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51. REVEL: An Ensemble Method for Predicting the Pathogenicity of Rare Missense Variants.

Author

Rothstein, Joseph, Pejaver, Vikas, Middha, Sumit, McDonnell, Shannon, Baheti, Saurabh, Musolf, Anthony, Li, Qing, Holzinger, Emily, Karyadi, Danielle, Cannon-Albright, Lisa, Teerlink, Craig, Stanford, Janet, Isaacs, William, Xu, Jianfeng, Cooney, Kathleen, Lange, Ethan, Schleutker, Johanna, Carpten, John, Powell, Isaac, Cussenot, Olivier, Cancel-Tassin, Geraldine, Giles, Graham, MacInnis, Robert, Maier, Christiane, Hsieh, Chih-Lin, Wiklund, Fredrik, Catalona, William, Foulkes, William, Mandal, Diptasri, Eeles, Rosalind, Kote-Jarai, Zsofia, Bustamante, Carlos, Schaid, Daniel, Hastie, Trevor, Ostrander, Elaine, Bailey-Wilson, Joan, Radivojac, Predrag, Thibodeau, Stephen, Whittemore, Alice, Sieh, Weiva, and Ioannidis, Nilah

Subjects
Area Under Curve, DNA Mutational Analysis, Disease, Exome, Gene Frequency, Humans, Mutation, Missense, ROC Curve, Software
Abstract

The vast majority of coding variants are rare, and assessment of the contribution of rare variants to complex traits is hampered by low statistical power and limited functional data. Improved methods for predicting the pathogenicity of rare coding variants are needed to facilitate the discovery of disease variants from exome sequencing studies. We developed REVEL (rare exome variant ensemble learner), an ensemble method for predicting the pathogenicity of missense variants on the basis of individual tools: MutPred, FATHMM, VEST, PolyPhen, SIFT, PROVEAN, MutationAssessor, MutationTaster, LRT, GERP, SiPhy, phyloP, and phastCons. REVEL was trained with recently discovered pathogenic and rare neutral missense variants, excluding those previously used to train its constituent tools. When applied to two independent test sets, REVEL had the best overall performance (p < 10-12) as compared to any individual tool and seven ensemble methods: MetaSVM, MetaLR, KGGSeq, Condel, CADD, DANN, and Eigen. Importantly, REVEL also had the best performance for distinguishing pathogenic from rare neutral variants with allele frequencies

Published
2016

52. Organic nanoparticle-doped microdroplets as dual-modality contrast agents for ultrasound microvascular flow and photoacoustic imaging

Author

Yu Xu, Guoyun Sun, Eshu Middha, Yu-Hang Liu, Kim Chuan Chan, Bin Liu, Chia-Hung Chen, and Nitish V. Thakor

Subjects
Medicine, Science
Abstract

Abstract Tumor blood vessels are chaotic and abundantly distributed, owing to their heterogeneity. Therefore, imaging techniques which reveal abnormalities of tumor vasculature play significant roles in both mechanistic and clinical diagnostic tumor studies. Photoacoustic (PA) imaging uses the intrinsic characteristics of hemoglobin, to acquire tumor hemodynamic information, while ultrasound (US) imaging provides information about tumoral vessel structures and blood flow. To improve the imaging contrast performance, hydrogel-based microdroplets were designed for both US blood flow and PA imaging in this study. The microdroplets served as carriers for PA contrast agent solution in the innermost part while oil and hydrogel formed the inner and outer layers of the droplets. In vitro experiments firstly demonstrated the dual modality contrast effects of the microdroplets on US flow determination and PA imaging. In vivo experiments were then carried out in both healthy nude mice and nude mice with subcutaneous tumor to validate the contrast effects and to monitor the duration of contrast effects in animals. Using the dual-modality microdroplets, we were able to obtain distinct edges of tumor and blood flow mapping of the tumor microvascular with improved sensitivity up to 11.09 dB for PA and 6.69 dB for US flow. Besides, the in vivo evaluation with microdroplets showed US flow enhancement for more than 60 min. Therefore, the microdroplets are able to provide the contrast effects for both US flow and PA in a relative long duration and have potential to be applied in the tumor related diagnoses and studies.

Published
2020
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53. Microbiomics and cloud-based analytics advance sustainable soil management

Author

Anupam J. Das, Renuka Ravinath, Budiyal Ramesh Shilpa, Bilgi Sampgod Rohith, Arvind Kumar Goyal, Nijalingappa Ramesh, Mothukapalli Krishnareddy Prasannakumar, Hemavathy Ekambaram, Talambedu Usha, and Sushil Kumar Middha

Subjects
microbiomics, soil, metagenomics, dna, sequencing, review, Biochemistry, QD415-436, Biology (General), QH301-705.5
Abstract

Soil constitutes a major component of the agro-ecosystem. Unrestrained uses of chemical pesticides and increased human activities have contributed to unprecedented changes in soil microflora affecting productivity. Modern microbiomics has proven to be an indispensable tool to understand the adaptations underlying complex soil microbial communities and their beneficial applications. In this review, we seek to emphasize the scope of microbiomics in enhancing soil productivity by providing an overview of the various sequencing platforms considering key parameters such as the accuracy, read lengths, reads per run, time involved and weighing out their pros and cons. The advances in modern ultra-high-throughput microbiomics platforms in combination with cloud-based analytics for in-depth exploration of soil-microbe associations can help achieve sustainable soil management contributing to better plant yield and productivity.

Published
2020
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54. A network analysis to identify mediators of germline-driven differences in breast cancer prognosis

Author

Maria Escala-Garcia, Jean Abraham, Irene L. Andrulis, Hoda Anton-Culver, Volker Arndt, Alan Ashworth, Paul L. Auer, Päivi Auvinen, Matthias W. Beckmann, Jonathan Beesley, Sabine Behrens, Javier Benitez, Marina Bermisheva, Carl Blomqvist, William Blot, Natalia V. Bogdanova, Stig E. Bojesen, Manjeet K. Bolla, Anne-Lise Børresen-Dale, Hiltrud Brauch, Hermann Brenner, Sara Y. Brucker, Barbara Burwinkel, Carlos Caldas, Federico Canzian, Jenny Chang-Claude, Stephen J. Chanock, Suet-Feung Chin, Christine L. Clarke, Fergus J. Couch, Angela Cox, Simon S. Cross, Kamila Czene, Mary B. Daly, Joe Dennis, Peter Devilee, Janet A. Dunn, Alison M. Dunning, Miriam Dwek, Helena M. Earl, Diana M. Eccles, A. Heather Eliassen, Carolina Ellberg, D. Gareth Evans, Peter A. Fasching, Jonine Figueroa, Henrik Flyger, Manuela Gago-Dominguez, Susan M. Gapstur, Montserrat García-Closas, José A. García-Sáenz, Mia M. Gaudet, Angela George, Graham G. Giles, David E. Goldgar, Anna González-Neira, Mervi Grip, Pascal Guénel, Qi Guo, Christopher A. Haiman, Niclas Håkansson, Ute Hamann, Patricia A. Harrington, Louise Hiller, Maartje J. Hooning, John L. Hopper, Anthony Howell, Chiun-Sheng Huang, Guanmengqian Huang, David J. Hunter, Anna Jakubowska, Esther M. John, Rudolf Kaaks, Pooja Middha Kapoor, Renske Keeman, Cari M. Kitahara, Linetta B. Koppert, Peter Kraft, Vessela N. Kristensen, Diether Lambrechts, Loic Le Marchand, Flavio Lejbkowicz, Annika Lindblom, Jan Lubiński, Arto Mannermaa, Mehdi Manoochehri, Siranoush Manoukian, Sara Margolin, Maria Elena Martinez, Tabea Maurer, Dimitrios Mavroudis, Alfons Meindl, Roger L. Milne, Anna Marie Mulligan, Susan L. Neuhausen, Heli Nevanlinna, William G. Newman, Andrew F. Olshan, Janet E. Olson, Håkan Olsson, Nick Orr, Paolo Peterlongo, Christos Petridis, Ross L. Prentice, Nadege Presneau, Kevin Punie, Dhanya Ramachandran, Gad Rennert, Atocha Romero, Mythily Sachchithananthan, Emmanouil Saloustros, Elinor J. Sawyer, Rita K. Schmutzler, Lukas Schwentner, Christopher Scott, Jacques Simard, Christof Sohn, Melissa C. Southey, Anthony J. Swerdlow, Rulla M. Tamimi, William J. Tapper, Manuel R. Teixeira, Mary Beth Terry, Heather Thorne, Rob A. E. M. Tollenaar, Ian Tomlinson, Melissa A. Troester, Thérèse Truong, Clare Turnbull, Celine M. Vachon, Lizet E. van der Kolk, Qin Wang, Robert Winqvist, Alicja Wolk, Xiaohong R. Yang, Argyrios Ziogas, Paul D. P. Pharoah, Per Hall, Lodewyk F. A. Wessels, Georgia Chenevix-Trench, Gary D. Bader, Thilo Dörk, Douglas F. Easton, Sander Canisius, and Marjanka K. Schmidt

Subjects
Science
Abstract

In breast cancer the contribution of different genetic variants to disease heritability is complex and not fully understood. Here, the authors present a network-based analysis in 84,567 patients studying ~7.3 million variants, identifying gene modules associated with breast cancer survival.

Published
2020
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55. A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

Author

Coignard, Juliette, Lush, Michael, Beesley, Jonathan, O’Mara, Tracy A., Dennis, Joe, Tyrer, Jonathan P., Barnes, Daniel R., McGuffog, Lesley, Leslie, Goska, Bolla, Manjeet K., Adank, Muriel A., Agata, Simona, Ahearn, Thomas, Aittomäki, Kristiina, Andrulis, Irene L., Anton-Culver, Hoda, Arndt, Volker, Arnold, Norbert, Aronson, Kristan J., Arun, Banu K., Augustinsson, Annelie, Azzollini, Jacopo, Barrowdale, Daniel, Baynes, Caroline, Becher, Heiko, Bermisheva, Marina, Bernstein, Leslie, Białkowska, Katarzyna, Blomqvist, Carl, Bojesen, Stig E., Bonanni, Bernardo, Borg, Ake, Brauch, Hiltrud, Brenner, Hermann, Burwinkel, Barbara, Buys, Saundra S., Caldés, Trinidad, Caligo, Maria A., Campa, Daniele, Carter, Brian D., Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Chung, Wendy K., Claes, Kathleen B. M., Clarke, Christine L., Collée, J. Margriet, Conroy, Don M., Czene, Kamila, Daly, Mary B., Devilee, Peter, Diez, Orland, Ding, Yuan Chun, Domchek, Susan M., Dörk, Thilo, dos-Santos-Silva, Isabel, Dunning, Alison M., Dwek, Miriam, Eccles, Diana M., Eliassen, A. Heather, Engel, Christoph, Eriksson, Mikael, Evans, D. Gareth, Fasching, Peter A., Flyger, Henrik, Fostira, Florentia, Friedman, Eitan, Fritschi, Lin, Frost, Debra, Gago-Dominguez, Manuela, Gapstur, Susan M., Garber, Judy, Garcia-Barberan, Vanesa, García-Closas, Montserrat, García-Sáenz, José A., Gaudet, Mia M., Gayther, Simon A., Gehrig, Andrea, Georgoulias, Vassilios, Giles, Graham G., Godwin, Andrew K., Goldberg, Mark S., Goldgar, David E., González-Neira, Anna, Greene, Mark H., Guénel, Pascal, Haeberle, Lothar, Hahnen, Eric, Haiman, Christopher A., Håkansson, Niclas, Hall, Per, Hamann, Ute, Harrington, Patricia A., Hart, Steven N., He, Wei, Hogervorst, Frans B. L., Hollestelle, Antoinette, Hopper, John L., Horcasitas, Darling J., Hulick, Peter J., Hunter, David J., Imyanitov, Evgeny N., Jager, Agnes, Jakubowska, Anna, James, Paul A., Jensen, Uffe Birk, John, Esther M., Jones, Michael E., Kaaks, Rudolf, Kapoor, Pooja Middha, Karlan, Beth Y., Keeman, Renske, Khusnutdinova, Elza, Kiiski, Johanna I., Ko, Yon-Dschun, Kosma, Veli-Matti, Kraft, Peter, Kurian, Allison W., Laitman, Yael, Lambrechts, Diether, Le Marchand, Loic, Lester, Jenny, Lesueur, Fabienne, Lindstrom, Tricia, Lopez-Fernández, Adria, Loud, Jennifer T., Luccarini, Craig, Mannermaa, Arto, Manoukian, Siranoush, Margolin, Sara, Martens, John W. M., Mebirouk, Noura, Meindl, Alfons, Miller, Austin, Milne, Roger L., Montagna, Marco, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Nielsen, Finn C., O’Brien, Katie M., Olopade, Olufunmilayo I., Olson, Janet E., Olsson, Håkan, Osorio, Ana, Ottini, Laura, Park-Simon, Tjoung-Won, Parsons, Michael T., Pedersen, Inge Sokilde, Peshkin, Beth, Peterlongo, Paolo, Peto, Julian, Pharoah, Paul D. P., Phillips, Kelly-Anne, Polley, Eric C., Poppe, Bruce, Presneau, Nadege, Pujana, Miquel Angel, Punie, Kevin, Radice, Paolo, Rantala, Johanna, Rashid, Muhammad U., Rennert, Gad, Rennert, Hedy S., Robson, Mark, Romero, Atocha, Rossing, Maria, Saloustros, Emmanouil, Sandler, Dale P., Santella, Regina, Scheuner, Maren T., Schmidt, Marjanka K., Schmidt, Gunnar, Scott, Christopher, Sharma, Priyanka, Soucy, Penny, Southey, Melissa C., Spinelli, John J., Steinsnyder, Zoe, Stone, Jennifer, Stoppa-Lyonnet, Dominique, Swerdlow, Anthony, Tamimi, Rulla M., Tapper, William J., Taylor, Jack A., Terry, Mary Beth, Teulé, Alex, Thull, Darcy L., Tischkowitz, Marc, Toland, Amanda E., Torres, Diana, Trainer, Alison H., Truong, Thérèse, Tung, Nadine, Vachon, Celine M., Vega, Ana, Vijai, Joseph, Wang, Qin, Wappenschmidt, Barbara, Weinberg, Clarice R., Weitzel, Jeffrey N., Wendt, Camilla, Wolk, Alicja, Yadav, Siddhartha, Yang, Xiaohong R., Yannoukakos, Drakoulis, Zheng, Wei, Ziogas, Argyrios, Zorn, Kristin K., Park, Sue K., Thomassen, Mads, Offit, Kenneth, Schmutzler, Rita K., Couch, Fergus J., Simard, Jacques, Chenevix-Trench, Georgia, Easton, Douglas F., Andrieu, Nadine, and Antoniou, Antonis C.

