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Biomedical subjects

Junhua Zhang

Publications and source records attributed to Junhua Zhang.

5 recordsLinked to original sources

Multi-context modeling of driver pathways reveals common and specific mechanisms across 23 cancer types.

Discovery of cancer driver pathways is essential for targeted therapies, since these pathways govern tumor progression and treatment resistance. However, their context-specific patterns across populations remain poorly understood. Leveraging pan-cancer genomic data, we apply our two models, EntCDP and ModSDP, to perform stratified analyses from four perspectives: region, tumor type, age group, and risk factors. Our results reveal the regional biases in perturbed pathways, such as PI3K-Akt in Chinese patients and GPCR in American patients with bladder cancer. Subtype comparisons highlight the mTOR signaling in lung adenocarcinoma and the FoxO signaling in lung squamous cell carcinoma. Pediatric-adult comparisons emphasize the enrichment of Ras signaling in pediatric acute myeloid leukemia and PAK signaling in pediatric glioblastoma, respectively. Risk factor associations further link Notch-mediated pathways to alcohol consumption and CDKN-regulated pathways to obesity-related cancers. Our findings demonstrate the utility of stratified driver pathway analysis in uncovering common and specific mechanisms, which can help prioritize context-aware therapeutic targets.

Humans↗

Sonographic feature extraction of cervical lymph nodes and its relationship with segmentation methods.

OBJECTIVE: The purpose of this study was to extract quantitative features for characterization of cervical lymph nodes on sonographic images and analyze the effect of a semiautomated segmentation method on the feature extraction. METHODS: Contours of 186 cervical lymph nodes on sonographic images were separately delineated by 2 radiologists (R1 and R2) and a semiautomated segmentation method. For each node, 10 kinds of sonographic features (including 3 parameters of size; 12 parameters of margin; 4 parameters of nodal border; 10 parameters of echogeneity; and 1 parameter of shape, echogenicity, medulla ratio, medulla distribution, vascular density, and vascular pattern, respectively) were quantified by a computerized scheme based on the segmented contour. Correlations between the quantitative parameter and the radiologists' consensus grading were computed to assess the effectiveness of these parameters. Concerning the 14 best correlated parameters, the effect of the segmentation stage on the feature extraction was estimated by comparing the parameter values calculated under different segmentations in terms of relative ultimate measurement accuracy. RESULTS: Good correlations between the computerized scheme and radiologists were seen in features of size, nodal border, shape, echogenicity, medulla ratio, medulla distribution, vascular density, and vascular pattern, whereas 10 of 12 parameters of margin features and 8 of 10 parameters of echogeneity features showed poor correlations. Paired t tests comparing the relative ultimate measurement accuracy computed using the R1-R2 and the R1-computer pairing showed no significant difference on 11 parameters for the 14 parameters analyzed. CONCLUSIONS: The computerized feature parameters may be used as assisted indices for evaluating cervical lymphadenopathies from sonographic images. The semiautomated segmentation method satisfied the accuracy requirement of the feature extraction.

Adolescent↗

Proliferation and anti-apoptotic effects of human urotensin II on human endothelial cells.

BACKGROUND: Human urotensin II (hU-II) is a potent vasoconstrictor, highly expressed in cardiac tissues and blood vessels. Recent studies indicate that hU-II participates in vascular and myocardial remodeling after injury. This study was designed to study the role of hU-II in cell DNA synthesis and apoptosis in human umbilical vein endothelial cells (HUVECs) and underlying intracellular signaling mechanisms. METHODS AND RESULTS: Cultured HUVECs were incubated with hU-II (10(-10)-10(-8)M) for 24h. Cell DNA synthesis was examined by 3H thymidine incorporation. Apoptosis was detected by flow cytometry and TUNEL. hU-II increased the 3H thymidine incorporation into DNA in a concentration-dependent manner. hU-II inhibited endothelial apoptosis induced by serum withdrawal (5.74+/-0.64% versus 13.20+/-1.96%, P<0.01) and TNFalpha (6.76+/-0.70% versus 13.80+/-1.02%, P<0.01). The data from flow cytometry and TUNEL are consistent. Further studies showed that hU-II caused the phosphorylation of mitogen-activated protein kinasep42/44 (MAPKp42/44) in a concentration-dependent manner and this effect of hU-II was inhibited by pretreatment of cells with the MEK inhibitor (PD98059, 10muM). In addition, the use of PD98059 also attenuated 3H thymidine incorporation and anti-apoptotic effect elicited by hU-II (both P<0.01 versus hU-II alone). CONCLUSIONS: Our observations provide evidence that hU-II promotes cell proliferation and inhibits apoptosis in HUVECs, and MAPKp42/44 activation may play a signal transduction role in this process.

Apoptosis↗

MSAID: multiple sequence alignment based on a measure of information discrepancy.

We propose an algorithm of global multiple sequence alignment that is based on a measure of what we call information discrepancy. The algorithm follows a progressive alignment iteration strategy that makes use of what we call a function of degree of disagreement (FDOD). MSAID begins with distance calculation of pairwise sequences, based on FDOD as a numerical scoring measure. In the next step, the resulting distance matrix is used to construct a guide tree via the neighbor-joining method. The tree is then used to produce a multiple alignment. Current alignment is next used to produce a new matrix and a new tree (with FDOD scoring measure again). This iterative process continues until convergence criteria (or a stopping rule) are satisfied. MSAID was tested and compared with other prior methods by using reference alignments from BAliBASE 2.01. For the alignments with no large N/C-terminal extensions or internal insertions MSAID received the top overall average in the tests. Moreover, the results of testing indicate that MSAID performs as well as other alignment methods with an occasional tendency to perform better than these prior techniques. We, therefore, believe that MSAID is a solid and reliable method of choice, which is often (if not always) superior to other global alignment techniques.

Algorithms↗

Motorcycle ownership and injury in China.

BACKGROUND: China has made tremendous progress in its economic development in the past two decades. Accompanying this economic development has been an evident shift in the modes of transport, from walking and cycling to the use of motorcycles and, increasingly, four-wheel vehicles. Such changes are likely to have also produced changes in the patterns and numbers of road traffic injuries, including increases in motorcycle injuries. However, such changes have not been well documented. The work described in this paper sought, therefore, to document the changes in motorcycle ownership, motorcyclist mortality and injury rates in China since 1987. METHODS: National traffic ownership and injury data from 1987 to 2001 were obtained from the National Bureau for Traffic Administration. Additionally, traffic ownership and injury records from 1997 to 2001 were collected from local police offices from 20 counties in Guangxi Region. Population data were obtained from the national and county statistics bureaus. Motorcycle ownership, fatality and injury trends over time were calculated. RESULTS: Nationally, motorcycles accounted for 23.4% of all registered motor vehicles in 1987, increasing to 63.2% in 2001. Motorcyclist fatalities and injuries increased 5.5-fold and 9.3-fold, respectively, between 1987 and 2001. In 1987, 7.5% of all traffic fatalities and 8.8% of all traffic injuries were sustained by motorcyclists, with the corresponding proportions increasing to 18.9% and 22.8%, respectively, in 2001. The changing proportions of both traffic fatalities and injuries sustained by motorcyclists were positively correlated with the change in the proportion of motorcycles among all motor vehicles. In the 20 counties in Guangxi, motorcyclist fatality and injury rates also increased between 1997 and 2001. Moreover, these rates were considerably higher than the national rates. CONCLUSIONS: Motorcyclist injury in China is a serious public health problem. Motorcyclist fatalities and injuries are likely to continue to increase unless appropriate intervention programmes are implemented.

Accidents, Traffic↗