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1. Geographic variation of mutagenic exposures in kidney cancer genomes

Author

Senkin, Sergey, Moody, Sarah, Díaz-Gay, Marcos, Abedi-Ardekani, Behnoush, Cattiaux, Thomas, Ferreiro-Iglesias, Aida, Wang, Jingwei, Fitzgerald, Stephen, Kazachkova, Mariya, Vangara, Raviteja, Le, Anh Phuong, Bergstrom, Erik N., Khandekar, Azhar, Otlu, Burçak, Cheema, Saamin, Latimer, Calli, Thomas, Emily, Atkins, Joshua Ronald, Smith-Byrne, Karl, Cortez Cardoso Penha, Ricardo, Carreira, Christine, Chopard, Priscilia, Gaborieau, Valérie, Keski-Rahkonen, Pekka, Jones, David, Teague, Jon W., Ferlicot, Sophie, Asgari, Mojgan, Sangkhathat, Surasak, Attawettayanon, Worapat, Świątkowska, Beata, Jarmalaite, Sonata, Sabaliauskaite, Rasa, Shibata, Tatsuhiro, Fukagawa, Akihiko, Mates, Dana, Jinga, Viorel, Rascu, Stefan, Mijuskovic, Mirjana, Savic, Slavisa, Milosavljevic, Sasa, Bartlett, John M. S., Albert, Monique, Phouthavongsy, Larry, Ashton-Prolla, Patricia, Botton, Mariana R., Silva Neto, Brasil, Bezerra, Stephania Martins, Curado, Maria Paula, Zequi, Stênio de Cássio, Reis, Rui Manuel, Faria, Eliney Ferreira, de Menezes, Nei Soares, Ferrari, Renata Spagnoli, Banks, Rosamonde E., Vasudev, Naveen S., Zaridze, David, Mukeriya, Anush, Shangina, Oxana, Matveev, Vsevolod, Foretova, Lenka, Navratilova, Marie, Holcatova, Ivana, Hornakova, Anna, Janout, Vladimir, Purdue, Mark P., Rothman, Nathaniel, Chanock, Stephen J., Ueland, Per Magne, Johansson, Mattias, McKay, James, Scelo, Ghislaine, Chanudet, Estelle, Humphreys, Laura, de Carvalho, Ana Carolina, Perdomo, Sandra, Alexandrov, Ludmil B., Stratton, Michael R., and Brennan, Paul

Published
2024
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2. The Mutographs biorepository: A unique genomic resource to study cancer around the world

Author

Perdomo, Sandra, Abedi-Ardekani, Behnoush, de Carvalho, Ana Carolina, Ferreiro-Iglesias, Aida, Gaborieau, Valérie, Cattiaux, Thomas, Renard, Hélène, Chopard, Priscilia, Carreira, Christine, Spanu, Andreea, Nikmanesh, Arash, Cardoso Penha, Ricardo Cortez, Antwi, Samuel O., Ashton-Prolla, Patricia, Canova, Cristina, Chitapanarux, Taned, Cox, Riley, Curado, Maria Paula, de Oliveira, José Carlos, Dzamalala, Charles, Fabianova, Elenora, Ferri, Lorenzo, Fitzgerald, Rebecca, Foretova, Lenka, Gallinger, Steven, Goldstein, Alisa M., Holcatova, Ivana, Huertas, Antonio, Janout, Vladimir, Jarmalaite, Sonata, Kaneva, Radka, Kowalski, Luiz Paulo, Kulis, Tomislav, Lagiou, Pagona, Lissowska, Jolanta, Malekzadeh, Reza, Mates, Dana, McCorrmack, Valerie, Menya, Diana, Mhatre, Sharayu, Mmbaga, Blandina Theophil, de Moricz, André, Nyirády, Péter, Ognjanovic, Miodrag, Papadopoulou, Kyriaki, Polesel, Jerry, Purdue, Mark P., Rascu, Stefan, Rebolho Batista, Lidia Maria, Reis, Rui Manuel, Ribeiro Pinto, Luis Felipe, Rodríguez-Urrego, Paula A., Sangkhathat, Surasak, Sangrajrang, Suleeporn, Shibata, Tatsuhiro, Stakhovsky, Eduard, Świątkowska, Beata, Vaccaro, Carlos, Vasconcelos de Podesta, Jose Roberto, Vasudev, Naveen S., Vilensky, Marta, Yeung, Jonathan, Zaridze, David, Zendehdel, Kazem, Scelo, Ghislaine, Chanudet, Estelle, Wang, Jingwei, Fitzgerald, Stephen, Latimer, Calli, Moody, Sarah, Humphreys, Laura, Alexandrov, Ludmil B., Stratton, Michael R., and Brennan, Paul

Published
2024
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5. SARS-CoV-2 RNA levels in Scotland’s wastewater

Author

Scorza, Livia C. T., Cameron, Graeme J., Murray-Williams, Roisin, Findlay, David, Bolland, Julie, Cerghizan, Brindusa, Campbell, Kirsty, Thomson, David, Corbishley, Alexander, Gally, David, Fitzgerald, Stephen, Low, Alison, McAteer, Sean, Roberts, Adrian M. I., Fang, Zhou, Mayer, Claus-Dieter, Frantsuzova, Anastasia, Baby, Sumy V., Zieliński, Tomasz, and Millar, Andrew J.

