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2. Shared neutrophil and T cell dysfunction is accompanied by a distinct interferon signature during severe febrile illnesses in children

Author

Patel, Harsita, Carter, Michael J., Jackson, Heather, Powell, Oliver, Fish, Matthew, Terranova-Barberio, Manuela, Spada, Filomena, Petrov, Nedyalko, Wellman, Paul, Darnell, Sarah, Mustafa, Sobia, Todd, Katrina, Bishop, Cynthia, Cohen, Jonathan M., Kenny, Julia, van den Berg, Sarah, Sun, Thomas, Davis, Francesca, Jennings, Aislinn, Timms, Emma, Thomas, Jessica, Nyirendra, Maggie, Nichols, Samuel, Estamiana Elorieta, Leire, D’Souza, Giselle, Wright, Victoria, De, Tisham, Habgood-Coote, Dominic, Ramnarayan, Padmanabhan, Tissières, Pierre, Whittaker, Elizabeth, Herberg, Jethro, Cunnington, Aubrey, Kaforou, Myrsini, Ellis, Richard, Malim, Michael H., Tibby, Shane M., Shankar-Hari, Manu, and Levin, Michael

Published
2024
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3. Longitudinal immune monitoring to identify immune states in sepsis

Author

Fish, Matthew and Swanson, Chad Michael

Abstract

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host (immune and non-immune) responses to infection. Although it is well recognised that innate and adaptive immune systems are profoundly altered in sepsis and in the causal pathway to death, immunomodulators do not seem to improve outcomes in sepsis patients. It is also well recognised that many of the early immune responses (particularly innate immune responses) are conserved responses (i.e., similar immune responses to different injuries and different pathogens). Therefore, I hypothesised that by comparing sepsis immune responses to a cohort with sterile injury, immune responses that are observed only in sepsis in my dataset could be identified. I also hypothesised that sepsis subgroups (subphenotypes and endotypes) reported in the literature might represent different immune states in their sepsis illness, rather than true sepsis subpopulations. To address my hypotheses, I recruited 69 sepsis patients, and 30 elective cardiac surgical patients. In sepsis patients, I collected blood samples at four time points (admission, day 3, day 5, critical care discharge), and two time points in cardiac surgical patients (pre surgery, 24 hours post-surgery). I measured and compared the panleukocyte transcriptome, limited mass spectrometry proteomics, protein bead arrays, and deep immune phenotyping using flow and mass cytometry. Cardiac surgical patients were chosen as control populations as they are of similar age to sepsis patients, and have similar comorbid conditions, which are the main confounders. Further, cardiac surgical patients provide an opportunity to compare the immune states at baseline, and at a fixed time after major surgical insult. In the cardiac surgical cohort, post-surgery samples, compared with pre-surgery samples, highlight reprioritization in the canonical pathways within the pan leukocyte transcriptome, changes in proteome (including cytokines and chemokines CCL/CXCL), and in immune cell subsets, that I infer as evidence of acute inflammation from noninfectious injury. Although many of these changes were also observed in sepsis, certain changes differed either in magnitude or in direction. Examples include greater magnitude of interleukin-6 signalling, greater reduction in Th1 signalling, and lesser reduction in Th2 signalling in sepsis. In contrast to cardiac surgical response, in sepsis patients' integrin signalling was increased and P53 signalling was decreased. Further, I identified immune responses that are unique to sepsis within the pan leukocyte transcriptome (dysregulation of CXCL-8 signalling, glucose metabolism and cell cycle pathways), in cytokine networks that consisted of IL-6, CXCL8, CCL2, CCL4, CCL11 and CCL20, and in immune cell subsets (decrease in all antigen experienced T cells, and increase in transitional (T3) B cell subsets). Unsupervised analyses host transcriptome responses to infection manifests as three distinct immune states, with variable transitions between states. My results suggest that matching timing of immunotherapies to immune states may be more successful to identify new treatments for sepsis, compared with the current paradigm of immunomodulating as soon as sepsis diagnosis is made. Sepsis immune responses share many features of inflammatory responses to injury as evidenced in my comparison between sepsis and cardiac surgical controls. I report there are biologically relevant unique features of sepsis, that appear asynchronous with clinical timepoints, and highlighting different immune states in patients with sepsis observable at admission to critical care discharge.

Published
2023

7. Changes in Phenotypic and Molecular Features of Naïve and Central Memory T Helper Cell Subsets following SARS-CoV-2 Vaccination.

Author

Mosavie, Mia, Rynne, Jennifer, Fish, Matthew, Smith, Peter, Jennings, Aislinn, Singh, Shivani, Millar, Jonathan, Harvala, Heli, Mora, Ana, Kaloyirou, Fotini, Griffiths, Alexandra, Hopkins, Valerie, Washington, Charlotte, Estcourt, Lise J., Roberts, David, and Shankar-Hari, Manu

Subjects
T helper cells, T cell receptors, T cells, IMMUNOLOGIC memory, GENETIC translation
Abstract

Molecular changes in lymphocytes following SARS-CoV-2 vaccination are incompletely understood. We hypothesized that studying the molecular (transcriptomic, epigenetic, and T cell receptor (TCR) repertoire) changes in CD4+ T cells following SARS-CoV-2 vaccination could inform protective mechanisms and refinement of future vaccines. We tested this hypothesis by reporting alterations in CD4+ T cell subsets and molecular features of CD4+ naïve and CD4+ central memory (CM) subsets between the unvaccinated and vaccinated groups. Compared with the unvaccinated, the vaccinated had higher HLA-DR expression in CD4+ T subsets, a greater number of differentially expressed genes (DEGs) that overlapped with key differentially accessible regions (DARs) along the chromatin linked to inflammasome activation, translation, regulation (of apoptosis, inflammation), and significant changes in clonal architecture beyond SARS-CoV-2 specificity. Several of these differences were more pronounced in the CD4+CM subset. Taken together, our observations imply that the COVID-19 vaccine exerts its protective effects via modulation of acute inflammation to SARS-CoV-2 challenge. [ABSTRACT FROM AUTHOR]

Published
2024
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8. The Pirate Wellness Program: Lessons Learned from the 'Pivot'

Author

Loy, David P., Autry, Cari, Janke, Megan C., Fish, Matthew, Burnworth, Rebecca, Whisner, Wendy, and Harrell, Lauren

Abstract

In response to academic and healthcare restrictions from the COVID-19 pandemic, the Pirate Wellness Program (PWP), a recreational therapy telehealth program, was developed and implemented in May of 2020 by East Carolina University Recreational Therapy (RT) faculty to provide virtual services and interventions to quarantined individuals with disabilities. PWP was the first virtual RT treatment program and served as a model for virtual RT internship training programs during COVID-19. This article provides a brief overview of the lessons learned and post-COVID legacy of the Pirate Wellness Program.

Published
2023
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9. Assessment of longitudinal changes in immune responses in critically ill adults with COVID-19

Author

Rynne, Jennifer, primary, Fish, Matthew, additional, Jennings, Aislinn, additional, Smith, Peter, additional, Mosavie, Mia, additional, Lam, Carolyn, additional, Kelly, Sarah, additional, Sanderson, Barnaby, additional, Arbane, Gill, additional, Lucchese, Gianluca, additional, Bosco, Paolo, additional, Camporota, Luigi, additional, Ostermann, Marlies, additional, and Shankar-Hari, Manu, additional

Published
2024
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10. SARS-CoV-2 RNAemia and proteomic trajectories inform prognostication in COVID-19 patients admitted to intensive care

Author

Gutmann, Clemens, Takov, Kaloyan, Burnap, Sean A., Singh, Bhawana, Ali, Hashim, Theofilatos, Konstantinos, Reed, Ella, Hasman, Maria, Nabeebaccus, Adam, Fish, Matthew, McPhail, Mark JW., O’Gallagher, Kevin, Schmidt, Lukas E., Cassel, Christian, Rienks, Marieke, Yin, Xiaoke, Auzinger, Georg, Napoli, Salvatore, Mujib, Salma F., Trovato, Francesca, Sanderson, Barnaby, Merrick, Blair, Niazi, Umar, Saqi, Mansoor, Dimitrakopoulou, Konstantina, Fernández-Leiro, Rafael, Braun, Silke, Kronstein-Wiedemann, Romy, Doores, Katie J., Edgeworth, Jonathan D., Shah, Ajay M., Bornstein, Stefan R., Tonn, Torsten, Hayday, Adrian C., Giacca, Mauro, Shankar-Hari, Manu, and Mayr, Manuel

