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Armstrong, scott a

Nancy E Davidson, Scott A Armstrong, Lisa M Coussens, Marcia R Cruz-Correa, Ralph J DeBerardinis, James H Doroshow, Margaret Foti, Patrick Hwu, Thomas W Kensler, Monica Morrow, Charles G Mulligan, William Pao, Elizabeth A Platz, Thomas J Smith, Cheryl L Willman
No abstract text is available yet for this article.
October 1, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Isabel Morgado-Palacin, Amanda Day, Matilde Murga, Vanesa Lafarga, Marta Elena Anton, Anthony Tubbs, Hua-Tang Chen, Aysegul Ergan, Rhonda Anderson, Avinash Bhandoola, Kurt G Pike, Bernard Barlaam, Elaine Cadogan, Xi Wang, Andrew J Pierce, Chad Hubbard, Scott A Armstrong, André Nussenzweig, Oscar Fernandez-Capetillo
Among the various subtypes of acute myeloid leukemia (AML), those with chromosomal rearrangements of the MLL oncogene (AML-MLL) have a poor prognosis. AML-MLL tumor cells are resistant to current genotoxic therapies because of an attenuated response by p53, a protein that induces cell cycle arrest and apoptosis in response to DNA damage. In addition to chemicals that damage DNA, efforts have focused on targeting DNA repair enzymes as a general chemotherapeutic approach to cancer treatment. Here, we found that inhibition of the kinase ATR, which is the primary sensor of DNA replication stress, induced chromosomal breakage and death of mouse AML(MLL) cells (with an MLL-ENL fusion and a constitutively active N-RAS independently of p53...
September 13, 2016: Science Signaling
Michael W M Kühn, Evelyn Song, Zhaohui Feng, Amit Sinha, Chun-Wei Chen, Aniruddha J Deshpande, Monica Cusan, Noushin Farnoud, Annalisa Mupo, Carolyn Grove, Richard Koche, James E Bradner, Elisa de Stanchina, George S Vassiliou, Takayuki Hoshii, Scott A Armstrong
: Homeobox (HOX) proteins and the receptor tyrosine kinase FLT3 are frequently highly expressed and mutated in acute myeloid leukemia (AML). Aberrant HOX expression is found in nearly all AMLs that harbor a mutation in the Nucleophosmin (NPM1) gene, and FLT3 is concomitantly mutated in approximately 60% of these cases. Little is known about how mutant NPM1 (NPM1(mut)) cells maintain aberrant gene expression. Here, we demonstrate that the histone modifiers MLL1 and DOT1L control HOX and FLT3 expression and differentiation in NPM1(mut) AML...
October 2016: Cancer Discovery
Anton G Henssen, Eileen Jiang, Jiali Zhuang, Luca Pinello, Nicholas D Socci, Richard Koche, Mithat Gonen, Camila M Villasante, Scott A Armstrong, Daniel E Bauer, Zhiping Weng, Alex Kentsis
BACKGROUND: Numerous human genes encode potentially active DNA transposases or recombinases, but our understanding of their functions remains limited due to shortage of methods to profile their activities on endogenous genomic substrates. RESULTS: To enable functional analysis of human transposase-derived genes, we combined forward chemical genetic hypoxanthine-guanine phosphoribosyltransferase 1 (HPRT1) screening with massively parallel paired-end DNA sequencing and structural variant genome assembly and analysis...
2016: BMC Genomics
Christopher P Jones, Ceri M Brenner, Camilla A Stitt, Chris Armstrong, Dean R Rusby, Seyed R Mirfayzi, Lucy A Wilson, Aarón Alejo, Hamad Ahmed, Ric Allott, Nicholas M H Butler, Robert J Clarke, David Haddock, Cristina Hernandez-Gomez, Adam Higginson, Christopher Murphy, Margaret Notley, Charilaos Paraskevoulakos, John Jowsey, Paul McKenna, David Neely, Satya Kar, Thomas B Scott
A small scale sample nuclear waste package, consisting of a 28mm diameter uranium penny encased in grout, was imaged by absorption contrast radiography using a single pulse exposure from an X-ray source driven by a high-power laser. The Vulcan laser was used to deliver a focused pulse of photons to a tantalum foil, in order to generate a bright burst of highly penetrating X-rays (with energy >500keV), with a source size of <0.5mm. BAS-TR and BAS-SR image plates were used for image capture, alongside a newly developed Thalium doped Caesium Iodide scintillator-based detector coupled to CCD chips...