Published
2022
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7. Mutational signatures in esophageal squamous cell carcinoma from eight countries with varying incidence

Author

Moody, Sarah, Senkin, Sergey, Islam, S. M. Ashiqul, Wang, Jingwei, Nasrollahzadeh, Dariush, Cortez Cardoso Penha, Ricardo, Fitzgerald, Stephen, Bergstrom, Erik N., Atkins, Joshua, He, Yudou, Khandekar, Azhar, Smith-Byrne, Karl, Carreira, Christine, Gaborieau, Valerie, Latimer, Calli, Thomas, Emily, Abnizova, Irina, Bucciarelli, Pauline E., Jones, David, Teague, Jon W., Abedi-Ardekani, Behnoush, Serra, Stefano, Scoazec, Jean-Yves, Saffar, Hiva, Azmoudeh-Ardalan, Farid, Sotoudeh, Masoud, Nikmanesh, Arash, Poustchi, Hossein, Niavarani, Ahmadreza, Gharavi, Samad, Eden, Michael, Richman, Paul, Campos, Lia S., Fitzgerald, Rebecca C., Ribeiro, Luis Felipe, Soares-Lima, Sheila Coelho, Dzamalala, Charles, Mmbaga, Blandina Theophil, Shibata, Tatsuhiro, Menya, Diana, Goldstein, Alisa M., Hu, Nan, Malekzadeh, Reza, Fazel, Abdolreza, McCormack, Valerie, McKay, James, Perdomo, Sandra, Scelo, Ghislaine, Chanudet, Estelle, Humphreys, Laura, Alexandrov, Ludmil B., Brennan, Paul, and Stratton, Michael R.

Published
2021
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8. Population data evidence of interdependence of the limbs of hormonal feedback loops.

Author

Fitzgerald, Stephen P., Bean, Nigel G., Falhammar, Henrik, Hoermann, Rudolf, Kohanim, Yael Korem, Pohlabeln, Hermann, Beverborg, Niels Grote, and Tomassetti, Sarah

Abstract

The fundamental models underlying hormonal physiological regulation and homeostasis remain poorly understood. We aimed to derive quantitative evidence regarding these models from the study of population data of balance points of different parameters and their respective controlling hormones. We studied the slopes of correlations between concentrations of circulating free thyroxine and thyrotropin, calcium and parathyroid hormone, hemoglobin and erythropoietin, and glucose and insulin in such population data, as well as the slopes of the limbs of various feedback loops estimated empirically and by reverse engineering of the population data. We used computer simulations to model the factors that influence the slopes derived from the population data, and then matched these simulations with the empirically derived slopes. Our simulations showed that changes to the population distribution of feedback loop limbs may alter the slopes of correlations within population data in specific ways. Non-random (interdependent) associations of the limbs of feedback loops may also have this effect, as well as producing discrepancies between the slopes of feedback limb loops determined experimentally and the same slopes determined by derivation from population data. Our corresponding empirical findings were consistent with the presence of such interdependence in the free thyroxine/thyrotropin, hemoglobin/erythropoietin, and glucose/insulin systems. The glucose/insulin data provided evidence consistent with increasing interdependence with age in childhood. Our findings therefore provide strong evidence that the interdependence of the limbs of feedback loops is a general feature of endocrine homeostatic regulation. This interdependence potentially bestows evolutionary homeostatic and regulatory advantages. [ABSTRACT FROM AUTHOR]

Published
2024
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10. The Fire and Tree Mortality Database, for empirical modeling of individual tree mortality after fire

Author

Cansler, C. Alina, Hood, Sharon M., Varner, J. Morgan, van Mantgem, Phillip J., Agne, Michelle C., Andrus, Robert A., Ayres, Matthew P., Ayres, Bruce D., Bakker, Jonathan D., Battaglia, Michael A., Bentz, Barbara J., Breece, Carolyn R., Brown, James K., Cluck, Daniel R., Coleman, Tom W., Corace, III, R. Gregory, Covington, W. Wallace, Cram, Douglas S., Cronan, James B., Crouse, Joseph E., Das, Adrian J., Davis, Ryan S., Dickinson, Darci M., Fitzgerald, Stephen A., Fulé, Peter Z., Ganio, Lisa M., Grayson, Lindsay M., Halpern, Charles B., Hanula, Jim L., Harvey, Brian J., Kevin Hiers, J., Huffman, David W., Keifer, MaryBeth, Keyser, Tara L., Kobziar, Leda N., Kolb, Thomas E., Kolden, Crystal A., Kopper, Karen E., Kreitler, Jason R., Kreye, Jesse K., Latimer, Andrew M., Lerch, Andrew P., Lombardero, Maria J., McDaniel, Virginia L., McHugh, Charles W., McMillin, Joel D., Moghaddas, Jason J., O’Brien, Joseph J., Perrakis, Daniel D. B., Peterson, David W., Prichard, Susan J., Progar, Robert A., Raffa, Kenneth F., Reinhardt, Elizabeth D., Restaino, Joseph C., Roccaforte, John P., Rogers, Brendan M., Ryan, Kevin C., Safford, Hugh D., Santoro, Alyson E., Shearman, Timothy M., Shumate, Alice M., Sieg, Carolyn H., Smith, Sheri L., Smith, Rebecca J., Stephenson, Nathan L., Stuever, Mary, Stevens, Jens T., Stoddard, Michael T., Thies, Walter G., Vaillant, Nicole M., Weiss, Shelby A., Westlind, Douglas J., Woolley, Travis J., and Wright, Micah C.