Published
2021
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11. A dynamic COVID-19 immune signature includes associations with poor prognosis

Author

Laing, Adam G., Lorenc, Anna, del Molino del Barrio, Irene, Das, Abhishek, Fish, Matthew, Monin, Leticia, and Muñoz-Ruiz, Miguel

Subjects
Immune response -- Health aspects, Biological sciences, Health
Abstract

Improved understanding and management of COVID-19, a potentially life-threatening disease, could greatly reduce the threat posed by its etiologic agent, SARS-CoV-2. Toward this end, we have identified a core peripheral blood immune signature across 63 hospital-treated patients with COVID-19 who were otherwise highly heterogeneous. The signature includes discrete changes in B and myelomonocytic cell composition, profoundly altered T cell phenotypes, selective cytokine/chemokine upregulation and SARS-CoV-2-specific antibodies. Some signature traits identify links with other settings of immunoprotection and immunopathology; others, including basophil and plasmacytoid dendritic cell depletion, correlate strongly with disease severity; while a third set of traits, including a triad of IP-10, interleukin-10 and interleukin-6, anticipate subsequent clinical progression. Hence, contingent upon independent validation in other COVID-19 cohorts, individual traits within this signature may collectively and individually guide treatment options; offer insights into COVID-19 pathogenesis; and aid early, risk-based patient stratification that is particularly beneficial in phasic diseases such as COVID-19. A common immune signature in the blood of patients with COVID-19, who are otherwise clinically heterogeneous, sheds light into the pathogenesis and clinical progression of the disease., Author(s): Adam G. Laing [sup.1] , Anna Lorenc [sup.1] , Irene del Molino del Barrio [sup.1] [sup.2] , Abhishek Das [sup.1] [sup.3] , Matthew Fish [sup.1] [sup.4] , Leticia Monin [...]

Published
2020
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13. The Use of Biofeedback in College Counseling

Author

Fish, Matthew, Russoniello, Carmen, and Clemmons-James, Dominiquie M.

Abstract

The authors present a biofeedback training model and explore 4 specific biofeedback modalities--electromyography, electrodermal activity, thermal, and neurofeedback--that can be integrated into the clinical setting by college counselors. In addition, the authors provide information about how college counselors can become board certified in biofeedback and neurofeedback. Clinical implications and applications for college counselors are also discussed.

Published
2018
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14. Are certain types of leisure activities associated with happiness and life satisfaction among college students?

Author

Kim, Jaehyun, Park, Chulwoo, Fish, Matthew, Kim, Yeo Jin, and Kim, Brandon

Abstract

It is well-documented that participation in leisure activities plays an essential role in coping with stress and improving health. However, we know less about what types of leisure activities are more relevant to life satisfaction and happiness among college students. Thus, the purpose of this study was to investigate how various leisure activities relate to happiness and life satisfaction among college students. Data were collected using a sample of 266 in Indiana, United States. Results from hierarchical multiple regression analysis indicate that certain types of activities (i.e. outdoor, sports, social, cultural and civic activities) were particularly associated with life satisfaction and happiness. In this regard, this study confirmed that the relationships of leisure activity with life satisfaction and happiness vary across leisure activity types. Furthermore, this study highlights the importance of providing a variety of campus recreational programmes and cultural and social events to foster and sustain adequate physical activity, which will lead to improved life satisfaction and happiness. [ABSTRACT FROM AUTHOR]

Published
2024
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15. Immunology of severe febrile illness in children in the COVID-19 era

Author

Shankar-Hari, Manu, primary, Patel, Harsita, additional, Carter, Michael, additional, Jackson, Heather, additional, Powell, Oliver, additional, Fish, Matthew, additional, Barberio, Manuela Terranova, additional, Spada, Filomena, additional, Petrov, Nedyalko, additional, Wellman, Paul, additional, Darnell, Sara, additional, Mustafa, Sobia, additional, Todd, Katrina, additional, Bishop, Cynthia, additional, Cohen, Jonathan, additional, Kenny, Julia, additional, Berg, Sarah van den, additional, Sun, Thomas, additional, Davis, Francesca, additional, Jennings, Aislinn, additional, Timms, Emma, additional, Thomas, Jessica, additional, Nyirendra, Maggie, additional, Nichols, Samuel, additional, Elorrieta, Leire Estramiana, additional, D'Souza, Giselle, additional, Wright, Victoria, additional, De, Tisham, additional, Habgood-Coote, Dominic, additional, Ramnarayan, Padmanabhan, additional, Tissières, Pierre, additional, Whittaker, Liz, additional, Herberg, Jethro, additional, Cunnington, Aubrey, additional, Kaforou, Myrsini, additional, Ellis, Richard, additional, Malim, Michael, additional, Tibby, Shane, additional, and Levin, Michael, additional

Published
2023
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19. Intermittent fasting induces rapid hepatocyte proliferation to restore the hepatostat in the mouse liver

Author

Sarkar, Abby, primary, Jin, Yinhua, additional, DeFelice, Brian C, additional, Logan, Catriona Y, additional, Yang, Yan, additional, Anbarchian, Teni, additional, Wu, Peng, additional, Morri, Maurizio, additional, Neff, Norma F, additional, Nguyen, Huy, additional, Rulifson, Eric, additional, Fish, Matthew, additional, Kaye, Avi Gurion, additional, Martínez Jaimes, Azalia M, additional, and Nusse, Roel, additional

Published
2023
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20. Author Correction: A dynamic COVID-19 immune signature includes associations with poor prognosis

Author

Laing, Adam G., Lorenc, Anna, del Molino del Barrio, Irene, Das, Abhishek, Fish, Matthew, Monin, Leticia, Muñoz-Ruiz, Miguel, McKenzie, Duncan R., Hayday, Thomas S., Francos-Quijorna, Isaac, Kamdar, Shraddha, Joseph, Magdalene, Davies, Daniel, Davis, Richard, Jennings, Aislinn, Zlatareva, Iva, Vantourout, Pierre, Wu, Yin, Sofra, Vasiliki, Cano, Florencia, Greco, Maria, Theodoridis, Efstathios, Freedman, Joshua D., Gee, Sarah, Chan, Julie Nuo En, Ryan, Sarah, Bugallo-Blanco, Eva, Peterson, Pärt, Kisand, Kai, Haljasmägi, Liis, Chadli, Loubna, Moingeon, Philippe, Martinez, Lauren, Merrick, Blair, Bisnauthsing, Karen, Brooks, Kate, Ibrahim, Mohammad A. A., Mason, Jeremy, Lopez Gomez, Federico, Babalola, Kola, Abdul-Jawad, Sultan, Cason, John, Mant, Christine, Seow, Jeffrey, Graham, Carl, Doores, Katie J., Di Rosa, Francesca, Edgeworth, Jonathan, Shankar-Hari, Manu, and Hayday, Adrian C.