Published
2021
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56. Expectations and realities of digital public spaces: A case study of digital community engagement in Melbourne, Australia

Author

Ian McShane and Bhavna Middha

Subjects
Digital community engagement, relational space, expectations and realities, digital public space, urban planning, Australia, Human ecology. Anthropogeography, GF1-900, Urban groups. The city. Urban sociology, HT101-395
Abstract

This article analyses expectations and experiences of digital public spaces that facilitate community engagement with urban planning. While viewing digital spaces as part of an expanding repertoire of public spaces and events – physical and digital – that signify the participatory turn in municipal governance, we argue that local officials and residents are overly optimistic about the democratic and administrative capacities of the digital sphere. Through a case study from Melbourne, Australia – a city with significant growth pressures – we argue that the experience of new participatory digital platforms falls short of expectations, for both residents and officials. Data show that well-documented problems with established modes of community engagement such as agenda control and ‘black boxing’ of responses, are replicated in on-line settings. The wariness residents have of administrators and elected officials are overlaid by new concerns of digital distrust and digital exclusion. For officials, using these digital spaces effectively requires time to develop and apply new skills. Our study suggests that digital spaces are not homogenous but are made up of diverse and complex practices and interrelationships. The multiplex relationships making up these digital spaces suggest that strategic and contextual combinations of online and offline engagement may be a path towards inclusive and democratic community engagement.

Published
2021
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59. Publisher Correction: Shared heritability and functional enrichment across six solid cancers

Author

Xia Jiang, Hilary K. Finucane, Fredrick R. Schumacher, Stephanie L. Schmit, Jonathan P. Tyrer, Younghun Han, Kyriaki Michailidou, Corina Lesseur, Karoline B. Kuchenbaecker, Joe Dennis, David V. Conti, Graham Casey, Mia M. Gaudet, Jeroen R. Huyghe, Demetrius Albanes, Melinda C. Aldrich, Angeline S. Andrew, Irene L. Andrulis, Hoda Anton-Culver, Antonis C. Antoniou, Natalia N. Antonenkova, Susanne M. Arnold, Kristan J. Aronson, Banu K. Arun, Elisa V. Bandera, Rosa B. Barkardottir, Daniel R. Barnes, Jyotsna Batra, Matthias W. Beckmann, Javier Benitez, Sara Benlloch, Andrew Berchuck, Sonja I. Berndt, Heike Bickeböller, Stephanie A. Bien, Carl Blomqvist, Stefania Boccia, Natalia V. Bogdanova, Stig E. Bojesen, Manjeet K. Bolla, Hiltrud Brauch, Hermann Brenner, James D. Brenton, Mark N. Brook, Joan Brunet, Hans Brunnström, Daniel D. Buchanan, Barbara Burwinkel, Ralf Butzow, Gabriella Cadoni, Trinidad Caldés, Maria A. Caligo, Ian Campbell, Peter T. Campbell, Géraldine Cancel-Tassin, Lisa Cannon-Albright, Daniele Campa, Neil Caporaso, André L. Carvalho, Andrew T. Chan, Jenny Chang-Claude, Stephen J. Chanock, Chu Chen, David C. Christiani, Kathleen B. M. Claes, Frank Claessens, Judith Clements, J. Margriet Collée, Marcia Cruz Correa, Fergus J. Couch, Angela Cox, Julie M. Cunningham, Cezary Cybulski, Kamila Czene, Mary B. Daly, Anna deFazio, Peter Devilee, Orland Diez, Manuela Gago-Dominguez, Jenny L. Donovan, Thilo Dörk, Eric J. Duell, Alison M. Dunning, Miriam Dwek, Diana M. Eccles, Christopher K. Edlund, Digna R. Velez Edwards, Carolina Ellberg, D. Gareth Evans, Peter A. Fasching, Robert L. Ferris, Triantafillos Liloglou, Jane C. Figueiredo, Olivia Fletcher, Renée T. Fortner, Florentia Fostira, Silvia Franceschi, Eitan Friedman, Steven J. Gallinger, Patricia A. Ganz, Judy Garber, José A. García-Sáenz, Simon A. Gayther, Graham G. Giles, Andrew K. Godwin, Mark S. Goldberg, David E. Goldgar, Ellen L. Goode, Marc T. Goodman, Gary Goodman, Kjell Grankvist, Mark H. Greene, Henrik Gronberg, Jacek Gronwald, Pascal Guénel, Niclas Håkansson, Per Hall, Ute Hamann, Freddie C. Hamdy, Robert J. Hamilton, Jochen Hampe, Aage Haugen, Florian Heitz, Rolando Herrero, Peter Hillemanns, Michael Hoffmeister, Estrid Høgdall, Yun-Chul Hong, John L. Hopper, Richard Houlston, Peter J. Hulick, David J. Hunter, David G. Huntsman, Gregory Idos, Evgeny N. Imyanitov, Sue Ann Ingles, Claudine Isaacs, Anna Jakubowska, Paul James, Mark A. Jenkins, Mattias Johansson, Mikael Johansson, Esther M. John, Amit D. Joshi, Radka Kaneva, Beth Y. Karlan, Linda E. Kelemen, Tabea Kühl, Kay-Tee Khaw, Elza Khusnutdinova, Adam S. Kibel, Lambertus A. Kiemeney, Jeri Kim, Susanne K. Kjaer, Julia A. Knight, Manolis Kogevinas, Zsofia Kote-Jarai, Stella Koutros, Vessela N. Kristensen, Jolanta Kupryjanczyk, Martin Lacko, Stephan Lam, Diether Lambrechts, Maria Teresa Landi, Philip Lazarus, Nhu D. Le, Eunjung Lee, Flavio Lejbkowicz, Heinz-Josef Lenz, Goska Leslie, Davor Lessel, Jenny Lester, Douglas A. Levine, Li Li, Christopher I. Li, Annika Lindblom, Noralane M. Lindor, Geoffrey Liu, Fotios Loupakis, Jan Lubiński, Lovise Maehle, Christiane Maier, Arto Mannermaa, Loic Le Marchand, Sara Margolin, Taymaa May, Lesley McGuffog, Alfons Meindl, Pooja Middha, Austin Miller, Roger L. Milne, Robert J. MacInnis, Francesmary Modugno, Marco Montagna, Victor Moreno, Kirsten B. Moysich, Lorelei Mucci, Kenneth Muir, Anna Marie Mulligan, Katherine L. Nathanson, David E. Neal, Andrew R. Ness, Susan L. Neuhausen, Heli Nevanlinna, Polly A. Newcomb, Lisa F. Newcomb, Finn Cilius Nielsen, Liene Nikitina-Zake, Børge G. Nordestgaard, Robert L. Nussbaum, Kenneth Offit, Edith Olah, Ali Amin Al Olama, Olufunmilayo I. Olopade, Andrew F. Olshan, Håkan Olsson, Ana Osorio, Hardev Pandha, Jong Y. Park, Nora Pashayan, Michael T. Parsons, Tanja Pejovic, Kathryn L. Penney, Wilbert H. M. Peters, Catherine M. Phelan, Amanda I. Phipps, Dijana Plaseska-Karanfilska, Miranda Pring, Darya Prokofyeva, Paolo Radice, Kari Stefansson, Susan J. Ramus, Leon Raskin, Gad Rennert, Hedy S. Rennert, Elizabeth J. van Rensburg, Marjorie J. Riggan, Harvey A. Risch, Angela Risch, Monique J. Roobol, Barry S. Rosenstein, Mary Anne Rossing, Kim De Ruyck, Emmanouil Saloustros, Dale P. Sandler, Elinor J. Sawyer, Matthew B. Schabath, Johanna Schleutker, Marjanka K. Schmidt, V. Wendy Setiawan, Hongbing Shen, Erin M. Siegel, Weiva Sieh, Christian F. Singer, Martha L. Slattery, Karina Dalsgaard Sorensen, Melissa C. Southey, Amanda B. Spurdle, Janet L. Stanford, Victoria L. Stevens, Sebastian Stintzing, Jennifer Stone, Karin Sundfeldt, Rebecca Sutphen, Anthony J. Swerdlow, Eloiza H. Tajara, Catherine M. Tangen, Adonina Tardon, Jack A. Taylor, M. Dawn Teare, Manuel R. Teixeira, Mary Beth Terry, Kathryn L. Terry, Stephen N. Thibodeau, Mads Thomassen, Line Bjørge, Marc Tischkowitz, Amanda E. Toland, Diana Torres, Paul A. Townsend, Ruth C. Travis, Nadine Tung, Shelley S. Tworoger, Cornelia M. Ulrich, Nawaid Usmani, Celine M. Vachon, Els Van Nieuwenhuysen, Ana Vega, Miguel Elías Aguado-Barrera, Qin Wang, Penelope M. Webb, Clarice R. Weinberg, Stephanie Weinstein, Mark C. Weissler, Jeffrey N. Weitzel, Catharine M. L. West, Emily White, Alice S. Whittemore, H-Erich Wichmann, Fredrik Wiklund, Robert Winqvist, Alicja Wolk, Penella Woll, Michael Woods, Anna H. Wu, Xifeng Wu, Drakoulis Yannoukakos, Wei Zheng, Shanbeh Zienolddiny, Argyrios Ziogas, Kristin K. Zorn, Jacqueline M. Lane, Richa Saxena, Duncan Thomas, Rayjean J. Hung, Brenda Diergaarde, James McKay, Ulrike Peters, Li Hsu, Montserrat García-Closas, Rosalind A. Eeles, Georgia Chenevix-Trench, Paul J. Brennan, Christopher A. Haiman, Jacques Simard, Douglas F. Easton, Stephen B. Gruber, Paul D. P. Pharoah, Alkes L. Price, Bogdan Pasaniuc, Christopher I. Amos, Peter Kraft, and Sara Lindström

