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https://www.readbyqxmd.com/read/29218813/association-of-pnpla3-rs738409-polymorphism-with-liver-steatosis-but-not-with-cirrhosis-in-patients-with-hbv-infection-systematic-review-with-meta-analysis
#1
REVIEW
Saman Ghalamkari, Heidar Sharafi, Seyed Moayed Alavian
BACKGROUND AND AIM: Hepatitis B virus (HBV) infection is a worldwide health issue and is well known to be the main cause of developing secondary liver complications such as cirrhosis and hepatocellular carcinoma (HCC). The PNPLA3 rs738409 polymorphism has been investigated conclusively with occurrence risk of steatosis and cirrhosis. Therefore, performing a meta-analysis of the available studies with the aim of clarifying the association between rs738409 and occurrence risk of steatosis and cirrhosis among HBV-infected patients would be helpful...
December 7, 2017: Journal of Gene Medicine
https://www.readbyqxmd.com/read/29193269/additive-effects-of-pnpla3-and-tm6sf2-on-the-histological-severity-of-non-alcoholic-fatty-liver-disease
#2
Bo Kyung Koo, Sae Kyung Joo, Donghee Kim, Jeong Mo Bae, Jeong Hwan Park, Jung Ho Kim, Won Kim
BACKGROUND AND AIM: We investigated the effects of PNPLA3 rs738409, TM6SF2 rs58542926, and MBOAT7-TMC4 rs641738 variants on metabolic phenotypes and their combined effects on the histological severity of non-alcoholic fatty liver disease (NAFLD). METHODS: We genotyped rs738409, rs58542926, and rs641738 in biopsy-proven NAFLD patients (n = 416) and healthy controls (n = 109). Homeostasis model assessment of insulin resistance (HOMA-IR) and adipose tissue insulin resistance (adipo-IR) were calculated...
November 29, 2017: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29160303/the-pnpla3-i148m-variant-is-associated-with-transaminase-elevations-in-type-2-diabetes-patients-treated-with-basal-insulin-peglispro
#3
S Pillai, S Duvvuru, P Bhatnagar, W Foster, M Farmen, S Shankar, C Harris, E Bastyr, B Hoogwerf, A Haupt
Basal insulin peglispro (BIL) is a novel insulin with hepato-preferential action. In phase 3 trials, BIL showed significantly improved glycemic control but higher levels of transaminases (alanine aminotransferase (ALT) and aspartate aminotransferase (AST)), triglycerides (TGs) and liver fat content (LFC) compared with insulin glargine (GL). As variants in PNPLA3 (I148M) and TM6SF2 (E167K) are associated with nonalcoholic fatty liver disease, we assessed these variants in type 2 diabetes (T2D) patients randomized to receive BIL (n=1822) or GL (n=1270) in three phase 3 trials...
November 21, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/29158695/pnpla3-expression-and-its-impact-on-the-liver-current-perspectives
#4
REVIEW
Francesca Virginia Bruschi, Matteo Tardelli, Thierry Claudel, Michael Trauner
A single-nucleotide polymorphism occurring in the sequence of the human patatin-like phospholipase domain-containing 3 gene (PNPLA3), known as I148M variant, is one of the best characterized and deeply investigated variants in several clinical scenarios, because of its tight correlation with increased risk for developing hepatic steatosis and more aggressive part of the disease spectrum, such as nonalcoholic steatohepatitis, advanced fibrosis and cirrhosis. Further, the I148M variant is positively associated with alcoholic liver diseases, chronic hepatitis C-related cirrhosis and hepatocellular carcinoma...
2017: Hepatic Medicine: Evidence and Research
https://www.readbyqxmd.com/read/29150621/pnpla3-variant-and-portal-periportal-histological-pattern-in-patients-with-biopsy-proven-non-alcoholic-fatty-liver-disease-a-possible-role-for-oxidative-stress
#5
Guido Carpino, Daniele Pastori, Francesco Baratta, Diletta Overi, Giancarlo Labbadia, Licia Polimeni, Alessia Di Costanzo, Gaetano Pannitteri, Roberto Carnevale, Maria Del Ben, Marcello Arca, Francesco Violi, Francesco Angelico, Eugenio Gaudio
Pathogenesis of non-alcoholic fatty liver disease (NAFLD) is influenced by predisposing genetic variations, dysmetabolism, systemic oxidative stress, and local cellular and molecular cross-talks. Patatin-like phospholipase domain containing 3 (PNPLA3) gene I148M variant is a known determinant of NAFLD. Aims were to evaluate whether PNPLA3 I148M variant was associated with a specific histological pattern, hepatic stem/progenitor cell (HpSC) niche activation and serum oxidative stress markers. Liver biopsies were obtained from 54 NAFLD patients...