Published
2020
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21. Coronavirus disease 2019 subphenotypes and differential treatment response to convalescent plasma in critically ill adults: secondary analyses of a randomized clinical trial

Author

Fish, Matthew, Rynne, Jennifer, Jennings, Aislinn, Lam, C, Lamikanra, A, Ratcliff, J, Cellone-Trevelin, S, Timms, E, Jeriha, Jakob, Tosi, I, Pramanik, R, Simmonds, P, Seth, Sohan, Williams, J, Gordon, A C, Knight, J, Smith, D J, Whalley, J, Harrison, D, Rowan, K, Harvala, H, Klenerman, P, Estcourt, L, Menon, D K, Roberts, D, Shankar-Hari, Manu, NIHR, and National Institute for Health Research

Subjects
Adult, Science & Technology, Convalescent plasma, sub-phenotypes, Critical Illness, Precision medicine, COVID-19, 1103 Clinical Sciences, Critical Care and Intensive Care Medicine, Subphenotypes, Emergency & Critical Care Medicine, 1117 Public Health and Health Services, REMAP-CAP Immunoglobulin Domain UK Investigators, Treatment Outcome, Critical Care Medicine, General & Internal Medicine, convalescent plasma, Humans, Cytokines, Life Sciences & Biomedicine, COVID-19 Serotherapy, Biomarkers
Abstract

Purpose Benefit from convalescent plasma therapy for coronavirus disease 2019 (COVID-19) has been inconsistent in randomized clinical trials (RCTs) involving critically ill patients. As COVID-19 patients are immunologically heterogeneous, we hypothesized that immunologically similar COVID-19 subphenotypes may differ in their treatment responses to convalescent plasma and explain inconsistent findings between RCTs . Methods We tested this hypothesis in a substudy involving 1239 patients, by measuring 26 biomarkers (cytokines, chemokines, endothelial biomarkers) within the randomized, embedded, multifactorial, adaptive platform trial for community-acquired pneumonia (REMAP-CAP) that assigned 2097 critically ill COVID-19 patients to either high-titer convalescent plasma or usual care. Primary outcome was organ support free days at 21 days (OSFD-21) . Results Unsupervised analyses identified three subphenotypes/endotypes. In contrast to the more homogeneous subphenotype-2 (N = 128 patients, 10.3%; with elevated type i and type ii effector immune responses) and subphenotype-3 (N = 241, 19.5%; with exaggerated inflammation), the subphenotype-1 had variable biomarker patterns (N = 870 patients, 70.2%). Subphenotypes-2, and -3 had worse outcomes, and subphenotype-1 had better outcomes with convalescent plasma therapy compared with usual care (median (IQR). OSFD-21 in convalescent plasma vs usual care was 0 (− 1, 21) vs 10 (− 1, to 21) in subphenotype-2; 1.5 (− 1, 21) vs 12 (− 1, to 21) in suphenotype-3, and 0 (− 1, 21) vs 0 (− 1, to 21) in subphenotype-1 (test for between-subphenotype differences in treatment effects p = 0.008). Conclusions We reported three COVID-19 subphenotypes, among critically ill adults, with differential treatment effects to ABO-compatible convalescent plasma therapy. Differences in subphenotype prevalence between RCT populations probably explain inconsistent results with COVID-19 immunotherapies.

Published
2022

22. Author response: Intermittent fasting induces rapid hepatocyte proliferation to restore the hepatostat in the mouse liver

Author

Sarkar, Abby, primary, Jin, Yinhua, additional, DeFelice, Brian C, additional, Logan, Catriona Y, additional, Yang, Yan, additional, Anbarchian, Teni, additional, Wu, Peng, additional, Morri, Maurizio, additional, Neff, Norma F, additional, Nguyen, Huy, additional, Rulifson, Eric, additional, Fish, Matthew, additional, Kaye, Avi Gurion, additional, Martínez Jaimes, Azalia M, additional, and Nusse, Roel, additional

Published
2022
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23. Pituitary stem cells produce paracrine WNT signals to control the expansion of their descendant progenitor cells

Author

P, Russell John, primary, Lim, Xinhong, additional, Santambrogio, Alice, additional, Yianni, Val, additional, Kemkem, Yasmine, additional, Wang, Bruce, additional, Fish, Matthew, additional, Haston, Scott, additional, Grabek, Anaeëlle, additional, Hallang, Shirleen, additional, J, Lodge Emily, additional, L, Patist Amanda, additional, Schedl, Andreas, additional, Mollard, Patrice, additional, Nusse, Roel, additional, and Andoniadou, Cynthia L, additional

Published
2022
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24. Highly Sensitive Lineage Discrimination of SARS-CoV-2 Variants through Allele-Specific Probe PCR

Author

Ratcliff, Jeremy, primary, Al-Beidh, Farah, additional, Bibi, Sagida, additional, Bonsall, David, additional, Costa Clemens, Sue Ann, additional, Estcourt, Lise, additional, Evans, Amy, additional, Fish, Matthew, additional, Folegatti, Pedro M., additional, Gordon, Anthony C., additional, Jay, Cecilia, additional, Jennings, Aislinn, additional, Laing, Emma, additional, Lambe, Teresa, additional, MacIntyre-Cockett, George, additional, Menon, David, additional, Mouncey, Paul R., additional, Nguyen, Dung, additional, Pollard, Andrew J., additional, Ramasamy, Maheshi N., additional, Roberts, David J., additional, Rowan, Kathryn M., additional, Rynne, Jennifer, additional, Shankar-Hari, Manu, additional, Williams, Sarah, additional, Harvala, Heli, additional, Golubchik, Tanya, additional, and Simmonds, Peter, additional

Published
2022
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25. Highly sensitive lineage discrimination of SARS-CoV-2 variants through allele-specific probe PCR

Author

Ratcliff, Jeremy, Al-Beidh, Farah, Bibi, Sagida, Bonsall, David, Costa Clemens, Sue Ann, Estcourt, Lise, Evans, Amy, Fish, Matthew, Folegatti, Pedro M, Gordon, Anthony C, Jay, Cecilia, Jennings, Aislinn, Laing, Emma, Lambe, Teresa, MacIntyre-Cockett, George, Menon, David, Mouncey, Paul R, Nguyen, Dung, Pollard, Andrew J, Ramasamy, Maheshi N, Roberts, David J, Rowan, Kathryn M, Rynne, Jennifer, Shankar-Hari, Manu, Williams, Sarah, Harvala, Heli, Golubchik, Tanya, Simmonds, Peter, AMPHEUS Project, REMAP-CAP Immunoglobulin Domain UK Investigators, NIHR, Ratcliff, Jeremy [0000-0001-6522-138X], Bonsall, David [0000-0003-2187-0550], Jay, Cecilia [0000-0003-2387-9225], Shankar-Hari, Manu [0000-0002-5338-2538], Golubchik, Tanya [0000-0003-2765-9828], Simmonds, Peter [0000-0002-7964-4700], Apollo - University of Cambridge Repository, Project, AMPHEUS, Investigators, REMAP-CAP Immunoglobulin Domain UK, and Group, Oxford COVID-19 Vaccine Trial

Subjects
Microbiology (medical), allele-specific probe PCR, SARS-CoV-2, viruses, COVID-19, AMPHEUS Project, REMAP-CAP Immunoglobulin Domain UK Investigators, and Oxford COVID-19 Vaccine Trial Group, 06 Biological Sciences, variants of concern, Polymerase Chain Reaction, Microbiology, 07 Agricultural and Veterinary Sciences, diagnostics, Humans, next-generation sequencing, variant identification, Alleles, 11 Medical and Health Sciences
Abstract

Tools to detect SARS-CoV-2 variants of concern and track the ongoing evolution of the virus are necessary to support public health efforts and the design and evaluation of novel COVID-19 therapeutics and vaccines. Although next-generation sequencing (NGS) has been adopted as the gold standard method for discriminating SARS-CoV-2 lineages, alternative methods may be required when processing samples with low viral loads or low RNA quality. To this aim, an allele-specific probe PCR (ASP-PCR) targeting lineage-specific single nucleotide polymorphisms (SNPs) was developed and used to screen 1,082 samples from two clinical trials in the United Kingdom and Brazil. Probit regression models were developed to compare ASP-PCR performance against 1,771 NGS results for the same cohorts. Individual SNPs were shown to readily identify specific variants of concern. ASP-PCR was shown to discriminate SARS-CoV-2 lineages with a higher likelihood than NGS over a wide range of viral loads. The comparative advantage for ASP-PCR over NGS was most pronounced in samples with cycle threshold (CT) values between 26 and 30 and in samples that showed evidence of degradation. Results for samples screened by ASP-PCR and NGS showed 99% concordant results. ASP-PCR is well suited to augment but not replace NGS. The method can differentiate SARS-CoV-2 lineages with high accuracy and would be best deployed to screen samples with lower viral loads or that may suffer from degradation. Future work should investigate further destabilization from primer-target base mismatch through altered oligonucleotide chemistry or chemical additives.

