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            "title": "Early diagnosis of complex diseases by molecular biomarkers, network biomarkers, and dynamical network biomarkers",
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                    "firstName": "Rui",
                    "lastName": "Liu"
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                    "firstName": "Xiangdong",
                    "lastName": "Wang"
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                    "firstName": "Kazuyuki",
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            "publicationTitle": "Medicinal research reviews",
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            "title": "Post-Acute Brain Injury Urinary Signature: A New Resource for Molecular Diagnostics",
            "creators": [
                {
                    "creatorType": "author",
                    "firstName": "Andrew K.",
                    "lastName": "Ottens"
                },
                {
                    "creatorType": "author",
                    "firstName": "Jillian E.",
                    "lastName": "Stafflinger"
                },
                {
                    "creatorType": "author",
                    "firstName": "Hailey E.",
                    "lastName": "Griffin"
                },
                {
                    "creatorType": "author",
                    "firstName": "Richard D.",
                    "lastName": "Kunz"
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                {
                    "creatorType": "author",
                    "firstName": "David X.",
                    "lastName": "Cifu"
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                {
                    "creatorType": "author",
                    "firstName": "Janet P.",
                    "lastName": "Niemeier"
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            "abstractNote": "Heterogeneity within brain injury presents a challenge to the development of informative molecular diagnostics. Recent studies show progress, particularly in cerebrospinal fluid, with biomarker assays targeting one or a few structural proteins. Protein-based assays in peripheral fluids, however, have been more challenging to develop, in part because of restricted and intermittent barrier access. Further, a greater number of molecular variables may be required to inform on patient status given the multi-factorial nature of brain injury. Presented is an alternative approach profiling peripheral fluid for a class of small metabolic by-products rendered by ongoing brain pathobiology. Urine specimens were collected for head trauma subjects upon admission to acute brain injury rehabilitation and non-traumatized matched controls. An innovative data-independent mass spectrometry approach was employed for reproducible molecular quantification across osmolarity-normalized samples. The postacute human traumatic brain injury urinary signature encompassed 2476 discriminant variables reproducibly measured in specimens for subject classification. Multiple subprofiles were then discerned in correlation with injury severity per the Glasgow Comma Scale and behavioral and neurocognitive function per the Patient Competency Rating Scale and Frontal Systems Behavioral Scale. Identified peptide constituents were enriched for outgrowth and guidance, extracellular matrix, and post-synaptic density proteins, which were reflective of ongoing post-acute neuroplastic processes demonstrating pathobiological relevance. Taken together, these findings support further development of diagnostics based on brain injury urinary signatures using either combinatorial quantitative models or pattern-recognition methods. Particularly, these findings espouse assay development to address unmet diagnostic and theragnostic needs in brain injury rehabilitative medicine.",
            "publicationTitle": "Journal of Neurotrauma",
            "publisher": "",
            "place": "",
            "date": "décembre 29, 2013",
            "volume": "31",
            "issue": "8",
            "section": "",
            "partNumber": "",
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            "pages": "782-788",
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            "journalAbbreviation": "Journal of Neurotrauma",
            "DOI": "10.1089/neu.2013.3116",
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            "shortTitle": "Post-Acute Brain Injury Urinary Signature",
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            "title": "Assessment of Endothelial Dysfunction: The Role of Symmetrical Dimethylarginine and Proinflammatory Markers in Chronic Kidney Disease and Renal Transplant Recipients",
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                    "creatorType": "author",
                    "firstName": "Lidija",
                    "lastName": "Memon"
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                    "firstName": "Vesna",
                    "lastName": "Spasojevic-Kalimanovska"
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                    "firstName": "Natasa",
                    "lastName": "Bogavac-Stanojevic"
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                    "firstName": "Jelena",
                    "lastName": "Kotur-Stevuljevic"
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                {
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                    "firstName": "Sanja",
                    "lastName": "Simic-Ogrizovic"
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                {
                    "creatorType": "author",
                    "firstName": "Vojislav",
                    "lastName": "Giga"
                },
                {
                    "creatorType": "author",
                    "firstName": "Violeta",
                    "lastName": "Dopsaj"
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                {
                    "creatorType": "author",
                    "firstName": "Zorana",
                    "lastName": "Jelic-Ivanovic"
                },
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                    "creatorType": "author",
                    "firstName": "Slavica",
                    "lastName": "Spasic"
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            "abstractNote": "Objectives. The study was designed to evaluate associations between symmetric dimethylarginine (SDMA), inflammation, and superoxide anion () with endothelial function and to determine their potential for screening of endothelial dysfunction in patients with chronic kidney disease (CKD) and renal transplant (RT) recipients. Materials and Methods. We included 64 CKD and 52 RT patients. Patients were stratified according to brachial artery flow-mediated dilation (FMD). Results. Logistic regression analysis showed that high SDMA and high sensitive C-reactive protein (hs-CRP) were associated with impaired FMD in CKD and RT patients, after adjustment for glomerular filtration rate. The ability of inflammation, SDMA, and to detect impaired FMD was investigated by receiving operative characteristic analysis. Hs-CRP (area under the curves (AUC) = 0.754, ), IL-6 (AUC = 0.699, ), and SDMA (AUC = 0.689, ) had the highest ability to detect impaired FMD. SDMA in combination with inflammatory parameters and/or had better screening performance than SDMA alone. Conclusions. Our results indicate a strong predictable association between hs-CRP, SDMA, and endothelial dysfunction in CKD patients and RT recipients. The individual marker that showed the strongest discriminative ability for endothelial dysfunction is hs-CRP, but its usefulness as a discriminatory marker for efficient diagnosis of endothelial dysfunction should be examined in prospective studies.",
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            "date": "2013/08/26",
            "volume": "35",
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            "title": "Assessing the Performance of 3D Pharmacophore Models in Virtual Screening: How Good are They?",
