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151. P173: Precision animal modeling and VUS-resolution in a novel AXIN2-related disorder

Author: Lindsay Burrage, Denise Lanza, Paul Marcogliese, Di Lu, Chih-Wei Logan Hsu, Nathalie Aceves, Matthew Gonzalez, Audrey Christiansen, Tara Rasmussen, Angelina Gaspero, John Seavitt, Mary Dickinson, Brian Shayota, Stephanie Pachter, Debra-Lynn Day-Salvatore, Oguz Kanca, Michael Wangler, Lorraine Potocki, Jill Rosenfeld, Brendan Lee, Shinya Yamamoto, Hugo Bellen, and Jason Heaney
Subjects: Genetics, QH426-470, Medicine
Published: 2024
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152. A paradoxical switch: the implications of excitatory GABAergic signaling in neurological disorders

Author: Colin J. McArdle, Alana A. Arnone, Chelcie F. Heaney, and Kimberly F. Raab-Graham
Subjects: GABA, depolarizing, excitatory, diseases, GABAARs, neurological, Psychiatry, RC435-571
Abstract: Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the central nervous system. In the mature brain, inhibitory GABAergic signaling is critical in maintaining neuronal homeostasis and vital human behaviors such as cognition, emotion, and motivation. While classically known to inhibit neuronal function under physiological conditions, previous research indicates a paradoxical switch from inhibitory to excitatory GABAergic signaling that is implicated in several neurological disorders. Various mechanisms have been proposed to contribute to the excitatory switch such as chloride ion dyshomeostasis, alterations in inhibitory receptor expression, and modifications in GABAergic synaptic plasticity. Of note, the hypothesized mechanisms underlying excitatory GABAergic signaling are highlighted in a number of neurodevelopmental, substance use, stress, and neurodegenerative disorders. Herein, we present an updated review discussing the presence of excitatory GABAergic signaling in various neurological disorders, and their potential contributions towards disease pathology.
Published: 2024
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153. An autoencoder-based reduced-order model for eigenvalue problems with application to neutron diffusion

Author: Phillips, Toby, Heaney, Claire E., Smith, Paul N., and Pain, Christopher C.
Subjects: Mathematics - Numerical Analysis, Computer Science - Machine Learning, Physics - Computational Physics, Statistics - Machine Learning
Abstract: Using an autoencoder for dimensionality reduction, this paper presents a novel projection-based reduced-order model for eigenvalue problems. Reduced-order modelling relies on finding suitable basis functions which define a low-dimensional space in which a high-dimensional system is approximated. Proper orthogonal decomposition (POD) and singular value decomposition (SVD) are often used for this purpose and yield an optimal linear subspace. Autoencoders provide a nonlinear alternative to POD/SVD, that may capture, more efficiently, features or patterns in the high-fidelity model results. Reduced-order models based on an autoencoder and a novel hybrid SVD-autoencoder are developed. These methods are compared with the standard POD-Galerkin approach and are applied to two test cases taken from the field of nuclear reactor physics., Comment: 35 pages, 33 figures
Published: 2020
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154. A time-symmetric formulation of quantum entanglement

Author: Heaney, Michael B.
Subjects: Quantum Physics
Abstract: I numerically simulate and compare the entanglement of two quanta using the conventional formulation of quantum mechanics and a time-symmetric formulation that has no collapse postulate. The experimental predictions of the two formulations are identical, but the entanglement predictions are significantly different. The time-symmetric formulation reveals an experimentally testable discrepancy in the original quantum analysis of the Hanbury Brown-Twiss experiment, suggests solutions to some parts of the nonlocality and measurement problems, fixes known time asymmetries in the conventional formulation, and answers Bell's question "How do you convert an 'and' into an 'or'?'", Comment: 19 pages, 9 figures
Published: 2020
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155. Interactions among national and supranational identities: mobilizing the independence movement in Scotland

Author: Michael T. Heaney, Erika L. Anderson, Madilyn E. Cancro, and Grace E. Martin
Subjects: nationalism, national identity, social movements, interaction effects, independence, Scotland, Political science
Abstract: As nationalism rises worldwide, understanding the relevance of national identities is at a premium in both the study of mass political behavior and the analysis of social movements. Drawing on research in social psychology, this study explores interactions among national and supranational identities using the concepts of identity interference (i.e., negative interactions) and identity complementarity (i.e., positive interactions). These interactions extend beyond the direct effects of identity considered in many previous studies. Focusing on interactions centers the analysis on the contextual aspects of identity during nationalist mobilizations. Survey data from Scotland demonstrate that interactions among Scottish, British, and European identities were consequential for mobilizing support for Scottish independence in 2019. Strong evidence indicates interference between Scottish and British identities. European and Scottish identities complement one another among independence supporters but not in the general population. The possibility of interference between European and British identities is backed by only mixed results. The timing of this study in the aftermath of the Brexit referendum was likely relevant to its findings on European identity. Overall, this research illustrates the benefits of widening the empirical examination of multiple identities in the social sciences.
Published: 2023
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156. Specimen collection is essential for modern science.

Author: Michael W Nachman, Elizabeth J Beckman, Rauri Ck Bowie, Carla Cicero, Chris J Conroy, Robert Dudley, Tyrone B Hayes, Michelle S Koo, Eileen A Lacey, Christopher H Martin, Jimmy A McGuire, James L Patton, Carol L Spencer, Rebecca D Tarvin, Marvalee H Wake, Ian J Wang, Anang Achmadi, Sergio Ticul Álvarez-Castañeda, Michael J Andersen, Jairo Arroyave, Christopher C Austin, F Keith Barker, Lisa N Barrow, George F Barrowclough, John Bates, Aaron M Bauer, Kayce C Bell, Rayna C Bell, Allison W Bronson, Rafe M Brown, Frank T Burbrink, Kevin J Burns, Carlos Daniel Cadena, David C Cannatella, Todd A Castoe, Prosanta Chakrabarty, Jocelyn P Colella, Joseph A Cook, Joel L Cracraft, Drew R Davis, Alison R Davis Rabosky, Guillermo D'Elía, John P Dumbacher, Jonathan L Dunnum, Scott V Edwards, Jacob A Esselstyn, Julián Faivovich, Jon Fjeldså, Oscar A Flores-Villela, Kassandra Ford, Jérôme Fuchs, Matthew K Fujita, Jeffrey M Good, Eli Greenbaum, Harry W Greene, Shannon Hackett, Amir Hamidy, James Hanken, Tri Haryoko, Melissa Tr Hawkins, Lawrence R Heaney, David M Hillis, Bradford D Hollingsworth, Angela D Hornsby, Peter A Hosner, Mohammad Irham, Sharon Jansa, Rosa Alicia Jiménez, Leo Joseph, Jeremy J Kirchman, Travis J LaDuc, Adam D Leaché, Enrique P Lessa, Hernán López-Fernández, Nicholas A Mason, John E McCormack, Caleb D McMahan, Robert G Moyle, Ricardo A Ojeda, Link E Olson, Chan Kin Onn, Lynne R Parenti, Gabriela Parra-Olea, Bruce D Patterson, Gregory B Pauly, Silvia E Pavan, A Townsend Peterson, Steven Poe, Daniel L Rabosky, Christopher J Raxworthy, Sushma Reddy, Alejandro Rico-Guevara, Awal Riyanto, Luiz A Rocha, Santiago R Ron, Sean M Rovito, Kevin C Rowe, Jodi Rowley, Sara Ruane, David Salazar-Valenzuela, Allison J Shultz, Brian Sidlauskas, Derek S Sikes, Nancy B Simmons, Melanie L J Stiassny, Jeffrey W Streicher, Bryan L Stuart, Adam P Summers, Jose Tavera, Pablo Teta, Cody W Thompson, Robert M Timm, Omar Torres-Carvajal, Gary Voelker, Robert S Voss, Kevin Winker, Christopher Witt, Elizabeth A Wommack, and Robert M Zink
Subjects: Biology (General), QH301-705.5
Abstract: Natural history museums are vital repositories of specimens, samples and data that inform about the natural world; this Formal Comment revisits a Perspective that advocated for the adoption of compassionate collection practices, querying whether it will ever be possible to completely do away with whole animal specimen collection.
Published: 2023
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157. New Transcriptional Insights into Silent and Active Corticotroph Pituitary Tumors at Single Cell Resolution

Author: Vinters, Harry, Heaney, Anthony, Zhang, Dongyun, Hugo, Willy, Bergsneider, Marvin, Wang, Marilene, and Kim, Won
Abstract: Abstract Silent pituitary corticotroph tumors derive from the Tpit (aka TBX19) pituitary lineage. Accounting for ~ 30% of corticotroph tumors, they are not infrequently clinically aggressive and invade locally into adjacent sellar structures, making complete surgical resection challenging and contributing to their higher recurrence rates. How silent and active corticotroph tumor subtypes differ is not clear although some studies reported that silent corticotroph tumors exhibit reduced PC1 expression causing impaired POMC processing. We used single cell RNAseq to compare the transcriptome between silent (n = 2) and active (n = 4) corticotroph tumors at the single cell level. We obtained an average of 265 million reads, and 24,682 genes per patient with an average of 1,240 genes expressed and 3,5442 unique molecular identifiers (UMIs) detected per cell. We further defined 5 distinct cell populations from a total of 23,269 cells, namely tumor cells (62%), stromal cells (25%), immune cells (7%), progenitor cells (5%), and a minor population of erythrocytes (1%). Tumor cells clustered in an origin-dependent manner and all expressed POMC and TBX19. However, the gene signatures of silent and active corticotroph tumors differed in 3 major aspects. Firstly, and supporting prior studies, a series of hormone processing peptidase genes, including PC1 (aka PCSK1), PDIA3, SEC11C, SPCS1 and CTSB, were reduced in silent corticotroph tumors (p=5.54e-5) compared to active corticotroph tumors. Secondly, genes involved in organization of secretory vesicles such as SCG5, TIMP1, VGF, SYT17, LGALS3 and CALY were also reduced in silent corticotroph tumors, which could further compound their inability to secrete ACTH. Thirdly, the silent corticotroph tumors exhibited several features of endothelial-to-mesenchymal transition (EMT), including increased expression of the mesenchymal genes CDH2 (aka NCAD), COL1A1, PCDH9, FGF5, ID2 (p=8.4e-3), and loss of EPCAM, which regulate cell migration and movement. Upstream analysis suggested that aberrant STAT3 activation may be related to these changes. Consequently, we noted that the stromal content was higher in silent corticotroph tumors (47.5% vs. 18.13%), concordant with the observed EMT de-differentiation of tumor cells. In summary, our scRNAseq analysis provides an unprecedented precise investigation of the transcriptomic features of thousands of heterogenous corticotroph tumor cells simultaneously. We demonstrate that although silent corticotroph tumor cells still express the pituitary lineage markers PITX1 and TBX19, they exhibit EMT, potentially affording increased migratory capacity at the cost of reduced neuroendocrine function with inability to produce and secrete mature ACTH. Our findings provide novel insights into the pathogenesis of silent versus active corticotroph tumor, but may reveal novel molecular targets for treatment of these challenging tumors.
Published: 2021

158. EUFOREA pocket guide on the diagnosis and management of asthma: An educational and practical tool for general practitioners, non-respiratory physicians, paramedics and patients

