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2. Common conditions of use elements. Atomic concepts for consistent and effective information governance

Author

Sanchez Gonzalez, Maria del Carmen, Kamerling, Pim, Iermito, Mariapia, Casati, Sara, Riaz, Umar, Veal, Colin D., Maini, Monika, Jeanson, Francis, Benhamed, Oussama Mohammed, van Enckevort, Esther, Landi, Annalisa, Mimouni, Yanis, Le Cornec, Clèmence, Coviello, Domenico A., Franchin, Tiziana, Fusco, Francesca, Ramírez García, Jose Antonio, van der Zanden, Loes F. M., Bernier, Alexander, Wilkinson, Mark D., Mueller, Heimo, Gibson, Spencer J., and Brookes, Anthony J.

Published
2024
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3. Getting your DUCs in a row - standardising the representation of Digital Use Conditions

Author

Jeanson, Francis, Gibson, Spencer J., Alper, Pinar, Bernier, Alexander, Woolley, J. Patrick, Mietchen, Daniel, Strug, Andrzej, Becker, Regina, Kamerling, Pim, Sanchez Gonzalez, Maria del Carmen, Mah, Nancy, Novakowski, Ann, Wilkinson, Mark D., Benhamed, Oussama Mohammed, Landi, Annalisa, Krog, Georg Philip, Müller, Heimo, Riaz, Umar, Veal, Colin, Holub, Petr, van Enckevort, Esther, and Brookes, Anthony J.

Published
2024
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4. EURO-NMD registry: federated FAIR infrastructure, innovative technologies and concepts of a patient-centred registry for rare neuromuscular disorders

Author

Atalaia, Antonio, Wandrei, Dagmar, Lalout, Nawel, Thompson, Rachel, Tassoni, Adrian, ’t Hoen, Peter A. C., Athanasiou, Dimitrios, Baker, Suzie-Ann, Sakellariou, Paraskevi, Paliouras, Georgios, D’Angelo, Carla, Horvath, Rita, Mancuso, Michelangelo, van der Beek, Nadine, Kornblum, Cornelia, Kirschner, Janbernd, Pareyson, Davide, Bassez, Guillaume, Blacas, Laura, Jacoupy, Maxime, Eng, Catherine, Lamy, François, Plançon, Jean-Philippe, Haberlova, Jana, Brusse, Esther, Hoeijmakers, Janneke G. J., de Visser, Marianne, Claeys, Kristl G., Paradas, Carmen, Toscano, Antonio, Silani, Vincenzo, Gyenge, Melinda, Reviers, Evy, Hamroun, Dalil, Vroom, Elisabeth, Wilkinson, Mark D., Lochmuller, Hanns, and Evangelista, Teresinha

Published
2024
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8. The Emergent Discipline of Health Web Science

Author

Luciano, Joanne S, Cumming, Grant P, Wilkinson, Mark D, and Kahana, Eva

Subjects
Computer applications to medicine. Medical informatics, R858-859.7, Public aspects of medicine, RA1-1270
Abstract

The transformative power of the Internet on all aspects of daily life, including health care, has been widely recognized both in the scientific literature and in public discourse. Viewed through the various lenses of diverse academic disciplines, these transformations reveal opportunities realized, the promise of future advances, and even potential problems created by the penetration of the World Wide Web for both individuals and for society at large. Discussions about the clinical and health research implications of the widespread adoption of information technologies, including the Internet, have been subsumed under the disciplinary label of Medicine 2.0. More recently, however, multi-disciplinary research has emerged that is focused on the achievement and promise of the Web itself, as it relates to healthcare issues. In this paper, we explore and interrogate the contributions of the burgeoning field of Web Science in relation to health maintenance, health care, and health policy. From this, we introduce Health Web Science as a subdiscipline of Web Science, distinct from but overlapping with Medicine 2.0. This paper builds on the presentations and subsequent interdisciplinary dialogue that developed among Web-oriented investigators present at the 2012 Medicine 2.0 Conference in Boston, Massachusetts.

Published
2013
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9. The SADI Personal Health Lens: A Web Browser-Based System for Identifying Personally Relevant Drug Interactions

Author

Vandervalk, Ben, McCarthy, E Luke, Cruz-Toledo, José, Klein, Artjom, Baker, Christopher J O, Dumontier, Michel, and Wilkinson, Mark D

Subjects
Medicine, Computer applications to medicine. Medical informatics, R858-859.7
Abstract

BackgroundThe Web provides widespread access to vast quantities of health-related information that can improve quality-of-life through better understanding of personal symptoms, medical conditions, and available treatments. Unfortunately, identifying a credible and personally relevant subset of information can be a time-consuming and challenging task for users without a medical background. ObjectiveThe objective of the Personal Health Lens system is to aid users when reading health-related webpages by providing warnings about personally relevant drug interactions. More broadly, we wish to present a prototype for a novel, generalizable approach to facilitating interactions between a patient, their practitioner(s), and the Web. MethodsWe utilized a distributed, Semantic Web-based architecture for recognizing personally dangerous drugs consisting of: (1) a private, local triple store of personal health information, (2) Semantic Web services, following the Semantic Automated Discovery and Integration (SADI) design pattern, for text mining and identifying substance interactions, (3) a bookmarklet to trigger analysis of a webpage and annotate it with personalized warnings, and (4) a semantic query that acts as an abstract template of the analytical workflow to be enacted by the system. ResultsA prototype implementation of the system is provided in the form of a Java standalone executable JAR file. The JAR file bundles all components of the system: the personal health database, locally-running versions of the SADI services, and a javascript bookmarklet that triggers analysis of a webpage. In addition, the demonstration includes a hypothetical personal health profile, allowing the system to be used immediately without configuration. Usage instructions are provided. ConclusionsThe main strength of the Personal Health Lens system is its ability to organize medical information and to present it to the user in a personalized and contextually relevant manner. While this prototype was limited to a single knowledge domain (drug/drug interactions), the proposed architecture is generalizable, and could act as the foundation for much richer personalized-health-Web clients, while importantly providing a novel and personalizable mechanism for clinical experts to inject their expertise into the browsing experience of their patients in the form of customized semantic queries and ontologies.