Published
2022

27. Effect of Convalescent Plasma on Organ Support-Free Days in Critically Ill Patients With COVID-19: A Randomized Clinical Trial

Author

Writing Committee for the REMAP-CAP Investigators, Estcourt, Lise J, Turgeon, Alexis F, McQuilten, Zoe K, McVerry, Bryan J, Al-Beidh, Farah, Annane, Djillali, Arabi, Yaseen M, Arnold, Donald M, Beane, Abigail, Bégin, Philippe, van Bentum-Puijk, Wilma, Berry, Lindsay R, Bhimani, Zahra, Birchall, Janet E, Bonten, Marc JM, Bradbury, Charlotte A, Brunkhorst, Frank M, Buxton, Meredith, Callum, Jeannie L, Chassé, Michaël, Cheng, Allen C, Cove, Matthew E, Daly, James, Derde, Lennie, Detry, Michelle A, De Jong, Menno, Evans, Amy, Fergusson, Dean A, Fish, Matthew, Fitzgerald, Mark, Foley, Claire, Goossens, Herman, Gordon, Anthony C, Gosbell, Iain B, Green, Cameron, Haniffa, Rashan, Harvala, Heli, Higgins, Alisa M, Hills, Thomas E, Hoad, Veronica C, Horvat, Christopher, Huang, David T, Hudson, Cara L, Ichihara, Nao, Laing, Emma, Lamikanra, Abigail A, Lamontagne, François, Lawler, Patrick R, Linstrum, Kelsey, Litton, Edward, Lorenzi, Elizabeth, MacLennan, Sheila, Marshall, John, McAuley, Daniel F, McDyer, John F, McGlothlin, Anna, McGuinness, Shay, Miflin, Gail, Montgomery, Stephanie, Mouncey, Paul R, Murthy, Srinivas, Nichol, Alistair, Parke, Rachael, Parker, Jane C, Priddee, Nicole, Purcell, Damian FJ, Reyes, Luis F, Richardson, Peter, Robitaille, Nancy, Rowan, Kathryn M, Rynne, Jennifer, Saito, Hiroki, Santos, Marlene, Saunders, Christina T, Serpa Neto, Ary, Seymour, Christopher W, Silversides, Jon A, Tinmouth, Alan A, Triulzi, Darrell J, Turner, Anne M, van de Veerdonk, Frank, Walsh, Timothy S, Wood, Erica M, Berry, Scott, Lewis, Roger J, Menon, David K, McArthur, Colin, Zarychanski, Ryan, Angus, Derek C, Webb, Steve A, Roberts, David J, Shankar-Hari, Manu, Menon, David [0000-0002-3228-9692], Apollo - University of Cambridge Repository, Investigators, Writing Committee for the REMAP-CAP, Writing Comm REMAP-CAP Investigators, Hôpital Raymond Poincaré [AP-HP], Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), National Institutes of Health, NIH, National Institute of Child Health and Human Development, NICHD, Pittsburgh Foundation, Breast Cancer Research Foundation, BCRF, Bristol-Myers Squibb, BMS, GlaxoSmithKline, GSK, Medtronic, Baxter International, Manitoba Medical Service Foundation, MMSF, CancerCare Manitoba Foundation, CCMF, Wellcome Trust, WT, University of Manitoba, UM, Health Research Board, HRB: PHRC-20-0147, National Blood Authority, NBA, Llywodraeth Cymru, Translational Breast Cancer Research Consortium, TBCRC, Canadian Institutes of Health Research, IRSC: 158584, CTN 2014-012, Medical Research Council, MRC, National Institute for Health Research, NIHR, Department of Health and Social Care, DH, European Commission, EC: APP194811, National Heart and Lung Institute, NHLI, National Health and Medical Research Council, NHMRC: 2015-06-18, 2016-16-011, APP1101719, APP2002132, Health Research Council of New Zealand, HRC: 16/631, 447335, Monash University, MU, Ministère des Affaires Sociales et de la Santé: 215522, Seventh Framework Programme, FP7, Université Pierre et Marie Curie, UPMC, Innovate UK, Horizon 2020, Pharmaceuticals Bayer, Minderoo Foundation, Dr Fitzgerald reported receiving grants from the PREPARE Network and the European Commission. Dr Gordon reported receiving grants from the National Institute for Health Research and receiving personal fees from 30 Respiratory, GlaxoSmithKline, and Bristol Myers Squibb. Dr Gosbell reported receiving grants from the Australian Red Cross Lifeblood, which is funded by the Australian government. Dr Haniffa reported receiving grants from the Wellcome Trust Innovations Project, the Minderoo Foundation, and the UK Research and Innovation African Critical Care Registry Network. Dr Higgins reported receiving grants from the National Health and Medical Research Council, the Minderoo Foundation, and the National Blood Authority. Dr Hills reported receiving grants from the Health Research Council of New Zealand. Dr Hoad reported receiving grants from the Australian Red Cross Lifeblood, which is funded by the Australian government. Dr Horvat reported receiving grants from the National Institute of Child Health and Human Development. Dr Huang reported receiving grants from the Breast Cancer Research Foundation. Dr Lamontagne reported receiving grants from the Canadian Institutes of Health Research. Dr Lawler reported receiving consulting fees from Novartis, Coronna LLC, and Brigham and Women’s Hospital, receiving royalties from McGraw-Hill Publishing, and receiving grants from the Canadian Institutes of Health Research, the LifeArc Foundation, the National Institutes of Health, the Peter Munk Cardiac Centre, the Ted Rogers Centre for Heart Research, the Thistledown Foundation, and the province of Ontario. Dr Lorenzi reported receiving personal fees from Berry Consultants. Dr Marshall reported receiving personal fees from AM-Pharma (data and safety monitoring board chair) and Critical Care Medicine (associate editor). Dr McAuley reported receiving personal fees from Bayer, GlaxoSmithKline, Boehringer Ingelheim, Novartis, Eli Lilly, Vir Biotechnology, Faron Pharmaceuticals, and Sobi, receiving grants from the National Institute for Health Research, Wellcome Trust, Innovate UK, the Medical Research Council, and the Northern Ireland Health and Social Care Research and Development Division, and holding a patent for an anti-inflammatory treatment that was issued to Queen’s University Belfast. Dr McGlothlin reported receiving grants from the PREPARE Network, the European Commission, and the Global Coalition for Adapative Research. Mr Mouncey reported receiving grants from the European Union, the PREPARE Network, the National Institute for Health Research, and European Union Horizon 2020. Dr Nichol reported receiving grants from the Health Research Board of Ireland and Baxter and receiving personal fees from AM-Pharma. Dr Parke reported receiving grants from Fisher and Paykel Healthcare Ltd. Ms Parker reported receiving grants from Monash University. Mr Richardson reported receiving funding from the Welsh government. Dr Rowan reported receiving grants from the European Commission and the National Institute for Health Research. Dr Saunders reported receiving grants from the PREPARE Network, the European Commission, and the Global Coalition for Adapative Research. Dr Serpa Neto reported receiving personal fees from Drager and Endpoint Health. Dr Tinmouth reported receiving grants and personal fees from the Canadian Blood Services. Ms Turner reported receiving grants from the Health Research Council of New Zealand. Dr van de Veerdonk reported receiving personal fees from Gilead, Sobi, and GlaxoSmithKline. Dr Wood reported receiving grants from the Australian Medical Research Future Fund. Dr S. Berry reported being an employee of Berry Consultants with an ownership role. Dr Lewis reported being an employee of Berry Consultants. Dr Menon reported receiving grants from the National Institute for Health Research. Dr McArthur reported receiving grants from the Health Research Council of New Zealand. Dr Zarychanski reported receiving grants from the Canadian Institutes of Health Research, the University of Manitoba, LifeArc, the Thistledown Foundation, Research Manitoba, the CancerCare Manitoba Foundation, the Victoria General Hospital Foundation, the Peter Munk Cardiac Centre, and the Manitoba Medical Services Foundation. Dr Webb reported receiving grants from the National Health and Medical Research Council and the Minderoo Foundation. Dr Shankar-Hari reported receiving grants from the National Institute for Clinical Research. No other disclosures were reported., nonprofit sponsors: Monash University, Melbourne, Australia (Australasian sponsor), Utrecht Medical Center, Utrecht, the Netherlands (European sponsor), St Michael’s Hospital, Toronto, Ontario, Canada (Canadian sponsor), and the Global Coalition for Adaptive Research, San Francisco, California (US sponsor). This study was additionally funded by grant 602525 FP7-health-2013-innovation-1 from the European Union Platform for European Preparedness Against Reemerging Epidemics, grants APP1101719 and APP1116530 from the Australian National Health and Medical Research Council, grant APP2002132 from the Australian Medical Research Future Fund, grant 16/631 from the New Zealand Health Research Council, grant 447335 from the Canadian Institutes of Health Research COVID-19 Rapid Research, grant 158584 from the Canadian Institutes of Health Research Strategy for Patient-Oriented Research Innovative Clinical Trials Program, grant CTN 2014-012 from the Health Research Board of Ireland, grant PHRC-20-0147 from the French Ministry of Health, and grant 215522 from the Wellcome Trust Innovations Project and funding from the National Institute for Health Research, the Department of Health and Social Care, the EU Programme Emergency Support Instrument, the NHS Blood and Transplant Research and Development Programme, the National Institute for Health Research, the National Institute for Health Research Imperial Biomedical Research Centre, the UPMC Learning While Doing Program, the Translational Breast Cancer Research Consortium, the Pittsburgh Foundation, and the Minderoo Foundation. The Australian government funds the Australian Red Cross Lifeblood for the provision of blood products and services. The collection of plasma in the United Kingdom was funded by European Union SoHo grants from the Department of Health and Social Care. Dr Turgeon is the Canada Research Chair in Critical Care Neurology and Trauma. Dr McQuilten is supported by emerging leader fellowship APP194811 from the National Health and Medical Research Council. Dr Gordon is funded by research professorship 2015-06-18 from the National Institute for Health Research. Dr Shankar-Hari is funded by clinician scientist fellowship 2016-16-011 from the National Institute for Health Research., In Canada, the trial has been funded by the Canadian Institute of Health Research, Strategy for Patient-Oriented Research (CIHR-SPOR) Innovative Clinical Trials Program Grant (no. 158584) for CAD $1,497,200, for the recruitment of 300 patients., The Platform for European Preparedness Against (Re-)emerging Epidemics (PREPARE) consortium is funded by the European Union (FP7-HEALTH-2013-INNOVATION-1, grant number 602525). Within the PREPARE consortium, the trial has funding for the recruitment of approximately 4000 patients., REMAP-CAP was supported in the Netherlands by the Research Collaboration Critical Care the Netherlands (RCC-Net)., Funding sources for the REMAP-CAP trial are specified in the core protocol documents. This domain has received domain-specific funding from the Australian Medical Research Future Fund (MRFF)., reported receiving grants from the National Institute for Health Research and European Union Horizon 2020. Dr Turgeon reported receiving grants from the Canadian Institutes of Health Research. Dr McQuilten reported receiving grants from the Australian Medical Research Future Fund. Dr McVerry reported receiving grants from the Pittsburgh Foundation, the Translational Breast Cancer Research Consortium, UPMC Learning While Doing Program, National Heart, Lung, and Blood Institute, and Bayer Pharmaceuticals and receiving personal fees from Boehringer Ingelheim. Dr Annane reported receiving grants from the French Ministry of Health and Solidarity. Dr Arnold reported receiving grants from the Canadian Institutes of Health Research. Ms Beane reported receiving grants and salary support from Wellcome Trust. Ms Bentum-Puijk reported receiving grants from the European Commission and the European Union. Dr L. Berry reported receiving grants from Berry Consultants. Dr Bradbury reported receiving personal fees from Lilly, Bristol Myers Squibb, Pfizer, Bayer, Amgen, Novartis, Janssen, Portola Advisors, and Ablynx. Dr Buxton reported receiving personal fees from the Breast Cancer Research Foundation, Amgen, and Eisai. Dr Callum reported receiving grants from the Canadian Blood Services and Octapharma. Dr Cove reported receiving grants from National University Health System, receiving consulting fees from Medtronic and Baxter, and holding a US patent for removal of carbon dioxide via dialysis. Dr Daly reported receiving grants from the Australian Red Cross Lifeblood, which is funded by the Australian government. Dr Derde reported receiving grants from University Medical Center Utrecht, being a member of the COVID-19 guideline committee of the Surviving Sepsis Campaign/ European Society of Intensive Care Medicine and European Society of Intensive Care Medicine COVID-19 taskforce, and serving as chair of the Dutch intensivists taskforce acute infectious threats. Dr Detry reported receiving grants from the European Union Platform for European Preparedness Against Reemerging Epidemics (PREPARE) consortium, the Australian National Health and Medical Research Council, the Health Research Council of New Zealand, and the UPMC Learning While Doing Program. Dr De Jong reported receiving personal fees from Roche Scientific, Shionogi Scientific, and Janssen., The current regions are: x Europe, with funding from a European Union FP7 grant (FP7-HEALTH-2013-INNOVATION-1, grant number 602525), to support the enrollment of 4000 participants. This funding terminates in 2021. x Australia and New Zealand. In Australia the project has received funding from a NHMRC Project Grant (APP1101719), to support the enrollment of 2000 participants. This funding terminates in December 2021, although some extension may be feasible. In New Zealand the project has received funding from a HRC Programme Grant (16/631), to support the enrollment of 800 participants. This funding terminates in November 2021. x Canada. In Canada the project has received funding for a CIHR grant (158584), to support the enrollment of 300 participants. This funding terminates in 2022. x United States. In the US, funding has been received from UPMC health system for recruitment internally at all UPMC hospitals (>40) and to support a US regional coordinating center. Philanthropic support is being provided through GCAR. Additional funds are being pursued., The REMAP-CAP platform is supported by the Australian and New Zealand Intensive Care Society Clinical Trials Group, the Canadian Critical Care Trials Group, the Irish Critical Care, European Project: 602525,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-1,PREPARE(2014), NIHR, National Institute for Health Research, Medical Microbiology and Infection Prevention, AII - Infectious diseases, and Intensive Care Medicine

