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542 results on '"Chinnery, P"'

1. Posthospitalization COVID-19 cognitive deficits at 1 year are global and associated with elevated brain injury markers and gray matter volume reduction

Author: Wood, Greta K., Sargent, Brendan F., Ahmad, Zain-Ul-Abideen, Tharmaratnam, Kukatharmini, Dunai, Cordelia, Egbe, Franklyn N., Martin, Naomi H., Facer, Bethany, Pendered, Sophie L., Rogers, Henry C., Hübel, Christopher, van Wamelen, Daniel J., Bethlehem, Richard A. I., Giunchiglia, Valentina, Hellyer, Peter J., Trender, William, Kalsi, Gursharan, Needham, Edward, Easton, Ava, Jackson, Thomas A., Cunningham, Colm, Upthegrove, Rachel, Pollak, Thomas A., Hotopf, Matthew, Solomon, Tom, Pett, Sarah L., Shaw, Pamela J., Wood, Nicholas, Harrison, Neil A., Miller, Karla L., Jezzard, Peter, Williams, Guy, Duff, Eugene P., Williams, Steven, Zelaya, Fernando, Smith, Stephen M., Keller, Simon, Broome, Matthew, Kingston, Nathalie, Husain, Masud, Vincent, Angela, Bradley, John, Chinnery, Patrick, Menon, David K., Aggleton, John P., Nicholson, Timothy R., Taylor, John-Paul, David, Anthony S., Carson, Alan, Bullmore, Ed, Breen, Gerome, Hampshire, Adam, Michael, Benedict D., Paddick, Stella-Maria, and Leek, E. Charles
Published: 2024
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2. Retraction Note: Development and evaluation of rapid data-enabled access to routine clinical information to enhance early recruitment to the national clinical platform trial of COVID-19 community treatments

Author: Cake, Caroline, Ogburn, Emma, Pinches, Heather, Coleman, Garry, Seymour, David, Woodard, Fran, Manohar, Sinduja, Monsur, Marjia, Landray, Martin, Dalton, Gaynor, Morris, Andrew D., Chinnery, Patrick F., Hobbs, F. D. Richard, and Butler, Christopher
Published: 2024
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3. Author Correction: Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses

Author: Michael, Benedict D., Dunai, Cordelia, Needham, Edward J., Tharmaratnam, Kukatharmini, Williams, Robyn, Huang, Yun, Boardman, Sarah A., Clark, Jordan J., Sharma, Parul, Subramaniam, Krishanthi, Wood, Greta K., Collie, Ceryce, Digby, Richard, Ren, Alexander, Norton, Emma, Leibowitz, Maya, Ebrahimi, Soraya, Fower, Andrew, Fox, Hannah, Tato, Esteban, Ellul, Mark A., Sunderland, Geraint, Held, Marie, Hetherington, Claire, Egbe, Franklyn N., Palmos, Alish, Stirrups, Kathy, Grundmann, Alexander, Chiollaz, Anne-Cecile, Sanchez, Jean-Charles, Stewart, James P., Griffiths, Michael, Solomon, Tom, Breen, Gerome, Coles, Alasdair J., Kingston, Nathalie, Bradley, John R., Chinnery, Patrick F., Cavanagh, Jonathan, Irani, Sarosh R., Vincent, Angela, Baillie, J. Kenneth, Openshaw, Peter J., Semple, Malcolm G., Taams, Leonie S., and Menon, David K.
Published: 2024
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4. Dynamics of cognitive variability with age and its genetic underpinning in NIHR BioResource Genes and Cognition cohort participants

Author: Rahman, Md Shafiqur, Harrison, Emma, Biggs, Heather, Seikus, Chloe, Elliott, Paul, Breen, Gerome, Kingston, Nathalie, Bradley, John R., Hill, Steven M., Tom, Brian D. M., and Chinnery, Patrick F.
Published: 2024
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5. Clearance and transport of amyloid β by peripheral monocytes correlate with Alzheimer’s disease progression

Author: Xin Huang, Chris Fowler, Yihan Li, Qiao-Xin Li, Jiaqi Sun, Yijun Pan, Liang Jin, Keyla A. Perez, Céline Dubois, Yen Y. Lim, Candace Drysdale, Rebecca L. Rumble, Holly R. Chinnery, Christopher C. Rowe, Ralph N. Martins, Paul Maruff, James D. Doecke, Yong Lin, Abdel A. Belaidi, Kevin J. Barnham, Colin L. Masters, and Ben J. Gu
Subjects: Science
Abstract: Abstract Impaired clearance of amyloid β (Aβ) in late-onset Alzheimer’s disease (AD) affects disease progression. The role of peripheral monocytes in Aβ clearance from the central nervous system (CNS) is unclear. We use a flow cytometry assay to identify Aβ-binding monocytes in blood, validated by confocal microscopy, Western blotting, and mass spectrometry. Flow cytometry immunophenotyping and correlation with AD biomarkers are studied in 150 participants from the AIBL study. We also examine monocytes in human cerebrospinal fluid (CSF) and their migration in an APP/PS1 mouse model. The assay reveals macrophage-like Aβ-binding monocytes with high phagocytic potential in both the periphery and CNS. We find lower surface Aβ levels in mild cognitive impairment (MCI) and AD-dementia patients compared to cognitively unimpaired individuals. Monocyte infiltration from blood to CSF and migration from CNS to peripheral lymph nodes and blood are observed. Here we show that Aβ-binding monocytes may play a role in CNS Aβ clearance, suggesting their potential as a biomarker for AD diagnosis and monitoring.
Published: 2024
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6. Youth not engaged in education, employment, or training: a discrete choice experiment of service preferences in Canada

Author: Meaghen Quinlan-Davidson, Mahalia Dixon, Gina Chinnery, Lisa D. Hawke, Srividya Iyer, Katherine Moxness, Matthew Prebeg, Lehana Thabane, and J. L. Henderson
Subjects: Youth mental health and substance use, Youth not in education, Employment, Or training, Service preferences, Discrete choice experiment, Public aspects of medicine, RA1-1270
Abstract: Abstract Background Prior research has showed the importance of providing integrated support services to prevent and reduce youth not in education, employment, or training (NEET) related challenges. There is limited evidence on NEET youth’s perspectives and preferences for employment, education, and training services. The objective of this study was to identify employment, education and training service preferences of NEET youth. We acknowledge the deficit-based lens associated with the term NEET and use ‘upcoming youth’ to refer to this population group. Methods Canadian youth (14–29 years) who reported Upcoming status or at-risk of Upcoming status were recruited to the study. We used a discrete choice experiment (DCE) survey, which included ten attributes with three levels each indicating service characteristics. Sawtooth software was used to design and administer the DCE. Participants also provided demographic information and completed the Global Appraisal of Individual Needs–Short Screener. We analyzed the data using hierarchical Bayesian methods to determine service attribute importance and latent class analyses to identify groups of participants with similar service preferences. Results A total of n=503 youth participated in the study. 51% of participants were 24–29 years of age; 18.7% identified as having Upcoming status; 41.1% were from rural areas; and 36.0% of youth stated that they met basic needs with a little left. Participants strongly preferred services that promoted life skills, mentorship, basic income, and securing a work or educational placement. Three latent classes were identified and included: (i) job and educational services (38.9%), or services that include career counseling and securing a work or educational placement; (ii) mental health and wellness services (34.9%), or services that offer support for mental health and wellness in the workplace and free mental health and substance use services; and (iii) holistic skills building services (26.1%), or services that endorsed skills for school and job success, and life skills. Conclusions This study identified employment, education, and training service preferences among Upcoming youth. The findings indicate a need to create a service model that supports holistic skills building, mental health and wellness, and long-term school and job opportunities.
Published: 2024
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7. 7T MRI detects widespread brain iron deposition in neuroferritinopathy

Author: Alexander G. Murley, Catarina Rua, Heather Biggs, Christopher T. Rodgers, Tomasz Matys, Jelle van denAmeele, Rita Horvath, and Patrick F. Chinnery
Subjects: Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429
Abstract: Abstract Neuroferritinopathy is a disorder of neurodegeneration with brain iron accumulation that has no proven disease‐modifying treatments. Clinical trials require biomarkers of iron deposition. We examined brain iron accumulation in one presymptomatic FTL mutation carrier, two individuals with neuroferritinopathy and one healthy control using ultra‐high‐field 7T MRI. There was increased magnetic susceptibility, suggestive of iron deposition, in superficial and deep gray matter in both presymptomatic and symptomatic neuroferritinopathy. Cavitation of the putamen and globus pallidus increased with disease stage and at follow up. The widespread brain iron deposition in presymptomatic and early disease provides an opportunity for monitoring disease‐modifying intervention.
Published: 2024
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8. Retraction Note: Development and evaluation of rapid data-enabled access to routine clinical information to enhance early recruitment to the national clinical platform trial of COVID-19 community treatments

Author: Caroline Cake, Emma Ogburn, Heather Pinches, Garry Coleman, David Seymour, Fran Woodard, Sinduja Manohar, Marjia Monsur, Martin Landray, Gaynor Dalton, Andrew D. Morris, Patrick F. Chinnery, UK COVID-19 National Core Studies Consortium, F. D. Richard Hobbs, and Christopher Butler
Subjects: Medicine (General), R5-920
Abstract: This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s13063-021-05965-4.
Published: 2024
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9. Education Systems Response to COVID-19: Reflections on the Contributions of Research to USAID's Education and Resilience Agenda

Author: Jennifer Flemming, Ritesh Shah, Nina Weisenhorn, Julie Chinnery, and Gwendolyn Heaner
Abstract: Over the course of the COVID-19 pandemic, education systems have grappled with the complexity of protecting the wellbeing of learners and educators, along with ensuring learners' continued engagement with learning. This has led to an increasing number of calls to strengthen education-sector resilience to future shocks and stressors, particularly for the most marginalized, in order to maintain momentum toward achieving Sustainable Development Goal 4. Resilience has been and continues to be a key focal point for the US Agency for International Development (USAID), both across the agency and within its education portfolio. In this paper, we reflect on case study research in five contexts--Colombia, Georgia, Lebanon, Nigeria, and Zambia--during the COVID-19 pandemic and apply it to USAID's resilience framework for education. We identify practices and structures used in each context that were either operationalized or could be leveraged further to absorb, adapt, and ultimately transform these education systems when facing a pandemic and other types of stressors and shocks.
Published: 2023
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10. Evidence for sodium valproate toxicity in mitochondrial diseases: a systematic analysis

Author: Patrick F Chinnery, Rita Horvath, Nour Elkhateeb, Katherine Schon, Thiloka E Ratnaike, Angela Lochmüller, and Christopher Gilmartin
Subjects: Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Background We aimed to determine whether sodium valproate (VPA) should be contraindicated in all mitochondrial diseases, due to known VPA-induced severe hepatotoxicity in some mitochondrial diseases.Methods We systematically reviewed the published literature for mitochondrial DNA (mtDNA) and common nuclear genotypes of mitochondrial diseases using PubMed, Ovid Embase, Ovid Medline and MitoPhen databases. We extracted patient-level data from peer-reviewed articles, published until July 2022, using the Human Phenotype Ontology to manually code clinical presentations for 156 patients with genetic diagnoses from 90 publications.Results There were no fatal adverse drug reactions (ADRs) in the mtDNA disease group (35 patients), and only 1 out of 54 patients with a non-POLG mitochondrial disease developed acute liver failure. There were fatal outcomes in 53/102 (52%) POLG VPA-exposed patients who all harboured recessive mutations.Conclusions Our findings confirm the high risk of severe ADRs in any patient with recessive POLG variants irrespective of the phenotype, and therefore recommend that VPA is contraindicated in this group. However, there was limited evidence of toxicity to support a similar recommendation in other genotypes of mitochondrial diseases.
Published: 2024
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11. Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses

Author: Benedict D. Michael, Cordelia Dunai, Edward J. Needham, Kukatharmini Tharmaratnam, Robyn Williams, Yun Huang, Sarah A. Boardman, Jordan J. Clark, Parul Sharma, Krishanthi Subramaniam, Greta K. Wood, Ceryce Collie, Richard Digby, Alexander Ren, Emma Norton, Maya Leibowitz, Soraya Ebrahimi, Andrew Fower, Hannah Fox, Esteban Tato, Mark A. Ellul, Geraint Sunderland, Marie Held, Claire Hetherington, Franklyn N. Egbe, Alish Palmos, Kathy Stirrups, Alexander Grundmann, Anne-Cecile Chiollaz, Jean-Charles Sanchez, James P. Stewart, Michael Griffiths, Tom Solomon, Gerome Breen, Alasdair J. Coles, Nathalie Kingston, John R. Bradley, Patrick F. Chinnery, Jonathan Cavanagh, Sarosh R. Irani, Angela Vincent, J. Kenneth Baillie, Peter J. Openshaw, Malcolm G. Semple, ISARIC4C Investigators, COVID-CNS Consortium, Leonie S. Taams, and David K. Menon
Subjects: Science
Abstract: Abstract To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1–11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury. Autoantibodies are more common in COVID-19 than controls and some (including against MYL7, UCH-L1, and GRIN3B) are more frequent with altered consciousness. Additionally, convalescent participants with neurological complications show elevated GFAP and NfL, unrelated to attenuated systemic inflammatory mediators and to autoantibody responses. Overall, neurological complications of COVID-19 are associated with evidence of neuroglial injury in both acute and late disease and these correlate with dysregulated innate and adaptive immune responses acutely.
Published: 2023
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12. Nuclear genetic control of mtDNA copy number and heteroplasmy in humans

Author: Gupta, Rahul, Kanai, Masahiro, Durham, Timothy J., Tsuo, Kristin, McCoy, Jason G., Kotrys, Anna V., Zhou, Wei, Chinnery, Patrick F., Karczewski, Konrad J., Calvo, Sarah E., Neale, Benjamin M., and Mootha, Vamsi K.
Published: 2023
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13. Author Correction: Nuclear genetic control of mtDNA copy number and heteroplasmy in humans

Author: Gupta, Rahul, Kanai, Masahiro, Durham, Timothy J., Tsuo, Kristin, McCoy, Jason G., Kotrys, Anna V., Zhou, Wei, Chinnery, Patrick F., Karczewski, Konrad J., Calvo, Sarah E., Neale, Benjamin M., and Mootha, Vamsi K.
Published: 2024
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14. Toward a Bold Agenda for Moral Education

Author: Chinnery, Ann
Abstract: In his 2006 essay, "Moral Education's Modest Agenda," Robin Barrow argues for a clearly bounded conception of morality; he presents the moral domain as concerned with moral principles, and moral education as the cultivation of moral understanding. Barrow rejects behaviourism, character education, values clarification, developmentalism, and what he calls "the insidious influence of political and moral correctness" as practices and ideas that are irrelevant and inappropriate for moral education. While I share some of Barrow's concerns about some of these approaches, I believe he over-restricts the scope of legitimately moral concerns and what educators ought to do in the name of moral education. In this paper, I make a case for a broader and bolder agenda for moral education, putting the question of what constitutes a human life (which Barrow takes to be a non-moral question) at the very heart of morality and moral education.
Published: 2019

15. Building back better? The role of education sector responses in strengthening or eroding societal resilience during the COVID-19 pandemic

Author: Ritesh Shah, Jennifer Flemming, Julie Chinnery, and Gwen Heaner
Subjects: COVID-19, resilience, social capital, social cohesion, education, crisis, Education (General), L7-991
Abstract: COVID-19 laid bare many failings and shortcomings of state systems, institutions and structures which aim to protect citizens against harm. As observed from the outcomes of the pandemic in many parts of the Global South and Global North, the resilience of health, social protection, governance, economic, education, and social welfare systems has been significantly eroded or challenged, leaving large segments of the population open to heightened risk and vulnerability. This has been noted to have significantly eroded social capital, namely the trust, communication, and dialogue between citizens in the state as well as citizens with each other. Based on comparative research carried out on the return to schooling process in five countries, Lebanon, Nigeria, Colombia, Georgia, and Zambia, the paper highlights the important role and function that educational governance, decision-making, and control throughout the pandemic has played a key role in either maintaining or erode social capital, and ultimately the resilience of the entire education system. Much of this was based on how well state officials and local education officials both considered and communicated their actions to educators, students and their families. The importance of education as a site where both bridging and linking social capital is both strengthened, but also capitalized on is also discussed. Specifically, the paper highlights, using the example of COVID-19 education responses, how a state that is responsive and accountable to its citizenry in a time of crisis, stands the greatest chance of ensuring such periods do not lead to an erosion of social capital.
Published: 2024
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16. Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses

Author: Michael, Benedict D., Dunai, Cordelia, Needham, Edward J., Tharmaratnam, Kukatharmini, Williams, Robyn, Huang, Yun, Boardman, Sarah A., Clark, Jordan J., Sharma, Parul, Subramaniam, Krishanthi, Wood, Greta K., Collie, Ceryce, Digby, Richard, Ren, Alexander, Norton, Emma, Leibowitz, Maya, Ebrahimi, Soraya, Fower, Andrew, Fox, Hannah, Tato, Esteban, Ellul, Mark A., Sunderland, Geraint, Held, Marie, Hetherington, Claire, Egbe, Franklyn N., Palmos, Alish, Stirrups, Kathy, Grundmann, Alexander, Chiollaz, Anne-Cecile, Sanchez, Jean-Charles, Stewart, James P., Griffiths, Michael, Solomon, Tom, Breen, Gerome, Coles, Alasdair J., Kingston, Nathalie, Bradley, John R., Chinnery, Patrick F., Cavanagh, Jonathan, Irani, Sarosh R., Vincent, Angela, Baillie, J. Kenneth, Openshaw, Peter J., Semple, Malcolm G., Taams, Leonie S., and Menon, David K.
Published: 2023
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17. Correction: Development and evaluation of rapid data-enabled access to routine clinical information to enhance early recruitment to the national clinical platform trial of COVID-19 community treatments

Author: Cake, Caroline, Ogburn, Emma, Pinches, Heather, Coleman, Garry, Seymour, David, Woodard, Fran, Manohar, Sinduja, Monsur, Marjia, Landray, Martin, Dalton, Gaynor, Morris, Andrew D., Chinnery, Patrick F., Hobbs, F. D. Richard, and Butler, Christopher
Published: 2023
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18. Author Correction: Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses

Author: Benedict D. Michael, Cordelia Dunai, Edward J. Needham, Kukatharmini Tharmaratnam, Robyn Williams, Yun Huang, Sarah A. Boardman, Jordan J. Clark, Parul Sharma, Krishanthi Subramaniam, Greta K. Wood, Ceryce Collie, Richard Digby, Alexander Ren, Emma Norton, Maya Leibowitz, Soraya Ebrahimi, Andrew Fower, Hannah Fox, Esteban Tato, Mark A. Ellul, Geraint Sunderland, Marie Held, Claire Hetherington, Franklyn N. Egbe, Alish Palmos, Kathy Stirrups, Alexander Grundmann, Anne-Cecile Chiollaz, Jean-Charles Sanchez, James P. Stewart, Michael Griffiths, Tom Solomon, Gerome Breen, Alasdair J. Coles, Nathalie Kingston, John R. Bradley, Patrick F. Chinnery, Jonathan Cavanagh, Sarosh R. Irani, Angela Vincent, J. Kenneth Baillie, Peter J. Openshaw, Malcolm G. Semple, ISARIC4C Investigators, COVID-CNS Consortium, Leonie S. Taams, and David K. Menon
Subjects: Science
Published: 2024
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19. Case report: Mutations in DNAJC30 causing autosomal recessive Leber hereditary optic neuropathy are common amongst Eastern European individuals

Author: Toby Charles Major, Eszter Sara Arany, Katherine Schon, Magdolna Simo, Veronika Karcagi, Jelle van den Ameele, Patrick Yu Wai Man, Patrick F. Chinnery, Catarina Olimpio, and Rita Horvath
Subjects: Leber hereditary optic neuropathy (LHON), mitochondrial LHON (mtLHON), autosomal recessive LHON (arLHON), DNA-J heat shock protein family (Hsp40) member C30 (DNAJC30), G+%28p%2ETyr51Cys%29%22">c.152A>G (p.Tyr51Cys), recessive optic neuropathy, Neurology. Diseases of the nervous system, RC346-429
Abstract: BackgroundLeber Hereditary Optic Neuropathy (LHON) is the most common inherited mitochondrial disease characterized by bilateral, painless, subacute visual loss with a peak age of onset in the second to third decade. Historically, LHON was thought to be exclusively maternally inherited due to mutations in mitochondrial DNA (mtDNA); however, recent studies have identified an autosomal recessive form of LHON (arLHON) caused by point mutations in the nuclear gene, DNAJC30.Case PresentationsIn this study, we report the cases of three Eastern European individuals presenting with bilateral painless visual loss, one of whom was also exhibiting motor symptoms. After a several-year-long diagnostic journey, all three patients were found to carry the homozygous c.152A>G (p.Tyr51Cys) mutation in DNAJC30. This has been identified as the most common arLHON pathogenic variant and has been shown to exhibit a significant founder effect amongst Eastern European individuals.ConclusionThis finding adds to the growing cohort of patients with arLHON and demonstrates the importance of DNAJC30 screening in patients with molecularly undiagnosed LHON, particularly in Eastern European individuals. It is of heightened translational significance as patients diagnosed with arLHON exhibit a better prognosis and response to therapeutic treatment with the co-enzyme Q10 analog idebenone.
Published: 2023
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20. Correction to: A nonsynonymous mutation in PLCG2 reduces the risk of Alzheimer's disease, dementia with Lewy bodies and frontotemporal dementia, and increases the likelihood of longevity.