Published
2020
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12. Re-annotation of 191 developmental and epileptic encephalopathy-associated genes unmasks de novo variants in SCN1A

Author

Steward, Charles A., Roovers, Jolien, Suner, Marie-Marthe, Gonzalez, Jose M., Uszczynska-Ratajczak, Barbara, Pervouchine, Dmitri, Fitzgerald, Stephen, Viola, Margarida, Stamberger, Hannah, Hamdan, Fadi F., Ceulemans, Berten, Leroy, Patricia, Nava, Caroline, Lepine, Anne, Tapanari, Electra, Keiller, Don, Abbs, Stephen, Sanchis-Juan, Alba, Grozeva, Detelina, Rogers, Anthony S., Diekhans, Mark, Guigó, Roderic, Petryszak, Robert, Minassian, Berge A., Cavalleri, Gianpiero, Vitsios, Dimitrios, Petrovski, Slavé, Harrow, Jennifer, Flicek, Paul, Lucy Raymond, F., Lench, Nicholas J., Jonghe, Peter De, Mudge, Jonathan M., Weckhuysen, Sarah, Sisodiya, Sanjay M., and Frankish, Adam

Published
2019
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15. Genome-wide epitope mapping across multiple host species reveals significant diversity in antibody responses to Coxiella burnetii vaccination and infection.

Author

Bach, Emil, Fitzgerald, Stephen F., Williams-MacDonald, Sarah E., Mitchell, Mairi, Golde, William T., Longbottom, David, Nisbet, Alasdair J., Dinkla, Annemieke, Sullivan, Eric, Pinapati, Richard S., Tan, John C., Joosten, Leo A. B., Roest, Hendrik-Jan, Østerbye, Thomas, Koets, Ad P., Buus, Søren, and McNeilly, Tom N.

Subjects
ANTIBODY diversity, COXIELLA burnetii, ANTIBODY formation, Q fever, PROTEIN microarrays, SCHMALLENBERG virus, HUMORAL immunity, CATTLE
Abstract

Coxiella burnetii is an important zoonotic bacterial pathogen of global importance, causing the disease Q fever in a wide range of animal hosts. Ruminant livestock, in particular sheep and goats, are considered the main reservoir of human infection. Vaccination is a key control measure, and two commercial vaccines based on formalin-inactivated C. burnetii bacterins are currently available for use in livestock and humans. However, their deployment is limited due to significant reactogenicity in individuals previously sensitized to C. burnetii antigens. Furthermore, these vaccines interfere with available serodiagnostic tests which are also based on C. burnetii bacterin antigens. Defined subunit antigen vaccines offer significant advantages, as they can be engineered to reduce reactogenicity and co-designed with serodiagnostic tests to allow discrimination between vaccinated and infected individuals. This study aimed to investigate the diversity of antibody responses to C. burnetii vaccination and/or infection in cattle, goats, humans, and sheep through genome-wide linear epitope mapping to identify candidate vaccine and diagnostic antigens within the predicted bacterial proteome. Using high-density peptide microarrays, we analyzed the seroreactivity in 156 serum samples from vaccinated and infected individuals to peptides derived from 2,092 open-reading frames in the C. burnetii genome. We found significant diversity in the antibody responses within and between species and across different types of C. burnetii exposure. Through the implementation of three different vaccine candidate selection methods, we identified 493 candidate protein antigens for protein subunit vaccine design or serodiagnostic evaluation, of which 65 have been previously described. This is the first study to investigate multi-species seroreactivity against the entire C. burnetii proteome presented as overlapping linear peptides and provides the basis for the selection of antigen targets for next-generation Q fever vaccines and diagnostic tests. [ABSTRACT FROM AUTHOR]

Published
2023
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16. Modeling Above-Ground Carbon Dynamics under Different Silvicultural Treatments on the McDonald–Dunn Research Forest.

Author

Carlisle, Catherine, Fitzgerald, Stephen, and Temesgen, Hailemariam

Subjects
FOREST thinning, FOREST management, CARBON sequestration, FOREST plants, CARBON, HARVESTING, BIOMASS conversion
Abstract

Forest management decisions affect carbon stock and rates of sequestration. One subject of debate is the rotation age that will optimize sequestration over extended periods. Some argue that shorter rotations facilitate greater sequestration rates due to the accelerated growth rates of younger trees compared to mature or old-growth trees. Others maintain that frequent harvesting will not allow forest carbon to rebound after each subsequent rotation, and thus more extended periods between clearcutting is the superior choice. These contrasting viewpoints are mirrored regarding the impact of thinning treatments, in that either thinning will enhance forest carbon uptake by facilitating improved and sustained r growth of residual trees or removing any above-ground biomass will outweigh the yields. This study aims to compare the different suites of management decisions and identify practical combinations of rotation ages and thinning applications that will optimize carbon sequestration while meeting other objectives over a 240-year projection timeframe. Stand development under different harvest rotations and thinning specifications was modeled using a Forest Vegetation Simulator (FVS). We found that site productivity was the primary determinant in stand-above-ground carbon dynamics under various management scenarios. Thus, the optimal rotation age/thinning treatment combinations differed between site classes. High productivity stands were estimated to sequester the most above-ground live carbon with 60-year rotations with a low-intensity thin at age 40. Moderately productive stands performed the best with 80-year rotations when two low-intensity thinning treatments were applied between harvests. For high and moderate productivity stands, estimates of gross carbon increased when two low or moderate-intensity thinning treatments were applied within 80- or 120-year rotations. High-intensity thinning treatments reduced total carbon sequestered over the 240-year projection timeframe for all productivity levels and rotation ages, except for low productivity stands under 120-year rotations. [ABSTRACT FROM AUTHOR]

Published
2023
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17. Prevalence of Shiga Toxin-Producing Escherichia coli O157 in Wild Scottish Deer with High Human Pathogenic Potential.

Author

Fitzgerald, Stephen F., Mitchell, Mairi C., Holmes, Anne, Allison, Lesley, Chase-Topping, Margo, Lupolova, Nadejda, Wells, Beth, Gally, David L., and McNeilly, Tom N.