Author: Diamant, Zuzana, Jesenak, Milos, Hanania, Nicola A., Heaney, Liam G., Djukanovic, Ratko, Ryan, Dermot, Quirce, Santiago, Backer, Vibeke, Gaga, Mina, Pavord, Ian, Antolín-Amérigo, Darío, Assaf, Sara, Bakakos, Petros, Bobcakova, Anna, Busse, William, Kappen, Jasper, Loukides, Stelios, van Maaren, Maurits, Panzner, Petr, Pite, Helena, Spanevello, Antonio, Stenberg, Henning, Striz, Ilja, Thio, Boony, Vasakova, Martina Koziar, Conti, Diego, Fokkens, Wytske, Lau, Susanne, Scadding, Glenis K., Van Staeyen, Elizabeth, Hellings, Peter W., and Bjermer, Leif
Published: 2023
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159. Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Author: Raman, Betty, McCracken, Celeste, Cassar, Mark P, Moss, Alastair J, Finnigan, Lucy, Samat, Azlan Helmy A, Ogbole, Godwin, Tunnicliffe, Elizabeth M, Alfaro-Almagro, Fidel, Menke, Ricarda, Xie, Cheng, Gleeson, Fergus, Lukaschuk, Elena, Lamlum, Hanan, McGlynn, Kevin, Popescu, Iulia A, Sanders, Zeena-Britt, Saunders, Laura C, Piechnik, Stefan K, Ferreira, Vanessa M, Nikolaidou, Chrysovalantou, Rahman, Najib M, Ho, Ling-Pei, Harris, Victoria C, Shikotra, Aarti, Singapuri, Amisha, Pfeffer, Paul, Manisty, Charlotte, Kon, Onn M, Beggs, Mark, O'Regan, Declan P, Fuld, Jonathan, Weir-McCall, Jonathan R, Parekh, Dhruv, Steeds, Rick, Poinasamy, Krisnah, Cuthbertson, Dan J, Kemp, Graham J, Semple, Malcolm G, Horsley, Alexander, Miller, Christopher A, O'Brien, Caitlin, Shah, Ajay M, Chiribiri, Amedeo, Leavy, Olivia C, Richardson, Matthew, Elneima, Omer, McAuley, Hamish J C, Sereno, Marco, Saunders, Ruth M, Houchen-Wolloff, Linzy, Greening, Neil J, Bolton, Charlotte E, Brown, Jeremy S, Choudhury, Gourab, Diar Bakerly, Nawar, Easom, Nicholas, Echevarria, Carlos, Marks, Michael, Hurst, John R, Jones, Mark G, Wootton, Daniel G, Chalder, Trudie, Davies, Melanie J, De Soyza, Anthony, Geddes, John R, Greenhalf, William, Howard, Luke S, Jacob, Joseph, Man, William D-C, Openshaw, Peter J M, Porter, Joanna C, Rowland, Matthew J, Scott, Janet T, Singh, Sally J, Thomas, David C, Toshner, Mark, Lewis, Keir E, Heaney, Liam G, Harrison, Ewen M, Kerr, Steven, Docherty, Annemarie B, Lone, Nazir I, Quint, Jennifer, Sheikh, Aziz, Zheng, Bang, Jenkins, R Gisli, Cox, Eleanor, Francis, Susan, Halling-Brown, Mark, Chalmers, James D, Greenwood, John P, Plein, Sven, Hughes, Paul J C, Thompson, A A Roger, Rowland-Jones, Sarah L, Wild, James M, Kelly, Matthew, Treibel, Thomas A, Bandula, Steven, Aul, Raminder, Miller, Karla, Jezzard, Peter, Smith, Stephen, Nichols, Thomas E, McCann, Gerry P, Evans, Rachael A, Wain, Louise V, Brightling, Christopher E, Neubauer, Stefan, Baillie, J K, Shaw, Alison, Hairsine, Brigid, Kurasz, Claire, Henson, Helen, Armstrong, Lisa, Shenton, Liz, Dobson, H, Dell, Amanda, Lucey, Alice, Price, Andrea, Storrie, Andrew, Pennington, Chris, Price, Claire, Mallison, Georgia, Willis, Gemma, Nassa, Heeah, Haworth, Jill, Hoare, Michaela, Hawkings, Nancy, Fairbairn, Sara, Young, Susan, Walker, S, Jarrold, I, Sanderson, Amy, David, C, Chong-James, K, Zongo, O, James, W Y, Martineau, A, King, Bernie, Armour, C, McAulay, D, Major, E, McGinness, Jade, McGarvey, L, Magee, N, Stone, Roisin, Drain, S, Craig, T, Bolger, A, Haggar, Ahmed, Lloyd, Arwel, Subbe, Christian, Menzies, Daniel, Southern, David, McIvor, Emma, Roberts, K, Manley, R, Whitehead, Victoria, Saxon, W, Bularga, A, Mills, N L, El-Taweel, Hosni, Dawson, Joy, Robinson, Leanne, Saralaya, Dinesh, Regan, Karen, Storton, Kim, Brear, Lucy, Amoils, S, Bermperi, Areti, Elmer, Anne, Ribeiro, Carla, Cruz, Isabel, Taylor, Jessica, Worsley, J, Dempsey, K, Watson, L, Jose, Sherly, Marciniak, S, Parkes, M, McQueen, Alison, Oliver, Catherine, Williams, Jenny, Paradowski, Kerry, Broad, Lauren, Knibbs, Lucy, Haynes, Matthew, Sabit, Ramsey, Milligan, L, Sampson, Claire, Hancock, Alyson, Evenden, Cerys, Lynch, Ceri, Hancock, Kia, Roche, Lisa, Rees, Meryl, Stroud, Natalie, Thomas-Woods, T, Heller, S, Robertson, E, Young, B, Wassall, Helen, Babores, M, Holland, Maureen, Keenan, Natalie, Shashaa, Sharlene, Price, Carly, Beranova, Eva, Ramos, Hazel, Weston, Heather, Deery, Joanne, Austin, Liam, Solly, Reanne, Turney, Sharon, Cosier, Tracey, Hazelton, Tracy, Ralser, M, Wilson, Ann, Pearce, Lorraine, Pugmire, S, Stoker, Wendy, McCormick, W, Dewar, A, Arbane, Gill, Kaltsakas, G, Kerslake, Helen, Rossdale, J, Bisnauthsing, Karen, Aguilar Jimenez, Laura A, Martinez, L M, Ostermann, Marlies, Magtoto, Murphy M, Hart, Nicholas, Marino, Philip, Betts, Sarah, Solano, Teresa S, Arias, Ava Maria, Prabhu, A, Reed, Annabel, Wrey Brown, Caroline, Griffin, Denise, Bevan, Emily, Martin, Jane, Owen, J, Alvarez Corral, Maria, Williams, Nick, Payne, Sheila, Storrar, Will, Layton, Alison, Lawson, Cathy, Mills, Clare, Featherstone, James, Stephenson, Lorraine, Burdett, Tracy, Ellis, Y, Richards, A, Wright, C, Sykes, D L, Brindle, K, Drury, Katie, Holdsworth, L, Crooks, M G, Atkin, Paul, Flockton, Rachel, Thackray-Nocera, Susannah, Mohamed, Abdelrahman, Taylor, Abigail, Perkins, Emma, Ross, Gavin, McGuinness, Heather, Tench, Helen, Phipps, Janet, Loosley, Ronda, Wolf-Roberts, Rebecca, Coetzee, S, Omar, Zohra, Ross, Alexandra, Card, Bethany, Carr, Caitlin, King, Clara, Wood, Chloe, Copeland, D, Calvelo, Ellen, Chilvers, Edwin R, Russell, Emily, Gordon, Hussain, Nunag, Jose Lloyd, Schronce, J, March, Katherine, Samuel, Katherine, Burden, L, Evison, Lynsey, McLeavey, Laura, Orriss-Dib, Lorna, Tarusan, Lawrence, Mariveles, Myril, Roy, Maura, Mohamed, Noura, Simpson, Neil, Yasmin, Najira, Cullinan, P, Daly, Patrick, Haq, Sulaimaan, Moriera, Silvia, Fayzan, Tamanah, Munawar, Unber, Nwanguma, Uchechi, Lingford-Hughes, A, Altmann, Danny, Johnston, D, Mitchell, J, Valabhji, J, Price, L, Molyneaux, P L, Thwaites, Ryan S, Walsh, S, Frankel, A, Lightstone, L, Wilkins, M, Willicombe, M, McAdoo, S, Touyz, R, Guerdette, Anne-Marie, Warwick, Katie, Hewitt, Melanie, Reddy, R, White, Sonia, McMahon, A, Hoare, Amy, Knighton, Abigail, Ramos, Albert, Te, Amelie, Jolley, Caroline J, Speranza, Fabio, Assefa-Kebede, Hosanna, Peralta, Ida, Breeze, Jonathon, Shevket, K, Powell, Natassia, Adeyemi, Oluwaseun, Dulawan, Pearl, Adrego, Rita, Byrne, S, Patale, Sheetal, Hayday, A, Malim, M, Pariante, C, Sharpe, C, Whitney, J, Bramham, K, Ismail, K, Wessely, S, Nicholson, T, Ashworth, Andrew, Humphries, Amy, Tan, Ai Lyn, Whittam, Beverley, Coupland, C, Favager, Clair, Peckham, D, Wade, Elaine, Saalmink, Gwen, Clarke, Jude, Glossop, Jodie, Murira, Jennifer, Rangeley, Jade, Woods, Janet, Hall, Lucy, Dalton, Matthhew, Window, Nicola, Beirne, Paul, Hardy, Tim, Coakley, G, Turtle, Lance, Berridge, Anthony, Cross, Andy, Key, Angela L, Rowe, Anna, Allt, Ann Marie, Mears, Chloe, Malein, Flora, Madzamba, Gladys, Hardwick, H E, Earley, Joanne, Hawkes, Jenny, Pratt, James, Wyles, J, Tripp, K A, Hainey, Kera, Allerton, Lisa, Lavelle-Langham, L, Melling, Lucy, Wajero, Lilian O, Poll, L, Noonan, Matthew J, French, N, Lewis-Burke, N, Williams-Howard, S A, Cooper, Shirley, Kaprowska, Sabina, Dobson, S L, Marsh, Sophie, Highett, Victoria, Shaw, V, Beadsworth, M, Defres, S, Watson, Ekaterina, Tiongson, Gerlynn F, Papineni, Padmasayee, Gurram, Sambasivarao, Diwanji, Shalin N, Quaid, Sheena, Briggs, A, Hastie, Claire, Rogers, Natalie, Stensel, D, Bishop, L, McIvor, K, Rivera-Ortega, P, Al-Sheklly, B, Avram, Cristina, Faluyi, David, Blaikely, J, Piper Hanley, K, Radhakrishnan, K, Buch, M, Hanley, N A, Odell, Natasha, Osbourne, Rebecca, Stockdale, Sue, Felton, T, Gorsuch, T, Hussell, T, Kausar, Zunaira, Kabir, T, McAllister-Williams, H, Paddick, S, Burn, D, Ayoub, A, Greenhalgh, Alan, Sayer, A, Young, A, Price, D, Burns, G, MacGowan, G, Fisher, Helen, Tedd, H, Simpson, J, Jiwa, Kasim, Witham, M, Hogarth, Philip, West, Sophie, Wright, S, McMahon, Michael J, Neill, Paula, Dougherty, Andrew, Morrow, A, Anderson, David, Grieve, D, Bayes, Hannah, Fallon, K, Mangion, K, Gilmour, L, Basu, N, Sykes, R, Berry, C, McInnes, I B, Donaldson, A, Sage, E K, Barrett, Fiona, Welsh, B, Bell, Murdina, Quigley, Jackie, Leitch, Karen, Macliver, L, Patel, Manish, Hamil, R, Deans, Andrew, Furniss, J, Clohisey, S, Elliott, Anne, Solstice, A R, Deas, C, Tee, Caroline, Connell, David, Sutherland, Debbie, George, J, Mohammed, S, Bunker, Jenny, Holmes, Katie, Dipper, A, Morley, Anna, Arnold, David, Adamali, H, Welch, H, Morrison, Leigh, Stadon, Louise, Maskell, Nick, Barratt, Shaney, Dunn, Sarah, Waterson, Samuel, Jayaraman, Bhagy, Light, Tessa, Selby, N, Hosseini, A, Shaw, Karen, Almeida, Paula, Needham, Robert, Thomas, Andrew K, Matthews, Laura, Gupta, Ayushman, Nikolaidis, Athanasios, Dupont, Catherine, Bonnington, J, Chrystal, Melanie, Greenhaff, P L, Linford, S, Prosper, Sabrina, Jang, W, Alamoudi, Asma, Bloss, Angela, Megson, Clare, Nicoll, Debby, Fraser, Emily, Pacpaco, Edmund, Conneh, Florence, Ogg, G, McShane, H, Koychev, Ivan, Chen, Jin, Pimm, John, Ainsworth, Mark, Pavlides, M, Sharpe, M, Havinden-Williams, May, Petousi, Nayia, Talbot, Nick, Carter, Penny, Kurupati, Prathiba, Dong, T, Peng, Yanchun, Burns, A, Kanellakis, N, Korszun, A, Connolly, B, Busby, J, Peto, T, Patel, B, Nolan, C M, Cristiano, Daniele, Walsh, J A, Liyanage, Kamal, Gummadi, Mahitha, Dormand, N, Polgar, Oliver, George, P, Barker, R E, Patel, Suhani, Gibbons, M, Matila, Darwin, Jarvis, Hannah, Lim, Lai, Olaosebikan, Olaoluwa, Ahmad, Shanaz, Brill, Simon, Mandal, S, Laing, C, Michael, Alice, Reddy, A, Johnson, C, Baxendale, H, Parfrey, H, Mackie, J, Newman, J, Pack, Jamie, Parmar, J, Paques, K, Garner, Lucie, Harvey, Alice, Summersgill, C, Holgate, D, Hardy, E, Oxton, J, Pendlebury, Jessica, McMorrow, L, Mairs, N, Majeed, N, Dark, P, Ugwuoke, R, Knight, Sean, Whittaker, S, Strong-Sheldrake, Sophia, Matimba-Mupaya, Wadzanai, Chowienczyk, P, Pattenadk, Dibya, Hurditch, E, Chan, Flora, Carborn, H, Foot, H, Bagshaw, J, Hockridge, J, Sidebottom, J, Lee, Ju Hee, Birchall, K, Turner, Kim, Haslam, L, Holt, L, Milner, L, Begum, M, Marshall, M, Steele, N, Tinker, N, Ravencroft, Phillip, Butcher, Robyn, Misra, S, Coburn, Zach, Fairman, Alexandra, Ford, Amber, Holbourn, Ailsa, Howell, Alice, Lawrie, Allan, Lye, Alison, Mbuyisa, Angeline, Zawia, Amira, Holroyd-Hind, B, Thamu, B, Clark, Cameron, Jarman, Claire, Norman, C, Roddis, C, Foote, David, Lee, Elvina, Ilyas, F, Stephens, G, Newell, Helen, Turton, Helena, Macharia, Irene, Wilson, Imogen, Cole, Joby, McNeill, J, Meiring, J, Rodger, J, Watson, James, Chapman, Kerry, Harrington, Kate, Chetham, Luke, Hesselden, L, Nwafor, Lorenza, Dixon, Myles, Plowright, Megan, Wade, Phillip, Gregory, Rebecca, Lenagh, Rebecca, Stimpson, R, Megson, Sharon, Newman, Tom, Cheng, Yutung, Goodwin, Camelia, Heeley, Cheryl, Sissons, D, Sowter, D, Gregory, Heidi, Wynter, Inez, Hutchinson, John, Kirk, Jill, Bennett, Kaytie, Slack, Katie, Allsop, Lynne, Holloway, Leah, Flynn, Margaret, Gill, Mandy, Greatorex, M, Holmes, Megan, Buckley, Phil, Shelton, Sarah, Turner, Sarah, Sewell, Terri Ann, Whitworth, V, Lovegrove, Wayne, Tomlinson, Johanne, Warburton, Louise, Painter, Sharon, Vickers, Carinna, Redwood, Dawn, Tilley, Jo, Palmer, Sue, Wainwright, Tania, Breen, G, Hotopf, M, Dunleavy, A, Teixeira, J, Ali, Mariam, Mencias, Mark, Msimanga, N, Siddique, Sulman, Samakomva, T, Tavoukjian, Vera, Forton, D, Ahmed, R, Cook, Amanda, Thaivalappil, Favas, Connor, Lynda, Rees, Tabitha, McNarry, M, Williams, N, McCormick, Jacqueline, McIntosh, Jerome, Vere, Joanne, Coulding, Martina, Kilroy, Susan, Turner, Victoria, Butt, Al-Tahoor, Savill, Heather, Fraile, Eva, Ugoji, Jacinta, Landers, G, Lota, Harpreet, Portukhay, Sofiya, Nasseri, Mariam, Daniels, Alison, Hormis, Anil, Ingham, Julie, Zeidan, Lisa, Osborne, Lynn, Chablani, Manish, Banerjee, A, David, A, Pakzad, A, Rangelov, B, Williams, B, Denneny, E, Willoughby, J, Xu, M, Mehta, P, Batterham, R, Bell, R, Aslani, S, Lilaonitkul, W, Checkley, A, Bang, Dongchun, Basire, Donna, Lomas, D, Wall, E, Plant, Hannah, Roy, K, Heightman, M, Lipman, M, Merida Morillas, Marta, Ahwireng, Nyarko, Chambers, R C, Jastrub, Roman, Logan, S, Hillman, T, Botkai, A, Casey, A, Neal, A, Newton-Cox, A, Cooper, B, Atkin, C, McGee, C, Welch, C, Wilson, D, Sapey, E, Qureshi, H, Hazeldine, J, Lord, J M, Nyaboko, J, Short, J, Stockley, J, Dasgin, J, Draxlbauer, K, Isaacs, K, Mcgee, K, Yip, K P, Ratcliffe, L, Bates, M, Ventura, M, Ahmad Haider, N, Gautam, N, Baggott, R, Holden, S, Madathil, S, Walder, S, Yasmin, S, Hiwot, T, Jackson, T, Soulsby, T, Kamwa, V, Peterkin, Z, Suleiman, Z, Chaudhuri, N, Wheeler, H, Djukanovic, R, Samuel, R, Sass, T, Wallis, T, Marshall, B, Childs, C, Marouzet, E, Harvey, M, Fletcher, S, Dickens, C, Beckett, P, Nanda, U, Daynes, E, Charalambou, A, Yousuf, A J, Lea, A, Prickett, A, Gooptu, Bibek, Hargadon, Beverley, Bourne, Charlotte, Christie, C, Edwardson, C, Lee, D, Baldry, E, Stringer, E, Woodhead, F, Mills, G, Arnold, H, Aung, H, Qureshi, I N, Finch, J, Skeemer, J, Hadley, K, Khunti, Kamlesh, Carr, Liesel, Ingram, L, Aljaroof, M, Bakali, M, Bakau, M, Baldwin, M, Bourne, Michelle, Pareek, Manish, Soares, M, Tobin, Martin, Armstrong, Natalie, Brunskill, Nigel, Goodman, N, Cairns, P, Haldar, Pranab, McCourt, P, Dowling, R, Russell, Richard, Diver, Sarah, Edwards, Sarah, Glover, Sarah, Parker, S, Siddiqui, Salman, Ward, T J C, Mcnally, T, Thornton, T, Yates, Tom, Ibrahim, W, Monteiro, Will, Thickett, D, Wilkinson, D, Broome, M, McArdle, P, Upthegrove, R, Wraith, D, Langenberg, C, Summers, C, Bullmore, E, Heeney, J L, Schwaeble, W, Sudlow, C L, Adeloye, D, Newby, D E, Rudan, I, Shankar-Hari, M, Thorpe, M, Pius, R, Walmsley, S, McGovern, A, Ballard, C, Allan, L, Dennis, J, Cavanagh, J, Petrie, J, O'Donnell, K, Spears, M, Sattar, N, MacDonald, S, Guthrie, E, Henderson, M, Guillen Guio, Beatriz, Zhao, Bang, Lawson, C, Overton, Charlotte, Taylor, Chris, Tong, C, Mukaetova-Ladinska, Elizabeta, Turner, E, Pearl, John E, Sargant, J, Wormleighton, J, Bingham, Michelle, Sharma, M, Steiner, Mike, Samani, Nilesh, Novotny, Petr, Free, Rob, Allen, R J, Finney, Selina, Terry, Sarah, Brugha, Terry, Plekhanova, Tatiana, McArdle, A, Vinson, B, Spencer, L G, Reynolds, W, Ashworth, M, Deakin, B, Chinoy, H, Abel, K, Harvie, M, Stanel, S, Rostron, A, Coleman, C, Baguley, D, Hufton, E, Khan, F, Hall, I, Stewart, I, Fabbri, L, Wright, L, Kitterick, P, Morriss, R, Johnson, S, Bates, A, Antoniades, C, Clark, D, Bhui, K, Channon, K M, Motohashi, K, Sigfrid, L, Husain, M, Webster, M, Fu, X, Li, X, Kingham, L, Klenerman, P, Miiler, K, Carson, G, Simons, G, Huneke, N, Calder, P C, Baldwin, D, Bain, S, Lasserson, D, Daines, L, Bright, E, Stern, M, Crisp, P, Dharmagunawardena, R, Reddington, A, Wight, A, Bailey, L, Ashish, A, Robinson, E, Cooper, J, Broadley, A, Turnbull, A, Brookes, C, Sarginson, C, Ionita, D, Redfearn, H, Elliott, K, Barman, L, Griffiths, L, Guy, Z, Gill, Rhyan, Nathu, Rashmita, Harris, Edward, Moss, P, Finnigan, J, Saunders, Kathryn, Saunders, Peter, Kon, S, Kon, Samantha S, O'Brien, Linda, Shah, K, Shah, P, Richardson, Emma, Brown, V, Brown, M, Brown, Jo, Brown, J, Brown, Ammani, Brown, Angela, Choudhury, N, Jones, S, Jones, H, Jones, L, Jones, I, Jones, G, Jones, Heather, Jones, Don, Davies, Ffyon, Davies, Ellie, Davies, Kim, Davies, Gareth, Davies, Gwyneth A, Howard, K, Porter, Julie, Rowland, J, Rowland, A, Scott, Kathryn, Singh, Suver, Singh, Claire, Thomas, S, Thomas, Caradog, Lewis, Victoria, Lewis, J, Lewis, D, Harrison, P, Francis, C, Francis, R, Hughes, Rachel Ann, Hughes, Joan, Hughes, A D, Thompson, T, Kelly, S, Smith, D, Smith, Nikki, Smith, Andrew, Smith, Jacqui, Smith, Laurie, Smith, Susan, Evans, Teriann, Evans, Ranuromanana I, Evans, D, Evans, R, Evans, H, and Evans, J
Published: 2023
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160. Rapid analysis of the chemical composition of black tea leaves using vibrational spectroscopy techniques