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                    "firstName": "Rodolpho C.",
                    "lastName": "Braga"
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                    "creatorType": "author",
                    "firstName": "Carolina H.",
                    "lastName": "Andrade"
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            ],
            "abstractNote": "Pharmacophore approaches have evolved to be one of the most successful tools in drug discovery, especially since the past two decades. 3D pharmacophore methods are now commonly used as part of more complex workflows in drug discovery campaigns, and have been successfully and extensively applied in virtual screening (VS) approaches. This review provides a perspective of how to assess the performance of 3D pharmacophore models to be used in VS. Since 3D VS protocols are in general assessed by their ability to discriminate between active and inactive compounds, we summarize the impact of the composition and preparation of modeling and external sets on the outcome of evaluations. Moreover, we highlight the significance of both classic enrichment parameters and advanced descriptors for the performance of 3D pharmacophore-based virtual screening methods.",
            "publicationTitle": "Current Topics in Medicinal Chemistry",
            "publisher": "",
            "place": "",
            "date": "2013",
            "volume": "13",
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            "creatorSummary": "Yu et al.",
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            "itemType": "journalArticle",
            "title": "Development of candidate biomarkers for pancreatic ductal adenocarcinoma using multiple reaction monitoring",
            "creators": [
                {
                    "creatorType": "author",
                    "firstName": "Jiyoung",
                    "lastName": "Yu"
                },
                {
                    "creatorType": "author",
                    "firstName": "Kyunggon",
                    "lastName": "Kim"
                },
                {
                    "creatorType": "author",
                    "firstName": "MeeJoo",
                    "lastName": "Kang"
                },
                {
                    "creatorType": "author",
                    "firstName": "Hyunsoo",
                    "lastName": "Kim"
                },
                {
                    "creatorType": "author",
                    "firstName": "Sun Whe",
                    "lastName": "Kim"
                },
                {
                    "creatorType": "author",
                    "firstName": "Jin-Young",
                    "lastName": "Jang"
                },
                {
                    "creatorType": "author",
                    "firstName": "Youngsoo",
                    "lastName": "Kim"
                }
            ],
            "abstractNote": "Pancreatic ductal adenocarcinoma (PDAC) is the fourth most frequent cause of cancer mortality in the United States. Because CA 19-9 increases not only in PDAC, but also in benign conditions, there is urgent need for an additional PDAC biomarker. Isotope tags for relative and absolute quantification (iTRAQ) were performed using 6 pairs of PDAC and normal tissues from the same patients, to obtain preliminary PDAC-specific proteins; and verification was performed by multiple reactions monitoring (MRM), using 30 PDAC and 20 normal serum, targeting high-abundant serum proteins without any pre-preparation. As a result, 17 candidate proteins from tissue iTRAQ were verified as potential markers (AUC values > 0.7). Multivariate analysis (MA) demonstrated that a 6-marker panel, consisting of alpha-1 antitrypsin, haptoglobin beta chain, hemopexin, transferrin, zinc alpha-2 glycoprotein, and apolipoprotein A4 from the MRM result, had comparable discriminatory power versus CA 19-9. Our study demonstrated that a combination of iTRAQ on PDAC tissue and verification MRM-MA on individual serum was an efficient method for the development of PDAC multimarkers.",
            "publicationTitle": "Biotechnology and Bioprocess Engineering",
            "publisher": "",
            "place": "",
            "date": "2013/09/01",
            "volume": "18",
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            "pages": "1038-1047",
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            "journalAbbreviation": "Biotechnol Bioproc E",
            "DOI": "10.1007/s12257-013-0421-2",
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            "url": "http://link.springer.com/article/10.1007/s12257-013-0421-2",
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                {
                    "tag": "cancer biomarker",
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            "creatorSummary": "Leichtle et al.",
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            "title": "Pancreatic carcinoma, pancreatitis, and healthy controls: metabolite models in a three-class diagnostic dilemma",
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                    "firstName": "Alexander Benedikt",
                    "lastName": "Leichtle"
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                {
                    "creatorType": "author",
                    "firstName": "Uta",
                    "lastName": "Ceglarek"
                },
                {
                    "creatorType": "author",
                    "firstName": "Peter",
                    "lastName": "Weinert"
                },
                {
                    "creatorType": "author",
                    "firstName": "Christos T.",
                    "lastName": "Nakas"
                },
                {
                    "creatorType": "author",
                    "firstName": "Jean-Marc",
                    "lastName": "Nuoffer"
                },
                {
                    "creatorType": "author",
                    "firstName": "Julia",
                    "lastName": "Kase"
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                {
                    "creatorType": "author",
                    "firstName": "Tim",
                    "lastName": "Conrad"
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                    "creatorType": "author",
                    "firstName": "Helmut",
                    "lastName": "Witzigmann"
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                    "firstName": "Joachim",
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                    "firstName": "Georg Martin",
                    "lastName": "Fiedler"
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            ],
            "abstractNote": "Metabolomics as one of the most rapidly growing technologies in the “-omics” field denotes the comprehensive analysis of low molecular-weight compounds and their pathways. Cancer-specific alterations of the metabolome can be detected by high-throughput mass-spectrometric metabolite profiling and serve as a considerable source of new markers for the early differentiation of malignant diseases as well as their distinction from benign states. However, a comprehensive framework for the statistical evaluation of marker panels in a multi-class setting has not yet been established. We collected serum samples of 40 pancreatic carcinoma patients, 40 controls, and 23 pancreatitis patients according to standard protocols and generated amino acid profiles by routine mass-spectrometry. In an intrinsic three-class bioinformatic approach we compared these profiles, evaluated their selectivity and computed multi-marker panels combined with the conventional tumor marker CA 19-9. Additionally, we tested for non-inferiority and superiority to determine the diagnostic surplus value of our multi-metabolite marker panels. Compared to CA 19-9 alone, the combined amino acid-based metabolite panel had a superior selectivity for the discrimination of healthy controls, pancreatitis, and pancreatic carcinoma patients [volume under ROC surface(VUS)=0.891(95% CI 0.794−0.968)]. [ {\\text{volume under ROC surface}}\\;\\left( {\\text{VUS}} \\right) = 0. 8 9 1 { }\\left( { 9 5\\,\\% {\\text{ CI }}0. 7 9 4- 0. 9 6 8} \\right)]. We combined highly standardized samples, a three-class study design, a high-throughput mass-spectrometric technique, and a comprehensive bioinformatic framework to identify metabolite panels selective for all three groups in a single approach. Our results suggest that metabolomic profiling necessitates appropriate evaluation strategies and—despite all its current limitations—can deliver marker panels with high selectivity even in multi-class settings.",
