, Leeds, W Yorkshire, England IRCCS Ist Giannina Gaslini, UOC Genet Med, Genoa, Italy Res Diets Inc, Sci, New Brunswick, NJ USA Univ Perugia, Dept Phys & Geol, Perugia, Italy Walter Reed Natl Mil Med Ctr, Cellular Immunol, Bethesda, MD USA Univ Fed Santa Catarina, Biol Sci Ctr, Microbiol Immunol & Parasitol Dept, Florianopolis, SC, Brazil Univ Edinburgh, Royal Infirm, Ctr Liver & Digest Disorders, Edinburgh, Midlothian, Scotland Orion Pharma, Crit Care Proprietary Prod Div, Espoo, Finland MIT, Dept Civil & Environm Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA Univ Turin, Dept Vet Sci, Turin, Italy Univ G dAnnunzio, Dept Psychol Hlth & Territorial Sci, Chieti, Italy NYU, Sch Med, OB GYN, New York, NY USA Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland Univ Turku, Dept Biol, Turku, Finland Tech Univ Berlin, Bioanalyt, Berlin, Germany Univ Goettingen, Inst Phys Biophys 3, Gottingen, Germany Univ Texas MD Anderson Canc Ctr, Inst Appl Canc Sci, Translat Res Adv Therapeut & Innovat Oncol TRACTI, Houston, TX 77030 USA Univ Liege, Life Sci, Liege, Belgium Tarbiat Modares Univ, Fac Med Sci, Dept Toxicol, Tehran, Iran ARS, USDA, Stoneville, MS USA Univ Regensburg, RCI Regensburg Ctr Intervent Immunol, Regensburg, Germany Univ Nottingham, Sch Psychol, Nottingham, England NIH, Pathol Lab, Bethesda, MD 20892 USA Univ Carlos III Madrid, Elect Engn, Madrid, Spain Inst Med Mol, Chem Biol, Lisbon, Portugal Univ Costa Rica, CIET, San Jose, Costa Rica Univ Stavanger, Fac Hlth Sci, Stavanger, Norway Erasmus MC, Urol, Rotterdam, Netherlands Univ Edinburgh, Sch Biol Sci, Edinburgh, Midlothian, Scotland German Res Ctr Environm Hlth GmbH, Helmholtz Zentrum Munchen, Inst Bioinformat & Syst Biol IBIS, Ingolstadter Landstr 1, D-85764 Neuherberg, Germany Leiden Univ, Huygens Kamerlingh Onnes Lab, Leiden, Netherlands Univ Vienna, Nutr Sci, Vienna, Austria Kolling Inst Med Res, Med, St Leonards, NSW, Australia Johns Hopkins Sch Med, Biol Chem, Baltimore, MD USA Univ Montreal, Med Nutr & Microbiome Lab, Montreal, PQ, Canada GlaxoSmithKline, Cell & Gene Therapy, Stevenage, Herts, England Univ Trieste, Life Sci, Trieste, Italy Rhein Westfal TH Aachen, Dept Radiol, Aachen, Germany Univ Duisburg Essen, Univ Hosp Essen, West German Canc Ctr, Dept Med Oncol, Essen, Germany Med Univ Vienna, Obstet & Gynecol, Vienna, Austria FHI 360, Social & Behav Hlth Sci Div, Washington, DC USA KU Leuven VIB, Switch Lab, Leuven, Belgium Bielefeld Univ, Fac Technol, Bielefeld, Germany Capital Med Univ, Beijing Shijitan Hosp, Dept Clin Nutr, Dept Gastrointestinal Surg, Beijing, Peoples R China Meiji Univ, Dept Agr Chem, Kawasaki, Japan Yonsei Univ, Coll Med, Microbiol, Seoul, South Korea Johnson & Johnson EAME, Maidenhead, Berks, England Penn State Coll Med, Pediat, Hershey, PA USA Univ N Carolina, Dept Social Med, Chapel Hill, NC 27515 USA Univ Western Australia, ARC CoE Plant Energy Biol, Perth, WA, Australia Wageningen Univ, Div Human Nutr & Hlth, Wageningen, Netherlands Kings Coll London, Dept Neuroimaging, London, England Univ Murcia, Biochem & Mol Biol, Murcia, Spain Old Dominion Univ, Dept Biol Sci, Norfolk, VA 23529 USA Monash Univ, Biochem & Mol Biol, Melbourne, Vic, Australia Chinese Acad Sci, Inst Genet & Dev Biol, Beijing, Peoples R China Univ Pittsburgh, Pharmacol & Chem Biol, Pittsburgh, PA USA Univ Lausanne, Ctr Integrat Genom, Lausanne, Switzerland Univ Queensland, Sch Pharm, Brisbane, Qld, Australia Leibniz Inst Plant Genet & Crop Plant Res IPK Gat, Genebank, Gatersleben, Germany Piramal Imaging, Res & Dev, Berlin, Germany Univ Leeds, Civil Engn, Leeds, W Yorkshire, England Univ Missouri, Chem & Biochem, St Louis, MO 63121 USA US Geol Survey, Coastal & Marine Geol Program, Pacific Coastal & Marine Sci Ctr, Santa Cruz, CA USA Ajinomoto Genet Res Inst, Moscow, Russia Jagiellonian Univ, Fac Biochem Biophys & Biotechnol, Dept Plant Biotechnol, Krakow, Poland Univ Puerto Rico, Engn Sci & Mat, Mayaguez, PR USA Univ Regina, Dept Chem & Biochem, Regina, SK, Canada Argonne Natl Lab, Ctr Nanoscale Mat, 9700 S Cass Ave, Argonne, IL 60439 USA Univ Sunshine Coast, Sunshine Coast Mind & Neurosci Thompson Inst, Sippy Downs, Qld, Australia Chinese Peoples Liberat Army Gen Hosp, Dept Gastroenterol & Hepatol, Beijing, Peoples R China Griffith Univ, Griffith Ctr Social & Cultural Res, Gold Coast, Qld, Australia Tohoku Univ, Inst Dev Aging Canc, Dept Mol Oncol, Sendai, Miyagi, Japan Indiana Univ, Comp Sci, Bloomington, IN USA Fukushima Med Univ, Sch Med, Dept Pulm Med, Fukushima, Japan MEDIVIR AB, Biol, Huddinge, Sweden Western Sydney Univ, Neuroimmunol, Sydney, NSW, Australia Univ Jordan, Nutr & Food Technol, Amman, Jordan Thunen Inst Forest Genet, Fed Res Ctr Rura Areas Forestry & Fisheries, Inst Biodivers, Grosshansdorf, Germany Univ Edinburgh, Inst Cell Biol, Edinburgh, Midlothian, Scotland Univ Edinburgh, Ctr Integrat Physiol, Edinburgh, Midlothian, Scotland Univ Toronto, Struct Genom Consortium, Toronto, ON, Canada Canadian Mem Chiropract Coll, Grad Educ & Res, Toronto, ON, Canada Agilent Technol, R&D, Leuven, Belgium Univ British Columbia, Sch Nursing, Vancouver, BC, Canada Monash Univ, Monash Hlth, Sch Clin Sci, Stroke & Ageing Res,Dept Med, Melbourne, Vic, Australia French Natl Canc Inst, Innovat, Transfer, Biol, Boulogne, France Ludwig Maximilians Univ Munchen, Phys Chem, NanoBioSci, Munich, Germany Bandung Inst Technol, Sch Pharm, Med Chem, Bandung, Indonesia Univ Luxembourg, Life Sci Res Unit, Luxembourg, Luxembourg Lund Univ, Skane Univ Hosp, Dept Gastroenterol, Malmo, Sweden Millennium Hlth, Translat Genet, San Diego, CA USA Aristotle Univ Thessaloniki, Med Dept 2, Clin Res & Evidence Based Med Unit, Thessaloniki, Greece Jan Kochanowski Univ Humanities & Sci, Piotrkow Trybunalski Branch, Dept Psychol, Kielce, Poland McMaster Univ, Engn Phys, Hamilton, ON, Canada Marche Polytech Univ, Dept Agr Food & Environm Sci, Ancona, Italy Kuwait Univ, Fac Med, Microbiol, Kuwait, Kuwait Fujita Hlth Univ, Dept Breast Surg, Toyoake, Aich, Japan North West Reg Spinal Injuries Ctr, Spinal Injuries Ctr, Southport, Merseyside, England Luxembourg Inst Hlth, Competence Ctr Methodol & Stat, Luxembourg, Luxembourg Nestle Inst Hlth Sci SA, Metab Hlth, Ecublens, Vaud, Switzerland Ctr Inflammat Res VIB, Ghent, Belgium Univ Ghent, Dept Biomed Mol Biol, Ghent, Belgium Univ Lisbon, Inst Educ, Curriculo Formacao Prof & Tecnol, Lisbon, Portugal Univ Edinburgh, Ctr Inflammat Res, Edinburgh, Midlothian, Scotland Univ Melbourne, Sch BioSci, Parkville, Vic, Australia Northumbria Univ, Comp & Informat Sci, Newcastle Upon Tyne, Tyne & Wear, England Univ Valencia, Endocrinol, Valencia, Spain INRS, Inst Armand Frappier, Laval, PQ, Canada Univ Laval, INAF, Sch Nutr, Quebec City, PQ, Canada Univ Konstanz, Dept Biol, Constance, Germany Univ Cote dAzur, LAMHESS, Nice, France Scion, Syst Ecol, Christchurch, New Zealand CUNY, Grad Sch Publ Hlth & Hlth Policy, Epidemiol & Biostat, New York, NY 10021 USA Univ Queensland, Sch Dent, Brisbane, Qld, Australia George Inst Global Hlth, Renal & Metab Div, Sydney, NSW, Australia Wuhan Univ, Coll Chem & Mol Sci, Wuhan, Hubei, Peoples R China Griffith Univ, Sch Environm & Sci, Gold Coast, Qld, Australia Univ Minnesota, Radiat Oncol, Minneapolis, MN USA Goethe Univ, Fac Med, Frankfurt, Germany Natl Yunlin Univ Sci & Technol, Dept & Grad Sch Safety & Environm Engn, Touliu, Yunlin, Taiwan Massey Univ, Sch Sport Exercise & Nutr, Auckland, New Zealand Univ Florida, Wildlife Ecol & Conservat, Gainesville, FL USA Bournemouth Univ, Dept Psychol, Poole, Dorset, England Robert Koch Inst, Project Grp P2, Berlin, Germany Univ Edinburgh, MRC Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland Univ Basel, Biozentrum, Basel, Switzerland Univ Wollongong, Sch Med, Wollongong, NSW, Australia Univ Cologne, Inst Human Genet, Cologne, Germany Rural Econ Branch, Econ Res Serv, Washington, DC USA Uivers Bordeaux, CNRS, Inst Neurosci Cognit & Integrat Aquitaine, Bordeaux, France Univ Calif Riverside, Dept Chem & Environm Engn, Riverside, CA 92521 USA Univ Calif Riverside, Mat Sci & Engn Program, Riverside, CA 92521 USA Mackay Med Coll, Dept Med, New Taipei, Taiwan Univ Bern, Div Anim Welf, Bern, Switzerland Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97201 USA Shanghai Univ Tradit Chinese Med, Inst Interdisciplinary Med Sci, Shanghai, Peoples R China McMaster Univ, Biol, Hamilton, ON, Canada Univ S Florida, Dept Cell Biol Microbiol & Mol Biol, Tampa, FL USA Hacettepe Univ, Inst Canc, Med Oncol, Ankara, Turkey City Univ Hong Kong, Dept Elect Engn, Hong Kong, Peoples R China Natl Taiwan Univ, Dept Entomol, Taipei, Taiwan Chinese Acad Agr Sci, Inst Environm & Sustainable Dev Agr, Ecol Secur, Beijing, Peoples R China Florida State Univ, Inst Mol Biophys, Chem & Biochem, Tallahassee, FL USA Peking Univ, Shenzhen Grad Sch, State