November 15, 2016: Journal of Hazardous Materials
Caroline G Watts, Christine M Madronio, Rachael L Morton, Chris Goumas, Bruce K Armstrong, Austin Curtin, Scott W Menzies, Graham J Mann, John F Thompson, Anne E Cust
BACKGROUND/OBJECTIVES: To describe the method of diagnosis, clinical management and adherence to clinical practice guidelines for melanoma patients at high risk of a subsequent primary melanoma, and compare this with melanoma patients at lower risk. METHODS: The Melanoma Patterns of Care study was a population-based, observational study based on doctors' reported clinical management of melanoma patients in New South Wales, Australia, diagnosed with in situ or invasive melanoma over a 12-month period from October 2006...
August 1, 2016: Australasian Journal of Dermatology
Anna J Podolanczuk, Elizabeth C Oelsner, R Graham Barr, Eric A Hoffman, Hilary F Armstrong, John H M Austin, Robert C Basner, Matthew N Bartels, Jason D Christie, Paul L Enright, Bernadette R Gochuico, Karen Hinckley Stukovsky, Joel D Kaufman, P Hrudaya Nath, John D Newell, Scott M Palmer, Dan Rabinowitz, Ganesh Raghu, Jessica L Sell, Jered Sieren, Sushil K Sonavane, Russell P Tracy, Jubal R Watts, Kayleen Williams, Steven M Kawut, David J Lederer
Evidence suggests that lung injury, inflammation and extracellular matrix remodelling precede lung fibrosis in interstitial lung disease (ILD). We examined whether a quantitative measure of increased lung attenuation on computed tomography (CT) detects lung injury, inflammation and extracellular matrix remodelling in community-dwelling adults sampled without regard to respiratory symptoms or smoking.We measured high attenuation areas (HAA; percentage of lung voxels between -600 and -250 Hounsfield Units) on cardiac CT scans of adults enrolled in the Multi-Ethnic Study of Atherosclerosis...
July 28, 2016: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
Nicole D Bolter, Yong Gao, Kristin Armstrong, Scott A Conger, Stacy Beeson, Hilary Flint-Wagner
No abstract text is available yet for this article.
May 2016: Medicine and Science in Sports and Exercise
Stanley Chun-Wei Lee, Heidi Dvinge, Eunhee Kim, Hana Cho, Jean-Baptiste Micol, Young Rock Chung, Benjamin H Durham, Akihide Yoshimi, Young Joon Kim, Michael Thomas, Camille Lobry, Chun-Wei Chen, Alessandro Pastore, Justin Taylor, Xujun Wang, Andrei Krivtsov, Scott A Armstrong, James Palacino, Silvia Buonamici, Peter G Smith, Robert K Bradley, Omar Abdel-Wahab
No abstract text is available yet for this article.
June 7, 2016: Nature Medicine
Lindsay M LaFave, Wendy Béguelin, Richard Koche, Matt Teater, Barbara Spitzer, Alan Chramiec, Efthymia Papalexi, Matthew D Keller, Todd Hricik, Katerina Konstantinoff, Jean-Baptiste Micol, Benjamin Durham, Sarah K Knutson, John E Campbell, Gil Blum, Xinxu Shi, Emma H Doud, Andrei V Krivtsov, Young Rock Chung, Inna Khodos, Elisa de Stanchina, Ouathek Ouerfelli, Prasad S Adusumilli, Paul M Thomas, Neil L Kelleher, Minkui Luo, Heike Keilhack, Omar Abdel-Wahab, Ari Melnick, Scott A Armstrong, Ross L Levine
No abstract text is available yet for this article.
June 7, 2016: Nature Medicine
Xi Wang, Chun-Wei Chen, Scott A Armstrong
Chromatin based (Epigenetic) mechanisms have been shown to play important roles in the regulation of gene expression during tumorigenesis and development. Mouse modeling suggests the methyltransferase DOT1L as a potential therapeutic target for MLL-rearranged leukemia. Epigenomic profiling indicates an abnormal H3K79me2 pattern on MLL-fusion targeted genes, but the molecular mechanism underlying this epigenetic dependency is not well understood. In this review, we will discuss recent advances in understanding the epigenetic mechanisms governed by DOT1L in the maintenance of gene expression...