Subjects
Science
Abstract

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Published
2019
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60. Forensic chemical profiling of flavouring additives in seized mu’assel (shisha) by gas chromatography-mass spectrometry (GC-MS)

Author

Deepak Middha and Archna Negi

Subjects
Forensic chemistry, Carcinogenic, Flavour, GC-MS, Nicotine, Smoking, Law in general. Comparative and uniform law. Jurisprudence, K1-7720, Medicine (General), R5-920
Abstract

Abstract Background Water-pipe tobacco smoking obsession has again spread worldwide. Especially, the younger generation is besotted with mu’assel (shisha) and avidly use these for smoking. Numbers of additives are being added in commercial brands of mu’assel (shisha) to impart diverse taste with amusing aroma. The name of only one of the masking flavours like strawberry, chocolate, vanilla etc. and not the chemical ingredients are printed on the packets of mu’assel. The manufactures remain silent about mentioning the chemical ingredients used for flavourings as they may not have scientific data about chemical compounds attributing to multiple flavours. There is also a shortfall in quality control owing to non-availability of technical procedure(s) to identify masking multiple flavouring additives. Many of these flavoured additives are either carcinogenic or potentially hazardous for human health. Ignoring health hazards, the avaricious manufacturers are intentionally adding multiple additives to make their products more addictive in order to increase their sales. The need of the hour is to unequivocally establish a technique for chemical profiling of the flavouring additives in mu’assel. In this paper, seven popular commercial brands of mu’assel were extracted, sonicated and analysed by GC-MS technique for detection of flavouring additives. Results Twenty-eight flavouring additives, i.e. camphor, linalool, benzyl ethanol, β-citronellol, menthol, vanillin, ethyl vanillin, eugenol, eucalptol, patchouli alcohol, nerol, rheosmin, musk ambrette, musk ketone, phenyl ethyl methyl ether, anethole, estragole, limonene, benzaldehyde, terpineol, phenyl ethyl butyrate, phenethyl isobutyrate, piperonal, methyl isobutyrate, methyl dihydro jasmonate, anisyl alcohol, trans-geraniol and sabinene along with nicotine were detected in varied proportions by GC-MS technique in seven seized popular commercial brands of mu’assel. Conclusion A study on chemical profiling of flavouring additives in commercial mu’assel has yet not been reported. Henceforth, this forensic attempt was aimed to secure public health by chemically profiling the flavouring additives of mu’assel. Many of the detected additives may cause severe health problems. Moreover, the smoker may suffer from neuroticism and psychoticism that may lead to a number of cases pertaining to physical assaults and sexual harassment.

Published
2019
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61. Shared heritability and functional enrichment across six solid cancers

Author

Xia Jiang, Hilary K. Finucane, Fredrick R. Schumacher, Stephanie L. Schmit, Jonathan P. Tyrer, Younghun Han, Kyriaki Michailidou, Corina Lesseur, Karoline B. Kuchenbaecker, Joe Dennis, David V. Conti, Graham Casey, Mia M. Gaudet, Jeroen R. Huyghe, Demetrius Albanes, Melinda C. Aldrich, Angeline S. Andrew, Irene L. Andrulis, Hoda Anton-Culver, Antonis C. Antoniou, Natalia N. Antonenkova, Susanne M. Arnold, Kristan J. Aronson, Banu K. Arun, Elisa V. Bandera, Rosa B. Barkardottir, Daniel R. Barnes, Jyotsna Batra, Matthias W. Beckmann, Javier Benitez, Sara Benlloch, Andrew Berchuck, Sonja I. Berndt, Heike Bickeböller, Stephanie A. Bien, Carl Blomqvist, Stefania Boccia, Natalia V. Bogdanova, Stig E. Bojesen, Manjeet K. Bolla, Hiltrud Brauch, Hermann Brenner, James D. Brenton, Mark N. Brook, Joan Brunet, Hans Brunnström, Daniel D. Buchanan, Barbara Burwinkel, Ralf Butzow, Gabriella Cadoni, Trinidad Caldés, Maria A. Caligo, Ian Campbell, Peter T. Campbell, Géraldine Cancel-Tassin, Lisa Cannon-Albright, Daniele Campa, Neil Caporaso, André L. Carvalho, Andrew T. Chan, Jenny Chang-Claude, Stephen J. Chanock, Chu Chen, David C. Christiani, Kathleen B. M. Claes, Frank Claessens, Judith Clements, J. Margriet Collée, Marcia Cruz Correa, Fergus J. Couch, Angela Cox, Julie M. Cunningham, Cezary Cybulski, Kamila Czene, Mary B. Daly, Anna deFazio, Peter Devilee, Orland Diez, Manuela Gago-Dominguez, Jenny L. Donovan, Thilo Dörk, Eric J. Duell, Alison M. Dunning, Miriam Dwek, Diana M. Eccles, Christopher K. Edlund, Digna R Velez Edwards, Carolina Ellberg, D. Gareth Evans, Peter A. Fasching, Robert L. Ferris, Triantafillos Liloglou, Jane C. Figueiredo, Olivia Fletcher, Renée T. Fortner, Florentia Fostira, Silvia Franceschi, Eitan Friedman, Steven J. Gallinger, Patricia A. Ganz, Judy Garber, José A. García-Sáenz, Simon A. Gayther, Graham G. Giles, Andrew K. Godwin, Mark S. Goldberg, David E. Goldgar, Ellen L. Goode, Marc T. Goodman, Gary Goodman, Kjell Grankvist, Mark H. Greene, Henrik Gronberg, Jacek Gronwald, Pascal Guénel, Niclas Håkansson, Per Hall, Ute Hamann, Freddie C. Hamdy, Robert J. Hamilton, Jochen Hampe, Aage Haugen, Florian Heitz, Rolando Herrero, Peter Hillemanns, Michael Hoffmeister, Estrid Høgdall, Yun-Chul Hong, John L. Hopper, Richard Houlston, Peter J. Hulick, David J. Hunter, David G. Huntsman, Gregory Idos, Evgeny N. Imyanitov, Sue Ann Ingles, Claudine Isaacs, Anna Jakubowska, Paul James, Mark A. Jenkins, Mattias Johansson, Mikael Johansson, Esther M. John, Amit D. Joshi, Radka Kaneva, Beth Y. Karlan, Linda E. Kelemen, Tabea Kühl, Kay-Tee Khaw, Elza Khusnutdinova, Adam S. Kibel, Lambertus A. Kiemeney, Jeri Kim, Susanne K. Kjaer, Julia A. Knight, Manolis Kogevinas, Zsofia Kote-Jarai, Stella Koutros, Vessela N. Kristensen, Jolanta Kupryjanczyk, Martin Lacko, Stephan Lam, Diether Lambrechts, Maria Teresa Landi, Philip Lazarus, Nhu D. Le, Eunjung Lee, Flavio Lejbkowicz, Heinz-Josef Lenz, Goska Leslie, Davor Lessel, Jenny Lester, Douglas A. Levine, Li Li, Christopher I. Li, Annika Lindblom, Noralane M. Lindor, Geoffrey Liu, Fotios Loupakis, Jan Lubiński, Lovise Maehle, Christiane Maier, Arto Mannermaa, Loic Le Marchand, Sara Margolin, Taymaa May, Lesley McGuffog, Alfons Meindl, Pooja Middha, Austin Miller, Roger L. Milne, Robert J. MacInnis, Francesmary Modugno, Marco Montagna, Victor Moreno, Kirsten B. Moysich, Lorelei Mucci, Kenneth Muir, Anna Marie Mulligan, Katherine L. Nathanson, David E. Neal, Andrew R. Ness, Susan L. Neuhausen, Heli Nevanlinna, Polly A. Newcomb, Lisa F. Newcomb, Finn Cilius Nielsen, Liene Nikitina-Zake, Børge G. Nordestgaard, Robert L. Nussbaum, Kenneth Offit, Edith Olah, Ali Amin Al Olama, Olufunmilayo I. Olopade, Andrew F. Olshan, Håkan Olsson, Ana Osorio, Hardev Pandha, Jong Y. Park, Nora Pashayan, Michael T. Parsons, Tanja Pejovic, Kathryn L. Penney, Wilbert H M. Peters, Catherine M. Phelan, Amanda I. Phipps, Dijana Plaseska-Karanfilska, Miranda Pring, Darya Prokofyeva, Paolo Radice, Kari Stefansson, Susan J. Ramus, Leon Raskin, Gad Rennert, Hedy S. Rennert, Elizabeth J. van Rensburg, Marjorie J. Riggan, Harvey A. Risch, Angela Risch, Monique J. Roobol, Barry S. Rosenstein, Mary Anne Rossing, Kim De Ruyck, Emmanouil Saloustros, Dale P. Sandler, Elinor J. Sawyer, Matthew B. Schabath, Johanna Schleutker, Marjanka K. Schmidt, V. Wendy Setiawan, Hongbing Shen, Erin M. Siegel, Weiva Sieh, Christian F. Singer, Martha L. Slattery, Karina Dalsgaard Sorensen, Melissa C. Southey, Amanda B. Spurdle, Janet L. Stanford, Victoria L. Stevens, Sebastian Stintzing, Jennifer Stone, Karin Sundfeldt, Rebecca Sutphen, Anthony J. Swerdlow, Eloiza H. Tajara, Catherine M. Tangen, Adonina Tardon, Jack A. Taylor, M. Dawn Teare, Manuel R. Teixeira, Mary Beth Terry, Kathryn L. Terry, Stephen N. Thibodeau, Mads Thomassen, Line Bjørge, Marc Tischkowitz, Amanda E. Toland, Diana Torres, Paul A. Townsend, Ruth C. Travis, Nadine Tung, Shelley S. Tworoger, Cornelia M. Ulrich, Nawaid Usmani, Celine M. Vachon, Els Van Nieuwenhuysen, Ana Vega, Miguel Elías Aguado-Barrera, Qin Wang, Penelope M. Webb, Clarice R. Weinberg, Stephanie Weinstein, Mark C. Weissler, Jeffrey N. Weitzel, Catharine M. L. West, Emily White, Alice S. Whittemore, H-Erich Wichmann, Fredrik Wiklund, Robert Winqvist, Alicja Wolk, Penella Woll, Michael Woods, Anna H. Wu, Xifeng Wu, Drakoulis Yannoukakos, Wei Zheng, Shanbeh Zienolddiny, Argyrios Ziogas, Kristin K. Zorn, Jacqueline M. Lane, Richa Saxena, Duncan Thomas, Rayjean J. Hung, Brenda Diergaarde, James McKay, Ulrike Peters, Li Hsu, Montserrat García-Closas, Rosalind A. Eeles, Georgia Chenevix-Trench, Paul J. Brennan, Christopher A. Haiman, Jacques Simard, Douglas F. Easton, Stephen B. Gruber, Paul D. P. Pharoah, Alkes L. Price, Bogdan Pasaniuc, Christopher I. Amos, Peter Kraft, and Sara Lindström

Subjects
Science
Abstract

Similarities in cancers can be studied to interrogate their etiology. Here, the authors use genome-wide association study summary statistics from six cancer types based on 296,215 cases and 301,319 controls of European ancestry, showing that solid tumours arising from different tissues share a degree of common germline genetic basis.