Author: Heaney, Stephanie, Koidis, Anastasios, and Redfern, Sally
Subjects: 664
Abstract: The introduction of rapid methods to monitor tea quality during the oxidation stage in black tea manufacturing is essential for increasing the sustainability of tea production. During this significant stage, the catechins in the tea leaves are converted to theaflavin and the thearubigin compounds and their ratios at the end point of this process plays a major role in the quality of the final product. The implementation of rapid techniques to monitor this process would ultimately increase quality assurance standards resulting in higher yields to quality tea. Fulfilling this challenge requires the exploration of rapid analytical methods and their ability to provide essential information of the chemical compounds, which are associated with tea oxidation status. This thesis explores the use of vibrational spectroscopy techniques and chemotic methods for the rapid analysis of chemical components which can indicate tea quality and oxidation status to ultimately enhance process control in tea manufacturing. Initially, Near-Infrared (NIR) and Mid-Infrared (MIR) were investigated to explore their potential to classify a variety of tea samples by a range of tea quality attributes. The use of NIR and MIR as off-line methods for monitoring oxidation status was assessed by oxidising teas for various times and collecting the spectral fingerprints of these samples after drying. An oxidation unit which was connected toa portable NIR sensor was used to instantly collect spectra of tea during oxidation. This data was used to explore the ability of NIR to rapidly predict oxidation status of teas during this processing. The findings from the research demonstrates that vibrational spectroscopy techniques coupled with chemometric analysis can predict important quality compounds associated with oxidation when tea has been dried (off-line) and during processing (on-line). The results demonstrate potential for methods to be developed and scaled up for application in black tea manufacturing to aid to oxidation control and ultimately produce higher quality yields of sustainable tea.
Published: 2021

161. Fructose impairs glucose-induced hepatic triglyceride synthesis

Author: Boros Laszlo G, Yong William H, Young Stephen, Dhawan Tania, Huang Danshan, and Heaney Anthony P
Subjects: Nutritional diseases. Deficiency diseases, RC620-627
Abstract: Abstract Obesity, type 2 diabetes and hyperlipidemia frequently coexist and are associated with significantly increased morbidity and mortality. Consumption of refined carbohydrate and particularly fructose has increased significantly in recent years and has paralled the increased incidence of obesity and diabetes. Human and animal studies have demonstrated that high dietary fructose intake positively correlates with increased dyslipidemia, insulin resistance, and hypertension. Metabolism of fructose occurs primarily in the liver and high fructose flux leads to enhanced hepatic triglyceride accumulation (hepatic steatosis). This results in impaired glucose and lipid metabolism and increased proinflammatory cytokine expression. Here we demonstrate that fructose alters glucose-stimulated expression of activated acetyl CoA carboxylase (ACC), pSer hormone sensitive lipase (pSerHSL) and adipose triglyceride lipase (ATGL) in hepatic HepG2 or primary hepatic cell cultures in vitro. This was associated with increased de novo triglyceride synthesis in vitro and hepatic steatosis in vivo in fructose- versus glucose-fed and standard-diet fed mice. These studies provide novel insight into the mechanisms involved in fructose-mediated hepatic hypertriglyceridemia and identify fructose-uptake as a new potential therapeutic target for lipid-associated diseases.
Published: 2011
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162. School closures reduced social mixing of children during COVID-19 with implications for transmission risk and school reopening policies.

Author: Head, Jennifer R, Andrejko, Kristin L, Cheng, Qu, Collender, Philip A, Phillips, Sophie, Boser, Anna, Heaney, Alexandra K, Hoover, Christopher M, Wu, Sean L, Northrup, Graham R, Click, Karen, Bardach, Naomi S, Lewnard, Joseph A, and Remais, Justin V
Subjects: Humans, Schools, Child, Policy, COVID-19, SARS-CoV-2, Physical Distancing, children social networks, contact rate, school closures and reopening, transmission model, General Science & Technology
Abstract: School closures may reduce the size of social networks among children, potentially limiting infectious disease transmission. To estimate the impact of K-12 closures and reopening policies on children's social interactions and COVID-19 incidence in California's Bay Area, we collected data on children's social contacts and assessed implications for transmission using an individual-based model. Elementary and Hispanic children had more contacts during closures than high school and non-Hispanic children, respectively. We estimated that spring 2020 closures of elementary schools averted 2167 cases in the Bay Area (95% CI: -985, 5572), fewer than middle (5884; 95% CI: 1478, 11.550), high school (8650; 95% CI: 3054, 15 940) and workplace (15 813; 95% CI: 9963, 22 617) closures. Under assumptions of moderate community transmission, we estimated that reopening for a four-month semester without any precautions will increase symptomatic illness among high school teachers (an additional 40.7% expected to experience symptomatic infection, 95% CI: 1.9, 61.1), middle school teachers (37.2%, 95% CI: 4.6, 58.1) and elementary school teachers (4.1%, 95% CI: -1.7, 12.0). However, we found that reopening policies for elementary schools that combine universal masking with classroom cohorts could result in few within-school transmissions, while high schools may require masking plus a staggered hybrid schedule. Stronger community interventions (e.g. remote work, social distancing) decreased the risk of within-school transmission across all measures studied, with the influence of community transmission minimized as the effectiveness of the within-school measures increased.
Published: 2021

163. The NIH Somatic Cell Genome Editing program

Author: Saha, Krishanu, Sontheimer, Erik J, Brooks, PJ, Dwinell, Melinda R, Gersbach, Charles A, Liu, David R, Murray, Stephen A, Tsai, Shengdar Q, Wilson, Ross C, Anderson, Daniel G, Asokan, Aravind, Banfield, Jillian F, Bankiewicz, Krystof S, Bao, Gang, Bulte, Jeff WM, Bursac, Nenad, Campbell, Jarryd M, Carlson, Daniel F, Chaikof, Elliot L, Chen, Zheng-Yi, Cheng, R Holland, Clark, Karl J, Curiel, David T, Dahlman, James E, Deverman, Benjamin E, Dickinson, Mary E, Doudna, Jennifer A, Ekker, Stephen C, Emborg, Marina E, Feng, Guoping, Freedman, Benjamin S, Gamm, David M, Gao, Guangping, Ghiran, Ionita C, Glazer, Peter M, Gong, Shaoqin, Heaney, Jason D, Hennebold, Jon D, Hinson, John T, Khvorova, Anastasia, Kiani, Samira, Lagor, William R, Lam, Kit S, Leong, Kam W, Levine, Jon E, Lewis, Jennifer A, Lutz, Cathleen M, Ly, Danith H, Maragh, Samantha, McCray, Paul B, McDevitt, Todd C, Mirochnitchenko, Oleg, Morizane, Ryuji, Murthy, Niren, Prather, Randall S, Ronald, John A, Roy, Subhojit, Roy, Sushmita, Sabbisetti, Venkata, Saltzman, W Mark, Santangelo, Philip J, Segal, David J, Shimoyama, Mary, Skala, Melissa C, Tarantal, Alice F, Tilton, John C, Truskey, George A, Vandsburger, Moriel, Watts, Jonathan K, Wells, Kevin D, Wolfe, Scot A, Xu, Qiaobing, Xue, Wen, Yi, Guohua, and Zhou, Jiangbing
Subjects: Biological Sciences, Biomedical and Clinical Sciences, Genetics, Gene Therapy, Biotechnology, Human Genome, 5.2 Cellular and gene therapies, Generic health relevance, Animals, Cells, Gene Editing, Genetic Therapy, Genome, Human, Goals, Humans, National Institutes of Health (U.S.), United States, SCGE Consortium, General Science & Technology
Abstract: The move from reading to writing the human genome offers new opportunities to improve human health. The United States National Institutes of Health (NIH) Somatic Cell Genome Editing (SCGE) Consortium aims to accelerate the development of safer and more-effective methods to edit the genomes of disease-relevant somatic cells in patients, even in tissues that are difficult to reach. Here we discuss the consortium's plans to develop and benchmark approaches to induce and measure genome modifications, and to define downstream functional consequences of genome editing within human cells. Central to this effort is a rigorous and innovative approach that requires validation of the technology through third-party testing in small and large animals. New genome editors, delivery technologies and methods for tracking edited cells in vivo, as well as newly developed animal models and human biological systems, will be assembled-along with validated datasets-into an SCGE Toolkit, which will be disseminated widely to the biomedical research community. We visualize this toolkit-and the knowledge generated by its applications-as a means to accelerate the clinical development of new therapies for a wide range of conditions.
Published: 2021