Key Lab Chem Oncogen, Lab Computat Chem & Drug Design, Shenzhen, Peoples R China Univ Helsinki, Fac Pharm, Div Pharmaceut Chem & Technol, Drug Res Program, Helsinki, Finland Tohoku Univ, Microbial Biotechnol, Sendai, Miyagi, Japan Tianjin Med Univ, Sch Basical Med Sci, Dept Pharmacol, Tianjin, Peoples R China Dana Farber Canc Inst, Biostat & Computat Biol, Boston, MA 02115 USA Natl Hlth Res Inst, Inst Mol & Genom Med, Zhunan, Taiwan Univ Oxford, Physiol Anat & Genet, Oxford, England George Washington Univ, Phys, Washington, DC USA Univ Nebraska, Sch Biol Sci, Lincoln, NE USA Toronto Gen Hosp, Res Inst, Dept Lab Med & Pathobiol, Toronto, ON, Canada Univ Texas Dallas, Biol Sci, Richardson, TX 75083 USA NYU, Dept Chem, New York, NY USA Shandong Univ, Sch Math & Stat, Jinan, Shandong, Peoples R China Univ Sci & Technol China, Hefei Natl Lab Phys Sci Microscale, Hefei, Anhui, Peoples R China Purdue Univ, Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA NIBSC, Adv Therapies, Ridge, Herts, England Shanghai Jiao Tong Univ, Ruijin Hosp, Dept Pulm & Crit Care Med, Shanghai, Peoples R China Charite Med Univ Berlin, Dermatol & Allergy, Berlin, Germany Univ Hosp St Etienne, Hematol, St Etienne, France Inland Norway Univ Appl Sci, Inst Biotechnol, Elverum, Norway Univ Jordan, Pediat, Amman, Jordan Inst Pasteur, Mol Mycol Unit, Paris, France Cardiff Univ, Sch Med, Inst Psychol Med & Clin Neurosci, Med Res Council Ctr Neuropsychiat Genet & Genom, Cardiff, S Glam, Wales Zurich Univ Appl Sci, Social Work, Zurich, Switzerland Jawaharlal Nehru Univ, Sch Life Sci, New Delhi, India Univ Burgundy Franche Comte, LE2I, Dijon, France Univ Roehampton, Life Sci, London, England Ghent Univ Hosp, Gen & HPB Surg, Ghent, Belgium Univ Wurzburg, Insect Fungus Symbiosis Lab, Wurzburg, Germany Radboud Univ Nijmegen, Behav Sci Inst, Nijmegen, Netherlands Fraunhofer WKI, Applicat Ctr HOFZET, Hannover, Germany UCL, Struct & Mol Biol, London, England Univ Amsterdam, Dev Psychol, Amsterdam, Netherlands Aalborg Univ, Hlth Sci & Technol, CNAP, SMI, Aalborg, Denmark VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA Cedars Sinai Med Ctr, Neurosurg, Los Angeles, CA 90048 USA Sun Yat Sen Univ, Sch Data & Comp Sci, Guangzhou, Guangdong, Peoples R China Dezhou Univ, Shandong Prov Key Lab Biophys, Guangzhou, Guangdong, Peoples R China Maison Teledetection, Inst Rech Dev, UMR Espace DEv, Montpellier, France Xiamen Univ, Sch Life Sci, Xiamen, Fujian, Peoples R China Nanjing Univ, Sch Med, Jinling Hosp, Natl Clin Res Ctr Kidney Dis,Dept Med Imaging, Nanjing, Jiangsu, Peoples R China Univ Kent, Sch Social Policy Sociol & Social Res, Canterbury, Kent, England Univ Fed Minas Gerais, Infect Dis & Trop Med, Belo Horizonte, MG, Brazil Univ Minho, Sch Med, Life & Hlth Sci Res Inst ICVS, Braga, Portugal Univ Montreal, Biochim & Med Mol, Montreal, PQ, Canada Johns Hopkins Bloomberg Sch Publ Hlth, Epidemiol, Baltimore, MD USA Max Planck Inst Biol Ageing, Metab & Genet Regulat Ageing, Cologne, Germany Univ Swaziland, Hlth Sci, Kwaluseni, Eswatini Queensland Univ Technol, Inst Future Environm, Brisbane, Qld, Australia Ctr Sci Monaco, Dept Biol Med, Monaco, Monaco HELIOS Hosp, Urol, Bad Saarow Pieskow, Germany Tech Univ Carolo Wilhelmina Braunschweig, Inst Microbiol, Braunschweig, Germany Univ Barcelona, Barcelona Ctr Maternal Fetal & Neonatal Med, Fetal i D Fetal Med Res Ctr, IDIBAPS BCNatal,Hosp Clin, Barcelona, Spain Univ Barcelona, Hosp St Joan de Deu, Barcelona, Spain Friedrich Loeffler Inst, Inst Bacterial Infect & Zoonoses, Jena, Germany Charite Med Univ Berlin, Neurol, Berlin, Germany Dublin City Univ, Natl Inst Cellular Biotechnol, Mol Therapeut Canc Ireland, Dublin, Ireland Schoen Clin Roseneck, Prien Am Chiemsee, Germany Univ Med Ctr Hamburg Eppendorf, Inst Sex Res & Forens Psychiat, Hamburg, Germany Nankai Univ, Sch Math Sci, Tianjin, Peoples R China Nankai Univ, LPMC, Tianjin, Peoples R China Univ Oxford, Oncol, Oxford, England Royal Holloway Univ London, Class, Egham, Surrey, England Cornell Univ, Clin Sci, Ithaca, NY USA Univ KwaZulu Natal, Pharmaceut Chem, Westville Campus, Durban, South Africa Royal Coll Surgeons Ireland, Med, Dublin, Ireland Univ Oslo, Dept Immunol, Oslo, Norway Bermuda Inst Ocean Sci, Marine Nitrogen Cycling Lab, St Georges, Bermuda Kanazawa Univ, Inst Liberal Arts & Sci, Kanazawa, Ishikawa, Japan World Hlth Org Reg Off Africa, Brazzaville, Rep Congo Univ Hosp BesanCon, Infect Control Dept, Besancon, France Galapagos NV, Clin Dev, Mechelen, Belgium Univ Tasmania, Integrated Marine Observing Syst, Hobart, Tas, Australia Georg August Univ Gottingen, Albrecht von Haller Inst Plant Sci, Dept Systemat Biodivers & Evolut Plants, Gottingen, Germany Univ Occupat & Environm Hlth, Dept Psychiat, Fukuoka, Fukuoka, Japan IMDEA Food, Program Precis Nutr & Aging, Madrid, Spain Radboud Univ Nijmegen, Med Sch, IQHealthcare, Nijmegen, Netherlands Maastricht Univ, Dept Cardiovasc Surg, Maastricht, Netherlands German Diabet Ctr, Inst Clin Biochem & Pathobiochem, Dusseldorf, Germany Juntendo Univ, Grad Sch Med, Dept Radiol, Tokyo, Japan Deakin Univ, Sch Informat Technol, Melbourne, Vic, Australia Max Planck Inst Eusenforschung, Dept Interface Chem & Surface Sci, Dusseldorf, Germany Edge Hill Univ, Dept Psychol, Ormskirk, England Aga Khan Univ, Psychiat, Karachi, Pakistan KRIBB, Korean Bioinformat Ctr, Seoul, South Korea Cardinal Hlth Specialty Solut, Hlth Econ & Outcomes Res, Dallas, TX USA Klinikum Univ Munchen, Div Clin Pharmacol, Munich, Germany Univ Pittsburgh, Neurol Surg, Pittsburgh, PA USA Rhein Westfal TH Aachen, Dept Child & Adolescent Psychiat Psychosomat & Ps, Aachen, Germany Univ Copenhagen, Inst Mol & Cellular Biol, Copenhagen, Denmark St Jude Childrens Res Hosp, Struct Biol, 332 N Lauderdale St, Memphis, TN 38105 USA Royal Shrewsbury Hosp, Colorectal Surg, Shrewsbury, Salop, England Univ Nottingham, Fac Med & Hlth Sci, Nottingham, England Karolinska Inst, Dept Physiol & Pharmacol, Solna, Sweden Chinese Acad Sci, Changchun Inst Appl Chem, State Key Lab Electroanalyt Chem, Jilin, Jilin, Peoples R China Univ British Columbia, Pediat, Vancouver, BC, Canada Chinese Acad Agr Sci, State Key Lab Cotton Biol, Res Base Anyang Inst Technol, Cotton Germplasm Resources,Inst Cotton Res, Beijing, Peoples R China Chinese Univ Hong Kong, Anaesthesia & Intens Care, Hong Kong, Peoples R China Univ Macau, ICMS, Zhuhai, Guangdong, Peoples R China North China Elect Power Univ, Sch Renewable Energy, Beijing, Peoples R China Justus Liegbig Univ, Dept Internal Med, Giessen, Germany Aarhus Univ, Biosci, Aarhus, Denmark Univ Dublin, Trinity Coll Dublin, Irish Longitudinal Study Ageing TILDA, Dublin, Ireland Univ Groningen, Univ Med Ctr Groningen, Hematol, Groningen, Netherlands Vrije Univ Amsterdam Med Ctr, Child Neurol, Amsterdam, Netherlands EBI, EMBL, Cambridge, England Max Planck Inst Marine Microbiol, HGF MPG Joint Res Grp Deep Sea Ecol & Technol, Bremen, Germany Max Planck Inst Human Dev, Ctr Adapt Rat, Berlin, Germany King Faisal Univ, Math, Al Hufuf, Saudi Arabia Griffith Univ, Sch Nursing & Midwifery, Gold Coast, Qld, Australia Iowa State Univ, Roy J Carver Dept Biochemsitry Biophys & Mol Biol, Ames, IA USA Delft Univ Technol, Fac Mech Maritime & Mat Engn, Engn Thermodynam Proc & Energy Dept, Leeghwaterstr 39, NL-2628 CB Delft, Netherlands Univ Nebraska Med Ctr, Coll Allied Hlth Profess, Cytotechnol Educ, Omaha, NE USA Shinko Mem Hosp, Dept Cardiovasc Med, Kobe, Hyogo, Japan Imperial Coll London, Mat, London, England Tech Univ Munich, Dept Surg, Munich, Germany Chinese Acad Agr Sci, Res Inst Pomol, Minist Agr, Lab Qual & Safety Risk Assessment Fruit Xingcheng, Shenyang, Liaoning, Peoples R China James Madison Univ, Commun Sci & Disorders, Harrisonburg, VA 22807 USA Univ Hosp Ulm, Inst Orthopaed Res & Biomech, Ulm, Germany Univ Essex, Sch Hlth & Social Care, Colchester, Essex, England Alpha Altis, Res Serv, Nottingham, England Erasmus MC, Med Oncol, Rotterdam, Netherlands Fed Univ Oye, Dept Ind Chem, Ekiti, Nigeria Duke Univ, Med Ctr, Cell Biol, Durham, NC USA Univ Oxford, Nuffield Dept Clin Neurosci, Oxford, England Univ Manchester, Canc Res UK Manchester Inst, Manchester, Lancs, England Helsinki Univ Hosp, Childrens Hosp, Helsinki, Finland Univ Aveiro, CESAM Ctr Environm & Marine Studies, Dept Biol, Aveiro, Portugal Univ Botswana, Psychol, Gaborone, Botswana Univ Fed Bahia, Nursing Sch, Salvador, BA, Brazil Queen Mary Univ London, Biol & Expt Psychol, London, England Natl Univ Pharm, Med Chem Dept, Kharkov, Ukraine Univ Bolton, Dept Educ & Psychol, Bolton, England La Trobe Univ, Dept Chem & Phys, Melbourne, Vic, Australia Gen Hosp Northern Theater Command, Dept Gastroenterol, Shenyang, Liaoning, Peoples R China Doctors Hosp, Dept Nephrol, Athens, Greece Univ Hosp Essen, Pediat 3, Essen, Germany Imperial Coll London, Infect