Author: van der Lee, Sven J, Conway, Olivia J, Jansen, Iris, Carrasquillo, Minerva M, Kleineidam, Luca, van den Akker, Erik, Hernández, Isabel, van Eijk, Kristel R, Stringa, Najada, Chen, Jason A, Zettergren, Anna, Andlauer, Till FM, Diez-Fairen, Monica, Simon-Sanchez, Javier, Lleó, Alberto, Zetterberg, Henrik, Nygaard, Marianne, Blauwendraat, Cornelis, Savage, Jeanne E, Mengel-From, Jonas, Moreno-Grau, Sonia, Wagner, Michael, Fortea, Juan, Keogh, Michael J, Blennow, Kaj, Skoog, Ingmar, Friese, Manuel A, Pletnikova, Olga, Zulaica, Miren, Lage, Carmen, de Rojas, Itziar, Riedel-Heller, Steffi, Illán-Gala, Ignacio, Wei, Wei, Jeune, Bernard, Orellana, Adelina, Then Bergh, Florian, Wang, Xue, Hulsman, Marc, Beker, Nina, Tesi, Niccolo, Morris, Christopher M, Indakoetxea, Begoña, Collij, Lyduine E, Scherer, Martin, Morenas-Rodríguez, Estrella, Ironside, James W, van Berckel, Bart NM, Alcolea, Daniel, Wiendl, Heinz, Strickland, Samantha L, Pastor, Pau, Rodríguez Rodríguez, Eloy, DESGESCO (Dementia Genetics Spanish Consortium), EADB (Alzheimer Disease European DNA biobank), IFGC (International FTD-Genomics Consortium), IPDGC (The International Parkinson Disease Genomics Consortium), RiMod-FTD (Risk and Modifying factors in Fronto-Temporal Dementia), Netherlands Brain Bank (NBB), Boeve, Bradley F, Petersen, Ronald C, Ferman, Tanis J, van Gerpen, Jay A, Reinders, Marcel JT, Uitti, Ryan J, Tárraga, Lluís, Maier, Wolfgang, Dols-Icardo, Oriol, Kawalia, Amit, Dalmasso, Maria Carolina, Boada, Mercè, Zettl, Uwe K, van Schoor, Natasja M, Beekman, Marian, Allen, Mariet, Masliah, Eliezer, de Munain, Adolfo López, Pantelyat, Alexander, Wszolek, Zbigniew K, Ross, Owen A, Dickson, Dennis W, Graff-Radford, Neill R, Knopman, David, Rademakers, Rosa, Lemstra, Afina W, Pijnenburg, Yolande AL, Scheltens, Philip, Gasser, Thomas, Chinnery, Patrick F, Hemmer, Bernhard, Huisman, Martijn A, Troncoso, Juan, Moreno, Fermin, Nohr, Ellen A, Sørensen, Thorkild IA, Heutink, Peter, Sánchez-Juan, Pascual, Posthuma, Danielle, GIFT (Genetic Investigation in Frontotemporal Dementia and Alzheimer’s Disease) Study Group, and Clarimón, Jordi
Subjects: DESGESCO, EADB, IFGC, IPDGC, RiMod-FTD, Netherlands Brain Bank, GIFT (Genetic Investigation in Frontotemporal Dementia and Alzheimer’s Disease) Study Group, Acquired Cognitive Impairment, Brain Disorders, Neurodegenerative, Alzheimer's Disease, Dementia, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Neurosciences, Aging, Parkinson's Disease, Genetics, 2.1 Biological and endogenous factors, Neurological, Neurology & Neurosurgery, Clinical Sciences
Abstract: The IPDGC (The International Parkinson Disease Genomics Consortium) and EADB (Alzheimer Disease European DNA biobank) are listed correctly as an author to the article, however, they were incorrectly listed more than once.
Published: 2020

21. Early economic benefits of perioperative nasojejunal tube feeding in non-critical care adult surgical patients with gastric feed intolerance

Author: Galya Chinnery, Anna-Lena du Toit, Chanel Robinson, Ilhaam Kippie, Eduard Jonas, and Matthias Scriba
Subjects: economic benefits, enteral nutrition, medium-term feeding, nasojejunal tubes, Nutrition. Foods and food supply, TX341-641, Nutritional diseases. Deficiency diseases, RC620-627
Abstract: Background: Fluoroscopy-guided endoscopic placement of nasojejunal tubes (NJT) for perioperative short- or medium-term enteral nutrition (EN) is potentially required for anatomical gastric feed intolerance. Methods: Indication for NJT and successful insertion rates was determined. NJT insertion costs were calculated and compared with central venous catheter (CVC) insertion. Duration of NJT patency in non-critical care surgical patients was determined in days in a local cohort. EN costs were calculated over a hypothetical 28-day period factoring in expected NJT replacements due to blockage and compared with parenteral nutrition (PN) via CVC, which included routine CVC changes every 10 days. Public and private sectors were compared. Results: One hundred and two (93.6%) NJTs were placed successfully, with gastric outlet obstruction the most frequent indication (40.4%) with a median 10 days’ (range 1–68 days, IQR 6–16.75 days) usage. Irrevocable blockage occurred in 33 tubes after a median 9 days (range 3–34 days; IQR 4.75–16 days). Calculated EN costs over 28 days, including NJT replacement every 9 days, reached US$1 676.12 and PN costs with CVC replacement every 10 days, US$3 461.35 (p
Published: 2023
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22. Nuclear-embedded mitochondrial DNA sequences in 66,083 human genomes

Author: Wei, Wei, Schon, Katherine R., Elgar, Greg, Orioli, Andrea, Tanguy, Melanie, Giess, Adam, Tischkowitz, Marc, Caulfield, Mark J., and Chinnery, Patrick F.
Published: 2022
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23. In vivo micro-computed tomography imaging in liver tumor study of mice using Fenestra VC and Fenestra HDVC

Author: Ming Jia Tan, Nazarine Fernandes, Karla Chinnery Williams, and Nancy Lee Ford
Subjects: Medicine, Science
Abstract: Abstract Contrast agents are used to enhance the visibility of rodent organs during in vivo micro-computed tomography imaging. Specifically, this non-invasive technique can study liver tumor growth and progression in small animals. Fenestra VC and the novel Fenestra HDVC were compared for enhancement in the liver of healthy and tumor-bearing mice, and the images were compared for their ability to define the tumor border, volume and quantity of tumors. Fenestra VC and Fenestra HDVC were injected into healthy eight-week-old female mice (C57BL/6) via the tail vein then imaged at seven different time points. The experimental results showed that 0.005 mL/g of Fenestra HDVC resulted in the same enhancement for all eight organs as 0.01 mL/g of Fenestra VC across all time points. For the tumor study, B16F10 tumors were surgically introduced into ten eight-week-old female mice (C57BL/6) then imaged in vivo over a 3 day period. Ex vivo micro-CT images of the excised livers were also obtained. The tumor volume and quantity were measured in each image, and the tumour progression observed over 3 days. We showed Fenestra HDVC is effective for in vivo imaging in rodents because the optimal enhancement level in organs is maintained at a reduced injection volume.
Published: 2022
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24. Ocular development after highly effective modulator treatment early in life

Author: Yimin Zhu, Danni Li, Felisa Reyes-Ortega, Holly R. Chinnery, and Elena K. Schneider-Futschik
Subjects: cystic fibrosis, ocular development, CFTR modulator, catarat, eye malformations, Therapeutics. Pharmacology, RM1-950
Abstract: Highly effective cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulator therapies (HEMT), including elexacaftor-tezacaftor-ivacaftor, correct the underlying molecular defect causing CF. HEMT decreases general symptom burden by improving clinical metrics and quality of life for most people with CF (PwCF) with eligible CFTR variants. This has resulted in more pregnancies in women living with CF. All HEMT are known to be able pass through the placenta and into breast milk in mothers who continue on this therapy while pregnant and breast feeding. Toxicity studies of HEMT in young rats demonstrated infant cataracts, and case reports have reported the presence of congenital cataracts in early life exposure to HEMT. This article reviews the evidence for how HEMT influences the dynamic and interdependent processes of healthy and abnormal lens development in the context of HEMT exposure during pregnancy and breastfeeding, and raises questions that remain unanswered.
Published: 2023
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25. Domperidone: Pharmacists Stimulating Clinical Change for Lactation Consultants

Author: Katherine Chinnery, Stephanie Wai Khuan Teoh, Tamara Lebedevs, and Myra Kildunne
Subjects: domperidone, galactagogue, lactation insufficiency, lactation consultant, General Works
Abstract: Domperidone is a commonly prescribed galactagogue used off-label for lactation insufficiency. Prescriber unfamiliarity or safety concerns can lead to therapeutic delay and potential early breastfeeding discontinuation. To facilitate access, the study site pharmacy department developed a structured administration and supply arrangement (SASA) for International Board Certified Lactation Consultants to screen and initiate domperidone using a checklist. The study aimed to validate a domperidone screening tool via an analysis of its use and compliance. Records were extracted from the RedCAP® database for the first 50 women with a documented domperidone supply and reviewed against medical records. A staff survey was distributed assessing compliance and attitudes towards the SASA. Records of supply from the RedCAP® database revealed 34% (17/50) of patients were referred to a physician, revealing a discrepancy between RedCAP® reporting and checklists as no referrals were documented. Overall staff satisfaction with the SASA was rated 4.6/5. In total, 77.7% (7/9) felt confident counselling and supplying domperidone with the SASA in place, and 88.9% (8/9) felt confident using the checklist to identify the appropriateness of therapy and referral to a physician. Only 55.6% (5/9) indicated the checklist was used with each screening. The SASA education package is being updated to clarify the requirements for checklist completion and standardise frameworks to document follow-up.
Published: 2024
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26. A nonsynonymous mutation in PLCG2 reduces the risk of Alzheimer's disease, dementia with Lewy bodies and frontotemporal dementia, and increases the likelihood of longevity.

Author: van der Lee, Sven J, Conway, Olivia J, Jansen, Iris, Carrasquillo, Minerva M, Kleineidam, Luca, van den Akker, Erik, Hernández, Isabel, van Eijk, Kristel R, Stringa, Najada, Chen, Jason A, Zettergren, Anna, Andlauer, Till FM, Diez-Fairen, Monica, Simon-Sanchez, Javier, Lleó, Alberto, Zetterberg, Henrik, Nygaard, Marianne, Blauwendraat, Cornelis, Savage, Jeanne E, Mengel-From, Jonas, Moreno-Grau, Sonia, Wagner, Michael, Fortea, Juan, Keogh, Michael J, Blennow, Kaj, Skoog, Ingmar, Friese, Manuel A, Pletnikova, Olga, Zulaica, Miren, Lage, Carmen, de Rojas, Itziar, Riedel-Heller, Steffi, Illán-Gala, Ignacio, Wei, Wei, Jeune, Bernard, Orellana, Adelina, Then Bergh, Florian, Wang, Xue, Hulsman, Marc, Beker, Nina, Tesi, Niccolo, Morris, Christopher M, Indakoetxea, Begoña, Collij, Lyduine E, Scherer, Martin, Morenas-Rodríguez, Estrella, Ironside, James W, van Berckel, Bart NM, Alcolea, Daniel, Wiendl, Heinz, Strickland, Samantha L, Pastor, Pau, Rodríguez Rodríguez, Eloy, DESGESCO (Dementia Genetics Spanish Consortium), EADB (Alzheimer Disease European DNA biobank), EADB (Alzheimer Disease European DNA biobank), IFGC (International FTD-Genomics Consortium), IPDGC (The International Parkinson Disease Genomics Consortium), IPDGC (The International Parkinson Disease Genomics Consortium), RiMod-FTD (Risk and Modifying factors in Fronto-Temporal Dementia), Netherlands Brain Bank (NBB), Boeve, Bradley F, Petersen, Ronald C, Ferman, Tanis J, van Gerpen, Jay A, Reinders, Marcel JT, Uitti, Ryan J, Tárraga, Lluís, Maier, Wolfgang, Dols-Icardo, Oriol, Kawalia, Amit, Dalmasso, Maria Carolina, Boada, Mercè, Zettl, Uwe K, van Schoor, Natasja M, Beekman, Marian, Allen, Mariet, Masliah, Eliezer, de Munain, Adolfo López, Pantelyat, Alexander, Wszolek, Zbigniew K, Ross, Owen A, Dickson, Dennis W, Graff-Radford, Neill R, Knopman, David, Rademakers, Rosa, Lemstra, Afina W, Pijnenburg, Yolande AL, Scheltens, Philip, Gasser, Thomas, Chinnery, Patrick F, Hemmer, Bernhard, Huisman, Martijn A, Troncoso, Juan, Moreno, Fermin, Nohr, Ellen A, Sørensen, Thorkild IA, Heutink, Peter, Sánchez-Juan, Pascual, Posthuma, Danielle, GIFT (Genetic Investigation in Frontotemporal Dementia and Alzheimer’s Disease) Study Group, and Clarimón, Jordi
Subjects: DESGESCO (Dementia Genetics Spanish Consortium), EADB, EADB, IFGC (International FTD-Genomics Consortium), IPDGC, IPDGC, RiMod-FTD, Netherlands Brain Bank, GIFT (Genetic Investigation in Frontotemporal Dementia and Alzheimer’s Disease) Study Group, Alzheimer’s disease, Amyotrophic lateral sclerosis, Dementia with Lewy bodies, Frontotemporal dementia, Longevity, Multiple sclerosis, Neurodegenerative disease, PLCG2, Parkinson’s disease, Phospholipase C Gamma 2, Progressive supranuclear palsy, Alzheimer's disease, Parkinson's disease, Alzheimer's Disease, frontotemporal dementia, dementia with Lewy-bodies, progressive suprauclear palsy, Parkinson's Disease, amyotrophic lateral sclerosis, multiple sclerosis, neurodegenerative disease, longevity, Clinical Sciences, Neurosciences, Neurology & Neurosurgery
Abstract: The genetic variant rs72824905-G (minor allele) in the PLCG2 gene was previously associated with a reduced Alzheimer's disease risk (AD). The role of PLCG2 in immune system signaling suggests it may also protect against other neurodegenerative diseases and possibly associates with longevity. We studied the effect of the rs72824905-G on seven neurodegenerative diseases and longevity, using 53,627 patients, 3,516 long-lived individuals and 149,290 study-matched controls. We replicated the association of rs72824905-G with reduced AD risk and we found an association with reduced risk of dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD). We did not find evidence for an effect on Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) risks, despite adequate sample sizes. Conversely, the rs72824905-G allele was associated with increased likelihood of longevity. By-proxy analyses in the UK Biobank supported the associations with both dementia and longevity. Concluding, rs72824905-G has a protective effect against multiple neurodegenerative diseases indicating shared aspects of disease etiology. Our findings merit studying the PLCγ2 pathway as drug-target.
Published: 2019

27. Cell-Free Mitochondrial DNA in Acute Brain Injury

Author: Saeed Kayhanian, Angelos Glynos, Richard Mair, Andras Lakatos, Peter J.A. Hutchinson, Adel E. Helmy, and Patrick F. Chinnery
Subjects: acute brain injury, brain inflammation, DAMP, mitochondrial DNA, subarachnoid hemorrhage, traumatic brain injury, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Traumatic brain injury and aneurysmal subarachnoid haemorrhage are a major cause of morbidity and mortality worldwide. Treatment options remain limited and are hampered by our understanding of the cellular and molecular mechanisms, including the inflammatory response observed in the brain. Mitochondrial DNA (mtDNA) has been shown to activate an innate inflammatory response by acting as a damage-associated molecular pattern (DAMP). Here, we show raised circulating cell-free (ccf) mtDNA levels in both cerebrospinal fluid (CSF) and serum within 48?h of brain injury. CSF ccf-mtDNA levels correlated with clinical severity and the interleukin-6 cytokine response. These findings support the use of ccf-mtDNA as a biomarker after acute brain injury linked to the inflammatory disease mechanism.
Published: 2022
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28. Gastrointestinal stromal tumours in patients presenting to an academic hospital in South Africa

Author: Barbara M. Robertson, Galya E. Chinnery, Michael L. Locketz, Michelle Parker, Alvera A. Vorster, Raj Ramesar, Eugenio Panieri, and Alistair J. Hunter
Subjects: gastrointestinal stromal tumours, africa, treatment, imatinib, mutations, survival, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Background: Published information on African patients with gastrointestinal stromal tumours (GISTs) is limited. Aim: The aim of this study was to review patient and tumour characteristics, and treatment, for a cohort of African patients and compare findings to studies from other centres. Setting: Groote Schuur Hospital, South Africa. Methods: Data were collected on all patients referred to Groote Schuur Hospital (GSH) during the period October 2003 to November 2019, including demographics, tumour characteristics and treatment outcomes. Results: There were 124 patients in total. There was a slight male predominance (55.6%) and the median age was 56 years. The most common primary tumour sites were the stomach (66.2%) and small bowel (21.8%) with a median primary tumour diameter of 95.5 mm. Mutational analysis was conducted for 39 patients with 66.7% of these patients having mutations in KIT exon 11. The primary tumour was resected in 72 patients, with 48.6% having high-risk tumours according to the National Institutes of Health (NIH) risk assessment. The 10-year overall survival (OS) values for patients by risk group were 83% (very low and low risk), 73% (intermediate risk) and 66% (high risk). The disease control rate for patients treated with imatinib was 84.6%. The median progression-free survival (PFS) for patients treated with imatinib for palliation was 23 months with OS of 31 months. Conclusion: In contrast to patients from other centres, our patients were younger and had larger tumours. Contribution: The distribution of primary tumour site, mutational analysis and response to imatinib was consistent with the literature.
Published: 2023
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29. The effect of topical decorin on temporal changes to corneal immune cells after epithelial abrasion