February 2016: Current Opinion in Genetics & Development
Stanley Chun-Wei Lee, Heidi Dvinge, Eunhee Kim, Hana Cho, Jean-Baptiste Micol, Young Rock Chung, Benjamin H Durham, Akihide Yoshimi, Young Joon Kim, Michael Thomas, Camille Lobry, Chun-Wei Chen, Alessandro Pastore, Justin Taylor, Xujun Wang, Andrei Krivtsov, Scott A Armstrong, James Palacino, Silvia Buonamici, Peter G Smith, Robert K Bradley, Omar Abdel-Wahab
Mutations in genes encoding splicing factors (which we refer to as spliceosomal genes) are commonly found in patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). These mutations recurrently affect specific amino acid residues, leading to perturbed normal splice site and exon recognition. Spliceosomal gene mutations are always heterozygous and rarely occur together with one another, suggesting that cells may tolerate only a partial deviation from normal splicing activity. To test this hypothesis, we engineered mice to express a mutated allele of serine/arginine-rich splicing factor 2 (Srsf2(P95H))-which commonly occurs in individuals with MDS and AML-in an inducible, hemizygous manner in hematopoietic cells...
June 2016: Nature Medicine
Paul O'connor, Angela O'dea, Sinéad Lydon, Gozie Offiah, Jennifer Scott, Antoinette Flannery, Bronagh Lang, Anthony Hoban, Catherine Armstrong, Dara Byrne
OBJECTIVES: This study aimed to collect and analyse examples of poor teamwork between junior doctors and nurses; identify the teamwork failures contributing to poor team function; and ascertain if particular teamwork failures are associated with higher levels of risk to patients. DESIGN: Critical Incident Technique interviews were carried out with junior doctors and nurses. SETTING: Two teaching hospitals in the Republic of Ireland. PARTICIPANTS: Junior doctors (n = 28) and nurses (n = 8) provided descriptions of scenarios of poor teamwork...
June 2016: International Journal for Quality in Health Care
Jun Li, Susan L Woods, Sue Healey, Jonathan Beesley, Xiaoqing Chen, Jason S Lee, Haran Sivakumaran, Nicci Wayte, Katia Nones, Joshua J Waterfall, John Pearson, Anne-Marie Patch, Janine Senz, Manuel A Ferreira, Pardeep Kaurah, Robertson Mackenzie, Alireza Heravi-Moussavi, Samantha Hansford, Tamsin R M Lannagan, Amanda B Spurdle, Peter T Simpson, Leonard da Silva, Sunil R Lakhani, Andrew D Clouston, Mark Bettington, Florian Grimpen, Rita A Busuttil, Natasha Di Costanzo, Alex Boussioutas, Marie Jeanjean, George Chong, Aurélie Fabre, Sylviane Olschwang, Geoffrey J Faulkner, Evangelos Bellos, Lachlan Coin, Kevin Rioux, Oliver F Bathe, Xiaogang Wen, Hilary C Martin, Deborah W Neklason, Sean R Davis, Robert L Walker, Kathleen A Calzone, Itzhak Avital, Theo Heller, Christopher Koh, Marbin Pineda, Udo Rudloff, Martha Quezado, Pavel N Pichurin, Peter J Hulick, Scott M Weissman, Anna Newlin, Wendy S Rubinstein, Jone E Sampson, Kelly Hamman, David Goldgar, Nicola Poplawski, Kerry Phillips, Lyn Schofield, Jacqueline Armstrong, Cathy Kiraly-Borri, Graeme K Suthers, David G Huntsman, William D Foulkes, Fatima Carneiro, Noralane M Lindor, Stacey L Edwards, Juliet D French, Nicola Waddell, Paul S Meltzer, Daniel L Worthley, Kasmintan A Schrader, Georgia Chenevix-Trench
Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) is an autosomal-dominant cancer-predisposition syndrome with a significant risk of gastric, but not colorectal, adenocarcinoma. We mapped the gene to 5q22 and found loss of the wild-type allele on 5q in fundic gland polyps from affected individuals. Whole-exome and -genome sequencing failed to find causal mutations but, through Sanger sequencing, we identified point mutations in APC promoter 1B that co-segregated with disease in all six families...