Dis Epidemiol, London, England Sorbonne Univ, Dept Psychiat, Paris, France UNSW Sydney, Educ, Sydney, NSW, Australia Stanford Univ, Dept Psychiat & Behav Sci, Palo Alto, CA 94304 USA Hannover Med Sch, Clin Laryngol Rhinol & Otol, Hannover, Germany Curtin Univ, Ctr Aboriginal Studies, Perth, WA, Australia Iran Univ Sci & Technol, Biomed Engn Dept, Tehran, Iran Univ Calif San Francisco, Anesthesiol, San Francisco, CA 94143 USA Khalifa Univ Sci & Technol, Mech Engn, Abu Dhabi, U Arab Emirates Univ Florida, Hort Sci, Gainesville, FL USA James Cook Univ, Australian Inst Trop Hlth & Med, Ctr Biodiscovery & Mol Dev Therapeut, Cairns, Qld, Australia Univ Porto, Fac Med, CINTESIS, Porto, Portugal Shaoxing Peoples Hosp, Med Res Ctr, Shaoxing, Zhejiang, Peoples R China NIH, Dept Transfus Med, Bethesda, MD 20892 USA AIIMS, Dept Biotechnol, New Delhi, India Univ Ottawa, Biochem Microbiol & Immunol, Ottawa, ON, Canada Univ Oslo, Inst Clin Med, Div Mental Hlth & Addict, Oslo, Norway Univ Groningen, Univ Med Ctr Groningen, Dept Radiol, Groningen, Netherlands Univ Hong Kong, Sch Nursing, Hong Kong, Peoples R China Tokyo Med Univ, Ibaraki Med Ctr, Urol, Tokyo, Japan Univ Hosp Zurich, Dept Radiat Oncol, Zurich, Switzerland Univ Maryland, Inst Human Virol, Div Immunotherapy, Baltimore, MD 21201 USA Univ Maryland, Dept Surg, Baltimore, MD 21201 USA Stellenbosch Univ, Fac Med & Hlth Sci, Div Mol Biol & Human Genet, Stellenbosch, South Africa China Agr Univ, Coll Biol Sci, Beijing, Peoples R China Osaka Univ, Grad Sch Pharmaceut Sci, Suita, Osaka, Japan Univ Washington, Biochem, Seattle, WA 98195 USA Natl Res Council Italy, Inst Biosci & BioResources, Naples, Italy Univ Lyon, Phys, Lyon, France Univ Basel, Fac Psychol, Ctr Social Psychol, Basel, Switzerland Queen Mary Univ London, Barts Canc Inst, Ctr Mol Oncol, London, England EBI, EMBL, Samples Phenotypes & Ontol Team, Cambridge, England Charles Sturt Univ, Fac Arts & Educ, Bathurst, NSW, Australia Shandong Univ, Helmholtz Inst Biotechnol, Sch Life Sci, State Key Lab Microbial Technol, Jinan, Shandong, Peoples R China Shantou Univ, Dept Biol, Shantou, Guangdong, Peoples R China Shanxi Univ, Inst Biomed Sci, Taiyuan, Shanxi, Peoples R China St Jude Childrens Res Hosp, Computat Biol, 332 N Lauderdale St, Memphis, TN 38105 USA Harbin Med Univ, Coll Bioinformat Sci & Technol, Harbin, Heilongjiang, Peoples R China NIH, Radiol & Imaging Sci, Bldg 10, Bethesda, MD 20892 USA Georgia Inst Technol, Dept Biol Sci, Atlanta, GA 30332 USA XtalPi Inc, Cambridge, MA USA Consejo Nacl Invest Cient & Tecn, Partner Inst Max Planck Soc, Inst Invest Biomed Buenos Aires IBioBA, Bioinformat, Buenos Aires, DF, Argentina Univ Sydney, Save Sight Inst, Sydney, NSW, Australia Univ South Australia, Canc Res Inst, Australian Ctr Precis Hlth, Adelaide, SA, Australia Jinan Univ, Inst Life & Hlth Engn, Guangdong Higher Educ Inst, Key Lab Funct Prot Res, Guangzhou, Guangdong, Peoples R China Univ Texas Hlth Sci Ctr Houston, Epidemiol Human Genet & Environm Sci, Houston, TX 77030 USA Weill Cornell Med, Dept Microbiol & Immunol, New York, NY USA Guangdong Inst Appl Biol Resources, Biotechnol Lab, Guangzhou, Guangdong, Peoples R China Shandong Normal Univ, Coll Life Sci, Jinan, Shandong, Peoples R China Shandong Univ, Life Sci Dept, Jinan, Shandong, Peoples R China South China Agr Univ, Integrat Microbiol Res Ctr, Guangzhou, Guangdong, Peoples R China Liaoning Acad Agr Sci, Crop Mol Improving Lab, Shenyang, Liaoning, Peoples R China Lawson Hlth Res Inst, Med Biophys, London, ON, Canada Univ Melbourne, Infrastruct Engn, Parkville, Vic, Australia Univ Canberra, Fac Hlth, Canberra, ACT, Australia Univ Cambridge, MRC Cognit & Brain Sci Unit, Cambridge, England Emory Univ, Biostat & Bioinformat, Atlanta, GA 30322 USA Johns Hopkins Sch Med, Anesthesiol & Crit Care Med, Baltimore, MD USA Nottingham Trent Univ, Sch Anim Rural & Environm Sci, Nottingham, England Univ Exeter, Biosci, Exeter, Devon, England Hillingdon Hosp NHS Fdn Trust, London, England Univ Glasgow, MRC CSO Social & Publ Hlth Sci Unit, Glasgow, Lanark, Scotland Natl & Kapodistrian Univ Athens, Evaggelismos Athens Hosp, ICU, Athens, Greece Univ Newcastle, Biol Sci, Callaghan, NSW, Australia Coventry Univ, Fac Hlth & Life Sci, Ctr Innovat Res Life Course, Coventry, W Midlands, England Lausanne Univ Hosp, Serv Endocrinol Diabet & Metab, Lausanne, Switzerland Charles Sturt Univ, Sch Community Hlth, Bathurst, NSW, Australia Queens Univ Belfast, Inst Global Food Secur, Belfast, Antrim, North Ireland Natl Univ Singapore, Inst Policy Studies, Singapore, Singapore Univ Penn, Intitute Med & Engn, Philadelphia, PA 19104 USA Cold Spring Harbor Lab, POB 100, Cold Spring Harbor, NY 11724 USA Univ Michigan, EECS, Ann Arbor, MI 48109 USA Univ British Columbia, Ctr Blood Res, Vancouver, BC, Canada UiT Arctic Univ Norway, Dept Hlth & Care Sci, Fac Hlth Sci, Tromso, Norway Hosp Clin Porto Alegre, Physiotherapy, Porto Alegre, RS, Brazil Univ Paris 05, Med Sch, Paris, France Chinese Acad Agr Sci, Inst Crop Sci, Natl Key Facil Crop Gene Resources & Genet Improv, Beijing, Peoples R China Univ Ghent, Expt Clin & Hlth Psychol, Ghent, Belgium Indian Inst Adv Res, Bioinformat & Struct Biol, Gandhinagar, Gujart, India Bambino Ges Childrens Res Hosp, Lab Mol Med, Rome, Italy Heidelberg Univ, Ctr Infect Dis Parasitol, Heidelberg, Germany Stanford Univ, Elect Engn, Palo Alto, CA 94304 USA Univ Cadiz, Biol, Andalucia, Spain Mansoura Univ Hosp, Gen Surg, Mansoura, Egypt Inst Pasteur, Virol Pole, Dakar, Senegal Cardiff Univ, Div Canc & Genet, Cardiff, S Glam, Wales Ctr Expertise & Biol Diagnost Cameroon, Food Safety & Environm Microbiol, Yaounde, Cameroon Swiss Fed Labs Mat Sci & Technol, Lab Thin Films & Photovolta, Dubendorf, Switzerland Assiut Univ, Assiut Urol & Nephrol Hosp, Fac Med, Assiut, Egypt UCL, GEE, London, England UCL, IHA, London, England Univ Derby, Univ Derby Online Learning, Derby, England SUNY Stony Brook, Family Populat & Prevent Med, Stony Brook, NY 11794 USA Walter & Eliza Hall Inst Med Res, Mol Med Div, Melbourne, Vic, Australia Newcastle Univ, Northern Inst Canc Res, Newcastle Upon Tyne, Tyne & Wear, England German Ctr Neurodegenerat Dis, Clin Dementia Res, Bonn, Germany Sorbonne Univ, CNRS, UMR 7144, Stn Biol, Paris, France Univ Barcelona, Odontoestomatol, Barcelona, Spain Janelia Res Campus, Comp Sci, Ashburn, VA USA Univ Oxford, Ctr Trop Med & Global Hlth, Oxford, England Univ Bern, ARTORG Ctr Biomed Engn Res, Bern, Switzerland Australian Natl Univ, Eccles Inst Neurosci, John Curtain Sch Med Res, Canberra, ACT, Australia John Innes Ctr, Metab Biol, Norwich, Norfolk, England USDA ARS, Genom & Bioinformat Res Unit, Raleigh, NC 27695 USA Med Univ Graz, Inst Med Informat Stat & Documentat, Holzinger Grp, Graz, Austria Ajou Univ, Pharm, Suwon, South Korea City Univ Hong Kong, Sch Energy & Environm, Hong Kong, Peoples R China Univ British Columbia, Sch Kinseiol, Vancouver, BC, Canada Univ Copenhagen, Marine Biol Sect, Dept Biol, Copenhagen, Denmark Univ Vienna, Dept Commun, Vienna, Austria Univ Dundee, Sch Social Sci, Dundee, Scotland Tech Univ Dresden, Inst Bot, Dresden, Germany Univ Oxford, Div Struct Biol, Oxford, England Natl Univ Hlth Syst, Med, Singapore, Singapore Univ Canterbury, Sch Biol Sci, Christchurch, New Zealand Univ Hosp Southern Denmark, Focused Res Unit Mol Diagnost & Clin Res, Odense, Denmark Univ Oxford, Primary Care Hlth Sci, Oxford, England Baylor Coll Med, Verna & Marrs McLean Dept Biochem & Mol Biol, Houston, TX 77030 USA Adnan Menderes Univ Aydin, Fac Nursing, Dept Publ Hlth Nursing, Aydin, Turkey Oasi Res Inst IRCCS, Dept Neurol IC, Troina, Italy Purdue Univ, Weldon Sch Biomed Engn, W Lafayette, IN 47907 USA Kings Coll London, Kings Ctr Mil Hlth Res, London, England LSHTM, Dept Infect Dis Epidemiol, London, England Leibniz Univ Hannover, BMWZ Organ Chem, Hannover, Germany Xi An Jiao Tong Univ, Sch Basic Med Sci, Dept Physiol & Pathophysiol, Xian, Shaanxi, Peoples R China Univ South Australia, Sch Pharm & Med Sci, Adelaide, SA, Australia Univ Fed Santa Catarina, Dept Phys Educ, Florianopolis, SC, Brazil Southern Med Univ, Nanfang Hosp, Dept Oncol, Guangzhou, Guangdong, Peoples R China Stanford Univ, Hansen Expt Phys Lab, Palo Alto, CA 94304 USA Shenzhen Univ, Affiliated Hosp 1, Shenzhen Peoples Hosp 2, Inst Translat Med, Shenzhen, Guangdong, Peoples R China Univ Hong Kong, Dept Stat & Actuarial Sci, Hong Kong, Peoples R China UCL, Dept Mech Engn, London, England ASTAR, Singapore Immunol Network, Lab Microbial Immun, Singapore, Singapore Cent South Univ, State Key Lab Powder Met, Changsha, Hunan, Peoples R China Univ Aberdeen, Inst Appl Hlth Sci, Aberdeen, Scotland Univ Bridgeport, Biomed Engn, Bridgeport, CT 06601 USA Texas Tech Univ, Hlth Sci Ctr, Pharmaceut Sci, Lubbock, TX 79430 USA Univ Montana, Ecosyst & Conservat