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Michael Doherty

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https://www.readbyqxmd.com/read/28799350/critical-length-of-a-one-dimensional-nucleus
#1
Mark N Joswiak, Michael F Doherty, Baron Peters
One-dimensional (1D) nucleation is important in crystal growth, amyloid fibril formation, and supramolecular polymerization. The nucleation rate can be readily calculated, but there is no consensus on the critical length. In this work, we employ a splitting probability to derive an analytical expression for the critical length, which corresponds to a 50% survival probability. For a 1D nucleus on a crystal step, this critical length depends on the supersaturation (driving force) and is nearly independent of the kink (surface) energy...
December 7, 2016: Journal of Chemical Physics
https://www.readbyqxmd.com/read/28797283/incident-gout-and-erectile-dysfunction-is-hyperuricaemia-the-elephant-in-the-room
#2
EDITORIAL
Abhishek Abhishek, Michael Doherty
The first prospective population-based study to examine risk of erectile dysfunction in men with gout in the western world has been published. It reports that following their first diagnosis of gout, men have a 31% higher risk of erectile dysfunction than matched controls, although the absolute increase in risk is small. Of interest, the incidence of erectile dysfunction reported in this study is tenfold higher than those reported in nation-wide cohort studies from Taiwan. There is a need for further prospective cohort studies to examine the possible mechanistic association between gout, hyperuricaemia and erectile dysfunction...
August 10, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28794514/discordant-american-college-of-physicians-and-international-rheumatology-guidelines-for-gout-management-consensus-statement-of-the-gout-hyperuricemia-and-crystal-associated-disease-network-g-can
#3
REVIEW
Nicola Dalbeth, Thomas Bardin, Michael Doherty, Frédéric Lioté, Pascal Richette, Kenneth G Saag, Alexander K So, Lisa K Stamp, Hyon K Choi, Robert Terkeltaub
In November 2016, the American College of Physicians (ACP) published a clinical practice guideline on the management of acute and recurrent gout. This guideline differs substantially from the latest guidelines generated by the American College of Rheumatology (ACR), European League Against Rheumatism (EULAR) and 3e (Evidence, Expertise, Exchange) Initiative, despite reviewing largely the same body of evidence. The Gout, Hyperuricemia and Crystal-Associated Disease Network (G-CAN) convened an expert panel to review the methodology and conclusions of these four sets of guidelines and examine possible reasons for discordance between them...
August 10, 2017: Nature Reviews. Rheumatology
https://www.readbyqxmd.com/read/28777934/mutations-in-trappc12-manifest-in-progressive-childhood-encephalopathy-and-golgi-dysfunction
#4
Miroslav P Milev, Megan E Grout, Djenann Saint-Dic, Yong-Han Hank Cheng, Ian A Glass, Christopher J Hale, David S Hanna, Michael O Dorschner, Keshika Prematilake, Avraham Shaag, Orly Elpeleg, Michael Sacher, Dan Doherty, Simon Edvardson
Progressive childhood encephalopathy is an etiologically heterogeneous condition characterized by progressive central nervous system dysfunction in association with a broad range of morbidity and mortality. The causes of encephalopathy can be either non-genetic or genetic. Identifying the genetic causes and dissecting the underlying mechanisms are critical to understanding brain development and improving treatments. Here, we report that variants in TRAPPC12 result in progressive childhood encephalopathy. Three individuals from two unrelated families have either a homozygous deleterious variant (c...
August 3, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/28776014/new-tricks-of-the-trade-for-crystal-structure-refinement
#5
Jinjin Li, Yuriy A Abramov, Michael F Doherty
Accurate crystal structures and their experimental uncertainties, determined by X-ray diffraction/neutron diffraction techniques, are vital for crystal engineering studies, such as polymorph stability and crystal morphology calculations. Because of differences in crystal growth and data measurement conditions, crystallographic databases often contain multiple entries of varying quality of the same compound. The choice of the most reliable and best quality crystal structure from many very similar structures remains an unresolved problem, especially for nonexperts...