            "publicationTitle": "Metabolomics",
            "publisher": "",
            "place": "",
            "date": "2013/06/01",
            "volume": "9",
            "issue": "3",
            "section": "",
            "partNumber": "",
            "partTitle": "",
            "pages": "677-687",
            "series": "",
            "seriesTitle": "",
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            "journalAbbreviation": "Metabolomics",
            "DOI": "10.1007/s11306-012-0476-7",
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            "archiveLocation": "",
            "shortTitle": "Pancreatic carcinoma, pancreatitis, and healthy controls",
            "language": "en",
            "libraryCatalog": "link.springer.com",
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            "tags": [
                {
                    "tag": "Amino Acids",
                    "type": 1
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                {
                    "tag": "Biochemistry, general",
                    "type": 1
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                {
                    "tag": "Biomedicine general",
                    "type": 1
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                    "tag": "Cell Biology",
                    "type": 1
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                    "tag": "Marker panels",
                    "type": 1
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                {
                    "tag": "Modeling",
                    "type": 1
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                {
                    "tag": "Molecular Medicine",
                    "type": 1
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                {
                    "tag": "Pancreatic cancer",
                    "type": 1
                },
                {
                    "tag": "developmental biology",
                    "type": 1
                },
                {
                    "tag": "metabolomics",
                    "type": 1
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            ],
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            "title": "Computational Biomarker Pipeline from Discovery to Clinical Implementation: Plasma Proteomic Biomarkers for Cardiac Transplantation",
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                    "creatorType": "author",
                    "firstName": "Gabriela V.",
                    "lastName": "Cohen Freue"
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                {
                    "creatorType": "author",
                    "firstName": "Anna",
                    "lastName": "Meredith"
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                {
                    "creatorType": "author",
                    "firstName": "Derek",
                    "lastName": "Smith"
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                {
                    "creatorType": "author",
                    "firstName": "Axel",
                    "lastName": "Bergman"
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                {
                    "creatorType": "author",
                    "firstName": "Mayu",
                    "lastName": "Sasaki"
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                {
                    "creatorType": "author",
                    "firstName": "Karen K. Y.",
                    "lastName": "Lam"
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                {
                    "creatorType": "author",
                    "firstName": "Zsuzsanna",
                    "lastName": "Hollander"
                },
                {
                    "creatorType": "author",
                    "firstName": "Nina",
                    "lastName": "Opushneva"
                },
                {
                    "creatorType": "author",
                    "firstName": "Mandeep",
                    "lastName": "Takhar"
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                {
                    "creatorType": "author",
                    "firstName": "David",
                    "lastName": "Lin"
                },
                {
                    "creatorType": "author",
                    "firstName": "Janet",
                    "lastName": "Wilson-McManus"
                },
                {
                    "creatorType": "author",
                    "firstName": "Robert",
                    "lastName": "Balshaw"
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                {
                    "creatorType": "author",
                    "firstName": "Paul A.",
                    "lastName": "Keown"
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                {
                    "creatorType": "author",
                    "firstName": "Christoph H.",
                    "lastName": "Borchers"
                },
                {
                    "creatorType": "author",
                    "firstName": "Bruce",
                    "lastName": "McManus"
                },
                {
                    "creatorType": "author",
                    "firstName": "Raymond T.",
                    "lastName": "Ng"
                },
                {
                    "creatorType": "author",
                    "firstName": "W. Robert",
                    "lastName": "McMaster"
                },
                {
                    "creatorType": "author",
                    "name": "for the Biomarkers in Transplantation and the NCE CECR Prevention of Organ Failure Centre of Excellence Teams"
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            ],
            "abstractNote": "Author SummaryNovel proteomic technology has led to the generation of vast amounts of biological data and the identification of numerous potential biomarkers. However, computational approaches to translate this information into knowledge capable of impacting clinical care have been lagging. We propose a computational proteomic pipeline for biomarker studies that is founded on the combination of advanced statistical methodologies. We demonstrate our approach through the analysis of data obtained from heart transplant patients. Heart transplantation is the gold standard treatment for patients with end-stage heart failure, but is complicated by episodes of immune rejection that can adversely impact patient outcomes. Current rejection monitoring approaches are highly invasive, requiring a biopsy of the heart. This work aims to reduce the need for biopsies, and demonstrate the power and utility of computational approaches in proteomic biomarker discovery. Our work utilizes novel high-throughput proteomic technology combined with advanced statistical techniques to identify blood markers that guide the decision as to whether a biopsy is warranted, reduce the number of unnecessary biopsies, and ultimately diagnose the presence of rejection in heart transplant patients. Additionally, the proposed computational methodologies can be applied to a range of proteomic biomarker studies of various diseases and conditions.",
            "publicationTitle": "PLoS Comput Biol",
            "publisher": "",
            "place": "",
            "date": "avril 4, 2013",
            "volume": "9",
            "issue": "4",
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            "pages": "e1002963",
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            "PMID": "",
