Next Issue
Previous Issue

Table of Contents

Diagnostics, Volume 3, Issue 1 (March 2013), Pages 1-209

  • Issues are regarded as officially published after their release is announced to the table of contents alert mailing list.
  • You may sign up for e-mail alerts to receive table of contents of newly released issues.
  • PDF is the official format for papers published in both, html and pdf forms. To view the papers in pdf format, click on the "PDF Full-text" link, and use the free Adobe Readerexternal link to open them.
View options order results:
result details:
Displaying articles 1-11
Export citation of selected articles as:

Research

Jump to: Review

Open AccessArticle Soluble Human Epidermal Growth Factor Receptor 2 (sHER2) as a Potential Risk Assessment, Screening, and Diagnostic Biomarker of Lung Adenocarcinoma
Diagnostics 2013, 3(1), 13-32; doi:10.3390/diagnostics3010013
Received: 17 November 2012 / Revised: 17 December 2012 / Accepted: 4 January 2013 / Published: 14 January 2013
PDF Full-text (1028 KB) | HTML Full-text | XML Full-text
Abstract
Lung cancer is the leading cause of cancer-related death in the United States. Here, we evaluated the potential clinical utility of soluble human epidermal growth factor receptor 2 (sHER2) for the risk assessment, screening, and diagnosis of non-small cell lung cancer (NSCLC) [...] Read more.
Lung cancer is the leading cause of cancer-related death in the United States. Here, we evaluated the potential clinical utility of soluble human epidermal growth factor receptor 2 (sHER2) for the risk assessment, screening, and diagnosis of non-small cell lung cancer (NSCLC) using an unmatched case-control study design. Serum sHER2 concentrations were measured by immunoassay in 244 primary NSCLC cases and 218 healthy controls. Wilcoxon rank-sum tests, logistic regression models, and receiver operating characteristic plots were used to assess whether sHER2 is associated with lung cancer. Median serum sHER2 concentrations are higher in patients with adenocarcinoma than squamous cell carcinoma regardless of gender, and sHER2 is a weak, independent biomarker of adenocarcinoma, but not of squamous cell carcinoma, adjusted for age and gender. The age-adjusted relative risk (odds) of adenocarcinoma is 3.95 (95% CI: 1.22, 12.81) and 7.93 (95% CI: 2.26, 27.82) greater for women and men with high sHER2 concentrations (≥6.60 ng/mL) vs. low sHER2 concentrations (≤1.85 ng/mL), respectively. When adjusted for each other, sHER2, age, and gender discern healthy controls from patients with primary adenocarcinomas of the lung with 85.9% accuracy. We conclude that even though serum sHER2 is not a strong, stand-alone discriminatory biomarker of adenocarcinoma, sHER2 may be a useful, independent covariate in multivariate risk assessment, screening, and diagnostic models of lung cancer. Full article
(This article belongs to the Special Issue Molecular Biomarkers for Cancer Targeted Therapeutics)
Open AccessArticle TD-GC-MS Investigation of the VOCs Released from Blood Plasma of Dogs with Cancer
Diagnostics 2013, 3(1), 68-83; doi:10.3390/diagnostics3010068
Received: 8 December 2012 / Revised: 31 December 2012 / Accepted: 15 January 2013 / Published: 16 January 2013
Cited by 1 | PDF Full-text (474 KB) | HTML Full-text | XML Full-text
Abstract
An analytical TD-GC-MS method was developed and used for the assessment of volatile organic compounds (VOCs) released from the blood plasma of dogs with/without cancer. VOCs released from 40 samples of diseased blood and 10 control samples were compared in order to [...] Read more.
An analytical TD-GC-MS method was developed and used for the assessment of volatile organic compounds (VOCs) released from the blood plasma of dogs with/without cancer. VOCs released from 40 samples of diseased blood and 10 control samples were compared in order to examine the difference between both sample groups that were showing qualitatively similar results independent from the disease’s presence. However, mild disturbances in the spectra of dogs with cancer in comparison with the control group were observed, and six peaks (tentatively identified by comparison with mass spectral library as hexanal, octanal, toluene, 2-butanone, 1-octen-3-ol and pyrrole) revealed statistically significant differences between both sample groups, thereby suggesting that these compounds are potential biomarkers that can be used for cancer diagnosis based on the blood plasma TD-GC-MS analysis. Statistical comparison with the application of principal component analysis (PCA) provided accurate discrimination between the cancer and control groups, thus demonstrating stronger biochemical perturbations in blood plasma when cancer is present. Full article
(This article belongs to the Special Issue Molecular Biomarkers for Cancer Targeted Therapeutics)
Open AccessCommunication Performance Evaluation of Fast Microfluidic Thermal Lysis of Bacteria for Diagnostic Sample Preparation
Diagnostics 2013, 3(1), 105-116; doi:10.3390/diagnostics3010105
Received: 10 December 2012 / Revised: 10 January 2013 / Accepted: 16 January 2013 / Published: 17 January 2013
Cited by 5 | PDF Full-text (502 KB) | HTML Full-text | XML Full-text
Abstract
Development of new diagnostic platforms that incorporate lab-on-a-chip technologies for portable assays is driving the need for rapid, simple, low cost methods to prepare samples for downstream processing or detection. An important component of the sample preparation process is cell lysis. In [...] Read more.
Development of new diagnostic platforms that incorporate lab-on-a-chip technologies for portable assays is driving the need for rapid, simple, low cost methods to prepare samples for downstream processing or detection. An important component of the sample preparation process is cell lysis. In this work, a simple microfluidic thermal lysis device is used to quickly release intracellular nucleic acids and proteins without the need for additional reagents or beads used in traditional chemical or mechanical methods (e.g., chaotropic salts or bead beating). On-chip lysis is demonstrated in a multi-turn serpentine microchannel with external temperature control via an attached resistive heater. Lysis was confirmed for Escherichia coli by fluorescent viability assay, release of ATP measured with bioluminescent assay, release of DNA measured by fluorometry and qPCR, as well as bacterial culture. Results comparable to standard lysis techniques were achievable at temperatures greater than 65 °C and heating durations between 1 and 60 s. Full article
(This article belongs to the Special Issue Microfluidic Lab-on-a-Chip Platforms for High-Performance Diagnostics)
Open AccessArticle A Disposable Microfluidic Virus Concentration Device Based on Evaporation and Interfacial Tension
Diagnostics 2013, 3(1), 155-169; doi:10.3390/diagnostics3010155
Received: 18 December 2012 / Revised: 12 February 2013 / Accepted: 20 February 2013 / Published: 28 February 2013
Cited by 5 | PDF Full-text (724 KB) | HTML Full-text | XML Full-text
Abstract
We report a disposable and highly effective polymeric microfluidic viral sample concentration device capable of increasing the concentration of virus in a human nasopharyngeal specimen more than one order of magnitude in less than 30 min without the use of a centrifuge. [...] Read more.
We report a disposable and highly effective polymeric microfluidic viral sample concentration device capable of increasing the concentration of virus in a human nasopharyngeal specimen more than one order of magnitude in less than 30 min without the use of a centrifuge. The device is fabricated using 3D maskless xurography method using commercially available polymeric materials, which require no cleanroom operations. The disposable components can be fabricated and assembled in five minutes. The device can concentrate a few milliliters (mL) of influenza virus in solution from tissue culture or clinical nasopharyngeal swab specimens, via reduction of the fluid volume, to tens of microliters (mL). The performance of the device was evaluated by nucleic acid extraction from the concentrated samples, followed by a real-time quantitative polymerase chain reaction (qRT-PCR). The viral RNA concentration in each sample was increased on average over 10-fold for both cultured and patient specimens compared to the starting samples, with recovery efficiencies above 60% for all input concentrations. Highly concentrated samples in small fluid volumes can increase the downstream process speed of on-chip nucleic acid extraction, and result in improvements in the sensitivity of many diagnostic platforms that interrogate small sample volumes. Full article
(This article belongs to the Special Issue Microfluidic Lab-on-a-Chip Platforms for High-Performance Diagnostics)
Figures