November 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29128053/nonalcoholic-fatty-liver-disease-and-metabolic-syndrome
#6
REVIEW
Donghee Kim, Alexis Touros, W Ray Kim
Nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome (MS) are highly prevalent, affecting approximately one-third of the US population. The relationship between NAFLD and MS is complex and may be bidirectionally associated. NAFLD is strongly associated with MS, the components of which include abdominal obesity, hyperglycemia, hypertension, and dyslipidemia. NAFLD associated with certain genetic factors such as the PNPLA3 G allele variant is not accompanied by insulin resistance and MS. Lifestyle modification, including diet and physical activity targeting visceral adiposity, remains the standard of care for patients with NAFLD and MS...
February 2018: Clinics in Liver Disease
https://www.readbyqxmd.com/read/29122391/genetics-and-epigenetics-of-nafld-and-nash-clinical-impact
#7
REVIEW
Mohammed Eslam, Luca Valenti, Stefano Romeo
Non-alcoholic fatty liver disease (NAFLD) is now recognised as the most common liver disease worldwide. It encompasses a broad spectrum of conditions, from simple steatosis, through non-alcoholic steatohepatitis, to fibrosis and ultimately cirrhosis and hepatocellular carcinoma. A hallmark of NAFLD is the substantial inter-patient variation in disease progression. NAFLD is considered a complex disease trait such that interactions between the environment and a susceptible polygenic host background determine disease phenotype and influence progression...
November 2, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/29116096/aqp3-is-regulated-by-ppar%C3%AE-and-jnk-in-hepatic-stellate-cells-carrying-pnpla3-i148m
#8
Matteo Tardelli, Francesca V Bruschi, Thierry Claudel, Veronica Moreno-Viedma, Emina Halilbasic, Fabio Marra, Merima Herac, Thomas M Stulnig, Michael Trauner
Aquaglyceroporins (AQPs) allow the movement of glycerol that is required for triglyceride formation in hepatic stellate cells (HSC), as key cellular source of fibrogenesis in the liver. The genetic polymorphism I148M of the patatin-like phospholipase domain-containing 3 (PNPLA3) is associated with hepatic steatosis and its progression to steatohepatitis (NASH), fibrosis and cancer. We aimed to explore the role of AQP3 for HSC activation and unveil its potential interactions with PNPLA3. HSC were isolated from human liver, experiments were performed in primary HSC and human HSC line LX2...
November 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29089161/association-between-pnpla3-rs738409-c-g-variant-and-hepatocellular-carcinoma-in-asian-chronic-hepatitis-c-patients-a-longitudinal-study
#9
Yi-Hao Yen, Ming-Chao Tsai, Cheng-Kun Wu, Kuo-Chin Chang, Chao-Hung Hung, King-Wah Chiu, Sheng-Nan Lu, Jing-Houng Wang, Chien-Hung Chen, Kwong-Ming Kee, Yuan-Hung Kuo, Po-Lin Tseng, Ming-Tsung Lin, Chao-Min Huang, Jung-Ting Lin, Tsung-Hui Hu
BACKGROUND/PURPOSE: Prdevious meta-analyses assess whether or not patatin-like phospholipase domain containing 3 (PNPLA3) (rs738409 C > G) was associated with increased risk of hepatocellular carcinoma (HCC) in Caucasians patients with hepatitis C virus (HCV)-related cirrhosis, these meta-analyses did not provide firm conclusions. Only one cross-sectional study involving Asian patients has previously been conducted to explore this issue. We aim to investigate this in a longitudinal cohort of Asian chronic hepatitis C (CHC) patients...
October 28, 2017: Journal of the Formosan Medical Association, Taiwan Yi Zhi
https://www.readbyqxmd.com/read/29083408/exome-wide-association-study-of-plasma-lipids-in-300-000-individuals
#10
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/29055919/the-expression-of-pnpla3-polymorphism-could-be-the-key-for-severe-liver-disease-in-nafld-in-hispanic-population
#11
Leonardo A Martínez, Elena Larrieta, David Kershenobich, Aldo Torre
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) encompasses: fatty liver (SS), steatohepatitis (NASH) with or without fibrosis and cirrhosis. Patatine-like phosphatas in domain 3 (PNPLA3; adiponutrin; SNP rs738409 C/G, M148I) shows anabolic and catabolic activities on lipid metabolism and significant association to fatty liver content; however, I148M demographics and ethnics, as its role with NAFLD have not been fully elucidated. MATERIAL AND METHODS: PNPLA3 genotyping from peripheral blood DNA by polymerase chain reaction (PCR) and direct sequencing, 211 patients diagnosed with NAFLD including SS, NASH and fibrosis spectrum...