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            "shortTitle": "Computational Biomarker Pipeline from Discovery to Clinical Implementation",
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            "version": 69,
            "itemType": "journalArticle",
            "title": "PanelomiX: A threshold-based algorithm to create panels of biomarkers",
            "creators": [
                {
                    "creatorType": "author",
                    "firstName": "Xavier",
                    "lastName": "Robin"
                },
                {
                    "creatorType": "author",
                    "firstName": "Natacha",
                    "lastName": "Turck"
                },
                {
                    "creatorType": "author",
                    "firstName": "Alexandre",
                    "lastName": "Hainard"
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                {
                    "creatorType": "author",
                    "firstName": "Natalia",
                    "lastName": "Tiberti"
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                {
                    "creatorType": "author",
                    "firstName": "Frédérique",
                    "lastName": "Lisacek"
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                {
                    "creatorType": "author",
                    "firstName": "Jean-Charles",
                    "lastName": "Sanchez"
                },
                {
                    "creatorType": "author",
                    "firstName": "Markus",
                    "lastName": "Müller"
                }
            ],
            "abstractNote": "Abstract \nIn order to increase their predictive power, medical biomarkers can be combined into panels. However, the lack of ready-to-use tools generating interpretable results and implementing rigorous validation standards hampers the more widespread application of panels and their translation into clinical practice. \n \nThe computational toolbox we present here – PanelomiX – uses the iterative combination of biomarkers and thresholds (ICBT) method. This method combines biomarkers and clinical scores by selecting thresholds that provide optimal classification performance. To speed up the calculation for a large number of biomarkers, PanelomiX selects a subset of thresholds and parameters based on the random forest method. The panels’ robustness and performance are analysed by cross-validation (CV) and receiver operating characteristic (ROC) analysis. \n \nUsing 8 biomarkers, we compared this method against classic combination procedures in the determination of outcome for 113 patients with an aneurysmal subarachnoid haemorrhage. The panel classified the patients better than the best single biomarker (p &lt; 0.005) and compared favourably with other off-the-shelf classification methods. \n \nIn conclusion, the PanelomiX toolbox combines biomarkers and evaluates the performance of panels to classify patients better than single markers or other classifiers. The ICBT algorithm proved to be an efficient classifier, the results of which can easily be interpreted.",
            "publicationTitle": "Translational Proteomics",
            "publisher": "",
            "place": "",
            "date": "2013",
            "volume": "1",
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            "pages": "57-64",
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            "ISSN": "2212-9634",
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                    "tag": "Aneurysmal subarachnoid haemorrhage",
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                    "tag": "Clinical study",
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                    "tag": "Combination of biomarkers",
                    "type": 1
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            "dateAdded": "2013-06-08T16:17:55Z",
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            "title": "New biomarkers for stage determination in Trypanosoma brucei rhodesiense sleeping sickness patients",
            "creators": [
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                    "creatorType": "author",
                    "firstName": "Natalia",
                    "lastName": "Tiberti"
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                    "lastName": "Matovu"
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                    "lastName": "Lejon"
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                    "lastName": "Robin"
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                    "lastName": "Turck"
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                    "firstName": "Dieudonné Mumba",
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                    "firstName": "Sanjeev",
                    "lastName": "Krishna"
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                    "firstName": "Sylvie",
                    "lastName": "Bisser"
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                    "firstName": "Bertrand",
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                    "firstName": "Krister",
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                    "firstName": "Joseph Mathu",
                    "lastName": "Ndung'u"
                },
                {
                    "creatorType": "author",
                    "firstName": "Jean-Charles",
                    "lastName": "Sanchez"
                }
            ],
            "abstractNote": "Accurate stage determination is crucial in the choice of treatment for patients suffering from sleeping sickness, also known as human African trypanosomiasis (HAT). Current staging methods, based on the counting of white blood cells (WBC) and the detection of parasites in the cerebrospinal fluid (CSF) have limited accuracy. We hypothesized that immune mediators reliable for staging T. b. gambiense HAT could also be used to stratify T. b. rhodesiense patients, the less common form of HAT.",
            "publicationTitle": "Clinical and Translational Medicine",
            "publisher": "",
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            "DOI": "10.1186/2001-1326-2-1",
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                    "tag": "Biomarkers",
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                {
                    "tag": "Cerebrospinal fluid",
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                    "tag": "Sleeping sickness",
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                    "firstName": "Ryan C.",
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            "abstractNote": "Herein, we describe the utility of chaperone probes and a bead-based signal enhancement strategy for the analysis of full length mRNA transcripts using arrays of silicon photonic microring resonators. Changes in the local refractive index near microring sensors associated with biomolecular binding events are transduced as a shift in the resonant wavelength supported by the cavity, enabling the sensitive analysis of numerous analytes of interest. We employ the sensing platform for both the direct and bead-enhanced detection of three different mRNA transcripts, achieving a dynamic range spanning over 4 orders of magnitude and demonstrating expression profiling capabilities in total RNA extracts from the HL-60 cell line. Small, dual-use DNA chaperone molecules were developed and found to both enhance the binding kinetics of mRNA transcripts by disrupting complex secondary structure and serve as sequence-specific linkers for subsequent bead amplification. Importantly, this approach does not require amplification of the mRNA transcript, thereby allowing for simplified analyses that do not require expensive enzymatic reagents or temperature ramping capabilities associated with RT-PCR-based methods.",
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                    "firstName": "A.",
                    "lastName": "Fassbender"
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                    "firstName": "D.",
