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https://www.readbyqxmd.com/read/29234452/genetic-variations-of-cholesteryl-ester-transfer-protein-and-diet-interactions-in-relation-to-lipid-profiles-and-coronary-heart-disease-a-systematic-review
#1
REVIEW
Parvin Mirmiran, Zohre Esfandiar, Firoozeh Hosseini-Esfahani, Gelareh Koochakpoor, Maryam S Daneshpour, Bahar Sedaghati-Khayat, Fereidoun Azizi
Data on diet-genotype interactions in the prevention or treatment of dyslipidemia have increased remarkably. This systematic review aimed to assess nutrigenetic studies regarding the modulating effect of diet on cholesteryl ester transfer protein (CETP) polymorphisms in relation to metabolic traits. Data were collected through studies published between 2000 and SEP. 2016 using five electronic databases. The quality of eligible studies was assessed using a 12-item quality checklist, derived from the STrengthening the REporting of Genetic Association Studies (STREGA) statement...
2017: Nutrition & Metabolism
https://www.readbyqxmd.com/read/29197506/cadmium-exposure-exacerbates-severe-hyperlipidemia-and-fatty-liver-changes-in-zebrafish-via-impairment-of-high-density-lipoproteins-functionality
#2
Jae-Yong Kim, Suk-Jeong Kim, Myung Ae Bae, Jae-Ryong Kim, Kyung-Hyun Cho
Cadmium (Cd) is a heavy metal with several toxicities that have destructive effect on most organ systems. However, its toxic effects on human lipoproteins are largely remained unknown especially in hyperlipidemic zebrafish model. Treatment of human high-density lipoprotein (HDL) with cadmium chloride (CdCl2, final 12 and 24μM) caused spontaneous formation of multimeric apoA-I as well as increased production of glycated extent products. Cd-HDL3 accelerated uptake of oxidized LDL (oxLDL) into macrophages and induced severe senescence in human dermal fibroblast (HDF) cells...
November 29, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29188294/genetic-association-of-lipids-and-lipid-drug-targets-with-abdominal-aortic-aneurysm-a-meta-analysis
#3
Seamus C Harrison, Michael V Holmes, Stephen Burgess, Folkert W Asselbergs, Gregory T Jones, Annette F Baas, F N van 't Hof, Paul I W de Bakker, Jan D Blankensteijn, Janet T Powell, Athanasios Saratzis, Gert J de Borst, Daniel I Swerdlow, Yolanda van der Graaf, Andre M van Rij, David J Carey, James R Elmore, Gerard Tromp, Helena Kuivaniemi, Robert D Sayers, Nilesh J Samani, Matthew J Bown, Steve E Humphries
Importance: Risk factors for abdominal aortic aneurysm (AAA) are largely unknown, which has hampered the development of nonsurgical treatments to alter the natural history of disease. Objective: To investigate the association between lipid-associated single-nucleotide polymorphisms (SNPs) and AAA risk. Design, Setting, and Participants: Genetic risk scores, composed of lipid trait-associated SNPs, were constructed and tested for their association with AAA using conventional (inverse-variance weighted) mendelian randomization (MR) and data from international AAA genome-wide association studies...
November 29, 2017: JAMA Cardiology
https://www.readbyqxmd.com/read/29187200/apoa-i-a-ii-hdl-positively-associates-with-apob-lipoproteins-as-a-potential-atherogenic-indicator
#4
Toshimi Kido, Kazuo Kondo, Hideaki Kurata, Yoko Fujiwara, Takeyoshi Urata, Hiroshige Itakura, Shinji Yokoyama
BACKGROUND: We recently reported distinct nature of high-density lipoproteins (HDL) subgroup particles with apolipoprotein (apo) A-I but not apoA-II (LpAI) and HDL having both (LpAI:AII) based on the data from 314 Japanese. While plasma HDL level almost exclusively depends on concentration of LpAI having 3 to 4 apoA-I molecules, LpAI:AII appeared with almost constant concentration regardless of plasma HDL levels having stable structure with two apoA-I and one disulfide-dimeric apoA-II molecules (Sci...