Open AccessArticle Analysis of Predictive Values Based on Individual Risk Factors in Multi-Modality Trials
Diagnostics 2013, 3(1), 192-209; doi:10.3390/diagnostics3010192
Received: 23 January 2013 / Revised: 25 February 2013 / Accepted: 13 March 2013 / Published: 15 March 2013
Cited by 1 | PDF Full-text (232 KB) | HTML Full-text | XML Full-text
Abstract
The accuracy of diagnostic tests with binary end-points is most frequently measured by sensitivity and specificity. However, from the clinical perspective, the main purpose of a diagnostic agent is to assess the probability of a patient actually being diseased and hence predictive [...] Read more.
The accuracy of diagnostic tests with binary end-points is most frequently measured by sensitivity and specificity. However, from the clinical perspective, the main purpose of a diagnostic agent is to assess the probability of a patient actually being diseased and hence predictive values are more suitable here. As predictive values depend on the pre-test probability of disease, we provide a method to take risk factors influencing the patient’s prior probability of disease into account, when calculating predictive values. Furthermore, approaches to assess confidence intervals and a methodology to compare predictive values by statistical tests are presented. Hereby the methods can be used to analyze predictive values of factorial diagnostic trials, such as multi-modality, multi-reader-trials. We further performed a simulation study assessing length and coverage probability for different types of confidence intervals, and we present the R-Package facROC that can be used to analyze predictive values in factorial diagnostic trials in particular. The methods are applied to a study evaluating CT-angiography as a noninvasive alternative to coronary angiography for diagnosing coronary artery disease. Hereby the patients’ symptoms are considered as risk factors influencing the respective predictive values. Full article
(This article belongs to the collection Feature Papers)