                    "lastName": "Börnigen"
                },
                {
                    "creatorType": "author",
                    "firstName": "C. M.",
                    "lastName": "Kyama"
                },
                {
                    "creatorType": "author",
                    "firstName": "A.",
                    "lastName": "Bokor"
                },
                {
                    "creatorType": "author",
                    "firstName": "A.",
                    "lastName": "Vodolazkaia"
                },
                {
                    "creatorType": "author",
                    "firstName": "K.",
                    "lastName": "Peeraer"
                },
                {
                    "creatorType": "author",
                    "firstName": "C.",
                    "lastName": "Tomassetti"
                },
                {
                    "creatorType": "author",
                    "firstName": "C.",
                    "lastName": "Meuleman"
                },
                {
                    "creatorType": "author",
                    "firstName": "O.",
                    "lastName": "Gevaert"
                },
                {
                    "creatorType": "author",
                    "firstName": "R. Van de",
                    "lastName": "Plas"
                },
                {
                    "creatorType": "author",
                    "firstName": "F.",
                    "lastName": "Ojeda"
                },
                {
                    "creatorType": "author",
                    "firstName": "B. De",
                    "lastName": "Moor"
                },
                {
                    "creatorType": "author",
                    "firstName": "Y.",
                    "lastName": "Moreau"
                },
                {
                    "creatorType": "author",
                    "firstName": "E.",
                    "lastName": "Waelkens"
                },
                {
                    "creatorType": "author",
                    "firstName": "T. M.",
                    "lastName": "D'Hooghe"
                }
            ],
            "abstractNote": "BACKGROUND An early semi-invasive diagnosis of endometriosis has the potential to allow early treatment and minimize disease progression but no such test is available at present. Our aim was to perform a combined mRNA microarray and proteomic analysis on the same eutopic endometrium sample obtained from patients with and without endometriosis.\nMETHODS mRNA and protein fractions were extracted from 49 endometrial biopsies obtained from women with laparoscopically proven presence (n= 31) or absence (n= 18) of endometriosis during the early luteal (n= 27) or menstrual phase (n= 22) and analyzed using microarray and proteomic surface enhanced laser desorption ionization-time of flight mass spectrometry, respectively. Proteomic data were analyzed using a least squares-support vector machines (LS-SVM) model built on 70% (training set) and 30% of the samples (test set).\nRESULTS mRNA analysis of eutopic endometrium did not show any differentially expressed genes in women with endometriosis when compared with controls, regardless of endometriosis stage or cycle phase. mRNA was differentially expressed (P< 0.05) in women with (925 genes) and without endometriosis (1087 genes) during the menstrual phase when compared with the early luteal phase. Proteomic analysis based on five peptide peaks [2072 mass/charge (m/z); 2973 m/z; 3623 m/z; 3680 m/z and 21133 m/z] using an LS-SVM model applied on the luteal phase endometrium training set allowed the diagnosis of endometriosis (sensitivity, 91; 95% confidence interval (CI): 74–98; specificity, 80; 95% CI: 66–97 and positive predictive value, 87.9%; negative predictive value, 84.8%) in the test set.\nCONCLUSION mRNA expression of eutopic endometrium was comparable in women with and without endometriosis but different in menstrual endometrium when compared with luteal endometrium in women with endometriosis. Proteomic analysis of luteal phase endometrium allowed the diagnosis of endometriosis with high sensitivity and specificity in training and test sets. A potential limitation of our study is the fact that our control group included women with a normal pelvis as well as women with concurrent pelvic disease (e.g. fibroids, benign ovarian cysts, hydrosalpinges), which may have contributed to the comparable mRNA expression profile in the eutopic endometrium of women with endometriosis and controls.",
            "publicationTitle": "Human Reproduction",
            "publisher": "",
            "place": "",
            "date": "07/01/2012",
            "volume": "27",
            "issue": "7",
            "section": "",
            "partNumber": "",
            "partTitle": "",
            "pages": "2020-2029",
            "series": "",
            "seriesTitle": "",
            "seriesText": "",
            "journalAbbreviation": "Hum. Reprod.",
            "DOI": "10.1093/humrep/des127",
            "citationKey": "",
            "url": "http://humrep.oxfordjournals.org/content/27/7/2020",
            "accessDate": "2012-07-23T07:53:41Z",
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            "ISSN": "0268-1161, 1460-2350",
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            "shortTitle": "",
            "language": "en",
            "libraryCatalog": "humrep.oxfordjournals.org",
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            "tags": [
                {
                    "tag": "Biomarker",
                    "type": 1
                },
                {
                    "tag": "Microarray",
                    "type": 1
                },
                {
                    "tag": "endometriosis",
                    "type": 1
                },
                {
                    "tag": "eutopic endometrium",
                    "type": 1
                },
                {
                    "tag": "surface enhanced laser desorption ionization-time of flight mass spectrometry",
                    "type": 1
                }
            ],
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            "relations": {},
            "dateAdded": "2012-07-23T07:53:50Z",
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            "version": 1,
            "itemType": "journalArticle",
            "title": "Evaluation of a panel of 28 biomarkers for the non-invasive diagnosis of endometriosis",
            "creators": [
                {
                    "creatorType": "author",
                    "firstName": "A.",
                    "lastName": "Vodolazkaia"
                },
                {
                    "creatorType": "author",
                    "firstName": "Y.",
                    "lastName": "El-Aalamat"
                },
                {
                    "creatorType": "author",
                    "firstName": "D.",
                    "lastName": "Popovic"
                },
                {
                    "creatorType": "author",
                    "firstName": "A.",
                    "lastName": "Mihalyi"
                },
                {
                    "creatorType": "author",
                    "firstName": "X.",
                    "lastName": "Bossuyt"
                },
                {
                    "creatorType": "author",
                    "firstName": "C. M.",
                    "lastName": "Kyama"
                },
                {
                    "creatorType": "author",
                    "firstName": "A.",
                    "lastName": "Fassbender"
                },
                {
                    "creatorType": "author",
                    "firstName": "A.",
                    "lastName": "Bokor"
                },
                {
                    "creatorType": "author",
                    "firstName": "D.",
                    "lastName": "Schols"
                },
                {
                    "creatorType": "author",
                    "firstName": "D.",
                    "lastName": "Huskens"
                },
                {