Author: Mengliang Wu, Laura E. Downie, Lisa J. Hill, and Holly R. Chinnery
Subjects: Decorin, Small leucine-rich proteoglycan, Dendritic cells, Macrophages, Neutrophils, Nerve regeneration, Neurology. Diseases of the nervous system, RC346-429
Abstract: Abstract Background Corneal immune cells interact with corneal sensory nerves during both homeostasis and inflammation. This study sought to evaluate temporal changes to corneal immune cell density in a mouse model of epithelial abrasion and nerve injury, and to investigate the immunomodulatory effects of topical decorin, which we have shown previously to promote corneal nerve regeneration. Methods Bilateral corneal epithelial abrasions (2 mm) were performed on C57BL/6J mice. Topical decorin or saline eye drops were applied three times daily for 12 h, 24 h, 3 days or 5 days. Optical coherence tomography imaging was performed to measure the abrasion area. The densities of corneal sensory nerves (β-tubulin III) and immune cells, including dendritic cells (DCs; CD11c+), macrophages (Iba-1+) and neutrophils (NIMP-R14+) were measured. Cx3cr1gfp/gfp mice that spontaneously lack resident corneal intraepithelial DCs were used to investigate the specific contribution of epithelial DCs. Neuropeptide and cytokine gene expression was evaluated using qRT-PCR at 12 h post-injury. Results In decorin-treated corneas, higher intraepithelial DC densities and lower neutrophil densities were observed at 24 h after injury, compared to saline controls. At 12 h post-injury, topical decorin application was associated with greater re-epithelialisation. At 5 days post-injury, corneal stromal macrophage density in the decorin-treated and contralateral eyes was lower, and nerve density was higher, compared to eyes treated with saline only. Lower expression of transforming growth factor beta (TGF-β) and higher expression of CSPG4 mRNA was detected in corneas treated with topical decorin. There was no difference in corneal neutrophil density in Cx3cr1gfp/gfp mice treated with or without decorin at 12 h. Conclusions Topical decorin regulates immune cell dynamics after corneal injury, by inhibiting neutrophils and recruiting intraepithelial DCs during the acute phase (
Published: 2022
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30. RETRACTED ARTICLE: Development and evaluation of rapid data-enabled access to routine clinical information to enhance early recruitment to the national clinical platform trial of COVID-19 community treatments

Author: Caroline Cake, Emma Ogburn, Heather Pinches, Garry Coleman, David Seymour, Fran Woodard, Sinduja Manohar, Marjia Monsur, Martin Landray, Gaynor Dalton, Andrew D. Morris, Patrick F. Chinnery, UK COVID-19 National Core Studies Consortium, F. D. Richard Hobbs, and Christopher Butler
Subjects: COVID-19, Data, Healthcare, Clinical trials, Public and patient involvement and engagement, Recruitment, Medicine (General), R5-920
Abstract: Abstract Background The COVID-19 pandemic has presented unique challenges for rapidly designing, initiating, and delivering therapeutic clinical trials. PRINCIPLE (Platform Randomised Trial of Treatments in the Community for Epidemic and Pandemic Illnesses) is the UK national platform investigating repurposed therapies for COVID-19 treatment of older people in the community at high risk of complications. Standard methods of patient recruitment were failing to meet the required pace and scale of enrolment. This paper describes the development and appraisal of a near real-time, data-driven, ethical approach for enhancing recruitment in community care by contacting people with a recent COVID-19 positive test result from the central NHS Test and Trace service within approximately 24–48 h of their test result. Methods A multi-disciplinary team was formed to solve the technical, ethical, public perception, logistical and information governance issues required to provide a near-real time (approximately within 24–48 h of receiving a positive test) feed of potential trial participants from test result data to the research team. PRINCIPLE was also given unique access to the Summary Care Record (SCR) to ensure safe prescribing, and to enable the trial team to quickly and safely bring consented patients into the trial. A survey of the public was used to understand public perceptions of the use of test data for this proposed methodology. Results Prior to establishing the data service, PRINCIPLE registered on average 87 participants per week. This increased by up to 87 additional people registered per week from the test data, contributing to an increase from 1013 recruits to PRINCIPLE at the start of October 2020 to 2802 recruits by 20 December 2020. Whilst procedural caveats were identified by the public consultation, out of 2639 people contacted by PRINCIPLE following a positive test result, no one raised a concern about being approached. Conclusions This paper describes a novel approach to using near-real time NHS operational data to recruit community-based patients within a few days of presentation with acute illness. This approach increased recruitment and reduced time between positive test and randomisation, allowing more rapid evaluation of treatments and increased safety for participants. End-to-end public and patient involvement in the design of the approach provided evidence to inform information governance decisions. Trial registration PRINCIPLE is funded by UK Research and Innovation and the Department of Health and Social Care through the National Institute for Health Research. EudraCT number: 2020-001209-22 . 26/03/2020 ISRCTN registry: ISRCTN86534580 . 20/03/2020 REC number: 20/SC/058 IRAS number: 281958
Published: 2022
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31. Complement lectin pathway activation is associated with COVID-19 disease severity, independent of MBL2 genotype subgroups

Author: Lisa Hurler, Ágnes Szilágyi, Federica Mescia, Laura Bergamaschi, Blanka Mező, György Sinkovits, Marienn Réti, Veronika Müller, Zsolt Iványi, János Gál, László Gopcsa, Péter Reményi, Beáta Szathmáry, Botond Lakatos, János Szlávik, Ilona Bobek, Zita Z. Prohászka, Zsolt Förhécz, Dorottya Csuka, Erika Kajdácsi, László Cervenak, Petra Kiszel, Tamás Masszi, István Vályi-Nagy, Reinhard Würzner, Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) COVID BioResource Collaboration, Paul A. Lyons, Erik J. M. Toonen, Zoltán Prohászka, Stephen Baker, John R. Bradley, Patrick F. Chinnery, Daniel J. Cooper, Gordon Dougan, Ian G. Goodfellow, Ravindra K. Gupta, Nathalie Kingston, Paul J. Lehner, Nicholas J. Matheson, Caroline Saunders, Kenneth G. C. Smith, Charlotte Summers, James Thaventhiran, M. Estee Torok, Mark R. Toshner, Michael P. Weekes, Gisele Alvio, Sharon Baker, Areti Bermperi, Karen Brookes, Ashlea Bucke, Jo Calder, Laura Canna, Cherry Crucusio, Isabel Cruz, Rnalie de Jesus, Katie Dempsey, Giovanni Di Stephano, Jason Domingo, Anne Elmer, Julie Harris, Sarah Hewitt, Heather Jones, Sherly Jose, Jane Kennet, Yvonne King, Jenny Kourampa, Emily Li, Caroline McMahon, Anne Meadows, Vivien Mendoza, Criona O’Brien, Charmain Ocaya, Ciro Pascuale, Marlyn Perales, Jane Price, Rebecca Rastall, Carla Ribeiro, Jane Rowlands, Valentina Ruffolo, Hugo Tordesillas, Phoebe Vargas, Bensi Vergese, Laura Watson, Jieniean Worsley, Julie-Ann Zerrudo, Ariana Betancourt, Georgie Bower, Ben Bullman, Chiara Cossetti, Aloka De Sa, Benjamin J. Dunore, Maddie Epping, Stuart Fawke, Stefan Gräf, Richard Grenfell, Andrew Hinch, Josh Hodgson, Christopher Huang, Oisin Huhn, Kelvin Hunter, Isobel Jarvis, Emma Jones, Maša Josipović, Ekaterina Legchenko, Daniel Lewis, Joe Marsden, Jennifer Martin, Francesca Nice, Ciara O’Donnell, Ommar Omarjee, Marianne Perera, Linda Pointon, Nicole Pond, Nathan Richoz, Nika Romashova, Natalia Savoinykh, Rahul Sharma, Joy Shih, Mateusz Strezlecki, Rachel Sutcliffe, Tobias Tilly, Zhen Tong, Carmen Treacy, Lori Turner, Jennifer Wood, Marta Wylot, John Allison, Heather Biggs, Helen Butcher, Daniela Caputo, Debbie Clapham-Riley, Eleanor Dewhurst, Christian Fernandez, Anita Furlong, Barbara Graves, Jennifer Gray, Tasmin Ivers, Emma Le Gresley, Rachel Linger, Mary Kasanicki, Sarah Meloy, Francesca Muldoon, Nigel Ovington, Sofia Papadia, Christopher J. Penkett, Isabel Phelan, Venkatesh Ranganath, Jennifer Sambrook, Katherine Schon, Hannah Stark, Kathleen E. Stirrups, Paul Townsend, Julie von Ziegenweidt, Jennifer Webster, Ali Asaripour, Lucy Mwaura, Caroline Patterson, Gary Polwarth, Katherine Bunclark, Michael Mackay, Alice Michael, Sabrina Rossi, Mayurun Selvan, Sarah Spencer, Cissy Yong, and Petra Polgarova
Subjects: mannose binding lectin (MBL), MBL2 genotypes, COVID-19, severe acute respiratory coronavirus 2 (SARS-CoV-2), lectin pathway activation, lectin pathway of complement, Immunologic diseases. Allergy, RC581-607
Abstract: IntroductionWhile complement is a contributor to disease severity in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, all three complement pathways might be activated by the virus. Lectin pathway activation occurs through different pattern recognition molecules, including mannan binding lectin (MBL), a protein shown to interact with SARS-CoV-2 proteins. However, the exact role of lectin pathway activation and its key pattern recognition molecule MBL in COVID-19 is still not fully understood.MethodsWe therefore investigated activation of the lectin pathway in two independent cohorts of SARS-CoV-2 infected patients, while also analysing MBL protein levels and potential effects of the six major single nucleotide polymorphisms (SNPs) found in the MBL2 gene on COVID-19 severity and outcome.ResultsWe show that the lectin pathway is activated in acute COVID-19, indicated by the correlation between complement activation product levels of the MASP-1/C1-INH complex (p=0.0011) and C4d (p
Published: 2023
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32. Precision mitochondrial medicine

Author: Patrick F. Chinnery
Subjects: genetic polymorphism, genetic risk score, genetics, genomics, metabolic diseases, Internal medicine, RC31-1245, Therapeutics. Pharmacology, RM1-950
Abstract: Mitochondria play a key role in cell homeostasis as a major source of intracellular energy (adenosine triphosphate), and as metabolic hubs regulating many canonical cell processes. Mitochondrial dysfunction has been widely documented in many common diseases, and genetic studies point towards a causal role in the pathogenesis of specific late-onset disorder. Together this makes targeting mitochondrial genes an attractive strategy for precision medicine. However, the genetics of mitochondrial biogenesis is complex, with over 1,100 candidate genes found in two different genomes: the nuclear DNA and mitochondrial DNA (mtDNA). Here, we review the current evidence associating mitochondrial genetic variants with distinct clinical phenotypes, with some having clear therapeutic implications. The strongest evidence has emerged through the investigation of rare inherited mitochondrial disorders, but genome-wide association studies also implicate mtDNA variants in the risk of developing common diseases, opening to door for the incorporation of mitochondrial genetic variant analysis in population disease risk stratification.
Published: 2023
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33. A role for BCL2L13 and autophagy in germline purifying selection of mtDNA.

Author: Laura S Kremer, Lyuba V Bozhilova, Diana Rubalcava-Gracia, Roberta Filograna, Mamta Upadhyay, Camilla Koolmeister, Patrick F Chinnery, and Nils-Göran Larsson
Subjects: Genetics, QH426-470
Abstract: Mammalian mitochondrial DNA (mtDNA) is inherited uniparentally through the female germline without undergoing recombination. This poses a major problem as deleterious mtDNA mutations must be eliminated to avoid a mutational meltdown over generations. At least two mechanisms that can decrease the mutation load during maternal transmission are operational: a stochastic bottleneck for mtDNA transmission from mother to child, and a directed purifying selection against transmission of deleterious mtDNA mutations. However, the molecular mechanisms controlling these processes remain unknown. In this study, we systematically tested whether decreased autophagy contributes to purifying selection by crossing the C5024T mouse model harbouring a single pathogenic heteroplasmic mutation in the tRNAAla gene of the mtDNA with different autophagy-deficient mouse models, including knockouts of Parkin, Bcl2l13, Ulk1, and Ulk2. Our study reveals a statistically robust effect of knockout of Bcl2l13 on the selection process, and weaker evidence for the effect of Ulk1 and potentially Ulk2, while no statistically significant impact is seen for knockout of Parkin. This points at distinctive roles of these players in germline purifying selection. Overall, our approach provides a framework for investigating the roles of other important factors involved in the enigmatic process of purifying selection and guides further investigations for the role of BCL2L13 in the elimination of non-synonymous mutations in protein-coding genes.
Published: 2023
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34. RETRACTED ARTICLE: Development and evaluation of rapid data-enabled access to routine clinical information to enhance early recruitment to the national clinical platform trial of COVID-19 community treatments

Author: Cake, Caroline, Ogburn, Emma, Pinches, Heather, Coleman, Garry, Seymour, David, Woodard, Fran, Manohar, Sinduja, Monsur, Marjia, Landray, Martin, Dalton, Gaynor, Morris, Andrew D., Chinnery, Patrick F., Hobbs, F. D. Richard, and Butler, Christopher
Published: 2022
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35. The effect of topical decorin on temporal changes to corneal immune cells after epithelial abrasion

Author: Wu, Mengliang, Downie, Laura E., Hill, Lisa J., and Chinnery, Holly R.
Published: 2022
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36. In vivo micro-computed tomography imaging in liver tumor study of mice using Fenestra VC and Fenestra HDVC

Author: Tan, Ming Jia, Fernandes, Nazarine, Williams, Karla Chinnery, and Ford, Nancy Lee
Published: 2022
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37. Distinction of early complement classical and lectin pathway activation via quantification of C1s/C1-INH and MASP-1/C1-INH complexes using novel ELISAs

Author: Lisa Hurler, Erik J. M. Toonen, Erika Kajdácsi, Bregje van Bree, Ricardo J. M. G. E. Brandwijk, Wieke de Bruin, Paul A. Lyons, Laura Bergamaschi, Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) COVID BioResource Collaboration, György Sinkovits, László Cervenak, Reinhard Würzner, Zoltán Prohászka, Stephen Baker, John R. Bradley, Patrick F. Chinnery, Daniel J. Cooper, Gordon Dougan, Ian G. Goodfellow, Ravindra K. Gupta, Nathalie Kingston, Paul J. Lehner, Nicholas J. Matheson, Caroline Saunders, Kenneth G. C. Smith, Charlotte Summers, James Thaventhiran, M. Estee Torok, Mark R. Toshner, Michael P. Weekes, Gisele Alvio, Sharon Baker, Areti Bermperi, Karen Brookes, Ashlea Bucke, Jo Calder, Laura Canna, Cherry Crucusio, Isabel Cruz, Rnalie de Jesus, Katie Dempsey, Giovanni Di Stephano, Jason Domingo, Anne Elmer, Julie Harris, Sarah Hewitt, Heather Jones, Sherly Jose, Jane Kennet, Yvonne King, Jenny Kourampa, Emily Li, Caroline McMahon, Anne Meadows, Vivien Mendoza, Criona O’Brien, Charmain Ocaya, Ciro Pascuale, Marlyn Perales, Jane Price, Rebecca Rastall, Carla Ribeiro, Jane Rowlands, Valentina Ruffolo, Hugo Tordesillas, Phoebe Vargas, Bensi Vergese, Laura Watson, Jieniean Worsley, Julie-Ann Zerrudo, Ariana Betancourt, Georgie Bower, Ben Bullman, Chiara Cossetti, Aloka De Sa, Benjamin J. Dunore, Maddie Epping, Stuart Fawke, Stefan Gräf, Richard Grenfell, Andrew Hinch, Josh Hodgson, Christopher Huang, Oisin Huhn, Kelvin Hunter, Isobel Jarvis, Emma Jones, Maša Josipović, Ekaterina Legchenko, Daniel Lewis, Joe Marsden, Jennifer Martin, Federica Mescia, Francesca Nice, Ciara O’Donnell, Ommar Omarjee, Marianne Perera, Linda Pointon, Nicole Pond, Nathan Richoz, Nika Romashova, Natalia Savoinykh, Rahul Sharma, Joy Shih, Mateusz Strezlecki, Rachel Sutcliffe, Tobias Tilly, Zhen Tong, Carmen Treacy, Lori Turner, Jennifer Wood, Marta Wylot, John Allison, Heather Biggs, Helen Butcher, Daniela Caputo, Debbie Clapham-Riley, Eleanor Dewhurst, Christian Fernandez, Anita Furlong, Barbara Graves, Jennifer Gray, Tasmin Ivers, Emma Le Gresley, Rachel Linger, Mary Kasanicki, Sarah Meloy, Francesca Muldoon, Nigel Ovington, Sofia Papadia, Christopher J. Penkett, Isabel Phelan, Venkatesh Ranganath, Jennifer Sambrook, Katherine Schon, Hannah Stark, Kathleen E. Stirrups, Paul Townsend, Julie von Ziegenweidt, Jennifer Webster, Ali Asaripour, Lucy Mwaura, Caroline Patterson, Gary Polwarth, Katherine Bunclark, Michael Mackay, Alice Michael, Sabrina Rossi, Mayurun Selvan, Sarah Spencer, Cissy Yong, and Petra Polgarova
Subjects: early complement activation, classical pathway activation, lectin pathway activation, C1-INH complexes, assay development and validation, C1s/C1-INH complex, Immunologic diseases. Allergy, RC581-607
Abstract: The most commonly used markers to assess complement activation are split products that are produced through activation of all three pathways and are located downstream of C3. In contrast, C4d derives from the cleavage of C4 and indicates either classical (CP) or lectin pathway (LP) activation. Although C4d is perfectly able to distinguish between CP/LP and alternative pathway (AP) activation, no well-established markers are available to differentiate between early CP and LP activation. Active enzymes of both pathways (C1s/C1r for the CP, MASP-1/MASP-2 for the LP) are regulated by C1 esterase inhibitor (C1-INH) through the formation of covalent complexes. Aim of this study was to develop validated immunoassays detecting C1s/C1-INH and MASP-1/C1-INH complex levels. Measurement of the complexes reveals information about the involvement of the respective pathways in complement-mediated diseases. Two sandwich ELISAs detecting C1s/C1-INH and MASP-1/C1-INH complex were developed and tested thoroughly, and it was investigated whether C1s/C1-INH and MASP-1/C1-INH complexes could serve as markers for either early CP or LP activation. In addition, a reference range for these complexes in healthy adults was defined, and the assays were clinically validated utilizing samples of 414 COVID-19 patients and 96 healthy controls. The immunoassays can reliably measure C1s/C1-INH and MASP-1/C1-INH complex concentrations in EDTA plasma from healthy and diseased individuals. Both complex levels are increased in serum when activated with zymosan, making them suitable markers for early classical and early lectin pathway activation. Furthermore, measurements of C1-INH complexes in 96 healthy adults showed normally distributed C1s/C1-INH complex levels with a physiological concentration of 1846 ± 1060 ng/mL (mean ± 2SD) and right-skewed distribution of MASP-1/C1-INH complex levels with a median concentration of 36.9 (13.18 - 87.89) ng/mL (2.5-97.5 percentile range), while levels of both complexes were increased in COVID-19 patients (p
Published: 2022
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38. Levels of soluble complement regulators predict severity of COVID-19 symptoms