Published
2013
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12. A Retrospective Longitudinal Study of 460 Patients with ABCA4-Associated Retinal Disease

Author

Fenner, Beau J., Whitmore, S. Scott, DeLuca, Adam P., Andorf, Jean L., Daggett, Heather T., Luse, Meagan A., Haefeli, Lorena M., Riley, Janet B., Critser, Douglas B., Wilkinson, Mark E., Dumitrescu, Alina V., Drack, Arlene V., Boyce, Timothy M., Russell, Jonathan F., Binkley, Elaine M., Sohn, Elliott H., Russell, Stephen R., Boldt, H. Culver, Mullins, Robert F., Tucker, Budd A., Scheetz, Todd E., Han, Ian C., and Stone, Edwin M.

Published
2024
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13. Hyper acute stroke : the specialist nursing impact ; Exploring feelings of secondary traumatic stress : a qualitative enquiry

Author

Wilkinson, Mark

Abstract

Secondary Traumatic Stress (STS) has been defined as the natural consequent behaviours and emotions resulting from knowing about a traumatizing event experienced by a significant other- the stress resulting from helping or wanting to help a traumatized or suffering person (Figley, 1995). STS significantly impacts on nursing practice and performance, patient satisfaction and has organizational negative implications. Stroke specialist nurses are at risk of developing STS due to patients presenting with acute and often unpredictable illness. However, the emotional impact on their practice has not been investigated. This study aimed to perform a qualitative exploration of stroke specialist nurses' feelings of STS encountered in caring for patients with hyper acute presentations. Design: Narrative Methodology. Methods: Following university study ethical approval, stroke specialist nurses from across the UK were asked to participate and were asked to provide stories of their traumatic or stressful experiences related to hyper acute stroke. Data was collected electronically where participants contributed their narratives by email (n=10) and by audiotaped semi structured interviews (n=14). Results: Narrative analysis resulted in the emergence of four core themes: trigger situations, stress reactions, factors which exacerbate STS reactions and coping strategies. Conclusions: The data suggests that stroke specialist nurses are exposed to traumatic events occasioned during the hyper acute care episode. This subjection led to them describing feelings commensurate with STS. The physical and psychosocial effects have implications for nurses, patients and acute stroke services.

Published
2022

17. Targeting protein folding in the malaria parasite

Author

Wilkinson, Mark Dale, Baum, Jake, and Willison, Keith

Abstract

The protein folding machinery in Plasmodium falciparum, the main causative agent of malaria disease, has been directly linked to emerging parasite drug resistance. The Chaperonin Containing TCP-1 ring (CCT) complex is the most up-regulated chaperonin in these drug resistant parasites and is therefore an attractive target to antagonize resistance in the field. Whilst there is a wealth of information about the CCT complex in higher eukaryotes, there is a paucity of information about the complex in more divergent species, such as the malaria parasite. The work presented in this thesis explores the CCT complex in P. falciparum (PfCCT) and the folding of its substrates, including the essential and abundant protein actin. First, I present a technique for studying actin on a single molecule level. Using this system, I observe the dynamic changes in actin's macromolecular structure, its folding and drug-binding in real-time. To understand PfCCT, I biochemically char- acterise one of its essential cofactors, PhLP2, and isolate the complex from parasite lysate. I identify the PfCCT interactome and obtain a low-resolution structure of the complex, which has a highly conserved interactome and structure. Towards targeting the complex, I use a biosynthetic platform that expresses a puta- tive CCT-targeting compound, violacein, to conduct a high-throughput screen. I test the effect of violacein and biosynthetically-derived violacein derivatives on parasite growth. I show that violacein inhibits both wild type and drug-resistant parasite iso- lates from the field and identify a number of derivatives that are more potent than the parent compound. I show that violacein affects actin dynamics in vivo, resulting in an accumulation of actin signal indicative of incorrect protein folding, supporting the hypothesis that violacein targets the CCT complex. The work presented in this thesis provides a clear route for antimalarial drug development, ultimately towards targeting protein folding to stem the deadly disease.

Published
2020
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18. Intra-professional specialist differentiation in the UK surgical profession

Author

Wilkinson, Mark and Richards, Martin

Subjects
617, Professionalisation, Surgery, Capital
Abstract

This thesis studies specialist differentiation in the surgical profession of the United Kingdom, seeking to clarify what the combinations of factors favour or hinder it. It draws on interviews with two hundred surgeons, general practitioners and hospital CEO’s, as well as on sociological literature, especially Bucher and Strauss’s (1961) ‘Process Model’, the concept of ‘profession’ developed by Freidson (1970), Larson’s (1977) model of the ‘Professional Project’ and Bourdieu’s (1981, 1984, 1986, 1988, 1990, 1991, 2005) seminal work on ‘Capital’ and ‘Power’ in ‘Social fields’. The thesis aims to interpret specialisation as a dynamic political process influenced by different groups’ deployment of accumulated specific types of ‘capital’, challenging the view, widespread in the profession itself and still present in functionalist sociological literature, that specialist differentiation is an inevitable consequence of advances in knowledge and technology. In addition to the introduction, conclusion and appendices, the thesis includes chapters on: (1) theoretical framework; (2) methodology; (3) the role of knowledge and technology in specialist differentiation; (4) the role of institutions before the establishment of the NHS; (5) the role of the relationship between the profession and the state in the period 1948-1990; (6) ditto in the period 1991-1997; (7) the current situation and how it might develop.

Published
2020
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20. The genomic landscape of pediatric acute lymphoblastic leukemia