Sci, Missoula, MT 59812 USA Univ Goettingen, Dept Syst Neurosci, Gottingen, Germany NHLBI, Lab Syst Genet, Bldg 10, Bethesda, MD 20892 USA Cleveland Clin, Lou Ruvo Ctr Brain Hlth, Imaging, Las Vegas, NV USA Flinders Univ S Australia, Coll Nursing & Hlth Sci, Nutr & Dietet, Adelaide, SA, Australia Univ Padua, Dept Math, Padua, Italy Lund Univ, Fac Law, Lund, Sweden Univ Gothenburg, Dept Microbiol & Immunol, Gothenburg, Sweden NARO, Kachwekano Zardi, Entebbe, Uganda Natl Yunlin Univ Sci & Technol, Bachelor Program Interdisciplinary Studies, Touliu, Yunlin, Taiwan Aarhus Univ, Dept Biomed, Danish Res Inst Translat Neurosci DANDRITE, Aarhus, Denmark Eduardo Mondlane Univ, Math & Comp Sci, Maputo, Mozambique Univ Bern, Dept Old Age Psychiat & Psychotherapy, Bern, Switzerland RAS, Inst Cytol, Lab Cytol Unicellular Organisms, St Petersburg, Russia Beijing Inst Technol, Sch Chem & Chem Engn, Beijing, Peoples R China Univ Queensland, Queensland Alliance Agr & Food Innovat, Brisbane, Qld, Australia Fraunhofer Inst Toxicol & Expt Med ITEM, Inhalat Toxicol, Hannover, Germany Univ Hong Kong, Publ Hlth, Hong Kong, Peoples R China Univ Hlth Network, Anesthesia & Pain Med, Toronto, ON, Canada Univ Toronto, Toronto, ON, Canada Univ Bath, Dept Hlth, Bath, Avon, England Univ Copenhagen, Computat & RNA Biol, Copenhagen, Denmark Fisheries & Oceans Canada, Bedford Inst Oceanog, Dartmouth, NS, Canada Goethe Univ, CEF MC, BMLS, Phys Biol, Frankfurt, Germany Albert Einstein Coll Med, Anat & Struct Biol, New York, NY USA Queensland Govt, Dept Environm & Sci, Brisbane, Qld, Australia Uppsala Univ, Vasc Surg Sect, Dept Surg Sci, Uppsala, Sweden Childrens Canc Hosp, Res, Cairo, Egypt Leibniz Inst Nat Prod Res & Infect Biol, Bio Pilot Plant, Jena, Germany Duy Tan Univ, Inst Res & Dev, Da Nang, Vietnam Univ Helsinki, Helsinki Inst Life Sci HiLIFE, Helsinki, Finland Univ Queensland, Australian Inst Bioengn & Nanotechnol, Brisbane, Qld, Australia George Inst Global Hlth, Sydney, NSW, Australia Griffith Univ, Griffith Inst Drug Discovery, Brisbane, Qld, Australia Dezhou Univ, Coll Phys & Elect Informat, Shandong Prov Key Lab Biophys, Dezhou, Peoples R China Henan Agr Univ, Coll Life Sci, Zhengzhou, Henan, Peoples R China Univ Tokyo, Publ Hlth, Tokyo, Japan Sun Yat Sen Univ, Affiliated Hosp 1, Guangzhou, Guangdong, Peoples R China Univ Illinois, Dept Med, Chicago, IL USA Beijing Inst Microbiol & Epidemiol, State Key Lab Pathogen & Biosecur, Beijing, Peoples R China Minist Hlth, Key Lab Neonatal Dis, Shanghai, Peoples R China Covenant Univ, Dept Phys, Ota, Nigeria Prince Sattam Bin Abdulaziz Univ, Dept Phys Therapy & Hlth Rehabil, Al Kharj, Saudi Arabia Lund Univ, Cognit Sci, Malmo, Sweden Natl Open Univ Nigeria, Dept Publ & Environm Hlth, Abuja, Nigeria Peking Univ, Sch Publ Hlth, Dept Lab Sci & Technol, Beijing, Peoples R China Univ Sydney, Sch Publ Hlth, Menzies Ctr Hlth Policy, Sydney, NSW, Australia Univ Auckland, Dept Elect & Comp Engn, Auckland, New Zealand Beijing Univ Chinese Med, Res Ctr TCM Informat Engn, Beijing, Peoples R China Osped Niguarda Ca Granda, Cardiac Surg, Milan, Italy Univ Vet Med, Clin Horses, Hannover, Germany Harbin Med Univ, Lab Med Genet, Harbin, Heilongjiang, Peoples R China Univ Saskatchewan, Dept Psychol, Saskatoon, SK, Canada Univ Coimbra, Ctr Studies Geog & Spatial Planning CEGOT, Coimbra, Portugal Univ Groningen, Univ Med Ctr Groningen, Epidemiol, Groningen, Netherlands South Cent High Specialty Hosp, Dept Neurol & Neurosurg, Pemex, Mexico Shandong Agr Univ, Coll Informat Sci & Engn, Tai An, Shandong, Peoples R China Curtin Univ, Natl Drug Res Inst, Perth, WA, Australia Wageningen Bioveterinary Res, Bacteriol & Epidemiol, Lelystad, Netherlands Guangdong Second Prov Gen Hosp, Dept Rheumatol & Immunol, Guangzhou, Guangdong, Peoples R China Erasmus MC, Biomed Rngineering, Rotterdam, Netherlands Hiroshima Univ, Grad Sch Biomed & Hlth Sci, Hiroshima, Japan Univ Iceland, Sch Hlth Sci, Reykjavik, Iceland Ohio State Univ, Mat Sci & Engn, Columbus, OH 43210 USA Kathmandu Univ, Sch Med Sci, Dept Physiotherapy, Dhulikhel, Nepal Univ Queensland, Sch Biomed Sci, Brisbane, Qld, Australia Fraunhofer MEVIS, Image Guided Therapies, Bremen, Germany Natl Univ Hlth Syst, Haematol Oncol, Singapore, Singapore Sun Yat Sen Univ, Canc Ctr, Breast Oncol, Guangzhou, Guangdong, Peoples R China Med Coll Wisconsin, Pharmacol & Toxicol, Wauwatosa, WI USA Queensland Univ Technol, Sci & Engn Fac, Sch Chem Phys & Mech Engn, Brisbane, Qld, Australia Univ Turin, Dept Mol Biotechnol & Hlth Sci, Turin, Italy Univ Tehran Med Sci, Sch Rehabil, Physiotherapy Dept, Tehran, Iran Univ Helsinki, Dept Forest Sci, Helsinki, Finland Univ Messina, Human Pathol, Messina, Italy AO Papardo Hosp Messina, Messina, Italy Univ Ibadan, Coll Med, Inst Child Hlth, Ibadan, Nigeria King Faisal Univ, Coll Med, Fac Ophthalmol, Al Hasa, Saudi Arabia Univ Stirling, Inst Social Mkt, Stirling, Scotland Saveh Univ Med Sci, Social Determinants Hlth Res Ctr, Saveh, Iran Gakujutsu Shien Co Ltd, Tokyo, Japan Chinese Acad Sci, Inst Geochem, Guiyang, Guizhou, Peoples R China Univ Plymouth, Med Sch, Plymouth, Devon, England CHU Toulouse, Immunol, Toulouse, France Azorean Biodivers Grp, Ctr Ecol Evolut & Environm Changes, Azores, Portugal Univ Acores, Azores, Portugal RIKEN, Ctr Integrat Med Sci, Yokohama, Kanagawa, Japan Peking Univ, Sch Publ Hlth, Dept Global Hlth, Beijing, Peoples R China Chang Gung Univ, Chang Gung Mem Hosp, Dept Neurol, Linkou Med Ctr, Taoyuan, Taiwan Chang Gung Univ, Coll Med, Taoyuan, Taiwan Univ Malawi, Coll Med, Biomed Sci Dept, Blantyre, Malawi Univ Malawi, Coll Med, Pharm Dept, Blantyre, Malawi Bioself Commun, Biocurat, Marseille, France Peking Univ, Hosp 3, Dept Neurol, Beijing, Peoples R China Ahmadu Bello Univ, Fac Basic Clin Sci, Coll Hlth Sci, Dept Pathol, Zaria, Nigeria Dalhousie Univ, Dept Anesthesia Pain Management & Perioperat Med, Halifax, NS, Canada VisMederi Srl, Siena, Italy UCL, Canc Res UK, London, England UCL, UCL Canc Trials Ctr, London, England Univ Ottawa, Family Med, Ottawa, ON, Canada China Agr Univ, Coll Engn, Beijing, Peoples R China Leiden Univ, Leiden Acad Ctr Drug Res, Div Drug Discovery & Safety, Leiden, Netherlands Sun Yat Sen Univ, Affiliated Hosp 1, Dept Intervent Radiol, Guangzhou, Guangdong, Peoples R China Amer Univ Beirut, Med Ctr, Infect Dis, Beirut, Lebanon Sheffield Hallam Univ, Dept Social Work Social Care & Community Studies, Sheffield, S Yorkshire, England Mechnikov Res Inst Vaccines & Sera, Viral Hepatitis, Moscow, Russia Univ Ottawa, Pediat, Ottawa, ON, Canada Vreden Russian Res Inst Traumatol & Orthopaed, Dept Wound Infect Treatment & Prevent, St Petersburg, Russia Hangzhou Ctr Dis Control & Prevent, Dept TB Control & Prevent, Hangzhou, Zhejiang, Peoples R China Kaohsiung Med Univ, Dept Biotechnol, Kaohsiung, Taiwan Zoetis, Diagnost, Kalamazoo, MI USA Aintree Univ Hosp NHS Fdn Trust, Head & Neck Oncol Res, Liverpool, Merseyside, England Wrightington Hosp, Trauma & Orthopaed, Manchester, Lancs, England Loyola Univ, Med Ctr, Dept Psychiat, 2160 S 1st Ave, Maywood, IL 60153 USA Atkins Vet Serv, Microbiol, Calgary, AB, Canada Univ Porto, FADEUP, CIAFEL, Porto, Portugal Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore Kangwon Natl Univ, Coll Biotechnol & Biosci, Dept Food Sci & Biotechnol, Chunchon, South Korea Kakatiya Med Coll, Internal Med, Warangal, Telangana, India Univ Antioquia, Vet Med Sch, CIBAV Res Grp, Medellin, Colombia IISER, Dept Phys, Soft & Act Matter Grp, Tirupati 517507, Andhra Pradesh, India Univ Rosario, Sch Med & Hlth, Ctr Studies Phys Activ Measurements, Bogota, Colombia Univ Hosp Essen, Cardiol & Vasc Med, Essen, Germany Univ Hosp Basel, Endocrinol, Basel, Switzerland Univ Tubingen, Inst Med Genet & Appl Genom, Tubingen, Germany Univ Hosp Munster, Div Gen Internal Med Nephrol & Rheumatolog, Dept Med D, Munster, Germany Univ Kentucky, Dept Nephrol, Lexington, KY USA Univ Freiburg, Dept Anaesthesiol & Crit Care, Med Ctr, Freiburg, Germany Univ Calif Irvine, Dept Med, Orange, CA 92668 USA Univ Hosp Leuven, Dept Urol, Leuven, Belgium Chinese Acad Sci, Coll Life Sci, Beijing, Peoples R China Univ Florida, Orthopaed & Rehabil, Gainesville, FL USA Chongqing Med Univ, Affiliated Hosp 1, Chongqing Key Lab Mol Oncol & Epigenet, Chongqing, Peoples R China Tsinghua Univ, Dept Chem Engn, Beijing, Peoples R China Yonsei Univ, Coll Med, Dept Pharmacol, Seoul, South Korea Childrens Hosp Kings Daughters, Eastern Virginia Med Sch, Dept Pediat, Norfolk, VA USA China Three Gorges Univ, Coll Sci, Dept Math, Yichang, Peoples R China Xiangtan Univ, Coll Informat Engn, Xiangtan, Hunan, Peoples R China Univ Hlth Network, Mood Disorders & Psychopharmacol, Toronto, ON, Canada Sao Paulo State Univ UNESP, Dept Anim Sci, Sao Paulo, Brazil Sao Paulo State Univ, Vet Clin, Sao Paulo, Brazil

