Enhanced anti-HIV-1 activity of CC-chemokine LD78β, a non-allelic variant of MIP-1α/LD78α

AbstractWe compared the anti-HIV-1 activity of CC-chemokine LD78β with that of MIP-1α, another CC-chemokine which shows 94% sequence homology with LD78β. Despite its close similarity to MIP-1α, the anti-HIV-1 activity of LD78β appeared to be nearly 10 times higher than that of MIP-1α. Mutagenesis of MIP-1α showed that the N-terminal additional tetrapeptide, which was present in LD78β and absent in MIP-1α, is responsible for enhanced anti-HIV-1 activity. The N-terminal structure-function relationship of LD78β described here will be of value in understanding the chemokine-receptor interactions and designing anti-HIV-1 compounds based on LD78β

Clue-based Spatio-textual Query

Along with the proliferation of online digital map and location-based service, very large POI (point of interest) databases have been constructed where a record corresponds to a POI with information including name, category, address, geographical location and other features. A basic spatial query in POI database is POI retrieval. In many scenarios, a user cannot provide enough information to pinpoint the POI except some clue. For example, a user wants to identify a caf é in a city visited many years ago. SHe cannot remember the name and address but she still recalls that "the caf é is about 200 meters away from a restaurant; and turning left at the restaurant there is a bakery 500 meters away, etc.". Intuitively, the clue, even partial and approximate, describes the spatio-textual context around the targeted POI. Motivated by this observation, this work investigates clue-based spatio-textual query which allows user providing clue, i.e., some nearby POIs and the spatial relationships between them, in POI retrieval. The objective is to retrieve k POIs from a POI database with the highest spatio-textual context similarities against the clue. This work has deliberately designed data-quality-tolerant spatio-textual context similarity metric to cope with various data quality problems in both the clue and the POI database. Through crossing valuation, the query accuracy is further enhanced by ensemble method. Also, this work has developed an index called roll-out-star R-tree (RSR-tree) to dramatically improve the query processing efficiency. The extensive tests on data sets from the real world have verified the superiority of our methods in all aspects. </jats:p

Clinical outcomes of active specific immunotherapy in advanced colorectal cancer and suspected minimal residual colorectal cancer: a meta-analysis and system review

<p>Abstract</p> <p>Background</p> <p>To evaluate the objective clinical outcomes of active specific immunotherapy (ASI) in advanced colorectal cancer (advanced CRC) and suspected minimal residual colorectal cancer (suspected minimal residual CRC).</p> <p>Methods</p> <p>A search was conducted on Medline and Pub Med from January 1998 to January 2010 for original studies on ASI in colorectal cancer (CRC). All articles included in this study were assessed with the application of predetermined selection criteria and were divided into two groups: ASI in advanced CRC and ASI in suspected minimal residual CRC. For ASI in suspected minimal residual CRC, a meta-analysis was executed with results regarding the overall survival (OS) and disease-free survival (DFS). Regarding ASI in advanced colorectal cancer, a system review was performed with clinical outcomes.</p> <p>Results</p> <p>1375 colorectal carcinoma patients with minimal residual disease have been enrolled in Meta-analysis. A significantly improved OS and DFS was noted for suspected minimal residual CRC patients utilizing ASI (For OS: HR = 0.76, P = 0.007; For DFS: HR = 0.76, P = 0.03). For ASI in stage II suspected minimal residual CRC, OS approached significance when compared with control (HR = 0.71, P = 0.09); however, the difference in DFS of ASI for the stage II suspected minimal residual CRC reached statistical significance (HR = 0.66, P = 0.02). For ASI in stage III suspected minimal residual CRC compared with control, The difference in both OS and DFS achieved statistical significance (For OS: HR = 0.76, P = 0.02; For DFS: HR = 0.81, P = 0.03). 656 advanced colorectal patients have been evaluated on ASI in advanced CRC. Eleven for CRs and PRs was reported, corresponding to an overall response rate of 1.68%. No serious adverse events have been observed in 2031 patients.</p> <p>Conclusions</p> <p>It is unlikely that ASI will provide a standard complementary therapeutic approach for advanced CRC in the near future. However, the clinical responses to ASI in patients with suspected minimal residual CRC have been encouraging, and it has become clear that immunotherapy works best in situations of patients with suspected minimal residual CRC.</p