Author

Brady, Samuel W., Roberts, Kathryn G., Gu, Zhaohui, Shi, Lei, Pounds, Stanley, Pei, Deqing, Cheng, Cheng, Dai, Yunfeng, Devidas, Meenakshi, Qu, Chunxu, Hill, Ashley N., Payne-Turner, Debbie, Ma, Xiaotu, Iacobucci, Ilaria, Baviskar, Pradyuamna, Wei, Lei, Arunachalam, Sasi, Hagiwara, Kohei, Liu, Yanling, Flasch, Diane A., Liu, Yu, Parker, Matthew, Chen, Xiaolong, Elsayed, Abdelrahman H., Pathak, Omkar, Li, Yongjin, Fan, Yiping, Michael, J. Robert, Rusch, Michael, Wilkinson, Mark R., Foy, Scott, Hedges, Dale J., Newman, Scott, Zhou, Xin, Wang, Jian, Reilly, Colleen, Sioson, Edgar, Rice, Stephen V., Pastor Loyola, Victor, Wu, Gang, Rampersaud, Evadnie, Reshmi, Shalini C., Gastier-Foster, Julie, Guidry Auvil, Jaime M., Gesuwan, Patee, Smith, Malcolm A., Winick, Naomi, Carroll, Andrew J., Heerema, Nyla A., Harvey, Richard C., Willman, Cheryl L., Larsen, Eric, Raetz, Elizabeth A., Borowitz, Michael J., Wood, Brent L., Carroll, William L., Zweidler-McKay, Patrick A., Rabin, Karen R., Mattano, Leonard A., Maloney, Kelly W., Winter, Stuart S., Burke, Michael J., Salzer, Wanda, Dunsmore, Kimberly P., Angiolillo, Anne L., Crews, Kristine R., Downing, James R., Jeha, Sima, Pui, Ching-Hon, Evans, William E., Yang, Jun J., Relling, Mary V., Gerhard, Daniela S., Loh, Mignon L., Hunger, Stephen P., Zhang, Jinghui, and Mullighan, Charles G.

Published
2022
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25. Two new species of Caecilia (Gymnophiona: Caeciliidae) from the Ecuadorian humid Chocó.

Author

BOCK, SARAH, ARROBA-LÓPEZ, THALIA E., VELEZ-GILER, HOLGER L., MOREIRA, VANESSA, WIEDEBUSCH, MOIRA L. M., NEIRA-SALAMEA, KARLA, WILKINSON, MARK, FUCHS, NIKLAS, SCHÖNLEITNER, MARKUS, RÖDEL, MARK-OLIVER, and RON, SANTIAGO R.

Abstract

Copyright of Salamandra is the property of Deutsche Gesellschaft fuer Herpetologie und Terrarienkunde eV and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Published
2024

26. Intraspecific venom variation in the medically important puff adder (Bitis arietans): Comparative venom gland transcriptomics, in vitro venom activity and immunological recognition by antivenom.

Author

Dawson, Charlotte A., Bartlett, Keirah E., Wilkinson, Mark C., Ainsworth, Stuart, Albulescu, Laura-Oana, Kazandijan, Taline, Hall, Steven R., Westhorpe, Adam, Clare, Rachel, Wagstaff, Simon, Modahl, Cassandra M., Harrison, Robert A., and Casewell, Nicholas R.

Subjects
SNAKE venom, VENOM glands, ANTIVENINS, VENOM, TRANSCRIPTOMES
Abstract

Background: Variation in snake venoms is well documented, both between and within species, with intraspecific venom variation often correlated with geographically distinct populations. The puff adder, Bitis arietans, is widely distributed across sub-Saharan Africa and into the Arabian Peninsula where it is considered a leading cause of the ~310,000 annual snakebites across the region, with its venom capable of causing substantial morbidity and mortality. Despite its medical importance and wide geographic distribution, there is little known about venom variation between different B. arietans populations and the potential implications of this variation on antivenom efficacy. Methodology: We applied a range of analyses, including venom gland transcriptomics, in vitro enzymatic assays and reverse phase chromatography to comparatively analyse B. arietans venoms originating from Nigeria, Tanzania, and South Africa. Immunological assays and in vitro enzymatic neutralisation assays were then applied to investigate the impact of venom variation on the potential efficacy of three antivenom products; SAIMR Polyvalent, EchiTAb-Plus and Fav-Afrique. Findings: Through the first comparison of venom gland transcriptomes of B. arietans from three geographically distinct regions (Nigeria, Tanzania, and South Africa), we identified substantial variation in toxin expression. Findings of venom variation were further supported by chromatographic venom profiling, and the application of enzymatic assays to quantify the activity of three pathologically relevant toxin families. However, the use of western blotting, ELISA, and in vitro enzymatic inhibition assays revealed that variation within B. arietans venom does not appear to substantially impact upon the efficacy of three African polyvalent antivenoms. Conclusions: The large distribution and medical importance of B. arietans makes this species ideal for understanding venom variation and the impact this has on therapeutic efficacy. The findings in this study highlight the likelihood for considerable venom toxin variation across the range of B. arietans, but that this may not dramatically impact upon the utility of treatment available in the region. Author summary: The puff adder (Bitis arietans) is found across sub-Saharan Africa and the Arabian Peninsula and is capable of causing life threatening pathology due to its potent venom. The extensive range of B. arietans exposes populations to different ecological pressures which may impact upon the composition of venom toxins. In this study, we examined the venom composition of B. arietans from three countries separated by large geographic distance: Nigeria, Tanzania and South Africa. By integrating venom gland transcriptomes, venom chromatography, and in vitro functional assays to profile B. arietans venom composition, we uncovered extensive variation between the three locales. Given that venom variation can have a significant impact on the efficacy of antivenom treatment, we also investigated the ability of three African antivenoms to recognise and inhibit in vitro venom activity. Through these analyses, we were able to determine that venom variation did not have a substantial impact on the neutralising effect of selected antivenoms. This study has highlighted the potentially extensive venom variation found across the range of B. arietans and initiated valuable investigations into the efficacy of African antivenoms to protect human populations vulnerable to snakebite envenoming. [ABSTRACT FROM AUTHOR]

Published
2024
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27. The first fossil record of an aquatic caecilian (Gymnophiona: Typhlonectidae).

Author

Santos, Rodolfo Otávio, Wilkinson, Mark, Ribeiro, Graziella do Couto, Carvalho, Alberto B, and Zaher, Hussam

Subjects
*COMPARATIVE anatomy, *FOSSIL vertebrates, *FOSSILS, *OLIGOCENE Epoch, *VERTEBRAE
Abstract

The lissamphibian clade Gymnophiona includes approximately 220 recognized modern species known by the English vernacular as caecilians and characterized by their elongated and annulated bodies, without girdles or limbs. Fossils of caecilians are particularly rare and mostly limited to isolated vertebrae. Until now, only four bona fide Gymnophionomorpha species have been named based on fossils. Only one of these (Apodops pricei) is a crown-group caecilian, but its affinities with modern caecilians are uncertain because the material is limited to one damaged vertebra and is currently lost. Here we describe a new genus and species of caecilian from the Oligocene Tremembé Formation, Brazil, based on a partially preserved fossil skeleton (including elements of the skull and postcranium) that is damaged but still partly articulated. We investigated the fossil caecilian's anatomy using high-resolution microcomputed tomography, and then compared it to the osteology of modern species. We interpret the fossil as a member of Typhlonectidae, a family of caecilians well known for their aquatic and semi-aquatic lifestyles. This new record represents the first record for caecilians from the Oligocene and also the first fossil species confidently assigned to an extant caecilian family. [ABSTRACT FROM AUTHOR]

Published
2024
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28. Current frequency of contact allergy to isothiazolinones (methyl‐, benz‐ and octylisothiazolinone) across Europe.

