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Clinical omics

Hai-Jing Yu, Hua Deng, Jian Ma, Shu-Jun Huang, Jian-Min Yang, Yan-Fen Huang, Xiao-Ping Mu, Liang Zhang, Qi Wang
BACKGROUND: Granulomatous mastitis (GM) is a chronic inflammatory breast lesion and its etiology remains incompletely defined. Although mounting evidence suggests the involvement of Corynebacterium in GM, there has been no systematic study of GM bacteriology using -omics technology. METHODS: The bacterial diversity and relative abundances in breast abscesses from 19 women with GM were investigated using 16S rDNA metagenomic sequencing and Sanger sequencing. A quantitative PCR (qPCR) assay was also developed to identify C...
October 21, 2016: International Journal of Infectious Diseases: IJID
Rachel S Kelly, Amber Dahlin, Michael J McGeachie, Weiliang Qiu, Joanne Sordillo, Emily S Wan, Ann Chen Wu, Jessica Lasky-Su
Asthma is a complex disease well suited to metabolomic profiling, both for the development of novel biomarkers and for the improved understanding of pathophysiology. In this review, we summarize the 21 existing metabolomic studies of asthma in humans, all of which reported significant findings and concluded that individual metabolites and metabolomic profiles measured in exhaled breath condensate, urine, plasma and serum could identify asthmatics and asthma phenotypes with high discriminatory ability. There was considerable consistency across the studies in terms of the reported biomarkers, regardless of biospecimen, profiling technology and population age...
October 21, 2016: Chest
Gabrielle Bertier, Jian Carrot-Zhang, Vassilis Ragoussis, Yann Joly
Precision medicine (PM) can be defined as a predictive, preventive, personalized, and participatory healthcare service delivery model. Recent developments in molecular biology and information technology make PM a reality today through the use of massive amounts of genetic, 'omics', clinical, environmental, and lifestyle data. With cancer being one of the most prominent public health threats in developed countries, both the research community and governments have been investing significant time, money, and efforts in precision cancer medicine (PCM)...
October 24, 2016: Genome Medicine
Diane Lefaudeux, Bertrand De Meulder, Matthew J Loza, Nancy Peffer, Anthony Rowe, Frédéric Baribaud, Aruna T Bansal, Rene Lutter, Ana R Sousa, Julie Corfield, Ioannis Pandis, Per S Bakke, Massimo Caruso, Pascal Chanez, Sven-Erik Dahlén, Louise J Fleming, Stephen J Fowler, Ildiko Horvath, Norbert Krug, Paolo Montuschi, Marek Sanak, Thomas Sandstrom, Dominic E Shaw, Florian Singer, Peter J Sterk, Graham Roberts, Ian M Adcock, Ratko Djukanovic, Charles Auffray, Kian F Chung
BACKGROUND: Asthma is a heterogeneous disease in which there is a differential response to asthma treatments. This heterogeneity needs to be evaluated so that a personalised management approach can be provided. OBJECTIVES: We stratified patients with moderate-to-severe asthma based on clinico-physiological parameters and performed an -omics analysis of sputum. METHODS: Partition-around-medoid clustering was applied to a training set of 266 asthma participants from the European U-BIOPRED adult cohort using 8 pre-specified clinic-physiological variables...
October 20, 2016: Journal of Allergy and Clinical Immunology
Elin T G Kersten, Gerard H Koppelman
PURPOSE OF REVIEW: Although currently available drugs to treat asthma are effective in most patients, a proportion of patients do not respond or experience side-effects; which is partly genetically determined. Pharmacogenetics is the study of how genetic variations influence drug response. In this review, we summarize prior results and recent studies in pharmacogenetics to determine if we can use genetic profiles for personalized treatment of asthma. RECENT FINDINGS: The field of pharmacogenetics has moved from candidate gene studies in single populations toward genome-wide association studies and meta-analysis of multiple studies...
October 18, 2016: Current Opinion in Pulmonary Medicine
Ajit Dash, Robert A Figler, Arun J Sanyal, B R Wamhoff
Drug induced steatohepatitis (DISH), a form of drug induced liver injury (DILI) is characterized by intracellular accumulation of lipids in hepatocytes and subsequent inflammatory events, in some ways similar to the pathology seen with other metabolic, viral and genetic causes of non alcoholic fatty liver disease and steatohepatitis (NAFLD and NASH). Areas covered: This paper provides a comprehensive review of the main underlying mechanisms by which various drugs cause DISH, and outlines existing preclinical tools to predict it and study underlying pathways involved...