Published
2019

77. Real-world treatment patterns and outcomes for patients with advanced hepatocellular carcinoma initially treated with PD-1 inhibitors.

Author

Zou H, Ge Y, Chen W, Yao D, Oi Lam Ung C, Lai Y, and Hu H

Subjects
Humans, Male, Female, Middle Aged, Aged, China, Treatment Outcome, Adult, Chemoembolization, Therapeutic, Retrospective Studies, Carcinoma, Hepatocellular drug therapy, Carcinoma, Hepatocellular mortality, Liver Neoplasms drug therapy, Liver Neoplasms mortality, Immune Checkpoint Inhibitors therapeutic use, Antibodies, Monoclonal, Humanized therapeutic use, Programmed Cell Death 1 Receptor antagonists & inhibitors
Abstract

Background: Programmed cell death protein-1 (PD-1) inhibitors have shown promising clinical efficacy in treating advanced hepatocellular carcinoma (HCC). However, little evidence exists regarding their treatment patterns and outcomes in real-world practice in China. This study aimed to investigate real-world treatment patterns and outcomes of PD-1 inhibitors as first-line therapies for patients with advanced HCC in China., Methods: The study population included adult patients with advanced HCC who were initially treated with PD-1 inhibitors from April 2020 to November 2022 in China. Descriptive statistics were used to report first-line treatment patterns and associations between patient characteristics and the most frequently used treatment patterns. The effectiveness of first-line treatment with PD-1 inhibitors was also evaluated according to survival and tumor response., Results: The analyses enrolled 480 patients. The four most frequently used first-line treatment patterns of camrelizumab, tislelizumab, camrelizumab + TACE, and tislelizumab + TACE showed statistical differences in patient characteristics of gender, HBV infection, liver cirrhosis, BCLC stage, and portal vein tumor thrombus (all P < 0.05). However, there was no significant difference in median progression-free survival among the first-line treatments of tislelizumab, camrelizumab, and tislelizumab + TACE (not reached vs. 4.4 months vs. 3.6 months, P = 0.5178). The three groups had similar objective response rates (25.0 % vs. 28.6 % vs. 28.6 %, P = 0.927), and disease control rates (73.1 % vs. 78.6 % vs. 64.3 %, P = 0.573) with no statistical significance., Conclusions: Our findings provided insights into potential therapeutic strategies of PD-1 inhibitors in first-line settings for advanced HCC in real-world practice in China. It was recommended to consider patient characteristics associated with therapeutic options when making clinical decisions. Prospective randomized controlled studies with larger sample sizes and longer follow-up times were warranted further to verify the potential clinical benefits of PD-1 inhibitors., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Published
2024
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78. Results From a Prospective, Clinical Study (US-nPower) Evaluating a Miniature Spinal Cord Stimulator for the Management of Chronic, Intractable Pain.

Author

Desai MJ, Raju T, Ung C, Arulkumar S, Kapural L, Gupta M, Amirdelfan K, Rosenfeld D, Calodney A, Sayed D, Antony A, Li S, Naidu R, Ackerman J, Ball R, Fishman M, Staats P, Heit G, Kottalgi S, and Makous J

Subjects
Humans, Prospective Studies, Treatment Outcome, Pain Measurement methods, Spinal Cord, Low Back Pain therapy, Pain, Intractable, Chronic Pain therapy, Spinal Cord Stimulation methods, Neuralgia therapy
Abstract

Background: Chronic, intractable, neuropathic pain is readily treatable with spinal cord stimulation (SCS). Technological advancements, including device miniaturization, are advancing the field of neuromodulation., Objectives: We report here the results of an SCS clinical trial to treat chronic, low back and leg pain, with a micro-implantable pulse generator (micro-IPG)., Study Design: This was a single-arm, prospective, multicenter, postmarket, observational study., Setting: Patients were recruited from 15 US-based comprehensive pain centers., Methods: This open-label clinical trial was designed to evaluate the performance of the Nalu™ Neurostimulation System (Nalu Medical, Inc., Carlsbad, CA) in the treatment of low back and leg pain. Patients, who provided informed consent and were successfully screened for study entry, were implanted with temporary trial leads. Patients went on to receive a permanent implant of the leads and micro-IPG if they demonstrated a >= 50% reduction in pain during the temporary trial period. Patient-reported outcomes (PROs), such as pain scores, functional disability, mood, patient impression of change, comfort, therapy use profile, and device ease of use, were captured., Results: At baseline, the average pain Visual Analog Scale (VAS) score was 72.1 ± 17.9 in the leg and 78.0 ± 15.4 in the low back. At 90 days following permanent implant (end of study), pain scores improved by 76% (VAS 18.5 ± 18.8) in the leg and 75% (VAS 19.7 ± 20.8) in the low back. Eighty-six percent  of both leg pain and low back pain patients demonstrated a >= 50% reduction in pain at 90 days following implant. The comfort of the external wearable (Therapy Disc and Adhesive Clip) was rated 1.16 ± 1.53, on average, at 90 days on an 11-point rating scale (0 = very comfortable, 10 = very uncomfortable). All PROs demonstrated statistically significant symptomatic improvement at 90 days following implant of the micro-IPG., Limitations:   Limitations of this study include the lack of long-term results (beyond 90 days) and a relatively small sample size of 35 patients who were part of the analysis; additionally, there was no control arm or randomization as this was a single-arm study, without a comparator, designed to document the efficacy and safety of the device. Therefore, no direct comparisons to other SCS systems were possible., Conclusions: This clinical study demonstrated profound leg and low back pain relief in terms of overall pain reduction, as well as the proportion of therapy responders. The study patients reported the wearable aspects of the system to be very comfortable.

Published
2023

79. Network Biology-Inspired Machine Learning Features Predict Cancer Gene Targets and Reveal Target Coordinating Mechanisms.

Author

Weiskittel TM, Cao A, Meng-Lin K, Lehmann Z, Feng B, Correia C, Zhang C, Wisniewski P, Zhu S, Yong Ung C, and Li H

Abstract

Anticipating and understanding cancers' need for specific gene activities is key for novel therapeutic development. Here we utilized DepMap, a cancer gene dependency screen, to demonstrate that machine learning combined with network biology can produce robust algorithms that both predict what genes a cancer is dependent on and what network features coordinate such gene dependencies. Using network topology and biological annotations, we constructed four groups of novel engineered machine learning features that produced high accuracies when predicting binary gene dependencies. We found that in all examined cancer types, F1 scores were greater than 0.90, and model accuracy remained robust under multiple hyperparameter tests. We then deconstructed these models to identify tumor type-specific coordinators of gene dependency and identified that in certain cancers, such as thyroid and kidney, tumors' dependencies are highly predicted by gene connectivity. In contrast, other histologies relied on pathway-based features such as lung, where gene dependencies were highly predictive by associations with cell death pathway genes. In sum, we show that biologically informed network features can be a valuable and robust addition to predictive pharmacology models while simultaneously providing mechanistic insights.

Published
2023
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80. 27-GAUGE PARS PLANA/PLICATA VITRECTOMY FOR PEDIATRIC VITREORETINAL SURGERY.

Author

Ung C, Yonekawa Y, Chung MM, Berrocal AM, Kusaka S, Oshima Y, Chan RVP, Inoue M, Read SP, Kuriyan AE, Todorich B, Thanos A, Thomas BJ, Wolfe JD, Hassan TS, and Capone A Jr

Subjects
Infant, Newborn, Humans, Child, Infant, Child, Preschool, Vitrectomy, Retrospective Studies, Treatment Outcome, Vitreous Hemorrhage surgery, Retina, Postoperative Complications surgery, Vitreoretinal Surgery, Endophthalmitis etiology, Endophthalmitis surgery, Retinal Degeneration surgery
Abstract

Purpose: To report on the feasibility of 27-gauge (G) vitrectomy for pediatric patients., Methods: This study is an international, multicenter, retrospective, interventional case series. Participants were patients 17 years or younger who underwent 27-G vitrectomy for various indications., Results: The records of 56 eyes from 47 patients were reviewed. Mean age was 5.7 ± 5.2 years. Diagnoses included retinopathy of prematurity (Stages 3 with vitreous hemorrhage, 4A, 4B, and 5), Terson's syndrome, traumatic macular hole, posterior capsular opacification, endophthalmitis, and others. Instruments used were the 27-G infusion, 27-G vitreous cutter, 27-G light pipe, and 27-G internal limiting membrane forceps. Instrument bending was noted in one (1.8%) case. There were no cases with intraoperative complications, infusion issues, or postoperative endophthalmitis. There were 67/145 (46%) sclerotomies that required suturing, of which most (51/145) were sutured out of precaution. There were four cases (7.1%) that required conversion to a larger gauge and three cases (5.3%) that developed postoperative hypotony. Mean visual acuity improved from logarithm of the minimum angle of resolution 1.32 (20/420) to 0.72 (20/105), after a mean follow-up of 125.1 days (P = 0.01). Anatomic success was achieved in 96.4% of eyes after a single surgery., Conclusion: Twenty-seven-gauge vitrectomy was safe and feasible in selected pediatric vitreoretinopathies. Further studies are warranted to examine indications and outcomes.

Published
2023
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81. Polychromatic Aqueous and Vitreous Crystals Due to Phacolytic Glaucoma in a Patient With Marfan Syndrome and Lens Dislocation.

Author

Lains I, Ung C, Gong D, Parikh D, and Eliott D

Abstract

Purpose: To describe a patient with Marfan syndrome and crystalline lens luxation who developed phacolytic glaucoma with polychromatic crystals in the anterior chamber and vitreous. Methods: We present a retrospective case report. Results: A 58-year-old man with Marfan syndrome and crystalline lens luxation since childhood presented with 2 days of pain in the left eye. The visual acuity was 20/30 OS with an aphakic contact lens, and the intraocular pressure (IOP) was 31 mm Hg. Polychromatic crystals were evident in the anterior chamber and vitreous. The retina was attached. Despite medical treatment, the IOP remained elevated; therefore, a pars plana vitrectomy and lensectomy were performed. At the last follow-up, the IOP was normal and the retina remained attached. Conclusions: Phacolytic glaucoma can be seen in eyes with a subluxated or luxated mature or hypermature lens. In these rare cases, iridescent crystals can be observed in the aqueous and vitreous. Vitrectomy with lensectomy is the definitive treatment., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Published
2022
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82. Challenges and opportunities to penetrate the blood-brain barrier for brain cancer therapy.

Author

Upton DH, Ung C, George SM, Tsoli M, Kavallaris M, and Ziegler DS

Subjects
Biological Transport, Brain pathology, Drug Delivery Systems, Humans, Blood-Brain Barrier pathology, Brain Neoplasms pathology
Abstract

Despite significant advances in research, the prognosis for both primary and secondary brain cancers remains poor. The blood-brain barrier (BBB) is a complex and unique semi-permeable membrane that serves as a protective structure to maintain homeostasis within the brain. However, it presents a significant challenge for the delivery of therapeutics into the brain and tumor. Some brain tumors are known to compromise BBB integrity, producing a highly heterogeneous vasculature known as the blood-tumor-barrier (BTB). Identifying strategies to bypass these obstacles to improve the penetrability of anticancer therapeutics has been the focus of research in this area. In this review, we discuss the strategies that have been investigated to evade or alter the cellular and molecular barriers of both the BBB and the BTB and detail the methods currently under preclinical or clinical investigation, including molecular, biological, and physical processes to overcome the BBB or BTB. Increased understanding of the BBB and BTB and the current methods of overcoming these barriers will enable the development of new and more effective treatment strategies for brain tumors., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Published
2022
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83. In vitro and in vivo drug screens of tumor cells identify novel therapies for high-risk child cancer.

Author

Lau LMS, Mayoh C, Xie J, Barahona P, MacKenzie KL, Wong M, Kamili A, Tsoli M, Failes TW, Kumar A, Mould EVA, Gifford A, Chow SO, Pinese M, Fletcher JI, Arndt GM, Khuong-Quang DA, Wadham C, Batey D, Eden G, Trebilcock P, Joshi S, Alfred S, Gopalakrishnan A, Khan A, Grebert Wade D, Strong PA, Manouvrier E, Morgan LT, Span M, Lim JY, Cadiz R, Ung C, Thomas DM, Tucker KM, Warby M, McCowage GB, Dalla-Pozza L, Byrne JA, Saletta F, Fellowes A, Fox SB, Norris MD, Tyrrell V, Trahair TN, Lock RB, Cowley MJ, Ekert PG, Haber M, Ziegler DS, and Marshall GM

Subjects
Animals, Child, Disease Models, Animal, Genomics methods, Humans, Precision Medicine methods, Xenograft Model Antitumor Assays, Antineoplastic Agents pharmacology, Antineoplastic Agents therapeutic use, Neoplasms pathology
Abstract

Biomarkers which better match anticancer drugs with cancer driver genes hold the promise of improved clinical responses and cure rates. We developed a precision medicine platform of rapid high-throughput drug screening (HTS) and patient-derived xenografting (PDX) of primary tumor tissue, and evaluated its potential for treatment identification among 56 consecutively enrolled high-risk pediatric cancer patients, compared with conventional molecular genomics and transcriptomics. Drug hits were seen in the majority of HTS and PDX screens, which identified therapeutic options for 10 patients for whom no targetable molecular lesions could be found. Screens also provided orthogonal proof of drug efficacy suggested by molecular analyses and negative results for some molecular findings. We identified treatment options across the whole testing platform for 70% of patients. Only molecular therapeutic recommendations were provided to treating oncologists and led to a change in therapy in 53% of patients, of whom 29% had clinical benefit. These data indicate that in vitro and in vivo drug screening of tumor cells could increase therapeutic options and improve clinical outcomes for high-risk pediatric cancer patients., (© 2021 The Authors. Published under the terms of the CC BY 4.0 license.)