Author

Schwensen, Jakob F. B., Uter, Wolfgang, Aerts, Olivier, Agner, Tove, Brans, Richard, Bruze, Magnus, Foti, Caterina, Giménez‐Arnau, Ana Maria, Gonçalo, Margarida, Svedman, Cecilia, Stingeni, Luca, Wilkinson, Mark, and Johansen, Jeanne Duus

Subjects
CONTACT dermatitis, CLINICAL epidemiology, CONFIDENCE intervals, ALLERGIES, CONSUMERS
Abstract

Background: The use of methylisothiazolinone (MI) as a preservative in cosmetic products caused an alarming increase in MI contact allergy across Europe in the 2010s. This was followed by regulations of use with a total ban on leave‐on (implemented in 2017) and reduced use concentrations in rinse‐off cosmetics (2018). Objective: To follow‐up on the prevalence of contact allergy to MI and the related benzisothiazolinone (BIT) and octylisothiazolinone (OIT) in consecutively patch‐tested patients in Europe. Methods: A cross‐sectional audit following the design of two previous audits on MI contact allergy from 1 May 2022 to 31 October 2022 included all patients patch tested with the European baseline series, including or supplemented with MI, BIT and OIT across 10 departments in eight European countries. Results: A total of 2554 patients were consecutively patch tested with the three isothiazolinones during the study period. The prevalence of MI and BIT contact allergy was 2.9% (95% confidence interval [CI]: 2.3%–3.7%; range 1.1%–5.8%) and 3.1% (95% CI: 2.4%–3.9%; range 0.0%–6.6%), respectively; that of OIT was 0.7% (95% CI: 0.4%–1.1%; range 0%–3.2%). Rinse‐off cosmetic (73.3%) and leave‐on cosmetic products (13.3%) were still associated with eliciting allergic contact dermatitis to MI. Conclusion: We confirmed a positive impact of regulatory measures on the prevalence of MI contact allergy in Europe, which halved compared to 2015. However, our data suggest that consumers may still be exposed to older cosmetic products containing MI. BIT has superseded MI in causing contact allergy, despite not being allowed for use in cosmetic products. [ABSTRACT FROM AUTHOR]

Published
2024
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33. Semantic modelling of common data elements for rare disease registries, and a prototype workflow for their deployment over registry data

Author

Kaliyaperumal, Rajaram, Wilkinson, Mark D., Moreno, Pablo Alarcón, Benis, Nirupama, Cornet, Ronald, dos Santos Vieira, Bruna, Dumontier, Michel, Bernabé, César Henrique, Jacobsen, Annika, Le Cornec, Clémence M. A., Godoy, Mario Prieto, Queralt-Rosinach, Núria, Schultze Kool, Leo J., Swertz, Morris A., van Damme, Philip, van der Velde, K. Joeri, Lalout, Nawel, Zhang, Shuxin, and Roos, Marco

Published
2022
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39. X Chromosome Contribution to the Genetic Architecture of Primary Biliary Cholangitis