164. A resource of targeted mutant mouse lines for 5,061 genes

Author: Birling, Marie-Christine, Yoshiki, Atsushi, Adams, David J, Ayabe, Shinya, Beaudet, Arthur L, Bottomley, Joanna, Bradley, Allan, Brown, Steve DM, Bürger, Antje, Bushell, Wendy, Chiani, Francesco, Chin, Hsian-Jean Genie, Christou, Skevoulla, Codner, Gemma F, DeMayo, Francesco J, Dickinson, Mary E, Doe, Brendan, Donahue, Leah Rae, Fray, Martin D, Gambadoro, Alessia, Gao, Xiang, Gertsenstein, Marina, Gomez-Segura, Alba, Goodwin, Leslie O, Heaney, Jason D, Hérault, Yann, de Angelis, Martin Hrabe, Jiang, Si-Tse, Justice, Monica J, Kasparek, Petr, King, Ruairidh E, Kühn, Ralf, Lee, Ho, Lee, Young Jae, Liu, Zhiwei, Lloyd, KC Kent, Lorenzo, Isabel, Mallon, Ann-Marie, McKerlie, Colin, Meehan, Terrence F, Fuentes, Violeta Munoz, Newman, Stuart, Nutter, Lauryl MJ, Oh, Goo Taeg, Pavlovic, Guillaume, Ramirez-Solis, Ramiro, Rosen, Barry, Ryder, Edward J, Santos, Luis A, Schick, Joel, Seavitt, John R, Sedlacek, Radislav, Seisenberger, Claudia, Seong, Je Kyung, Skarnes, William C, Sorg, Tania, Steel, Karen P, Tamura, Masaru, Tocchini-Valentini, Glauco P, Wang, Chi-Kuang Leo, Wardle-Jones, Hannah, Wattenhofer-Donzé, Marie, Wells, Sara, Wiles, Michael V, Willis, Brandon J, Wood, Joshua A, Wurst, Wolfgang, Xu, Ying, Teboul, Lydia, and Murray, Stephen A
Subjects: Biological Sciences, Genetics, Animals, Gene Deletion, Genetic Association Studies, Genome, Genotype, Information Dissemination, International Cooperation, Internet, Mice, Mice, Knockout, Mouse Embryonic Stem Cells, Mutagenesis, Phenotype, International Mouse Phenotyping Consortium, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract: The International Mouse Phenotyping Consortium reports the generation of new mouse mutant strains for over 5,000 genes, including 2,850 novel null, 2,987 novel conditional- ready, and 4,433 novel reporter alleles.
Published: 2021

165. A human ACTH-secreting corticotroph tumoroid model Novel Human ACTH-Secreting Tumor Cell in vitro Model

Author: Zhang, Dongyun, Hugo, Willy, Redublo, Peter, Miao, Hui, Bergsneider, Marvin, Wang, Marilene B, Kim, Won, Yong, William H, and Heaney, Anthony P
Subjects: Biomedical and Clinical Sciences, Clinical Sciences, Human Genome, Genetics, Rare Diseases, Brain Cancer, Cancer, Brain Disorders, ACTH-Secreting Pituitary Adenoma, Biomarkers, Cell Line, Tumor, Cell Proliferation, Cells, Cultured, Computational Biology, Gene Expression Profiling, High-Throughput Nucleotide Sequencing, Humans, Pituitary ACTH Hypersecretion, Single-Cell Analysis, Spheroids, Cellular, Tumor Cells, Cultured, Adrenocorticotropic hormone, Cushing disease, 3D culture, Proopiomelanocortin, Public Health and Health Services, Clinical sciences, Epidemiology
Abstract: BackgroundCushing disease (CD), although rare, is a life-threatening disorder caused by an adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma, which leads to excess adrenal-derived cortisol. Efficacious and safe medical therapies that control both hormonal hypersecretion and pituitary corticotroph tumor growth remain an unmet need in the management of CD. Translational research in pituitary tumors has been significantly hampered by limited quantities of surgically resected tissue for ex vivo studies, and unavailability of human pituitary tumor cell models.MethodsTo characterize human corticotroph tumors at the cellular level, we employed single cell RNA-sequencing (scRNA-seq) to study 4 surgically resected tumors. We also used microarrays to compare individualized paired consecutive culture passages to understand transcriptional shifts as in vitro cultures lost ACTH secretion. Based on these findings, we then modified our in vitro culture methods to develop sustained ACTH-secreting human corticotroph tumoroid cultures.FindingsscRNA-seq identified 4 major cell populations, namely corticotroph tumor (73.6%), stromal (11.2%), progenitor (8.3%), and immune cells (6.8%). Microarray analysis revealed striking changes in extracellular matrix, cell adhesion and motility-related genes concordant with loss of ACTH secretion during conventional 2D culture. Based on these findings, we subsequently defined a series of crucial culture nutrients and scaffold modifications that provided a more favorable trophic and structural environment that could maintain ACTH secretion in in vitro human corticotroph tumor cultures for up to 4 months.InterpretationOur human corticotroph tumoroid model is a significant advance in the field of pituitary tumors and will further enable translational research studies to identify critically needed therapies for CD.FundingThis work was partly funded by NCI P50-CA211015 and the Warley Trust Foundation.
Published: 2021

166. Todo en familia: El actor Oscar Nuñez tiene muchos familiares con demencia. Él cree que toda persona con el padecimiento merece una atención mejor y menos costosa.

Author: West, Caitlin Heaney
Published: 2024
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167. Jersey Company Law Series: Buyback / Repurchase Of Own Shares

Author: Heaney, Jonathan
Subjects: Stock redemption -- Laws, regulations and rules, Government regulation, Business, international
Abstract: KEY TAKEAWAYS Statutory requirements Solvency statement implications Funding and treatment of buybacks The Companies (Jersey) Law 1991, as amended, (the 'Law') gives Jersey companies a considerable degree of flexibility to [...]
Published: 2024

168. Jersey Company Law Series: Mergers - Which Entities, The Process And The Effect

Author: Heaney, Jonathan
Subjects: Corporation law -- Interpretation and construction, Acquisitions and mergers -- Laws, regulations and rules, Government regulation, Business, international, Jersey. Companies Law 1991
Abstract: KEY TAKEAWAYS Eligibility to merge Statutory process Regulatory treatment and merger completion The Companies (Jersey) Law 1991, as amended, (the 'Law') provides a modern, simple and flexible merger regime for [...]
Published: 2024

169. Jersey Company Law Series: Reduction Of Capital Without Court Approval

Author: Heaney, Jonathan
Subjects: Capital formation -- Laws, regulations and rules, Corporation law -- Interpretation and construction, Government regulation, Business, international, Jersey. Companies Law 1991
Abstract: KEY TAKEAWAYS Required documents and the solvency statement Content of the 'Minute' Procedure and effectiveness The Companies (Jersey) Law 1991, as amended, (the 'Law') includes a simple procedure by which [...]
Published: 2024

170. Genome-wide screening reveals the genetic basis of mammalian embryonic eye development

Author: Justine M. Chee, Louise Lanoue, Dave Clary, Kendall Higgins, Lynette Bower, Ann Flenniken, Ruolin Guo, David J. Adams, Fatima Bosch, Robert E. Braun, Steve D. M. Brown, H.-J. Genie Chin, Mary E. Dickinson, Chih-Wei Hsu, Michael Dobbie, Xiang Gao, Sanjeev Galande, Anne Grobler, Jason D. Heaney, Yann Herault, Martin Hrabe de Angelis, Fabio Mammano, Lauryl M. J. Nutter, Helen Parkinson, Chuan Qin, Toshi Shiroishi, Radislav Sedlacek, J-K Seong, Ying Xu, The International Mouse Phenotyping Consortium, Brian Brooks, Colin McKerlie, K. C. Kent Lloyd, Henrik Westerberg, and Ala Moshiri
Subjects: MAC spectrum, Eye development, Mouse, IMPC, Serine-glycine biosynthesis, CPLANE, Biology (General), QH301-705.5
Abstract: Abstract Background Microphthalmia, anophthalmia, and coloboma (MAC) spectrum disease encompasses a group of eye malformations which play a role in childhood visual impairment. Although the predominant cause of eye malformations is known to be heritable in nature, with 80% of cases displaying loss-of-function mutations in the ocular developmental genes OTX2 or SOX2, the genetic abnormalities underlying the remaining cases of MAC are incompletely understood. This study intended to identify the novel genes and pathways required for early eye development. Additionally, pathways involved in eye formation during embryogenesis are also incompletely understood. This study aims to identify the novel genes and pathways required for early eye development through systematic forward screening of the mammalian genome. Results Query of the International Mouse Phenotyping Consortium (IMPC) database (data release 17.0, August 01, 2022) identified 74 unique knockout lines (genes) with genetically associated eye defects in mouse embryos. The vast majority of eye abnormalities were small or absent eyes, findings most relevant to MAC spectrum disease in humans. A literature search showed that 27 of the 74 lines had previously published knockout mouse models, of which only 15 had ocular defects identified in the original publications. These 12 previously published gene knockouts with no reported ocular abnormalities and the 47 unpublished knockouts with ocular abnormalities identified by the IMPC represent 59 genes not previously associated with early eye development in mice. Of these 59, we identified 19 genes with a reported human eye phenotype. Overall, mining of the IMPC data yielded 40 previously unimplicated genes linked to mammalian eye development. Bioinformatic analysis showed that several of the IMPC genes colocalized to several protein anabolic and pluripotency pathways in early eye development. Of note, our analysis suggests that the serine-glycine pathway producing glycine, a mitochondrial one-carbon donator to folate one-carbon metabolism (FOCM), is essential for eye formation. Conclusions Using genome-wide phenotype screening of single-gene knockout mouse lines, STRING analysis, and bioinformatic methods, this study identified genes heretofore unassociated with MAC phenotypes providing models to research novel molecular and cellular mechanisms involved in eye development. These findings have the potential to hasten the diagnosis and treatment of this congenital blinding disease.
Published: 2023
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171. Blood transcriptomic signature in type-2 biomarker-low severe asthma and asthma control

Author: Zeng, Xue, Qing, Jing, Li, Chi-Ming, Lu, Jiamiao, Yamawaki, Tracy, Hsu, Yi-Hsiang, Vander Lugt, Bryan, Hsu, Hailing, Busby, John, McDowell, P.J., Jackson, David J., Djukanovic, Ratko, Matthews, John G., Arron, Joseph R., Bradding, Peter, Brightling, Christopher E., Chaudhuri, Rekha, Choy, David F., Cowan, D., Fowler, S.J., Hardman, Timothy C., Harrison, Tim, Howarth, Peter, Lordan, James, Mansur, A.H., Menzies-Gow, Andrew, Pavord, Ian D., Walker, Samantha, Woodcock, Ashley, and Heaney, Liam G.
Published: 2023
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172. Antimicrobial overproduction sustains intestinal inflammation by inhibiting Enterococcus colonization

Author: Jang, Kyung Ku, Heaney, Thomas, London, Mariya, Ding, Yi, Putzel, Gregory, Yeung, Frank, Ercelen, Defne, Chen, Ying-Han, Axelrad, Jordan, Gurunathan, Sakteesh, Zhou, Chaoting, Podkowik, Magdalena, Arguelles, Natalia, Srivastava, Anusha, Shopsin, Bo, Torres, Victor J., Keestra-Gounder, A. Marijke, Pironti, Alejandro, Griffin, Matthew E., Hang, Howard C., and Cadwell, Ken
Published: 2023
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173. Impact of Initiating Biologics in Patients With Severe Asthma on Long-Term Oral Corticosteroids or Frequent Rescue Steroids (GLITTER): Data From the International Severe Asthma Registry

Author: Chen, Wenjia, Tran, Trung N., Sadatsafavi, Mohsen, Murray, Ruth, Wong, Nigel Chong Boon, Ali, Nasloon, Ariti, Con, Bulathsinhala, Lakmini, Gil, Esther Garcia, FitzGerald, J. Mark, Alacqua, Marianna, Al-Ahmad, Mona, Altraja, Alan, Al-Lehebi, Riyad, Bhutani, Mohit, Bjermer, Leif, Bjerrum, Anne-Sofie, Bourdin, Arnaud, von Bülow, Anna, Busby, John, Canonica, Giorgio Walter, Carter, Victoria, Christoff, George C., Cosio, Borja G., Costello, Richard W., Fonseca, João A., Gibson, Peter G., Yoo, Kwang-Ha, Heaney, Liam G., Heffler, Enrico, Hew, Mark, Hilberg, Ole, Hoyte, Flavia, Iwanaga, Takashi, Jackson, David J., Jones, Rupert C., Koh, Mariko Siyue, Kuna, Piotr, Larenas-Linnemann, Désirée, Lehmann, Sverre, Lehtimäki, Lauri, Lyu, Juntao, Mahboub, Bassam, Maspero, Jorge, Menzies-Gow, Andrew N., Newell, Anthony, Sirena, Concetta, Papadopoulos, Nikolaos G., Papaioannou, Andriana I., Perez-de-Llano, Luis, Perng (Steve), Diahn-Warng, Peters, Matthew, Pfeffer, Paul E., Porsbjerg, Celeste M., Popov, Todor A., Rhee, Chin Kook, Salvi, Sundeep, Taillé, Camille, Taube, Christian, Torres-Duque, Carlos A., Ulrik, Charlotte, Ra, Seung-Won, Wang, Eileen, Wechsler, Michael E., and Price, David B.
Published: 2023
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174. Concern for Caregivers: When actor Hector Elizondoʼs mother was diagnosed with dementia, his father took on her care. The enormous demands took a devastating toll, a fate Elizondo hopes to spare others.