October 16, 2017: Annals of Hepatology
https://www.readbyqxmd.com/read/28989566/regional-differences-in-genetic-susceptibility-to-non-alcoholic-liver-disease-in-two-distinct-indian-ethnicities
#12
Govardhan Bale, Avanthi Urmila Steffie, Vishnubhotla Venkata Ravi Kanth, Padaki Nagaraja Rao, Mithun Sharma, Mitnala Sasikala, Duvvur Nageshwar Reddy
AIM: To validate the association of variants in PNPLA3 (rs2281135) and TM6SF2 (rs58542926) genes with ultrasound detected non-alcoholic fatty liver disease (NAFLD). METHODS: A total of 503 individuals with and without fatty infiltration were recruited. Fatty infiltration was confirmed based on ultrasound findings. Anthropometric data and blood samples were collected from the study group. DNA was isolated from peripheral blood, quality and quantity was assessed by gel electrophoresis and spectrophotometer respectively...
September 18, 2017: World Journal of Hepatology
https://www.readbyqxmd.com/read/28975533/association-of-single-nucleotide-polymorphism-at-pnpla3-with-fatty-liver-steatohepatitis-and-cirrhosis-of-liver
#13
Shahinul Alam, Mohammad Shaiful Islam, Saiful Islam, Golam Mustafa, Ahmed Abu Saleh, Nooruddin Ahmad
BACKGROUND/PURPOSE: The aim of this study was to determine the association of single nucleotide polymorphism (SNP) in patatin-like phospholipase domain-containing 3 (PNPLA3) at I148 with histological severity of non-alcoholic fatty liver disease (NAFLD). METHODS: Patients were selected for the study if they had histological evidence of NAFLD and clinical evidence of non-alcoholic steatohepatits (NASH) cirrhosis. We included 50 NASH cirrhosis, 99 patients of NAFLD including 36 non-NASH fatty liver (NNFL) along with 63 NASH and 75 healthy controls...
October 4, 2017: Indian Journal of Gastroenterology: Official Journal of the Indian Society of Gastroenterology
https://www.readbyqxmd.com/read/28972878/role-of-nutrition-gene-polymorphism-and-gut-microbiota-in-non-alcoholic-fatty-liver-disease
#14
Lingbo Kong, Yu Lu, Siyu Zhang, Yuemin Nan, Liang Qiao
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the world. The nutrients play important roles in the development and progression of NAFLD. High-calorie diet, especially the diet rich in saturated fatty acids and cholesterol, as well as sugary drinks with high fructose content, induces hepatic steatosis and triggers progression of steatohepatitis, fibrosis, and even hepatocellular carcinoma. Disordered micronutrient status and gut microbiota are also involved in the pathogenesis of NAFLD...
September 2017: Discovery Medicine
https://www.readbyqxmd.com/read/28950858/identification-of-deleterious-rare-variants-in-mttp-pnpla3-and-tm6sf2-in-japanese-males-and-association-studies-with-nafld
#15
Supichaya Boonvisut, Ken Yoshida, Kazuhiro Nakayama, Kazuhisa Watanabe, Hiroshi Miyashita, Sadahiko Iwamoto
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a disorder characterized by excessive fat deposits in hepatocytes without excessive alcohol intake. NAFLD is influenced by genetic factors, and the heritability has been estimated at 0.35 to 0.6 by twin studies. We explored rare variants in known NAFLD-associated genes to investigate whether these rare variants are involved in the susceptibility to NAFLD. METHODS: The target genes for re-sequencing were PNPLA3, TM6SF2, and MTTP...
September 26, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28928439/polymorphisms-in-mica-but-not-in-depdc5-hcp5-or-pnpla3-are-associated-with-chronic-hepatitis-c-related-hepatocellular-carcinoma
#16
Hoang Hai, Akihiro Tamori, Le Thi Thanh Thuy, Kanako Yoshida, Atsushi Hagihara, Etsushi Kawamura, Sawako Uchida-Kobayashi, Hiroyasu Morikawa, Masaru Enomoto, Yoshiki Murakami, Norifumi Kawada
Recently, the MICA rs2596542 and DEPDC5 rs1012068 variants in Japanese individuals as well as the HCP5 rs2244546 and PNPLA3 rs738409 variants in European individuals have been found associated with hepatocellular carcinoma (HCC). The present study determined which single nucleotide polymorphism (SNP) is the most predictive for developing hepatitis C virus (HCV)-related HCC in a Japanese cohort. Of the 4 SNPs analysed, only the MICA genotypes were significantly associated with development of HCC (p = 0.0185)...