Published
2019
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63. Genome-wide association study of germline variants and breast cancer-specific mortality

Author

Escala-Garcia, Maria, Guo, Qi, Dörk, Thilo, Canisius, Sander, Keeman, Renske, Dennis, Joe, Beesley, Jonathan, Lecarpentier, Julie, Bolla, Manjeet K., Wang, Qin, Abraham, Jean, Andrulis, Irene L., Anton-Culver, Hoda, Arndt, Volker, Auer, Paul L., Beckmann, Matthias W., Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Bernstein, Leslie, Blomqvist, Carl, Boeckx, Bram, Bojesen, Stig E., Bonanni, Bernardo, Børresen-Dale, Anne-Lise, Brauch, Hiltrud, Brenner, Hermann, Brentnall, Adam, Brinton, Louise, Broberg, Per, Brock, Ian W., Brucker, Sara Y., Burwinkel, Barbara, Caldas, Carlos, Caldés, Trinidad, Campa, Daniele, Canzian, Federico, Carracedo, Angel, Carter, Brian D., Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Chenevix-Trench, Georgia, Cheng, Ting-Yuan David, Chin, Suet-Feung, Clarke, Christine L., NBCS Collaborators, Cordina-Duverger, Emilie, Couch, Fergus J., Cox, David G., Cox, Angela, Cross, Simon S., Czene, Kamila, Daly, Mary B., Devilee, Peter, Dunn, Janet A., Dunning, Alison M., Durcan, Lorraine, Dwek, Miriam, Earl, Helena M., Ekici, Arif B., Eliassen, A. Heather, Ellberg, Carolina, Engel, Christoph, Eriksson, Mikael, Evans, D. Gareth, Figueroa, Jonine, Flesch-Janys, Dieter, Flyger, Henrik, Gabrielson, Marike, Gago-Dominguez, Manuela, Galle, Eva, Gapstur, Susan M., García-Closas, Montserrat, García-Sáenz, José A., Gaudet, Mia M., George, Angela, Georgoulias, Vassilios, Giles, Graham G., Glendon, Gord, Goldgar, David E., González-Neira, Anna, Alnæs, Grethe I. Grenaker, Grip, Mervi, Guénel, Pascal, Haeberle, Lothar, Hahnen, Eric, Haiman, Christopher A., Håkansson, Niclas, Hall, Per, Hamann, Ute, Hankinson, Susan, Harkness, Elaine F., Harrington, Patricia A., Hart, Steven N., Hartikainen, Jaana M., Hein, Alexander, Hillemanns, Peter, Hiller, Louise, Holleczek, Bernd, Hollestelle, Antoinette, Hooning, Maartje J., Hoover, Robert N., Hopper, John L., Howell, Anthony, Huang, Guanmengqian, Humphreys, Keith, Hunter, David J., Janni, Wolfgang, John, Esther M., Jones, Michael E., Jukkola-Vuorinen, Arja, Jung, Audrey, Kaaks, Rudolf, Kabisch, Maria, Kaczmarek, Katarzyna, Kerin, Michael J., Khan, Sofia, Khusnutdinova, Elza, Kiiski, Johanna I., Kitahara, Cari M., Knight, Julia A., Ko, Yon-Dschun, Koppert, Linetta B., Kosma, Veli-Matti, Kraft, Peter, Kristensen, Vessela N., Krüger, Ute, Kühl, Tabea, Lambrechts, Diether, Le Marchand, Loic, Lee, Eunjung, Lejbkowicz, Flavio, Li, Lian, Lindblom, Annika, Lindström, Sara, Linet, Martha, Lissowska, Jolanta, Lo, Wing-Yee, Loibl, Sibylle, Lubiński, Jan, Lux, Michael P., MacInnis, Robert J., Maierthaler, Melanie, Maishman, Tom, Makalic, Enes, Mannermaa, Arto, Manoochehri, Mehdi, Manoukian, Siranoush, Margolin, Sara, Martinez, Maria Elena, Mavroudis, Dimitrios, McLean, Catriona, Meindl, Alfons, Middha, Pooja, Miller, Nicola, Milne, Roger L., Moreno, Fernando, Mulligan, Anna Marie, Mulot, Claire, Nassir, Rami, Neuhausen, Susan L., Newman, William T., Nielsen, Sune F., Nordestgaard, Børge G., Norman, Aaron, Olsson, Håkan, Orr, Nick, Pankratz, V. Shane, Park-Simon, Tjoung-Won, Perez, Jose I. A., Pérez-Barrios, Clara, Peterlongo, Paolo, Petridis, Christos, Pinchev, Mila, Prajzendanc, Karoliona, Prentice, Ross, Presneau, Nadege, Prokofieva, Darya, Pylkäs, Katri, Rack, Brigitte, Radice, Paolo, Ramachandran, Dhanya, Rennert, Gadi, Rennert, Hedy S., Rhenius, Valerie, Romero, Atocha, Roylance, Rebecca, Saloustros, Emmanouil, Sawyer, Elinor J., Schmidt, Daniel F., Schmutzler, Rita K., Schneeweiss, Andreas, Schoemaker, Minouk J., Schumacher, Fredrick, Schwentner, Lukas, Scott, Rodney J., Scott, Christopher, Seynaeve, Caroline, Shah, Mitul, Simard, Jacques, Smeets, Ann, Sohn, Christof, Southey, Melissa C., Swerdlow, Anthony J., Talhouk, Aline, Tamimi, Rulla M., Tapper, William J., Teixeira, Manuel R., Tengström, Maria, Terry, Mary Beth, Thöne, Kathrin, Tollenaar, Rob A. E. M., Tomlinson, Ian, Torres, Diana, Truong, Thérèse, Turman, Constance, Turnbull, Clare, Ulmer, Hans-Ulrich, Untch, Michael, Vachon, Celine, van Asperen, Christi J., van den Ouweland, Ans M. W., van Veen, Elke M., Wendt, Camilla, Whittemore, Alice S., Willett, Walter, Winqvist, Robert, Wolk, Alicja, Yang, Xiaohong R., Zhang, Yan, Easton, Douglas F., Fasching, Peter A., Nevanlinna, Heli, Eccles, Diana M., Pharoah, Paul D. P., and Schmidt, Marjanka K.

Published
2019
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64. Author Correction: A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

Author

Juliette Coignard, Michael Lush, Jonathan Beesley, Tracy A. O’Mara, Joe Dennis, Jonathan P. Tyrer, Daniel R. Barnes, Lesley McGuffog, Goska Leslie, Manjeet K. Bolla, Muriel A. Adank, Simona Agata, Thomas Ahearn, Kristiina Aittomäki, Irene L. Andrulis, Hoda Anton-Culver, Volker Arndt, Norbert Arnold, Kristan J. Aronson, Banu K. Arun, Annelie Augustinsson, Jacopo Azzollini, Daniel Barrowdale, Caroline Baynes, Heko Becher, Marina Bermisheva, Leslie Bernstein, Katarzyna Białkowska, Carl Blomqvist, Stig E. Bojesen, Bernardo Bonanni, Ake Borg, Hiltrud Brauch, Hermann Brenner, Barbara Burwinkel, Saundra S. Buys, Trinidad Caldés, Maria A. Caligo, Daniele Campa, Brian D. Carter, Jose E. Castelao, Jenny Chang-Claude, Stephen J. Chanock, Wendy K. Chung, Kathleen B. M. Claes, Christine L. Clarke, GEMO Study Collaborators, EMBRACE Collaborators, J. Margriet Collée, Don M. Conroy, Kamila Czene, Mary B. Daly, Peter Devilee, Orland Diez, Yuan Chun Ding, Susan M. Domchek, Thilo Dörk, Isabel dos-Santos-Silva, Alison M. Dunning, Miriam Dwek, Diana M. Eccles, A. Heather Eliassen, Christoph Engel, Mikael Eriksson, D. Gareth Evans, Peter A. Fasching, Henrik Flyger, Florentia Fostira, Eitan Friedman, Lin Fritschi, Debra Frost, Manuela Gago-Dominguez, Susan M. Gapstur, Judy Garber, Vanesa Garcia-Barberan, Montserrat García-Closas, José A. García-Sáenz, Mia M. Gaudet, Simon A. Gayther, Andrea Gehrig, Vassilios Georgoulias, Graham G. Giles, Andrew K. Godwin, Mark S. Goldberg, David E. Goldgar, Anna González-Neira, Mark H. Greene, Pascal Guénel, Lothar Haeberle, Eric Hahnen, Christopher A. Haiman, Niclas Håkansson, Per Hall, Ute Hamann, Patricia A. Harrington, Steven N. Hart, Wei He, Frans B. L. Hogervorst, Antoinette Hollestelle, John L. Hopper, Darling J. Horcasitas, Peter J. Hulick, David J. Hunter, Evgeny N. Imyanitov, KConFab Investigators, HEBON Investigators, ABCTB Investigators, Agnes Jager, Anna Jakubowska, Paul A. James, Uffe Birk Jensen, Esther M. John, Michael E. Jones, Rudolf Kaaks, Pooja Middha Kapoor, Beth Y. Karlan, Renske Keeman, Elza Khusnutdinova, Johanna I. Kiiski, Yon-Dschun Ko, Veli-Matti Kosma, Peter Kraft, Allison W. Kurian, Yael Laitman, Diether Lambrechts, Loic Le Marchand, Jenny Lester, Fabienne Lesueur, Tricia Lindstrom, Adria Lopez-Fernández, Jennifer T. Loud, Craig Luccarini, Arto Mannermaa, Siranoush Manoukian, Sara Margolin, John W. M. Martens, Noura Mebirouk, Alfons Meindl, Austin Miller, Roger L. Milne, Marco Montagna, Katherine L. Nathanson, Susan L. Neuhausen, Heli Nevanlinna, Finn C. Nielsen, Katie M. O’Brien, Olufunmilayo I. Olopade, Janet E. Olson, Håkan Olsson, Ana Osorio, Laura Ottini, Tjoung-Won Park-Simon, Michael T. Parsons, Inge Sokilde Pedersen, Beth Peshkin, Paolo Peterlongo, Julian Peto, Paul D. P. Pharoah, Kelly-Anne Phillips, Eric C. Polley, Bruce Poppe, Nadege Presneau, Miquel Angel Pujana, Kevin Punie, Paolo Radice, Johanna Rantala, Muhammad U. Rashid, Gad Rennert, Hedy S. Rennert, Mark Robson, Atocha Romero, Maria Rossing, Emmanouil Saloustros, Dale P. Sandler, Regina Santella, Maren T. Scheuner, Marjanka K. Schmidt, Gunnar Schmidt, Christopher Scott, Priyanka Sharma, Penny Soucy, Melissa C. Southey, John J. Spinelli, Zoe Steinsnyder, Jennifer Stone, Dominique Stoppa-Lyonnet, Anthony Swerdlow, Rulla M. Tamimi, William J. Tapper, Jack A. Taylor, Mary Beth Terry, Alex Teulé, Darcy L. Thull, Marc Tischkowitz, Amanda E. Toland, Diana Torres, Alison H. Trainer, Thérèse Truong, Nadine Tung, Celine M. Vachon, Ana Vega, Joseph Vijai, Qin Wang, Barbara Wappenschmidt, Clarice R. Weinberg, Jeffrey N. Weitzel, Camilla Wendt, Alicja Wolk, Siddhartha Yadav, Xiaohong R. Yang, Drakoulis Yannoukakos, Wei Zheng, Argyrios Ziogas, Kristin K. Zorn, Sue K. Park, Mads Thomassen, Kenneth Offit, Rita K. Schmutzler, Fergus J. Couch, Jacques Simard, Georgia Chenevix-Trench, Douglas F. Easton, Nadine Andrieu, and Antonis C. Antoniou

Subjects
Science
Abstract

A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-23162-4

Published
2021
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65. Novel late-onset Alzheimer disease loci variants associate with brain gene expression.