Review

Jump to: Research

Open AccessReview Natriuretic Peptides in Kawasaki Disease: the Myocardial Perspective
Diagnostics 2013, 3(1), 1-12; doi:10.3390/diagnostics3010001
Received: 5 December 2012 / Revised: 20 December 2012 / Accepted: 31 December 2012 / Published: 10 January 2013
Cited by 2 | PDF Full-text (240 KB) | HTML Full-text | XML Full-text
Abstract
Making a diagnosis of Kawasaki disease with certainty may be challenging, especially since the recognition of cases with incomplete diagnostic criteria and its consequences. In order to build the diagnostic case in daily practice, clinicians rely on clinical criteria established over four [...] Read more.
Making a diagnosis of Kawasaki disease with certainty may be challenging, especially since the recognition of cases with incomplete diagnostic criteria and its consequences. In order to build the diagnostic case in daily practice, clinicians rely on clinical criteria established over four decades ago, aided by non specific laboratory tests, and above all inspired by experience. We have recently studied the diagnostic value of N-terminal pro B-type natriuretic peptide to improve the diagnostic certainty of cases with complete or incomplete clinical criteria. Our working hypothesis was based on the fact that myocarditis is present in nearly all Kawasaki disease patients supported by histology data. In this paper, we review these facts and the myocardial perspective from the diagnostic and the mechanistic standpoints. Full article
(This article belongs to the collection Feature Papers)
Open AccessReview A Review of Heating and Temperature Control in Microfluidic Systems: Techniques and Applications
Diagnostics 2013, 3(1), 33-67; doi:10.3390/diagnostics3010033
Received: 23 November 2012 / Revised: 19 December 2012 / Accepted: 4 January 2013 / Published: 15 January 2013
Cited by 34 | PDF Full-text (1601 KB) | HTML Full-text | XML Full-text
Abstract
This review presents an overview of the different techniques developed over the last decade to regulate the temperature within microfluidic systems. A variety of different approaches has been adopted, from external heating sources to Joule heating, microwaves or the use of lasers [...] Read more.
This review presents an overview of the different techniques developed over the last decade to regulate the temperature within microfluidic systems. A variety of different approaches has been adopted, from external heating sources to Joule heating, microwaves or the use of lasers to cite just a few examples. The scope of the technical solutions developed to date is impressive and encompasses for instance temperature ramp rates ranging from 0.1 to 2,000 °C/s leading to homogeneous temperatures from −3 °C to 120 °C, and constant gradients from 6 to 40 °C/mm with a fair degree of accuracy. We also examine some recent strategies developed for applications such as digital microfluidics, where integration of a heating source to generate a temperature gradient offers control of a key parameter, without necessarily requiring great accuracy. Conversely, Temperature Gradient Focusing requires high accuracy in order to control both the concentration and separation of charged species. In addition, the Polymerase Chain Reaction requires both accuracy (homogeneous temperature) and integration to carry out demanding heating cycles. The spectrum of applications requiring temperature regulation is growing rapidly with increasingly important implications for the physical, chemical and biotechnological sectors, depending on the relevant heating technique. Full article
(This article belongs to the Special Issue Microfluidic Lab-on-a-Chip Platforms for High-Performance Diagnostics)
Open AccessReview MicroRNAs as Biomarkers in Cancer
Diagnostics 2013, 3(1), 84-104; doi:10.3390/diagnostics3010084
Received: 15 November 2012 / Revised: 28 December 2012 / Accepted: 14 January 2013 / Published: 16 January 2013
Cited by 3 | PDF Full-text (715 KB) | HTML Full-text | XML Full-text
Abstract
MicroRNAs (miRNAs) are small non-coding RNA molecules, which in recent years have emerged to have enormous potential as biomarkers. Recently, there have been significant developments in understanding miRNA biogenesis, their regulatory mechanisms and role in disease process, and their potential as effective [...] Read more.
MicroRNAs (miRNAs) are small non-coding RNA molecules, which in recent years have emerged to have enormous potential as biomarkers. Recently, there have been significant developments in understanding miRNA biogenesis, their regulatory mechanisms and role in disease process, and their potential as effective therapies. The identification of miRNAs as biomarkers provides possibilities for development of less or non-invasive and more specific methods for monitoring tumor growth and progression. This review summarizes the recent developments in methods to detect and quantitate miRNAs in body fluids and their applications as biomarkers in cancers. The prospect of miRNAs as potential diagnostic and prognostic biomarkers with clinical applications is significant as more evidence points to their central role in cancer pathobiology. Full article