Published
2022
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84. Persistent Opioid Use after Ophthalmic Surgery in Opioid-Naive Patients and Associated Risk Factors.

Author

Ung C, Yonekawa Y, Waljee JF, Gunaseelan V, Lai YL, and Woodward MA

Subjects
Adolescent, Adult, Aged, Aged, 80 and over, Female, Humans, Insurance Claim Review, Male, Middle Aged, Retrospective Studies, Risk Factors, United States epidemiology, Analgesics, Opioid therapeutic use, Drug Prescriptions statistics & numerical data, Ophthalmologic Surgical Procedures, Opioid-Related Disorders epidemiology, Pain, Postoperative drug therapy, Prescription Drug Overuse statistics & numerical data
Abstract

Purpose: To determine the rate and risk factors for new persistent opioid use after ophthalmic surgery in the United States., Design: Retrospective claims-based cohort analysis., Participants: Opioid-naive patients 13 years of age and older who underwent incisional ophthalmic surgery between January 1, 2012, and June 30, 2017, and were included in Optum's de-identified Clinformatics Data Mart database., Methods: New persistent opioid use was defined as filling an opioid prescription in the 90-day and the 91- to 180-day periods after the surgical procedure. The outcome variable was an initial perioperative opioid prescription fill. Rates of new persistent opioid use were calculated, and multivariate logistic regression models were used to identify variables increasing the risk of new persistent use and refill of an opioid prescription after the initial perioperative prescription in first 30 days., Main Outcome Measures: New persistent opioid use and refill., Results: A total of 327 379 opioid-naive patients (mean age, 67 years [standard deviation, 16 years]; 178 067 women [54.4%]) who underwent ophthalmic surgery were examined. Among these patients, 14 841 (4.5%) had an initial perioperative opioid fill. The rate of new persistent opioid use was 3.4% (498 of 14 841 patients) compared with 0.6% (1833 of 312 538 patients) in patients who did not have an initial perioperative opioid fill. After adjusting for patient characteristics, initial perioperative opioid fill was associated independently with increased odds of new persistent use (adjusted odds ratio [OR], 6.21; 95% confidence interval [CI], 5.57-6.91; P < 0.001). Among patients who had filled an initial perioperative prescription, a prescription size of 150 morphine milligram equivalents or more was associated with an increased odds of refill (adjusted OR, 1.87; 95% CI, 1.58-2.22; P < 0.001)., Conclusions: Exposure to opioids in the perioperative period is associated with new persistent use in patients who were previously opioid-naive. This suggests that exposure to opioids is an independent risk factor for persistent use in patients undergoing incisional ophthalmic surgery. Surgeons should be aware of those risks to identify at-risk patients given the current national opioid crisis and to minimize prescribing opioids when possible., (Copyright © 2021 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Published
2021
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85. Opioid Prescribing Patterns among Retina Specialists in the United States.

Author

Ung C, Ung R, and Yonekawa Y

Subjects
Female, Follow-Up Studies, Humans, Male, Retrospective Studies, Societies, Medical, United States, Analgesics, Opioid pharmacology, Drug Prescriptions statistics & numerical data, Ophthalmologists, Practice Patterns, Physicians', Retinal Diseases drug therapy
Abstract

Purpose: To determine the opioid prescribing patterns among retina specialists and to assess predictors for high-volume prescribing., Design: Retrospective cohort study., Participants: American Society of Retina Specialists (ASRS) members in the 2013 through 2016 Medicare Part D Prescriber database., Methods: American Society of Retina Specialists members within the United States were profiled from the ASRS member directory as of April 2019. The Centers for Medicare and Medicaid Services Medicare Part D Prescriber Public Use Files for 2013, 2014, 2015, and 2016 were accessed. Data were collected and analyzed regarding the prescribing patterns for opioid drugs for all participating ASRS members., Main Outcome Measures: Mean number of opioid prescriptions written annually by retina specialists, prescriber rates compared with all prescriptions written, and geographic distribution of opioid prescriptions written by retina specialists., Results: The authors identified 1518 ASRS members in the Medicare database in 2016. Members had written a total of 14 127 prescriptions in 2016, with 66% of members writing at least 1 opioid prescription. On average, members wrote 11 opioid prescriptions per year. Almost one fifth (21%) wrote more than 10 prescriptions annually. A minority (6%) wrote more than 50 prescriptions. Among those writing more than 10 prescriptions annually, approximately 35 opioid prescriptions were written annually with a mean supply of 4 days. Using multivariate analysis, the factors associated with increased number of opioid prescriptions were male gender (β = 2.80; P < 0.001), a practice location in the South (β = 5.61; P < 0.001), and larger patient panel size (β = 0.029; P < 0.001). The total number of opioid prescriptions, including refills, written by members also decreased by 18% from 2013 to 2016 (P < 0.001)., Conclusions: American Society of Retina Specialists members prescribed opioids at a rate (1.5%) lower than the national mean of all prescribers across all medical specialties (6.8%). Male gender and a practice location in the South were correlated to number of prescriptions. Further research is needed to elucidate the appropriate indications for the prescription of opioids among retina specialists., (Copyright © 2021 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Published
2021
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86. Dual targeting of the epigenome via FACT complex and histone deacetylase is a potent treatment strategy for DIPG.

Author

Ehteda A, Simon S, Franshaw L, Giorgi FM, Liu J, Joshi S, Rouaen JRC, Pang CNI, Pandher R, Mayoh C, Tang Y, Khan A, Ung C, Tolhurst O, Kankean A, Hayden E, Lehmann R, Shen S, Gopalakrishnan A, Trebilcock P, Gurova K, Gudkov AV, Norris MD, Haber M, Vittorio O, Tsoli M, and Ziegler DS

Subjects
Acetylation, Animals, Brain Stem Neoplasms genetics, Brain Stem Neoplasms mortality, Brain Stem Neoplasms pathology, Carbazoles pharmacology, Cell Cycle Proteins genetics, Cell Cycle Proteins metabolism, Cell Line, Tumor, Child, Chromatin chemistry, Chromatin metabolism, DNA-Binding Proteins metabolism, Diffuse Intrinsic Pontine Glioma genetics, Diffuse Intrinsic Pontine Glioma mortality, Diffuse Intrinsic Pontine Glioma pathology, Drug Synergism, E2F1 Transcription Factor genetics, E2F1 Transcription Factor metabolism, Epigenome, High Mobility Group Proteins metabolism, Histones antagonists & inhibitors, Histones metabolism, Humans, Methylation, Mice, Neuroglia metabolism, Neuroglia pathology, Panobinostat pharmacology, Primary Cell Culture, Retinoblastoma Protein genetics, Retinoblastoma Protein metabolism, Signal Transduction, Survival Analysis, Transcription Factors genetics, Transcription Factors metabolism, Transcriptional Elongation Factors metabolism, Tumor Suppressor Protein p53 genetics, Tumor Suppressor Protein p53 metabolism, Xenograft Model Antitumor Assays, Antineoplastic Agents pharmacology, Brain Stem Neoplasms drug therapy, DNA-Binding Proteins genetics, Diffuse Intrinsic Pontine Glioma drug therapy, Epigenesis, Genetic, High Mobility Group Proteins genetics, Histones genetics, Neuroglia drug effects, Transcriptional Elongation Factors genetics
Abstract

Diffuse intrinsic pontine glioma (DIPG) is an aggressive and incurable childhood brain tumor for which new treatments are needed. CBL0137 is an anti-cancer compound developed from quinacrine that targets facilitates chromatin transcription (FACT), a chromatin remodeling complex involved in transcription, replication, and DNA repair. We show that CBL0137 displays profound cytotoxic activity against a panel of patient-derived DIPG cultures by restoring tumor suppressor TP53 and Rb activity. Moreover, in an orthotopic model of DIPG, treatment with CBL0137 significantly extends animal survival. The FACT subunit SPT16 is found to directly interact with H3.3K27M, and treatment with CBL0137 restores both histone H3 acetylation and trimethylation. Combined treatment of CBL0137 with the histone deacetylase inhibitor panobinostat leads to inhibition of the Rb/E2F1 pathway and induction of apoptosis. The combination of CBL0137 and panobinostat significantly prolongs the survival of mice bearing DIPG orthografts, suggesting a potential treatment strategy for DIPG., Competing Interests: Declaration of interests K.G. and A.V.G. are co-inventors on patents describing CBL0137. The remaining authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Published
2021
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87. Doxorubicin-Loaded Gold Nanoarchitectures as a Therapeutic Strategy against Diffuse Intrinsic Pontine Glioma.

Author

Ung C, Tsoli M, Liu J, Cassano D, Pocoví-Martínez S, Upton DH, Ehteda A, Mansfeld FM, Failes TW, Farfalla A, Katsinas C, Kavallaris M, Arndt GM, Vittorio O, Cirillo G, Voliani V, and Ziegler DS

Abstract

Diffuse Intrinsic Pontine Gliomas (DIPGs) are highly aggressive paediatric brain tumours. Currently, irradiation is the only standard treatment, but is palliative in nature and most patients die within 12 months of diagnosis. Novel therapeutic approaches are urgently needed for the treatment of this devastating disease. We have developed non-persistent gold nano-architectures (NAs) functionalised with human serum albumin (HSA) for the delivery of doxorubicin. Doxorubicin has been previously reported to be cytotoxic in DIPG cells. In this study, we have preclinically evaluated the cytotoxic efficacy of doxorubicin delivered through gold nanoarchitectures (NAs-HSA-Dox). We found that DIPG neurospheres were equally sensitive to doxorubicin and doxorubicin-loaded NAs. Colony formation assays demonstrated greater potency of NAs-HSA-Dox on colony formation compared to doxorubicin. Western blot analysis indicated increased apoptotic markers cleaved Parp, cleaved caspase 3 and phosphorylated H2AX in NAs-HSA-Dox treated DIPG neurospheres. Live cell content and confocal imaging demonstrated significantly higher uptake of NAs-HSA-Dox into DIPG neurospheres compared to doxorubicin alone. Despite the potency of the NAs in vitro, treatment of an orthotopic model of DIPG showed no antitumour effect. This disparate outcome may be due to the integrity of the blood-brain barrier and highlights the need to develop therapies to enhance penetration of drugs into DIPG.

Published
2021
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88. Dual targeting of polyamine synthesis and uptake in diffuse intrinsic pontine gliomas.

Author

Khan A, Gamble LD, Upton DH, Ung C, Yu DMT, Ehteda A, Pandher R, Mayoh C, Hébert S, Jabado N, Kleinman CL, Burns MR, Norris MD, Haber M, Tsoli M, and Ziegler DS

Subjects
Animals, Cell Death drug effects, Cell Line, Tumor, Cell Proliferation drug effects, DNA Replication drug effects, Dicarboxylic Acid Transporters, Disease Models, Animal, Eflornithine pharmacology, Eflornithine therapeutic use, Female, Gene Expression Regulation, Neoplastic drug effects, Humans, Mice, Mice, Inbred BALB C, Mice, Nude, Mitochondrial Membrane Transport Proteins, Ornithine Decarboxylase drug effects, Ornithine Decarboxylase metabolism, Polyamines therapeutic use, Biological Transport drug effects, Brain Stem Neoplasms drug therapy, Diffuse Intrinsic Pontine Glioma drug therapy, Polyamines metabolism, Polyamines pharmacology
Abstract

Diffuse intrinsic pontine glioma (DIPG) is an incurable malignant childhood brain tumor, with no active systemic therapies and a 5-year survival of less than 1%. Polyamines are small organic polycations that are essential for DNA replication, translation and cell proliferation. Ornithine decarboxylase 1 (ODC1), the rate-limiting enzyme in polyamine synthesis, is irreversibly inhibited by difluoromethylornithine (DFMO). Herein we show that polyamine synthesis is upregulated in DIPG, leading to sensitivity to DFMO. DIPG cells compensate for ODC1 inhibition by upregulation of the polyamine transporter SLC3A2. Treatment with the polyamine transporter inhibitor AMXT 1501 reduces uptake of polyamines in DIPG cells, and co-administration of AMXT 1501 and DFMO leads to potent in vitro activity, and significant extension of survival in three aggressive DIPG orthotopic animal models. Collectively, these results demonstrate the potential of dual targeting of polyamine synthesis and uptake as a therapeutic strategy for incurable DIPG.