Author: Heaney West, Caitlin
Published: 2023
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175. Effects of sleep disturbance on dyspnoea and impaired lung function following hospital admission due to COVID-19 in the UK: a prospective multicentre cohort study

Author: Jackson, C, Stewart, I D, Plekhanova, T, Cunningham, P S, Hazel, A L, Al-Sheklly, B, Aul, R, Bolton, C E, Chalder, T, Chalmers, J D, Chaudhuri, N, Docherty, A B, Donaldson, G, Edwardson, C L, Elneima, O, Greening, N J, Hanley, N A, Harris, V C, Harrison, E M, Ho, L-P, Houchen-Wolloff, L, Howard, L S, Jolley, C J, Jones, M G, Leavy, O C, Lewis, K E, Lone, N I, Marks, M, McAuley, H J C, McNarry, M A, Patel, B, Piper-Hanley, K, Poinasamy, K, Raman, B, Richardson, M, Rivera-Ortega, P, Rowland-Jones, S L, Rowlands, A V, Saunders, R M, Scott, J T, Sereno, M, Shah, A M, Shikotra, A, Singapuri, A, Stanel, S C, Thorpe, M, Wootton, D G, Yates, T, Jenkins, G, Singh, S J, Man, W D-C, Brightling, C E, Wain, L V, Porter, J C, Thompson, R, Horsley, A, Molyneaux, P L, Evans, R A, Jones, S E, Rutter, M K, Blaikley, J F, Abel, K, Adamali, H, Adeloye, D, Adeyemi, O, Adrego, R, Aguilar Jimenez, L A, Ahmad, S, Ahmad Haider, N, Ahmed, R, Ahwireng, N, Ainsworth, M, Alamoudi, A, Ali, M, Aljaroof, M, All, AM, Allan, L, Allen, R J, Allerton, L, Allsop, L, Almeida, P, Altmann, D, Alvarez Corral, M, Amoils, S, Anderson, D, Antoniades, C, Arbane, G, Arias, A, Armour, C, Armstrong, L, Armstrong, N, Arnold, D, Arnold, H, Ashish, A, Ashworth, A, Ashworth, M, Aslani, S, Assefa-Kebede, H, Atkin, C, Atkin, P, Aung, H, Austin, L, Avram, C, Ayoub, A, Babores, M, Baggott, R, Bagshaw, J, Baguley, D, Bailey, L, Baillie, J K, Bain, S, Bakali, M, Bakau, M, Baldry, E, Baldwin, D, Baldwin, M, Ballard, C, Banerjee, A, Bang, B, Barker, R E, Barman, L, Barratt, S, Barrett, F, Basire, D, Basu, N, Bates, M, Bates, A, Batterham, R, Baxendale, H, Bayes, H, Beadsworth, M, Beckett, P, Beggs, M, Begum, M, Beirne, P, Bell, D, Bell, R, Bennett, K, Beranova, E, Bermperi, A, Berridge, A, Berry, C, Betts, S, Bevan, E, Bhui, K, Bingham, M, Birchall, K, Bishop, L, Bisnauthsing, K, Blaikely, J, Bloss, A, Bolger, A, Bonnington, J, Botkai, A, Bourne, C, Bourne, M, Bramham, K, Brear, L, Breen, G, Breeze, J, Briggs, A, Bright, E, Brill, S, Brindle, K, Broad, L, Broadley, A, Brookes, C, Broome, M, Brown, A, Brown, J, Brown, J S, Brown, M, Brown, V, Brugha, T, Brunskill, N, Buch, M, Buckley, P, Bularga, A, Bullmore, E, Burden, L, Burdett, T, Burn, D, Burns, G, Burns, A, Busby, J, Butcher, R, Butt, A, Byrne, S, Cairns, P, Calder, P C, Calvelo, E, Carborn, H, Card, B, Carr, C, Carr, L, Carson, G, Carter, P, Casey, A, Cassar, M, Cavanagh, J, Chablani, M, Chambers, R C, Chan, F, Channon, K M, Chapman, K, Charalambou, A, Checkley, A, Chen, J, Cheng, Y, Chetham, L, Childs, C, Chilvers, E R, Chinoy, H, Chiribiri, A, Chong-James, K, Choudhury, G, Choudhury, N, Chowienczyk, P, Christie, C, Chrystal, M, Clark, D, Clark, C, Clarke, J, Clohisey, S, Coakley, G, Coburn, Z, Coetzee, S, Cole, J, Coleman, C, Conneh, F, Connell, D, Connolly, B, Connor, L, Cook, A, Cooper, B, Cooper, J, Cooper, S, Copeland, D, Cosier, T, Coulding, M, Coupland, C, Cox, E, Craig, T, Crisp, P, Cristiano, D, Crooks, M G, Cross, A, Cruz, I, Cullinan, P, Cuthbertson, D, Daines, L, Dalton, M, Daly, P, Daniels, A, Dark, P, Dasgin, J, David, A, David, C, Davies, E, Davies, F, Davies, G, Davies, G A, Davies, K, Davies, M J, Dawson, J, Daynes, E, De Soyza, A, Deakin, B, Deans, A, Deas, C, Deery, J, Defres, S, Dell, A, Dempsey, K, Denneny, E, Dennis, J, Dewar, A, Dharmagunawardena, R, Diar-Bakerly, N, Dickens, C, Dipper, A, Diver, S, Diwanji, S N, Dixon, M, Djukanovic, R, Dobson, H, Dobson, S L, Donaldson, A, Dong, T, Dormand, N, Dougherty, A, Dowling, R, Drain, S, Draxlbauer, K, Drury, K, Dulawan, P, Dunleavy, A, Dunn, S, Dupont, C, Earley, J, Easom, N, Echevarria, C, Edwards, S, Edwardson, C, El-Taweel, H, Elliott, A, Elliott, K, Ellis, Y, Elmer, A, Evans, D, Evans, H, Evans, J, Evans, R, Evans, R I, Evans, T, Evenden, C, Evison, L, Fabbri, L, Fairbairn, S, Fairman, A, Fallon, K, Faluyi, D, Favager, C, Fayzan, T, Featherstone, J, Felton, T, Finch, J, Finney, S, Finnigan, J, Finnigan, L, Fisher, H, Fletcher, S, Flockton, R, Flynn, M, Foot, H, Foote, D, Ford, A, Forton, D, Fraile, E, Francis, C, Francis, R, Francis, S, Frankel, A, Fraser, E, Free, R, French, N, Fu, X, Fuld, J, Furniss, J, Garner, L, Gautam, N, Geddes, J R, George, J, George, P M, Gibbons, M, Gill, M, Gilmour, L, Gleeson, F, Glossop, J, Glover, S, Goodman, N, Goodwin, C, Gooptu, B, Gordon, H, Gorsuch, T, Greatorex, M, Greenhaff, P L, Greenhalf, W, Greenhalgh, A, Greenwood, J, Gregory, H, Gregory, R, Grieve, D, Griffin, D, Griffiths, L, Guerdette, A-M, Guillen Guio, B, Gummadi, M, Gupta, A, Gurram, S, Guthrie, E, Guy, Z, Henson, H, Hadley, K, Haggar, A, Hainey, K, Hairsine, B, Haldar, P, Hall, I, Hall, L, Halling-Brown, M, Hamil, R, Hancock, A, Hancock, K, Haq, S, Hardwick, H E, Hardy, E, Hardy, T, Hargadon, B, Harrington, K, Harris, E, Harrison, P, Hart, N, Harvey, A, Harvey, M, Harvie, M, Haslam, L, Havinden-Williams, M, Hawkes, J, Hawkings, N, Haworth, J, Hayday, A, Haynes, M, Hazeldine, J, Hazelton, T, Heaney, L G, Heeley, C, Heeney, J L, Heightman, M, Heller, S, Henderson, M, Hesselden, L, Hewitt, M, Highett, V, Hillman, T, Hiwot, T, Hoare, A, Hoare, M, Hockridge, J, Hogarth, P, Holbourn, A, Holden, S, Holdsworth, L, Holgate, D, Holland, M, Holloway, L, Holmes, K, Holmes, M, Holroyd-Hind, B, Holt, L, Hormis, A, Hosseini, A, Hotopf, M, Howard, K, Howell, A, Hufton, E, Hughes, A D, Hughes, J, Hughes, R, Humphries, A, Huneke, N, Hurditch, E, Hurst, J, Husain, M, Hussell, T, Hutchinson, J, Ibrahim, W, Ilyas, F, Ingham, J, Ingram, L, Ionita, D, Isaacs, K, Ismail, K, Jackson, T, Jacob, J, James, W Y, Jang, W, Jarman, C, Jarrold, I, Jarvis, H, Jastrub, R, Jayaraman, B, Jenkins, R G, Jezzard, P, Jiwa, K, Johnson, C, Johnson, S, Johnston, D, Jones, D, Jones, G, Jones, H, Jones, I, Jones, L, Jones, S, Jose, S, Kabir, T, Kaltsakas, G, Kamwa, V, Kanellakis, N, Kaprowska, S, Kausar, Z, Keenan, N, Kelly, S, Kemp, G, Kerr, S, Kerslake, H, Key, A L, Khan, F, Khunti, K, Kilroy, S, King, B, King, C, Kingham, L, Kirk, J, Kitterick, P, Klenerman, P, Knibbs, L, Knight, S, Knighton, A, Kon, O, Kon, S, Kon, S S, Koprowska, S, Korszun, A, Koychev, I, Kurasz, C, Kurupati, P, Laing, C, Lamlum, H, Landers, G, Langenberg, C, Lasserson, D, Lavelle-Langham, L, Lawrie, A, Lawson, C, Layton, A, Lea, A, Lee, D, Lee, J-H, Lee, E, Leitch, K, Lenagh, R, Lewis, D, Lewis, J, Lewis, V, Lewis-Burke, N, Li, X, Light, T, Lightstone, L, Lilaonitkul, W, Lim, L, Linford, S, Lingford-Hughes, A, Lipman, M, Liyanage, K, Lloyd, A, Logan, S, Lomas, D, Loosley, R, Lord, J M, Lota, H, Lovegrove, W, Lucey, A, Lukaschuk, E, Lye, A, Lynch, C, MacDonald, S, MacGowan, G, Macharia, I, Mackie, J, Macliver, L, Madathil, S, Madzamba, G, Magee, N, Magtoto, M M, Mairs, N, Majeed, N, Major, E, Malein, F, Malim, M, Mallison, G, Mandal, S, Mangion, K, Manisty, C, Manley, R, March, K, Marciniak, S, Marino, P, Mariveles, M, Marouzet, E, Marsh, S, Marshall, B, Marshall, M, Martin, J, Martineau, A, Martinez, L M, Maskell, N, Matila, D, Matimba-Mupaya, W, Matthews, L, Mbuyisa, A, McAdoo, S, McAllister-Williams, H, McArdle, A, McArdle, P, McAulay, D, McCann, G P, McCormick, J, McCormick, W, McCourt, P, McGarvey, L, McGhee, C, Mcgee, K, McGinness, J, McGlynn, K, McGovern, A, McGuinness, H, McInnes, I B, McIntosh, J, McIvor, E, McIvor, K, McLeavey, L, McMahon, A, McMahon, M J, McMorrow, L, Mcnally, T, McNarry, M, McNeill, J, McQueen, A, McShane, H, Mears, C, Megson, C, Megson, S, Mehta, P, Meiring, J, Melling, L, Mencias, M, Menzies, D, Merida Morillas, M, Michael, A, Miller, C, Milligan, L, Mills, C, Mills, G, Mills, N L, Milner, L, Misra, S, Mitchell, J, Mohamed, A, Mohamed, N, Mohammed, S, Monteiro, W, Moriera, S, Morley, A, Morrison, L, Morriss, R, Morrow, A, Moss, A J, Moss, P, Motohashi, K, Msimanga, N, Mukaetova-Ladinska, E, Munawar, U, Murira, J, Nanda, U, Nassa, H, Nasseri, M, Neal, A, Needham, R, Neill, P, Neubauer, S, Newby, D E, Newell, H, Newman, T, Newman, J, Newton-Cox, A, Nicholson, T, Nicoll, D, Nikolaidis, A, Nolan, C M, Noonan, M J, Norman, C, Novotny, P, Nunag, J, Nwafor, L, Nwanguma, U, Nyaboko, J, O'Brien, C, O'Donnell, K, O'Regan, D, O'Brien, L, Odell, N, Ogg, G, Olaosebikan, O, Oliver, C, Omar, Z, Openshaw, P J M, Orriss-Dib, L, Osborne, L, Osbourne, R, Ostermann, M, Overton, C, Owen, J, Oxton, J, Pack, J, Pacpaco, E, Paddick, S, Painter, S, Pakzad, A, Palmer, S, Papineni, P, Paques, K, Paradowski, K, Pareek, M, Parekh, D, Parfrey, H, Pariante, C, Parker, S, Parkes, M, Parmar, J, Patale, S, Patel, M, Patel, S, Pattenadk, D, Pavlides, M, Payne, S, Pearce, L, Pearl, J E, Peckham, D, Pendlebury, J, Peng, Y, Pennington, C, Peralta, I, Perkins, E, Peterkin, Z, Peto, T, Petousi, N, Petrie, J, Pfeffer, P, Phipps, J, Pimm, J, Pius, R, Plant, H, Plein, S, Plowright, M, Polgar, O, Poll, L, Porter, J, Portukhay, S, Powell, N, Prabhu, A, Pratt, J, Price, A, Price, C, Price, D, Price, L, Prickett, A, Propescu, J, Prosper, S, Pugmire, S, Quaid, S, Quigley, J, Quint, J, Qureshi, H, Qureshi, I N, Radhakrishnan, K, Rahman, N M, Ralser, M, Ramos, A, Ramos, H, Rangeley, J, Rangelov, B, Ratcliffe, L, Ravencroft, P, Reddington, A, Reddy, R, Reddy, A, Redfearn, H, Redwood, D, Reed, A, Rees, M, Rees, T, Regan, K, Reynolds, W, Ribeiro, C, Richards, A, Richardson, E, Roberts, K, Robertson, E, Robinson, E, Robinson, L, Roche, L, Roddis, C, Rodger, J, Ross, A, Ross, G, Rossdale, J, Rostron, A, Rowe, A, Rowland, A, Rowland, J, Rowland, M J, Roy, K, Roy, M, Rudan, I, Russell, R, Russell, E, Saalmink, G, Sabit, R, Sage, E K, Samakomva, T, Samani, N, Sampson, C, Samuel, K, Samuel, R, Sanderson, A, Sapey, E, Saralaya, D, Sargent, J, Sarginson, C, Sass, T, Sattar, N, Saunders, K, Saunders, P, Saunders, L C, Savill, H, Saxon, W, Sayer, A, Schronce, J, Schwaeble, W, Scott, K, Selby, N, Semple, M G, Sewell, T A, Shah, K, Shah, P, Shankar-Hari, M, Sharma, M, Sharpe, C, Sharpe, M, Shashaa, S, Shaw, A, Shaw, K, Shaw, V, Sheikh, A, Shelton, S, Shenton, L, Shevket, K, Short, J, Siddique, S, Siddiqui, S, Sidebottom, J, Sigfrid, L, Simons, G, Simpson, J, Simpson, N, Singh, C, Sissons, D, Skeemer, J, Slack, K, Smith, A, Smith, D, Smith, S, Smith, J, Smith, L, Soares, M, Solano, T S, Solly, R, Solstice, A R, Soulsby, T, Southern, D, Sowter, D, Spears, M, Spencer, L G, Speranza, F, Stadon, L, Stanel, S, Steele, N, Steiner, M, Stensel, D, Stephens, G, Stephenson, L, Stern, M, Stimpson, R, Stockdale, S, Stockley, J, Stoker, W, Stone, R, Storrar, W, Storrie, A, Storton, K, Stringer, E, Strong-Sheldrake, S, Stroud, N, Subbe, C, Sudlow, C L, Suleiman, Z, Summers, C, Summersgill, C, Sutherland, D, Sykes, D L, Sykes, R, Talbot, N, Tan, A L, Tarusan, L, Tavoukjian, V, Taylor, A, Taylor, C, Taylor, J, Te, A, Tedd, H, Tee, C J, Teixeira, J, Tench, H, Terry, S, Thackray-Nocera, S, Thaivalappil, F, Thamu, B, Thickett, D, Thomas, C, Thomas, D C, Thomas, S, Thomas, A K, Thomas-Woods, T, Thompson, T, Thompson, A A R, Thornton, T, Thwaites, R S, Tilley, J, Tinker, N, Tiongson, G F, Tobin, M, Tomlinson, J, Tong, C, Toshner, M, Touyz, R, Tripp, K A, Tunnicliffe, E, Turnbull, A, Turner, E, Turner, S, Turner, V, Turner, K, Turney, S, Turtle, L, Turton, H, Ugoji, J, Ugwuoke, R, Upthegrove, R, Valabhji, J, Ventura, M, Vere, J, Vickers, C, Vinson, B, Wade, E, Wade, P, Wainwright, T, Wajero, L O, Walder, S, Walker, S, Wall, E, Wallis, T, Walmsley, S, Walsh, J A, Walsh, S, Warburton, L, Ward, T J C, Warwick, K, Wassall, H, Waterson, S, Watson, E, Watson, L, Watson, J, Weir McCall, J, Welch, C, Welch, H, Welsh, B, Wessely, S, West, S, Weston, H, Wheeler, H, White, S, Whitehead, V, Whitney, J, Whittaker, S, Whittam, B, Whitworth, V, Wight, A, Wild, J M, Wilkins, M, Wilkinson, D, Williams, B, Williams, N, Williams, J, Williams-Howard, S A, Willicombe, M, Willis, G, Willoughby, J, Wilson, A, Wilson, D, Wilson, I, Window, N, Witham, M, Wolf-Roberts, R, Wood, C, Woodhead, F, Woods, J, Wormleighton, J, Worsley, J, Wraith, D, Wrey Brown, C, Wright, C, Wright, L, Wright, S, Wyles, J, Wynter, I, Xu, M, Yasmin, N, Yasmin, S, Yip, K P, Young, B, Young, S, Young, A, Yousuf, A J, Zawia, A, Zeidan, L, Zhao, B, Zheng, B, Zongo, O, Jackson, Callum, Stewart, Iain D, Plekhanova, Tatiana, Cunningham, Peter S, Hazel, Andrew L, Al-Sheklly, Bashar, Aul, Raminder, Bolton, Charlotte E, Chalder, Trudie, Chalmers, James D, Chaudhuri, Nazia, Docherty, Annemarie B, Donaldson, Gavin, Edwardson, Charlotte L, Elneima, Omer, Greening, Neil J, Hanley, Neil A, Harris, Victoria C, Harrison, Ewen M, Ho, Ling-Pei, Houchen-Wolloff, Linzy, Howard, Luke S, Jolley, Caroline J, Jones, Mark G, Leavy, Olivia C, Lewis, Keir E, Lone, Nazir I, Marks, Michael, McAuley, Hamish J C, McNarry, Melitta A, Patel, Brijesh V, Piper-Hanley, Karen, Poinasamy, Krisnah, Raman, Betty, Richardson, Matthew, Rivera-Ortega, Pilar, Rowland-Jones, Sarah L, Rowlands, Alex V, Saunders, Ruth M, Scott, Janet T, Sereno, Marco, Shah, Ajay M, Shikotra, Aarti, Singapuri, Amisha, Stanel, Stefan C, Thorpe, Mathew, Wootton, Daniel G, Yates, Thomas, Gisli Jenkins, R, Singh, Sally J, Man, William D-C, Brightling, Christopher E, Wain, Louise V, Porter, Joanna C, Thompson, A A Roger, Horsley, Alex, Molyneaux, Philip L, Evans, Rachael A, Jones, Samuel E, Rutter, Martin K, and Blaikley, John F
Published: 2023
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176. COVID-19 Serology at Population Scale: SARS-CoV-2-Specific Antibody Responses in Saliva