Author

Allen, Mariet, Zou, Fanggeng, Chai, High Seng, Younkin, Curtis S, Crook, Julia, Pankratz, V Shane, Carrasquillo, Minerva M, Rowley, Christopher N, Nair, Asha A, Middha, Sumit, Maharjan, Sooraj, Nguyen, Thuy, Ma, Li, Malphrus, Kimberly G, Palusak, Ryan, Lincoln, Sarah, Bisceglio, Gina, Georgescu, Constantin, Schultz, Debra, Rakhshan, Fariborz, Kolbert, Christopher P, Jen, Jin, Haines, Jonathan L, Mayeux, Richard, Pericak-Vance, Margaret A, Farrer, Lindsay A, Schellenberg, Gerard D, Petersen, Ronald C, Graff-Radford, Neill R, Dickson, Dennis W, Younkin, Steven G, Ertekin-Taner, Nilüfer, Alzheimer's Disease Genetics Consortium (ADGC), Apostolova, Liana G, Arnold, Steven E, Baldwin, Clinton T, Barber, Robert, Barmada, Michael M, Beach, Thomas, Beecham, Gary W, Beekly, Duane, Bennett, David A, Bigio, Eileen H, Bird, Thomas D, Blacker, Deborah, Boeve, Bradley F, Bowen, James D, Boxer, Adam, Burke, James R, Buros, Jacqueline, Buxbaum, Joseph D, Cairns, Nigel J, Cantwell, Laura B, Cao, Chuanhai, Carlson, Chris S, Carney, Regina M, Carroll, Steven L, Chui, Helena C, Clark, David G, Corneveaux, Jason, Cotman, Carl W, Crane, Paul K, Cruchaga, Carlos, Cummings, Jeffrey L, De Jager, Philip L, DeCarli, Charles, DeKosky, Steven T, Demirci, F Yesim, Diaz-Arrastia, Ramon, Dick, Malcolm, Dombroski, Beth A, Duara, Ranjan, Ellis, William D, Evans, Denis, Faber, Kelley M, Fallon, Kenneth B, Farlow, Martin R, Ferris, Steven, Foroud, Tatiana M, Frosch, Matthew, Galasko, Douglas R, Gallins, Paul J, Ganguli, Mary, Gearing, Marla, Geschwind, Daniel H, Ghetti, Bernardino, Gilbert, John R, Gilman, Sid, Giordani, Bruno, Glass, Jonathan D, Goate, Alison M, Green, Robert C, Growdon, John H, Hakonarson, Hakon, Hamilton, Ronald L, Hardy, John, Harrell, Lindy E, Head, Elizabeth, Honig, Lawrence S, and Huentelman, Matthew J

Subjects
Alzheimer's Disease Genetics Consortium, Temporal Lobe, Humans, Alzheimer Disease, Genetic Predisposition to Disease, RNA, Autopsy, Linear Models, Risk Factors, Gene Expression, Brain Chemistry, Genotype, Gene Dosage, Polymorphism, Single Nucleotide, Alleles, Aged, Female, Male, Apolipoprotein E4, Clinical Research, Alzheimer's Disease, Aging, Acquired Cognitive Impairment, Human Genome, Neurosciences, Dementia, Neurodegenerative, Genetics, Brain Disorders, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Aetiology, 2.1 Biological and endogenous factors, Neurological, Clinical Sciences, Cognitive Sciences, Neurology & Neurosurgery
Abstract

ObjectiveRecent genome-wide association studies (GWAS) of late-onset Alzheimer disease (LOAD) identified 9 novel risk loci. Discovery of functional variants within genes at these loci is required to confirm their role in Alzheimer disease (AD). Single nucleotide polymorphisms that influence gene expression (eSNPs) constitute an important class of functional variants. We therefore investigated the influence of the novel LOAD risk loci on human brain gene expression.MethodsWe measured gene expression levels in the cerebellum and temporal cortex of autopsied AD subjects and those with other brain pathologies (∼400 total subjects). To determine whether any of the novel LOAD risk variants are eSNPs, we tested their cis-association with expression of 6 nearby LOAD candidate genes detectable in human brain (ABCA7, BIN1, CLU, MS4A4A, MS4A6A, PICALM) and an additional 13 genes ±100 kb of these SNPs. To identify additional eSNPs that influence brain gene expression levels of the novel candidate LOAD genes, we identified SNPs ±100 kb of their location and tested for cis-associations.ResultsCLU rs11136000 (p = 7.81 × 10(-4)) and MS4A4A rs2304933/rs2304935 (p = 1.48 × 10(-4)-1.86 × 10(-4)) significantly influence temporal cortex expression levels of these genes. The LOAD-protective CLU and risky MS4A4A locus alleles associate with higher brain levels of these genes. There are other cis-variants that significantly influence brain expression of CLU and ABCA7 (p = 4.01 × 10(-5)-9.09 × 10(-9)), some of which also associate with AD risk (p = 2.64 × 10(-2)-6.25 × 10(-5)).ConclusionsCLU and MS4A4A eSNPs may at least partly explain the LOAD risk association at these loci. CLU and ABCA7 may harbor additional strong eSNPs. These results have implications in the search for functional variants at the novel LOAD risk loci.

Published
2012

67. Microbiome Analysis of the Rhizosphere from Wilt Infected Pomegranate Reveals Complex Adaptations in Fusarium—A Preliminary Study

Author

Anupam J. Das, Renuka Ravinath, Talambedu Usha, Biligi Sampgod Rohith, Hemavathy Ekambaram, Mothukapalli Krishnareddy Prasannakumar, Nijalingappa Ramesh, and Sushil Kumar Middha

Subjects
microbiomics, soil metagenomics, DNA sequencing, wilt, rot, Punica granatum, Agriculture (General), S1-972
Abstract

Wilt disease affecting pomegranate crops results in rapid soil-nutrient depletion, reduced or complete loss in yield, and crop destruction. There are limited studies on the phytopathogen Fusarium oxysporum prevalence and associated genomic information with respect to Fusarium wilt in pomegranate. In this study, soil samples from the rhizosphere of different pomegranate plants showing early stage symptoms of wilt infection to an advanced stage were collected from an orchard situated in Karnataka, India. A whole metagenome sequencing approach was employed to gain insights into the adaptations of the causative pathogen F. oxysporum. Physicochemical results showed a drop in the pH levels, N, Fe, and Mn, and increase in electrical conductivity, B, Zn, Cl, Cu was observed in the early and intermediate stage samples. Comparative abundance analysis of the experimental samples ESI and ISI revealed an abundance of Proteobacteria phyla Achromobacter sp. 2789STDY5608625, Achromobacter sp. K91, and Achromobacter aegrifaciens and Eukaryota namely Aspergillus arachidicola, Aspergillus candidus, and Aspergillus campestris. Functional pathway predictions implied carbohydrate binding to be significant (p < 0.05) among the three experimental samples. Microbiological examination and whole microbiome analysis confirmed the prevalence of F. oxysporum in the soil samples. Variant analysis of F. oxysporum revealed multiple mutations in the 3IPD gene with high impact effects. 3-Isopropylmalate dehydratase and carbohydrate-active enzymes could be good targets for the development of antifungals that could aid in biocontrol of F. oxysporum. The present study demonstrates the capabilities of the whole metagenome sequencing approach for rapid identification of potential key players of wilt disease pathogenesis wherein the symptomatology is complex.

Published
2021
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69. Genome-wide association study of prostate-specific antigen levels identifies novel loci independent of prostate cancer

Author

Thomas J. Hoffmann, Michael N. Passarelli, Rebecca E. Graff, Nima C. Emami, Lori C. Sakoda, Eric Jorgenson, Laurel A. Habel, Jun Shan, Dilrini K. Ranatunga, Charles P. Quesenberry, Chun R. Chao, Nirupa R. Ghai, David Aaronson, Joseph Presti, Tobias Nordström, Zhaoming Wang, Sonja I. Berndt, Stephen J. Chanock, Jonathan D. Mosley, Robert J. Klein, Mridu Middha, Hans Lilja, Olle Melander, Mark N. Kvale, Pui-Yan Kwok, Catherine Schaefer, Neil Risch, Stephen K. Van Den Eeden, and John S. Witte

Subjects
Science
Abstract

Prostate-specific antigen is used as a biomarker of prostate cancer, but levels can be affected by other factors not related to cancer. Here, the authors find genes associated with prostate specific antigen levels in healthy men, which could be used to reduce over-diagnosis and over-treatment.

Published
2017
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70. Cathine and alcohol involved fatality: A rare case report with a brief review of the literature

Author

Atul Bajaj, Cijo John, Sukhminder Kaur, and Deepak Middha

Subjects
Cathine, Alcohol, Khat, Hemorrhage, Law in general. Comparative and uniform law. Jurisprudence, K1-7720, Medicine (General), R5-920
Abstract

Toxicology screening of unusual poisons is important. We report a case of death of a young female suspected to die due to drug overdose. Medico legal autopsy was indicative of cerebral hemorrhage. The deceased had no previous history of drug dependence. Toxicological analysis revealed the presence of cathine {(+)-norpseudoephedrine} and alcohol in the blood. The concentration of ethyl alcohol in blood was determined as 85.57 mg per dL. An overview of toxicology of cathine and its side effects are presented. The reports due to fatal intoxication of cathine in combination with alcohol are rarely reported. The present case substantiates that an intake of low potent drug like cathine in combination with alcohol can cause fatal intoxication.

Published
2016
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71. Factors causing stress in postgraduate dental students during COVID-19 pandemic: A cross-sectional survey

Author

Ruchi Juneja, Neha Sikka, Varun Kumar, Savita Chahal, Mayank Arora, Mitali Middha, and Ruchi Singhal

Subjects
covid-19 pandemic, cross-sectional study, dental students, psychological stress, Dentistry, RK1-715
Abstract

Background: COVID-19 pandemic has impacted the academic and clinical training of postgraduate dental students. This study aimed to assess various factors causing psychological stress in them, and the extent of stress perception during pandemic. Materials and Methods: In this cross-sectional study, 250 postgraduate students from nine dental colleges of Haryana and National Capital Region, India, responded to an online questionnaire sent electronically to them in September 2020, which included modified dental environment stress (DES) score, Perceived Stress Scale (PSS), and questions regarding COVID-associated stress (CAS). Students already diagnosed with any psychiatric disorder or having a history of any major adverse event during the last 6 months likely to affect their psychological health were excluded from this study. The data obtained were analyzed using Chi-square test, Independent t-test, univariate ANOVA with post hoc tests, Pearson moment correlation, and multiple hierarchical regression tests. P < 0.05 was considered statistically significant. Results: DES score was moderate for 48.8% and high for 34.4% of the participants. PSS was moderate for 69.2% and high for 18.8% of the participants. The most stressful factor in dental environment was the pattern of university examination, while the most stressful factor specific to COVID-19 was the fear of family members contracting the infection. PSS score was significantly higher in female participants. DES and CAS scores were significantly higher in students staying in hostels. Multiple hierarchical regression model depicted gender, mean health, and DES score as significant predictors of PSS. Conclusion: Postgraduate dental students reported the adverse impact of COVID-19 pandemic upon their training and prospects as a reason for the increase in stress.

Published
2021
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72. Publisher Correction: Shared heritability and functional enrichment across six solid cancers

