Clinically Relevant Characterization of Lung Adenocarcinoma Subtypes Based on Cellular Pathways: An International Validation Study

Lung adenocarcinoma (AD) represents a predominant type of lung cancer demonstrating significant morphologic and molecular heterogeneity. We sought to understand this heterogeneity by utilizing gene expression analyses of 432 AD samples and examining associations between 27 known cancer-related pathways and the AD subtype, clinical characteristics and patient survival. Unsupervised clustering of AD and gene expression enrichment analysis reveals that cell proliferation is the most important pathway separating tumors into subgroups. Further, AD with increased cell proliferation demonstrate significantly poorer outcome and an increased solid AD subtype component. Additionally, we find that tumors with any solid component have decreased survival as compared to tumors without a solid component. These results lead to the potential to use a relatively simple pathological examination of a tumor in order to determine its aggressiveness and the patient's prognosis. Additional results suggest the ability to use a similar approach to determine a patient's sensitivity to targeted treatment. We then demonstrated the consistency of these findings using two independent AD cohorts from Asia (N = 87) and Europe (N = 89) using the identical analytic procedures

New fluoroscopic imaging technique for investigation of 6DOF knee kinematics during treadmill gait

<p>Abstract</p> <p>Introduction</p> <p>This report presents a new imaging technique for non-invasive study of six degrees of freedom (DOF) knee kinematics during treadmill gait.</p> <p>Materials and methods</p> <p>A treadmill was integrated into a dual fluoroscopic imaging system (DFIS) to formulate a gait analysis system. To demonstrate the application of the system, a healthy subject walked on the treadmill at four different speeds (1.5, 2.0, 2.5 and 3.0 MPH) while the DFIS captured the knee motion during three strides under each speed. Characters of knee joint motion were analyzed in 6DOF during the treadmill walking.</p> <p>Results</p> <p>The speed of the knee motion was lower than that of the treadmill. Flexion amplitudes increased with increasing walking speed. Motion patterns in other DOF were not affected by increase in walking speed. The motion character was repeatable under each treadmill speed.</p> <p>Conclusion</p> <p>The presented technique can be used to accurately measure the 6DOF knee kinematics at normal walking speeds.</p

A Bioinformatics Filtering Strategy for Identifying Radiation Response Biomarker Candidates

The number of biomarker candidates is often much larger than the number of clinical patient data points available, which motivates the use of a rational candidate variable filtering methodology. The goal of this paper is to apply such a bioinformatics filtering process to isolate a modest number (<10) of key interacting genes and their associated single nucleotide polymorphisms involved in radiation response, and to ultimately serve as a basis for using clinical datasets to identify new biomarkers. In step 1, we surveyed the literature on genetic and protein correlates to radiation response, in vivo or in vitro, across cellular, animal, and human studies. In step 2, we analyzed two publicly available microarray datasets and identified genes in which mRNA expression changed in response to radiation. Combining results from Step 1 and Step 2, we identified 20 genes that were common to all three sources. As a final step, a curated database of protein interactions was used to generate the most statistically reliable protein interaction network among any subset of the 20 genes resulting from Steps 1 and 2, resulting in identification of a small, tightly interacting network with 7 out of 20 input genes. We further ranked the genes in terms of likely importance, based on their location within the network using a graph-based scoring function. The resulting core interacting network provides an attractive set of genes likely to be important to radiation response

On Practical Issues of ENF Based Audio Forensics

The transmission frequency of power grids, i.e., electric network frequency (ENF), has become a common criterion to authenticate audio recordings during the past decade, drawing much attention from both academic researchers and law enforcement agencies world widely. The properties of ENF enable forensic applications such as audio evidence timestamp verification and tampering detection. In this paper, based on a general review of existing works, we discuss several important practical problems and facts that have drawn less research attention or have not been formally studied, including ENF detection problems, limitations of ENF based tampering detection systems, and the difficulties in ENF analysis. During ENF detection, the challenges come from not only the noise and interference, but also the fact that audio recordings without captured ENF can still have signal components in the frequency band of interest (false positive). In ENF based tampering detection systems, the weakness of commonly used assumptions and the limitations of several existing solutions are discussed. In addition, we reveal that in the most intensively studied ENF based audio evidence timestamp verification, many works aiming at improving ENF estimation could only produce marginal performance improvement, while the main problems due to noise and interference remain open. All these analysis and discussions are related by a proposed big picture of ENF based audio authentication systems. After that, we also investigate the strategies to design more reliable audio authentication systems based on the ENF, which consists of a series of research and investigation works.MOE (Min. of Education, S’pore)Published versio