Author: Anna L. Tierney, Wajd Mohammed Alali, Thomas Scott, Karen S. Rees-Unwin, CITIID-NIHR BioResource COVID-19 Collaboration, Simon J. Clark, Richard D. Unwin, Stephen Baker, John Bradley, Patrick Chinnery, Daniel Cooper, Gordon Dougan, Ian Goodfellow, Ravindra Gupta, Nathalie Kingston, Paul J. Lehner, Paul A. Lyons, Nicholas J. Matheson, Caroline Saunders, Kenneth G. C. Smith, Charlotte Summers, James Thaventhiran, M. Estee Torok, Mark R. Toshner, Michael P. Weekes, Gisele Alvio, Sharon Baker, Areti Bermperi, Karen Brookes, Ashlea Bucke, Jo Calder, Laura Canna, Cherry Crucusio, Isabel Cruz, Ranalie de Jesus, Katie Dempsey, Giovanni Di Stephano, Jason Domingo, Anne Elmer, Julie Harris, Sarah Hewitt, Heather Jones, Sherly Jose, Jane Kennet, Yvonne King, Jenny Kourampa, Emily Li, Caroline McMahon, Anne Meadows, Vivien Mendoza, Criona O’Brien, Charmain Ocaya, Ciro Pasquale, Marlyn Perales, Jane Price, Rebecca Rastall, Carla Ribeiro, Jane Rowlands, Valentina Ruffolo, Hugo Tordesillas, Phoebe Vargas, Bensi Vergese, Laura Watson, Jieniean Worsley, Julie-Ann Zerrudo, Laura Bergamashi, Ariana Betancourt, Georgie Bower, Ben Bullman, Chiara Cossetti, Aloka De Sa, Benjamin J. Dunmore, Maddie Epping, Stuart Fawke, Stefan Gräf, Richard Grenfell, Andrew Hinch, Josh Hodgson, Christopher Huang, Oisin Huhn, Kelvin Hunter, Isobel Jarvis, Emma Jones, Maša Josipović, Ekaterina Legchenko, Daniel Lewis, Joe Marsden, Jennifer Martin, Federica Mescia, Ciara O’Donnell, Ommar Omarjee, Marianne Perera, Linda Pointon, Nicole Pond, Nathan Richoz, Nika Romashova, Natalia Savoinykh, Rahul Sharma, Joy Shih, Mateusz Strezlecki, Rachel Sutcliffe, Tobias Tilly, Zhen Tong, Carmen Treacy, Lori Turner, Jennifer Wood, Marta Wylot, John Allison, Heather Biggs, John R. Bradley, Helen Butcher, Daniela Caputo, Matt Chandler, Debbie Clapham-Riley, Eleanor Dewhurst, Christian Fernandez, Anita Furlong, Barbara Graves, Jennifer Gray, Sabine Hein, Tasmin Ivers, Emma Le Gresley, Rachel Linger, Mary Kasanicki, Rebecca King, Sarah Meloy, Alexei Moulton, Francesca Muldoon, Nigel Ovington, Sofia Papadia, Christopher J. Penkett, Isabel Phelan, Venkatesh Ranganath, Roxana Paraschiv, Abigail Sage, Jennifer Sambrook, Ingrid Scholtes, Katherine Schon, Hannah Stark, Kathleen E. Stirrups, Paul Townsend, Neil Walker, Jennifer Webster, Mayurun Selvan, Petra Polgarova, Sarah L. Caddy, Laura G. Caller, Yasmin Chaudhry, Martin D. Curran, Theresa Feltwell, Stewart Fuller, Iliana Georgana, Grant Hall, William L. Hamilton, Myra Hosmillo, Charlotte J. Houldcroft, Rhys Izuagbe, Aminu S. Jahun, Fahad A. Khokhar, Anna G. Kovalenko, Luke W. Meredith, Surendra Parmar, Malte L. Pinckert, Anna Yakovleva, Emily C. Horner, Lucy Booth, Alexander Ferreira, Rebecca Boston, Robert Hughes, Juan Carlos Yam Puc, Nonantzin Beristain-Covarrubias, Maria Rust, Thevinya Gurugama, Lihinya Gurugama, Thomas Mulroney, Sarah Spencer, Zhaleh Hosseini, and Kate Williamson
Subjects: COVID-19, SARS-CoV-2, complement, factor H, factor H-related proteins, biomarkers, Immunologic diseases. Allergy, RC581-607
Abstract: The SARS-CoV-2 virus continues to cause significant morbidity and mortality worldwide from COVID-19. One of the major challenges of patient management is the broad range of symptoms observed. While the majority of individuals experience relatively mild disease, a significant minority of patients require hospitalisation, with COVID-19 still proving fatal for some. As such, there remains a desperate need to better understand what drives this severe disease, both in terms of the underlying biology, but also to potentially predict at diagnosis which patients are likely to require further interventions, thus enabling better outcomes for both patients and healthcare systems. Several lines of evidence have pointed to dysregulation of the complement cascade as a major factor in severe COVID-19 outcomes. How this is underpinned mechanistically is not known. Here, we have focussed on the role of the soluble complement regulators Complement Factor H (FH), its splice variant Factor H-like 1 (FHL-1) and five Factor H-Related proteins (FHR1-5). Using a targeted mass spectrometry approach, we quantified these proteins in a cohort of 188 plasma samples from controls and SARS-CoV-2 patients taken at diagnosis. This analysis revealed significant elevations in all FHR proteins, but not FH, in patients with more severe disease, particularly FHR2 and FHR5 (FHR2: 1.97-fold, p
Published: 2022
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39. Correction: Development and evaluation of rapid data-enabled access to routine clinical information to enhance early recruitment to the national clinical platform trial of COVID-19 community treatments

Author: Caroline Cake, Emma Ogburn, Heather Pinches, Garry Coleman, David Seymour, Fran Woodard, Sinduja Manohar, Marjia Monsur, Martin Landray, Gaynor Dalton, Andrew D. Morris, Patrick F. Chinnery, UK COVID-19 National Core Studies Consortium, F. D. Richard Hobbs, and Christopher Butler
Subjects: Medicine (General), R5-920
Published: 2023
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40. Cell reprogramming shapes the mitochondrial DNA landscape

Author: Wei Wei, Daniel J. Gaffney, and Patrick F. Chinnery
Subjects: Science
Abstract: Here the authors describe high depth mitochondrial DNA (mtDNA) sequence analysis of 146 human induced pluripotent stem cell (hiPSC) lines as well as single cell RNA-seq (scRNAseq) of hiPSCs undergoing differentiation from 125 donors; reporting mtDNA diversity and some variants favoured after reprogramming.
Published: 2021
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41. The pattern of retinal ganglion cell dysfunction in Leber hereditary optic neuropathy

Author: Majander, A, Robson, AG, João, C, Holder, GE, Chinnery, PF, Moore, AT, Votruba, M, Stockman, A, and Yu-Wai-Man, P
Subjects: Biochemistry and Cell Biology, Genetics, Biological Sciences, Eye Disease and Disorders of Vision, Clinical Research, Neurosciences, Neurological, Eye, Adolescent, Adult, Child, Female, Humans, Male, Middle Aged, Optic Atrophy, Hereditary, Leber, Prospective Studies, Retinal Ganglion Cells, Visual Pathways, Young Adult, Chromatic resolution, Critical flicker fusion, Leber hereditary optic neuropathy, Spatial contrast sensitivity, The pattern electroretinogram, The photopic negative responses, Biochemistry & Molecular Biology, Biochemistry and cell biology
Abstract: Leber inherited optic neuropathy (LHON) is characterized by subacute bilateral loss of central vision due to dysfunction and loss of retinal ganglion cells (RGCs). Comprehensive visual electrophysiological investigations (including pattern reversal visual evoked potentials, pattern electroretinography and the photopic negative response) performed on 13 patients with acute and chronic LHON indicate early impairment of RGC cell body function and severe axonal dysfunction. Temporal, spatial and chromatic psychophysical tests performed on 7 patients with acute LHON and 4 patients with chronic LHON suggest severe involvement or loss of the midget, parasol and bistratified RGCs associated with all three principal visual pathways.
Published: 2017

42. Biallelic Mutation of ARHGEF18, Involved in the Determination of Epithelial Apicobasal Polarity, Causes Adult-Onset Retinal Degeneration

Author: Arno, Gavin, Carss, Keren J, Hull, Sarah, Zihni, Ceniz, Robson, Anthony G, Fiorentino, Alessia, Hardcastle, Alison J, Holder, Graham E, Cheetham, Michael E, Plagnol, Vincent, Moore, Anthony, Raymond, F Lucy, Matter, Karl, Balda, Maria S, Webster, Andrew R, Black, Graeme, Hall, Georgina, Ingram, Stuart, Gillespie, Rachel, Manson, Forbes, Sergouniotis, Panagiotis, Inglehearn, Chris, Toomes, Carmel, Ali, Manir, McKibbin, Martin, Poulter, James, Khan, Kamron, Lord, Emma, Nemeth, Andrea, Downes, Susan, Halford, Stephanie, Yu, Jing, Lise, Stefano, Ponitkos, Nikos, Michaelides, Michel, Webster, Andrew, van Heyningen, Veronica, Aitman, Timothy, Alachkar, Hana, Ali, Sonia, Allen, Louise, Allsup, David, Ambegaonkar, Gautum, Anderson, Julie, Antrobus, Richard, Armstrong, Ruth, Arumugakani, Gururaj, Ashford, Sofie, Astle, William, Attwood, Antony, Austin, Steve, Bacchelli, Chiara, Bakchoul, Tamam, Bariana, Tadbir K, Baxendale, Helen, Bennett, David, Bethune, Claire, Bibi, Shahnaz, Bitner-Glindzicz, Maria, Bleda, Marta, Boggard, Harm, Bolton-Maggs, Paula, Booth, Claire, Bradley, John R, Brady, Angie, Brown, Matthew, Browning, Michael, Bryson, Christine, Burns, Siobhan, Calleja, Paul, Canham, Natalie, Carmichael, Jenny, Carss, Keren, Caulfield, Mark, Chalmers, Elizabeth, Chandra, Anita, Chinnery, Patrick, Chitre, Manali, Church, Colin, Clement, Emma, Clements-Brod, Naomi, Clowes, Virginia, Coghlan, Gerry, Collins, Peter, Cooper, Nichola, Creaser-Myers, Amanda, DaCosta, Rosa, Daugherty, Louise, Davies, Sophie, Davis, John, De Vries, Minka, Deegan, Patrick, Deevi, Sri VV, and Deshpande, Charu
Subjects: Biological Sciences, Bioinformatics and Computational Biology, Biomedical and Clinical Sciences, Genetics, Ophthalmology and Optometry, Human Genome, Rare Diseases, Neurosciences, Eye Disease and Disorders of Vision, Aetiology, 2.1 Biological and endogenous factors, Eye, Adult, Alleles, Amino Acid Sequence, Cell Polarity, Epithelial Cells, Exome, Eye Proteins, Female, Genetic Variation, Genome-Wide Association Study, Genotype, Humans, Male, Membrane Proteins, Middle Aged, Mutation, Missense, Nerve Tissue Proteins, Pedigree, Phenotype, Retina, Retinal Degeneration, Retinal Dystrophies, Rho Guanine Nucleotide Exchange Factors, rhoA GTP-Binding Protein, UK Inherited Retinal Disease Consortium, NIHR Bioresource - Rare Diseases Consortium, ARHGEF18, apicobasal polarity, inherited retinal dystrophy, p114RhoGEF, retinal degeneration, retinitis pigmentosa, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract: Mutations in more than 250 genes are implicated in inherited retinal dystrophy; the encoded proteins are involved in a broad spectrum of pathways. The presence of unsolved families after highly parallel sequencing strategies suggests that further genes remain to be identified. Whole-exome and -genome sequencing studies employed here in large cohorts of affected individuals revealed biallelic mutations in ARHGEF18 in three such individuals. ARHGEF18 encodes ARHGEF18, a guanine nucleotide exchange factor that activates RHOA, a small GTPase protein that is a key component of tight junctions and adherens junctions. This biological pathway is known to be important for retinal development and function, as mutation of CRB1, encoding another component, causes retinal dystrophy. The retinal structure in individuals with ARHGEF18 mutations resembled that seen in subjects with CRB1 mutations. Five mutations were found on six alleles in the three individuals: c.808A>G (p.Thr270Ala), c.1617+5G>A (p.Asp540Glyfs∗63), c.1996C>T (p.Arg666∗), c.2632G>T (p.Glu878∗), and c.2738_2761del (p.Arg913_Glu920del). Functional tests suggest that each disease genotype might retain some ARHGEF18 activity, such that the phenotype described here is not the consequence of nullizygosity. In particular, the p.Thr270Ala missense variant affects a highly conserved residue in the DBL homology domain, which is required for the interaction and activation of RHOA. Previously, knock-out of Arhgef18 in the medaka fish has been shown to cause larval lethality which is preceded by retinal defects that resemble those seen in zebrafish Crumbs complex knock-outs. The findings described here emphasize the peculiar sensitivity of the retina to perturbations of this pathway, which is highlighted as a target for potential therapeutic strategies.
Published: 2017

43. The Human Phenotype Ontology in 2017

Author: Köhler, Sebastian, Vasilevsky, Nicole A, Engelstad, Mark, Foster, Erin, McMurry, Julie, Aymé, Ségolène, Baynam, Gareth, Bello, Susan M, Boerkoel, Cornelius F, Boycott, Kym M, Brudno, Michael, Buske, Orion J, Chinnery, Patrick F, Cipriani, Valentina, Connell, Laureen E, Dawkins, Hugh JS, DeMare, Laura E, Devereau, Andrew D, de Vries, Bert BA, Firth, Helen V, Freson, Kathleen, Greene, Daniel, Hamosh, Ada, Helbig, Ingo, Hum, Courtney, Jähn, Johanna A, James, Roger, Krause, Roland, Laulederkind, Stanley JF, Lochmüller, Hanns, Lyon, Gholson J, Ogishima, Soichi, Olry, Annie, Ouwehand, Willem H, Pontikos, Nikolas, Rath, Ana, Schaefer, Franz, Scott, Richard H, Segal, Michael, Sergouniotis, Panagiotis I, Sever, Richard, Smith, Cynthia L, Straub, Volker, Thompson, Rachel, Turner, Catherine, Turro, Ernest, Veltman, Marijcke WM, Vulliamy, Tom, Yu, Jing, von Ziegenweidt, Julie, Zankl, Andreas, Züchner, Stephan, Zemojtel, Tomasz, Jacobsen, Julius OB, Groza, Tudor, Smedley, Damian, Mungall, Christopher J, Haendel, Melissa, and Robinson, Peter N
Subjects: Biological Sciences, Bioinformatics and Computational Biology, Genetics, Networking and Information Technology R&D (NITRD), Human Genome, 2.6 Resources and infrastructure (aetiology), 4.5 Resources and infrastructure (detection), Generic health relevance, Good Health and Well Being, Algorithms, Biological Ontologies, Computational Biology, Genetic Association Studies, Genomics, Humans, Phenotype, Precision Medicine, Rare Diseases, Software, Translational Research, Biomedical, Environmental Sciences, Information and Computing Sciences, Developmental Biology, Biological sciences, Chemical sciences, Environmental sciences
Abstract: Deep phenotyping has been defined as the precise and comprehensive analysis of phenotypic abnormalities in which the individual components of the phenotype are observed and described. The three components of the Human Phenotype Ontology (HPO; www.human-phenotype-ontology.org) project are the phenotype vocabulary, disease-phenotype annotations and the algorithms that operate on these. These components are being used for computational deep phenotyping and precision medicine as well as integration of clinical data into translational research. The HPO is being increasingly adopted as a standard for phenotypic abnormalities by diverse groups such as international rare disease organizations, registries, clinical labs, biomedical resources, and clinical software tools and will thereby contribute toward nascent efforts at global data exchange for identifying disease etiologies. This update article reviews the progress of the HPO project since the debut Nucleic Acids Research database article in 2014, including specific areas of expansion such as common (complex) disease, new algorithms for phenotype driven genomic discovery and diagnostics, integration of cross-species mapping efforts with the Mammalian Phenotype Ontology, an improved quality control pipeline, and the addition of patient-friendly terminology.
Published: 2017

44. Comprehensive Rare Variant Analysis via Whole-Genome Sequencing to Determine the Molecular Pathology of Inherited Retinal Disease

Author: Carss, Keren J, Arno, Gavin, Erwood, Marie, Stephens, Jonathan, Sanchis-Juan, Alba, Hull, Sarah, Megy, Karyn, Grozeva, Detelina, Dewhurst, Eleanor, Malka, Samantha, Plagnol, Vincent, Penkett, Christopher, Stirrups, Kathleen, Rizzo, Roberta, Wright, Genevieve, Josifova, Dragana, Bitner-Glindzicz, Maria, Scott, Richard H, Clement, Emma, Allen, Louise, Armstrong, Ruth, Brady, Angela F, Carmichael, Jenny, Chitre, Manali, Henderson, Robert HH, Hurst, Jane, MacLaren, Robert E, Murphy, Elaine, Paterson, Joan, Rosser, Elisabeth, Thompson, Dorothy A, Wakeling, Emma, Ouwehand, Willem H, Michaelides, Michel, Moore, Anthony T, Consortium, NIHR-BioResource Rare Diseases, Aitman, Timothy, Alachkar, Hana, Ali, Sonia, Allsup, David, Ambegaonkar, Gautum, Anderson, Julie, Antrobus, Richard, Arumugakani, Gururaj, Ashford, Sofie, Astle, William, Attwood, Antony, Austin, Steve, Bacchelli, Chiara, Bakchoul, Tamam, Bariana, Tadbir K, Baxendale, Helen, Bennett, David, Bethune, Claire, Bibi, Shahnaz, Bleda, Marta, Boggard, Harm, Bolton-Maggs, Paula, Booth, Claire, Bradley, John R, Brady, Angie, Brown, Matthew, Browning, Michael, Bryson, Christine, Burns, Siobhan, Calleja, Paul, Canham, Natalie, Carss, Keren, Caulfield, Mark, Chalmers, Elizabeth, Chandra, Anita, Chinnery, Patrick, Church, Colin, Clements-Brod, Naomi, Clowes, Virginia, Coghlan, Gerry, Collins, Peter, Cooper, Nichola, Creaser-Myers, Amanda, DaCosta, Rosa, Daugherty, Louise, Davies, Sophie, Davis, John, De Vries, Minka, Deegan, Patrick, Deevi, Sri VV, Deshpande, Charu, Devlin, Lisa, Doffinger, Rainer, Dormand, Natalie, Drewe, Elizabeth, and Edgar, David
Subjects: Genetics, Neurosciences, Eye Disease and Disorders of Vision, Human Genome, Clinical Research, 2.1 Biological and endogenous factors, Aetiology, Eye, Good Health and Well Being, Adaptor Proteins, Signal Transducing, Alleles, Base Sequence, Choroideremia, DNA Mutational Analysis, Ethnicity, Exome, Female, Genes, Recessive, Genetic Variation, Genome, Human, Humans, Introns, Male, Mutation, Rare Diseases, Retinal Diseases, NIHR-BioResource Rare Diseases Consortium, copy-number variants, rare sequence variant, retinal dystrophy, whole-genome sequence, Biological Sciences, Medical and Health Sciences, Genetics & Heredity
Abstract: Inherited retinal disease is a common cause of visual impairment and represents a highly heterogeneous group of conditions. Here, we present findings from a cohort of 722 individuals with inherited retinal disease, who have had whole-genome sequencing (n = 605), whole-exome sequencing (n = 72), or both (n = 45) performed, as part of the NIHR-BioResource Rare Diseases research study. We identified pathogenic variants (single-nucleotide variants, indels, or structural variants) for 404/722 (56%) individuals. Whole-genome sequencing gives unprecedented power to detect three categories of pathogenic variants in particular: structural variants, variants in GC-rich regions, which have significantly improved coverage compared to whole-exome sequencing, and variants in non-coding regulatory regions. In addition to previously reported pathogenic regulatory variants, we have identified a previously unreported pathogenic intronic variant in CHM in two males with choroideremia. We have also identified 19 genes not previously known to be associated with inherited retinal disease, which harbor biallelic predicted protein-truncating variants in unsolved cases. Whole-genome sequencing is an increasingly important comprehensive method with which to investigate the genetic causes of inherited retinal disease.
Published: 2017