May 5, 2016: American Journal of Human Genetics
Gerard L Brien, Daria G Valerio, Scott A Armstrong
The epigenome is a key determinant of transcriptional output. Perturbations within the epigenome are thought to be a key feature of many, perhaps all cancers, and it is now clear that epigenetic changes are instrumental in cancer development. The inherent reversibility of these changes makes them attractive targets for therapeutic manipulation, and a number of small molecules targeting chromatin-based mechanisms are currently in clinical trials. In this perspective we discuss how understanding the cancer epigenome is providing insights into disease pathogenesis and informing drug development...
April 11, 2016: Cancer Cell
Jennifer A MacDiarmid, Veronika Langova, Dale Bailey, Scott T Pattison, Stacey L Pattison, Neil Christensen, Luke R Armstrong, Vatsala N Brahmbhatt, Katarzyna Smolarczyk, Matthew T Harrison, Marylia Costa, Nancy B Mugridge, Ilya Sedliarou, Nicholas A Grimes, Debra L Kiss, Bruce Stillman, Christine L Hann, Gary L Gallia, Robert M Graham, Himanshu Brahmbhatt
BACKGROUND: Cytotoxic chemotherapy can be very effective for the treatment of cancer but toxicity on normal tissues often limits patient tolerance and often causes long-term adverse effects. The objective of this study was to assist in the preclinical development of using modified, non-living bacterially-derived minicells to deliver the potent chemotherapeutic doxorubicin via epidermal growth factor receptor (EGFR) targeting. Specifically, this study sought to evaluate the safety and efficacy of EGFR targeted, doxorubicin loaded minicells (designated EGFRminicellsDox) to deliver doxorubicin to spontaneous brain tumors in 17 companion dogs; a comparative oncology model of human brain cancers...
2016: PloS One
Karen A Mather, Anbupalam Thalamuthu, Christopher Oldmeadow, Fei Song, Nicola J Armstrong, Anne Poljak, Elizabeth G Holliday, Mark McEvoy, John B Kwok, Amelia A Assareh, Simone Reppermund, Nicole A Kochan, Teresa Lee, David Ames, Margaret J Wright, Julian N Trollor, Peter W Schofield, Henry Brodaty, Rodney J Scott, Peter R Schofield, John R Attia, Perminder S Sachdev
Apolipoprotein H (ApoH) is a multi-functional plasma glycoprotein that has been associated with negative health outcomes. ApoH levels have high heritability. We undertook a genome-wide association study of ApoH levels using the largest sample to date and replicated the results in an independent cohort (total N = 1,255). In the discovery phase, a meta-analysis of two cohorts, the Sydney Memory and Ageing Study (Sydney MAS) and the Older Australian Twins Study (OATS) (n = 942) revealed genome-wide significant results in or near the APOH gene on chromosome 17 (top SNP, rs7211380, p = 1 × 10(-11))...
2016: Scientific Reports
Jie He, Omar Abdel-Wahab, Michelle K Nahas, Kai Wang, Raajit K Rampal, Andrew M Intlekofer, Jay Patel, Andrei Krivstov, Garrett M Frampton, Lauren E Young, Shan Zhong, Mark Bailey, Jared R White, Steven Roels, Jason Deffenbaugh, Alex Fichtenholtz, Timothy Brennan, Mark Rosenzweig, Kimberly Pelak, Kristina M Knapp, Kristina W Brennan, Amy L Donahue, Geneva Young, Lazaro Garcia, Selmira T Beckstrom, Mandy Zhao, Emily White, Vera Banning, Jamie Buell, Kiel Iwanik, Jeffrey S Ross, Deborah Morosini, Anas Younes, Alan M Hanash, Elisabeth Paietta, Kathryn Roberts, Charles Mullighan, Ahmet Dogan, Scott A Armstrong, Tariq Mughal, Jo-Anne Vergilio, Elaine Labrecque, Rachel Erlich, Christine Vietz, Roman Yelensky, Philip J Stephens, Vincent A Miller, Marcel R M van den Brink, Geoff A Otto, Doron Lipson, Ross L Levine
The spectrum of somatic alterations in hematologic malignancies includes substitutions, insertions/deletions (indels), copy number alterations (CNAs), and a wide range of gene fusions; no current clinically available single assay captures the different types of alterations. We developed a novel next-generation sequencing-based assay to identify all classes of genomic alterations using archived formalin-fixed paraffin-embedded blood and bone marrow samples with high accuracy in a clinically relevant time frame, which is performed in our Clinical Laboratory Improvement Amendments-certified College of American Pathologists-accredited laboratory...