Author: Randad, Pranay R, Pisanic, Nora, Kruczynski, Kate, Manabe, Yukari C, Thomas, David, Pekosz, Andrew, Klein, Sabra L, Betenbaugh, Michael J, Clarke, William A, Laeyendecker, Oliver, Caturegli, Patrizio P, Larman, H Benjamin, Detrick, Barbara, Fairley, Jessica K, Sherman, Amy C, Rouphael, Nadine, Edupuganti, Srilatha, Granger, Douglas A, Granger, Steve W, Collins, Matthew, and Heaney, Christopher D
Subjects: SARS-CoV-2, COVID-19, saliva, oral fluid, serology, antibody test, multiplex, diagnostics, immunoserology, Biological Sciences, Agricultural and Veterinary Sciences, Medical and Health Sciences, Microbiology
Published: 2021

177. Coccidioidomycosis and COVID-19 Co-Infection, United States, 2020 - Volume 27, Number 5—May 2021 - Emerging Infectious Diseases journal - CDC

Author: Heaney, Alexandra K, Head, Jennifer R, Broen, Kelly, Click, Karen, Taylor, John, Balmes, John R, Zelner, Jon, and Remais, Justin V
Subjects: Biomedical and Clinical Sciences, Clinical Sciences, Biodefense, Vaccine Related, Rare Diseases, Lung, Emerging Infectious Diseases, Infectious Diseases, Prevention, Infection, Good Health and Well Being, Aged, COVID-19, Coccidioidomycosis, Coinfection, Ethnicity, Humans, Minority Groups, Pandemics, SARS-CoV-2, United States, Arizona, California, Coccidioides, co-infections, coccidioidomycosis, coronavirus disease, coronaviruses, diagnosis, fungi, respiratory infections, risk factors, severe acute respiratory syndrome coronavirus 2, viruses, zoonoses, Medical Microbiology, Public Health and Health Services, Microbiology, Clinical sciences, Epidemiology, Health services and systems
Abstract: We review the interaction between coronavirus disease (COVID-19) and coccidioidomycosis, a respiratory infection caused by inhalation of Coccidioides fungal spores in dust. We examine risk for co-infection among construction and agricultural workers, incarcerated persons, Black and Latino populations, and persons living in high dust areas. We further identify common risk factors for co-infection, including older age, diabetes, immunosuppression, racial or ethnic minority status, and smoking. Because these diseases cause similar symptoms, the COVID-19 pandemic might exacerbate delays in coccidioidomycosis diagnosis, potentially interfering with prompt administration of antifungal therapies. Finally, we examine the clinical implications of co-infection, including severe COVID-19 and reactivation of latent coccidioidomycosis. Physicians should consider coccidioidomycosis as a possible diagnosis when treating patients with respiratory symptoms. Preventive measures such as wearing face masks might mitigate exposure to dust and severe acute respiratory syndrome coronavirus 2, thereby protecting against both infections.
Published: 2021

178. PHYSICAL ACTIVITY AS STRESS MANAGEMENT DURING COVID-19

Author: Vogel, Erin A, Zhang, Janice, Peng, Katy, Heaney, Catherine A, Lu, Ying, Lounsbury, David W, Hsing, Ann W, and Prochaska, Judith J
Subjects: Medical and Health Sciences, Education, Psychology and Cognitive Sciences, Public Health
Published: 2021

179. Preface

Author: Heaney, Michael, primary
Published: 2023
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180. Modernist Memoir and the Social Structures of Sexual Violence

Author: Heaney, Emma, primary
Published: 2023
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181. Significant Texts and Generational Trends: Late Teens' Memories of Valued Literacy Learning in the Digital Age

Author: Heaney, April
Abstract: In the past thirty years, new technologies and communication systems have shaped social practices, literacy learning, and ways of interacting with texts in profound ways. However, scholarship in the dawn of the digital age neglects large-scale glimpses of people's important literacy memories. Deborah Brandt's (2001) influential Literacy in American Lives remains a unique model of holistic inquiry into the significant experiences and range of texts generational cohorts hold as most meaningful to their lives. This dissertation study built on Brandt's approach to explore the key moments that occur to first-year college students as they reflect on the texts that influenced them strongly during their primary and secondary grades-- including digital, print, and oral texts. Methods included surveying and interviewing first-year students at the University of Wyoming. Article 1 presents the findings from survey and interview data for students' important texts and the contexts and people who played a role in their engagement. Three types of texts emerged as particularly important to this generation of late teens: heirloom, through-line, and generational marker texts. Article 2 offers a conceptual model of social media literacies based on teens' descriptions of their encounters with social media during middle and high school. Both articles help teachers, literacy scholars, librarians, and parents gain critical insight into late teens' memories of significant texts and avenues for supporting their literacy learning. [The dissertation citations contained here are published with the permission of ProQuest LLC. Further reproduction is prohibited without permission. Copies of dissertations may be obtained by Telephone (800) 1-800-521-0600. Web page: http://www.proquest.com/en-US/products/dissertations/individuals.shtml.]
Published: 2022

182. Why Do I Teach Math This Way: A Qualitative Examination of How Teacher Experiences Impact the Implementation of Instructional Practices

Author: Heaney, Carrie A.
Abstract: Since the 1960s, there has been an effort among the mathematical education community to shift instructional practices from a focus on arithmetic, memorizing rules, and completing practice worksheets to instructional practices that allow students to see mathematics as content that requires thinking and pattern explorations. Many mathematics teachers have not fully embraced these shifts in instructional practice. This study aimed to examine secondary mathematics teachers' experiences and how those experiences connect to teachers' implementation of student-centered instructional practices in the lessons they design. This qualitative study utilized a grounded theory approach to examine how a teacher's experiences as a student of mathematics and instruction impact the instructional practices considered for use in their classroom. Two research questions guided this study: (a) How do teachers understand the student-centered instructional practices they implement in their classrooms? and (b) How do teachers experience the implementation of student-centered instructional practices? The study used two interviews and classroom observation to collect data from the 12 secondary mathematics teachers who were participants in this study. This study was conducted during the 2020-2021 and 2021-2022 school years. Student-centered instructional practices are significant ways to support students in developing their mathematical knowledge. For many teachers, these practices were not a part of the secondary mathematics instruction they experienced. Student-centered instructional practices can be challenging to incorporate into a teacher's instructional repertoire due to the misalignment with an educator's own student experience. This study has identified two key experiences that support teachers in considering student-centered instructional practices as a part of their instruction. These experiences are the failure of an individual's mathematical knowledge in a way that causes identity reconstruction and the belief that learning mathematics is a pursuit meant to increase mathematical knowledge and develop critical habits of mind. In addition, this study identified three key supports for helping teachers build their knowledge and skill in utilizing student-centered instructional practices. These supports for assisting teachers in incorporating these practices into their repertoire are (a) collaborating with others, (b) engaging in long-term learning opportunities around student-centered instructional practices, and (c) having student-centered instructional practices modeled through mathematical content. [The dissertation citations contained here are published with the permission of ProQuest LLC. Further reproduction is prohibited without permission. Copies of dissertations may be obtained by Telephone (800) 1-800-521-0600. Web page: http://www.proquest.com/en-US/products/dissertations/individuals.shtml.]
Published: 2022