45. Co-designing Improved Communication of Newborn Bloodspot Screening Results to Parents: Mixed Methods Study

Author: Jane Chudleigh, Lynette Shakespeare, Pru Holder, Holly Chinnery, Gemma Hack, Tanya Gill, Rachel Gould, Kevin W Southern, Ellinor K Olander, Stephen Morris, James R Bonham, Alan Simpson, and Louise Moody
Subjects: Medicine
Abstract: BackgroundEach year in England, almost 10,000 parents are informed of their child’s positive newborn bloodspot screening (NBS) results. This occurs approximately 2 to 8 weeks after birth depending on the condition. Communication of positive NBS results is a subtle and skillful task, demanding thought, preparation, and evidence to minimize potentially harmful negative sequelae. Evidence of variability in the content and the way the result is currently communicated has the potential to lead to increased parental anxiety and distress. ObjectiveThis study focused on the development of co-designed interventions to improve the experiences of parents receiving positive NBS results for their children and enhance communication between health care professionals and parents. MethodsAn experience-based co-design approach was used to explore experiences and co-design solutions with 17 health professionals employed in 3 National Health Service Trusts in England and 21 parents (13/21, 62% mothers and 8/21, 38% fathers) of 14 children recruited from the same 3 National Health Service Trusts. Experiences with existing services were gathered via semistructured interviews with health professionals. Filmed narrative interviews with parents were developed into a composite film. The co-design process identified priorities for improving communication of positive NBS results through separate parent and health professional feedback events followed by joint feedback events. In total, 4 interventions were then co-designed between the participants through a web-based platform. ResultsParents and health professionals provided positive feedback regarding the process of gathering experiences and identifying priorities. Themes identified from the parent interviews included impact of initial communication, parental reactions, attending the first clinic appointment, impact of health professionals’ communication strategies and skills, impact of diagnosis on family and friends, improvements to the communication of positive NBS results, and parents’ views on NBS. Themes identified from the health professional interviews included communication between health professionals, process of communicating with the family, parent- and family-centered care, and availability of resources and challenges to effective communication. In response to these themes, 4 interventions were co-designed: changes to the NBS card; standardized laboratory proformas; standardized communication checklists; and an email or letter for providing reliable, up-to-date, condition-specific information for parents following the communication of positive NBS results. ConclusionsParents and health professionals were able to successfully work together to identify priorities and develop co-designed interventions to improve communication of positive NBS results to parents. The resulting co-designed interventions address communication at different stages of the communication pathway to improve the experiences of parents receiving positive NBS results for their children. International Registered Report Identifier (IRRID)RR2-10.1186/s40814-019-0487-5
Published: 2022
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46. Co-designed strategies for delivery of positive newborn bloodspot screening results to parents: the ReSPoND mixed-methods study

Author: Jane Chudleigh, Pru Holder, Francesco Fusco, James R Bonham, Mandy Bryon, Louise Moody, Stephen Morris, Ellinor K Olander, Alan Simpson, Holly Chinnery, Fiona Ulph, and Kevin W Southern
Subjects: communication, cystic fibrosis, sickle cell disease, inherited metabolic diseases, congenital hypothyroid, co-production, Medicine (General), R5-920, Public aspects of medicine, RA1-1270
Abstract: Background: Newborn bloodspot screening identifies presymptomatic babies who are affected by genetic or congenital conditions. Each year, around 10,000 parents of babies born in England are given a positive newborn bloodspot screening result for one of nine conditions that are currently screened for. Despite national guidance, variation exists regarding the approaches used to communicate these results to families; poor communication practices can lead to various negative sequelae. Objectives: Identify and quantify approaches that are currently used to deliver positive newborn bloodspot screening results to parents (phase 1). Develop (phase 2), implement and evaluate (phase 3) co-designed interventions for improving the delivery of positive newborn bloodspot screening results. Quantify the resources required to deliver the co-designed interventions in selected case-study sites and compare these with costs associated with current practice (phase 3). Design: This was a mixed-methods study using four phases, with defined outputs underpinned by Family Systems Theory. Setting: All newborn bloodspot screening laboratories in England (n = 13). Participants: Laboratory staff and clinicians involved in processing or communicating positive newborn bloodspot screening results, and parents of infants who had received a positive or negative newborn bloodspot screening result. Interventions: Three co-designed interventions that were developed during phase 2 and implemented during phase 3 of the study. Main outcome measure: Acceptability of the co-designed interventions for the communication of positive newborn bloodspot screening results. Results: Staff were acutely aware of the significance of a positive newborn bloodspot screening result and the impact that this could have on families. Challenges existed when communicating results from laboratories to relevant clinicians, particularly in the case of congenital hypothyroidism. Clinicians who were involved in the communication of positive newborn bloodspot screening results were committed to making sure that the message, although distressing for parents, was communicated well. Despite this, variation in communication practices existed. This was influenced by many factors, including the available resources and lack of clear guidance. Although generally well received, implementation of the co-designed interventions in practice served to illuminate barriers to acceptability and feasibility. The interventions would not influence NHS expenditure and could be cost neutral when delivered by teleconsultations. Limitations: Participants with a pre-existing interest in this topic may have been more likely to self-select into the study. The researchers are experienced in this field, which may have biased data collection and analysis. COVID-19 hindered implementation and related data collection of the co-designed interventions. Conclusions: There was variation in the processes used to report positive newborn bloodspot screening results from newborn bloodspot screening laboratories to clinical teams and then to families. The various practices identified may reflect local needs, but more often reflected local resource. A more consistent ‘best practice’ approach is required, not just in the UK but perhaps globally. The co-designed interventions represent a starting point for achieving this. Future work: Future work should include a national evaluation study with predefined outcomes, accompanied by an economic evaluation, to assess the acceptability, feasibility and usability of the co-designed interventions in practice nationally. Trial registration: This trial is registered as ISRCTN15330120. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme and will be published in full in Health and Social Care Delivery Research; Vol. 10, No. 19. See the NIHR Journals Library website for further project information.
Published: 2022
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47. RRM1 variants cause a mitochondrial DNA maintenance disorder via impaired de novo nucleotide synthesis