June 16, 2016: Blood
Alison M Dunning, Kyriaki Michailidou, Karoline B Kuchenbaecker, Deborah Thompson, Juliet D French, Jonathan Beesley, Catherine S Healey, Siddhartha Kar, Karen A Pooley, Elena Lopez-Knowles, Ed Dicks, Daniel Barrowdale, Nicholas A Sinnott-Armstrong, Richard C Sallari, Kristine M Hillman, Susanne Kaufmann, Haran Sivakumaran, Mahdi Moradi Marjaneh, Jason S Lee, Margaret Hills, Monika Jarosz, Suzie Drury, Sander Canisius, Manjeet K Bolla, Joe Dennis, Qin Wang, John L Hopper, Melissa C Southey, Annegien Broeks, Marjanka K Schmidt, Artitaya Lophatananon, Kenneth Muir, Matthias W Beckmann, Peter A Fasching, Isabel Dos-Santos-Silva, Julian Peto, Elinor J Sawyer, Ian Tomlinson, Barbara Burwinkel, Frederik Marme, Pascal Guénel, Thérèse Truong, Stig E Bojesen, Henrik Flyger, Anna González-Neira, Jose I A Perez, Hoda Anton-Culver, Lee Eunjung, Volker Arndt, Hermann Brenner, Alfons Meindl, Rita K Schmutzler, Hiltrud Brauch, Ute Hamann, Kristiina Aittomäki, Carl Blomqvist, Hidemi Ito, Keitaro Matsuo, Natasha Bogdanova, Thilo Dörk, Annika Lindblom, Sara Margolin, Veli-Matti Kosma, Arto Mannermaa, Chiu-Chen Tseng, Anna H Wu, Diether Lambrechts, Hans Wildiers, Jenny Chang-Claude, Anja Rudolph, Paolo Peterlongo, Paolo Radice, Janet E Olson, Graham G Giles, Roger L Milne, Christopher A Haiman, Brian E Henderson, Mark S Goldberg, Soo H Teo, Cheng Har Yip, Silje Nord, Anne-Lise Borresen-Dale, Vessela Kristensen, Jirong Long, Wei Zheng, Katri Pylkäs, Robert Winqvist, Irene L Andrulis, Julia A Knight, Peter Devilee, Caroline Seynaeve, Jonine Figueroa, Mark E Sherman, Kamila Czene, Hatef Darabi, Antoinette Hollestelle, Ans M W van den Ouweland, Keith Humphreys, Yu-Tang Gao, Xiao-Ou Shu, Angela Cox, Simon S Cross, William Blot, Qiuyin Cai, Maya Ghoussaini, Barbara J Perkins, Mitul Shah, Ji-Yeob Choi, Daehee Kang, Soo Chin Lee, Mikael Hartman, Maria Kabisch, Diana Torres, Anna Jakubowska, Jan Lubinski, Paul Brennan, Suleeporn Sangrajrang, Christine B Ambrosone, Amanda E Toland, Chen-Yang Shen, Pei-Ei Wu, Nick Orr, Anthony Swerdlow, Lesley McGuffog, Sue Healey, Andrew Lee, Miroslav Kapuscinski, Esther M John, Mary Beth Terry, Mary B Daly, David E Goldgar, Saundra S Buys, Ramunas Janavicius, Laima Tihomirova, Nadine Tung, Cecilia M Dorfling, Elizabeth J van Rensburg, Susan L Neuhausen, Bent Ejlertsen, Thomas V O Hansen, Ana Osorio, Javier Benitez, Rachel Rando, Jeffrey N Weitzel, Bernardo Bonanni, Bernard Peissel, Siranoush Manoukian, Laura Papi, Laura Ottini, Irene Konstantopoulou, Paraskevi Apostolou, Judy Garber, Muhammad Usman Rashid, Debra Frost, Louise Izatt, Steve Ellis, Andrew K Godwin, Norbert Arnold, Dieter Niederacher, Kerstin Rhiem, Nadja Bogdanova-Markov, Charlotte Sagne, Dominique Stoppa-Lyonnet, Francesca Damiola, Olga M Sinilnikova, Sylvie Mazoyer, Claudine Isaacs, Kathleen B M Claes, Kim De Leeneer, Miguel de la Hoya, Trinidad Caldes, Heli Nevanlinna, Sofia Khan, Arjen R Mensenkamp, Maartje J Hooning, Matti A Rookus, Ava