Author

Jiang, Xia, Finucane, Hilary K., Schumacher, Fredrick R., Schmit, Stephanie L., Tyrer, Jonathan P., Han, Younghun, Michailidou, Kyriaki, Lesseur, Corina, Kuchenbaecker, Karoline B., Dennis, Joe, Conti, David V., Casey, Graham, Gaudet, Mia M., Huyghe, Jeroen R., Albanes, Demetrius, Aldrich, Melinda C., Andrew, Angeline S., Andrulis, Irene L., Anton-Culver, Hoda, Antoniou, Antonis C., Antonenkova, Natalia N., Arnold, Susanne M., Aronson, Kristan J., Arun, Banu K., Bandera, Elisa V., Barkardottir, Rosa B., Barnes, Daniel R., Batra, Jyotsna, Beckmann, Matthias W., Benitez, Javier, Benlloch, Sara, Berchuck, Andrew, Berndt, Sonja I., Bickeböller, Heike, Bien, Stephanie A., Blomqvist, Carl, Boccia, Stefania, Bogdanova, Natalia V., Bojesen, Stig E., Bolla, Manjeet K., Brauch, Hiltrud, Brenner, Hermann, Brenton, James D., Brook, Mark N., Brunet, Joan, Brunnström, Hans, Buchanan, Daniel D., Burwinkel, Barbara, Butzow, Ralf, Cadoni, Gabriella, Caldés, Trinidad, Caligo, Maria A., Campbell, Ian, Campbell, Peter T., Cancel-Tassin, Géraldine, Cannon-Albright, Lisa, Campa, Daniele, Caporaso, Neil, Carvalho, André L., Chan, Andrew T., Chang-Claude, Jenny, Chanock, Stephen J., Chen, Chu, Christiani, David C., Claes, Kathleen B. M., Claessens, Frank, Clements, Judith, Collée, J. Margriet, Correa, Marcia Cruz, Couch, Fergus J., Cox, Angela, Cunningham, Julie M., Cybulski, Cezary, Czene, Kamila, Daly, Mary B., deFazio, Anna, Devilee, Peter, Diez, Orland, Gago-Dominguez, Manuela, Donovan, Jenny L., Dörk, Thilo, Duell, Eric J., Dunning, Alison M., Dwek, Miriam, Eccles, Diana M., Edlund, Christopher K., Edwards, Digna R. Velez, Ellberg, Carolina, Evans, D. Gareth, Fasching, Peter A., Ferris, Robert L., Liloglou, Triantafillos, Figueiredo, Jane C., Fletcher, Olivia, Fortner, Renée T., Fostira, Florentia, Franceschi, Silvia, Friedman, Eitan, Gallinger, Steven J., Ganz, Patricia A., Garber, Judy, García-Sáenz, José A., Gayther, Simon A., Giles, Graham G., Godwin, Andrew K., Goldberg, Mark S., Goldgar, David E., Goode, Ellen L., Goodman, Marc T., Goodman, Gary, Grankvist, Kjell, Greene, Mark H., Gronberg, Henrik, Gronwald, Jacek, Guénel, Pascal, Håkansson, Niclas, Hall, Per, Hamann, Ute, Hamdy, Freddie C., Hamilton, Robert J., Hampe, Jochen, Haugen, Aage, Heitz, Florian, Herrero, Rolando, Hillemanns, Peter, Hoffmeister, Michael, Høgdall, Estrid, Hong, Yun-Chul, Hopper, John L., Houlston, Richard, Hulick, Peter J., Hunter, David J., Huntsman, David G., Idos, Gregory, Imyanitov, Evgeny N., Ingles, Sue Ann, Isaacs, Claudine, Jakubowska, Anna, James, Paul, Jenkins, Mark A., Johansson, Mattias, Johansson, Mikael, John, Esther M., Joshi, Amit D., Kaneva, Radka, Karlan, Beth Y., Kelemen, Linda E., Kühl, Tabea, Khaw, Kay-Tee, Khusnutdinova, Elza, Kibel, Adam S., Kiemeney, Lambertus A., Kim, Jeri, Kjaer, Susanne K., Knight, Julia A., Kogevinas, Manolis, Kote-Jarai, Zsofia, Koutros, Stella, Kristensen, Vessela N., Kupryjanczyk, Jolanta, Lacko, Martin, Lam, Stephan, Lambrechts, Diether, Landi, Maria Teresa, Lazarus, Philip, Le, Nhu D., Lee, Eunjung, Lejbkowicz, Flavio, Lenz, Heinz-Josef, Leslie, Goska, Lessel, Davor, Lester, Jenny, Levine, Douglas A., Li, Li, Li, Christopher I., Lindblom, Annika, Lindor, Noralane M., Liu, Geoffrey, Loupakis, Fotios, Lubiński, Jan, Maehle, Lovise, Maier, Christiane, Mannermaa, Arto, Marchand, Loic Le, Margolin, Sara, May, Taymaa, McGuffog, Lesley, Meindl, Alfons, Middha, Pooja, Miller, Austin, Milne, Roger L., MacInnis, Robert J., Modugno, Francesmary, Montagna, Marco, Moreno, Victor, Moysich, Kirsten B., Mucci, Lorelei, Muir, Kenneth, Mulligan, Anna Marie, Nathanson, Katherine L., Neal, David E., Ness, Andrew R., Neuhausen, Susan L., Nevanlinna, Heli, Newcomb, Polly A., Newcomb, Lisa F., Nielsen, Finn Cilius, Nikitina-Zake, Liene, Nordestgaard, Børge G., Nussbaum, Robert L., Offit, Kenneth, Olah, Edith, Olama, Ali Amin Al, Olopade, Olufunmilayo I., Olshan, Andrew F., Olsson, Håkan, Osorio, Ana, Pandha, Hardev, Park, Jong Y., Pashayan, Nora, Parsons, Michael T., Pejovic, Tanja, Penney, Kathryn L., Peters, Wilbert H. M., Phelan, Catherine M., Phipps, Amanda I., Plaseska-Karanfilska, Dijana, Pring, Miranda, Prokofyeva, Darya, Radice, Paolo, Stefansson, Kari, Ramus, Susan J., Raskin, Leon, Rennert, Gad, Rennert, Hedy S., van Rensburg, Elizabeth J., Riggan, Marjorie J., Risch, Harvey A., Risch, Angela, Roobol, Monique J., Rosenstein, Barry S., Rossing, Mary Anne, De Ruyck, Kim, Saloustros, Emmanouil, Sandler, Dale P., Sawyer, Elinor J., Schabath, Matthew B., Schleutker, Johanna, Schmidt, Marjanka K., Setiawan, V. Wendy, Shen, Hongbing, Siegel, Erin M., Sieh, Weiva, Singer, Christian F., Slattery, Martha L., Sorensen, Karina Dalsgaard, Southey, Melissa C., Spurdle, Amanda B., Stanford, Janet L., Stevens, Victoria L., Stintzing, Sebastian, Stone, Jennifer, Sundfeldt, Karin, Sutphen, Rebecca, Swerdlow, Anthony J., Tajara, Eloiza H., Tangen, Catherine M., Tardon, Adonina, Taylor, Jack A., Teare, M. Dawn, Teixeira, Manuel R., Terry, Mary Beth, Terry, Kathryn L., Thibodeau, Stephen N., Thomassen, Mads, Bjørge, Line, Tischkowitz, Marc, Toland, Amanda E., Torres, Diana, Townsend, Paul A., Travis, Ruth C., Tung, Nadine, Tworoger, Shelley S., Ulrich, Cornelia M., Usmani, Nawaid, Vachon, Celine M., Van Nieuwenhuysen, Els, Vega, Ana, Aguado-Barrera, Miguel Elías, Wang, Qin, Webb, Penelope M., Weinberg, Clarice R., Weinstein, Stephanie, Weissler, Mark C., Weitzel, Jeffrey N., West, Catharine M. L., White, Emily, Whittemore, Alice S., Wichmann, H-Erich, Wiklund, Fredrik, Winqvist, Robert, Wolk, Alicja, Woll, Penella, Woods, Michael, Wu, Anna H., Wu, Xifeng, Yannoukakos, Drakoulis, Zheng, Wei, Zienolddiny, Shanbeh, Ziogas, Argyrios, Zorn, Kristin K., Lane, Jacqueline M., Saxena, Richa, Thomas, Duncan, Hung, Rayjean J., Diergaarde, Brenda, McKay, James, Peters, Ulrike, Hsu, Li, García-Closas, Montserrat, Eeles, Rosalind A., Chenevix-Trench, Georgia, Brennan, Paul J., Haiman, Christopher A., Simard, Jacques, Easton, Douglas F., Gruber, Stephen B., Pharoah, Paul D. P., Price, Alkes L., Pasaniuc, Bogdan, Amos, Christopher I., Kraft, Peter, and Lindström, Sara

Published
2019
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75. Shared heritability and functional enrichment across six solid cancers

Author

Jiang, Xia, Finucane, Hilary K., Schumacher, Fredrick R., Schmit, Stephanie L., Tyrer, Jonathan P., Han, Younghun, Michailidou, Kyriaki, Lesseur, Corina, Kuchenbaecker, Karoline B., Dennis, Joe, Conti, David V., Casey, Graham, Gaudet, Mia M., Huyghe, Jeroen R., Albanes, Demetrius, Aldrich, Melinda C., Andrew, Angeline S., Andrulis, Irene L., Anton-Culver, Hoda, Antoniou, Antonis C., Antonenkova, Natalia N., Arnold, Susanne M., Aronson, Kristan J., Arun, Banu K., Bandera, Elisa V., Barkardottir, Rosa B., Barnes, Daniel R., Batra, Jyotsna, Beckmann, Matthias W., Benitez, Javier, Benlloch, Sara, Berchuck, Andrew, Berndt, Sonja I., Bickeböller, Heike, Bien, Stephanie A., Blomqvist, Carl, Boccia, Stefania, Bogdanova, Natalia V., Bojesen, Stig E., Bolla, Manjeet K., Brauch, Hiltrud, Brenner, Hermann, Brenton, James D., Brook, Mark N., Brunet, Joan, Brunnström, Hans, Buchanan, Daniel D., Burwinkel, Barbara, Butzow, Ralf, Cadoni, Gabriella, Caldés, Trinidad, Caligo, Maria A., Campbell, Ian, Campbell, Peter T., Cancel-Tassin, Géraldine, Cannon-Albright, Lisa, Campa, Daniele, Caporaso, Neil, Carvalho, André L., Chan, Andrew T., Chang-Claude, Jenny, Chanock, Stephen J., Chen, Chu, Christiani, David C., Claes, Kathleen B. M., Claessens, Frank, Clements, Judith, Collée, J. Margriet, Correa, Marcia Cruz, Couch, Fergus J., Cox, Angela, Cunningham, Julie M., Cybulski, Cezary, Czene, Kamila, Daly, Mary B., deFazio, Anna, Devilee, Peter, Diez, Orland, Gago-Dominguez, Manuela, Donovan, Jenny L., Dörk, Thilo, Duell, Eric J., Dunning, Alison M., Dwek, Miriam, Eccles, Diana M., Edlund, Christopher K., Edwards, Digna R Velez, Ellberg, Carolina, Evans, D. Gareth, Fasching, Peter A., Ferris, Robert L., Liloglou, Triantafillos, Figueiredo, Jane C., Fletcher, Olivia, Fortner, Renée T., Fostira, Florentia, Franceschi, Silvia, Friedman, Eitan, Gallinger, Steven J., Ganz, Patricia A., Garber, Judy, García-Sáenz, José A., Gayther, Simon A., Giles, Graham G., Godwin, Andrew K., Goldberg, Mark S., Goldgar, David E., Goode, Ellen L., Goodman, Marc T., Goodman, Gary, Grankvist, Kjell, Greene, Mark H., Gronberg, Henrik, Gronwald, Jacek, Guénel, Pascal, Håkansson, Niclas, Hall, Per, Hamann, Ute, Hamdy, Freddie C., Hamilton, Robert J., Hampe, Jochen, Haugen, Aage, Heitz, Florian, Herrero, Rolando, Hillemanns, Peter, Hoffmeister, Michael, Høgdall, Estrid, Hong, Yun-Chul, Hopper, John L., Houlston, Richard, Hulick, Peter J., Hunter, David J., Huntsman, David G., Idos, Gregory, Imyanitov, Evgeny N., Ingles, Sue Ann, Isaacs, Claudine, Jakubowska, Anna, James, Paul, Jenkins, Mark A., Johansson, Mattias, Johansson, Mikael, John, Esther M., Joshi, Amit D., Kaneva, Radka, Karlan, Beth Y., Kelemen, Linda E., Kühl, Tabea, Khaw, Kay-Tee, Khusnutdinova, Elza, Kibel, Adam S., Kiemeney, Lambertus A., Kim, Jeri, Kjaer, Susanne K., Knight, Julia A., Kogevinas, Manolis, Kote-Jarai, Zsofia, Koutros, Stella, Kristensen, Vessela N., Kupryjanczyk, Jolanta, Lacko, Martin, Lam, Stephan, Lambrechts, Diether, Landi, Maria Teresa, Lazarus, Philip, Le, Nhu D., Lee, Eunjung, Lejbkowicz, Flavio, Lenz, Heinz-Josef, Leslie, Goska, Lessel, Davor, Lester, Jenny, Levine, Douglas A., Li, Li, Li, Christopher I., Lindblom, Annika, Lindor, Noralane M., Liu, Geoffrey, Loupakis, Fotios, Lubiński, Jan, Maehle, Lovise, Maier, Christiane, Mannermaa, Arto, Marchand, Loic Le, Margolin, Sara, May, Taymaa, McGuffog, Lesley, Meindl, Alfons, Middha, Pooja, Miller, Austin, Milne, Roger L., MacInnis, Robert J., Modugno, Francesmary, Montagna, Marco, Moreno, Victor, Moysich, Kirsten B., Mucci, Lorelei, Muir, Kenneth, Mulligan, Anna Marie, Nathanson, Katherine L., Neal, David E., Ness, Andrew R., Neuhausen, Susan L., Nevanlinna, Heli, Newcomb, Polly A., Newcomb, Lisa F., Nielsen, Finn Cilius, Nikitina-Zake, Liene, Nordestgaard, Børge G., Nussbaum, Robert L., Offit, Kenneth, Olah, Edith, Olama, Ali Amin Al, Olopade, Olufunmilayo I., Olshan, Andrew F., Olsson, Håkan, Osorio, Ana, Pandha, Hardev, Park, Jong Y., Pashayan, Nora, Parsons, Michael T., Pejovic, Tanja, Penney, Kathryn L., Peters, Wilbert H M., Phelan, Catherine M., Phipps, Amanda I., Plaseska-Karanfilska, Dijana, Pring, Miranda, Prokofyeva, Darya, Radice, Paolo, Stefansson, Kari, Ramus, Susan J., Raskin, Leon, Rennert, Gad, Rennert, Hedy S., van Rensburg, Elizabeth J., Riggan, Marjorie J., Risch, Harvey A., Risch, Angela, Roobol, Monique J., Rosenstein, Barry S., Rossing, Mary Anne, De Ruyck, Kim, Saloustros, Emmanouil, Sandler, Dale P., Sawyer, Elinor J., Schabath, Matthew B., Schleutker, Johanna, Schmidt, Marjanka K., Setiawan, V. Wendy, Shen, Hongbing, Siegel, Erin M., Sieh, Weiva, Singer, Christian F., Slattery, Martha L., Sorensen, Karina Dalsgaard, Southey, Melissa C., Spurdle, Amanda B., Stanford, Janet L., Stevens, Victoria L., Stintzing, Sebastian, Stone, Jennifer, Sundfeldt, Karin, Sutphen, Rebecca, Swerdlow, Anthony J., Tajara, Eloiza H., Tangen, Catherine M., Tardon, Adonina, Taylor, Jack A., Teare, M. Dawn, Teixeira, Manuel R., Terry, Mary Beth, Terry, Kathryn L., Thibodeau, Stephen N., Thomassen, Mads, Bjørge, Line, Tischkowitz, Marc, Toland, Amanda E., Torres, Diana, Townsend, Paul A., Travis, Ruth C., Tung, Nadine, Tworoger, Shelley S., Ulrich, Cornelia M., Usmani, Nawaid, Vachon, Celine M., Van Nieuwenhuysen, Els, Vega, Ana, Aguado-Barrera, Miguel Elías, Wang, Qin, Webb, Penelope M., Weinberg, Clarice R., Weinstein, Stephanie, Weissler, Mark C., Weitzel, Jeffrey N., West, Catharine M. L., White, Emily, Whittemore, Alice S., Wichmann, H-Erich, Wiklund, Fredrik, Winqvist, Robert, Wolk, Alicja, Woll, Penella, Woods, Michael, Wu, Anna H., Wu, Xifeng, Yannoukakos, Drakoulis, Zheng, Wei, Zienolddiny, Shanbeh, Ziogas, Argyrios, Zorn, Kristin K., Lane, Jacqueline M., Saxena, Richa, Thomas, Duncan, Hung, Rayjean J., Diergaarde, Brenda, McKay, James, Peters, Ulrike, Hsu, Li, García-Closas, Montserrat, Eeles, Rosalind A., Chenevix-Trench, Georgia, Brennan, Paul J., Haiman, Christopher A., Simard, Jacques, Easton, Douglas F., Gruber, Stephen B., Pharoah, Paul D. P., Price, Alkes L., Pasaniuc, Bogdan, Amos, Christopher I., Kraft, Peter, and Lindström, Sara