July 26, 2017: ACS Central Science
https://www.readbyqxmd.com/read/28759580/knowledge-attitudes-and-practices-towards-yaws-and-yaws-like-skin-disease-in-ghana
#6
Michael Marks, Cynthia Kwakye-Maclean, Rachel Doherty, Paul Adwere, Abdul Aziz Abdulai, Fredrick Duah, Sally-Ann Ohene, Oriol Mitja, Blanche Oguti, Anthony W Solomon, David C W Mabey, Yaw Adu-Sarkodie, Kingsley Asiedu, Mercy M Ackumey
INTRODUCTION: Yaws is endemic in Ghana. The World Health Organization (WHO) has launched a new global eradication campaign based on total community mass treatment with azithromycin. Achieving high coverage of mass treatment will be fundamental to the success of this new strategy; coverage is dependent, in part, on appropriate community mobilisation. An understanding of community knowledge, attitudes and practices related to yaws in Ghana and other endemic countries will be vital in designing effective community engagement strategies...
July 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28754801/subgroup-analyses-of-the-effectiveness-of-oral-glucosamine-for-knee-and-hip-osteoarthritis-a-systematic-review-and-individual-patient-data-meta-analysis-from-the-oa-trail-bank
#7
Jos Runhaar, Rianne M Rozendaal, Marienke van Middelkoop, Hans J W Bijlsma, Michael Doherty, Krysia S Dziedzic, L Stefan Lohmander, Timothy McAlindon, Weiya Zhang, Sita Bierma Zeinstra
OBJECTIVE: To evaluate the effectiveness of oral glucosamine in subgroups of people with hip or knee osteoarthritis (OA) based on baseline pain severity, body mass index (BMI), sex, structural abnormalities and presence of inflammation using individual patient data. METHODS: After a systematic search of the literature and clinical trial registries, all randomised controlled trials (RCTs) evaluating the effect of any oral glucosamine substance in patients with clinically or radiographically defined hip or knee OA were contacted...
July 28, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28753313/neuroactive-steroids-2-3%C3%AE-hydroxy-3%C3%AE-methyl-21-4-cyano-1h-pyrazol-1-yl-19-nor-5%C3%AE-pregnan-20-one-sage-217-a-clinical-next-generation-neuroactive-steroid-positive-allosteric-modulator-of-the-%C3%AE-aminobutyric-acid-a-receptor
#8
Gabriel Martinez Botella, Francesco G Salituro, Boyd L Harrison, Richard T Beresis, Zhu Bai, Maria-Jesus Blanco, Gabriel M Belfort, Jing Dai, Carlos M Loya, Michael A Ackley, Alison L Althaus, Scott J Grossman, Ethan Hoffmann, James J Doherty, Albert J Robichaud
Certain classes of neuroactive steroids (NASs) are positive allosteric modulators (PAM) of synaptic and extrasynaptic GABAA receptors. Herein, we report new SAR insights in a series of 5β-nor-19-pregnan-20-one analogues bearing substituted pyrazoles and triazoles at C-21, culminating in the discovery of 3α-hydroxy-3β-methyl-21-(4-cyano-1H-pyrazol-1'-yl)-19-nor-5β-pregnan-20-one (SAGE-217, 3), a potent GABAA receptor modulator at both synaptic and extrasynaptic receptor subtypes, with excellent oral DMPK properties...
August 17, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28736278/efficacy-paradox-and-proportional-contextual-effect-pce
#9
Weiya Zhang, Michael Doherty
The "efficacy paradox" is when the effect of a treatment tested in an RCT, or evidence-based guideline advice, differs markedly from treatment benefits observed in clinical practice. This arises because in RCT reporting and guideline development treatment efficacy is judged by the separation of the treatment group from the placebo group (the specific treatment effect) whereas in clinical practice it is the overall treatment effect, which includes both specific and contextual responses, that patients experience...