Kwong, Edith Olah, Orland Diez, Joan Brunet, Miquel Angel Pujana, Jacek Gronwald, Tomasz Huzarski, Rosa B Barkardottir, Rachel Laframboise, Penny Soucy, Marco Montagna, Simona Agata, Manuel R Teixeira, Sue Kyung Park, Noralane Lindor, Fergus J Couch, Marc Tischkowitz, Lenka Foretova, Joseph Vijai, Kenneth Offit, Christian F Singer, Christine Rappaport, Catherine M Phelan, Mark H Greene, Phuong L Mai, Gad Rennert, Evgeny N Imyanitov, Peter J Hulick, Kelly-Anne Phillips, Marion Piedmonte, Anna Marie Mulligan, Gord Glendon, Anders Bojesen, Mads Thomassen, Maria A Caligo, Sook-Yee Yoon, Eitan Friedman, Yael Laitman, Ake Borg, Anna von Wachenfeldt, Hans Ehrencrona, Johanna Rantala, Olufunmilayo I Olopade, Patricia A Ganz, Robert L Nussbaum, Simon A Gayther, Katherine L Nathanson, Susan M Domchek, Banu K Arun, Gillian Mitchell, Beth Y Karlan, Jenny Lester, Gertraud Maskarinec, Christy Woolcott, Christopher Scott, Jennifer Stone, Carmel Apicella, Rulla Tamimi, Robert Luben, Kay-Tee Khaw, Åslaug Helland, Vilde Haakensen, Mitch Dowsett, Paul D P Pharoah, Jacques Simard, Per Hall, Montserrat García-Closas, Celine Vachon, Georgia Chenevix-Trench, Antonis C Antoniou, Douglas F Easton, Stacey L Edwards
We analyzed 3,872 common genetic variants across the ESR1 locus (encoding estrogen receptor α) in 118,816 subjects from three international consortia. We found evidence for at least five independent causal variants, each associated with different phenotype sets, including estrogen receptor (ER(+) or ER(-)) and human ERBB2 (HER2(+) or HER2(-)) tumor subtypes, mammographic density and tumor grade. The best candidate causal variants for ER(-) tumors lie in four separate enhancer elements, and their risk alleles reduce expression of ESR1, RMND1 and CCDC170, whereas the risk alleles of the strongest candidates for the remaining independent causal variant disrupt a silencer element and putatively increase ESR1 and RMND1 expression...
April 2016: Nature Genetics
Simone S Riedel, Jessica N Haladyna, Matthew Bezzant, Brett Stevens, Daniel A Pollyea, Amit U Sinha, Scott A Armstrong, Qi Wei, Roy M Pollock, Scott R Daigle, Craig T Jordan, Patricia Ernst, Tobias Neff, Kathrin M Bernt
Meningioma-1 (MN1) overexpression is frequently observed in patients with acute myeloid leukemia (AML) and is predictive of poor prognosis. In murine models, forced expression of MN1 in hematopoietic progenitors induces an aggressive myeloid leukemia that is strictly dependent on a defined gene expression program in the cell of origin, which includes the homeobox genes Hoxa9 and Meis1 as key components. Here, we have shown that this program is controlled by two histone methyltransferases, MLL1 and DOT1L, as deletion of either Mll1 or Dot1l in MN1-expressing cells abrogated the cell of origin-derived gene expression program, including the expression of Hoxa cluster genes...
April 1, 2016: Journal of Clinical Investigation
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