Published
2021
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89. Current Management of Age-Related Macular Degeneration.

Author

Ung C, Lains I, Miller JW, and Kim IK

Subjects
Angiogenesis Inhibitors therapeutic use, Fluorescein Angiography, Humans, Tomography, Optical Coherence, Choroidal Neovascularization, Macular Degeneration drug therapy, Macular Degeneration therapy
Abstract

Age-related macular degeneration (AMD) remains a leading cause of blindness worldwide. The assessment and management of patients with this condition has evolved in the last decades. In this chapter, current standards for diagnosis, follow-up, and treatment of patients with AMD are reviewed and summarized. Namely, we highlight how current assessment has moved from conventional ophthalmoscopy and fluorescein angiography testing to a multimodal approach, and its important advantages. Alternatives to visual acuity for functional assessment of patients with AMD are also presented. Regarding strategies for follow-up and treatment, we provide specific information for the different stages (i.e., early, intermediate, and late) and forms (for example, choroidal neovascularization and geographic atrophy) of AMD. Specifically, we discuss the relevance and options for self-monitoring and non-pharmacological interventions. Additionally, a summary of the important trials (both on exudative and non-exudative AMD) that have helped inform clinical practice is provided, including data on antiangiogenic agents currently available, and outcomes of the different regimens that have been studied. The influence of advances in imaging on treatment strategies is also discussed.In summary, this chapter is a resource for all clinicians engaged in providing state of the art care for patients with AMD, and can help improve diagnosis, management, and outcomes of individuals with this blinding condition.

Published
2021
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90. Cost-Utility Analysis of Mindfulness-Based Cognitive Therapy Versus Antidepressant Pharmacotherapy for Prevention of Depressive Relapse in a Canadian Context: Analyse coût-utilité de la thérapie cognitive basée sur la pleine conscience contre la pharmacothérapie antidépressive pour prévenir la rechute de la dépression en contexte canadien.

Author

Pahlevan T, Ung C, and Segal Z

Subjects
Adolescent, Adult, Aged, Canada, Cognitive Behavioral Therapy methods, Cost-Benefit Analysis, Depression, Female, Humans, Male, Middle Aged, Mindfulness economics, Quality of Life, Recurrence, Treatment Outcome, Young Adult, Antidepressive Agents therapeutic use, Cognitive Behavioral Therapy economics, Depressive Disorder, Major therapy, Health Care Costs, Mindfulness methods, Secondary Prevention economics
Abstract

Objective: Patients suffering from major depressive disorder (MDD) experience impaired functioning and reduced quality of life, including an elevated risk of episode return. MDD is associated with high societal burden due to increased healthcare utilization, productivity losses, and suicide-related costs, making the long-term management of this illness a priority. The purpose of this study is to evaluate the cost-effectiveness of mindfulness-based cognitive therapy (MBCT), a first-line preventative psychological treatment, compared to maintenance antidepressant medication (ADM), the current standard of care., Method: A cost-utility analysis was conducted over a 24-month time horizon to model differences between MBCT and ADM in cost and quality-adjusted life years (QALY). The analysis was conducted using a decision tree analytic model. Intervention efficacy, utility, and costing data estimates were derived from published sources and expert consultation., Results: MBCT was found to be cost-effective compared to maintenance ADM over a 24-month time horizon. Antidepressant pharmacotherapy resulted in 1.10 QALY and $17,255.37 per patient on average, whereas MBCT resulted in 1.18 QALY and $15,030.70 per patient on average. This resulted in a cost difference of $2,224.67 and a QALY difference of 0.08, in favor of MBCT. Multiple sensitivity analyses supported these findings., Conclusions: From both a societal and health system perspective, utilizing MBCT as a first-line relapse prevention treatment is potentially cost-effective in a Canadian setting. Future economic evaluations should consider combined treatment (e.g., ADM and psychotherapy) as a comparator and longer time horizons as the literature advances.

Published
2020
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91. Clinical and Economic Evaluation of Salvianolate Injection for Coronary Heart Disease: A Retrospective Study Based on National Health Insurance Data in China.

Author

Yang L, Chen X, Oi Lam Ung C, Zhu H, Hu H, and Han S

Abstract

Objective: The study aimed to conduct clinical and economic evaluation of salvianolate injection for patients with coronary heart disease (CHD) in comparison to Danhong injection and alprostadil injection., Method: This was a retrospective study using National Health Insurance Data about inpatients diagnosed with CHD in China in 2015 who met the inclusion criteria. The recruited patients were divided into two samples: surgery and non-surgery. The exposed group received salvianolate injection, while the control group received either alprostadil injection or Danhong injection. The medical cost per hospitalization, hospitalization duration, and the rehospitalization rates were used as outcome indicators. Heterogeneity was processed according to disease stratification. Propensity score matching and multivariate analysis were used for statistical analysis to control potential confounding factors., Results: The hospitalization duration of salvianolate injection group was significantly ( P < 0.05) shorter than that of Danhong injection group in the non-surgery sample. The hospitalization duration of salvianolate injection group was significantly ( P < 0.05) shorter than those of alprostadil injection group in both surgery and non-surgery samples. In the non-surgery sample, the medical cost per hospitalization of salvianolate injection group was significantly ( P < 0.05) lower than that of alprostadil injection group. However, there were no statistical differences of rehospitalization rates in salvianolate injection group versus alprostadil injection group or salvianolate injection group versus Danhong injection group in both surgery and non-surgery samples., Conclusion: Salvianolate injection showed advantages in reducing hospitalization duration for inpatients with CHD when comparing with alprostadil injection and Danhong injection. The results of this real-world study can help to inform clinical practice for CHD patients., (Copyright © 2020 Yang, Chen, Oi Lam Ung, Zhu, Hu and Han.)

Published
2020
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92. Late-Onset Retinal Findings and Complications in Untreated Retinopathy of Prematurity.

Author

Hamad AE, Moinuddin O, Blair MP, Schechet SA, Shapiro MJ, Quiram PA, Mammo DA, Berrocal AM, Prakhunhungsit S, Cernichiaro-Espinosa LA, Mukai S, Yonekawa Y, Ung C, Holz ER, Harper CA 3rd, Young RC, Besirli CG, Nagiel A, Lee TC, Gupta MP, Walsh MK, Khawly JA, Campbell JP, Kychenthal A, Nudleman ED, Robinson JE, Hartnett ME, Calvo CM, and Chang EY

Subjects
Adolescent, Adult, Aged, Child, Disease Progression, Female, Fundus Oculi, Humans, Male, Middle Aged, Retinal Detachment etiology, Retinal Perforations etiology, Retinopathy of Prematurity complications, Retrospective Studies, Time Factors, Young Adult, Fluorescein Angiography methods, Retina pathology, Retinal Detachment diagnosis, Retinal Perforations diagnosis, Retinopathy of Prematurity diagnosis, Visual Acuity
Abstract

Purpose: To investigate late retinal findings and complications of eyes with a history of retinopathy of prematurity (ROP) that did not meet treatment criteria and did not receive treatment during infancy., Design: Retrospective, nonconsecutive, noncomparative, multicenter case series., Participants: Three hundred sixty-three eyes of 186 patients., Methods: Data were requested from multiple providers on premature patients with a history of ROP and no treatment during infancy who demonstrated late retinal findings or complications and included age, gender, gestational age and weight, zone and stage at infancy, visual acuity, current retina vascularization status, vitreous character, presence of peripheral retinal findings such as lattice retinal tears and detachments (RDs), retinoschisis, and fluorescein findings., Main Outcome Measures: Rate of RDs and factors conferring a higher risk of RDs., Results: The average age was 34.5 years (range, 7-76 years), average gestational age was 26.6 weeks (range, 23-34 weeks), and average birth weight was 875 g (range, 425-1590 g). Findings included lattice in 196 eyes (54.0%), atrophic holes in 126 eyes (34.7%), retinal tears in 111 eyes (30.6%), RDs in 140 eyes (38.6 %), tractional retinoschisis in 44 eyes (11.9%), and visible vitreous condensation ridge-like interface in 112 eyes (30.5%). Fluorescein angiography (FA) was performed in 113 eyes, of which 59 eyes (52.2%) showed leakage and 16 eyes (14.2%) showed neovascularization. Incomplete vascularization posterior to zone 3 was common (71.6% of eyes). Retinal detachments were more likely in patients with a gestational age of 29 weeks or less (P < 0.05) and in eyes with furthest vascularization to posterior zone 2 eyes compared with zone 3 eyes (P = 0.009)., Conclusions: Eyes with ROP not meeting the treatment threshold during infancy showed various late retinal findings and complications, of which RDs were the most concerning. Complications were seen in all age groups, including patients born after the Early Treatment for Retinopathy of Prematurity Study. Contributing factors to RDs included atrophic holes within peripheral avascular retina, visible vitreous condensation ridge-like interface with residual traction, and premature vitreous syneresis. We recommend regular examinations and consideration of ultra-widefield FA examinations. Prospective studies are needed to explore the frequency of complications and benefit of prophylactic treatment and if eyes treated with anti-vascular endothelial growth factor therapy are at risk of similar findings and complications., (Copyright © 2019 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Published
2020
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93. Checkpoint inhibitor-induced sarcoid choroidal granulomas.

Author

Ung C and Gragoudas E

Abstract

Purpose: To present a novel case of sarcoid choroidal granulomas due to nivolumab therapy for metastatic cutaneous melanoma., Observations: A 55 year-old male with a history of stage III metastatic cutaneous melanoma treated by nivolumab presented with bilateral choroidal lesions. The ophthalmologic examination revealed bilateral creamy, yellow choroidal lesions with no ocular inflammation. The systemic workup revealed pulmonary sarcoidosis confirmed by biopsy., Conclusion: Nivolumab is an immune checkpoint inhibitor therapy used in the treatment of metastatic melanoma. With the increasing use of immune checkpoint inhibitors in patients with advanced melanoma, clinicians should be aware of this potential associated immune-related adverse event., Competing Interests: The following authors have no financial disclosures: CU, EG., (© 2020 The Authors.)

Published
2020
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94. Indications, Findings, and Outcomes of Pars Plana Vitrectomy after Open Globe Injury.