November 29, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/29174438/mendelian-randomization-analysis-of-cholesteryl-ester-transfer-protein-and-subclinical-atherosclerosis-a-population-based-study
#5
Tim Christen, Stella Trompet, Raymond Noordam, Lisanne L Blauw, Karin B Gast, Patrick C N Rensen, Ko Willems van Dijk, Frits R Rosendaal, Renée de Mutsert, J Wouter Jukema
BACKGROUND: Several trials to prevent cardiovascular disease by inhibiting cholesteryl ester transfer protein (CETP) have failed, except Randomized EValuation of the Effects of Anacetrapib through Lipid-modification. Thus far, it is unclear to what extent CETP is causally related to measures of atherosclerosis. OBJECTIVE: The aim of the article was to study the causal relationship between genetically determined CETP concentration and carotid intima-media thickness (cIMT) in a population-based cohort study...
November 2, 2017: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/29155143/obeticholic-acid-raises-ldl-cholesterol-and-reduces-hdl-cholesterol-in-the-diet-induced-nash-din-hamster-model
#6
François Briand, Emmanuel Brousseau, Marjolaine Quinsat, Rémy Burcelin, Thierry Sulpice
The use of rat and mouse models limits the translation to humans for developing novel drugs targeting nonalcoholic steatohepatitis (NASH). Obeticholic acid (OCA) illustrates this limitation since its dyslipidemic effect in humans cannot be observed in these rodents. Conversely, Golden Syrian hamsters have a lipoprotein metabolism mimicking human dyslipidemia since it does express the cholesteryl ester transfer protein (CETP). We therefore developed a Diet-induced NASH (DIN) hamster model and evaluated the impact of OCA...
November 16, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29141072/association-of-cetp-gene-variants-with-risk-for-vascular-and-nonvascular-diseases-among-chinese-adults
#7
Iona Y Millwood, Derrick A Bennett, Michael V Holmes, Ruth Boxall, Yu Guo, Zheng Bian, Ling Yang, Sam Sansome, Yiping Chen, Huaidong Du, Canqing Yu, Alex Hacker, Dermot F Reilly, Yunlong Tan, Michael R Hill, Junshi Chen, Richard Peto, Hongbing Shen, Rory Collins, Robert Clarke, Liming Li, Robin G Walters, Zhengming Chen
Importance: Increasing levels of high-density lipoprotein (HDL) cholesterol through pharmacologic inhibition of cholesteryl ester transfer protein (CETP) is a potentially important strategy for prevention and treatment of cardiovascular disease (CVD). Objective: To use genetic variants in the CETP gene to assess potential risks and benefits of lifelong lower CETP activity on CVD and other outcomes. Design, Setting, and Participants: This prospective biobank study included 151 217 individuals aged 30 to 79 years who were enrolled from 5 urban and 5 rural areas of China from June 25, 2004, through July 15, 2008...
November 15, 2017: JAMA Cardiology
https://www.readbyqxmd.com/read/29131320/a-translational-evidence-for-cholesteryl-ester-transfer-protein-cetp-modulation-by-glucocorticoids-a-time-for-reflection
#8
Luca Liberale, Fabrizio Montecucco, Aldo Bonaventura
In November 2017, the Council of the European Society of Clinical Investigation (ESCI) evaluated all basic research articles published in the European Journal of Clinical Investigation (EJCI) from November 2016 to October 2017. In the final selection round, five articles of outstanding quality have been selected based on their scientific impact, quality, and novelty [1-5]. Among finalists, the article by Jorien Werumeus Buning and Lidya G. Dimova et al. entitled "Downregulation of cholesteryl ester transfer protein by glucocorticoids: a randomized study on HDL" obtained the highest consideration by the ESCI Council and has been judged as the Best Basic Research Article published in EJCI [5]...
