Evaluation of the diagnostic performance of infrared imaging of the breast: a preliminary study

<p>Abstract</p> <p>Background</p> <p>The study was conducted to investigate the diagnostic performance of infrared (IR) imaging of the breast using an interpretive model derived from a scoring system.</p> <p>Methods</p> <p>The study was approved by the Institutional Review Board of our hospital. A total of 276 women (mean age = 50.8 years, SD 11.8) with suspicious findings on mammograms or ultrasound received IR imaging of the breast before excisional biopsy. The interpreting radiologists scored the lesions using a scoring system that combines five IR signs. The ROC (receiver operating characteristic) curve and AUC (area under the ROC curve) were analyzed by the univariate logistic regression model for each IR sign and an age-adjusted multivariate logistic regression model including 5 IR signs. The cut-off values and corresponding sensitivity, specificity, Youden's Index (Index = sensitivity+specificity-1), positive predictive value (PPV), negative predictive value (NPV) were estimated from the age-adjusted multivariate model. The most optimal cut-off value was determined by the one with highest Youden's Index.</p> <p>Results</p> <p>For the univariate model, the AUC of the ROC curve from five IR signs ranged from 0.557 to 0.701, and the AUC of the ROC from the age-adjusted multivariate model was 0.828. From the ROC derived from the multivariate model, the sensitivity of the most optimal cut-off value would be 72.4% with the corresponding specificity 76.6% (Youden's Index = 0.49), PPV 81.3% and NPV 66.4%.</p> <p>Conclusions</p> <p>We established an interpretive age-adjusted multivariate model for IR imaging of the breast. The cut-off values and the corresponding sensitivity and specificity can be inferred from the model in a subpopulation for diagnostic purpose.</p> <p>Trial Registration</p> <p>NCT00166998.</p

A spectral graph theoretic approach to quantification and calibration of collective morphological differences in cell images

Motivation: High-throughput image-based assay technologies can rapidly produce a large number of cell images for drug screening, but data analysis is still a major bottleneck that limits their utility. Quantifying a wide variety of morphological differences observed in cell images under different drug influences is still a challenging task because the result can be highly sensitive to sampling and noise

Objective comparison of particle tracking methods

Particle tracking is of key importance for quantitative analysis of intracellular dynamic processes from time-lapse microscopy image data. Because manually detecting and following large numbers of individual particles is not feasible, automated computational methods have been developed for these tasks by many groups. Aiming to perform an objective comparison of methods, we gathered the community and organized an open competition in which participating teams applied their own methods independently to a commonly defined data set including diverse scenarios. Performance was assessed using commonly defined measures. Although no single method performed best across all scenarios, the results revealed clear differences between the various approaches, leading to notable practical conclusions for users and developers

Automatic Morphological Subtyping Reveals New Roles of Caspases in Mitochondrial Dynamics

Morphological dynamics of mitochondria is associated with key cellular processes related to aging and neuronal degenerative diseases, but the lack of standard quantification of mitochondrial morphology impedes systematic investigation. This paper presents an automated system for the quantification and classification of mitochondrial morphology. We discovered six morphological subtypes of mitochondria for objective quantification of mitochondrial morphology. These six subtypes are small globules, swollen globules, straight tubules, twisted tubules, branched tubules and loops. The subtyping was derived by applying consensus clustering to a huge collection of more than 200 thousand mitochondrial images extracted from 1422 micrographs of Chinese hamster ovary (CHO) cells treated with different drugs, and was validated by evidence of functional similarity reported in the literature. Quantitative statistics of subtype compositions in cells is useful for correlating drug response and mitochondrial dynamics. Combining the quantitative results with our biochemical studies about the effects of squamocin on CHO cells reveals new roles of Caspases in the regulatory mechanisms of mitochondrial dynamics. This system is not only of value to the mitochondrial field, but also applicable to the investigation of other subcellular organelle morphology

Differences in gait and trunk movement between patients after ankle fracture and healthy subjects

Abstract Background Studies have shown that gait asymmetry and activity limitation can persist several months or years after ankle fracture. However, evidence of gait and trunk movement patterns following ankle fracture during the early rehabilitation period is scarce. Thus, we compared gait patterns and trunk movement during the early phase of rehabilitation between patients with ankle fracture and matched controls. Methods Ten patients with ankle fractures, and ten age- and sex-matched healthy controls were prospectively enrolled. An automated infrared-assisted, trunk accelerometer-based gait analysis system was used to measure walking speed, step length, and cadence. The median time of the evaluation following ankle fracture was 4.0 months. Trunk movement intensity was evaluated as acceleration root mean square. Trunk movement symmetry and regularity were analysed using the autocorrelation method. Differences in gait characteristics between the patient and control groups were analysed using the Mann–Whitney U test. Follow-up assessment of falls was performed 24 months after the fracture. The correlations between Lower Extremity Functional Scale (LEFS) scores/falls and gait parameters were evaluated using Spearman’s rank correlation coefficient. Results Walking speed (p = 0.019), step length (p = 0.023), cadence (p = 0.003), and trunk movement intensity in anterior–posterior and vertical axis (p = 0.001, p = 0.003, respectively) were all significantly lower in the ankle fracture group than in the control group. Trunk movement symmetry in vertical direction (p = 0.019) decreased significantly in patients with ankle fractures, whereas between-strides regularity did not differ between groups. LEFS scores were moderately correlated with walking speed (r = 0.60, p = 0.044) and step length (r = 0.68, p = 0.021). During the 24 months after the fracture, 3 falls were reported by 3 patients. Trunk acceleration root mean square ratio in mediolateral axis (r = 0.72, p = 0.018) was highly correlated with future falls. Conclusion During early rehabilitation, patients with ankle fracture may develop trunk movement asymmetry in the vertical direction accompanied with slower walking speed and cadence, and smaller step lengths, which can contribute to muscular imbalances and potential injury. Thus, proper rehabilitation strategies should be employed for these patients