Published
2019
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76. A cross strain Plasmodium falciparum microarray optimized for the transcriptome analysis of Plasmodium falciparum patient derived isolates

Author

Amit Kumar Subudhi, P.A. Boopathi, Sheetal Middha, Jyoti Acharya, Sudha Narayana Rao, Raja C. Mugasimangalam, Paramendra Sirohi, Sanjay K. Kochar, Dhanpat K. Kochar, and Ashis Das

Subjects
Plasmodium falciparum, Microarray, Uncomplicated malaria, Complicated malaria, PfEMP1, RIFIN, Genetics, QH426-470
Abstract

Malarial parasite P. falciparum, an apicomplexan protozoan has a 23.3 MB nuclear genome and encodes ~5600 transcripts. The genetic diversity of the parasite within and across geographical zones is a challenge to gene expression studies which are essential for understanding of disease process, outcome and developing markers for diagnostics and prognostics. Here, we describe the strategy involved in designing a custom P. falciparum 15K array using the Agilent platform and Genotypic's Right Design methodology to study the transcriptome of Indian field isolates for which genome sequence information is limited. The array contains probes representing genome sequences of two distinct geographical isolates (i.e. 3D7 and HB3) and sub-telomeric var gene sequences of a third isolate (IT4) known to adhere in culture condition. Probes in the array have been selected based on their efficiency to detect transcripts through a 244K array experimentation. Array performance for the 15K array, was evaluated and validated using RNA materials from P. falciparum clinical isolates. A large percentage (91%) of the represented transcripts was detected from Indian P. falciparum patient isolates. Replicated probes and multiple probes representing the same gene showed perfect correlation between them suggesting good probe performance. Additional transcripts could be detected due to inclusion of unique probes representing HB3 strain transcripts. Variant surface antigen (VSA) transcripts were detected by optimized probes representing the VSA genes of three geographically distinct strains. The 15K cross strain P. falciparum array has shown good efficiency in detecting transcripts from P. falciparum parasite samples isolated from patients. The low parasite loads and presence of host RNA makes arrays a preferred platform for gene expression studies over RNA-Seq.

Published
2016
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83. Novel pedigree analysis implicates DNA repair and chromatin remodeling in multiple myeloma risk.

Author

Rosalie G Waller, Todd M Darlington, Xiaomu Wei, Michael J Madsen, Alun Thomas, Karen Curtin, Hilary Coon, Venkatesh Rajamanickam, Justin Musinsky, David Jayabalan, Djordje Atanackovic, S Vincent Rajkumar, Shaji Kumar, Susan Slager, Mridu Middha, Perrine Galia, Delphine Demangel, Mohamed Salama, Vijai Joseph, James McKay, Kenneth Offit, Robert J Klein, Steven M Lipkin, Charles Dumontet, Celine M Vachon, and Nicola J Camp

Subjects
Genetics, QH426-470
Abstract

The high-risk pedigree (HRP) design is an established strategy to discover rare, highly-penetrant, Mendelian-like causal variants. Its success, however, in complex traits has been modest, largely due to challenges of genetic heterogeneity and complex inheritance models. We describe a HRP strategy that addresses intra-familial heterogeneity, and identifies inherited segments important for mapping regulatory risk. We apply this new Shared Genomic Segment (SGS) method in 11 extended, Utah, multiple myeloma (MM) HRPs, and subsequent exome sequencing in SGS regions of interest in 1063 MM / MGUS (monoclonal gammopathy of undetermined significance-a precursor to MM) cases and 964 controls from a jointly-called collaborative resource, including cases from the initial 11 HRPs. One genome-wide significant 1.8 Mb shared segment was found at 6q16. Exome sequencing in this region revealed predicted deleterious variants in USP45 (p.Gln691* and p.Gln621Glu), a gene known to influence DNA repair through endonuclease regulation. Additionally, a 1.2 Mb segment at 1p36.11 is inherited in two Utah HRPs, with coding variants identified in ARID1A (p.Ser90Gly and p.Met890Val), a key gene in the SWI/SNF chromatin remodeling complex. Our results provide compelling statistical and genetic evidence for segregating risk variants for MM. In addition, we demonstrate a novel strategy to use large HRPs for risk-variant discovery more generally in complex traits.

Published
2018
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84. Liquid chromatography/tandem mass spectrometry method for quantitative estimation of solutol HS15 and its applications

Author

V. Vijaya Bhaskar, Anil Middha, Pratima Srivastava, and Sriram Rajagopal

Subjects
Therapeutics. Pharmacology, RM1-950
Abstract

A rapid, sensitive and selective pseudoMRM (pMRM)-based method for the determination of solutol HS15 (SHS15) in rat plasma was developed using liquid chromatography/tandem mass spectrometry (LCâMS/MS). The most abundant ions corresponding to SHS15 free polyethyleneglycol (PEG) oligomers at m/z 481, 525, 569, 613, 657, 701, 745, 789, 833, 877, 921 and 965 were selected for pMRM in electrospray mode of ionization. Purity of the lipophilic and hydrophilic components of SHS15 was estimated using evaporative light scattering detector (ELSD). Plasma concentrations of SHS15 were measured after oral administration at 2.50Â g/kg dose and intravenous administration at 1.00Â g/kg dose in male Sprague Dawley rats. SHS15 has poor oral bioavailability of 13.74% in rats. Differences in pharmacokinetics of oligomers were studied. A novel proposal was conveyed to the scientific community, where formulation excipient could be analyzed as a qualifier in the analysis of new chemical entities (NCEs) to address the spiky plasma concentration profiles. Keywords: SHS15, LCâMS/MS, Spiky profiles, Validation

Published
2015
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85. Rosmarinic Acid, a New Polyphenol from Baccaurea ramiflora Lour. Leaf: A Probable Compound for Its Anti-Inflammatory Activity

Author

Talambedu Usha, Sushil Kumar Middha, Malay Bhattacharya, Prakash Lokesh, and Arvind Kumar Goyal

Subjects
Baccaurea ramiflora, rosmarinic acid, anti-inflammatory activity, cytokines, Therapeutics. Pharmacology, RM1-950
Abstract

Despite several pharmacological applications of Baccaurea ramiflora Lour., studies on the influence of its polyphenol content on pharmacological activity such as anti-inflammatory properties have been scarce. Here we evaluated in vitro antioxidant activity, poyphenolics by HPLC and the anti-inflammatory potential of the methanolic leaf extract of Baccaurea ramiflora (BME) and its protective effects in carrageenan-induced paw edema model of inflammation in rats. The BME extract contained 79.06 ± 0.03 mg gallic acid equivalent (GAE)/g total polyphenols, 28.80 ± 0.01 mg quercetin equivalent (QE)/g flavonoid and 29.42 ± 0.01 μg cathechin equivalent/g proanthocyanidin respectively and rosmarinic acid (8 mg/kg) as a main component was identified by HPLC. Results demonstrate that administration of BME at the dose of 200 mg/kg can reduce paw edema by over 63%, and it exhibits a dose-response effect. Depending on concentration, the extract exerted scavenging activity on DPPH radical (IC50 36.4 μg/mL), significantly inhibited IL-1β (4.4 pg/mg protein) and TNF-α (0.21 ng/μg protein). Therefore, we conclude BME causes a substantial reduction of inflammation in in vivo models. We propose that rosmarinic acid and similar phenolic compounds may be useful in the therapy of inflammation-related injuries.

Published
2014
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92. A prospective study on adult patients of severe malaria caused by Plasmodium falciparum, Plasmodium vivax and mixed infection from Bikaner, northwest India

Author

D. K. Kochar, Ashis Das, Abhishek Kochar, Sheetal Middha, Jyoti Acharya, G. S. Tanwar, Deepak Pakalapati, A. K. Subudhi, P. A. Boopathi, Shilpi Garg, and S. K. Kochar

Subjects
Mixed infection, Plasmodium falciparum, Plasmodium vivax, severe malaria, Infectious and parasitic diseases, RC109-216
Abstract

Background & objectives: Description of severe vivax malaria and mixed species infection requires good clinical study. The present study was undertaken to evalute the characteristics of severe malaria patients in Bikaner, northwest India. Methods: This prospective study included 539 admitted adult patients of severe malaria (Plasmodium falciparum 274, P. vivax 221, and mixed infection of Pv + Pf 44). The diagnosis was confirmed by polymerase chain reaction. The categorization of severe malaria was done strictly as per WHO criteria. Results: The distribution of severe manifestation was similar in severe vivax, falciparum and mixed infections except more cases of thrombocytopenia in P. vivax (p=0.030) and in mixed infection (p=0.004). The risk of developing severe malaria was greatest in patients of mixed infection [53.01% (44/83)] in comparison to Plasmodium falciparum malaria [49.37% (274/555), RR= 1.135; p=0.616] and P. vivax malaria [45.38% (221/ 487), RR = 1.299, p=0.243]. Hepatic dysfunction was the commonest pernicious syndrome [P. falciparum 50% (137/274), P. vivax 43.89% (97/221), and mixed infections 54.55% (24/44)]. Multiorgan dysfunction was present in 40.26% (217/539) patients, the risk was greatest in mixed infection [90.90% (40/44)] in comparison to P. falciparum monoinfection [37.59% (103/274), RR = 12.238; p=0.0001] or P. vivax monoinfection [33.48% (74/ 221), RR = 13.25; p=0.0001]. The risk of mortality in severe malaria was 6.31% (34/539) in which mixed infection had greater risk [9.09% (4/44)] in comparison to P. falciparum [7.30% (20/274); OR = 1.270 (CI 0.347-4.217); p=0.757] or P. vivax [4.52% (10/221); 0R 2.110 (CI 0.527-7.826); p=0.260]. Interpretation & conclusion: Severe vivax or falciparum malaria had almost similar features and prognosis including mortality. Risk of developing severe malaria, multiorgan dysfunction and mortality was more in patients of mixed infection in comparison to P. falciparum or P. vivax monoinfection. A multicentric study on larger number of patients requires further confirmation.