November 13, 2017: European Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29121499/atorvastatin-accelerates-clearance-of-lipoprotein-remnants-generated-by-activated-brown-fat-to-further-reduce-hypercholesterolemia-and-atherosclerosis
#9
Geerte Hoeke, Yanan Wang, Andrea D van Dam, Isabel M Mol, Eveline Gart, Henk G Klop, Susan M van den Berg, Elsbet H Pieterman, Hans M G Princen, Albert K Groen, Patrick C N Rensen, Jimmy F P Berbée, Mariëtte R Boon
BACKGROUND AND AIMS: Activation of brown adipose tissue (BAT) reduces both hyperlipidemia and atherosclerosis by increasing the uptake of triglyceride-derived fatty acids by BAT, accompanied by formation and clearance of lipoprotein remnants. We tested the hypothesis that the hepatic uptake of lipoprotein remnants generated by BAT activation would be accelerated by concomitant statin treatment, thereby further reducing hypercholesterolemia and atherosclerosis. METHODS: APOE*3-Leiden...
October 26, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/29112287/synthesis-biological-evaluation-and-molecular-modeling-study-of-substituted-benzyl-benzamides-as-cetp-inhibitors
#10
Reema Abu Khalaf, Dima Sabbah, Eveen Al-Shalabi, Samar Bishtawi, Ghadeer Albadawi, Ghassan Abu Sheikha
Cardiovascular disease is the most common cause for mortality and morbidity in the developed world; its risk is inversely related to the high-density lipoprotein (HDL) cholesterol levels. Therefore, there is a great interest in developing new cholesteryl ester transfer protein (CETP) inhibitors capable of raising HDL as a novel approach for the prevention of cardiovascular disease. Herein, the synthesis and characterization of ten benzyl benzamides 8a-j that aim at CETP inhibition was performed. The in vitro CETP inhibition bioassay revealed that benzamide 8j had the best activity, with a percent inhibition of 82...
November 7, 2017: Archiv der Pharmazie
https://www.readbyqxmd.com/read/29112169/design-synthesis-and-biological-evaluation-of-n-n-disubstituted-4-arylthiazole-2-methylamine-derivatives-as-cholesteryl-ester-transfer-inhibitors
#11
Xinran Wang, Xuehua Lin, Xuanqi Xu, Wei Li, Lijuan Hao, Chunchi Liu, Dongmei Zhao, Maosheng Cheng
Cholesteryl ester transfer protein (CETP) has been identified as a potential target for cardiovascular disease (CVD) for its important role in the reverse cholesteryl transfer (RCT) process. In our previous work, compound 5 was discovered as a moderate CETP inhibitor. The replacement of the amide linker by heterocyclic aromatics and then a series of N,N-substituted-4-arylthiazole-2-methylamine derivatives were designed by utilizing a conformational restriction strategy. Thirty-six compounds were synthesized and evaluated for their CETP inhibitory activities...
November 7, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29103089/hdl-cholesterol-metabolism-and-the-risk-of-chd-new-insights-from-human-genetics
#12
REVIEW
Cecilia Vitali, Sumeet A Khetarpal, Daniel J Rader
PURPOSE OF REVIEW: Elevated high-density lipoprotein cholesterol levels in the blood (HDL-C) represent one of the strongest epidemiological surrogates for protection against coronary heart disease (CHD), but recent human genetic and pharmacological intervention studies have raised controversy about the causality of this relationship. Here, we review recent discoveries from human genome studies using new analytic tools as well as relevant animal studies that have both addressed, and in some cases, fueled this controversy...
November 4, 2017: Current Cardiology Reports
https://www.readbyqxmd.com/read/29096859/lipoprotein-a-apheresis-in-the-light-of-new-drug-developments
#13
Anja Vogt
Elevated levels of lipoprotein(a) (Lp(a)) contribute to the risk of early and severe cardiovascular disease (CVD). Recently <50 mg/dl was recommended as the desirable level for clinical use and decision making. All established medical therapies to lower cholesterol levels have no impact on lowering Lp(a) except niacin which is all too often poorly tolerated and not obtainable everywhere. Lipoprotein apheresis is an extracorporeal treatment to lower levels of Lp(a) significantly by > 60%. In some countries it is recommended in very high risk patients with early or progressive CVD...