July 20, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28705940/characterisation-of-eppin-function-expression-and-activity-in-the-lung
#10
Aaron Scott, Arlene Glasgow, Donna Small, Simon Carlile, Maelíosa McCrudden, Denise McLean, Ryan Brown, Declan Doherty, Fionnuala T Lundy, Umar I Hamid, Cecilia M O'Kane, Daniel F McAuley, Malcolm Brodlie, Michael Tunney, J Stuart Elborn, Chris R Irwin, David J Timson, Clifford C Taggart, Sinéad Weldon
Eppin is a serine protease inhibitor expressed in male reproductive tissues.The aim of this study was to investigate the localisation and regulation of eppin expression in myeloid and epithelial cell lines, and explore its potential role as a multifunctional host defence protein.Using immunohistochemistry and Western blotting, eppin was detected in the lungs of patients with acute respiratory distress syndrome and cystic fibrosis lung disease. Expression of eppin in monocytic cells was unaffected by stimulation with Toll-like receptor agonists, cytokines and hormone receptor agonists...
July 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28699174/inherited-variation-in-circadian-rhythm-genes-and-risks-of-prostate-cancer-and-three-other-cancer-sites-in-combined-cancer-consortia
#11
Fangyi Gu, Han Zhang, Paula L Hyland, Sonja Berndt, Susan M Gapstur, William Wheeler, Christopher I Amos, Stephane Bezieau, Heike Bickeböller, Hermann Brenner, Paul Brennan, Jenny Chang-Claude, David V Conti, Jennifer Ann Doherty, Stephen B Gruber, Tabitha A Harrison, Richard B Hayes, Michael Hoffmeister, Richard S Houlston, Rayjean J Hung, Mark A Jenkins, Peter Kraft, Kate Lawrenson, James McKay, Sarah Markt, Lorelei Mucci, Catherine M Phelan, Conghui Qu, Angela Risch, Mary Anne Rossing, H-Erich Wichmann, Jianxin Shi, Eva Schernhammer, Kai Yu, Maria Teresa Landi, Neil E Caporaso
Circadian disruption has been linked to carcinogenesis in animal models, but the evidence in humans is inconclusive. Genetic variation in circadian rhythm genes provides a tool to investigate such associations. We examined associations of genetic variation in nine core circadian rhythm genes and six melatonin pathway genes with risk of colorectal, lung, ovarian and prostate cancers using data from the Genetic Associations and Mechanisms in Oncology (GAME-ON) network. The major results for prostate cancer were replicated in the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial, and for colorectal cancer in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO)...
July 12, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28678986/association-of-a-family-history-of-atrial-fibrillation-with-incidence-and-outcomes-of-atrial-fibrillation-a-population-based-family-cohort-study
#12
Shang-Hung Chang, Chang-Fu Kuo, I-Jun Chou, Lai-Chu See, Kuang-Hui Yu, Shue-Fen Luo, Lu-Hsiang Huang, Weiya Zhang, Michael Doherty, Ming-Shien Wen, Chi-Tai Kuo, Yung-Hsin Yeh
Importance: The heritability of atrial fibrillation (AF), the contribution of genetic and environmental factors, and the association of a family history of AF with prognosis are unclear. Objectives: To measure genetic and environmental factors in the familial aggregation of AF and to estimate the association of a family history of AF with major adverse cardiovascular events (MACE). Design, Setting, and Participants: In this Taiwanese nationwide population-based study among more than 23 million people, a custom data set was obtained using the data of all patients having a diagnosis of AF recorded between January 1996 and December 2013 in the Taiwan National Health Insurance Research Database...