Subjects
*ESCHERICHIA coli O157:H7, *DEER, *ESCHERICHIA coli, *WHOLE genome sequencing, *KIDNEY failure, *KNOWLEDGE gap theory
Abstract

Simple Summary: Shiga toxin-producing E. coli (STEC) serogroup O157 can cause serious infections in humans, with symptoms ranging from bloody diarrhoea to kidney failure, and, in some instances, can be life-threatening. The natural reservoir for these bacteria is livestock, particularly cattle; however, there is an increasing number of human cases associated with wildlife species such as deer. In Scotland, a human STEC O157 outbreak in 2015 that was associated with the consumption of venison prompted us to investigate the prevalence of STEC O157 in Scottish wild deer species. Although the estimated prevalence was low (0.28%), we found that STEC O157 isolates were shed at high levels from positive deer and that these isolates had the potential to cause severe disease in humans. Furthermore, retrospective analysis identified an isolate from this study as the likely source of another Scottish human outbreak in 2017. Shiga toxin-producing E. coli (STEC) infections associated with wildlife are increasing globally, highlighting many 'spillover' species as important reservoirs for these zoonotic pathogens. A human outbreak of STEC serogroup O157 in 2015 in Scotland, associated with the consumption of venison meat products, highlighted several knowledge gaps, including the prevalence of STEC O157 in Scottish wild deer and the potential risk to humans from wild deer isolates. In this study, we undertook a nationwide survey of wild deer in Scotland and determined that the prevalence of STEC O157 in wild deer is low 0.28% (95% confidence interval = 0.06–0.80). Despite the low prevalence of STEC O157 in Scottish wild deer, identified isolates were present in deer faeces at high levels (>104 colony forming units/g faeces) and had high human pathogenic potential based on whole genome sequencing and virulence gene profiling. A retrospective epidemiological investigation also identified one wild deer isolate from this study as a possible source of a Scottish human outbreak in 2017. These results emphasise the importance of food hygiene practices during the processing of wild deer carcasses for human consumption. [ABSTRACT FROM AUTHOR]

Published
2023
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21. Efficacy of Phase I and Phase II Coxiella burnetii Bacterin Vaccines in a Pregnant Ewe Challenge Model.

Author

Williams-Macdonald, Sarah E., Mitchell, Mairi, Frew, David, Palarea-Albaladejo, Javier, Ewing, David, Golde, William T., Longbottom, David, Nisbet, Alasdair J., Livingstone, Morag, Hamilton, Clare M., Fitzgerald, Stephen F., Buus, Søren, Bach, Emil, Dinkla, Annemieke, Roest, Hendrik-Jan, Koets, Ad P., and McNeilly, Tom N.

Subjects
COXIELLA burnetii, BACTERIAL vaccines, EWES, VACCINES, Q fever, SCHMALLENBERG virus, CATTLE
Abstract

The bacterium Coxiella burnetii can cause the disease Q-fever in a wide range of animal hosts. Ruminants, including sheep, are thought to play a pivotal role in the transmission of C. burnetii to humans; however, the only existing livestock vaccine, namely, Coxevac® (Ceva Animal Health Ltd., Libourne, France), a killed bacterin vaccine based on phase I C. burnetii strain Nine-Mile, is only approved for use in goats and cattle. In this study, a pregnant ewe challenge model was used to determine the protective effects of Coxevac® and an experimental bacterin vaccine based on phase II C. burnetii against C. burnetii challenge. Prior to mating, ewes (n = 20 per group) were vaccinated subcutaneously with either Coxevac®, the phase II vaccine, or were unvaccinated. A subset of pregnant ewes (n = 6) from each group was then challenged 151 days later (~100 days of gestation) with 106 infectious mouse doses of C. burnetii, Nine-Mile strain RSA493. Both vaccines provided protection against C. burnetii challenge as measured by reductions in bacterial shedding in faeces, milk and vaginal mucus, and reduced abnormal pregnancies, compared to unvaccinated controls. This work highlights that the phase I vaccine Coxevac® can protect ewes against C. burnetii infection. Furthermore, the phase II vaccine provided comparable levels of protection and may offer a safer and cost-effective alternative to the currently licensed vaccine. [ABSTRACT FROM AUTHOR]

Published
2023
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24. Simultaneous detection of colorectal cancer mutations in stool samples with biochip arrays

Author

Murray Helena A., Latten Mark J., Cartwright Andrew, Mcaleer Damien, and Fitzgerald Stephen P.

Subjects
biochip array technology, colorectal cancer, mutation, non-invasive, stool, Biochemistry, QD415-436
Abstract

Colorectal cancer (CRC) is the second main cause of cancer-related death in the Western world and like many other tumors is curable if detected at an early stage. Current detection options include faecal occult blood testing and invasive direct visualization techniques such as flexible sigmoidoscopy, colonoscopy and barium enema. The availability of a more simple, non-invasive test that detects tumor specific products with optimal analytical performance might overcome barriers among patients who are not willing to undergo more sensitive but invasive tests. One such emerging technology, which has shown promise in recent years, is the analysis of DNA alterations exfoliated from tumor cells into stool. Here we report an analytical platform for non-invasive detection of 28 common mutations within CRC-related genes APC, TP53, K-ras and BRAF in stool samples based on biochip array technology and applied to the semi-automated Evidence Investigator analyzer. Mutation detection was possible in 1000-fold excess of wild type DNA and analysis of 10 CRC-positive patient samples showed presence of targeted mutations with equivalent mutations also identified by an alternative method. This application represents an excellent tool for the multiplex detection of CRC-specific mutations using a single platform.