183. Exercise in the subchronic phencyclidine rat model for schizophrenia : mechanisms and effects on cognitive deficits

Author: Heaney, Lisa, Allan, Stuart, Yung, Alison, Neill, Joanna, and Harte, Michael
Subjects: behaviour, neuroscience, novel object recognition, NOR, animal model, rat, PCP, physical activity, psychosis, exercise, schizophrenia, wheel-running, Phencyclidine, voluntary exercise
Abstract: Schizophrenia is associated with substantial cognitive deficits that dramatically reduce patients' quality of life. Now recognised as a core feature of the disorder, cognitive impairments best predict functional outcome. However, the drugs used to treat schizophrenia do not improve cognition, and many have cardiometabolic side-effects that contribute substantially to the reduced life expectancy of people with the disease. Drug development targeting cognition in schizophrenia to date has been unsuccessful. Non-pharmacological interventions to improve cognition, such as cognitive remediation therapy, have had limited success. Therefore, treatments to ameliorate the cognitive impairments in schizophrenia remain an urgent, unmet clinical need. Exercise has emerged as a potential intervention to reduce cognitive impairment in schizophrenia. While there is growing clinical evidence that exercise improves cognition, how it does so is poorly understood. Animal models are useful tools for investigating disease, and the subchronic phencyclidine (scPCP) rat model for schizophrenia is well-established and widely used to model schizophrenia-like cognitive deficits. However, research examining the effect of exercise on cognition in this model is lacking. This thesis presents a body of work examining the effect of voluntary exercise on cognition in the scPCP rat model for schizophrenia. The studies described within it demonstrate a novel exercise protocol can improve the novel object recognition (NOR) deficit present in this model. Furthermore, the pro-cognitive effects of wheel running endured for at least two weeks of sedentary behaviour but by four weeks, the NOR deficit had returned. Brain tissue was collected and analysed for synaptic and y-aminobutyric acid (GABA)ergic markers with western blotting. Two significant relationships were reported but these results were deemed inconclusive. Additionally, brain-derived neurotrophic factor (BDNF) was measured in plasma but no effect of exercise was found. For the first time, exercise was shown to improve cognition in the scPCP rat model for schizophrenia. Furthermore, this effect lasted for at least two weeks after exercise cessation. Pathological changes were not observed, but the robust behavioural changes produced will provide the opportunity to explore the pro-cognitive mechanisms of exercise in an animal model for schizophrenia.
Published: 2020

184. The effects of biochar on trace element and nutrient solubility in the presence of low-molecular-weight organic acids

Author: Heaney, N.
Subjects: 631.4
Abstract: Low-molecular-weight organic acids (LMWOAs) secreted by plant roots play an essential role in regulating the phytoavailability of soil-borne trace elements and nutrients. Biochar is widely considered as a suitable soil remediation option, having shown an efficacy to retain both anions and cations. This study aims to unravel the roles of LMWOAs in affecting the functioning of biochar in aqueous and soil systems. Twelve biochar were characterised and rice husk biochar was selected for use. Firstly, aqueous batch experiments examined the biochar-driven immobilisation of trace elements and nutrients with and without LMWOAs. Then, batch studies tested if biochar would reduce the LMWOA-driven solubilisation of trace elements and nutrients in soil. Later, rice husk biochar and LMWOA-activated rice husk biochar were incorporated in greenhouse investigations to study the growth parameters of edible plant species and trace element uptake by pea (Pisum sativum). Solution sorption studies found that LMWOAs impeded the biochar-driven removal of cadmium and lead but enhanced nitrate removal. Biochar did not affect phosphate removal. Biochar inhibited the LMWOA-driven solubilisation of soil-borne cadmium and zinc. Nitrate immobilisation was not enhanced but biochar reduced the immobilisation of the added nitrate overall. Phosphate immobilisation was observed but was caused by the precipitation of practically insoluble phosphate minerals using biochar as a source of soluble calcium. Seven out of eleven trace elements accumulated in pea roots were reduced either by biochar and LMWOA-activated biochar but the uptake was variable with biochar type. The data obtained indicate LMWOAs complicate biochar functioning in solution and soil under the studied conditions. Based on the results, protonation of the biochar materials in acidic conditions impeded cation immobilisation whilst enhancing nitrate immobilisation. Acid neutralisation by the biochar materials likely reduced the LMWOA-solubilisation of trace elements which would affect trace element uptake by plants such as pea, within biochar-amended soils.
Published: 2020

185. COVID-19 Serology at Population Scale: SARS-CoV-2-Specific Antibody Responses in Saliva.

Author: Pisanic, Nora, Randad, Pranay R, Kruczynski, Kate, Manabe, Yukari C, Thomas, David L, Pekosz, Andrew, Klein, Sabra L, Betenbaugh, Michael J, Clarke, William A, Laeyendecker, Oliver, Caturegli, Patrizio P, Larman, H Benjamin, Detrick, Barbara, Fairley, Jessica K, Sherman, Amy C, Rouphael, Nadine, Edupuganti, Srilatha, Granger, Douglas A, Granger, Steve W, Collins, Matthew H, and Heaney, Christopher D
Subjects: Saliva, Humans, Immunoglobulin A, Immunoglobulin G, Immunoglobulin M, Antibodies, Viral, Female, Male, Spike Glycoprotein, Coronavirus, COVID-19, SARS-CoV-2, COVID-19 Nucleic Acid Testing, Coronavirus Nucleocapsid Proteins, antibody test, diagnostics, immunoserology, multiplex, oral fluid, saliva, serology, Antibodies, Viral, Spike Glycoprotein, Coronavirus, Biological Sciences, Agricultural and Veterinary Sciences, Medical and Health Sciences, Microbiology
Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of an ongoing pandemic that has infected over 36 million and killed over 1 million people. Informed implementation of government public health policies depends on accurate data on SARS-CoV-2 immunity at a population scale. We hypothesized that detection of SARS-CoV-2 salivary antibodies could serve as a noninvasive alternative to serological testing for monitoring of SARS-CoV-2 infection and seropositivity at a population scale. We developed a multiplex SARS-CoV-2 antibody immunoassay based on Luminex technology that comprised 12 CoV antigens, mostly derived from SARS-CoV-2 nucleocapsid (N) and spike (S). Saliva and sera collected from confirmed coronavirus disease 2019 (COVID-19) cases and from the pre-COVID-19 era were tested for IgG, IgA, and IgM to the antigen panel. Matched saliva and serum IgG responses (n = 28) were significantly correlated. The salivary anti-N IgG response resulted in the highest sensitivity (100%), exhibiting a positive response in 24/24 reverse transcription-PCR (RT-PCR)-confirmed COVID-19 cases sampled at >14 days post-symptom onset (DPSO), whereas the salivary anti-receptor binding domain (RBD) IgG response yielded 100% specificity. Temporal kinetics of IgG in saliva were consistent with those observed in blood and indicated that most individuals seroconvert at around 10 DPSO. Algorithms employing a combination of the IgG responses to N and S antigens result in high diagnostic accuracy (100%) by as early as 10 DPSO. These results support the use of saliva-based antibody testing as a noninvasive and scalable alternative to blood-based antibody testing.
Published: 2020

186. The DIOS framework for optimizing infectious disease surveillance: Numerical methods for simulation and multi-objective optimization of surveillance network architectures.

Author: Cheng, Qu, Collender, Philip A, Heaney, Alexandra K, Li, Xintong, Dasan, Rohini, Li, Charles, Lewnard, Joseph A, Zelner, Jonathan L, Liang, Song, Chang, Howard H, Waller, Lance A, Lopman, Benjamin A, Yang, Changhong, and Remais, Justin V
Subjects: Bioinformatics, Mathematical Sciences, Biological Sciences, Information and Computing Sciences
Abstract: Infectious disease surveillance systems provide vital data for guiding disease prevention and control policies, yet the formalization of methods to optimize surveillance networks has largely been overlooked. Decisions surrounding surveillance design parameters-such as the number and placement of surveillance sites, target populations, and case definitions-are often determined by expert opinion or deference to operational considerations, without formal analysis of the influence of design parameters on surveillance objectives. Here we propose a simulation framework to guide evidence-based surveillance network design to better achieve specific surveillance goals with limited resources. We define evidence-based surveillance design as an optimization problem, acknowledging the many operational constraints under which surveillance systems operate, the many dimensions of surveillance system design, the multiple and competing goals of surveillance, and the complex and dynamic nature of disease systems. We describe an analytical framework-the Disease Surveillance Informatics Optimization and Simulation (DIOS) framework-for the identification of optimal surveillance designs through mathematical representations of disease and surveillance processes, definition of objective functions, and numerical optimization. We then apply the framework to the problem of selecting candidate sites to expand an existing surveillance network under alternative objectives of: (1) improving spatial prediction of disease prevalence at unmonitored sites; or (2) estimating the observed effect of a risk factor on disease. Results of this demonstration illustrate how optimal designs are sensitive to both surveillance goals and the underlying spatial pattern of the target disease. The findings affirm the value of designing surveillance systems through quantitative and adaptive analysis of network characteristics and performance. The framework can be applied to the design of surveillance systems tailored to setting-specific disease transmission dynamics and surveillance needs, and can yield improved understanding of tradeoffs between network architectures.
Published: 2020

187. The Deep Genome Project

Author: Lloyd, KC Kent, Adams, David J, Baynam, Gareth, Beaudet, Arthur L, Bosch, Fatima, Boycott, Kym M, Braun, Robert E, Caulfield, Mark, Cohn, Ronald, Dickinson, Mary E, Dobbie, Michael S, Flenniken, Ann M, Flicek, Paul, Galande, Sanjeev, Gao, Xiang, Grobler, Anne, Heaney, Jason D, Herault, Yann, de Angelis, Martin Hrabě, Lupski, James R, Lyonnet, Stanislas, Mallon, Ann-Marie, Mammano, Fabio, MacRae, Calum A, McInnes, Roderick, McKerlie, Colin, Meehan, Terrence F, Murray, Stephen A, Nutter, Lauryl MJ, Obata, Yuichi, Parkinson, Helen, Pepper, Michael S, Sedlacek, Radislav, Seong, Je Kyung, Shiroishi, Toshihiko, Smedley, Damian, Tocchini-Valentini, Glauco, Valle, David, Wang, Chi-Kuang Leo, Wells, Sara, White, Jacqueline, Wurst, Wolfgang, Xu, Ying, and Brown, Steve DM
Subjects: Animals, Genes, Genome, Humans, Mice, Mutation, Phenotype, Proteins, Environmental Sciences, Biological Sciences, Information and Computing Sciences, Bioinformatics
Published: 2020

188. Intracranial haemorrhage and falls: cause or effect?

Author: Vrbanic, Lauren, Hunt, Ciara, Cooney, Maeve, Heffernan, Josephine, Walsh, Andrea, Heaney, Ciara, Collis, Sally Anne, Howley, Rachel, Fearon, Conor, Farrell, Michael, and Brett, Francesca
Published: 2022
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189. Well-being in Thailand: A Culturally Driven Grounded Inquiry Exploration of a Complex Construct

Author: Suavansri, Panita, Pichayayothin, Nipat, Espinosa, Patricia Rodriguez, Areekit, Poonsub, Nilchantuk, Chureerat, Jones, Torin S., French, Joanna J., Mam, Emily, Moore, Jessie B., and Heaney, Catherine A.
Published: 2022
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190. Drosophila Importin Alpha 1 (Dα1) Is Required to Maintain Germline Stem Cells in the Testis Niche

Author: James Heaney, Jiamin Zhao, Franca Casagranda, Kate L. Loveland, Nicole A. Siddall, and Gary R. Hime
Subjects: Drosophila, spermatogenesis, importin, Cytology, QH573-671
Abstract: Stem cell maintenance and differentiation can be regulated via the differential activity of transcription factors within stem cells and their progeny. For these factors to be active, they need to be transported from their site of synthesis in the cytoplasm into the nucleus. A tissue-specific requirement for factors involved in nuclear importation is a potential mechanism to regulate stem cell differentiation. We have undertaken a characterization of male sterile importin alpha 1 (Dα1) null alleles in Drosophila and found that Dα1 is required for maintaining germline stem cells (GSCs) in the testis niche. The loss of GSCs can be rescued by ectopic expression of Dα1 within the germline but the animals are still infertile, indicating a second role for Dα1 in spermatogenesis. Expression of a Dα1 dominant negative transgene in GSCs confirmed a functional requirement for Dα1 in GSC maintenance but expression of the transgene in differentiating spermatogonia did not exhibit a phenotype indicating a specific role for Dα1 within GSCs. Our data indicate that Dα1 is utilized as a regulatory protein within GSCs to facilitate nuclear importation of proteins that maintain the stem cell pool.
Published: 2024
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191. The Monmouth University Partnership: Redesigning Practice

Author: Henning, John E., Bragen, Bernard F., Mulvaney, Tracy, George, William O., III, Duffy, Greg, Aldarelli, Edward, Grabowski, Christine, Harriott, Wendy, Riddle, Meredith, Falco, James, Heaney, Patricia, Earle, Corina, Foster, Linda, and Borlan, Christine A.
Abstract: In this article, the Monmouth University partners describe our efforts to constantly explore new dimensions of learning, teaching, and teacher preparation. We begin by describing two recent initiatives developed by our partnership: the piloting and implementation of a yearlong clinical internship experience to replace traditional student teaching, and the Monmouth Teacher Residency Program, which is a paid internship that involves teacher candidates in clinical experiences year round. Description of additional initiatives are organized according to the PDS essentials; including projects to increase P-12 student learning, tools to facilitate the mentoring of teacher candidates, and initiatives to enhance the professional development of school partners.
Published: 2018

192. Using Short Questionnaires to Support Students' Emotion Awareness and Regulation During an Online Group Project

Author: Jake Hilliard, Helen Donelan, Caroline Heaney, Karen Kear, and Patrick Wong
Subjects: emotion, emotion regulation, emotion awareness, online group project, distance education, General Works
Abstract: Over the past two decades, research has highlighted the profound influence emotions can have on students’ learning, achievement, and wellbeing. Being able to successfully regulate one’s emotions is now viewed as crucial when learning in educational settings. To support students with this process, a growing line of research has explored various ways of helping students understand and manage their emotions (e.g., via the use of digital tools aimed at helping students become more aware of their emotions and prompting ways to regulate these emotions). Despite this, limited research has been undertaken in online group learning settings, where students work remotely together as part of their course using collaborative communication tools. These learning contexts present unique challenges which can make emotion regulation more difficult than in face-to-face learning environments (e.g., delayed response times when communicating with peers and teachers and a reduced sense of how others are feeling, due to limited emotional cues when learning online). In this paper, we describe an approach used at the UK Open University (UKOU) to assist students’ emotion awareness and regulation during a 9-week group project. This involves the use of short questionnaires which have been embedded into the Virtual Learning Environment (VLE) of a module. Since their inclusion, these questionnaires have been found to enhance emotional awareness in many students, as well as support the regulation of emotions in the group project. To conclude this paper, reflections on using the short questionnaires are discussed and implications for educators and institutions are identified.
Published: 2023
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193. Difficult‐to‐treat asthma patients from ethnic minority groups in central England are at an enhanced risk of house dust mite sensitisation