November 2017: Atherosclerosis. Supplements
https://www.readbyqxmd.com/read/29083408/exome-wide-association-study-of-plasma-lipids-in-300-000-individuals
#14
Dajiang J Liu, Gina M Peloso, Haojie Yu, Adam S Butterworth, Xiao Wang, Anubha Mahajan, Danish Saleheen, Connor Emdin, Dewan Alam, Alexessander Couto Alves, Philippe Amouyel, Emanuele Di Angelantonio, Dominique Arveiler, Themistocles L Assimes, Paul L Auer, Usman Baber, Christie M Ballantyne, Lia E Bang, Marianne Benn, Joshua C Bis, Michael Boehnke, Eric Boerwinkle, Jette Bork-Jensen, Erwin P Bottinger, Ivan Brandslund, Morris Brown, Fabio Busonero, Mark J Caulfield, John C Chambers, Daniel I Chasman, Y Eugene Chen, Yii-Der Ida Chen, Rajiv Chowdhury, Cramer Christensen, Audrey Y Chu, John M Connell, Francesco Cucca, L Adrienne Cupples, Scott M Damrauer, Gail Davies, Ian J Deary, George Dedoussis, Joshua C Denny, Anna Dominiczak, Marie-Pierre Dubé, Tapani Ebeling, Gudny Eiriksdottir, Tõnu Esko, Aliki-Eleni Farmaki, Mary F Feitosa, Marco Ferrario, Jean Ferrieres, Ian Ford, Myriam Fornage, Paul W Franks, Timothy M Frayling, Ruth Frikke-Schmidt, Lars G Fritsche, Philippe Frossard, Valentin Fuster, Santhi K Ganesh, Wei Gao, Melissa E Garcia, Christian Gieger, Franco Giulianini, Mark O Goodarzi, Harald Grallert, Niels Grarup, Leif Groop, Megan L Grove, Vilmundur Gudnason, Torben Hansen, Tamara B Harris, Caroline Hayward, Joel N Hirschhorn, Oddgeir L Holmen, Jennifer Huffman, Yong Huo, Kristian Hveem, Sehrish Jabeen, Anne U Jackson, Johanna Jakobsdottir, Marjo-Riitta Jarvelin, Gorm B Jensen, Marit E Jørgensen, J Wouter Jukema, Johanne M Justesen, Pia R Kamstrup, Stavroula Kanoni, Fredrik Karpe, Frank Kee, Amit V Khera, Derek Klarin, Heikki A Koistinen, Jaspal S Kooner, Charles Kooperberg, Kari Kuulasmaa, Johanna Kuusisto, Markku Laakso, Timo Lakka, Claudia Langenberg, Anne Langsted, Lenore J Launer, Torsten Lauritzen, David C M Liewald, Li An Lin, Allan Linneberg, Ruth J F Loos, Yingchang Lu, Xiangfeng Lu, Reedik Mägi, Anders Malarstig, Ani Manichaikul, Alisa K Manning, Pekka Mäntyselkä, Eirini Marouli, Nicholas G D Masca, Andrea Maschio, James B Meigs, Olle Melander, Andres Metspalu, Andrew P Morris, Alanna C Morrison, Antonella Mulas, Martina Müller-Nurasyid, Patricia B Munroe, Matt J Neville, Jonas B Nielsen, Sune F Nielsen, Børge G Nordestgaard, Jose M Ordovas, Roxana Mehran, Christoper J O'Donnell, Marju Orho-Melander, Cliona M Molony, Pieter Muntendam, Sandosh Padmanabhan, Colin N A Palmer, Dorota Pasko, Aniruddh P Patel, Oluf Pedersen, Markus Perola, Annette Peters, Charlotta Pisinger, Giorgio Pistis, Ozren Polasek, Neil Poulter, Bruce M Psaty, Daniel J Rader, Asif Rasheed, Rainer Rauramaa, Dermot F Reilly, Alex P Reiner, Frida Renström, Stephen S Rich, Paul M Ridker, John D Rioux, Neil R Robertson, Dan M Roden, Jerome I Rotter, Igor Rudan, Veikko Salomaa, Nilesh J Samani, Serena Sanna, Naveed Sattar, Ellen M Schmidt, Robert A Scott, Peter Sever, Raquel S Sevilla, Christian M Shaffer, Xueling Sim, Suthesh Sivapalaratnam, Kerrin S Small, Albert V Smith, Blair H Smith, Sangeetha Somayajula, Lorraine Southam, Timothy D Spector, Elizabeth K Speliotes, John M Starr, Kathleen E Stirrups, Nathan Stitziel, Konstantin Strauch, Heather M Stringham, Praveen Surendran, Hayato Tada, Alan R Tall, Hua Tang, Jean-Claude Tardif, Kent D Taylor, Stella Trompet, Philip S Tsao, Jaakko Tuomilehto, Anne Tybjaerg-Hansen, Natalie R van Zuydam, Anette Varbo, Tibor V Varga, Jarmo Virtamo, Melanie Waldenberger, Nan Wang, Nick J Wareham, Helen R Warren, Peter E Weeke, Joshua Weinstock, Jennifer Wessel, James G Wilson, Peter W F Wilson, Ming Xu, Hanieh Yaghootkar, Robin Young, Eleftheria Zeggini, He Zhang, Neil S Zheng, Weihua Zhang, Yan Zhang, Wei Zhou, Yanhua Zhou, Magdalena Zoledziewska, Joanna M M Howson, John Danesh, Mark I McCarthy, Chad A Cowan, Goncalo Abecasis, Panos Deloukas, Kiran Musunuru, Cristen J Willer, Sekar Kathiresan