Published
2009

26. Ensembl 2015

Author

Cunningham, Fiona, Amode, Ridwan M., Barrell, Daniel, Beal, Kathryn, Billis, Konstantinos, Brent, Simon, Carvalho-Silva, Denise, Clapham, Peter, Coates, Guy, Fitzgerald, Stephen, Gil, Laurent, Girón, Carlos García, Gordon, Leo, Hourlier, Thibaut, Hunt, Sarah E., Janacek, Sophie H., Johnson, Nathan, Juettemann, Thomas, Kähäri, Andreas K., Keenan, Stephen, Martin, Fergal J., Maurel, Thomas, McLaren, William, Murphy, Daniel N., Nag, Rishi, Overduin, Bert, Parker, Anne, Patricio, Mateus, Perry, Emily, Pignatelli, Miguel, Riat, Harpreet Singh, Sheppard, Daniel, Taylor, Kieron, Thormann, Anja, Vullo, Alessandro, Wilder, Steven P., Zadissa, Amonida, Aken, Bronwen L., Birney, Ewan, Harrow, Jennifer, Kinsella, Rhoda, Muffato, Matthieu, Ruffier, Magali, Searle, Stephen M.J., Spudich, Giulietta, Trevanion, Stephen J., Yates, Andy, Zerbino, Daniel R., and Flicek, Paul

Published
2015
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29. A mutation in the putative CRP binding site of the dctA promoter of Salmonella enterica serovar Typhimurium enables growth with low orotate concentrations.

Author

Amin, Mohammad R., Korchinski, Lisa, Yoneda, Joshua K., Thakkar, Rishi, Sanson, Carla L.A., Fitzgerald, Stephen F., Kelln, Rod A., and Cameron, Andrew D.S.

Subjects
SALMONELLA enterica serovar typhimurium, SALMONELLA enterica, BINDING sites, WHOLE genome sequencing, CYCLIC adenylic acid, SALMONELLA, MEMBRANE transport proteins
Abstract

Copyright of Canadian Journal of Microbiology is the property of Canadian Science Publishing 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
2022
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30. Clinical features and predictive biomarkers for bladder cancer in patients with type 2 diabetes presenting with haematuria.

Author

Tonry, Claire L., Evans, Raymond M., Ruddock, Mark W., Duggan, Brian, McCloskey, Oonagh, Maxwell, Alexander P., O'Rourke, Declan, Boyd, Ruth E., Watt, Joanne, Reid, Cherith N., Curry, David J., Stevenson, Michael, Young, Margaret K., Jamison, Catherine S., Gallagher, Joe, Fitzgerald, Stephen P., Lamont, John, and Watson, Chris J.

Abstract

Aims: To identify clinical features and protein biomarkers associated with bladder cancer (BC) in individuals with type 2 diabetes mellitus presenting with haematuria. Materials and Methods: Data collected from the Haematuria Biomarker (HaBio) study was used in this analysis. A matched sub‐cohort of patients with type 2 diabetes and patients without diabetes was created based on age, sex, and BC diagnosis, using approximately a 1:2 fixed ratio. Randox Biochip Array Technology and ELISA were applied for measurement of 66 candidate serum and urine protein biomarkers. Hazard ratios and 95% confidence intervals were estimated by chi‐squared and Wilcoxon rank sum test for clinical features and candidate protein biomarkers. Diagnostic protein biomarker models were identified using Lasso‐based binominal regression analysis. Results: There was no difference in BC grade, stage, and severity between individuals with type 2 diabetes and matched controls. Incidence of chronic kidney disease (CKD) was significantly higher in patients with type 2 diabetes (p = 0.008), and CKD was significantly associated with BC in patients with type 2 diabetes (p = 0.032). A biomarker model, incorporating two serum (monocyte chemoattractant protein 1 and vascular endothelial growth factor) and three urine (interleukin 6, cytokeratin 18, and cytokeratin 8) proteins, predicted incidence of BC with an Area Under the Curve (AUC) of 0.84 in individuals with type 2 diabetes. In people without diabetes, the AUC was 0.66. Conclusions: We demonstrate the potential clinical utility of a biomarker panel, which includes proteins related to BC pathogenesis and type 2 diabetes, for monitoring risk of BC in patients with type 2 diabetes. Earlier urology referral of patients with type 2 diabetes will improve outcomes for these patients. TRIAL REGISTRATION: http://www.isrctn.com/ISRCTN25823942. [ABSTRACT FROM AUTHOR]

Published
2022
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38. Ensembl 2014

Author

Flicek, Paul, Amode, Ridwan M., Barrell, Daniel, Beal, Kathryn, Billis, Konstantinos, Brent, Simon, Carvalho-Silva, Denise, Clapham, Peter, Coates, Guy, Fitzgerald, Stephen, Gil, Laurent, Girón, Carlos García, Gordon, Leo, Hourlier, Thibaut, Hunt, Sarah, Johnson, Nathan, Juettemann, Thomas, Kähäri, Andreas K., Keenan, Stephen, Kulesha, Eugene, Martin, Fergal J., Maurel, Thomas, McLaren, William M., Murphy, Daniel N., Nag, Rishi, Overduin, Bert, Pignatelli, Miguel, Pritchard, Bethan, Pritchard, Emily, Riat, Harpreet S., Ruffier, Magali, Sheppard, Daniel, Taylor, Kieron, Thormann, Anja, Trevanion, Stephen J., Vullo, Alessandro, Wilder, Steven P., Wilson, Mark, Zadissa, Amonida, Aken, Bronwen L., Birney, Ewan, Cunningham, Fiona, Harrow, Jennifer, Herrero, Javier, Hubbard, Tim J.P., Kinsella, Rhoda, Muffato, Matthieu, Parker, Anne, Spudich, Giulietta, Yates, Andy, Zerbino, Daniel R., and Searle, Stephen M.J.