Author

Walker, Erin, Xie, Gang, Mason, Andy, Myers, Robert, Peltekian, Kevork, Ghent, Cameron, Atkinson, Elizabeth, Juran, Bruce, Lazaridis, Kostas, Lu, Yue, Gu, Xiangjun, Jing, Kaiyan, Amos, Chris, Affronti, Andrea, Brunetto, Maurizia, Coco, Barbara, Spinzi, Giancarlo, Elia, Gianfranco, Ferrari, Carlo, Lleo, Ana, Muratori, Luigi, Muratori, Paolo, Portincasa, Piero, Colli, Agostino, Bruno, Savino, Colloredo, Guido, Azzaroli, Francesco, Andreone, Pietro, Bragazzi, MariaConsiglia, Alvaro, Domenico, Cardinale, Vincenzo, Cazzagon, Nora, Rigamonti, Cristina, Floreani, Annarosa, Rosina, Floriano, Ciaccio, Antonio, Cristoferi, Laura, D’Amato, Daphne, Malinverno, Federica, Mancuso, Clara, Massironi, Sara, Milani, Chiara, O’Donnell, Sarah E., Ronca, Vincenzo, Barisani, Donatella, Lampertico, Pietro, Donato, Francesca, Fagiuoli, Stefano, Almasio, Piero L., Giannini, Edoardo, Cursaro, Carmela, Colombo, Massimo, Valenti, Luca, Miele, Luca, Andriulli, Angelo, Niro, Grazia A., Grattagliano, Ignazio, Morini, Lorenzo, Casella, Giovanni, Vinci, Maria, Battezzati, Pier Maria, Crosignani, Andrea, Zuin, Massimo, Mattalia, Alberto, Calvaruso, Vincenza, Colombo, Silvia, Benedetti, Antonio, Marzioni, Marco, Galli, Andrea, Marra, Fabio, Tarocchi, Mirko, Picciotto, Antonio, Morisco, Filomena, Fabris, Luca, Crocè, Lory Saveria, Tiribelli, Claudio, Toniutto, Pierluigi, Strazzabosco, Mario, Ch’ng, Chin Lye, Rahman, Mesbah, Yapp, Tom, Sturgess, Richard, Healey, Christopher, Czajkowski, Marek, Gunasekera, Anton, Gyawali, Pranab, Premchand, Purushothaman, Kapur, Kapil, Marley, Richard, Foster, Graham, Watson, Alan, Dias, Aruna, Subhani, Javaid, Harvey, Rory, McCorry, Roger, Ramanaden, David, Gasem, Jaber, Evans, Richard, Mathialahan, Thiriloganathan, Shorrock, Christopher, Lipscomb, George, Southern, Paul, Tibble, Jeremy, Gorard, David, Palegwala, Altaf, Jones, Susan, Dawwas, Mohamed, Alexander, Graeme, Dolwani, Sunil, Prince, Martin, Foxton, Matthew, Elphick, David, Mitchison, Harriet, Gooding, Ian, Karmo, Mazn, Saksena, Sushma, Mendall, Mike, Patel, Minesh, Ede, Roland, Austin, Andrew, Sayer, Joanna, Hankey, Lorraine, Hovell, Christopher, Fisher, Neil, Carter, Martyn, Koss, Konrad, Piotrowicz, Andrzej, Grimley, Charles, Neal, David, Lim, Guan, Levi, Sass, Ala, Aftab, Broad, Andrea, Saeed, Athar, Wood, Gordon, Brown, Jonathan, Wilkinson, Mark, Gordon, Harriet, Ramage, John, Ridpath, Jo, Ngatchu, Theodore, Grover, Bob, Shaukat, Syed, Shidrawi, Ray, Abouda, George, Ali, Faiz, Rees, Ian, Salam, Imroz, Narain, Mark, Brown, Ashley, Taylor-Robinson, Simon, Williams, Simon, Grellier, Leonie, Banim, Paul, Das, Debasish, Chilton, Andrew, Heneghan, Michael, Curtis, Howard, Gess, Markus, Drake, Ian, Aldersley, Mark, Davies, Mervyn, Jones, Rebecca, McNair, Alastair, Srirajaskanthan, Raj, Pitcher, Maxton, Sen, Sambit, Bird, George, Barnardo, Adrian, Kitchen, Paul, Yoong, Kevin, Chirag, Oza, Sivaramakrishnan, Nurani, MacFaul, George, Jones, David, Shah, Amir, Evans, Chris, Saha, Subrata, Pollock, Katharine, Bramley, Peter, Mukhopadhya, Ashis, Fraser, Andrew, Mills, Peter, Shallcross, Christopher, Campbell, Stewart, Bathgate, Andrew, Shepherd, Alan, Dillon, John, Rushbrook, Simon, Przemioslo, Robert, Macdonald, Christopher, Metcalf, Jane, Shmueli, Udi, Davis, Andrew, Naqvi, Asifabbas, Lee, Tom, Ryder, Stephen D., Collier, Jane, Klass, Howard, Ninkovic, Mary, Cramp, Matthew, Sharer, Nicholas, Aspinall, Richard, Goggin, Patrick, Ghosh, Deb, Douds, Andrew, Hoeroldt, Barbara, Booth, Jonathan, Williams, Earl, Hussaini, Hyder, Stableforth, William, Ayres, Reuben, Thorburn, Douglas, Marshall, Eileen, Burroughs, Andrew, Mann, Steven, Lombard, Martin, Richardson, Paul, Patanwala, Imran, Maltby, Julia, Brookes, Matthew, Mathew, Ray, Vyas, Samir, Singhal, Saket, Gleeson, Dermot, Misra, Sharat, Butterworth, Jeff, George, Keith, Harding, Tim, Douglass, Andrew, Panter, Simon, Shearman, Jeremy, Bray, Gary, Butcher, Graham, Forton, Daniel, Mclindon, John, Cowan, Matthew, Whatley, Gregory, Mandal, Aditya, Gupta, Hemant, Sanghi, Pradeep, Jain, Sanjiv, Pereira, Steve, Prasad, Geeta, Watts, Gill, Wright, Mark, Neuberger, James, Gordon, Fiona, Unitt, Esther, Grant, Allister, Delahooke, Toby, Higham, Andrew, Brind, Alison, Cox, Mark, Ramakrishnan, Subramaniam, King, Alistair, Collins, Carole, Whalley, Simon, Li, Andy, Fraser, Jocelyn, Bell, Andrew, Wong, Voi Shim, Singhal, Amit, Gee, Ian, Ang, Yeng, Ransford, Rupert, Gotto, James, Millson, Charles, Bowles, Jane, Thomas, Caradog, Harrison, Melanie, Galaska, Roman, Kendall, Jennie, Whiteman, Jessica, Lawlor, Caroline, Gray, Catherine, Elliott, Keith, Mulvaney-Jones, Caroline, Hobson, Lucie, Van