October 19, 2016: Expert Opinion on Drug Metabolism & Toxicology
Hans Lehrach
Every human is unique. We differ in our genomes, environment, behavior, disease history, and past and current medical treatment-a complex catalog of differences that often leads to variations in the way each of us responds to a particular therapy. We argue here that true personalization of drug therapies will rely on "virtual patient" models based on a detailed characterization of the individual patient by molecular, imaging, and sensor techniques. The models will be based, wherever possible, on the molecular mechanisms of disease processes and drug action but can also expand to hybrid models including statistics/machine learning/artificial intelligence-based elements trained on available data to address therapeutic areas or therapies for which insufficient information on mechanisms is available...
September 2016: Dialogues in Clinical Neuroscience
Juan David Ospina-Villa, Absalom Zamorano-Carrillo, Carlos A Castañon-Sanchez, Esther Ramirez-Moreno, Laurence A Marchat
Aptamers are short single-stranded RNA or DNA oligonucleotides that are capable of binding various biological targets with high affinity and specificity. Their identification initially relies on a molecular process named SELEX (Systematic Evolution of Ligands by EXponential enrichment) that has been later modified in order to improve aptamer sensitivity, minimize duration and cost of the assay, as well as increase target types. Several biochemical modifications can help to enhance aptamer stability without affecting significantly target interaction...
October 15, 2016: Brazilian Journal of Infectious Diseases
Anna Dominiczak
Human primary or essential hypertension is a complex, polygenic trait with some 50% contribution from genes and environment. Richard Lifton and colleagues provided elegant dissection of several rare Mendelian forms of hypertension, exemplified by the glucocorticoid remediable aldosteronism and Liddle's syndrome. These discoveries illustrate that a single gene mutation can explain the entire pathogenesis of severe, early onset hypertension as well as dictating the best treatment.The dissection of the much more common polygenic hypertension has proven much more difficult...
September 2016: Journal of Hypertension
Clizia Chinello, Vincenzo L'Imperio, Martina Stella, Andrew James Smith, Giorgio Bovo, Angelica Grasso, Marco Grasso, Francesca Raimondo, Marina Pitto, Fabio Pagni, Fulvio Magni
Renal cell carcinoma (RCC) is the most fatal of the common urologic cancers, with approximately 35% of patients dying within 5 years following diagnosis. Therefore, there is a need for non-invasive markers that are capable of detecting and determining the severity of small renal masses at an early stage in order to tailor treatment and follow-up. Proteomic studies have proved to be very useful in the study of tumors. Areas covered: In this review, we will detail the current knowledge obtained by the different proteomic approaches, focusing on MS-based strategies, used to investigate RCC biology in order to identify diagnostic, prognostic and predictive biomarkers on tissue, cultured cells and biological fluids...
October 17, 2016: Expert Review of Proteomics
José E Belizário, Beatriz A Sangiuliano, Marcela Perez-Sosa, Jennifer M Neyra, Dayson F Moreira
With multiple omics strategies being applied to several cancer genomics projects, researchers have the opportunity to develop a rational planning of targeted cancer therapy. The investigation of such numerous and diverse pharmacogenomic datasets is a complex task. It requires biological knowledge and skills on a set of tools to accurately predict signaling network and clinical outcomes. Herein, we describe Web-based in silico approaches user friendly for exploring integrative studies on cancer biology and pharmacogenomics...
2016: Frontiers in Pharmacology
Priyakshi Kalita-de Croft, Fares Al-Ejeh, Amy E McCart Reed, Jodi M Saunus, Sunil R Lakhani
Our understanding of the natural history of breast cancer has evolved alongside technologies to study its genomic, transcriptomic, proteomic, and metabolomics landscapes. These technologies have helped decipher multiple molecular pathways dysregulated in breast cancer. First-generation 'omics analyses considered each of these dimensions individually, but it is becoming increasingly clear that more holistic, integrative approaches are required to fully understand complex biological systems. The 'omics represent an exciting era of discovery in breast cancer research, although important issues need to be addressed to realize the clinical utility of these data through precision cancer care...
November 2016: Advances in Anatomic Pathology
Paul A Insel, Susan G Amara, Terrence F Blaschke, Urs A Meyer
Major advances in scientific discovery and insights can result from the development and use of new techniques, as exemplified by the work of Solomon Snyder, who writes a prefatory article in this volume. The Editors have chosen "New Methods and Novel Therapeutic Approaches in Pharmacology and Toxicology" as the Theme for a number of articles in this volume. These include ones that review the development and use of new experimental tools and approaches (e.g., nanobodies and techniques to explore proteinprotein interactions), new types of therapeutics (e...