Published
2014
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39. The application of new concepts of the assessment of the thyroid state to pregnant women.

Author

Fitzgerald, Stephen P., Bean, Nigel G., Fitzgerald, Samuel P., and Falhammar, Henrik

Subjects
PREGNANT women, THYROID gland, THYROID hormones, PREGNANCY outcomes, FETAL tissues
Abstract

Recently proposed concepts regarding the nature and assessment of the thyroid state have provided a model more consistent with empiric evidence. It now appears likely that there are no such entities as thyroid set points and individual euthyroidism. Rather than there being discrete thyroid states, peripheral organ parameters are associated with thyroid function in a continuous manner. Thyroid hormone levels and, in particular, levels of free thyroxine now appear to be superior to thyrotropin levels as indicators of the thyroid state. Complicating the assessment of the correlations of the thyroid state with pregnancy outcomes are the contribution of the placenta to maternal thyroid function, fetal thyroid development, the multiple potential pathways to any particular outcome, the likely presence of small critical periods of time, the differing genetics of fetal and maternal tissues, and the unreliability of thyroid hormone assays. Nevertheless, there is no apparent reason for there to be a change in pregnancy to the basic principles of thyroid hormone action. The relationships between mild abnormalities of the thyroid state and pregnancy outcomes and the value of treating such mild abnormalities remain uncertain and controversial. The evidence suggests that further investigation of these clinical questions might better be based on thyroid hormone, particularly free thyroxine, levels. In the investigation of borderline low thyroid states, the categories of subclinical hypothyroidism and isolated hypothyroxinemia might both be abandoned with attention being directed to low free thyroxine levels regardless of the thyroid-stimulating hormone (TSH) levels. For these changes to occur, there would ideally be improvements in the assays for free thyroxine in pregnancy. The evidence suggests that, just as in the non-pregnant situation, pregnancy guidelines based on thyrotropin levels may need revision. [ABSTRACT FROM AUTHOR]

Published
2022
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40. Inhibition of IRE1α RNase activity sensitizes patient‐derived acute myeloid leukaemia cells to proteasome inhibitors.

Author

Creedican, Stuart, Robinson, Claire M., Mnich, Katarzyna, Islam, Md Nahidul, Szegezdi, Eva, Clifford, Ruth, Krawczyk, Janusz, Patterson, John B., FitzGerald, Stephen P., Summers, Mark, Richardson, Ciaran, Martin, Kenneth, Gorman, Adrienne M., and Samali, Afshin

Subjects
ACUTE myeloid leukemia, MYELOID cells, PROTEASOME inhibitors, MULTIPLE myeloma, PROTEASOMES, CHRONIC myeloid leukemia
Abstract

Inhibition of IRE1 RNase activity sensitizes patient-derived acute myeloid leukaemia cells to proteasome inhibitors The cells that were most responsive to MKC8866 plus CFZ co-treatment when compared with CFZ treatment alone had the highest XBP1s and vice versa. Significantly increased AML cell death was observed in the combination treatments that included CFZ ( I p i < 0.0001); increased cell death was observed in the combination treatments with BTZ but this was not significant (Figure 1D,E, right panels). We demonstrate that an IRE1 RNase inhibitor (MKC8866), in combination with proteasome inhibitors, significantly decreases XBP1s levels and increases cell death in AML cell lines and patient-derived AML cells. [Extracted from the article]

Published
2022
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41. Redefinition of Successful Treatment of Patients With Hypothyroidism. Is TSH the Best Biomarker of Euthyroidism?

Author

Fitzgerald, Stephen P. and Falhammar, Henrik

Subjects
TREATMENT effectiveness, THYROTROPIN, HYPOTHYROIDISM, THYROID hormones, BIOMARKERS
Abstract

In recent years evidence has accumulated supporting a revised view of the nature of euthyroidism and the biomarkers of thyroid function. Within the normal range, variations in thyroid hormone levels are associated with variations in clinical parameters and outcomes. There are therefore no readily identified individually specific optimum levels of thyroid hormones for any individual. Levels around the middle of the normal population range may best reflect euthyroidism. These levels may have evolutionary advantages on the basis that adverse outcomes often increase with divergence from such levels, and physiological processes tend to minimise such inter-individual and intra-individual divergence. In populations of predominantly untreated individuals, levels of thyroid hormones and in particular levels of free thyroxine (FT4) correlate more often with clinical parameters than do levels of thyrotropin (TSH). Levels of thyroid hormones may therefore be regarded as the best available biomarkers of euthyroidism and dysthyroidism. It follows that 'subclinical hypothyroidism' (normal FT4/raised TSH levels), rather than being an accurate marker of peripheral tissue hypothyroidism is more a marker of decreased thyroid reserve and prognosis. The recent evidence suggests that treatment of hypothyroxinemia, regardless of the TSH level, and monitoring therapy using FT4 and/or triiodothyronine levels, depending on the replacement regime, may result in more successful treatment of hypothyroidism than relying on thyrotropin levels for patient selection and subsequent treatment monitoring. The equivalents of mid-range levels of thyroid hormones (especially FT4), adjusted by individual comorbidity concerns, may be rational general replacement targets. These implications of the new evidence may create opportunities for novel trials of thyroid replacement therapy. [ABSTRACT FROM AUTHOR]

Published
2022
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42. Ensembl 2013