Duyvenvoorde, Greta, Loftus, Alison, Seward, Katie, Penn, Ruth, Maiden, Jane, Damant, Rose, Hails, Janeane, Cloudsdale, Rebecca, Silvestre, Valeria, Glenn, Sue, Dungca, Eleanor, Wheatley, Natalie, Doyle, Helen, Kent, Melanie, Hamilton, Caroline, Braim, Delyth, Wooldridge, Helen, Abrahams, Rachel, Paton, Alison, Lancaster, Nicola, Gibbins, Andrew, Hogben, Karen, Desousa, Phillipa, Muscariu, Florin, Musselwhite, Janine, McKay, Alexandra, Tan, LaiTing, Foale, Carole, Brighton, Jacqueline, Flahive, Kerry, Nambela, Estelle, Townshend, Paula, Ford, Chris, Holder, Sophie, Palmer, Caroline, Featherstone, James, Nasseri, Mariam, Sadeghian, Joy, Williams, Bronwen, Thomas, Carol, Rolls, Sally-Ann, Hynes, Abigail, Duggan, Claire, Jones, Sarah, Crossey, Mary, Stansfield, Glynis, MacNicol, Carolyn, Wilkins, Joy, Wilhelmsen, Elva, Raymode, Parizade, Lee, Hye-Jeong, Durant, Emma, Bishop, Rebecca, Ncube, Noma, Tripoli, Sherill, Casey, Rebecca, Cowley, Caroline, Miller, Richard, Houghton, Kathryn, Ducker, Samantha, Wright, Fiona, Bird, Bridget, Baxter, Gwen, Keggans, Janie, Hughes, Maggie, Grieve, Emma, Young, Karin, Williams, D., Ocker, Kate, Hines, Frances, Martin, Kirsty, Innes, Caron, Valliani, Talal, Fairlamb, Helen, Thornthwaite, Sarah, Eastick, Anne, Tanqueray, Elizabeth, Morrison, Jennifer, Holbrook, Becky, Browning, Julie, Walker, Kirsten, Congreave, Susan, Verheyden, Juliette, Slininger, Susan, Stafford, Lizzie, O’Donnell, Denise, Ainsworth, Mark, Lord, Susan, Kent, Linda, March, Linda, Dickson, Christine, Simpson, Diane, Longhurst, Beverley, Hayes, Maria, Shpuza, Ervin, White, Nikki, Besley, Sarah, Pearson, Sallyanne, Wright, Alice, Jones, Linda, Gunter, Emma, Dewhurst, Hannah, Fouracres, Anna, Farrington, Liz, Graves, Lyn, Marriott, Suzie, Leoni, Marina, Tyrer, David, Martin, Kate, Dali-kemmery, Lola, Lambourne, Victoria, Green, Marie, Sirdefield, Dawn, Amor, Kelly, Colley, Julie, Shinder, Bal, Jones, Jayne, Mills, Marisa, Carnahan, Mandy, Taylor, Natalie, Boulton, Kerenza, Tregonning, Julie, Brown, Carly, Clifford, Gayle, Archer, Emily, Hamilton, Maria, Curtis, Janette, Shewan, Tracey, Walsh, Sue, Warner, Karen, Netherton, Kimberley, Mupudzi, Mcdonald, Gunson, Bridget, Gitahi, Jane, Gocher, Denise, Batham, Sally, Pateman, Hilary, Desmennu, Senayon, Conder, Jill, Clement, Darren, Gallagher, Susan, Orpe, Jacky, Chan, PuiChing, Currie, Lynn, O’Donohoe, Lynn, Oblak, Metod, Morgan, Lisa, Quinn, Marie, Amey, Isobel, Baird, Yolanda, Cotterill, Donna, Cumlat, Lourdes, Winter, Louise, Greer, Sandra, Spurdle, Katie, Allison, Joanna, Dyer, Simon, Sweeting, Helen, Kordula, Jean, Aiba, Yoshihiro, Nakamura, Hitomi, Abiru, Seigo, Nagaoka, Shinya, Komori, Atsumasa, Yatsuhashi, Hiroshi, Ishibashi, Hiromi, Ito, Masahiro, Kawai, Yosuke, Kohn, Seik-Soon, Gervais, Olivier, Migita, Kiyoshi, Katsushima, Shinji, Naganuma, Atsushi, Sugi, Kazuhiro, Komatsu, Tatsuji, Mannami, Tomohiko, Matsushita, Kouki, Yoshizawa, Kaname, Makita, Fujio, Nikami, Toshiki, Nishimura, Hideo, Kouno, Hiroshi, Kouno, Hirotaka, Ota, Hajime, Komura, Takuya, Nakamura, Yoko, Shimada, Masaaki, Hirashima, Noboru, Komeda, Toshiki, Ario, Keisuke, Nakamuta, Makoto, Yamashita, Tsutomu, Furuta, Kiyoshi, Kikuchi, Masahiro, Naeshiro, Noriaki, Takahashi, Hironao, Mano, Yutaka, Tsunematsu, Seiji, Yabuuchi, Iwao, Shimada, Yusuke, Yamauchi, Kazuhiko, Sugimoto, Rie, Sakai, Hironori, Mita, Eiji, Koda, Masaharu, Tsuruta, Satoru, Kamitsukasa, Hiroshi, Sato, Takeaki, Masaki, Naohiko, Kobata, Tatsuro, Fukushima, Nobuyoshi, Higuchi, Nobito, Ohara, Yukio, Muro, Toyokichi, Takesaki, Eiichi, Takaki, Hitoshi, Yamamoto, Tetsuo, Kato, Michio, Nagaoki, Yuko, Hayashi, Shigeki, Ishida, Jinya, Watanabe, Yukio, Kobayashi, Masakazu, Koga, Michiaki, Saoshiro, Takeo, Yagura, Michiyasu, Hirata, Keisuke, Takikawa, Hajime, Ohira, Hiromasa, Zeniya, Mikio, Abe, Masanori, Onji, Morikazu, Kaneko, Shuichi, Honda, Masao, Arai, Kuniaki, Arinaga-Hino, Teruko, Hashimoto, Etsuko, Taniai, Makiko, Umemura, Takeji, Joshita, Satoru, Nakao, Kazuhiko, Ichikawa, Tatsuki, Shibata, Hidetaka, Yamagiwa, Satoshi, Seike, Masataka, Honda, Koichi, Sakisaka, Shotaro, Takeyama, Yasuaki, Harada, Masaru, Senju, Michio, Yokosuka, Osamu, Kanda, Tatsuo, Ueno, Yoshiyuki, Kikuchi, Kentaro, Ebinuma, Hirotoshi, Himoto, Takashi, Yasunami, Michio, Murata, Kazumoto, Mizokami, Masashi, Shimoda, Shinji, Miyake, Yasuhiro, Takaki, Akinobu, Yamamoto, Kazuhide, Hirano, Katsuji, Ichida, Takafumi, Ido, Akio, Tsubouchi, Hirohito, Chayama, Kazuaki, Harada, Kenichi, Nakanuma, Yasuni, Maehara, Yoshihiko, Taketomi, Akinobu, Shirabe, Ken, Soejima, Yuji, Mori, Akira, Yagi, Shintaro, Uemoto, Shinji, Tanaka, Tomohiro, Yamashiki, Noriyo, Tamura, Sumito, Sugawara, Yasuhiro, Kokudo, Norihiro, Asselta, Rosanna, Paraboschi, Elvezia M., Gerussi, Alessio, Cordell, Heather J., Mells, George F., Sandford, Richard N., Jones, David E., Nakamura, Minoru, Ueno, Kazuko, Hitomi, Yuki, Kawashima, Minae, Nishida, Nao, Tokunaga, Katsushi, Nagasaki, Masao, Tanaka, Atsushi, Tang, Ruqi, Li, Zhiqiang, Shi, Yongyong, Liu, Xiangdong, Xiong, Ma, Hirschfield, Gideon, Siminovitch, Katherine A., Carbone, Marco, Cardamone, Giulia, Duga, Stefano, Gershwin, M. Eric, Seldin, Michael F., and Invernizzi, Pietro