Published
2014

94. Dataset of natural antisense transcripts in P. vivax clinical isolates derived using custom designed strand-specific microarray

Author

P.A. Boopathi, Amit Kumar Subudhi, Shilpi Garg, Sheetal Middha, Jyoti Acharya, Deepak Pakalapati, Vishal Saxena, Mohammed Aiyaz, Bipin Chand, Raja C. Mugasimangalam, Sanjay K. Kochar, Parmendra Sirohi, Dhanpat K. Kochar, and Ashis Das

Subjects
Natural antisense transcripts, Strand specific microarray, Plasmodium vivax, Complicated malaria, Uncomplicated malaria, Genetics, QH426-470
Abstract

Natural antisense transcripts (NATs) have been detected in many organisms and shown to regulate gene expression. Similarly, NATs have also been observed in malaria parasites with most studies focused on Plasmodium falciparum. There were no reports on the presence of NATs in Plasmodium vivax, which has also been shown to cause severe malaria like P. falciparum, until a recent study published by us. To identify in vivo prevalence of antisense transcripts in P. vivax clinical isolates, we performed whole genome expression profiling using a custom designed strand-specific microarray that contains probes for both sense and antisense strands. Here we describe the experimental methods and analysis of the microarray data available in Gene Expression Omnibus (GEO) under GSE45165. Our data provides a resource for exploring the presence of antisense transcripts in P. vivax isolated from patients showing varying clinical symptoms. Related information about the description and interpretation of the data can be found in a recent publication by Boopathi and colleagues in Infection, Genetics and Evolution 2013.

Published
2014
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95. An in vivo transcriptome data set of natural antisense transcripts from Plasmodium falciparum clinical isolates

Author

Amit Kumar Subudhi, P.A. Boopathi, Shilpi Garg, Sheetal Middha, Jyoti Acharya, Deepak Pakalapati, Vishal Saxena, Mohammed Aiyaz, Harsha B. Orekondy, Raja C. Mugasimangalam, Paramendra Sirohi, Sanjay K. Kochar, Dhanpat K. Kochar, and Ashis Das

Subjects
Plasmodium falciparum, Uncomplicated malaria, Complicated malaria, Natural antisense transcripts, Strand-specific microarray, Genetics, QH426-470
Abstract

Antisense transcription is pervasive among biological systems and one of the products of antisense transcription is natural antisense transcripts (NATs). Emerging evidences suggest that they are key regulators of gene expression. With the discovery of NATs in Plasmodium falciparum, it has been suggested that these might also be playing regulatory roles in this parasite. However, all the reports describing the diversity of NATs have come from parasites in culture condition except for a recent study published by us. In order to explore the in vivo diversity of NATs in P. falciparum clinical isolates, we performed a whole genome expression profiling using a strand-specific 244 K microarray that contains probes for both sense and antisense transcripts. In this report, we describe the experimental procedure and analysis thereof of the microarray data published recently in Gene Expression Omnibus (GEO) under accession number GSE44921. This published data provide a wealth of information about the prevalence of NATs in P. falciparum clinical isolates from patients with diverse malaria related disease conditions. Supplementary information about the description and interpretation of the data can be found in a recent publication by Subudhi et al. in Experimental Parasitology (2014).

Published
2014
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96. Distinct Reproductive Risk Profiles for Intrinsic-Like Breast Cancer Subtypes: Pooled Analysis of Population-Based Studies

Author

Jung, AY, Ahearn, TU, Behrens, S, Middha, P, Bolla, MK, Wang, Q, Arndt, V, Aronson, KJ, Augustinsson, A, Freeman, LEB, Becher, H, Brenner, H, Canzian, F, Carey, LA, Consortium, C, Czene, K, Eliassen, AH, Eriksson, M, Evans, DG, Figueroa, JD, Fritschi, L, Gabrielson, M, Giles, GG, Guenel, P, Hadjisavvas, A, Haiman, CA, Hakansson, N, Hall, P, Hamann, U, Hoppe, R, Hopper, JL, Howell, A, Hunter, DJ, Huesing, A, Kaaks, R, Kosma, V-M, Koutros, S, Kraft, P, Lacey, J, Le Marchand, L, Lissowska, J, Loizidou, MA, Mannermaa, A, Maurer, T, Murphy, RA, Olshan, AF, Olsson, H, Patel, A, Perou, CM, Rennert, G, Shibli, R, Shu, X-O, Southey, MC, Stone, J, Tamimi, RM, Teras, LR, Troester, MA, Truong, T, Vachon, CM, Wang, SS, Wolk, A, Wu, AH, Yang, XR, Zheng, W, Dunning, AM, Pharoah, PDP, Easton, DF, Milne, RL, Chatterjee, N, Schmidt, MK, Garcia-Closas, M, Chang-Claude, J, Jung, AY, Ahearn, TU, Behrens, S, Middha, P, Bolla, MK, Wang, Q, Arndt, V, Aronson, KJ, Augustinsson, A, Freeman, LEB, Becher, H, Brenner, H, Canzian, F, Carey, LA, Consortium, C, Czene, K, Eliassen, AH, Eriksson, M, Evans, DG, Figueroa, JD, Fritschi, L, Gabrielson, M, Giles, GG, Guenel, P, Hadjisavvas, A, Haiman, CA, Hakansson, N, Hall, P, Hamann, U, Hoppe, R, Hopper, JL, Howell, A, Hunter, DJ, Huesing, A, Kaaks, R, Kosma, V-M, Koutros, S, Kraft, P, Lacey, J, Le Marchand, L, Lissowska, J, Loizidou, MA, Mannermaa, A, Maurer, T, Murphy, RA, Olshan, AF, Olsson, H, Patel, A, Perou, CM, Rennert, G, Shibli, R, Shu, X-O, Southey, MC, Stone, J, Tamimi, RM, Teras, LR, Troester, MA, Truong, T, Vachon, CM, Wang, SS, Wolk, A, Wu, AH, Yang, XR, Zheng, W, Dunning, AM, Pharoah, PDP, Easton, DF, Milne, RL, Chatterjee, N, Schmidt, MK, Garcia-Closas, M, and Chang-Claude, J

Abstract

BACKGROUND: Reproductive factors have been shown to be differentially associated with risk of estrogen receptor (ER)-positive and ER-negative breast cancer. However, their associations with intrinsic-like subtypes are less clear. METHODS: Analyses included up to 23 353 cases and 71 072 controls pooled from 31 population-based case-control or cohort studies in the Breast Cancer Association Consortium across 16 countries on 4 continents. Polytomous logistic regression was used to estimate the association between reproductive factors and risk of breast cancer by intrinsic-like subtypes (luminal A-like, luminal B-like, luminal B-HER2-like, HER2-enriched-like, and triple-negative breast cancer) and by invasiveness. All statistical tests were 2-sided. RESULTS: Compared with nulliparous women, parous women had a lower risk of luminal A-like, luminal B-like, luminal B-HER2-like, and HER2-enriched-like disease. This association was apparent only after approximately 10 years since last birth and became stronger with increasing time (odds ratio [OR] = 0.59, 95% confidence interval [CI] = 0.49 to 0.71; and OR = 0.36, 95% CI = 0.28 to 0.46 for multiparous women with luminal A-like tumors 20 to less than 25 years after last birth and 45 to less than 50 years after last birth, respectively). In contrast, parous women had a higher risk of triple-negative breast cancer right after their last birth (for multiparous women: OR = 3.12, 95% CI = 2.02 to 4.83) that was attenuated with time but persisted for decades (OR = 1.03, 95% CI = 0.79 to 1.34, for multiparous women 25 to less than 30 years after last birth). Older age at first birth (Pheterogeneity < .001 for triple-negative compared with luminal A-like breast cancer) and breastfeeding (Pheterogeneity < .001 for triple-negative compared with luminal A-like breast cancer) were associated with lower risk of triple-negative breast cancer but not with other disease subtypes. Younger age at menarche was associated with higher risk of all

Published
2022

98. Determination of cyclamate in urine by derivatized gas chromatography-mass spectrometry

Author

Mohd Idris, Deepak Middha, Shaik N Rasool, Sudhir K Shukla, and Tulsidas R Baggi

Subjects
Cyclamate, GC-MS, screening, toxicology, urine, Pharmacy and materia medica, RS1-441, Analytical chemistry, QD71-142
Abstract

Aim: It is important in toxicological/drug screening work to rule out the possible interfering analytes, to eliminate the false positive or negative results. In this paper, we describe a simple, selective, and sensitive derivatized GC-MS method for the determination of cyclohexylsulfamic acid (cyclamate) in urine. Materials and Methods: Elite- 5MS capillary column was used for the separation of analytes and detection using GC-MS. The analysis was carried out in selected ion monitoring mode (SIM) in the range of 26 to 200 using m/z values of 57, 30, 55, 41, 44, 67, 82, 98, and 39. Results and Discussion: The method is based on the conversion of cyclamate into nitroso derivative of cyclamate followed by its gas chromatography-mass spectrometry determination. The limit of detection, limit of quantitation, and linearity range of the proposed method were found to be 0.2 μg/ ml, 0.7 μg/ml, and 1-15 μg/ml, respectively. The recovery of the present method is in the range of 88-94%. Conclusion: The proposed method can be applied for detection and quantification of cyclamate in urine.

Published
2013
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100. The Influence of Explosion Relief Vent Layouts on Explosion Overpressures in Large Biomass Storage Vessels

Author

Prankul Middha, Rohan Samaraweera, Chris Coffey, David Price, and Kees van Wingerden

Subjects
Chemical engineering, TP155-156, Computer engineering. Computer hardware, TK7885-7895
Abstract

International standards for dust explosion relief design (NFPA 68 2013, EN 14491 2012, VDI 3673) have largely been developed for conventional bulk material handling silos with volumes of less than 10,000 m3, with empirical calculations being used to determine the total suitable vent areas required to achieve explosionprotection in the event of an internal incipient explosion. However, these standards generally do not advise on the effects of the distribution of this total area across the vessel. Some standards state that the distribution of the relief vent area is unimportant as long as the total required vent area is achieved. For larger vessels, suchas large biomass storage silos with volumes up to 100,000 m3, Computational Fluid Dynamics (CFD) codesare often used to undertake explosion simulations in order to determine the effects of likely worst-case explosions and subsequently determine a suitable area of explosion relief venting. The effects of the distribution of these vent areas is again not often considered in the design of such vessels. This paper presents the results of research undertaken by Gexcon using the FLACS-DustEx CFD code, showing the effects of various relief vent arrangements for a given vessel and given total relief vent area. The initial results suggest that flames emitted through relief vents during an explosion can interact with one another outside of the vessel, increasing turbulence and reducing the efficiency of the venting process. This subsequently results in an increase in the reduced explosion pressure (Pred) within the vessel during an explosion. The level of interaction, and hence the magnitude of the change in the reduced overpressure, has been found to vary with the manner in which the total vent area is distributed across the vessel. The results of this initial research are discussed, along with preliminary conclusions and recommendations. Other aspects are also discussed, such as statements in the standards that may be misleading and the effects of structures located in-between large areas of relief vents on a vessel.

Published
2016
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