Author

Flicek, Paul, Ahmed, Ikhlak, Amode, Ridwan M., Barrell, Daniel, Beal, Kathryn, Brent, Simon, Carvalho-Silva, Denise, Clapham, Peter, Coates, Guy, Fairley, Susan, Fitzgerald, Stephen, Gil, Laurent, García-Girón, Carlos, Gordon, Leo, Hourlier, Thibaut, Hunt, Sarah, Juettemann, Thomas, Kähäri, Andreas K., Keenan, Stephen, Komorowska, Monika, Kulesha, Eugene, Longden, Ian, Maurel, Thomas, McLaren, William M., Muffato, Matthieu, Nag, Rishi, Overduin, Bert, Pignatelli, Miguel, Pritchard, Bethan, Pritchard, Emily, Riat, Harpreet Singh, Ritchie, Graham R. S., Ruffier, Magali, Schuster, Michael, Sheppard, Daniel, Sobral, Daniel, Taylor, Kieron, Thormann, Anja, Trevanion, Stephen, White, Simon, Wilder, Steven P., Aken, Bronwen L., Birney, Ewan, Cunningham, Fiona, Dunham, Ian, Harrow, Jennifer, Herrero, Javier, Hubbard, Tim J. P., Johnson, Nathan, Kinsella, Rhoda, Parker, Anne, Spudich, Giulietta, Yates, Andy, Zadissa, Amonida, and Searle, Stephen M. J.

Published
2013
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43. Adsorption of CF4 on the internal and external surfaces of opened single-walled carbon nanotubes: a vibrational spectroscopy study

Author

Byl, Oleg, Kondratyuk, Petro, Forth, Scott T., Fitzgerald, Stephen A., Chen, Liang, Johnson, J. Karl, and Yates, John

Subjects
Carbon -- Research, Nanotubes -- Usage, Infrared spectroscopy -- Usage, Chemistry
Abstract

Infrared spectroscopy is used to make the first experimental discrimination between molecules bound by physisorption on the exterior surface of carbon single-walled nanotubes (SWNTs) and molecules bound in the interior. The selective displacement of the internally bound molecules is observed as a second adsorbate is added.

Published
2003

45. Insights into hominid evolution from the gorilla genome sequence

Author

Scally, Aylwyn, Dutheil, Julien Y., Hillier, LaDeana W., Jordan, Gregory E., Goodhead, Ian, Herrero, Javier, Hobolth, Asger, Lappalainen, Tuuli, Mailund, Thomas, Marques-Bonet, Tomas, McCarthy, Shane, Montgomery, Stephen H., Schwalie, Petra C., Tang, Amy Y., Ward, Michelle C., Xue, Yali, Yngvadottir, Bryndis, Alkan, Can, Andersen, Lars N., Ayub, Qasim, Ball, Edward V., Beal, Kathryn, Bradley, Brenda J., Chen, Yuan, Clee, Chris M., Fitzgerald, Stephen, Graves, Tina A., Gu, Yong, Heath, Paul, Heger, Andreas, Karakoc, Emre, Kolb-Kokocinski, Anja, Laird, Gavin K., Lunter, Gerton, Meader, Stephen, Mort, Matthew, Mullikin, James C., Munch, Kasper, O’Connor, Timothy D., Phillips, Andrew D., Prado-Martinez, Javier, Rogers, Anthony S., Sajjadian, Saba, Schmidt, Dominic, Shaw, Katy, Simpson, Jared T., Stenson, Peter D., Turner, Daniel J., Vigilant, Linda, Vilella, Albert J., Whitener, Weldon, Zhu, Baoli, Cooper, David N., de Jong, Pieter, Dermitzakis, Emmanouil T., Eichler, Evan E., Flicek, Paul, Goldman, Nick, Mundy, Nicholas I., Ning, Zemin, Odom, Duncan T., Ponting, Chris P., Quail, Michael A., Ryder, Oliver A., Searle, Stephen M., Warren, Wesley C., Wilson, Richard K., Schierup, Mikkel H., Rogers, Jane, Tyler-Smith, Chris, and Durbin, Richard

Published
2012
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46. Ensembl 2012

Author

Flicek, Paul, Amode, M. Ridwan, Barrell, Daniel, Beal, Kathryn, Brent, Simon, Carvalho-Silva, Denise, Clapham, Peter, Coates, Guy, Fairley, Susan, Fitzgerald, Stephen, Gil, Laurent, Gordon, Leo, Hendrix, Maurice, Hourlier, Thibaut, Johnson, Nathan, Kähäri, Andreas K., Keefe, Damian, Keenan, Stephen, Kinsella, Rhoda, Komorowska, Monika, Koscielny, Gautier, Kulesha, Eugene, Larsson, Pontus, Longden, Ian, McLaren, William, Muffato, Matthieu, Overduin, Bert, Pignatelli, Miguel, Pritchard, Bethan, Riat, Harpreet Singh, Ritchie, Graham R. S., Ruffier, Magali, Schuster, Michael, Sobral, Daniel, Tang, Y. Amy, Taylor, Kieron, Trevanion, Stephen, Vandrovcova, Jana, White, Simon, Wilson, Mark, Wilder, Steven P., Aken, Bronwen L., Birney, Ewan, Cunningham, Fiona, Dunham, Ian, Durbin, Richard, Fernández-Suarez, Xosé M., Harrow, Jennifer, Herrero, Javier, Hubbard, Tim J. P., Parker, Anne, Proctor, Glenn, Spudich, Giulietta, Vogel, Jan, Yates, Andy, Zadissa, Amonida, and Searle, Stephen M. J.