Published
2021
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42. Towards complete and error-free genome assemblies of all vertebrate species

Author

Rhie, Arang, McCarthy, Shane A., Fedrigo, Olivier, Damas, Joana, Formenti, Giulio, Koren, Sergey, Uliano-Silva, Marcela, Chow, William, Fungtammasan, Arkarachai, Kim, Juwan, Lee, Chul, Ko, Byung June, Chaisson, Mark, Gedman, Gregory L., Cantin, Lindsey J., Thibaud-Nissen, Francoise, Haggerty, Leanne, Bista, Iliana, Smith, Michelle, Haase, Bettina, Mountcastle, Jacquelyn, Winkler, Sylke, Paez, Sadye, Howard, Jason, Vernes, Sonja C., Lama, Tanya M., Grutzner, Frank, Warren, Wesley C., Balakrishnan, Christopher N., Burt, Dave, George, Julia M., Biegler, Matthew T., Iorns, David, Digby, Andrew, Eason, Daryl, Robertson, Bruce, Edwards, Taylor, Wilkinson, Mark, Turner, George, Meyer, Axel, Kautt, Andreas F., Franchini, Paolo, Detrich, III, H. William, Svardal, Hannes, Wagner, Maximilian, Naylor, Gavin J. P., Pippel, Martin, Malinsky, Milan, Mooney, Mark, Simbirsky, Maria, Hannigan, Brett T., Pesout, Trevor, Houck, Marlys, Misuraca, Ann, Kingan, Sarah B., Hall, Richard, Kronenberg, Zev, Sović, Ivan, Dunn, Christopher, Ning, Zemin, Hastie, Alex, Lee, Joyce, Selvaraj, Siddarth, Green, Richard E., Putnam, Nicholas H., Gut, Ivo, Ghurye, Jay, Garrison, Erik, Sims, Ying, Collins, Joanna, Pelan, Sarah, Torrance, James, Tracey, Alan, Wood, Jonathan, Dagnew, Robel E., Guan, Dengfeng, London, Sarah E., Clayton, David F., Mello, Claudio V., Friedrich, Samantha R., Lovell, Peter V., Osipova, Ekaterina, Al-Ajli, Farooq O., Secomandi, Simona, Kim, Heebal, Theofanopoulou, Constantina, Hiller, Michael, Zhou, Yang, Harris, Robert S., Makova, Kateryna D., Medvedev, Paul, Hoffman, Jinna, Masterson, Patrick, Clark, Karen, Martin, Fergal, Howe, Kevin, Flicek, Paul, Walenz, Brian P., Kwak, Woori, Clawson, Hiram, Diekhans, Mark, Nassar, Luis, Paten, Benedict, Kraus, Robert H. S., Crawford, Andrew J., Gilbert, M. Thomas P., Zhang, Guojie, Venkatesh, Byrappa, Murphy, Robert W., Koepfli, Klaus-Peter, Shapiro, Beth, Johnson, Warren E., Di Palma, Federica, Marques-Bonet, Tomas, Teeling, Emma C., Warnow, Tandy, Graves, Jennifer Marshall, Ryder, Oliver A., Haussler, David, O’Brien, Stephen J., Korlach, Jonas, Lewin, Harris A., Howe, Kerstin, Myers, Eugene W., Durbin, Richard, Phillippy, Adam M., and Jarvis, Erich D.

Published
2021
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43. Abemaciclib Therapy Using the MonarchE Criteria Results in Large Numbers of Excess Axillary Node Clearances—Time to Pause and Reflect?

Author

Ahari, Daniel, Wilkinson, Mark, Ali, Nisha, Taxiarchi, Vicky P., Dave, Rajiv V., and Gandhi, Ashu

Subjects
*THERAPEUTIC use of antineoplastic agents, *LYMPHEDEMA, *RISK assessment, *HORMONE receptor positive breast cancer, *AXILLARY lymph node dissection, *LONGITUDINAL method, *DISEASES, *WOMEN'S health, *CYCLIN-dependent kinases, *DISEASE risk factors, *CHEMICAL inhibitors
Abstract

Simple Summary: Abemaciclib is an important addition to the care of women with hormone receptor-positive breast cancer. To qualify for abemaciclib treatment, some women are advised to undergo axillary node clearance surgery as finding more than three axillary nodes with metastatic cancer allows access to abemaciclib. This paper explores the balance between the benefits of axillary node clearance in permitting access to abemaciclib and the harms of surgery. We examine how many women need to undergo axillary node clearance before one woman clinically benefits from the procedure. We show that for every 10 women undergoing axillary node clearance surgery, only one eventually qualifies for abemaciclib. The remaining nine would have axillary surgery but still not qualify for abemaciclib as less than four metastatic axillary nodes are found despite full axillary clearance. However, these women could still suffer the complications of axillary node clearance surgery. The monarchE study added the CDK4/6 inhibitor abemaciclib to the care of women with oestrogen-positive (ER+) breast cancers. Eligibility required meeting monarchE criteria—either >3 positive axillary nodes, or 1–3 positive sentinel nodes (SNB+) with tumour size >50 mm or grade 3 cancers. Women were advised to proceed to completion axillary node clearance (cANC) if size/grade criteria were not fulfilled for >3 positive nodes to be identified. However, cANC is associated with significant morbidity, conflicting with the potential benefits of abemaciclib. We analysed data of 229 consecutive women (2016-2022) with ER+ breast cancer and SNB+ who proceeded to cANC, keeping with contemporary treatment guidelines. We used this cohort to assess numbers that, under national guidance in place currently, would be advised to undergo cANC solely to check eligibility for abemaciclib treatment. Using monarchE criteria, 90 women (39%) would have accessed abemaciclib based on SNB+ and size/grade, without cANC. In total, 139 women would have been advised to proceed to cANC to check eligibility, with only 15/139 (11%) having >3 positive nodes after sentinel node biopsy and cANC. The remaining 124 (89%) would have undergone cANC but remained ineligible for abemaciclib. Size, age, grade, and Ki67 did not predict >3 nodes at cANC. Following cANC, a large majority of women with ER+, <50 mm, and grade 1–2 tumours remain ineligible for abemaciclib yet are subject to significant morbidity including lifelong lymphoedema risk. The monarchE authors state that 15 women need abemaciclib therapy for 1 to clinically benefit. Thus, in our cohort, 139 women undergoing cANC would lead to one woman benefitting. [ABSTRACT FROM AUTHOR]

Published
2024
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44. Differential diagnosis of contact dermatitis: A practical‐approach review by the EADV Task Force on contact dermatitis.