We screened variants on an exome-focused genotyping array in >300,000 participants (replication in >280,000 participants) and identified 444 independent variants in 250 loci significantly associated with total cholesterol (TC), high-density-lipoprotein cholesterol (HDL-C), low-density-lipoprotein cholesterol (LDL-C), and/or triglycerides (TG). At two loci (JAK2 and A1CF), experimental analysis in mice showed lipid changes consistent with the human data. We also found that: (i) beta-thalassemia trait carriers displayed lower TC and were protected from coronary artery disease (CAD); (ii) excluding the CETP locus, there was not a predictable relationship between plasma HDL-C and risk for age-related macular degeneration; (iii) only some mechanisms of lowering LDL-C appeared to increase risk for type 2 diabetes (T2D); and (iv) TG-lowering alleles involved in hepatic production of TG-rich lipoproteins (TM6SF2 and PNPLA3) tracked with higher liver fat, higher risk for T2D, and lower risk for CAD, whereas TG-lowering alleles involved in peripheral lipolysis (LPL and ANGPTL4) had no effect on liver fat but decreased risks for both T2D and CAD...
October 30, 2017: Nature Genetics
https://www.readbyqxmd.com/read/29080057/sex-differences-in-blood-hdl-c-the-total-cholesterol-hdl-c-ratio-and-palmitoleic-acid-are-not-associated-with-variants-in-common-candidate-genes
#15
Shannon L Klingel, Kaitlin Roke, Bertha Hidalgo, Stella Aslibekyan, Robert J Straka, Ping An, Michael A Province, Paul N Hopkins, Donna K Arnett, Jose M Ordovas, Chao-Qiang Lai, David M Mutch
Blood lipids are associated with cardiovascular disease (CVD) risk. Moreover, circulating lipid and fatty acid levels vary between men and women, and evidence demonstrates these traits may be influenced by single nucleotide polymorphisms (SNP). Sex-genotype interactions related to blood lipids and fatty acids have been poorly investigated and may help elucidate sex differences in CVD risk. The goal of this study was to investigate if the influence of SNPs previously associated with blood lipids and fatty acids varies in a sex-specific manner...
December 2017: Lipids
https://www.readbyqxmd.com/read/29076741/correlating-in-vitro-solubilization-and-supersaturation-profiles-with-in-vivo-exposure-for-lipid-based-formulations-of-the-cetp-inhibitor-cp-532-623
#16
Claire L McEvoy, Natalie L Trevaskis, Orlagh M Feeney, Glenn A Edwards, Michael E Perlman, Catherine M Ambler, Christopher J H Porter
Lipid based formulations (LBFs) are a promising formulation strategy for many poorly water-soluble drugs and have been shown previously to enhance the oral exposure of CP-532,623, an oral cholesteryl ester transfer protein inhibitor. In the current study, an in vitro lipid digestion model was used to probe the relationship between drug solubilization and supersaturation on in vitro dispersion and digestion of LBF containing long chain (LC) lipids and drug absorption in vivo. After in vitro digestion of LBF based on LC lipids, the proportion of CP-532,623 maintained in the solubilized state in the aqueous phase of the digest was highest in formulations containing Kolliphor RH 40, and in most cases outperformed equivalent formulations based on MC lipids...