Published
2012
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47. A high-resolution map of human evolutionary constraint using 29 mammals

Author

Lindblad-Toh, Kerstin, Garber, Manuel, Zuk, Or, Lin, Michael F., Parker, Brian J., Washietl, Stefan, Kheradpour, Pouya, Ernst, Jason, Jordan, Gregory, Mauceli, Evan, Ward, Lucas D., Lowe, Craig B., Holloway, Alisha K., Clamp, Michele, Gnerre, Sante, Alföldi, Jessica, Beal, Kathryn, Chang, Jean, Clawson, Hiram, Cuff, James, Di Palma, Federica, Fitzgerald, Stephen, Flicek, Paul, Guttman, Mitchell, Hubisz, Melissa J., Jaffe, David B., Jungreis, Irwin, Kent, James W., Kostka, Dennis, Lara, Marcia, Martins, Andre L., Massingham, Tim, Moltke, Ida, Raney, Brian J., Rasmussen, Matthew D., Robinson, Jim, Stark, Alexander, Vilella, Albert J., Wen, Jiayu, Xie, Xiaohui, Zody, Michael C., Baldwin, Jen, Bloom, Toby, Chin, Chee Whye, Heiman, Dave, Nicol, Robert, Nusbaum, Chad, Young, Sarah, Wilkinson, Jane, Worley, Kim C., Kovar, Christie L., Muzny, Donna M., Gibbs, Richard A., Cree, Andrew, Dihn, Huyen H., Fowler, Gerald, Jhangiani, Shalili, Joshi, Vandita, Lee, Sandra, Lewis, Lora R., Nazareth, Lynne V., Okwuonu, Geoffrey, Santibanez, Jireh, Warren, Wesley C., Mardis, Elaine R., Weinstock, George M., Wilson, Richard K., Delehaunty, Kim, Dooling, David, Fronik, Catrina, Fulton, Lucinda, Fulton, Bob, Graves, Tina, Minx, Patrick, Sodergren, Erica, Birney, Ewan, Margulies, Elliott H., Herrero, Javier, Green, Eric D., Haussler, David, Siepel, Adam, Goldman, Nick, Pollard, Katherine S., Pedersen, Jakob S., Lander, Eric S., and Kellis, Manolis

Published
2011
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48. Ensembl 2011

Author

Flicek, Paul, Amode, M. Ridwan, Barrell, Daniel, Beal, Kathryn, Brent, Simon, Chen, Yuan, Clapham, Peter, Coates, Guy, Fairley, Susan, Fitzgerald, Stephen, Gordon, Leo, Hendrix, Maurice, Hourlier, Thibaut, Johnson, Nathan, Kähäri, Andreas, Keefe, Damian, Keenan, Stephen, Kinsella, Rhoda, Kokocinski, Felix, Kulesha, Eugene, Larsson, Pontus, Longden, Ian, McLaren, William, Overduin, Bert, Pritchard, Bethan, Riat, Harpreet Singh, Rios, Daniel, Ritchie, Graham R. S., Ruffier, Magali, Schuster, Michael, Sobral, Daniel, Spudich, Giulietta, Tang, Y. Amy, Trevanion, Stephen, Vandrovcova, Jana, Vilella, Albert J., White, Simon, Wilder, Steven P., Zadissa, Amonida, Zamora, Jorge, Aken, Bronwen L., Birney, Ewan, Cunningham, Fiona, Dunham, Ian, Durbin, Richard, Fernández-Suarez, Xosé M., Herrero, Javier, Hubbard, Tim J. P., Parker, Anne, Proctor, Glenn, Vogel, Jan, and Searle, Stephen M. J.

Published
2011
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49. Molecular analysis of the tagF gene, encoding CDP-glycerol: poly(glycerophosphate) glycerophosphotransferase of Staphylococcus epidermidis ATCC 14990

Author

Fitzgerald, Stephen N. and Foster, Timothy J.

Subjects
Bacteriology -- Research, Glycerol -- Research, Gene expression -- Research, Staphylococcus -- Research, Cloning -- Analysis, Biological sciences
Abstract

Research has been conducted on the Staphylococcus epidermidis ATCC 14990. Results demonstrate that the S. epidermidis cloned gene can encode functional CDP-glycerol:poly(glycerophosphate) glycerophosphotransferase.

Published
2000

50. Ensembl’s 10th year

Author

Flicek, Paul, Aken, Bronwen L., Ballester, Benoit, Beal, Kathryn, Bragin, Eugene, Brent, Simon, Chen, Yuan, Clapham, Peter, Coates, Guy, Fairley, Susan, Fitzgerald, Stephen, Fernandez-Banet, Julio, Gordon, Leo, Gräf, Stefan, Haider, Syed, Hammond, Martin, Howe, Kerstin, Jenkinson, Andrew, Johnson, Nathan, Kähäri, Andreas, Keefe, Damian, Keenan, Stephen, Kinsella, Rhoda, Kokocinski, Felix, Koscielny, Gautier, Kulesha, Eugene, Lawson, Daniel, Longden, Ian, Massingham, Tim, McLaren, William, Megy, Karine, Overduin, Bert, Pritchard, Bethan, Rios, Daniel, Ruffier, Magali, Schuster, Michael, Slater, Guy, Smedley, Damian, Spudich, Giulietta, Tang, Y. Amy, Trevanion, Stephen, Vilella, Albert, Vogel, Jan, White, Simon, Wilder, Steven P., Zadissa, Amonida, Birney, Ewan, Cunningham, Fiona, Dunham, Ian, Durbin, Richard, Fernández-Suarez, Xosé M., Herrero, Javier, Hubbard, Tim J., Parker, Anne, Proctor, Glenn, Smith, James, and Searle, Stephen M.

Published
2010
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