Jun-APOE-LRP1 axis promotes tumor metastasis in colorectal cancer

Apolipoprotein E (apoE) has previously been reported to play vital roles in tumor progression. However, the impact of apoE on colorectal cancer (CRC) metastasis remains largely unexplored. This study aimed to investigate the role of apoE in CRC metastasis and to identify the transcription factor and receptor of apoE involved in regulation of CRC metastasis. Bioinformatic analyses were conducted to examine the expression pattern and prognosis of apolipoproteins. APOE-overexpressing cell lines were utilized to explore the effects of apoE on proliferation, migration and invasion of CRC cells. Additionally, the transcription factor and receptor of apoE were screened via bioinformatics, and further validated through knockdown experiments. We discovered that the mRNA levels of APOC1, APOC2, APOD and APOE were higher in lymphatic invasion group, and a higher apoE level indicated poorer overall survival and progression-free interval. In vitro studies demonstrated that APOE-overexpression did not affect proliferation but promoted the migration and invasion of CRC cells. We also reported that APOE-expression was modulated by the transcription factor Jun by activating the proximal promoter region of APOE, and APOE-overexpression reversed the metastasis suppression of JUN knockdown. Furthermore, bioinformatics analysis suggested an interaction between apoE and low-density lipoprotein receptor-related protein 1 (LRP1). LRP1 was highly expressed in both the lymphatic invasion group and the APOEHigh group. Additionally, we found that APOE-overexpression upregulated LRP1 protein levels, and LRP1 knockdown attenuated the metastasis-promoting function of APOE. Overall, our study suggests that the Jun-APOE-LRP1 axis contributes to tumor metastasis in CRC

Patient-physician mistrust and violence against physicians in Guangdong Province, China: a qualitative study.

OBJECTIVE: To better understand the origins, manifestations and current policy responses to patient-physician mistrust in China. DESIGN: Qualitative study using in-depth interviews focused on personal experiences of patient-physician mistrust and trust. SETTING: Guangdong Province, China. PARTICIPANTS: One hundred and sixty patients, patient family members, physicians, nurses and hospital administrators at seven hospitals varying in type, geography and stages of achieving goals of health reform. These interviews included purposive selection of individuals who had experienced both trustful and mistrustful patient-physician relationships. RESULTS: One of the most prominent forces driving patient-physician mistrust was a patient perception of injustice within the medical sphere, related to profit mongering, knowledge imbalances and physician conflicts of interest. Individual physicians, departments and hospitals were explicitly incentivised to generate revenue without evaluation of caregiving. Physicians did not receive training in negotiating medical disputes or humanistic principles that underpin caregiving. Patient-physician mistrust precipitated medical disputes leading to the following outcomes: non-resolution with patient resentment towards physicians; violent resolution such as physical and verbal attacks against physicians; and non-violent resolution such as hospital-mediated dispute resolution. Policy responses to violence included increased hospital security forces, which inadvertently fuelled mistrust. Instead of encouraging communication that facilitated resolution, medical disputes sometimes ignited a vicious cycle leading to mob violence. However, patient-physician interactions at one hospital that has implemented a primary care model embodying health reform goals showed improved patient-physician trust. CONCLUSIONS: The blind pursuit of financial profits at a systems level has eroded patient-physician trust in China. Restructuring incentives, reforming medical education and promoting caregiving are pathways towards restoring trust. Assessing and valuing the quality of caregiving is essential for transitioning away from entrenched profit-focused models. Moral, in addition to regulatory and legal, responses are urgently needed to restore trust

Matching stream patterns of various lengths and tolerances

Continuously identifying pre-defined patterns in a streaming time series has strong demand in various applications. While most existing works assume the patterns are in equal length and tolerance, this work focuses on the problem where the patterns have various lengths and tolerances, a common situation in the real world. The challenge of this problem roots on the strict space and time requirements of processing the arriving and expiring data in high-speed stream, combined with difficulty of coping with a large number of patterns with various lengths and tolerances. We introduce a novel concept of converging envelope which bounds the tolerance of a group of patterns in various tolerances and equal length and thus dramatically reduces the number of patterns for similarity computation. The basic idea of converging envelope has potential to more general index problems. To index patterns in various lengths and tolerances, we partition patterns into sub-patterns in equal length and an multi-tree index is developed in this paper. Copyright 2009 ACM