October 12, 2016: Annual Review of Pharmacology and Toxicology
Mandar S Joshi, Kelsey A Montgomery, Peter J Giannone, John A Bauer, Mina H Hanna
Preterm birth is associated with increased risks of morbidity and mortality along with increased healthcare costs. Advances in medicine have enhanced survival for preterm infants but the overall incidences of major morbidities have changed very little. Abnormal renal development is an important consequence of premature birth. Acute kidney injury (AKI) in the neonatal period is multifactorial and may increase lifetime risk of chronic kidney disease.Traditional biomarkers in newborns suffer from considerable confounders, limiting their use for early identification of AKI...
October 10, 2016: Pediatric Research
Maria Kaisar, Leon F A van Dullemen, Marie-Laëtitia Thézénas, M Zeeshan Akhtar, Honglei Huang, Sandrine Rendel, Philip D Charles, Roman Fischer, Rutger J Ploeg, Benedikt M Kessler
BACKGROUND: The successful application of-omics technologies in the discovery of novel biomarkers and targets of therapeutic interventions is facilitated by large collections of well curated clinical samples stored in bio banks. Mining the plasma proteome holds promise to improve our understanding of disease mechanisms and may represent a source of biomarkers. However, a major confounding factor for defining disease-specific proteomic signatures in plasma is the variation in handling and processing of clinical samples leading to protein degradation...
2016: Clinical Proteomics
Allison B Chambliss, Daniel W Chan
Disease progression and drug response may vary significantly from patient to patient. Fortunately, the rapid development of high-throughput 'omics' technologies has allowed for the identification of potential biomarkers that may aid in the understanding of the heterogeneities in disease development and treatment outcomes. However, mechanistic gaps remain when the genome or the proteome are investigated independently in response to drug treatment. In this article, we discuss the current status of pharmacogenomics in precision medicine and highlight the needs for concordant analysis at the proteome and metabolome levels via the more recently-evolved fields of pharmacoproteomics, toxicoproteomics, and pharmacometabolomics...
2016: Clinical Proteomics
Steffen Falgreen, Anders Ellern Bilgrau, Rasmus Froberg Brøndum, Lasse Hjort Jakobsen, Jonas Have, Kasper Lindblad Nielsen, Tarec Christoffer El-Galaly, Julie Støve Bødker, Alexander Schmitz, Ken H Young, Hans Erik Johnsen, Karen Dybkær, Martin Bøgsted
BACKGROUND: Dozens of omics based cancer classification systems have been introduced with prognostic, diagnostic, and predictive capabilities. However, they often employ complex algorithms and are only applicable on whole cohorts of patients, making them difficult to apply in a personalized clinical setting. RESULTS: This prompted us to create, an online web application providing an easy interface to one-by-one RMA normalization of microarrays and subsequent risk classifications of diffuse large B-cell lymphoma (DLBCL) into cell-of-origin and chemotherapeutic sensitivity classes...
2016: PloS One
Siyi Wanggou, Chengyuan Feng, Yuanyang Xie, Linrong Ye, Feiyifan Wang, Xuejun Li
Background: Glioblastoma is the most lethal primary brain tumor in adults. Aberrant signal transduction pathways, associated with the progression of glioblastoma, have been identified recently and may offer a potential gene therapy strategy. Methods and Findings: We first used the sample level enrichment analysis to transfer gene expression profile of TCGA dataset into pathway enrichment z-score matrix. Then, we classified glioblastoma into five subtypes (Cluster A to Cluster E) by the consensus clustering and silhouette analysis...
2016: Journal of Cancer
Kevin Maisey, Ruth Montero, Myron Christodoulides
Piscirickettsia salmonis (P. salmonis) is the aetiological bacterium of the contagious disease piscirickettsiosis or salmonid rickettsial septicaemia (SRS) and causes significant economic losses to aquaculture production in Chile. Current strategies to control infection are i) indiscriminate antibiotic use and ii) vaccination with predominantly P. salmonis bacterin vaccines that do not provide acceptable levels of protection against piscirickettsiosis. Areas covered: This review covers the basic biology of P...
October 3, 2016: Expert Review of Vaccines
Spiros C Denaxas, Folkert W Asselbergs, Jason H Moore
Modern cohort studies include self-reported measures on disease, behavior and lifestyle, sensor-based observations from mobile phones and wearables, and rich -omics data. Follow-up is often achieved through electronic health record (EHR) linkages across primary and secondary healthcare providers. Historically however, researchers typically only get to see the tip of the iceberg: coded administrative data relating to healthcare claims which mainly record billable diagnoses and procedures. The rich data generated during the clinical pathway remain submerged and inaccessible...
2016: BioData Mining
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