Test-Retest Reliability of an Automated Infrared-Assisted Trunk Accelerometer-Based Gait Analysis System

The aim of this study was to determine the test-retest reliability of an automated infrared-assisted, trunk accelerometer-based gait analysis system for measuring gait parameters of healthy subjects in a hospital. Thirty-five participants (28 of them females; age range, 23–79 years) performed a 5-m walk twice using an accelerometer-based gait analysis system with infrared assist. Measurements of spatiotemporal gait parameters (walking speed, step length, and cadence) and trunk control (gait symmetry, gait regularity, acceleration root mean square (RMS), and acceleration root mean square ratio (RMSR)) were recorded in two separate walking tests conducted 1 week apart. Relative and absolute test-retest reliability was determined by calculating the intra-class correlation coefficient (ICC3,1) and smallest detectable difference (SDD), respectively. The test-retest reliability was excellent for walking speed (ICC = 0.87, 95% confidence interval = 0.74–0.93, SDD = 13.4%), step length (ICC = 0.81, 95% confidence interval = 0.63–0.91, SDD = 12.2%), cadence (ICC = 0.81, 95% confidence interval = 0.63–0.91, SDD = 10.8%), and trunk control (step and stride regularity in anterior-posterior direction, acceleration RMS and acceleration RMSR in medial-lateral direction, and acceleration RMS and stride regularity in vertical direction). An automated infrared-assisted, trunk accelerometer-based gait analysis system is a reliable tool for measuring gait parameters in the hospital environment

IRSS: a web-based tool for automatic layout and analysis of IRES secondary structure prediction and searching system <it>in silico</it>

<p>Abstract</p> <p>Background</p> <p>Internal ribosomal entry sites (IRESs) provide alternative, cap-independent translation initiation sites in eukaryotic cells. IRES elements are important factors in viral genomes and are also useful tools for bi-cistronic expression vectors. Most existing RNA structure prediction programs are unable to deal with IRES elements.</p> <p>Results</p> <p>We designed an IRES search system, named IRSS, to obtain better results for IRES prediction. RNA secondary structure prediction and comparison software programs were implemented to construct our two-stage strategy for the IRSS. Two software programs formed the backbone of IRSS: the RNAL fold program, used to predict local RNA secondary structures by minimum free energy method; and the RNA Align program, used to compare predicted structures. After complete viral genome database search, the IRSS have low error rate and up to 72.3% sensitivity in appropriated parameters.</p> <p>Conclusion</p> <p>IRSS is freely available at this website <url>http://140.135.61.9/ires/</url>. In addition, all source codes, precompiled binaries, examples and documentations are downloadable for local execution. This new search approach for IRES elements will provide a useful research tool on IRES related studies.</p

Dysregulation of HER2/HER3 Signaling Axis in Epstein-Barr Virus-Infected Breast Carcinoma Cells▿

The role of Epstein-Barr virus (EBV) in the pathogenesis of breast cancer has been of long-standing interest to the field. Breast epithelial cells can be infected by EBV through direct contact with EBV-bearing lymphoblastoid cells, and EBV infection has recently been shown to confer breast cancer cells an increased resistance to chemotherapeutic drugs. In this study, we established EBV-infected breast cancer MCF7 and BT474 cells and demonstrated that EBV infection promotes tumorigenic activity of breast cancer cells. Firstly, we showed that the EBV-infected MCF7-A and BT474-A cells exhibited increased anchorage-independent growth in soft agar. The increased colony formation capacity in soft agar was associated with increased expression and activation of HER2/HER3 signaling cascades, as evidenced by the findings that the treatment of HER2 antibody trastuzumab (Herceptin), phosphatidylinositol 3-kinase inhibitor, or MEK inhibitor completely abolished the tumorigenic capacity. In the EBV-infected breast cancer cells, the expression of EBV latency genes including EBNA1, EBER1, and BARF0 was detected. We next showed that BARF0 alone was sufficient to efficiently up-regulate HER2/HER3 expression and promoted tumorigenic activity in MCF7 and BT474 cells by the use of both overexpression and small interfering RNA knock-down. Collectively, we demonstrated that EBV-encoded BARF0 promotes the tumorigenic activity of breast cancer cells through activation of HER2/HER3 signaling cascades