(This article belongs to the Special Issue Molecular Biomarkers for Cancer Targeted Therapeutics)
Open AccessReview Strain Elastography Ultrasound: An Overview with Emphasis on Breast Cancer Diagnosis
Diagnostics 2013, 3(1), 117-125; doi:10.3390/diagnostics3010117
Received: 31 December 2012 / Revised: 11 February 2013 / Accepted: 20 February 2013 / Published: 25 February 2013
Cited by 3 | PDF Full-text (248 KB) | HTML Full-text | XML Full-text
Abstract
Strain elastography (SE), which estimates tissue strain, is an adjunct to the conventional ultrasound B-mode examination. We present a short introduction to SE and its clinical use. Furthermore, we present an overview of the 10 largest studies performed on the diagnostic accuracy [...] Read more.
Strain elastography (SE), which estimates tissue strain, is an adjunct to the conventional ultrasound B-mode examination. We present a short introduction to SE and its clinical use. Furthermore, we present an overview of the 10 largest studies performed on the diagnostic accuracy of SE in breast cancer diagnostics. Eight of 10 studies presented data for both SE and B-mode imaging. Seven studies showed better specificity and accuracy for SE than for B-mode imaging in breast cancer diagnosis. Four studies showed an increase in specificity and accuracy when combining B-mode imaging with SE. The ways of combining B-mode imaging with SE in the diagnosis of breast cancer differed between the five studies. We believe that further studies are needed to establish an optimal algorithm for the combination of B-mode ultrasound and SE in breast cancer. Full article
(This article belongs to the collection Feature Papers)
Open AccessReview When Medicine Meets Engineering—Paradigm Shifts in Diagnostics and Therapeutics
Diagnostics 2013, 3(1), 126-154; doi:10.3390/diagnostics3010126
Received: 10 December 2012 / Revised: 10 January 2013 / Accepted: 23 January 2013 / Published: 27 February 2013
Cited by 2 | PDF Full-text (902 KB) | HTML Full-text | XML Full-text
Abstract
During the last two decades, the manufacturing techniques of microfluidics-based devices have been phenomenally advanced, offering unlimited potential for bio-medical technologies. However, the direct applications of these technologies toward diagnostics and therapeutics are still far from maturity. The present challenges lay at [...] Read more.
During the last two decades, the manufacturing techniques of microfluidics-based devices have been phenomenally advanced, offering unlimited potential for bio-medical technologies. However, the direct applications of these technologies toward diagnostics and therapeutics are still far from maturity. The present challenges lay at the interfaces between the engineering systems and the biocomplex systems. A precisely designed engineering system with narrow dynamic range is hard to seamlessly integrate with the adaptive biological system in order to achieve the design goals. These differences remain as the roadblock between two fundamentally non-compatible systems. This paper will not extensively review the existing microfluidic sensors and actuators; rather, we will discuss the sources of the gaps for integration. We will also introduce system interface technologies for bridging the differences to lead toward paradigm shifts in diagnostics and therapeutics. Full article
(This article belongs to the Special Issue Microfluidic Lab-on-a-Chip Platforms for High-Performance Diagnostics)
Open AccessReview Development of MicroRNA Therapeutics for Hepatocellular Carcinoma
Diagnostics 2013, 3(1), 170-191; doi:10.3390/diagnostics3010170
Received: 5 February 2013 / Revised: 1 March 2013 / Accepted: 11 March 2013 / Published: 15 March 2013
Cited by 2 | PDF Full-text (213 KB) | HTML Full-text | XML Full-text
Abstract
Hepatocellular carcinoma (HCC) is the most common form of liver cancer and is the third leading cause of cancer-related deaths worldwide. Treatment options for HCC are very limited, as it is often diagnosed at a late stage. Recent studies have demonstrated that [...] Read more.
Hepatocellular carcinoma (HCC) is the most common form of liver cancer and is the third leading cause of cancer-related deaths worldwide. Treatment options for HCC are very limited, as it is often diagnosed at a late stage. Recent studies have demonstrated that microRNAs (miRNAs), a class of non-coding RNAs, are aberrantly expressed in HCC. Some of these were shown to be functionally involved in carcinogenesis and tumor progression, suggesting that miRNAs can serve as novel molecular targets for HCC therapy. Several promising studies have recently demonstrated the therapeutic potential of miRNAs in animal models and in reducing the viral load in hepatitis C patients. In this review, these advances and strategies for modulating miRNAs for in vivo therapeutic delivery and replacement therapy are discussed. Full article
(This article belongs to the Special Issue Molecular Biomarkers for Cancer Targeted Therapeutics)

Journal Contact

MDPI AG
Diagnostics Editorial Office
St. Alban-Anlage 66, 4052 Basel, Switzerland
diagnostics@mdpi.com
Tel. +41 61 683 77 34
Fax: +41 61 302 89 18
Editorial Board
Contact Details Submit to Diagnostics
Back to Top