November 9, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29074298/variable-cartilage-degradation-in-mice-with-diet-induced-metabolic-dysfunction-food-for-thought
#17
A E Kozijn, L M Gierman, F van der Ham, P Mulder, M C Morrison, S Kühnast, R A van der Heijden, M P Stavro, A van Koppen, E J Pieterman, A M van den Hoek, R Kleemann, H M G Princen, S C Mastbergen, F P J G Lafeber, A-M Zuurmond, I Bobeldijk, H Weinans, R Stoop
OBJECTIVE: Human cohort studies have demonstrated a role for systemic metabolic dysfunction in osteoarthritis (OA) pathogenesis in obese patients. To explore the mechanisms underlying this metabolic phenotype of OA, we examined cartilage degradation in the knees of mice from different genetic backgrounds in which a metabolic phenotype was established by various dietary approaches. DESIGN: Wild-type C57BL/6J mice and genetically modified mice (hCRP, LDLr(-/-). Leiden and ApoE*3Leiden...
October 24, 2017: Osteoarthritis and Cartilage
https://www.readbyqxmd.com/read/29073716/antitumor-activity-of-lepidium-latifolium-and-identification-of-the-epithionitrile-1-cyano-2-3-epithiopropane-as-its-major-active-component
#18
María Conde-Rioll, Consuelo Gajate, José J Fernández, Janny A Villa-Pulgarin, José G Napolitano, Manuel Norte, Faustino Mollinedo
Consumption of Brassica (Cruciferae) vegetables is associated with a reduced risk of cancer, but identification of the active components and insights into the underlying molecular events are scarce. Here we found that an extract of Lepidium latifolium, a cruciferous plant native to southern Europe, Mediterranean countries and Asia, showed in vitro cytotoxic activity, inducing caspase-dependent apoptosis, in a variety of human tumor cells, and the plant juice showed in vivo antitumor activity in a HT-29 human colon cancer xenograft mouse model...
October 26, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/29058169/chronic-exercise-reduces-cetp-and-mesterolone-treatment-counteracts-exercise-benefits-on-plasma-lipoproteins-profile-studies-in-transgenic-mice
#19
Andrea Camargo Casquero, Jairo Augusto Berti, Laura Lauand Sampaio Teixeira, Helena Coutinho Franco de Oliveira
Regular exercise and anabolic androgenic steroids have opposing effects on the plasma lipoprotein profile and risk of cardio-metabolic diseases in humans. Studies in humans and animal models show conflicting results. Here, we used a mice model genetically modified to mimic human lipoprotein profile and metabolism. They under-express the endogenous LDL receptor gene (R1) and express a human transgene encoding the cholesteryl ester transfer protein (CETP), normally absent in mice. The present study was designed to evaluate the independent and interactive effects of testosterone supplementation, exercise training and CETP expression on the plasma lipoprotein profile and CETP activity...
October 20, 2017: Lipids
https://www.readbyqxmd.com/read/29038350/male-apoe-3-leiden-cetp-mice-on-high-fat-high-cholesterol-diet-exhibit-a-biphasic-dyslipidemic-response-mimicking-the-changes-in-plasma-lipids-observed-through-life-in-men
#20
Yared Paalvast, Albert Gerding, Yanan Wang, Vincent W Bloks, Theo H van Dijk, Rick Havinga, Ko Willems van Dijk, Patrick C N Rensen, Barbara M Bakker, Jan Albert Kuivenhoven, Albert K Groen
Physiological adaptations resulting in the development of the metabolic syndrome in man occur over a time span of several decades. This combined with the prohibitive financial cost and ethical concerns to measure key metabolic parameters repeatedly in subjects for the major part of their life span makes that comprehensive longitudinal human data sets are virtually nonexistent. While experimental mice are often used, little is known whether this species is in fact an adequate model to better understand the mechanisms that drive the metabolic syndrome in man...
October 2017: Physiological Reports
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