Author: Adel H. Mansur, Julie Marsh, Ali Bahron, Maximillian Thomas, Gareth Walters, John Busby, Liam G. Heaney, and Mamidipudi Thirumala Krishna
Subjects: biomarkers, disparities, ethnicity, house dust mite, severe asthma, Immunologic diseases. Allergy, RC581-607
Abstract: Abstract Background House dust mite (HDM) is the most common sensitising allergen in asthma. Ethnic minority groups (EMGs) in the UK are more likely to live in deprived conditionings with a greater exposure to HDM and other aero‐allergens. Aim To compare the ethnicity‐based patterns of sensitisation to aero‐allergens and the impact of ethnicity on clinical outcomes in patients with difficult‐to‐treat asthma (DTA). Methods Data of patients with DTA were extracted from the registry of the Birmingham Regional Severe Asthma Service (BRSAS), which have a catchment population of 7.3million from Central England. Patients from White and EMG backgrounds were compared in terms of the prevalence of atopy, total serum immunoglobulin E (IgE), specific serum IgE (ssIgE) and asthma related clinical outcomes. Logistic regression analysis was conducted to explore ethnicity‐based risk factors for HDM sensitisation. Results A total of 1272 patients [White 1016 (79.9%), EMG 256 (20.1%) EMG] with a median age of 51 years (range 16–97) were included in the analysis. Patients from EMG were more likely (64%) to reside in the worst scale of index of multiple deprivation (IMD) than the White patients (25.5%), p
Published: 2023
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194. Community-driven research and capacity building to address environmental justice concerns with industrial air pollution in Curtis Bay, South Baltimore

Author: Matthew A. Aubourg, Greg Sawtell, Lauren Deanes, Nicole Fabricant, Meleny Thomas, Kristoffer Spicer, Caila Wagar, Shashawnda Campbell, Abigail Ulman, and Christopher D. Heaney
Subjects: community-driven research, capacity building, environmental justice (EJ), environmental racism, hyperlocal air monitoring, industrial air pollution, Infectious and parasitic diseases, RC109-216
Abstract: IntroductionCurtis Bay (CB) is an environmental justice (EJ) community in South Baltimore. With a high concentration of industrial polluters and compounding non-chemical stressors, CB has experienced socioeconomic, quality of life, and health burdens for over 100 years. Today, these polluters include the open-air CSX Coal Terminal, waste-to-energy incinerators, and heavy diesel traffic through residential areas. The Community of Curtis Bay Association, Free Your Voice, and South Baltimore Community Land Trust are local organizations enacting a vision for equitable, healthy, and community-led development without industrial encroachment. In response to community-identified EJ concerns and an explosion at the CSX Coal Terminal, CB community groups partnered with academic researchers to develop a community-driven hyperlocal air monitoring and capacity building approach. This paper describes this approach to characterizing hyperlocal air quality in CB, building bridges between community residents and regulatory agencies, and nurturing a cohesive and effective community-academic partnership toward EJ.MethodsUsing hyperlocal air monitoring, we are collecting real-time air pollution (particulate matter, black carbon, and ground-level gas species) and meteorological data from 15 low-cost sensors in residential and industrial areas of CB. We also use trail cameras to record activities at the CSX Coal Terminal. We merge air pollution and industrial activity data to evaluate the following: overall air quality in CB, multi-air pollutant profiles of elevated events, spatiotemporal changes in air quality in the community, patterns of industrial activity, and potential correlations between air quality and observed industrial activity. Members of our partnership also lead a high school course educating students about the history and ongoing efforts of the EJ movement in their community. Students in this course learn how to employ qualitative and quantitative data collection and analysis methods to bring scientific support to community EJ concerns.Results and DiscussionOur hyperlocal air monitoring network and community-academic partnership are continuing to evolve and have already demonstrated the ability to respond to community-identified EJ issues with real-time data while developing future EJ leaders. Our reflections can assist other community and academic groups in developing strong and fruitful partnerships to address similar EJ issues.
Published: 2023
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195. The SeroNet Clinical and Translational Serology Task Force (CTTF) SARS-CoV-2 mucosal immunity methodological considerations and best practices workshop

Author: Heidi Hempel, Nicholas Mantis, Christopher D. Heaney, and Ligia A. Pinto
Subjects: mucosal immunology, secretory antibodies, serology, vaccines, standardization, Immunologic diseases. Allergy, RC581-607, Therapeutics. Pharmacology, RM1-950
Abstract: SARS-CoV-2 persists in certain populations, even with vaccination and boosters. Emerging evidence suggests that reductions in virus transmission and infection will likely require involvement of the mucosal immune system, especially secretory antibodies in the upper respiratory tract. The Clinical and Translational Serology Task Force (CTTF) within The National Cancer Institute (NCI)’s Serological Sciences Network for COVID-19 (SeroNet) hosted a workshop to review the status of development and standardization of mucosal sample collection methods and assays, identify challenges, and develop action plans to bridge gaps. Speakers presented data underscoring a role for secretory IgA in protection, mucosal markers as correlates of protection, methods for tracking and assessing mucosal antibodies, and lessons learned from other infectious agents. Perspectives from regulators and industry were put forward to guide mucosal vaccine development. Methodological considerations for optimizing collection protocols and assays and harmonizing data were highlighted. Rigorous studies, standardized protocols, controls, standards, and assay validation were identified as necessary to gain momentum in expanding SARS-CoV-2 vaccines to the mucosa.
Published: 2023
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196. Delayed skeletal development and IGF-1 deficiency in a mouse model of lysinuric protein intolerance

Author: Bridget M. Stroup, Xiaohui Li, Sara Ho, Haonan Zhouyao, Yuqing Chen, Safa Ani, Brian Dawson, Zixue Jin, Ronit Marom, Ming-Ming Jiang, Isabel Lorenzo, Daniel Rosen, Denise Lanza, Nathalie Aceves, Sara Koh, John R. Seavitt, Jason D. Heaney, Brendan Lee, and Lindsay C. Burrage
Subjects: osteoporosis, osteoblast, igf-1, lysinuric protein intolerance, slc7a7, arginine, Medicine, Pathology, RB1-214
Published: 2023
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197. Long-term efficacy and safety of osilodrostat in patients with Cushing’s disease: results from the LINC 4 study extension

Author: Mônica Gadelha, Peter J. Snyder, Przemysław Witek, Marie Bex, Zhanna Belaya, Adina F. Turcu, Richard A. Feelders, Anthony P. Heaney, Michaela Paul, Alberto M. Pedroncelli, and Richard J. Auchus
Subjects: Cushing’s disease, osilodrostat, hypercortisolism, 11β-hydroxylase, long-term treatment, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract: ObjectiveTo evaluate the long-term efficacy and safety of osilodrostat in patients with Cushing’s disease.MethodsThe multicenter, 48-week, Phase III LINC 4 clinical trial had an optional extension period that was initially intended to continue to week 96. Patients could continue in the extension until a managed-access program or alternative treatment became available locally, or until a protocol amendment was approved at their site that specified that patients should come for an end-of-treatment visit within 4 weeks or by week 96, whichever occurred first. Study outcomes assessed in the extension included: mean urinary free cortisol (mUFC) response rates; changes in mUFC, serum cortisol and late-night salivary cortisol (LNSC); changes in cardiovascular and metabolic-related parameters; blood pressure, waist circumference and weight; changes in physical manifestations of Cushing’s disease; changes in patient-reported outcomes for health-related quality of life; changes in tumor volume; and adverse events. Results were analyzed descriptively; no formal statistical testing was performed.ResultsOf 60 patients who entered, 53 completed the extension, with 29 patients receiving osilodrostat for more than 96 weeks (median osilodrostat duration: 87.1 weeks). The proportion of patients with normalized mUFC observed in the core period was maintained throughout the extension. At their end-of-trial visit, 72.4% of patients had achieved normal mUFC. Substantial reductions in serum cortisol and LNSC were also observed. Improvements in most cardiovascular and metabolic-related parameters, as well as physical manifestations of Cushing’s disease, observed in the core period were maintained or continued to improve in the extension. Osilodrostat was generally well tolerated; the safety profile was consistent with previous reports.ConclusionOsilodrostat provided long-term control of cortisol secretion that was associated with sustained improvements in clinical signs and physical manifestations of hypercortisolism. Osilodrostat is an effective long-term treatment for patients with Cushing’s disease.Clinical trial registrationClinicalTrials.gov, identifier NCT02180217
Published: 2023
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198. A Saliva-Based Serological and Behavioral Analysis of SARS-CoV-2 Antibody Prevalence in Howard County, Maryland

Author: Alan C. Brown, Phillip T. Koshute, Hannah P. Cowley, Michael S. Robinette, Sarah R. Gravelyn, Shraddha V. Patel, Eunice Y. Ju, Carolyn T. Frommer, Alexander E. Zambidis, Eric J. Schneider, Martina Y. Zhao, Benny K. Mugo, William Clarke, Kate Kruczynski, Nora Pisanic, Christopher D. Heaney, and Teresa A. Colella
Subjects: BNT162b2, Howard County, Maryland, SARS-CoV-2, antibody decay rate, community health study, Microbiology, QR1-502
Abstract: ABSTRACT The objective of the study was to estimate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence in the Howard County, Maryland, general population and demographic subpopulations attributable to natural infection or coronavirus disease 2019 (COVID-19) vaccination and to identify self-reported social behaviors that may affect the likelihood of recent or past SARS-CoV-2 infection. A cross-sectional, saliva-based serological study of 2,880 residents of Howard County, Maryland, was carried out from July through September 2021. Natural SARS-CoV-2 infection prevalence was estimated by inferring infections among individuals according to anti-nucleocapsid immunoglobin G levels and calculating averages weighted by sample proportions of various demographics. Antibody levels between BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) recipients were compared. Antibody decay rate was calculated by fitting exponential decay curves to cross-sectional indirect immunoassay data. Regression analysis was carried out to identify demographic factors, social behaviors, and attitudes that may be linked to an increased likelihood of natural infection. The estimated overall prevalence of natural infection in Howard County, Maryland, was 11.9% (95% confidence interval, 9.2% to 15.1%), compared with 7% reported COVID-19 cases. Antibody prevalence indicating natural infection was highest among Hispanic and non-Hispanic Black participants and lowest among non-Hispanic White and non-Hispanic Asian participants. Participants from census tracts with lower average household income also had higher natural infection rates. After accounting for multiple comparisons and correlations between participants, none of the behavior or attitude factors had significant effects on natural infection. At the same time, recipients of the mRNA-1273 vaccine had higher antibody levels than those of BNT162b2 vaccine recipients. Older study participants had overall lower antibody levels compared with younger study participants. The true prevalence of SARS-CoV-2 infection is higher than the number of reported COVID-19 cases in Howard County, Maryland. A disproportionate impact of infection-induced SARS-CoV-2 positivity was observed across different ethnic/racial subpopulations and incomes, and differences in antibody levels across different demographics were identified. Taken together, this information may inform public health policy to protect vulnerable populations. IMPORTANCE We employed a highly innovative noninvasive multiplex oral fluid SARS-CoV-2 IgG assay to ascertain our seroprevalence estimates. This laboratory-developed test has been applied in NCI’s SeroNet consortium, possesses high sensitivity and specificity according to FDA Emergency Use Authorization guidelines, correlates strongly with SARS-CoV-2 neutralizing antibody responses, and is Clinical Laboratory Improvement Amendments-approved by the Johns Hopkins Hospital Department of Pathology. It represents a broadly scalable public health tool to improve understanding of recent and past SARS-CoV-2 exposure and infection without drawing any blood. To our knowledge, this is the first application of a high-performance salivary SARS-CoV-2 IgG assay to estimate population-level seroprevalence, including identifying COVID-19 disparities. We also are the first to report differences in SARS-CoV-2 IgG responses by COVID-19 vaccine manufacturers (BNT162b2 [Pfizer-BioNTech] and mRNA-1273 [Moderna]). Our findings demonstrate remarkable consistency with those of blood-based SARS-CoV-2 IgG assays in terms of differences in the magnitude of SARS-CoV-2 IgG responses between COVID-19 vaccines.
Published: 2023
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199. The Glucocorticoid Toxicity Index-Metabolic Domains, an abridged version of the Glucocorticoid Toxicity Index: post-hoc analysis of data from the ADVOCATE trial

Author: Patel, Naomi J, Jayne, David R W, Merkel, Peter A, Bekker, Pirow, Zhang, Yuqing, McDowell, P Jane, Johal, Joslin, Heaney, Liam G, Murrell, Dedee, Stone, Martha N, Yue, Huibin, and Stone, John H
Published: 2023
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200. Use of digital measurement of medication adherence and lung function to guide the management of uncontrolled asthma (INCA Sun): a multicentre, single-blinded, randomised clinical trial

Author: Lombard, Lorna, Walsh, Joanne, Plunkett, Sinead, McCartan, Thomas A, Hale, Elaine Mac, Greene, Garrett, Mulvey, Christopher, Mokoka, Matshediso C, van Boven, Job F M, Cushen, Breda, Sulaiman, Imran, Brennan, Vincent, Kerr, Patrick J, Reilly, Richard B, Hughes, Cian, Kent, Brian D, Jackson, David J, Butler, Marcus, Counihan, Ian, Hayes, James, Faul, John, Kelly, Martin, Convery, Rory, Nanzer, Alexandra M, Fitzgerald, J Mark, Murphy, Desmond M, Heaney, Liam G, and Costello, Richard W
Published: 2023
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