Author: Jonathan Shintaku, Wolfgang M. Pernice, Wafaa Eyaid, Jeevan B. GC, Zuben P. Brown, Marti Juanola-Falgarona, Javier Torres-Torronteras, Ewen W. Sommerville, Debby M.E.I. Hellebrekers, Emma L. Blakely, Alan Donaldson, Ingrid van de Laar, Cheng-Shiun Leu, Ramon Marti, Joachim Frank, Kurenai Tanji, David A. Koolen, Richard J. Rodenburg, Patrick F. Chinnery, H.J.M. Smeets, Gráinne S. Gorman, Penelope E. Bonnen, Robert W. Taylor, and Michio Hirano
Subjects: Genetics, Medicine
Abstract: Mitochondrial DNA (mtDNA) depletion/deletions syndromes (MDDS) encompass a clinically and etiologically heterogenous group of mitochondrial disorders caused by impaired mtDNA maintenance. Among the most frequent causes of MDDS are defects in nucleoside/nucleotide metabolism, which is critical for synthesis and homeostasis of the deoxynucleoside triphosphate (dNTP) substrates of mtDNA replication. A central enzyme for generating dNTPs is ribonucleotide reductase, a critical mediator of de novo nucleotide synthesis composed of catalytic RRM1 subunits in complex with RRM2 or p53R2. Here, we report 5 probands from 4 families who presented with ptosis and ophthalmoplegia as well as other clinical manifestations and multiple mtDNA deletions in muscle. We identified 3 RRM1 loss-of-function variants, including a dominant catalytic site variant (NP_001024.1: p.N427K) and 2 homozygous recessive variants at p.R381, which has evolutionarily conserved interactions with the specificity site. Atomistic molecular dynamics simulations indicate mechanisms by which RRM1 variants affect protein structure. Cultured primary skin fibroblasts of probands manifested mtDNA depletion under cycling conditions, indicating impaired de novo nucleotide synthesis. Fibroblasts also exhibited aberrant nucleoside diphosphate and dNTP pools and mtDNA ribonucleotide incorporation. Our data reveal that primary RRM1 deficiency and, by extension, impaired de novo nucleotide synthesis are causes of MDDS.
Published: 2022
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48. Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Author: Stephen R Knight, Catherine A Shaw, Riinu Pius, Thomas M Drake, Lisa Norman, Adesoji O Ademuyiwa, Adewale O Adisa, Maria Lorena Aguilera, Sara W Al-Saqqa, Ibrahim Al-Slaibi, Aneel Bhangu, Bruce M Biccard, Peter Brocklehurst, Ainhoa Costas-Chavarri, Kathryn Chu, Anna Dare, Muhammed Elhadi, Cameron J Fairfield, J Edward Fitzgerald, Dhruv Ghosh, James Glasbey, Mark I. van Berge Henegouwen, J.C. Allen Ingabire, T Peter Kingham, Marie Carmela Lapitan, Ismaïl Lawani, Bettina Lieske, Richard Lilford, Janet Martin, Kenneth A McLean, Rachel Moore, Dion Morton, Dmitri Nepogodiev, Faustin Ntirenganya, Francesco Pata, Thomas Pinkney, Ahmad Uzair Qureshi, Antonio Ramos-De la Medina, Aya Riad, Hosni Khairy Salem, Joana Simões, Richard Spence, Neil Smart, Stephen Tabiri, Hannah Thomas, Thomas G Weiser, Malcolm West, John Whitaker, Ewen M Harrison, Arben Gjata, Maria Marta Modolo, Sebastian King, Erick Chan, Sayeda Nazmun Nahar, Ade Waterman, Dominique Vervoort, Alemayehu Ginbo Bedada, Bernardo De Azevedo, Ana Gabriela Figueiredo, Manol Sokolov, Venerand Barendegere, Gerald Ekwen, Arnav Agarwal, Qinyang Liu, Juan Camilo Correa, Kalisya Luc Malemo, Jacques Bake, Jakov Mihanovic, Kamila Kunčarová, Julius Orhalmi, Hosni Salem, Jyri Teras, Aristotelis Kechagias, Alexis P Arnaud, Judith Lindert, Vasileios Kalles, Maria-Lorena Aguilera-Arevalo, Gustavo Recinos, Zsolt Baranyai, Basant Kumar, Harish Neelamraju Lakshmi, Sanoop Koshy Zachariah, Philip Alexander, Sunil Kumar Venkatappa, C Pramesh, Radhian Amandito, Christina Fleming, Luca Ansaloni, Gianluca Pellino, Ahmed M. Altibi, Ibrahim Nour, Intisar Hamdun, Ali M. Ghellai, Donatas Venskutonis, Tomas Poskus, Justas Zilinskas, Precious Malemia, Yong Yong Tew, Elaine Borg, Sarah Ellul, fatima Zahraa Wafqui, David W Borowski, Anne Sophie van Dalen, Cameron Wells, Harissou Adamou, Adesoji Ademuyiwa, Adewale Adisa, Kjetil Søreide, Sara Al Saqqa, Osaid Alser, Haya Tahboub, Helmut Alfredo Segovia Lohse, Sebastian Shu Yip, Piotr Major, António Sampaio Soares, Matei Razvan Bratu, Andrey Litvin, Armen Vardanyan, JC Allen Ingabire, Ahmad Gudal, Naif Albati, Jovan Juloski, Miran Rems, Sarah Rayne, Stephanie Van Straten, Yoshan Moodley, Irene Ortega Vázquez, Jaime Ruiz-Tovar, Kithsiri Janakantha Senanayake, Sujeewa Priyantha Bandara Thalgaspitiya, Omer Abdelbagi Omer, Anmar Homeida, Yucel Cengiz, Daniel Clerc, Muhammad Alshaar, Hanen Bouaziz, Yuksel Altinel, Matthew Doe, Maryna Freigofer, Ella Teasdale, Rakan Kabariti, Joshua Michael Clements, Stephen Richard Knight, Ahsan Ashfaq, Ijeoma Azodo, Gabriela Wagner, Ivan Trostchansky, Mayaba Maimbo, David Linyama, Helidon Nina, Amanda Zeko, Claudio Gabriel Fermani, Santiago Villalobos, Federico Carballo, Pablo Farina, Sebastian Guckenheimer, Marilla Dickfos, Ankit Ajmera, Chester Chong, Ralph Gourlay, Sikandar Hussaini, Yi Jia Lee, Adeeb Majid, Peter Martin, Rebecca Miles, Owen James Morris, Jamie Phua, William Ridley, Tarunpreet Saluja, Ryan Renxin Tan, Jen Teh, Anna Wells, Bharti Arora, Qaasim Dollie, Debbie Ho, Yanru Ma, Omattage Mahasha Perera, Anthony Truong, Amanda Caroline Dawson, Bryan Lim, Upuli Pahalawatta, Jacqueline Phan, Xiao-Ming Sarah Woon-Shoo-Tong, Andrea Yeoh, Lillian Charman, Andrew Drane, Sharon Laura, Charmaine Chu Wen Lo, Amy Mozes, Rita Poon, Hao Han Tan, Ellen Wall, Prakshi Chopra, Jasmine De Giovanni, Bal Dhital, Brian Draganic, Alexander Duller, Jonathan Gani, Yao Kuan Goh, Jun Young Jeong, Brendan McManus, Prakash Nagappan, Peter Pockney, Anya Rugendyke, Mahsa Sarrami, Stephen Smith, Vanessa Wills, Hsu Ven Wong, Geoffrey Ye, Geoffrey Zhang, Ethan Brooker, Daniel Feng, Bonnie Lau, Carlin Ngai, Sarah Birks, David Gyorki, Jaime Otero de Pablos, Ali Abbosh, Chris Gillespie, Ahmed Mahmoud, Bianca Kwan, Joshua Lawson, Andrea Warwick, Janne Bingham, Andrew J Cockbain, Nagendra Naidu Dudi-Venkata, Jordan Ellaby-Hall, Ben Finlay, Emily Humphries, Jade Pisaniello, Monique Pisaniello, Salma Salih, Tarik Sammour, Haidar Hadri Abd Wahab, April De Silva, Nicola Hayward, Kartik Iyer, Guy Maddern, Gian Andrea Prevost, Naga Annapureddy, Krishna Pranathi Settipalli, Jeremy Yeo, Lucy Hempenstall, Lily Pham, Shaun Purcell, Cherry Talavera, Ashish I Vaska, Gurpreet Chaggar, Phillip Chrapko, Annelise Cocco, Sarah Michelle Crystal Jade Coulter-Nile, Grahame Ctercteko, James French, Houchen Gong, Martijn Gosselink, Thuvarahan Jegathees, Ivan Jin, Michelle Kalachov, Kathryn Kiefhaber, Katherine Lee, Jason Luong, Steven Phan, Henry Pleass, Kelly Veale, Zhi Zeng, Angela Au, Ashe DeBiasio, Idy Deng, Jananee Myooran, Amrita Nair, Peter Stewart, Anton Stift, Lukas Walter Unger, Kerstin Wimmer, Nabila Ahmed, Syed Hasan, Saber Rahman, Margaret O'Shea, Greg Padmore, Adrian Peters, Pietro Perduca, Guenda Pulcina, Nicolas Tinton, Frederic Buxant, Elsa Dabin, Giulia Garofalo, Francis Dossou, Freddy Houehanou Rodrigue Gnangnon, Yacoubou Imorou Souaibou, Pako Motlaleselelo, Omphile Tlhomelang, Igor Lima Buarque, Gustavo Mendonça Ataíde Gomes, Aldo Vieira Barros, Ilia Batashki, Nikolai Damianov, Vladislav Stoyanov, Dragomir Dardanov, Svilen Maslyankov, Plamen Petkov, George Todorov, Evgeni Zhivkov, Aygulya Akisheva, Miguel Angel Castilla Moreno, Geno Genov, Ivelina Ilieva, Tsvetomir Ivanov, Martin Karamanliev, Azhar Khan, Emil Mitkov, Tsanko Yotsov, Boyko Atanasov, Nikolay Belev, Mihail Slavchev, Carlos Nsengiyumva, Elgan Jones, Simon Stock, Steve Kyota, James Brown, Tresor Mabanza K., Lemery Nigo Samuel, Chidi Otuneme, Ngwang Prosper, Franklin Umenze, Marylise Boutros, Natasha Caminsky, Sinziana Dumitra, Richard Garfinkle, Dominique Morency, Ebram Salama, Alexander Banks, Lorenzo Ferri, Haitian He, Amit Katz, Alexander Sender Liberman, Sarkis Meterissian, Allison Pang, Elena Parvez, Usmaan Hameed, Fahima Osman, Sangita Sequeira, Natalie Coburn, Alisha Jaffer, Paul Karanicolas, Matthew Mosseler, Reilly Musselman, Xinyuan Liu, Ching Wan Yip, Juan Sebastian Garces-Otero, Carolina Guzman, Sebastian Sierra, Andres Uribe Valencia, Paulo Andrés Cabrera Rivera, Saul Camelo, Andrea Gonzalez, Alejandro González-Orozco, Manuel Santiago Mosquera Paz, Carlos J- Perez Rivera, Felipe Gonzalez, Andres Isaza-Restrepo, Laura Nino- Torres, Natalia Arias Madrid, Maria Clara Mendoza Arango, Justin Tsandiraki, Damir Jemendžić, Branislav Kocman, Oliver Šuman, Renata Canic, Darko Jurišić, Ivana Karakas, Ana Krizanovic Rupcic, Vlatka Pitlovic, Josip Samardžić, Mario Kopljar, Ivan Bacic, Edgar Domini, Robert Karlo, Danijela Miljanić, Andrea Simic, Mariam Ahmed, Majdi Al Nassrallah, Rabiya Altaf, Talal Amjad, Ruba Eltoum, Heba Haidar, Alhassan Hassan, Omar Khalil, Marwan Qasem, Rommel Ramesh, Gautham Sajith, Maham Wisal, Jan Žatecký, Michele Bujda, Katerina Jirankova, Ales Paclik, Aya Abdallah, Mariam Abdulgawad Almogy, Esraa Ayman El-sawy, Ahmed Moustafa ElFayoumy, Nourhan Elghareeb, Nourhan Ahmed Esmat, Ahmed Fadel, Abdullah Habater, Heba Hamdy, Amr Hefni, Marwa Kamal, Norhan Mohamed Abobakr, Ahmed Sayed, Nancy Shaker, Ehab Taha, Hoda Tharwat, Omar Zakaria, Ibrahem Abdelmotaleb, Ali Al-Dhufri, Hamza S. Al-Himyari, Enas El sheikh, Asmaa Eldmaty, Aya Elkhalawy, Ahmed M.Elkhashen, Kithara Magdy, Safa Mostafa, Habib Doutoum Sadia, Mohamed mahmoud Saleh, Dina Samir, Mohamed Yahia Mohamed Ali, Mahmoud A. Nassar, Samar Abdelhady, Aly Abdelrazek, Israa Abdelsalam, Aya El-Sawy, Eman Essam, Mohamed Gadelkarim, Khaled Ghaly, Mohamed Hassabalnaby, Rana Masarani, Nourhan Mohamed Shaaban, Ahmed Sabry, Menatalla Salem, Nourhan Akram Soliman, Diaaaldin Zahran, Moustafa Ramadan Abou El.soud, Esraa Tarek Badr, Hala Borham, Nehal Elmeslemany, Mohammad Elsayed, Fawzia Elsherif, Sara Eslam, Gehad Gaber, Sondos Ibrahim, Yara Kamh, Abdelrahman Mahmoud, Shimaa gamal Mohamed, Eman Morshedy, Cinderella Omar, Fatima Salem Soliman, Shaza Abdelkawy, Naglaa Abdelmohsen, Mahmoud Abdelshakour, Ahmed Dahy, Norhan Gamal, Mohammed Gamal, Ahmad Hasan, Helal Hetta, Nehad Mousa, Mohamed Omar, Somia Rabie, Mahmoud Saad, Bakeer Saleh, Marwa Sayed Mohamed, Muhammad Shawqi, Heba Abdelhady Mousa, Mostafa Alnoury, Mohamed Elbealawy, Ahmed Elshafey, Muhammad Essam Ibrahim El Desouki Muhammad Ahmed, Mennatullah Ghonaim, Fawzy Hgag, Mohamed Ibrahim, Mahmoud Morsy, Mohamed Reda Loaloa, Ahmed Refaat, Hadeer Samir, Fatma Shahien, Mohamed Sobhy, Fathy Sroor, Esraa Abdellatif, Marina Adel, Amr Abdelghani Afifi, Eman Afifi, Marco Antaky, Amr Dawoud, Naira El Zoghby, Amira El-remaily, Ali Abdelazez Elzanfaly, Ahmed Gadallah, Fatma Alzahraa Gamal, Omar Hashem, Shrouk Medhat Youssef, Aliaa Muhammad Attyah, Malak Munir, Omar Shazly, Esraa Taha, Karim Wilson, Sawsan Adel, Asmaa Ali, Esraa Eid, Esraa Elhelow, Marwa Elmahdy, Bassant Elshatby, Amany Hossam el-din Zakaria, Ahmad Hossny, Eman Ibrahim, Ahmed M.Yonis, Maram Metwalli, Basant Yousry, Esraa Zid, Mina A Yacoub, Ahmed Abdelhakim, Nervana Abouelsoad, Mo'min Alkhatib, Ahmed Ashraf, Alaa Ashraf, Yasmin Elazab, Mahmoud Elfanty, Osama Elkabir, Mai Elsayed, Ahmed Elshimy, Hager Elsobky, John Eskander, Ahmed Gad, Ward Hamsho, Noura Khaled Abdelwahed, Menna Magdy, Dalia Moharam, Abeer Osama, Shereen Ramadan, Radwa Roum, Taqwa Sayed, Tarneem Shehada, Ahmed Mohy Zidan, Khalid Abbas, Amr Ali, Mohamed Attia, Mohamed Balata, Ayman El Nakeeb, Mohamed Ibrahim Elsayed Elewaily, Ahmed Elfallal, Hossam Elfeki, Ahmed Elkhadragy, Sameh Emile, Helmy Ezzat, Hasnaa Hosni, Islam Mansour, Waleed Omar, Gehad Othman, Kareem Sadek, Mostafa Shalaby, Noura Shehab-Eldeen, Rawda Anas khalifa, Helmy Badr, Mostafa Eldeep, Ahmed Eldeep, Amany Eldoseuky mohammed, Salwa Khallaf, Eman Magdy Hegazy, Rokia Mahmoud, Pola Mikhail, Mahmoud Morsi, Sara Mowafy, Dina Raafat, Amina Safy, Marwa Sera, Ahmed shible Sera, Mostafa Salim Mohamed AbdAllah, Muhammad Abdelkader, Abdulrahman Osama Abdou, Ahmedgaber Ahmed, Shireen Gaafar, Fatma Ibrahim negm, Mina Lapic, Ahmed Maher, Hagar Mahmoud, Ahmed Mostafa, Mohamed Samir, Fatma Samy, Nourhan Semeda, Hind I. Shalaby, Alaa El-taweel, Ahmed Galal Elnagar, Ahmed Gamal Hemidan, Mohamed Hussein, Ahmed.A. Kandil, Mf Moawad, Ayat Allah Nasser Hamamah, Mostafa Soliman, Mohamed Abdelkhalek, Noura Abdelmaksoud Tawakel, Ahmed Mohamed Abdelwahed, Alrawy Abdou, Khalid Atallah, Mohammed Yasser Elsherbeny, Eman Emara, Mohamed Hamdy, Omar Hamdy, Amira Haron, Salma Ismail, Islam Hany Metwally, Nihal Mohamed Hamed Elgaml, Ahmed Nassar, Basel Refky, Mirna Sadek, Mahmoud Saleh, Asmaa Yunes, Mai Zakaria, Mohammed Zuhdy, Notila Fayed, Mohammed Mustafa Hassan Mohammed, Sander Kütner, Priit Melnik, Indrek Seire, Toomas Ümarik, Eppu Ainoa, Verner Eerola, Hanna Koppatz, Laura Koskenvuo, Ville Sallinen, Sini Takala, Jevgeni Katunin, Arto Turunen, Niki Christou, Muriel Mathonnet, Vincent Lavoue, Krystel Nyangoh Timoh, Lucie Soulabaille, Romain Lesourd, Aude Merdrignac, Laurent Sulpice, Benoît André, Elodie Chantalat, Charlotte Vaysse, Bertrand Dousset, Sebastien Gaujoux, Gregory Martin, Octavian Clonda, Domantas Juodis, Klaus Kienle, Andras Mravik, Samuel Palmer, Gabor Szabadhegyi, Anita Eseenam Agbeko, Solomon Gyabaah, Frank Enoch Gyamfi, Nuhu Naabo, Atta Owusu senior, Joseph Yorke, Frank Owusu, Francis Abantanga, Theophilus Teddy Kojo Anyomih, Abdul-Jalilu Mohammed Muntaka, Emmanuel Owusu Abem, Mohammed Sheriff, Paul M. Wondoh, Dimitrios Balalis, Dimitrios Korkolis, Georgios Gkiokas, Eirini Pantiora, Theodosios Theodosopoulos, Argyrios Ioannidis, Konstantinos Konstantinidis, Sofia Konstantinidou, Nikolaos Machairas, Anna Paspala, Anastasia Prodromidou, Christos Chouliaras, Konstantinos Papadopoulos, Ioannis Baloyiannis, Ioannis Mamaloudis, George Tzovaras, Ioanna Akrida, Maria-Ioanna Argentou, Stylianos Germanos, Evangelos Iliopoulos, Ioannis Maroulis, George Skroubis, George Theofanis, Christos Chatzakis, Orestis Ioannidis, Lydia Loutzidou, Panagiotis Karathanasis, Nikolaos Michalopoulos, Charalampos Theodoropoulos, Dimitrios Theodorou, Tania Triantafyllou, Zoe Garoufalia, Natasha Hasemaki, Michalis Kontos, Gregory Kouraklis, Stylianos Kykalos, Theodore Liakakos, Eustratia Mpaili, Alexandros Papalampros, Dimitrios Schizas, Athanasios Syllaios, Ekaterini Christina Tampaki, Antonios Tsimpoukelis, Maria Ioanna Antonopoulou, Eirini Deskou, Dimitrios K. Manatakis, Dimitrios Papageorgiou, Menelaos Zoulamoglou, Christos Anthoulakis, Michalis Margaritis, Nikolaos Nikoloudis, Veronica Campo, André Ceballos, Mario-Andrés Flores, Waleska Giron, Donghyun Ko, Gabriel Martinez, Verónica Rivera Lara, Nataly Rueda, Andres Sanchez, Jorge Carlos Guillermo Tejeda Garrido, Alvaro Eduardo Alvarez Rivera, Elvis Benjamin Bamaca Ixcajoc, Lilian Elizabeth Barreda Zelaya, Patricia Chacòn-Herrera, Ligia Margarita Corea Ruiz, Guillermo Echeverria-Davila, Mario Garcia, Danilo García, Edgar Fernando Gutiérrez Mayen, Noriega José, Nery Mazariegos, Diego Méndez, Michael Paniagua Espinoza, David Bardos, Marton Benke, Kristof Illes, Balint András Kokas, Réka Szabó, Akhila Appukuttan, Anjitha Asok, Vijaykumar D.k, Kapil Malik, Praveen Ravishankaran, Ritesh Tapkire, Guru Moorthy, Joyner Abraham, Ramesh Muthuvel, John Alapatt, Abhay Kattepur, Nizamudheen Pareekutty, Mebanshanbor Garod, Caleb Harris, Cliff Wanniang, Ashish Gupta, Deepak Nehra, Sanjeev Parshad, Rajgopal Acharya, Rajendra Badwe, Manish Bhandare, Urvashi Jain, Karishma Kirti, Nita Nair, Shailesh Shrikhande, Purvi Thakkar, Premkumar Anandan, Archana C S, Arun Holenarasipur Narasannaiah, Tejaswi Jagarlamudi, Rashmi M R, Mallikarjuna Manangi, Abhishek Raghavendra, K. Seshagiri Rao, Vinay S, Vinay Sajjan, Aneesh Shenoy, Santhosh Shivashankar Chikkanayakanahalli, Kavya Tharanath, Sushmita V, Peter Adidharma, Raksheeth Agarwal, Phebe Anggita Gultom, Ghafur Rasyid Arifin, Matthew Billy, Zatira Elfizri, Alessa Fahira, Devi Felicia, Triana Hardianti Gunardi, Nadya Johanna, Nadia Rahmadiani Nugrahadi, Sonar Soni Panigoro, Siti Rahmayanti, Retta Catherina Sihotang, Santi Yuanita Brata, Hadi Winoto, Nastaran Barati, Manoochehr Karami, Hamidreza Khorshidi, Homa Naderifar, Mazin A. Abdulla, Maggie Coleman, Ronan J Doherty, Rob Hannon, Brenda Murphy, Aine Stakelum, Des Winter, Lylas Aljohmani, Richard Farnan, Yeshey Seldon, Tanna Tan, Shriya Varghese, Mohammad Alherz, Muaaz Ather, Mohammad Bajilan, Vivien Graziadei, Isobel Pilkington, Omar Quidwai, Paul Ridgway, Haaris Shiwani, Abd al-Rahman Tahir, Eimear Blunnie, Daniel Burke, Niall Kennedy, Kate Macdonagh, Maeve O'Neill, Siobhan Rooney, Giuseppe Falco, Guglielmo Ferrari, Simone Mele, Gabriela Elisa Nita, Lara Ugoletti, Maurizio