Author

Pesqué, David, Aerts, Olivier, Bizjak, Mojca, Gonçalo, Margarida, Dugonik, Aleksandra, Simon, Dagmar, Ljubojević‐Hadzavdić, Suzana, Malinauskiene, Laura, Wilkinson, Mark, Czarnecka‐Operacz, Magdalena, Krecisz, Beata, John, Swen M., Balato, Anna, Ayala, Fabio, Rustemeyer, Thomas, and Giménez‐Arnau, Ana M.

Subjects
CONTACT dermatitis, SYMPTOMS, TASK forces, DIFFERENTIAL diagnosis, PHENOTYPES, ECZEMA
Abstract

The diagnosis of eczema ('dermatitis') is mostly clinical and depends on the clinical history and exploratory objective findings (primary lesions, patterns). Contact dermatitis remains as an important condition in the group of eczematous disorders, with important socioeconomic and occupational relevance. Although irritant and allergic contact dermatitis have a different pathogenesis, both are characterized by a rather typical morphology, are triggered by external factors and tend to occur primarily in the area of contact with the exogenous agent. In addition, allergic and irritant dermatitis may also co‐exist. The importance of diagnosing contact dermatitis, especially when allergic in nature, is both due to the possibility of avoiding the trigger, and due to its role in aggravating other skin conditions. Nevertheless, the heterogeneity of clinical presentations in daily practice may pose an important challenge for the suspicion and correct diagnosis of contact dermatitis. Furthermore, other conditions, with different pathogenesis and treatment, may clinically simulate contact dermatitis. The Task Force aims to conduct a review of the unifying clinical features of contact dermatitis and characterize its main clinical phenotypes, and its simulators, in order to contribute to an early suspicion or recognition of contact dermatitis and enable a correct differential diagnosis. [ABSTRACT FROM AUTHOR]

Published
2024
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45. Importance of the Cysteine-Rich Domain of Snake Venom Prothrombin Activators: Insights Gained from Synthetic Neutralizing Antibodies.

Author

Misson Mindrebo, Laetitia E., Mindrebo, Jeffrey T., Tran, Quoc, Wilkinson, Mark C., Smith, Jessica M., Verma, Megan, Casewell, Nicholas R., Lander, Gabriel C., and Jardine, Joseph G.

Subjects
POISONS, SNAKE venom, SYNTHETIC antibodies, ANTIVENINS, PROTHROMBIN, MONOCLONAL antibodies, VENOM
Abstract

Snake venoms are cocktails of biologically active molecules that have evolved to immobilize prey, but can also induce a severe pathology in humans that are bitten. While animal-derived polyclonal antivenoms are the primary treatment for snakebites, they often have limitations in efficacy and can cause severe adverse side effects. Building on recent efforts to develop improved antivenoms, notably through monoclonal antibodies, requires a comprehensive understanding of venom toxins. Among these toxins, snake venom metalloproteinases (SVMPs) play a pivotal role, particularly in viper envenomation, causing tissue damage, hemorrhage and coagulation disruption. One of the current challenges in the development of neutralizing monoclonal antibodies against SVMPs is the large size of the protein and the lack of existing knowledge of neutralizing epitopes. Here, we screened a synthetic human antibody library to isolate monoclonal antibodies against an SVMP from saw-scaled viper (genus Echis) venom. Upon characterization, several antibodies were identified that effectively blocked SVMP-mediated prothrombin activation. Cryo-electron microscopy revealed the structural basis of antibody-mediated neutralization, pinpointing the non-catalytic cysteine-rich domain of SVMPs as a crucial target. These findings emphasize the importance of understanding the molecular mechanisms of SVMPs to counter their toxic effects, thus advancing the development of more effective antivenoms. [ABSTRACT FROM AUTHOR]

Published
2024
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46. Molecular dissection of cobra venom highlights heparinoids as an antidote for spitting cobra envenoming.

Author

Du, Tian Y., Hall, Steven R., Chung, Felicity, Kurdyukov, Sergey, Crittenden, Edouard, Patel, Karishma, Dawson, Charlotte A., Westhorpe, Adam P., Bartlett, Keirah E., Rasmussen, Sean A., Moreno, Cesar L., Denes, Christopher E., Albulescu, Laura-Oana, Marriott, Amy E., Mackay, Joel P., Wilkinson, Mark C., Gutiérrez, José María, Casewell, Nicholas R., and Neely, G. Gregory

Subjects
COBRAS, SPIDER venom, VENOM, CYTOTOXINS, NEGLECTED diseases, INTRADERMAL injections
Abstract

Snakebites affect about 1.8 million people annually. The current standard of care involves antibody-based antivenoms, which can be difficult to access and are generally not effective against local tissue injury, the primary cause of morbidity. Here, we used a pooled whole-genome CRISPR knockout screen to define human genes that, when targeted, modify cell responses to spitting cobra venoms. A large portion of modifying genes that conferred resistance to venom cytotoxicity was found to control proteoglycan biosynthesis, including EXT1, B4GALT7, EXT2, EXTL3, XYLT2, NDST1, and SLC35B2, which we validated independently. This finding suggested heparinoids as possible inhibitors. Heparinoids prevented venom cytotoxicity through binding to three-finger cytotoxins, and the US Food and Drug Administration–approved heparinoid tinzaparin was found to reduce tissue damage in mice when given via a medically relevant route and dose. Overall, our systematic molecular dissection of cobra venom cytotoxicity provides insight into how we can better treat cobra snakebite envenoming. Editor's summary: Snakebite is considered a neglected tropical disease by the World Health Organization, and although antibody-based antivenoms exist, they are species specific, are expensive, and require cold storage as well as intravenous administration in a health care setting. Here, Du and colleagues conducted a whole-genome CRISPR knockout screen to identify genes required for spitting cobra venom cytotoxicity. This screen highlighted genes involved in proteoglycan biosynthesis, suggesting that heparinoids could potentially block spitting cobra venom cytotoxicity. The heparinoid tinzaparin, given subcutaneously at the time of intradermal venom injection, effectively reduced the size of the resulting dermonecrotic lesions in mice, supporting the further evaluation of this drug for the treatment of local tissue damage from spitting cobra envenoming. —Melissa L. Norton [ABSTRACT FROM AUTHOR]

Published
2024
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