Subjects
Male, medicine.medical_treatment, [SDV]Life Sciences [q-bio], lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], 030204 cardiovascular system & hematology, Logistic regression, law.invention, 0302 clinical medicine, Randomized controlled trial, law, Critical Illness/therapy, Vasoconstrictor Agents, 030212 general & internal medicine, Hospital Mortality, Treatment Failure, 11 Medical and Health Sciences, Original Investigation, Mortality rate, General Medicine, Middle Aged, Intensive care unit, Writing Committee for the REMAP-CAP Investigators, 3. Good health, Female, Life Sciences & Biomedicine, COVID-19/therapy, Adult, medicine.medical_specialty, Randomization, Respiration, Artificial/statistics & numerical data, Critical Illness, ABO Blood-Group System, 03 medical and health sciences, Medicine, General & Internal, Internal medicine, General & Internal Medicine, medicine, Humans, Adverse effect, COVID-19 Serotherapy, Aged, Mechanical ventilation, Science & Technology, business.industry, Immunization, Passive, Vasoconstrictor Agents/therapeutic use, COVID-19, Odds ratio, Length of Stay, Respiration, Artificial, Logistic Models, Human medicine, business
Abstract

Importance The evidence for benefit of convalescent plasma for critically ill patients with COVID-19 is inconclusive.Objective To determine whether convalescent plasma would improve outcomes for critically ill adults with COVID-19.Design, Setting, and Participants The ongoing Randomized, Embedded, Multifactorial, Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP) enrolled and randomized 4763 adults with suspected or confirmed COVID-19 between March 9, 2020, and January 18, 2021, within at least 1 domain; 2011 critically ill adults were randomized to open-label interventions in the immunoglobulin domain at 129 sites in 4 countries. Follow-up ended on April 19, 2021.Interventions The immunoglobulin domain randomized participants to receive 2 units of high-titer, ABO-compatible convalescent plasma (total volume of 550 mL ± 150 mL) within 48 hours of randomization (n = 1084) or no convalescent plasma (n = 916).Main Outcomes and Measures The primary ordinal end point was organ support–free days (days alive and free of intensive care unit–based organ support) up to day 21 (range, −1 to 21 days; patients who died were assigned –1 day). The primary analysis was an adjusted bayesian cumulative logistic model. Superiority was defined as the posterior probability of an odds ratio (OR) greater than 1 (threshold for trial conclusion of superiority >99%). Futility was defined as the posterior probability of an OR less than 1.2 (threshold for trial conclusion of futility >95%). An OR greater than 1 represented improved survival, more organ support–free days, or both. The prespecified secondary outcomes included in-hospital survival; 28-day survival; 90-day survival; respiratory support–free days; cardiovascular support–free days; progression to invasive mechanical ventilation, extracorporeal mechanical oxygenation, or death; intensive care unit length of stay; hospital length of stay; World Health Organization ordinal scale score at day 14; venous thromboembolic events at 90 days; and serious adverse events.Results Among the 2011 participants who were randomized (median age, 61 [IQR, 52 to 70] years and 645/1998 [32.3%] women), 1990 (99%) completed the trial. The convalescent plasma intervention was stopped after the prespecified criterion for futility was met. The median number of organ support–free days was 0 (IQR, –1 to 16) in the convalescent plasma group and 3 (IQR, –1 to 16) in the no convalescent plasma group. The in-hospital mortality rate was 37.3% (401/1075) for the convalescent plasma group and 38.4% (347/904) for the no convalescent plasma group and the median number of days alive and free of organ support was 14 (IQR, 3 to 18) and 14 (IQR, 7 to 18), respectively. The median-adjusted OR was 0.97 (95% credible interval, 0.83 to 1.15) and the posterior probability of futility (OR Conclusions and Relevance Among critically ill adults with confirmed COVID-19, treatment with 2 units of high-titer, ABO-compatible convalescent plasma had a low likelihood of providing improvement in the number of organ support–free days.Trial Registration ClinicalTrials.gov Identifier: NCT02735707