                    "creatorType": "author",
                    "firstName": "C.",
                    "lastName": "Meuleman"
                },
                {
                    "creatorType": "author",
                    "firstName": "K.",
                    "lastName": "Peeraer"
                },
                {
                    "creatorType": "author",
                    "firstName": "C.",
                    "lastName": "Tomassetti"
                },
                {
                    "creatorType": "author",
                    "firstName": "O.",
                    "lastName": "Gevaert"
                },
                {
                    "creatorType": "author",
                    "firstName": "E.",
                    "lastName": "Waelkens"
                },
                {
                    "creatorType": "author",
                    "firstName": "A.",
                    "lastName": "Kasran"
                },
                {
                    "creatorType": "author",
                    "firstName": "B. De",
                    "lastName": "Moor"
                },
                {
                    "creatorType": "author",
                    "firstName": "T. M.",
                    "lastName": "D'Hooghe"
                }
            ],
            "abstractNote": "Background At present, the only way to conclusively diagnose endometriosis is laparoscopic inspection, preferably with histological confirmation. This contributes to the delay in the diagnosis of endometriosis which is 6–11 years. So far non-invasive diagnostic approaches such as ultrasound (US), MRI or blood tests do not have sufficient diagnostic power. Our aim was to develop and validate a non-invasive diagnostic test with a high sensitivity (80% or more) for symptomatic endometriosis patients, without US evidence of endometriosis, since this is the group most in need of a non-invasive test.\nMethods A total of 28 inflammatory and non-inflammatory plasma biomarkers were measured in 353 EDTA plasma samples collected at surgery from 121 controls without endometriosis at laparoscopy and from 232 women with endometriosis (minimal–mild n = 148; moderate–severe n = 84), including 175 women without preoperative US evidence of endometriosis. Surgery was done during menstrual (n = 83), follicular (n = 135) and luteal (n = 135) phases of the menstrual cycle. For analysis, the data were randomly divided into an independent training (n = 235) and a test (n = 118) data set. Statistical analysis was done using univariate and multivariate (logistic regression and least squares support vector machines (LS-SVM) approaches in training- and test data set separately to validate our findings.\nResults In the training set, two models of four biomarkers (Model 1: annexin V, VEGF, CA-125 and glycodelin; Model 2: annexin V, VEGF, CA-125 and sICAM-1) analysed in plasma, obtained during the menstrual phase, could predict US-negative endometriosis with a high sensitivity (81–90%) and an acceptable specificity (68–81%). The same two models predicted US-negative endometriosis in the independent validation test set with a high sensitivity (82%) and an acceptable specificity (63–75%).\nConclusions In plasma samples obtained during menstruation, multivariate analysis of four biomarkers (annexin V, VEGF, CA-125 and sICAM-1/or glycodelin) enabled the diagnosis of endometriosis undetectable by US with a sensitivity of 81–90% and a specificity of 63–81% in independent training- and test data set. The next step is to apply these models for preoperative prediction of endometriosis in an independent set of patients with infertility and/or pain without US evidence of endometriosis, scheduled for laparoscopy.",
            "publicationTitle": "Human Reproduction",
            "publisher": "",
            "place": "",
            "date": "09/01/2012",
            "volume": "27",
            "issue": "9",
            "section": "",
            "partNumber": "",
            "partTitle": "",
            "pages": "2698-2711",
            "series": "",
            "seriesTitle": "",
            "seriesText": "",
            "journalAbbreviation": "Hum. Reprod.",
            "DOI": "10.1093/humrep/des234",
            "citationKey": "",
            "url": "http://humrep.oxfordjournals.org/content/27/9/2698",
            "accessDate": "2012-09-20T08:57:57Z",
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            "shortTitle": "",
            "language": "en",
            "libraryCatalog": "humrep.oxfordjournals.org",
            "callNumber": "",
            "rights": "",
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            "tags": [
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                    "tag": "endometriosis",
                    "type": 1
                },
                {
                    "tag": "multiplex immunoassay",
                    "type": 1
                },
                {
                    "tag": "non-invasive diagnosis",
                    "type": 1
                },
                {
                    "tag": "plasma biomarkers",
                    "type": 1
                }
            ],
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            "relations": {},
            "dateAdded": "2012-09-20T08:58:12Z",
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                    "creatorType": "author",
                    "firstName": "Alexander Benedikt",
                    "lastName": "Leichtle"
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                    "firstName": "Jean-Marc",
                    "lastName": "Nuoffer"
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                    "creatorType": "author",
                    "firstName": "Uta",
                    "lastName": "Ceglarek"
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                    "creatorType": "author",
                    "firstName": "Julia",
                    "lastName": "Kase"
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                {
                    "creatorType": "author",
                    "firstName": "Tim",
                    "lastName": "Conrad"
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                    "creatorType": "author",
                    "firstName": "Helmut",
                    "lastName": "Witzigmann"
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                    "creatorType": "author",
                    "firstName": "Joachim",
                    "lastName": "Thiery"
                },
                {
                    "creatorType": "author",
                    "firstName": "Georg Martin",
                    "lastName": "Fiedler"
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            ],
            "abstractNote": "Mass spectrometry-based serum metabolic profiling is a promising tool to analyse complex cancer associated metabolic alterations, which may broaden our pathophysiological understanding of the disease and may function as a source of new cancer-associated biomarkers. Highly standardized serum samples of patients suffering from colon cancer (n = 59) and controls (n = 58) were collected at the University Hospital Leipzig. We based our investigations on amino acid screening profiles using electrospray tandem-mass spectrometry. Metabolic profiles were evaluated using the Analyst 1.4.2 software. General, comparative and equivalence statistics were performed by R 2.12.2. 11 out of 26 serum amino acid concentrations were significantly different between colorectal cancer patients and healthy controls. We found a model including CEA, glycine, and tyrosine as best discriminating and superior to CEA alone with an AUROC of 0.878 (95% CI 0.815–0.941). Our serum metabolic profiling in colon cancer revealed multiple significant disease-associated alterations in the amino acid profile with promising diagnostic power. Further large-scale studies are necessary to elucidate the potential of our model also to discriminate between cancer and potential differential diagnoses. Serum glycine and tyrosine in combination with CEA are superior to CEA for the discrimination between colorectal cancer patients and controls.",