Author

Ung C, Stryjewski TP, and Eliott D

Subjects
Adolescent, Adult, Aged, Aged, 80 and over, Child, Child, Preschool, Eye Injuries complications, Eye Injuries diagnosis, Female, Follow-Up Studies, Humans, Male, Middle Aged, Recurrence, Retinal Detachment diagnosis, Retinal Detachment etiology, Retrospective Studies, Tomography, X-Ray Computed, Vitreoretinopathy, Proliferative diagnosis, Vitreoretinopathy, Proliferative etiology, Young Adult, Eye Injuries surgery, Retinal Detachment surgery, Visual Acuity, Vitrectomy methods, Vitreoretinopathy, Proliferative surgery
Abstract

Purpose: To determine the indications, findings, and outcomes of patients with open globe injury (OGI) requiring pars plana vitrectomy (PPV)., Design: Retrospective, single-vitreoretinal surgeon case series., Participants: Sixty-one consecutive eyes with OGI that required PPV., Methods: Retrospective chart review of consecutive patients who underwent PPV after OGI between March 1, 2011, and August 1, 2017, at Massachusetts Eye and Ear by 1 surgeon., Main Outcome Measures: Final visual acuity and rates of recurrent retinal detachment (RD) and proliferative vitreoretinopathy (PVR)., Results: Sixty-one eyes of 61 consecutive patients underwent PPV after sustaining OGI. Mean follow-up was 12.8±12.1 months (range, 0.5-65 months). At the time of presentation after OGI, 64% of eyes showed light perception or worse vision. The indications for PPV, which was performed on average of 15 days after injury, included RD without retinal incarceration (39%), RD with retinal incarceration in the scleral or corneal wound or both (13%), media opacity without RD (28%), vitreous traction without RD (11%), intraocular foreign body (5%), and endophthalmitis (3%). At the time of PPV, substantial comorbidities were noted, including corneal trauma (20%), hyphema (41%), iris trauma (62%), lens expulsion (54%), subretinal hemorrhage (51%), and choroidal hemorrhage (30%). Using multivariate analysis, factors associated with RD after initial PPV were preoperative subretinal hemorrhage (odds ratio [OR], 5.73; P = 0.03), PVR found at initial PPV (OR, 11.94; P = 0.021), and retinectomy (OR, 17.88; P = 0.003). No patients were inoperable, because all patients left the operating room with complete retinal reattachment. Of 35 eyes that showed RD, 19 (54%) redetached as a result of PVR. In 80% of eyes with RD at initial presentation (28/35 eyes), the retina remained completely attached at last follow-up, and 5 additional eyes remained partially attached (33/35 [94%]). Of 61 total eyes included in this study, 89% remained completely attached, and 42 (69%) achieved visual acuity of 20/200 or better at last follow-up., Conclusions: Despite substantial ocular comorbidities, PPV can result in retinal reattachment in even the most severe cases. Good visual outcomes can be achieved for most patients who undergo vitreoretinal surgery after open globe trauma., (Copyright © 2019. Published by Elsevier Inc.)

Published
2020
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95. Dysregulation of RNA Splicing in Tauopathies.

Author

Apicco DJ, Zhang C, Maziuk B, Jiang L, Ballance HI, Boudeau S, Ung C, Li H, and Wolozin B

Subjects
Alzheimer Disease genetics, Animals, Brain metabolism, Down-Regulation genetics, ErbB Receptors metabolism, Female, Heterozygote, Humans, Male, Mice, Inbred C57BL, Mice, Transgenic, Nerve Degeneration genetics, Nerve Degeneration pathology, Nerve Tissue Proteins genetics, Nerve Tissue Proteins metabolism, Proto-Oncogene Proteins c-myc metabolism, RNA, Messenger genetics, RNA, Messenger metabolism, RNA-Binding Proteins genetics, RNA-Binding Proteins metabolism, Sex Characteristics, Spliceosomes metabolism, Synapses metabolism, T-Cell Intracellular Antigen-1 genetics, T-Cell Intracellular Antigen-1 metabolism, RNA Splicing genetics, Tauopathies genetics
Abstract

Pathological aggregation of RNA binding proteins (RBPs) is associated with dysregulation of RNA splicing in PS19 P301S tau transgenic mice and in Alzheimer's disease brain tissues. The dysregulated splicing particularly affects genes involved in synaptic transmission. The effects of neuroprotective TIA1 reduction on PS19 mice are also examined. TIA1 reduction reduces disease-linked alternative splicing events for the major synaptic mRNA transcripts examined, suggesting that normalization of RBP functions is associated with the neuroprotection. Use of the NetDecoder informatics algorithm identifies key upstream biological targets, including MYC and EGFR, underlying the transcriptional and splicing changes in the protected compared to tauopathy mice. Pharmacological inhibition of MYC and EGFR activity in neuronal cultures tau recapitulates the neuroprotective effects of TIA1 reduction. These results demonstrate that dysfunction of RBPs and RNA splicing processes are major elements of the pathophysiology of tauopathies, as well as potential therapeutic targets for tauopathies., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Published
2019
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97. Degenerative Peripheral Retinoschisis: Observations From Ultra-Widefield Fundus Imaging.

Author

Thanos A, Todorich B, Pasadhika S, Khundkar T, Xu D, Jain A, Ung C, Faia LJ, Capone A Jr, Williams GA, Yonekawa Y, Sarraf D, and Wolfe JD

Subjects
Adult, Aged, Aged, 80 and over, Female, Fluorescein Angiography, Humans, Male, Middle Aged, Multimodal Imaging, Optical Imaging, Photography, Retrospective Studies, Tomography, Optical Coherence, Visual Acuity, Diagnostic Imaging methods, Retinoschisis diagnostic imaging
Abstract

Background and Objective: To describe the ultra-widefield (UWF) imaging characteristics of patients with degenerative peripheral retinoschisis (DPR) using Optomap technology., Patients and Methods: In this multicenter, retrospective, noncomparative, consecutive case series, eligible patients underwent detailed retinal examination including indirect ophthalmoscopy. UWF fundus imaging, including color fundus photography, autofluorescence, and angiography, was performed using standardized protocols and findings were recorded and reviewed and analyzed., Results: A total of 35 patients (58 eyes) with DPR were identified who underwent 55 sessions of UWF imaging. Mean age was 65 years, and the inferotemporal quadrant was most commonly affected (74% of eyes). Of these patients, 31 underwent fluorescein angiography and 90% of these studies illustrated abnormalities in the area affected by the schisis. The most common finding was retinal vascular leakage originating from the deep capillary plexus observed in 29 eyes (93.5%)., Conclusions: UWF imaging enables a more detailed identification of the clinical features associated with DPR and provides simple, practical, and noninvasive tools to monitor progression of disease. The breadth of retinal vascular complications identified with fluorescein angiography may suggest an important vascular component associated with the pathogenesis of this entity. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:557-564.]., (Copyright 2019, SLACK Incorporated.)

Published
2019
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98. Characterization of Epiretinal Proliferation in Full-Thickness Macular Holes and Effects on Surgical Outcomes.

Author

Lee Kim E, Weiner AJ, Ung C, Roh M, Wang J, Lee IJ, Huang NT, Stem M, Dahrouj M, Eliott D, Vavvas DG, Young LHY, Williams GA, Garretson BR, Kim IK, Hassan TS, Mukai S, Ruby AJ, Faia LJ, Capone A Jr, Comander J, Kim LA, Wu DM, Drenser KA, Woodward MA, Wolfe JD, and Yonekawa Y

Subjects
Adolescent, Adult, Aged, Aged, 80 and over, Case-Control Studies, Epiretinal Membrane diagnostic imaging, Female, Follow-Up Studies, Humans, Male, Middle Aged, Retrospective Studies, Tomography, Optical Coherence, Visual Acuity physiology, Endotamponade, Epiretinal Membrane etiology, Retinal Perforations complications, Retinal Perforations surgery, Vitrectomy
Abstract

Purpose: Epiretinal proliferation is a distinct clinical entity from epiretinal membrane that classically is associated with lamellar macular holes, but its prevalence and association with full-thickness macular holes (FTMH) have not been well described. We characterized macular hole-associated epiretinal proliferation (MHEP) and its effects on long-term surgical outcomes., Design: Multicenter, interventional, retrospective case-control study., Participants: Consecutive eyes that underwent surgery for FTMH with a minimum of 12 months follow-up., Methods: All eyes underwent pars plana vitrectomy, removal of any epiretinal membranes, and gas tamponade, with or without internal limiting membrane (ILM) peeling. Spectral-domain OCT imaging was obtained before and after surgery., Main Outcome Measures: Improvement in visual acuity and single-surgery hole closure rates in eyes with, versus without, MHEP at 12 months., Results: Seven hundred twenty-five charts were analyzed, and 113 patients met inclusion criteria. Of 113 eyes with FTMH, 30 (26.5%) showed MHEP. Patients with FTMH and MHEP were older (P < 0.002) and more often men (P = 0.001), and showed more advanced macular hole stages than those without MHEP (P = 0.010). A full posterior vitreous detachment was more common in eyes with MHEP (P < 0.004). Twelve months after surgery, FTMH with MHEP patients showed significantly less improvement in visual acuity (P = 0.019) with higher rates of ellipsoid and external limiting membrane defects (P < 0.05) and with a higher rate of failure to close with 1 surgery compared to FTMH without MHEP (26.7% vs. 4.8%; P = 0.002]). Peeling the ILM was associated with improved rates of hole closure in FTMH with MHEP (P < 0.001). Multivariate testing confirmed that the presence of MHEP was an independent risk factor for less visual improvement (P = 0.031) and for single-surgery nonclosure (P = 0.009) and that ILM peeling improved single-surgery closure rates (P = 0.026)., Conclusions: We found that FTMH with MHEP showed poorer anatomic and visual outcomes after vitrectomy compared with FTMH without MHEP. Internal limiting membrane peeling was associated with improved closure rates and should be considered when MHEP is detected before surgery., (Copyright © 2019. Published by Elsevier Inc.)

Published
2019
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99. Evaluation of choroidal lesions with swept-source optical coherence tomography.

Author

Ung C, Laíns I, Silverman RF, Woods R, Lane AM, Papakostas TD, Husain D, Miller JW, Gragoudas ES, Kim IK, and Miller JB

Subjects
Adult, Aged, Aged, 80 and over, Cross-Sectional Studies, Female, Humans, Male, Middle Aged, Prospective Studies, Young Adult, Choroid Diseases diagnostic imaging, Choroid Diseases pathology, Tomography, Optical Coherence methods, Tomography, Optical Coherence standards
Abstract

Aims: The aim of our study was to image choroidal lesions with swept-source optical coherence tomography (SS-OCT) and to identify the morphological characteristics associated with optimal visualisation., Methods: This was a prospective, cross-sectional study. Patients with choroidal melanocytic lesions <3 mm in thickness on B-scan ultrasonography were recruited. All participants underwent SS-OCT. On SS-OCT we evaluated qualitative (eg, lesion outline, detection of scleral-choroidal interface and quality of the image) and quantitative (measurement of maximum lesion thickness and the largest basal diameter) parameters. Probability of optimal image quality was examined using ordered logistic regression models. The main outcome measure was quality of the choroidal lesion images on SS-OCT, defined as: optimal, suboptimal or poor., Results: We included 85 choroidal lesions of 82 patients. There were 24 choroidal lesions (29%) for which image quality was classified as optimal, 31 lesions (37%) as suboptimal and 30 lesions (36%) as poor. The factors associated with optimal image quality were distance closer to the fovea (OR 0.76, p<0.001), posterior pole location (OR 3.87, p=0.05), lower ultrasonography thickness (OR 0.44, p=0.04), lighter lesion pigmentation (OR 0.12, p=0.003) and smaller lesion diameter (OR 0.73, p<0.001). In the multivariable analysis, closer distance to the fovea (OR 0.81, p=0.005), lighter lesion pigmentation (OR 0.11, p=0.01) and smaller lesion diameter (OR 0.76, p=0.006) remained statistically significant., Conclusion: SS-OCT is useful in imaging most choroidal melanocytic lesions. Image quality is best when the choroidal lesion is closer to the fovea, has a smaller diameter and a lighter choroidal pigmentation., Competing Interests: Competing interests: IL receives travel expenses from Allergan. IKK: Consultant to Allergan, Alcon, Genentech and Iconic Therapeutics. JWM: Consultant to Alcon Research Institute, KalVista Pharmaceuticals Ltd, Maculogix Inc; Patent with ONL Therapeutics LLC, Royalties from Valeant Pharmaceuticals. JBM: Consultant to Allergan. The following authors have no financial disclosures: CU, RFS, RW, AML, TDP, DH, ESG., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2019. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Published
2019
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100. Intraoperative Optical Coherence Tomography in Vitreoretinal Surgery.

Author

Ung C and Miller JB

Subjects
Humans, Imaging, Three-Dimensional methods, Intraoperative Period, Retinal Diseases diagnostic imaging, Tomography, Optical Coherence instrumentation, Surgery, Computer-Assisted methods, Tomography, Optical Coherence methods, Vitreoretinal Surgery methods
Abstract

Intraoperative OCT ( i OCT) is an emerging modality capable of displaying real-time OCT images to the surgeon during surgery. The use of iOCT during vitreoretinal surgery improves our understanding of the tissue alterations that occur during surgical manipulations, which may impact surgical decision-making. We review the current i OCT modalities and clinical applications of i OCT.

Published
2019
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