August 1, 2017: JAMA Cardiology
https://www.readbyqxmd.com/read/28667163/leukotriene-c4-potentiates-il-33-induced-group-2-innate-lymphoid-cell-activation-and-lung-inflammation
#13
Sean J Lund, Alex Portillo, Kellen Cavagnero, Rachel E Baum, Luay H Naji, Jana H Badrani, Amit Mehta, Michael Croft, David H Broide, Taylor A Doherty
Asthma is a complex disease that is promoted by dysregulated immunity and the presence of many cytokine and lipid mediators. Despite this, there is a paucity of data demonstrating the combined effects of multiple mediators in asthma pathogenesis. Group 2 innate lymphoid cells (ILC2s) have recently been shown to play important roles in the initiation of allergic inflammation; however, it is unclear whether lipid mediators, such as cysteinyl leukotrienes (CysLTs), which are present in asthma, could further amplify the effects of IL-33 on ILC2 activation and lung inflammation...
August 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28663061/family-aggregation-and-heritability-of-esrd-in-taiwan-a-population-based-study
#14
Hsin Hsu Wu, Chang Fu Kuo, I Jung Li, Cheng Hao Weng, Cheng Chia Lee, Kun Hua Tu, Shou Hsuan Liu, Yung Chang Chen, Chih Wei Yang, Shue Fen Luo, Lai Chu See, Kuang Hui Yu, Lu Hsiang Huang, Weiya Zhang, Michael Doherty, Ya Chung Tian
BACKGROUND: Aggregation of end-stage renal disease (ESRD) has been observed in families of European origin, as well as those of African origin. However, it is not well documented if this disease aggregates in Asian families. Furthermore, the contribution of genetic factors and shared environmental factors to family aggregation remains unclear. STUDY DESIGN: Population-based cross-sectional cohort study. SETTING & PARTICIPANTS: All 23,422,955 individuals registered in the Taiwan National Health Insurance Research Database in 2013...
June 26, 2017: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
https://www.readbyqxmd.com/read/28625504/mutations-in-armc9-which-encodes-a-basal-body-protein-cause-joubert-syndrome-in-humans-and-ciliopathy-phenotypes-in-zebrafish
#15
Julie C Van De Weghe, Tamara D S Rusterholz, Brooke Latour, Megan E Grout, Kimberly A Aldinger, Ranad Shaheen, Jennifer C Dempsey, Sateesh Maddirevula, Yong-Han H Cheng, Ian G Phelps, Matthias Gesemann, Himanshu Goel, Ohad S Birk, Talal Alanzi, Rifaat Rawashdeh, Arif O Khan, Michael J Bamshad, Deborah A Nickerson, Stephan C F Neuhauss, William B Dobyns, Fowzan S Alkuraya, Ronald Roepman, Ruxandra Bachmann-Gagescu, Dan Doherty
Joubert syndrome (JS) is a recessive neurodevelopmental disorder characterized by hypotonia, ataxia, abnormal eye movements, and variable cognitive impairment. It is defined by a distinctive brain malformation known as the "molar tooth sign" on axial MRI. Subsets of affected individuals have malformations such as coloboma, polydactyly, and encephalocele, as well as progressive retinal dystrophy, fibrocystic kidney disease, and liver fibrosis. More than 35 genes have been associated with JS, but in a subset of families the genetic cause remains unknown...
July 6, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/28619153/identification-of-candidate-protein-markers-of-bovine-parainfluenza-virus-type-3-infection-using-an-in-vitro-model
#16
Darren W Gray, Michael D Welsh, Simon Doherty, Mark H Mooney
Bovine Parainfluenza Virus Type 3 (BPI3V) infections are often asymptomatic, causing respiratory tissue damage and immunosuppression, predisposing animals to severe bacterial pneumonia, the leading cause of Bovine Respiratory Disease (BRD) mortality. As with many pathogens, routine BPI3V serology does not indicate the presence of damaged respiratory tissue or active infection. In vitro proteomic marker screening using disease relevant cell models could help identify markers of infection and tissue damage that are also detectable during in vivo infections...