Published
2021

28. Association of cardiometabolic microRNAs with COVID-19 severity and mortality

Author

Gutmann, Clemens, primary, Khamina, Kseniya, additional, Theofilatos, Konstantinos, additional, Diendorfer, Andreas B, additional, Burnap, Sean A, additional, Nabeebaccus, Adam, additional, Fish, Matthew, additional, McPhail, Mark J W, additional, O'Gallagher, Kevin, additional, Schmidt, Lukas E, additional, Cassel, Christian, additional, Auzinger, Georg, additional, Napoli, Salvatore, additional, Mujib, Salma F, additional, Trovato, Francesca, additional, Sanderson, Barnaby, additional, Merrick, Blair, additional, Roy, Roman, additional, Edgeworth, Jonathan D, additional, Shah, Ajay M, additional, Hayday, Adrian C, additional, Traby, Ludwig, additional, Hackl, Matthias, additional, Eichinger, Sabine, additional, Shankar-Hari, Manu, additional, and Mayr, Manuel, additional

Published
2021
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29. Carl Menconi case writing competition: brand x company's 300% tariff: a U.S. company wants to cut costs by importing products, but a high tariff might prevent it

Author

Fish, Matthew W. and Miller, William F.

Subjects
United States. Department of Commerce -- Research -- Analysis, Tariffs -- Evaluation, Financial statements -- Management -- Forecasts and trends, Company business management, Market trend/market analysis, Banking, finance and accounting industries, Business, general, Business
Abstract

The IMA® Committee on Ethics and Raef Lawson, CMA, CFA, CFP, CPA, Ph.D., IMA VP of Research and Professor-in-Residence, are proud to announce that Matthew W. Fish and William F. [...]

Published
2015

31. Cellular and molecular mechanisms of IMMunE dysfunction and Recovery from SEpsis-related critical illness in adults: An observational cohort study (IMMERSE) protocol paper.

Author

Fish, Matthew, Arkless, Kate, Jennings, Aislinn, Wilson, Julie, Carter, Michael J, Arbane, Gill, Campos, Sara, Novellas, Neus, Wester, Rianne, Petrov, Nedyalko, Niazi, Umar, Sanderson, Barney, Ellis, Richard, Saqi, Mansoor, Spencer, Jo, Singer, Mervyn, Martinez-Nunez, Rocio T, Pitchford, Simon, Swanson, Chad M, and Shankar-Hari, Manu

Published
2022
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32. Virological and serological characterization of critically ill patients with COVID-19 in the UK: a special focus on variant detection

Author

Ratcliff, Jeremy, primary, Nguyen, Dung, additional, Fish, Matthew, additional, Rhynne, Jennifer, additional, Jennings, Aislinn, additional, Williams, Sarah, additional, Al-Beidh, Farah, additional, Bonsall, David, additional, Evans, Amy, additional, Golubchik, Tanya, additional, Gordon, Anthony C, additional, Lamikanra, Abigail, additional, Tsang, Pat, additional, Ciccone, Nick, additional, Leuscher, Ullrich, additional, Slack, Wendy, additional, Laing, Emma, additional, Mouncey, Paul R, additional, Ziyenge, Sheba, additional, Olivera, Marta, additional, Ploeg, Rutger, additional, Rowan, Kathryn M, additional, Shankar-Hari, Manu, additional, Roberts, David J., additional, Menon, David K, additional, Estcourt, Lise, additional, Simmonds, Peter, additional, and Harvala, Heli, additional

Published
2021
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33. sj-pdf-1-inc-10.1177_1751143720966286 - Supplemental material for Cellular and molecular mechanisms of IMMunE dysfunction and Recovery from SEpsis-related critical illness in adults: An observational cohort study (IMMERSE) protocol paper

Author

Fish, Matthew, Arkless, Kate, Jennings, Aislinn, Wilson, Julie, Carter, Michael J, Arbane, Gill, Campos, Sara, Novellas, Neus, Wester, Rianne, Petrov, Nedyalko, Niazi, Umar, Sanderson, Barney, Ellis, Richard, Saqi, Mansoor, Spencer, Jo, Singer, Mervyn, Martinez-Nunez, Rocio T, Pitchford, Simon, Swanson, Chad M, and Shankar-Hari, Manu

Subjects
111708 Health and Community Services, FOS: Clinical medicine, Cardiology, 110323 Surgery, FOS: Health sciences, 110305 Emergency Medicine
Abstract

Supplemental material, sj-pdf-1-inc-10.1177_1751143720966286 for Cellular and molecular mechanisms of IMMunE dysfunction and Recovery from SEpsis-related critical illness in adults: An observational cohort study (IMMERSE) protocol paper by Matthew Fish, Kate Arkless, Aislinn Jennings, Julie Wilson, Michael J Carter, Gill Arbane, Sara Campos, Neus Novellas, Rianne Wester, Nedyalko Petrov, Umar Niazi, Barney Sanderson, Richard Ellis, Mansoor Saqi, Jo Spencer, Mervyn Singer, Rocio T Martinez-Nunez, Simon Pitchford, Chad M Swanson and Manu Shankar-Hari in Journal of the Intensive Care Society

Published
2020
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34. Thirty-one flavors of Drosophila Rab proteins

Author

Zhang, Jun, Schulze, Karen L., Hiesinger, P. Robin, Suyama, Kaye, Wang, Stream, Fish, Matthew, Acar, Melih, Hoskins, Roger A., Bellen, Hugo J., and Scott, Matthew P.

Subjects
Drosophila -- Genetic aspects, Drosophila -- Physiological aspects, Drosophila -- Chemical properties, G proteins -- Physiological aspects, G proteins -- Genetic aspects, Gene expression -- Evaluation, Biological sciences
Abstract

Rab proteins are small GTPases that play important roles in transport of vesicle cargo and recruitment, association of motor and other proteins with vesicles, and docking and fusion of vesicles at defined locations. In vertebrates, > 75 Rab genes have been identified, some of which have been intensively studied for their roles in endosome and synaptic vesicle trafficking. Recent studies of the functions of certain Rab proteins have revealed specific roles in mediating developmental signal transduction. We have begun a systematic genetic study of the 33 Rab genes in Drosophila. Most of the fly proteins are clearly related to specific vertebrate proteins. We report here the creation of a set of transgenic fly lines that allow spatially and temporally regulated expression of Drosophila Rab proteins. We generated fluorescent proteintagged wild-type, dominant-negative, and constitutively active forms of 31 Drosophila Rab proteins. We describe Drosophila Rab expression patterns during embryogenesis, the subcellular localization of some Rab proteins, and comparisons of the localization of wild-type, dominant-negative, and constitutively active forms of selected Rab proteins. The high evolutionary conservation and low redundancy of Drosophila Rab proteins make these transgenic lines a useful tool kit for investigating Rab functions in vivo.