Zizzo, Gianmaria Confalonieri, Giovanni Pesenti, Fulvio Tagliabue, Gianluca Baronio, Deborah Ongaro, Giacomo Pata, Bruno Compagnoni, Renato Salvadori, Lucio Taglietti, Nicola D'Alessandro, Pierpaolo Di Lascio, Giovanni Pascale, Luca Bortolasi, Tommaso Campagnaro, Massimo Carlini, Giorgio Lisi, Davide Lombardi, Corrado Pedrazzani, Domenico Spoletini, Giulia Turri, Paola Violi, Donato Francesco Altomare, Fabrizio Aquilino, Nicola Musa, Vincenzo Papagni, Arcangelo Picciariello, Leonardo Vincenti, Dario Andreotti, Savino Occhionorelli, Matteo Tondo, Stefano Maria Massimiliano. Basso, Paolo Ubiali, Riccardo Cirelli, Marco Enrico Mario Maino, Guglielmo Niccolò Piozzi, Emanuele Picone, Rosa Scaramuzzo, Giovanni Sinibaldi, Alfonso Amendola, Lorenzo Anastasio, Luigi Bucci, Emanuele Caruso, Antonio Castaldi, Sara Di Maso, Vincenza Paola Dinuzzi, Giovanni Esposito, Maria Gaudiello, Mariano Cesare Giglio, Paola Antonella Greco, Gaetano Luglio, Andrea Manfreda, Ester Marra, Federica Mastella, Gianluca Pagano, Roberto Peltrini, Vincenzo Pepe, Michele Sacco, Viviana Sollazzo, Giovanni Spiezio, Ettore Cianchetti, Nunzia Menduni, Michele Maria Carvello, Francesca Di Candido, Antonino Spinelli, Fabio Corsi, Luca Sorrentino, Fabio Marino, Emanuele Luigi Giuseppe Asti, Luigi Bonavina, Emanuele Rausa, Martina Asta, Andrea Belli, Francesco Bianco, Carmela Cervone, Paolo Delrio, Armando Falato, Andrea Fares Bucci, Rita Guarino, Ugo Pace, Daniela Rega, Emilia De Luca, Gaetano Gallo, Giuseppe Sammarco, Giuseppe Sena, Giuseppina Vescio, Letizia Santandrea, Giampaolo Ugolini, Davide Zattoni, Nicola Chetta, Gaetano Logrieco, Serafino Vanella, Gianluca Garulli, Nicola Zanini, Andrea Bondurri, Francesco Cammarata, Francesco Colombo, Diego Foschi, Giulia Maria Beatrice Lamperti, Anna Maffioli, Gianluca Matteo Sampietro, Al'ona Yakushkina, Gloria Zaffaroni, Enrico Cicuttin, Maria Grazia Sibilla, Harmony Impellizzeri, Marco Inama, Gianluigi Moretto, Sylvie Mochet, Elisa Ponte, Antonella Usai, Stefano Mancini, Andrea Sagnotta, Luigi Solinas, Elisa Bolzonaro, Nicolò Tamini, Gianluca Curletti, Raffaele Galleano, Michele Malerba, Sofia Campanella, Gianfranco Cocorullo, Francesco Colli, Paolino De Marco, Nicolò Falco, Tommaso Fontana, Leonel jospin Kamdem Mambou, Antonella La Brocca, Leo Licari, Brenda Randisi, Giovanna Rizzo, Giulia Rotolo, Giuseppe Salamone, Roberta Tutino, Paolina Venturelli, Stefano Malabarba, Alessandro Sgrò, Ivan Vella, Bruno Cirillo, Daniele Crocetti, Giorgio De Toma, Pierfrancesco Lapolla, Andrea Mingoli, Paolo Sapienza, Angela Belvedere, Stefania Bianchini, Margherita Binetti, Arianna Birindelli, Valeria Tonini, Mauro Podda, Fabio Pulighe, Michele De Rosa, Lorenzo Bono, Felice Borghi, Paolo Geretto, Maria Carmela Giuffrida, Corrado Lauro, Alessandra Marano, Luca Pellegrino, Paola Salusso, Diego Sasia, Michela Campanelli, Alberto Realis Luc, Mario Trompetto, Roberto Cardia, Nicola Cillara, Antonio Nicola Giordano, Antonio Costanzo, Mario Alessandro Giovilli, Luca Turati, Silvestro Canonico, Guido Sciaudone, Francesco Selvaggi, Lucio Selvaggi, Nader Albsoul, Ahmad AlBsoul, Ala'a Aldeen Alkhatib, Osama Alsallaq, Justin Z. Amarin, Rami Ayoub, Isam Bsisu, M S El Muhtaseb, Mohammad Jabaiti, Jamal Melhem, Yasmeen Z. Qwaider, Mohammad Hasan Salameh, Ahmad Suleihat, Haya H. Suradi, Mohammad Alammarin, Almoutuz Aljaafreh, Mohammad Bani hani, Zeina Bani hani, Farah Bani Hani, Toqa Fahmawee, Shadi Hamouri, Cyrine Katanani, Ra'fat Tawalbeh, Tamara Tawalbeh, Hassan Zawahrah, Mohamad K. Abou Chaar, Lana Abusalem, Mahmoud Al-Masri, Hani Al-Najjar, Lutfi Barghuthi, Zahra Ahmed, Adnan Maulana, Omar Ngotho, Charbel Kamau, Aruyaru Stanley Mwenda, Fridah Bosire, Elizabeth Mwachiro, Robert Parker, Ian Simel, Kimutai Sylvester, Abdulmunem Ahmed Mustafa Althini, Sofian Elbarouni, Aya Elseed Elbeshina, Ahmed Gwea, Ans Malek, Wedad Albashir Masoud Farag, Abdulwahab Abdalei, Abu Baker Abdel Malik, Areej Abo-khammash, Ma'aly Abuhlaiga, Nour Adnan, Marwa Albaggar, Asma Alfitory, Asma Aljanfi, Fakhruddin Almuzghi, Zohoor Altumei, Fatima Alzabti, Hana Ashoushan, Mohamed Assalhi, Joma Azzubia, Sondos Bnhameida, Malik Delhen, Houssein Elshafei, Hana Elteir, Fatima Esbaga, Abdel Aziz Gobbi, Fatma Hamouda, Hamdan Hilan, Rania Ismail, Fieruz Jebran, Muataz Kasbour, Galia Maderi, Saja Mohammad, Burooj Mohammed, Habib Murtadi, Hamassat Mustafa, Mohamed Rajab, Sarah Trenba, Mariam Wafaa, Eman Al Sagheir, Alabas Almigheerbi, Ahmed Alzahaf, Sumayyah Ghayth Bahroun, Najah Ben Dallah, Mahmoud Elshaibani, Haitem Eswaye, Maha Karar, Samah Omar, Eman Younes, Maha Younes, Dafer Zreeg, Saleh Abujamra, Firas Ashour, Mala Elgammudi, Wesal Omar F. Aljadidi, Enas Saddouh, Randa Sharif, Aya Alabuzidi, AbdulMawlay Alwerfally, Sarra Aribi, Fatma Bibas, Taha Elfaituri, Yasmine Elhajjaji, Ala Khaled, Wegdan Khalil, Tesneem Layas, Enas Soula, Ahmed Tarek, Muad fathi khalleefah Abu hallalah, Hazem Abdelkarem Ahmed, Tagwa Alsharef, Abdulsalam Ali Ben Saoud, Tasnim El Gharmoul, Ahmed Elhadi, Safa Elrais, Abdulhalim Shebani, Heba Zarti, Asaid Zeiton, Marijus Ambrazevicius, Nerijus Kaselis, Migle Stakyte, Oleg Aliosin, Agne Cizauskaite, Sarunas Dailidenas, Vitalijus Eismontas, Migle Kybransiene, Vitalija Nutautiene, Narimantas Samalavicius, Dainius Simcikas, Algirdas Slepavicius, Albinas Tamosiunas, Nerijus Ubartas, Paulius Zeromskas, Saulius Bradulskis, Edvinas Dainius, Juozas Juočas, Egle Kubiliute, Juozas Kutkevičius, Aurimas Opolskis, Audrius Parseliunas, Andrejus Subocius, Egle Virbickaite, Diana Zuikyte, Algirdas Bogusevicius, Kristina Buzaite, Daiva Čepuliené, Ieva Cesleviciene, Vaidotas Cesna, Jolanta Gribauskaite, Povilas Ignatavicius, Mantas Jokubauskas, Monika Liugailaitè, Ernest Margelis, Ruta Mazelyte, Lina Pankratjevaitè, Matas Pažusis, Agne Rackeviciute, Justina Saladyte, Monika Škimelytè, Vygintas Šlenfuktas, Monika Sudeikyte, Algimantas Tamelis, Tomas Vanagas, Žygimantas Žumbakys, Aivaras Atkociunas, Audrius Dulskas, Justas Kuliavas, Justas Birutis, Sigitas Paškevičius, Mindaugas Šatkauskas, Donatas Danys, Matas Jakubauskas, Lina Jakubauskiene, Marius Kryzauskas, Vytautas Lipnickas, Gabija Makūnaitè, Fanjandrainy Rasoaherinomenjanahary, Herizo Rasolofonarivo, Luc Hervé Samison, Bitiel Banda, Vanessa Msosa, Ahmad Imran Ahmad Izzuddin, Andre Das, Ying Yee Gan, Tan Shong Sheng, Jia yng Siaw, Mohd Fadliyazid Ab Rahim, Dyg Zahratul Hamrak Abang Jamari, Nurfariza Che Husin, Muhd Yusairi Kamarulzaman, Yi Ping Lim, Nil Amri Mohamed Kamil, Mohd Razeen Mohd Hassan, Saidah Mohd Sahid, Johari Mustafa, Elaine Hui Been Ng, Wan Khamizar Wan Khazim, Ng Chang Ern, P.g. Lingeshan, Syariz Ezuan Sulaiman, Sue Ean Ang, Muhammad Navid Bin Mohamad Sithik, Yih Jeng Cheong, Mahadevan Deva Tata, Law Jia Xian, Aravinthan Kadravello, I-Ern Koh, Li-Yen Ng, Yuki Julius Ng We Yong, Kandasami Palayan, Chi Xuan Sam, Phuah Siow Jin, Jeremy Tan Ern Hwei, Yita Tang, Alvin Zubin Ter, Michael Pak-Kai Wong, Andee Dzulkarnaen Zakaria, Zaidi Zakaria, Fitjerald Henry, Thyivya Kalaiselvan, Muhammad Fairuz Shah Abd Karim, Mohamed Rezal Abdul Aziz, Nora Abdul Aziz, Tak Loon Khong, Peng Choong Lau, Hiong Chin Lim, April Camilla Roslani, Jonathan Chen Ken Seak, Sui-Weng Wong, Lai Fen Wong, Leow Yeen Chin, Mercy Chinemerem Anyanwu, Zachary Busuttil, Thomas Calleja, Kurt Lee Chircop, Ruth Cutajar, Andrew Michael Dimech, Joseph Galea, Kiara Gascon Perai, Ruth Gatt, Lisa Kelman, Elizabeth Micallef, Favour Nwolu, Kim Sammut, Joanna Thompson, Sean Warwicker, Matthew Zammit, Fernando Cordera, Efraín Cruz González, Jorge Sánchez-García, Francisco José Barbosa Camacho, Francisco Javier Barrera López, Carlos Jose Zuloaga Fernandez del Valle, Eric Acosta, Iván Romarico González Espinoza, Perla Moreno, Ana Olivia Cortes-Flores, Clotilde Fuentes Orozco, Alejandro Gonzalez Ojeda, Samantha Corro Díaz González, Laura Martinez, Bonifacio Mosqueda Amador, Armando Novoa, Dennet Arturo Olazo Espejo, Alejandro Jimenez, Federico Lopez Rosales, Elva Gabriela Vanoye, Luis Alberto Garcia Gonzalez, Roberto Carlos Miranda-Ackerman, Manuel Solano-Genesta, Alethia Alvarez-Cano, Hector Hugo Romero-Garza, Heriberto Medina-Franco, Lorelí Mejía-Fernández, Noel Salgado-Nesme, Omar Vergara-Fernandez, Guadalupe Montserrat Gutiérrez-Mota, Francisco Xavier Hernandez Vera, Anabella Llantada Lopez, Gilberto Morgan Villela, Felipe de Jesus Ramirez Padilla, Walezka Tapia Marin, Mónica Martínez Maldonado, Ramses Sánchez Suárez, José Manuel Troche, Chaymae Benyaiche, Oumaima Outani, Souadka Amine, Amine Benkabbou, Anass Mohammed Majbar, Raouf Mohsine, Ali Rafik, Thida Oung, Moe Moe Tin, Philipp Plarre, Anna Alberga, Nina Sluiter, Jurriaan Tuynman, Robin Blok, Didem Cömert, Roel Hompes, Marianne Kalff, Merel Elisabeth Stellingwerf, Pieter Tanis, Mark van Berge Henegouwen, Elise Maria van Praag, Daan Wisselink, Michael Gerhards, Josephine Lopes Cardozo, Emma Westerduin, Joske de Jonge, Aaw van Geloven, Kaz van Schilt, Frank den Boer, Simone Stoots, Stijn Vlek, Jamie Adams, Ibrahim S. Al-Busaidi, Gabrielle Budd, Seung il Choi, Michael Jen Jie Chu, Anurag Ganugapati, Lucy McKinstry, Rebecca Pascoe, Simon Richards, Kenrick Rosser, Annie Stevenson, Rebecca White, Shebani Farik, Jin Kwun, Ahmed Murad, Sarah Cowan, Timothy Hall, Michael Hayton, Laminou Malam Sani, Souleymane Oumarou Garba, Ibrahim Amadou Magagi, Oumarou Habou, Halima Aliyu, Muhammad Daniyan, Tunde T. Sholadoye, Lawal Abdullahi, Lofty-John Anyanwu, Aminu Mohammad Mohammad, Abubakar Bala Muhammad, Abdurrahman Abba Sheshe, Ibrahim Suleiman, Alaba Adesina, Ajibola Awolowo, Clement Onuoha, Omotayo Salami, Ogechukwu Taiwo, Agboola Taiwo, Stephen Kache, Jerry Godfrey Makama, Danjuma Sale, Olajide Abiola, Akinlabi Ajao, Anthony Ajiboye, Amarachukwu Etonyeaku, Julius Olaogun, Ademola Adebanjo, Opeoluwa Adesanya, Michael Olatunji Afolayan, Olanrewaju Balogun, Ayomide Makanjuola, Samuel Nwokocha, Rufus Wale Ojewola, Thomas Olagboyega Olajide, Adewale Aderounmu, Abdul-Rashid Adesunkanmi, Augustine Agbakwuru, Adeleke Akeem Aderogba, Olusegun Isaac Alatise, Olukayode Arowolo, Oladejo Lawal, Tajudeen Mohammed, Chinedu Ndegbu, Olalekan Olasehinde, Funmilola Wuraola, Akinbolaji Akinkuolie, Arinzechukwu Mosanya, Omobolaji Ayandipo, Peter Elemile, Taiwo Akeem Lawal, Samuel Ali SANI, Stephen Garba, Rebecca Hauwa SANI, Samson Olori, Henry Onyebuashi, Ifeanyi Umoke, Adedire Adenuga, Ademola Adeyeye, Olufemi Habeeb, Bashir Lawal, Abdulrasheed Nasir, Eirik Kjus Aahlin, Didrik Kjønås, Elisabeth Myrseth, Jibran Abbasy, Abdul Alvi, Omair Saleem, Asma Afzal, Anam Nazir, Muhammad Farooq, Ayesha Liaqat, Syed Asghar Naqi, Ali Raza, Muzna Sarfraz, Muhammad Sarwar, Muntaha Banglani, Ambreen Munir, Rahmat Sehrish, Bushra Ayub, Raza Sayyed, Amna Altaf, Saima Ayub, Komal Saeed, Bilal Syed, Sana Amir Akbar, Abdul Wahid Anwer, Ruqayya Naheed Khan, Amina Iqbal Khan, Shahid Khattak, Sameen Mohtasham, Muhammad Asad Parvaiz, Aamir Ali Syed, Abdul Basit Ansari, Noman Shahzad, Tanwir Khaliq, Isbah Rashid, Shahzad Hussain Waqar, Hasan Abu Al-saleem, Amjad Abu Alqumboz, Mohammad Alqadi, Adham Amro, Rawan Assa, Eman Awesat, Rawan Ayyad, Mohammed Hammad, Ayat Haymony, Bassel Hijazi, Bara Hmeidat, Rowaa Lahaseh, Aseel Qawasmi, Alaa Rajabi, Mohammed Shehada, Sundus Shkokani, Yasmine Yaghi, Nadine Yaghi, Mohammad AlZohour, Mohammad Farid, Yousef Mahmoud Habes, Wesam Juba, Yanal Nubani, Abdelrahman Rabee, Mohammad Sa'deh, Saeed Abed, Iyad Al basos, Mohammad Alswerki, Dina Ashour, Israa Awad, Samar Diab, Alaa El Jamassi, Sahar El-Kahlout, Somaya Elhout, Ahmed N K Hajjaj, Doaa Hasanain, Baraa Nabil hajjaj, Mohammed Obaid, Eman Saikaly, Ahmed Salhi, Hiba Al-Tammam, Murad Almasri, Muath Baniowda, Doha Beshtawi, Ali Horoub, Rami Misk, Bayan Mohammad, Rami Qasrawi, Tasnim Sholi, Samar Abu-Nimeh, Abrar Abu-srour, Sadi A. Abukhalaf, Samer Adawi, Barah Alsalameh, Kholoud Ayesh, Muawiyah Elqadi, Ahmad Hammouri, Fatima Karim Mustafa, Natalie Marzouqa, Shatha Melhem, Dima Miqdad, Balqees Mohamad, Mhammed Rawhi, Ayman B. Abu Ahammala, Ahmed Abu Ataya, Israa Abu Jayyab, Samar Al-Shwaikh, Othman Alagha, Mohammed Alasttal, Haneen Awadallah, Mahmood Elblbessy, Jehad Fares, Akram Jarbou, Ibtisam Mahfouz, Moath A. Albahnasawi, Asmaa' Abo mahadi, Hasan Abuelhatal, Ayham Abuelqomboz, Abdelrahman Almoqayyad, Abdallah Alwali, Reem Balaawi, Mahmoud Hamouda, Mohammed Humeid, Abdullah Jedyan, Tasneem Mahmoud Abu hamam, Ghadeer Matar, Ali Salem, Tahani Samra, Nureddin Shaheen, Karam Shihada, Ayoob A.Nemer, Mahmoud Abu Al Amrain, Abdulwhhab Abu Alamrain, Najlaa Abu Jamie, Mohammed R. Abu-Rous, Nada Alfarra, Mohammed AlTaweel, Noor Alwhaidi, Ramadan Hamed, Bader Saqqa, Ahmad Shaheen, Dana Aljaber, Loay Aljaberi, Malak Alwaheidi, Assef Jawaada, Hani Khaldi, Rami Qahoush, Jalil Qari, Rana Saadeh, Ahlam Salim, Aseel Yacoub, Abbas Abbas, Rana Abu shua'ib, Baraa Abu Zainah, Mahmoud AbuSirrees, Basheer Babaa, Ola Barhoush, Asef Belal qadomi, Laith Daraghmeh, Reema Haji, Alaa Khatatbeh, Lana Khatib, Salsabeel Qarariah, Yara Quzmar, Khalil Safadi, Roqaya Salameh, Mohammad Hassan, Shifaa Herzallah, Loai Massad, Ahmed Nazzal, Ranin Nazzal, Dennis Escobar, Gustavo Miguel Machain V, Agustin Rodriguez Gonzalez, Jorge Emerson Chachaima Mar, Nathaly Olga Chinchihualpa Paredes, Vicente Cuba, Walter Lopez, Maria Milagros Niquen Jimenez, Nestor Alberto Sanchez Bartra, Olenka Sapallanay Ojeda, Diego Sequeiros, Andrea Toscano Pacheco, María Vergara, Sol Abarca, Rodrigo Alcorta, Giuliano Borda-Luque, Ivan Edward Eusebio Zegarra, Claudia Luján López, Mirella Marrufo, Cinthya Mogrovejo, Andrea Nomura, Yamile Rodríguez Angeles, Maitza Rosario Vidal Meza, Gabriela Zavala, José Neiser Castillo Arrascue, Jomara Caroline Hidrogo Cabrera, José Julio Mariano Larrea vera, Miguel Osorio, Edgar Alcides Ylatoma Díaz, Mark Anthony Fontanilla, Joseph Roy Fuentes, Anna Leah Salazar, Genieve Dominguez, Marc Paul Lopez, Shiela Macalindong, Mark Augustine Onglao, Arjel Ramirez, Marie Dione Sacdalan, Mayou Martin Tampo, Gemma Leonora Uy, Jeremiah Mangahas, Kenneth Yabut, Joannes Paul Cañete, Bernalynn Eris Cansana, Ernes John Castro, Maria Kaiserin Lipana, Manuel Francisco Roxas, Vlu Jean Zara, Maciej Chroł, Paula Franczak, Michał Orłowski, Piotr Budzyński, Andrzej Budzyński, Pawel Bury, Agata Czerwińska, Jadwiga Dworak, Jacek Dziedzic, Michał Kisielewski, Jan Kulawik, Anna Lasek, Piotr Małczak, Marcin Migaczewski, Michał Pędziwiatr, Magdalena Pisarska, Dorota Radkowiak, Mateusz Rubinkiewicz, Anna Rzepa, Tomasz Skoczylas, Maciej Stanek, Katarzyna Truszkiewicz, Mateusz Wierdak, Marek Winiarski, Piotr Zarzycki, Anna Zub-Pokrowiecka, Piotr Kowalewski, Rafał Roszkowski, Maciej Walędziak, Miguel Tomé, Sara Patrocinio, Ines Guerreiro, Filipe Almeida, Xavier de Sousa, Nuno Monteiro, Maria Teresa Costa Santos, Daniela de Oliveira, Marta Lopes Serra, Daniela Morgado, Christian Neves, Ana Carolina Oliveira, Alice Pimentel, Sofia Silva, Márcia Carvalho, Lúcia Carvalho, Joana Magalhães, Leonor Matos, Tânia Monteiro, Carlota Ramos, Vanessa Santos, José Barbosa, Jose Costa-Maia, Vítor Devezas, Ana Fareleira, Cristina Fernandes, Diana Gonçalves, Henrique Mora, Marina Morais, Fabiana Silva de Sousa, Sara Catarino Santos, Ana Logrado, André Tojal, Edgar Amorim, Miguel F. Cunha, Ana Fazenda, João Pedro Melo Neves, Inês Isabel Sampaio da Nóvoa Gomes Miguel, Diogo Veiga, José Azevedo, Hugo Cardoso Louro, Mariana Leite, Maria Bairos Menezes, Bárbara Gama, Diana Brito, Marta Cristina Cruz Martins, André Graça e Magalhães, Ana Catarina Longras, Rita Lourenço, Diana Matos, Luis Castro, Filipa Policarpo, Joana Romano, Cristina Monteiro, Diogo Pinto, Marina Duarte, Sónia Fortuna Martins, Mariline Oliveira, Diogo Galvão, Lisandra Martins, Anaisa Silva, Viorel Taranu, Bárbara Vieira, Jessica Neves, Simone Oliveira, Hugo Ribeiro, Margarida Cinza, Rosa Felix, Arnaldo Machado, Joana Oliveira, Joana Patrício, Rita Pedroso de Lima, Mário Pereira, Miguel Rocha Melo, Cristina Velez, Alberto Abreu da Silva, Mariana Claro, Daniel Costa Santos, Andreia Ferreira, Hugo Capote, Daniela Rosado, Filipa Taré, Oriana Nogueira, Miguel Ângelo, José Miguel Baiao, Andreia Guimarães, João Marques, Miguel Nico Albano, Marta Silva, Ana Valente da Costa, Teresa Vieira Caroço, Sara Almeida Braga, Ines Capunge, Marta Fragoso, João Guimarães, Bruno Pinto, João Ribeiro, Miguel Angel, Guilherme Fialho, Monica Guerrero, Filipa Campos Costa, Diogo Cardoso, Vasco Cardoso, Magda Alves, Inês Estalagem, Tiago Louro, Cláudia Marques, Rita Martelo, Miguel Morgado, Rita Canotilho, Ana Margarida Correia, Pedro Martins, Mariana Peyroteo, João