            "publicationTitle": "Metabolomics",
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                    "firstName": "Laura L",
                    "lastName": "Elo"
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                {
                    "creatorType": "author",
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                    "lastName": "Schwikowski"
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            ],
            "abstractNote": "The popularity of proteomics in biomedical research has grown with the development of advanced measurement technologies. This has enabled high-throughput protein expression profiling, modification-specific proteomics, and global protein–protein interaction maps. Although proteomics has great potential in providing deeper understanding of the role of individual proteins and protein networks in disease and in unveiling the underlying disease mechanisms, challenges arise in transforming the large-scale experimental data into biomedical knowledge for clinical practice and drug development. In particular, sophisticated computational tools are required to interpret the high-dimensional proteomic datasets that typically reflect not only biological information, but also technical biases and limitations. This review gives an overview of the role of data mining in biomedical applications of proteomics, with a focus on data from mass spectrometry-based expression profiling studies. © 2011 Wiley Periodicals, Inc.",
            "publicationTitle": "Wiley Interdisciplinary Reviews: Data Mining and Knowledge Discovery",
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            "abstractNote": "Cutaneous malignant melanoma (CMM) is the most serious type of skin cancer because of its tendency to metastasize. The prognosis and therapeutic management of patients are primarily based on clinical criteria (number of cancerous lymph nodes and/or the presence of distant metastases) and histopathological criteria (tumor depth, presence of ulceration and mitotic index). Although these factors are informative in advanced stages of the disease, they are less important in the early stages. In recent years, a number of attempts have been made to identify new serological prognostic biomarkers, especially for early forms of CMM. The recent development of proteomic techniques may offer new perspectives in this field. This article details the considerations of each of the proteomic techniques used today and describes the results of the most recent clinical studies conducted to identify new potential prognostic serum biomarkers for CMM. However, independent and large validation studies are needed before such markers can be used in everyday clinical practice.",
            "publicationTitle": "The International Journal of Biological Markers",
            "publisher": "",
            "place": "",
            "date": "2011 Apr-Jun",
            "volume": "26",
            "issue": "2",
            "section": "",
            "partNumber": "",
            "partTitle": "",
            "pages": "82-87",
            "series": "",
            "seriesTitle": "",
            "seriesText": "",
            "journalAbbreviation": "Int. J. Biol. Markers",
            "DOI": "10.5301/JBM.2011.8344",
            "citationKey": "",
            "url": "http://www.ncbi.nlm.nih.gov/pubmed/21607923",
            "accessDate": "2011-08-22T08:52:46Z",
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            "extra": "PMID: 21607923",
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            "creatorSummary": "Rogers et al.",
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            "version": 1,
            "itemType": "journalArticle",
            "title": "Using bacterial biomarkers to identify early indicators of cystic fibrosis pulmonary exacerbation onset",
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                {
                    "creatorType": "author",
                    "firstName": "Geraint B",
                    "lastName": "Rogers"
                },
                {
                    "creatorType": "author",
                    "firstName": "Lucas R",
                    "lastName": "Hoffman"
                },
                {
                    "creatorType": "author",
                    "firstName": "Matt W",
                    "lastName": "Johnson"
                },
                {
                    "creatorType": "author",
                    "firstName": "Nicole",
                    "lastName": "Mayer-Hamblett"
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                {
                    "creatorType": "author",
                    "firstName": "Jürgen",
                    "lastName": "Schwarze"
                },
                {
                    "creatorType": "author",
                    "firstName": "Mary P",
                    "lastName": "Carroll"
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                {
                    "creatorType": "author",
                    "firstName": "Kenneth D",
                    "lastName": "Bruce"
                }
            ],
            "abstractNote": "Acute periods of pulmonary exacerbation are the single most important cause of morbidity in cystic fibrosis patients, and may be associated with a loss of lung function. Intervening prior to the onset of a substantially increased inflammatory response may limit the associated damage to the airways. While a number of biomarker assays based on inflammatory markers have been developed, providing useful and important measures of disease during these periods, such factors are typically only elevated once the process of exacerbation has been initiated. Identifying biomarkers that can predict the onset of pulmonary exacerbation at an early stage would provide an opportunity to intervene before the establishment of a substantial immune response, with major implications for the advancement of cystic fibrosis care. The precise triggers of pulmonary exacerbation remain to be determined; however, the majority of models relate to the activity of microbes present in the patient’s lower airways of cystic fibrosis. Advances in diagnostic microbiology now allow for the examination of these complex systems at a level likely to identify factors on which biomarker assays can be based. In this article, we discuss key considerations in the design and testing of assays that could predict pulmonary exacerbations.",
            "publicationTitle": "Expert Review of Molecular Diagnostics",
            "publisher": "",
            "place": "",
            "date": "March 2011",
            "volume": "11",
            "issue": "2",
            "section": "",
            "partNumber": "",
            "partTitle": "",
            "pages": "197-206",
            "series": "",
            "seriesTitle": "",
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            "DOI": "10.1586/erm.10.117",
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    {
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            "creatorSummary": "Makawita et al.",
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            "title": "Integrated Proteomic Profiling of Cell Line Conditioned Media and Pancreatic Juice for the Identification of Pancreatic Cancer Biomarkers",
            "creators": [
                {
                    "creatorType": "author",
                    "firstName": "Shalini",
                    "lastName": "Makawita"
                },
                {
                    "creatorType": "author",
                    "firstName": "Chris",
                    "lastName": "Smith"
                },
                {
                    "creatorType": "author",
                    "firstName": "Ihor",
                    "lastName": "Batruch"
                },
                {
                    "creatorType": "author",
                    "firstName": "Yingye",
                    "lastName": "Zheng"
                },
                {
                    "creatorType": "author",
                    "firstName": "Felix",
                    "lastName": "Rückert"
                },
                {