Published
2007

35. Acute Immune Signatures and Their Legacies in Severe Acute Respiratory Syndrome Coronavirus-2 Infected Cancer Patients

Author

Abdul-Jawad, Sultan, primary, Baù, Luca, additional, Alaguthurai, Thanussuyah, additional, del Molino del Barrio, Irene, additional, Laing, Adam G., additional, Hayday, Thomas S., additional, Monin, Leticia, additional, Muñoz-Ruiz, Miguel, additional, McDonald, Louisa, additional, Francos Quijorna, Isaac, additional, McKenzie, Duncan, additional, Davis, Richard, additional, Lorenc, Anna, additional, Chan, Julie Nuo En, additional, Ryan, Sarah, additional, Bugallo-Blanco, Eva, additional, Yorke, Rozalyn, additional, Kamdar, Shraddha, additional, Fish, Matthew, additional, Zlatareva, Iva, additional, Vantourout, Pierre, additional, Jennings, Aislinn, additional, Gee, Sarah, additional, Doores, Katie, additional, Bailey, Katharine, additional, Hazell, Sophie, additional, De Naurois, Julien, additional, Moss, Charlotte, additional, Russell, Beth, additional, Khan, Aadil A., additional, Rowley, Mark, additional, Benjamin, Reuben, additional, Enting, Deborah, additional, Alrifai, Doraid, additional, Wu, Yin, additional, Zhou, You, additional, Barber, Paul, additional, Ng, Tony, additional, Spicer, James, additional, Van Hemelrijck, Mieke, additional, Kumar, Mayur, additional, Vidler, Jennifer, additional, Lwin, Yadanar, additional, Fields, Paul, additional, Karagiannis, Sophia N., additional, Coolen, Anthony C.C., additional, Rigg, Anne, additional, Papa, Sophie, additional, Hayday, Adrian C., additional, Patten, Piers E.M., additional, and Irshad, Sheeba, additional

Published
2021
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36. Pituitary stem cells produce paracrine WNT signals to control the expansion of their descendant progenitor cells

Author

Russell, John P, primary, Lim, Xinhong, additional, Santambrogio, Alice, additional, Yianni, Val, additional, Kemkem, Yasmine, additional, Wang, Bruce, additional, Fish, Matthew, additional, Haston, Scott, additional, Grabek, Anaëlle, additional, Hallang, Shirleen, additional, Lodge, Emily J, additional, Patist, Amanda L, additional, Schedl, Andreas, additional, Mollard, Patrice, additional, Nusse, Roel, additional, and Andoniadou, Cynthia L, additional

Published
2021
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37. Author response: Pituitary stem cells produce paracrine WNT signals to control the expansion of their descendant progenitor cells

Author

Russell, John P, primary, Lim, Xinhong, additional, Santambrogio, Alice, additional, Yianni, Val, additional, Kemkem, Yasmine, additional, Wang, Bruce, additional, Fish, Matthew, additional, Haston, Scott, additional, Grabek, Anaëlle, additional, Hallang, Shirleen, additional, Lodge, Emily J, additional, Patist, Amanda L, additional, Schedl, Andreas, additional, Mollard, Patrice, additional, Nusse, Roel, additional, and Andoniadou, Cynthia L, additional

Published
2020
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38. Construction of transgenic Drosophila by using the site-specific integrase from phage [phi]C31

Author

Groth, Amy C., Fish, Matthew, Nusse, Roel, and Calos, Michele P.

Subjects
Genetics -- Research, Biological sciences
Abstract

The [phi]C31 integrase functions efficiently in vitro and in Escherichia, yeast, and mammalian cells, mediating unidirectional site-specific recombination between its attB and attP recognition sites. Here we show that this site-specific integration system also functions efficiently in Drosophila melanogaster in cultured cells and in embryos. Intramolecular recombination in S2 cells on transfected plasmid DNA carrying the attB and attP recognition sites occurred at a frequency of 47%. In addition, several endogenous pseudo attP sites were identified in the fly genome that were recognized by the integrase and used as substrates for integration in S2 cells. Two lines of Drosophila were created by integrating an attP site into the genome with a P element. [phi]C31 integrase injected into embryos as mRNA functioned to promote integration of an attB-containing plasmid into the attP site, resulting in up to 55% of fertile adults producing transgenic offspring. A total of 100% of these progeny carried a precise integration event at the genomic attP site. These experiments demonstrate the potential for precise genetic engineering of the Drosophila genome with the [phi]C31 integrase system and will likely benefit research in Drosophila and other insects.

Published
2004

39. naked cuticle targets dishevelled to antagonize Wnt signal transduction

Author

Rouseet, Raphael, Mack, Judith A., Wharton, Keith A., Jr., Axelrod, Jeffrey D., Cadigan, Ken M., Fish, Matthew P., Nusse, Roel, and Scott, Matthew P.

Subjects
Drosophila -- Genetic aspects, Embryology, Experimental -- Genetic aspects, Cell differentiation -- Genetic aspects, Cellular signal transduction -- Research, Cytogenetics -- Research, Biological sciences
Abstract

The ways in which Nkd limits Wg signaling by using a combination of genetic and biochemical approaches are discussed. Study results indicate that Nkd likely can antagonize Wg signaling cell-autonomously through a direct interaction with Dsh. In Drosophila embryos the protein Naked cuticle limits effects of the Wnt signal Wingless in early segmentation.

Published
2001

40. SARS-CoV-2 RNAemia and proteomic biomarker trajectory inform prognostication in COVID-19 patients admitted to intensive care

Author

Mayr, Manuel, primary, Gutmann, Clemens, additional, Takov, Kaloyan, additional, Burnap, Sean, additional, Singh, Bhawana, additional, Theofilatos, Konstantinos, additional, Reed, Ella, additional, Hasman, Maria, additional, Nabeebaccus, Adam, additional, Fish, Matthew, additional, McPhail, Mark, additional, O'Gallagher, Kevin, additional, Schmidt, Lukas, additional, Cassel, Christian, additional, Rienks, Marieke, additional, Yin, Xiaoke, additional, Auzinger, Georg, additional, Napoli, Salvatore, additional, Mujib, Salma, additional, Trovato, Francesca, additional, Sanderson, Barnaby, additional, Merrick, Blair, additional, Niazi, Umar, additional, Saqi, Mansoor, additional, Dimitrakopoulou, Konstantina, additional, Braun, Silke, additional, Kronstein-Wiedemann, Romy, additional, Doores, Katie, additional, Edgeworth, Jonathan, additional, Shah, Ajay, additional, Bornstein, Stefan, additional, Tonn, Torsten, additional, Hayday, Adrian, additional, and Shankar-Hari, Manu, additional

Published
2020
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41. Cellular and molecular mechanisms of IMMunE dysfunction and Recovery from SEpsis-related critical illness in adults: An observational cohort study (IMMERSE) protocol paper

Author

Fish, Matthew, primary, Arkless, Kate, additional, Jennings, Aislinn, additional, Wilson, Julie, additional, Carter, Michael J, additional, Arbane, Gill, additional, Campos, Sara, additional, Novellas, Neus, additional, Wester, Rianne, additional, Petrov, Nedyalko, additional, Niazi, Umar, additional, Sanderson, Barney, additional, Ellis, Richard, additional, Saqi, Mansoor, additional, Spencer, Jo, additional, Singer, Mervyn, additional, Martinez-Nunez, Rocio T, additional, Pitchford, Simon, additional, Swanson, Chad M, additional, and Shankar-Hari, Manu, additional

Published
2020
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42. Immunophenotyping of Circulating Leukocytes Reveal Non-specific Activation of Innate and Adaptive Immune Systems in Multi-System Inflammatory Syndrome of Childhood Temporally Associated with SARS-Cov-2 Infection: Descriptive Cohort Study

Author

J. Carter, Michael, primary, Fish, Matthew, additional, Jennings, Aislinn, additional, Doores, Katie J., additional, Wellman, Paul, additional, Seow, Jeffrey, additional, Acors, Sam, additional, Timms, Emma, additional, Kenny, Julia, additional, Neil, Stuart, additional, H. Malim, Michael, additional, Tibby, Shane M., additional, and Shankar-Hari, Manu, additional

Published
2020
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43. A consensus Covid-19 immune signature combines immuno-protection with discrete sepsis-like traits associated with poor prognosis