Gomes, Rita Monteiro, Manuela Romano, Daniela Macedo Alves, Rita Peixoto, Catarina Quintela, Maria João Jervis, Débora Melo, André Pacheco, Valter Paixão, Vera Pedro, Joana Pimenta, João Pimenta de Castro, Ana Rocha, Mircea Beuran, Cezar Ciubotaru, Bogdan Diaconescu, Sorin Hostiuc, Ionut Negoi, Bogdan Stoica, Evgeny Anokhin, Georgy Kuznetsov, Giorgi Oganezov, Fedor Paramzin, Ekaterina Romanova, Valeryan Rutkovskii, Vasilii Rutkovskii, Mikhail Shushval, Mikhail Zabiyaka, Khasan Dzhumabaev, Valerii Ivanov, Zaman Mamedli, Sergey Achkasov, Artem Balkarov, Elnur Nabiev, Marat Nagudov, Evgeny Rybakov, Karina Saifutdinova, Oleg Sushkov, Lule Joseph, Isaac Ndayishimiye, Ntirenganya Faustin, Alphonse Zeta Mutabazi, Jean Paul Mvukiyehe, Vizir J.P Nsengimana, Carine Uwakunda, Mohammad Monir Abbas, Nouf Akeel, Murad Aljiffry, Kholoud Awaji, Ali Farsi, Ghader Jamjoum, Ahmad Khoja, Ashraf Maghrabi, Nadim Malibary, Mohammed Nassif, Abdulaziz Saleem, Abdullah Sultan, Wail Tashkandi, Hanaa Tashkandi, Nora Trabulsi, Mouhamadou Bachir Ba, Adja Coumba Diallo, Abdourahmane Ndong, Vladica Cuk, Uroš Janković, Sharon Zhiling Koh, Frederick Koh, Kuok Chung Lee, Kai Yin Lee, Sean Lee, Wei Qi Leong, Su Ann Lui, Prajwala Prakash, Jan Grosek, Gregor Norcic, Ales Tomazic, Nicolas Fitchat, Robert Jaich, Devorah Wineberg, Modise Zacharia Koto, Daniella Baiocchi, Damian Clarke, Christina Johanna Steenkamp, Sharon Bannister, Adam Boutall, Galya Chinnery, Anna Coccia, Angela Dell, Parveen Karjiker, Christo Kloppers, Nicholas Loxton, Tumi Mabogoane, Francois Malherbe, Eugenio Panieri, Shreya Rayamajhi, Tirsa van Wyngaard, Claire Warden, T E Madiba, Nivashen Pillay, Savannah Brooks, Charlise Kruger, Lisa Hannah Van Der Merwe, Ferhana Gool, Maahir Kariem, Heather Bougard, Nazmie Kariem, Fazlin Noor, Reantha Pillay, Leandi Steynfaardt, Lucía González González, José Miguel Marín Santos, Paula Martín-Borregón, Javier Martínez Caballero, Cristina Nevado García, Pastora Rodriguez Fraga, Gonzalo De Castro Parga, Maria Pilar Fernández Veiga, Lucía Garrido López, Hugo Infante Pino, Irene Lages Cal, Marta López Otero, Manuel Nogueira Sixto, Marta Paniagua García Señorans, Laura Rodríguez Fernández, Alejandro Ruano Poblador, Erika Rufo Crespo, Raquel Sanchez-Santos, Vincenzo Vigorita, Ester Alonso Batanero, Dorisme Asnel, Isabel Cifrian Canales, Elisa Contreras Saiz, Irene De Santiago Alvarez, Tamara Díaz Vico, Sebastian Fernandez Arias, Daniel Fernández Martínez, Carmen García Bernardo, Luis Joaquín García Flórez, Carmen Garcia Gutierrez, Manuel García Munar, Carlos Alberto Márquez Zorrilla Molina, Marta Merayo, José Luis Michi Campos, Maria Moreno Gijon, Jorge L. Otero-Diez, Jose Luis Rodicio Miravalles, Lorena Solar-Garcia, Aida Suárez Sánchez, Nuria Truan, Cristina Alejandre Villalobos, Yurena Caballero Díaz, Marta Jimenez, Dacil Montesdeoca, Antonio Navarro-Sánchez, Victor Vega, Juan Beltrán de Heredia, Zahira Gómez, Carlos Jezieniecki, Ana Patricia Legido Morán, Mario Montes-Manrique, Mario Rodriguez-Lopez, María Ruiz Soriano, Jeancarlos Trujillo Díaz, Andrea Vazquez Fernandez, Nuria Argudo, Miguel Pera, Laia Torrent Jansà, Melody García Domínguez, Ignacio Goded, Marta Roldón Golet, Issa Talal El-Abur, Alejandra Utrilla Fornals, Vanesa Zambrana Campos, Maria Del Mar Aguilar Martinez, Marina Bosch, Luis García-Catalá, Luis Sánchez-Guillén, Eva Artigau, Nuria Gomez Romeu, David Julià Bergkvist, Beatriz Espina Perez, Olga Morató, Carles Olona, Beatriz Diéguez, Alexander Forero-Torres, Manuel Losada, Segundo Gomez-Abril, Paula Gonzálvez, Rosario Martinez, Sergio Navarro Martínez, Carmen Payá-Llorente, Álvaro Pérez Rubio, Sandra Santarrufina Martinez, Juan Carlos Sebastián Tomás, Ramon Trullenque Juan, Alberto Gegúndez Simón, Paloma Maté, Maria Isabel Prieto-Nieto, Ines Rubio-Perez, Aitor Urbieta, Marina Vicario Bravo, David Abelló, Matteo Frasson, Alvaro Garcia-Granero, Alfredo Abad Gurumeta, Ane Abad-Motos, Elena Lucena-de Pablo, Beatriz Nozal, Javier Ripollés-Melchor, Rut Salvachúa, Esther Ferrero, Luis Garcia-Sancho Tellez, Antonio L. Picardo, Jose Alberto Rojo López, Laura Patricia Zorrilla Matilla, Carmen Cagigas Fernandez, Sonia Castanedo Bezanilla, José Estevez Tesouro, Maria Jose Fernandez-Diaz, Juan García Cardo, Marcos Gomez Ruiz, Erik Gonzalez-Tolaretxipi, Jaime Jimeno Fraile, Cristobal Poch, Montserrat Rodriguez-Aguirre, Noemí Troche Pesqueira, Maria Soledad Trugeda-Carrera, Javier de la Torre, Ruth Blanco-Colino, Eloy Espin-Basany, Martin Espinosa-Bravo, Clara Morales Comas, Eduardo Reyes Afonso, Joaquín Rivero Déniz, Christian Siso Raber, Mireia Verdaguer Tremolosa, Pramodh Chandrasinghe, Sumudu Kumarage, Nimeshi Wijekoon Arachchilage, Ahmed Abdalla Ahmed Elkamel, Mohammed A. Adam, Nina Blomme, Anders Thorell, Fredrik Wogensen, Andreas Älgå, Dhirar Ansarei, Fuat Celebioglu, Göran Heinius, Linda Nigard, Emil Pieniowski, Sandra Ahlqvist, Ida Björklund, Andreas Frånberg, Martina Håkansson, Karin Adamo, Oskar Franklin, Malin Sund, Rebecca Wiberg, Yvette Andersson, Abbas Chabok, Maziar Nikberg, Alexander Kugelberg, Claudia Canonica, Dimitrios Christoforidis, Fabrizio Fasolini, Paolo Gaffuri, Mauro Giuliani, Francesco Meani, Sotirios Georgios Popeskou, Silvia Pozza, Wiebke Wandschneider, Lorenz Peterer, Lukas Werner Widmer, Bernd Zimmermann, Panagiotis Bakoleas, Iris Chanousi, Lydia Charalampidou, Lukasz Filip Grochola, Franziska Heid, Sotirios Ntaoulas, Michail Outos, Georgios Peros, Hanna Podolska-Skoczek, Katharina Beate Reinisch, Christian Zielasek, Nicolas Demartines, Jérôme Gilgien, Amaniel Kefleyesus, Pénélope St-Amour, Arnaud Toussaint, Maryam Alhimyar, Bayan Alsaid, Amr Alyafi, Ahmad Alkhaledi, Basel Kouz, Ahmad Omarain, Yusra Al-Sabbagh, Haya Alkhatib, Samer Sara, Ahmad Alhaj, Aghyad Danial, Lama Kadoura, Sarah Maa Albared, Yamen Monawar, Louei Nahas, Barook Abd, Ahmad Saad, Habib Wakkaf, Hatem Bouzaiene, Montassar Ghalleb, Elif Akaydin, Ata Cem Akbaba, Onur Atakul, Ege Baltaci, Sevval Besli, Gökçen Burgu, Ulukan Cenal, Cansu de Muijnck, Hasan Can Demirkaya, Alper Dogruoz, Zeynep Ipek Gezer, Yasemin Gündoğdu, Merve Kara, Hasan Kürşad Korkmaz, Gökalp Kağan Kurtoğlu, Volkan Ozben, Berk Baris Ozmen, Ahmet Murat Pektaş, Eda Kübra Sel, Nilüfer Yenidünya, Fuat Baris Bengur, Berke Mustafa Oral, Tahir Koray Yozgatli, Seymur Abdullayev, Mehmet Emin Gunes, Nuri Alper Sahbaz, Tuba Banaz, Kübra Kargici, Omer Faruk Kuyumcu, Erkan Yanikoğlu, Merve Yeşilsancak, Duygu Yilmaz, Melik Kagan Aktas, Ahmet Rencuzogullari, Arda Isik, Sezai Leventoğlu, Ali Yalçinkaya, Osman Yüksel, Mustafa U Kalayci, Yasin Kara, Inanc Samil Sarici, Alp Akin, Gökçe nur Alemdağ, Ekin Arslan, Bahadir Emre Baki, Muhammed Selim Bodur, Adnan Calik, Bahar Candas Altinbas, Irem 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Henderson, Bilal Ibrahim, Thummini Jayasinghe, Jennifer Livie, Keir Mailley, Gopikrishnan Nair, Daniel Tan, Caitlin Baggaley, Aleksander Dawidziuk, Bartosz Szyszka, Charlotte Barter, Nirav Gandhi, Karen Hassell, Samantha Hitchin, Jennett Kelsall, Eva Nagy, Ashrafun Nessa, Lisa Whisker, Fady Yanni, Mahmoud Ali, Deeksha Arora, Sunanda Hediwattege, Navam Kumarasinghe, Munir Rathore, Athula Tennakoon, Syed Mustafa Ali Ahmad, Oreoluwa Bajomo, Fahema Nadira, Valerio Celentano, Ewen Griffiths, Rama Santhosh Karri, Jason Kei Chak Mak, Michelle Pipe, Muhammad Iqbal Bhatti, Mohamed Rabie, Connor Boyle, David Hamilton, Aishath Mihuna, James Chean Khun Ng, Gary Nicholson, Agata Oliwa, Robert Pearson, Anna Rose, Shun Qi Yong, Catherine Boereboom, Michael Hanna, Catherine Walter, Thomas Samuel Greensmith, Rachel Mitchell, Eimear Monaghan, James Crawford, Susan Moug, James Blackwell, Hannah Boyd-Carson, Philip Herrod, Omar Al-Allaf, Miriam Beattie, Cameron Bullock, Shivang Burman, Gemma Clark, Nicolas Flamey, Oliver Flannery, Alexander Harding, Ben Kodiatt, Samuel Lawday, Shivani Mahapatra, Navin Mukundu Nagesh, Michael Ng, Dupinderjit Rye, Andrel Yoong, Laura Clark, Chris Deans, Monisha Edirisooriya, Emma Victoria Carrington, Tsz Lun Ernest Wong, Baasil Yusuf, Carla Chamberlain, Kathryn Duke, Elizabeth Kmiotek, Azel Botes, Natalie Condie, Timothy Schrire, Reena Shah, Iolo Thomas-Jones, Charlotte Yates, Natasha Anthony, Edward Matthews, Kapil Sahnan, James Tankel, Sally Tucker, Jasmine Winter Beatty, Paul Ziprin, William Duggan, Anastasia Kantartzi, Shruthi Sridhar, Rachel Alys Khaw, Prakhar Srivastava, Charlotte Underwood, Homero Alves do Canto Brum, Sharat Chopra, Laura Davis, Rebecca Hughes, Joshua Tulley, Justin Alberts, Thomas Athisayaraj, Mojolaoluwa Olugbemi, Kasim Ahmad, Claudia Chan, Gavin Chapman, Hannah Fleming, Benjamin Fox, Julia Grewar, Kate Hulse, Duncan Rutherford, Mackay Sinead, Scott Smith, Doug Speake, Peter G Vaughan-Shaw, Natasha Christodoulides, Simrit Kudhail, Matthew Welch, Syed Muhibullah Husaini, Simon Lambracos, Chikamuche Anyanwu, Rishi Suresh, Jimmy Scott Thomas, Elizabeth Gleeson, Rebecca Platoff, Areeba Saif, Zachary Enumah, Eric Etchill, Alodia Gabre-Kidan, Mitchell Bernstein, Francesco Maria Carrano, Joseph Connors, Patricio Lynn, Marcovalerio Melis, Elliot Newman, Deshka S Foster, Kenneth Perrone, Ashley Titan, Sarwat Ahmad, Andrea Chao M.D. Bafford, Marco Dal Molin, Nader Hanna, Syed Nabeel Zafar, Mark Hemmila, Lena Napolitano, Jane J Wong, Julia Chandler, Lauren Wood, Sherry Wren, Taylor Ottesen, Lucia You, Kristin Yu, María del pilar Arciénega Yañez, Martin Ferreira Fernandes, Daniel González, Santiago Cubas, María Catalina González, Vanessa Zubiaurre, Rodrigo Demolin, Nicolas Giroff, Pablo Sciuto, Maite Campos, Gabriela Rodríguez Cantera, Garg Deepika, Elliot Simuchimba, Anadi Bulaya, Chali Chibuye, Bright Chirengendure, Mary-Rose Kabale, Kizito Kabongo, James Munthali, Oliver Mweso, Francis Pikiti, James Otieno, Log Tung Lai, Brighid Blackman, Sophie Richards, Suren Subramaniam, Rafid Karim, Nathan Kok, Yanni Dion Lee, Shabina Ali, Aanjaneya Sinha, Robert Corrigan, Nicole Barnes, Florence Wong, Grace Dennis, Julia Jedamzik, Emil Phillips, Wivine Piette, Marie Van hentenryck, Houenoukpo Koco, Souliath Lawani, Mamo Woldu Kassa, Tainá Santos Bezerra, Petar Gribnev, Dobromir Dimitrov, Panche Krastev, Sovannarith Oum, Divine Tim Bonghaseh, Maryam Al Farsi, Nourah Alsharqawi, Veronica Acevedo, Andrea Carolina Castillo Barbosa, Felipe Giron, Jimmy Paul Leon Rodriguez, Darko Kučan, Damir Rosko, Neven Barsic, Domagoj Župan, Amgad Hegazi, Vendula Trunčíková, Vladimir Fryba, Mostafa Mohamed, Ahmed Sultan, Ahmed Nagi, Abdallah Rashad Temerik, Mohamed Elemam Elshawy, Moustafa Ibrahim Mahmoud, Shrouk Omar, Mohamed Anwar, Tarek Rageh, Aya Elmokadem, Khaled Gaballa, Sandra Teppo, Antti Turunen, Pasi Pengermä, Quentin Ballouhey, Damien Bergeat, Ariane Weyl, Elisabeth Hain, Adam Gyedu, Edwin Yenli, Dorcas Osei-Poku, Vaia-Aliki Rompou, Athanasios Zoikas, Apostolos Gaitanidis, Georgios Koukis, Konstantinos Perivoliotis, Panagiotis Tavlas, Konstantinos Galanos-Demiris, George Zografos, Ioannis Karavokyros, Georgia Xanthopoulou, Eirini Iordanidou, Fernanda Ayau, Allan Garcia, Pekli Damján, Deepender Wason, Ashika B L, Ervandy Rangganata, Prerna Kamath, Donal B O'Connor, Margherita Pinto, Fabrizio Perrone, Francesca Paola Tropeano, Francesca Troilo, Daniela Bossi, Dario Scala, Lucrezia Pulitanò, Marcella Carella, Andrea Pietrabissa, Alice Gori, Giorgio Giraudo, Veronica De Simone, Alfio Alessandro Russo, Bartolomeo Braccio, Raed Al-Taher, Sarah Athamneh, Andrea Parker, Adnan Sawiee, Amina Kattia, Malik Salem, Osama Tababa, Zuhour Shaeeb, Vilius Syminas, Jonas Jurgaitis, Gytè Damulevičienè, Saulius Svagzdys, Narindra Njarasoa Mihaja Razafimanjato, Ling Chieng Loo, Ing Ching Tiong, Wan Farahiyah Wan Muhmad, Harinthiran Vijeyan, Teoh Li Ying, Gabriella Grech, Rodrigo Arrangoiz, Vania Brickelia Jimenez Ley, Daniel Arizpe, Elizabeth Lagunes Lara, Elizabeth Victoria Castro López, Jose Eaazim, Marije Gordinou de Gouberville, Vivian Bastiaenen, Simone Rottier, Fouad Nahab, Maria Yeonhee Ji, Mohammed Seyoji, Callistus Nwachukwu, Okechukwu Emeghara, Sayyid Egbunu Muhammed, Ayodeji Idowu, Olamiposi Sowemimo, Olakayode Ogundoyin, Oluwatosin Akande, Alexander Lott, Maliha Nadeem, Ahsan Ali Laghari, Asif Loya, Hassan Mushtaq, Muhammad Tariq Abdullah, Baseel Abuhilal, Mohammad Atawneh, Hamdan Hamdan, Belal Alhabil, Abedelrahman Srour, Ibrahim Mousa, Luis Da Silva Medina, Katarzyna Bartosiak, Pedro Ferreira, Vítor Francisco, Ricardo Lemos, Luísa Frutuoso, Sara Fernandes, Telma Fonseca, Jorge Pereira, Juan Rachadell, Ana Torre, Filipe Madeira Martins, Ana Cristina Carvalho, Joana Rodrigues Ferreira, Bruno Ribeiro da Silva, Helena Devesa, Ana Vieira, Inês Mónica, Margarida Amaro, Diogo Sousa, Marta Reia, João Louro, Ana Martins, Joaquina Dominguez, Inês Santos, Nuno Miguel Freitas Oliveira, José Carlos Pereira, Pedro Silva-Vaz, Ligia Freire, Ricardo Escrevente, Valentina Madalina Negoita, Dmitry Shakhmatov, Yves Nezerwa, Radosav Radulovic, Gareth Obery, Francois Viljoen, Tome Mendes, Antonio Suarez, Enrique Moncada, Maria Fernandez-Hevia, Carolina Curtis Martínez, Julia Maria Gil Garcia, Mariana González Zunzarren, Tarig Idris, Karolina Eklöv, Oskar Grahn, Leila Amin, Malin Blomqvist, Costanza Ajani, Rebecca Kraus, Nico Seeger, Melissa Willemin, Fadi Rayya, Mohammad Ayash, Raneem Msouti, Israa Kannas, Eias Abazid, Asil Esper, Skander Slim, Akil Serdar Kavcar, Erman Aytac, Ahmet Cem Dural, Ayse Ilker, Ismail Cem Eray, Eray Kurnaz, Saygin Altiner, Mustafa Deniz Tepe, Can Şahin, Evrim Savli, Aryon Innocent, Lilian Babirye, Andrii Diachenko, Vladislav Hordoskiy, Heather Curry, Charlene Yat Che Chau, Harry Robertson, Arin Mahmoud, Hannah Lennon, Lynette Loi, Emily Kirkham, Cameron McCann, Daniel Watts, Binay Gurung, Michael Wilson, Thomas Tribedi, Eleonora Garofalo, Baryab Zahra, Scott MacDonald, Ian Daniels, Nathan Ng, Shivun Khosla, James Olivier, Sum Yu Pansy Yue, Gayathri Suresh, Jack Wellington, Emmanuel Lorejo, Mafdi Mossaad, Madison Crutcher, Marjan Alimi, Ioana Baiu, Hossam Abdou, Alison Conway, Connor Peck, Mauro Andres Perdomo Perez, Stanley Zulu, Mildred Nakazwe, Sule Burger, Justine Davies, Rachel Donaldson, Chikwendu Ede, O James Garden, Chiapo Lesetedi, Charles Mabedi, Laura Magill, Felix Makinde Alakaloko, Alex Makupe, Mark Monahan, Soloman Mulira, Elmi Muller, Jospeh Musowoyo, Jean Léon Olory-Togbe, Tracey Roberts, Martin Smith, Viki Tayler, John Windsor, Raul Yepez, Sudha Sundar, Emmy Runigamugabo, Azmina Verjee, José Chen, Leonid Daya, Nouhaila El Aroussi, Valeria Farina, Tchianze Gnintedeme Olivier, Mauricio Gonzales Nacarino, Aamr Hammani, Sarah Honjo, Rebecca Jacobs, Hitomi Kimura, Mugisha Nkoronko, Jasson Javier Oscullo Yepez, Wei Pin Hung, Ankit Raj, Alina Romani Pozo, Muna Rommaneh, Samuel Chimbioputo Sassamela Fabiano, Camila Milagros Shiroma Gago, Abhishekh Srinivas, Chia-Yen Sung, Aswan Tai, Yener Cristyell Valle Aranda, Sara Venturini, and Jean Wilguens Lartigue
Subjects: Public aspects of medicine, RA1-1270
Abstract: Summary: Background: Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide. Methods: A multimethods analysis was performed as part of the GlobalSurg 3 study—a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital. Findings: Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3·85 [95% CI 2·58–5·75]; p
Published: 2022
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49. Call Me... Maybe: A Framework for Integrating the Internet into ELT

Author: Chinnery, George M.
Abstract: This article outlines reasons to use (or not use) the Internet in English language teaching, exploring the Internet as tutor and tool. Discussion of Internet content includes types of content and how to select, save, and use content. Various learning tasks, appropriate even for those without Internet access, are presented and highlighted in a table.
Published: 2014

50. Oxygen tension modulates the mitochondrial genetic bottleneck and influences the segregation of a heteroplasmic mtDNA variant in vitro

Author: Mikael G. Pezet, Aurora Gomez-Duran, Florian Klimm, Juvid Aryaman, Stephen Burr, Wei Wei, Mitinori Saitou, Julien Prudent, and Patrick F. Chinnery
Subjects: Biology (General), QH301-705.5
Abstract: Using an in vitro culture system, Pezet et al. studied the influence of oxygen on the mitochondrial DNA (mtDNA) in primordial germ cell-like cells (PGCLCs) in vitro. Low oxygen levels resembling in vivo reduced the cell mtDNA content causing a genetic bottleneck and the segregation of different mtDNA genotypes.
Published: 2021
Full Text: View/download PDF

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