May 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/28610984/sar-and-characterization-of-non-substrate-isoindoline-urea-inhibitors-of-nicotinamide-phosphoribosyltransferase-nampt
#17
Michael L Curtin, H Robin Heyman, Richard F Clark, Bryan K Sorensen, George A Doherty, T Matthew Hansen, Robin R Frey, Kathy A Sarris, Ana L Aguirre, Anurupa Shrestha, Noah Tu, Kevin Woller, Marina A Pliushchev, Ramzi F Sweis, Min Cheng, Julie L Wilsbacher, Peter J Kovar, Jun Guo, Dong Cheng, Kenton L Longenecker, Diana Raich, Alla V Korepanova, Nirupama B Soni, Mikkel A Algire, Paul L Richardson, Violeta L Marin, Ilaria Badagnani, Anil Vasudevan, F Greg Buchanan, David Maag, Gary G Chiang, Chris Tse, Michael R Michaelides
Herein we disclose SAR studies that led to a series of isoindoline ureas which we recently reported were first-in-class, non-substrate nicotinamide phosphoribosyltransferase (NAMPT) inhibitors. Modification of the isoindoline and/or the terminal functionality of screening hit 5 provided inhibitors such as 52 and 58 with nanomolar antiproliferative activity and preclinical pharmacokinetics properties which enabled potent antitumor activity when dosed orally in mouse xenograft models. X-ray crystal structures of two inhibitors bound in the NAMPT active-site are discussed...
August 1, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28605531/the-british-society-for-rheumatology-guideline-for-the-management-of-gout
#18
Michelle Hui, Alison Carr, Stewart Cameron, Graham Davenport, Michael Doherty, Harry Forrester, Wendy Jenkins, Kelsey M Jordan, Christian D Mallen, Thomas M McDonald, George Nuki, Anthony Pywell, Weiya Zhang, Edward Roddy
No abstract text is available yet for this article.
June 12, 2017: Rheumatology
https://www.readbyqxmd.com/read/28604730/large-scale-association-analysis-identifies-new-lung-cancer-susceptibility-loci-and-heterogeneity-in-genetic-susceptibility-across-histological-subtypes
#19
James D McKay, Rayjean J Hung, Younghun Han, Xuchen Zong, Robert Carreras-Torres, David C Christiani, Neil E Caporaso, Mattias Johansson, Xiangjun Xiao, Yafang Li, Jinyoung Byun, Alison Dunning, Karen A Pooley, David C Qian, Xuemei Ji, Geoffrey Liu, Maria N Timofeeva, Stig E Bojesen, Xifeng Wu, Loic Le Marchand, Demetrios Albanes, Heike Bickeböller, Melinda C Aldrich, William S Bush, Adonina Tardon, Gad Rennert, M Dawn Teare, John K Field, Lambertus A Kiemeney, Philip Lazarus, Aage Haugen, Stephen Lam, Matthew B Schabath, Angeline S Andrew, Hongbing Shen, Yun-Chul Hong, Jian-Min Yuan, Pier Alberto Bertazzi, Angela C Pesatori, Yuanqing Ye, Nancy Diao, Li Su, Ruyang Zhang, Yonathan Brhane, Natasha Leighl, Jakob S Johansen, Anders Mellemgaard, Walid Saliba, Christopher A Haiman, Lynne R Wilkens, Ana Fernandez-Somoano, Guillermo Fernandez-Tardon, Henricus F M van der Heijden, Jin Hee Kim, Juncheng Dai, Zhibin Hu, Michael P A Davies, Michael W Marcus, Hans Brunnström, Jonas Manjer, Olle Melander, David C Muller, Kim Overvad, Antonia Trichopoulou, Rosario Tumino, Jennifer A Doherty, Matt P Barnett, Chu Chen, Gary E Goodman, Angela Cox, Fiona Taylor, Penella Woll, Irene Brüske, H-Erich Wichmann, Judith Manz, Thomas R Muley, Angela Risch, Albert Rosenberger, Kjell Grankvist, Mikael Johansson, Frances A Shepherd, Ming-Sound Tsao, Susanne M Arnold, Eric B Haura, Ciprian Bolca, Ivana Holcatova, Vladimir Janout, Milica Kontic, Jolanta Lissowska, Anush