Author

Laing, Adam G., primary, Lorenc, Anna, additional, Del Molino Del Barrio, Irene, additional, Das, Abhishek, additional, Fish, Matthew, additional, Monin, Leticia, additional, Muñoz-Ruiz, Miguel, additional, McKenzie, Duncan R., additional, Hayday, Thomas S., additional, Francos-Quijorna, Isaac, additional, Kamdar, Shraddha, additional, Joseph, Magdalene, additional, Davies, Daniel, additional, Davis, Richard, additional, Jennings, Aislinn, additional, Zlatareva, Iva, additional, Vantourout, Pierre, additional, Wu, Yin, additional, Sofra, Vasiliki, additional, Cano, Florencia, additional, Greco, Maria, additional, Theodoridis, Efstathios, additional, Freedman, Joshua, additional, Gee, Sarah, additional, En Chan, Julie Nuo, additional, Ryan, Sarah, additional, Bugallo-Blanco, Eva, additional, Peterson, Pärt, additional, Kisand, Kai, additional, Haljasmägi, Liis, additional, Martinez, Lauren, additional, Merrick, Blair, additional, Bisnauthsing, Karen, additional, Brooks, Kate, additional, Ibrahim, Mohammad, additional, Mason, Jeremy, additional, Gomez, Federico Lopez, additional, Babalola, Kola, additional, Abdul- Jawad, Sultan, additional, Cason, John, additional, Mant, Christine, additional, Doores, Katie J, additional, Seow, Jeffrey, additional, Graham, Carl, additional, Rosa, Francesca Di, additional, Edgeworth, Jonathan, additional, Shankar-Hari, Manu, additional, and Hayday, Adrian C., additional

Published
2020
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44. Pituitary stem cells produce paracrine WNT signals to control the expansion of their descendant progenitor cells

Author

Russell, John Parkin, primary, Lim, Xinhong, additional, Santambrogio, Alice, additional, Yianni, Val, additional, Kemkem, Yasmine, additional, Wang, Bruce, additional, Fish, Matthew, additional, Haston, Scott, additional, Grabek, Anaëlle, additional, Hallang, Shirleen, additional, Lodge, Emily Jane, additional, Patist, Amanda Louise, additional, Schedl, Andreas, additional, Mollard, Patrice, additional, Nusse, Roeland, additional, and Andoniadou, Cynthia Lilian, additional

Published
2020
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45. Association of cardiometabolic microRNAs with COVID-19 severity and mortality.

Author

Gutmann, Clemens, Khamina, Kseniya, Theofilatos, Konstantinos, Diendorfer, Andreas B, Burnap, Sean A, Nabeebaccus, Adam, Fish, Matthew, McPhail, Mark J W, O'Gallagher, Kevin, Schmidt, Lukas E, Cassel, Christian, Auzinger, Georg, Napoli, Salvatore, Mujib, Salma F, Trovato, Francesca, Sanderson, Barnaby, Merrick, Blair, Roy, Roman, Edgeworth, Jonathan D, and Shah, Ajay M

Subjects
REVERSE transcriptase polymerase chain reaction, ACUTE phase proteins, COVID-19 pandemic, COVID-19, ACUTE phase reaction
Abstract

Aims Coronavirus disease 2019 (COVID-19) can lead to multiorgan damage. MicroRNAs (miRNAs) in blood reflect cell activation and tissue injury. We aimed to determine the association of circulating miRNAs with COVID-19 severity and 28 day intensive care unit (ICU) mortality. Methods and results We performed RNA-Seq in plasma of healthy controls (n  =   11), non-severe (n  =   18), and severe (n  =   18) COVID-19 patients and selected 14 miRNAs according to cell- and tissue origin for measurement by reverse transcription quantitative polymerase chain reaction (RT–qPCR) in a separate cohort of mild (n  =   6), moderate (n  =   39), and severe (n  =   16) patients. Candidates were then measured by RT–qPCR in longitudinal samples of ICU COVID-19 patients (n  =   240 samples from n  =   65 patients). A total of 60 miRNAs, including platelet-, endothelial-, hepatocyte-, and cardiomyocyte-derived miRNAs, were differentially expressed depending on severity, with increased miR-133a and reduced miR-122 also being associated with 28 day mortality. We leveraged mass spectrometry-based proteomics data for corresponding protein trajectories. Myocyte-derived (myomiR) miR-133a was inversely associated with neutrophil counts and positively with proteins related to neutrophil degranulation, such as myeloperoxidase. In contrast, levels of hepatocyte-derived miR-122 correlated to liver parameters and to liver-derived positive (inverse association) and negative acute phase proteins (positive association). Finally, we compared miRNAs to established markers of COVID-19 severity and outcome, i.e. SARS-CoV-2 RNAemia, age, BMI, D-dimer, and troponin. Whilst RNAemia, age and troponin were better predictors of mortality, miR-133a and miR-122 showed superior classification performance for severity. In binary and triplet combinations, miRNAs improved classification performance of established markers for severity and mortality. Conclusion Circulating miRNAs of different tissue origin, including several known cardiometabolic biomarkers, rise with COVID-19 severity. MyomiR miR-133a and liver-derived miR-122 also relate to 28 day mortality. MiR-133a reflects inflammation-induced myocyte damage, whilst miR-122 reflects the hepatic acute phase response. [ABSTRACT FROM AUTHOR]

Published
2022
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46. Wingless repression of Drosophila frizzled 2 expression shapes of wingless morphogen gradient in the wing

Author

Cadigan, Kenneth M., Fish, Matthew P., Rulifson, Eric J., and Nusse, Roel

Subjects
Drosophila -- Genetic aspects, Morphogenesis -- Analysis, Biological sciences
Abstract

The Drosophila frizzled 2 can stabilize Wingless (Wg) protein because of the high levels of Wg receptor which allow such protein to reach cells beyond its site of synthesis. The creation of a gradient decreasing Wg stability which is moving toward the dorsal/ventral boundary can be attributed to the repression of Drosophila frizzled 2 expression by Wg signaling. Such Drosophila frizzled is vital for the normal shape of Wingless morphogen gradient and to the response of cells to Wg signal.

Published
1998

47. Virological and serological characterization of critically ill patients with COVID-19 in the UK: Interactions of viral load, antibody status and B.1.1.7 variant infection.

Author

Ratcliff, Jeremy, Nguyen, Dung, Fish, Matthew, Rynne, Jennifer, Jennings, Aislinn, Williams, Sarah, Al-Beidh, Farah, Bonsall, David, Evans, Amy, Golubchik, Tanya, Gordon, Anthony C, Lamikanra, Abigail, Tsang, Pat, Ciccone, Nick A, Leuscher, Ullrich, Slack, Wendy, Laing, Emma, Mouncey, Paul R, Ziyenge, Sheba, and Oliveira, Marta

Subjects
COVID-19, VIRAL load, SARS-CoV-2, CONVALESCENT plasma, CRITICALLY ill
Abstract

Background: Convalescent plasma containing neutralising antibody to SARS-CoV-2 is under investigation for COVID-19 treatment. We report diverse virological characteristics of UK intensive care patients enrolled in the Immunoglobulin Domain of the REMAP-CAP randomised controlled trial that potentially influence treatment outcomes.Methods: SARS-CoV-2 RNA in nasopharyngeal swabs collected pre-treatment was quantified by PCR. Antibody status was determined by spike-protein ELISA. B.1.1.7 was differentiated from other SARS-CoV-2 strains using allele-specific probes or restriction site polymorphism (SfcI) targeting D1118H.Results: Of 1274 subjects, 90% were PCR-positive with viral loads 118-1.7x10 11 IU/ml. Median viral loads were 40-fold higher in those seronegative for IgG antibodies (n=354; 28%) compared to seropositives (n=939; 72%). Frequencies of B.1.1.7 increased from <1% in early November, 2020 to 82% of subjects in January 2021. Seronegative individuals with wild-type SARS-CoV-2 had significantly higher viral loads than seropositives (medians 5.8x10 6 and 2.0 x10 5 IU/ml respectively; p=2x10 -15). However, viral load distributions were elevated in both seronegative and seropositive subjects infected with B.1.1.7 (4.0x10 6 and 1.6x10 6 IU/ml respectively).Conclusions: High viral loads in seropositive B.1.1.7-infected subjects and resistance to seroconversion indicate less effective clearance by innate and adaptive immune responses. SARS-CoV-2 strain, viral loads and antibody status define subgroups for analysis of treatment efficacy. [ABSTRACT FROM AUTHOR]

Published
2021
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