September 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28914407/association-of-fetuin-b-with-markers-of-liver-fibrosis-in-nonalcoholic-fatty-liver-disease
#17
Thomas Ebert, Nicolas Linder, Alexander Schaudinn, Harald Busse, Joachim Berger, Ralf Lichtinghagen, Volker Keim, Johannes Wiegand, Thomas Karlas
OBJECTIVE: The liver-derived plasma protein fetuin B is associated with nonalcoholic fatty liver disease (NAFLD) and impaired glucose homeostasis in mice. However, its association with non-invasive ultrasound- and magnetic resonance (MR)-based markers of liver fibrosis and steatosis, the enhanced liver fibrosis (ELF) score, liver biopsy, as well as rs738409 in PNPLA3, has not been elucidated in NAFLD, so far. DESIGN AND METHODS: The association of circulating fetuin B and transient elastography (TE), controlled attenuation parameter (CAP), (1)H-MR-spectroscopy, the ELF score, liver biopsy, as well as risk alleles in rs738409 in PNPLA3, was studied in 101 NAFLD patients as compared to 15 healthy controls...
November 2017: Endocrine
https://www.readbyqxmd.com/read/28902428/nuclear-lamina-genetic-variants-including-a-truncated-lap2-in-twins-and-siblings-with-nonalcoholic-fatty-liver-disease
#18
Graham F Brady, Raymond Kwan, Peter J Ulintz, Phirum Nguyen, Shirin Bassirian, Venkatesha Basrur, Alexey I Nesvizhskii, Rohit Loomba, M Bishr Omary
Nonalcoholic fatty liver disease (NAFLD) is becoming the major chronic liver disease in many countries. Its pathogenesis is multifactorial but twin and familial studies indicate significant heritability, which is not fully explained by currently-known genetic susceptibility loci. Notably, mutations in genes encoding nuclear lamina proteins, including lamins, cause lipodystrophy syndromes that include NAFLD. We hypothesized that variants in lamina-associated proteins predispose to NAFLD and used a candidate gene-sequencing approach to test for variants in 10 nuclear lamina-related genes in a cohort of 37 twin and sibling pairs: 21 individuals with, and 53 without, NAFLD...
September 13, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28827398/network-analyses-identify-liver-specific-targets-for-treating-liver-diseases
#19
Sunjae Lee, Cheng Zhang, Zhengtao Liu, Martina Klevstig, Bani Mukhopadhyay, Mattias Bergentall, Resat Cinar, Marcus Ståhlman, Natasha Sikanic, Joshua K Park, Sumit Deshmukh, Azadeh M Harzandi, Tim Kuijpers, Morten Grøtli, Simon J Elsässer, Brian D Piening, Michael Snyder, Ulf Smith, Jens Nielsen, Fredrik Bäckhed, George Kunos, Mathias Uhlen, Jan Boren, Adil Mardinoglu
We performed integrative network analyses to identify targets that can be used for effectively treating liver diseases with minimal side effects. We first generated co-expression networks (CNs) for 46 human tissues and liver cancer to explore the functional relationships between genes and examined the overlap between functional and physical interactions. Since increased de novo lipogenesis is a characteristic of nonalcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC), we investigated the liver-specific genes co-expressed with fatty acid synthase (FASN)...
August 21, 2017: Molecular Systems Biology
https://www.readbyqxmd.com/read/28805745/insulin-resistance-and-nafld-a-dangerous-liaison-beyond-the-genetics
#20
REVIEW
Melania Manco
Over the last decade, the understanding of the association between insulin resistance (IR) and non-alcoholic fatty liver disease (NAFLD) has dramatically evolved. There is clear understanding that carriers of some common genetic variants, i.e., the patatin-like phospholipase domain-containing 3 (PNPLA3) or the transmembrane 6 superfamily member 2 (TM6SF2) are at risk of developing severe forms of NAFLD even in the presence of reduced or absent IR. In contrast, there are obese patients with "metabolic" (non-genetically driven) NAFLD who present severe IR...
August 14, 2017: Children
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