Mukeria, Simona Ognjanovic, Tadeusz M Orlowski, Ghislaine Scelo, Beata Swiatkowska, David Zaridze, Per Bakke, Vidar Skaug, Shanbeh Zienolddiny, Eric J Duell, Lesley M Butler, Woon-Puay Koh, Yu-Tang Gao, Richard S Houlston, John McLaughlin, Victoria L Stevens, Philippe Joubert, Maxime Lamontagne, David C Nickle, Ma'en Obeidat, Wim Timens, Bin Zhu, Lei Song, Linda Kachuri, María Soler Artigas, Martin D Tobin, Louise V Wain, Thorunn Rafnar, Thorgeir E Thorgeirsson, Gunnar W Reginsson, Kari Stefansson, Dana B Hancock, Laura J Bierut, Margaret R Spitz, Nathan C Gaddis, Sharon M Lutz, Fangyi Gu, Eric O Johnson, Ahsan Kamal, Claudio Pikielny, Dakai Zhu, Sara Lindströem, Xia Jiang, Rachel F Tyndale, Georgia Chenevix-Trench, Jonathan Beesley, Yohan Bossé, Stephen Chanock, Paul Brennan, Maria Teresa Landi, Christopher I Amos
Although several lung cancer susceptibility loci have been identified, much of the heritability for lung cancer remains unexplained. Here 14,803 cases and 12,262 controls of European descent were genotyped on the OncoArray and combined with existing data for an aggregated genome-wide association study (GWAS) analysis of lung cancer in 29,266 cases and 56,450 controls. We identified 18 susceptibility loci achieving genome-wide significance, including 10 new loci. The new loci highlight the striking heterogeneity in genetic susceptibility across the histological subtypes of lung cancer, with four loci associated with lung cancer overall and six loci associated with lung adenocarcinoma...
July 2017: Nature Genetics
https://www.readbyqxmd.com/read/28594918/obesity-metabolic-factors-and-risk-of-different-histological-types-of-lung-cancer-a-mendelian-randomization-study
#20
Robert Carreras-Torres, Mattias Johansson, Philip C Haycock, Kaitlin H Wade, Caroline L Relton, Richard M Martin, George Davey Smith, Demetrius Albanes, Melinda C Aldrich, Angeline Andrew, Susanne M Arnold, Heike Bickeböller, Stig E Bojesen, Hans Brunnström, Jonas Manjer, Irene Brüske, Neil E Caporaso, Chu Chen, David C Christiani, W Jay Christian, Jennifer A Doherty, Eric J Duell, John K Field, Michael P A Davies, Michael W Marcus, Gary E Goodman, Kjell Grankvist, Aage Haugen, Yun-Chul Hong, Lambertus A Kiemeney, Erik H F M van der Heijden, Peter Kraft, Mikael B Johansson, Stephen Lam, Maria Teresa Landi, Philip Lazarus, Loïc Le Marchand, Geoffrey Liu, Olle Melander, Sungshim L Park, Gad Rennert, Angela Risch, Eric B Haura, Ghislaine Scelo, David Zaridze, Anush Mukeriya, Milan Savić, Jolanta Lissowska, Beata Swiatkowska, Vladimir Janout, Ivana Holcatova, Dana Mates, Matthew B Schabath, Hongbing Shen, Adonina Tardon, M Dawn Teare, Penella Woll, Ming-Sound Tsao, Xifeng Wu, Jian-Min Yuan, Rayjean J Hung, Christopher I Amos, James McKay, Paul Brennan
BACKGROUND: Assessing the relationship between lung cancer and metabolic conditions is challenging because of the confounding effect of tobacco. Mendelian randomization (MR), or the use of genetic instrumental variables to assess causality, may help to identify the metabolic drivers of lung cancer. METHODS AND FINDINGS: We identified genetic instruments for potential metabolic risk factors and evaluated these in relation to risk using 29,266 lung cancer cases (including 11,273 adenocarcinomas, 7,426 squamous cell and 2,664 small cell cases) and 56,450 controls...
2017: PloS One
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