                    "creatorType": "author",
                    "firstName": "Robert",
                    "lastName": "Grützmann"
                },
                {
                    "creatorType": "author",
                    "firstName": "Christian",
                    "lastName": "Pilarsky"
                },
                {
                    "creatorType": "author",
                    "firstName": "Steven",
                    "lastName": "Gallinger"
                },
                {
                    "creatorType": "author",
                    "firstName": "Eleftherios P.",
                    "lastName": "Diamandis"
                }
            ],
            "abstractNote": "Pancreatic cancer is one of the leading causes of cancer-related deaths, for which serological biomarkers are urgently needed. Most discovery-phase studies focus on the use of one biological source for analysis. The present study details the combined mining of pancreatic cancer-related cell line conditioned media and pancreatic juice for identification of putative diagnostic leads. Using strong cation exchange chromatography, followed by LC-MS/MS on an LTQ-Orbitrap mass spectrometer, we extensively characterized the proteomes of conditioned media from six pancreatic cancer cell lines (BxPc3, MIA-PaCa2, PANC1, CAPAN1, CFPAC1, and SU.86.86), the normal human pancreatic ductal epithelial cell line HPDE, and two pools of six pancreatic juice samples from ductal adenocarcinoma patients. All samples were analyzed in triplicate. Between 1261 and 2171 proteins were identified with two or more peptides in each of the cell lines, and an average of 521 proteins were identified in the pancreatic juice pools. In total, 3479 nonredundant proteins were identified with high confidence, of which ∼40% were extracellular or cell membrane-bound based on Genome Ontology classifications. Three strategies were employed for identification of candidate biomarkers: (1) examination of differential protein expression between the cancer and normal cell lines using label-free protein quantification, (2) integrative analysis, focusing on the overlap of proteins among the multiple biological fluids, and (3) tissue specificity analysis through mining of publically available databases. Preliminary verification of anterior gradient homolog 2, syncollin, olfactomedin-4, polymeric immunoglobulin receptor, and collagen alpha-1(VI) chain in plasma samples from pancreatic cancer patients and healthy controls using ELISA, showed a significant increase (p < 0.01) of these proteins in plasma from pancreatic cancer patients. The combination of these five proteins showed an improved area under the receiver operating characteristic curve to CA19.9 alone. Further validation of these proteins is warranted, as is the investigation of the remaining group of candidates.",
            "publicationTitle": "Molecular & Cellular Proteomics",
            "publisher": "",
            "place": "",
            "date": "octobre 01 , 2011",
            "volume": "10",
            "issue": "10",
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            "DOI": "10.1074/mcp.M111.008599",
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    },
    {
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            "title": "Multimarker Panels in Sepsis",
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                    "firstName": "Brian",
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                {
                    "creatorType": "author",
                    "firstName": "Richard",
                    "lastName": "Read"
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                    "creatorType": "author",
                    "firstName": "Mitchell M.",
                    "lastName": "Levy"
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            "abstractNote": "",
            "publicationTitle": "Critical Care Clinics",
            "publisher": "",
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            "date": "avril 2011",
            "volume": "27",
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            "pages": "391-405",
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            "DOI": "10.1016/j.ccc.2010.12.011",
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            "url": "http://www.sciencedirect.com/science/article/B7RMB-52FVJJ4-F/2/c0388c2132a3e73534d668c298b3f0fa",
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    {
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        "version": 66,
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            "creatorSummary": "Robin et al.",
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            "itemType": "journalArticle",
            "title": "pROC: an open-source package for R and S+ to analyze and compare ROC curves.",
            "creators": [
                {
                    "creatorType": "author",
                    "firstName": "Xavier",
                    "lastName": "Robin"
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                {
                    "creatorType": "author",
                    "firstName": "Natacha",
                    "lastName": "Turck"
                },
                {
                    "creatorType": "author",
                    "firstName": "Alexandre",
                    "lastName": "Hainard"
                },
                {
                    "creatorType": "author",
                    "firstName": "Natalia",
                    "lastName": "Tiberti"
                },
                {
                    "creatorType": "author",
                    "firstName": "Frédérique",
                    "lastName": "Lisacek"
                },
                {
                    "creatorType": "author",
                    "firstName": "Jean-Charles",
                    "lastName": "Sanchez"
                },
                {
                    "creatorType": "author",
                    "firstName": "Markus",
                    "lastName": "Müller"
                }
            ],
            "abstractNote": "BACKGROUND:Receiver operating characteristic (ROC) curves are useful tools to evaluate classifiers in biomedical and bioinformatics applications. However, conclusions are often reached through inconsistent use or insufficient statistical analysis. To support researchers in their ROC curves analysis we developed pROC, a package for R and S+ that contains a set of tools displaying, analyzing, smoothing and comparing ROC curves in a user-friendly, object-oriented and flexible interface.RESULTS:With data previously imported into the R or S+ environment, the pROC package builds ROC curves and includes functions for computing confidence intervals, statistical tests for comparing total or partial area under the curve or the operating points of different classifiers, and methods for smoothing ROC curves. Intermediary and final results are visualised in user-friendly interfaces. A case study based on published clinical and biomarker data shows how to perform a typical ROC analysis with pROC.CONCLUSIONS:pROC is a package for R and S+ specifically dedicated to ROC analysis. It proposes multiple statistical tests to compare ROC curves, and in particular partial areas under the curve, allowing proper ROC interpretation. pROC is available in two versions: in the R programming language or with a graphical user interface in the S+ statistical software. It is accessible at http://expasy.org/tools/pROC/ under the GNU General Public License. It is also distributed through the CRAN and CSAN public repositories, facilitating its installation.",
            "publicationTitle": "BMC Bioinformatics",
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            "date": "2011-03-17",
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            "pages": "77",
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            "extra": "PMID: 21414208",
            "tags": [
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                    "tag": "ROC Curve"
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                    "tag": "confidence intervals"
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