Exploration of the association rules mining technique for the signal detection of adverse drug events in spontaneous reporting systems.

BACKGROUND: The detection of signals of adverse drug events (ADEs) has increased because of the use of data mining algorithms in spontaneous reporting systems (SRSs). However, different data mining algorithms have different traits and conditions for application. The objective of our study was to explore the application of association rule (AR) mining in ADE signal detection and to compare its performance with that of other algorithms. METHODOLOGY/PRINCIPAL FINDINGS: Monte Carlo simulation was applied to generate drug-ADE reports randomly according to the characteristics of SRS datasets. Thousand simulated datasets were mined by AR and other algorithms. On average, 108,337 reports were generated by the Monte Carlo simulation. Based on the predefined criterion that 10% of the drug-ADE combinations were true signals, with RR equaling to 10, 4.9, 1.5, and 1.2, AR detected, on average, 284 suspected associations with a minimum support of 3 and a minimum lift of 1.2. The area under the receiver operating characteristic (ROC) curve of the AR was 0.788, which was equivalent to that shown for other algorithms. Additionally, AR was applied to reports submitted to the Shanghai SRS in 2009. Five hundred seventy combinations were detected using AR from 24,297 SRS reports, and they were compared with recognized ADEs identified by clinical experts and various other sources. CONCLUSIONS/SIGNIFICANCE: AR appears to be an effective method for ADE signal detection, both in simulated and real SRS datasets. The limitations of this method exposed in our study, i.e., a non-uniform thresholds setting and redundant rules, require further research.

[Behavioral changes of rats under rotation stimulation].

OBJECTIVE: To assess the specification and efficiency of rotation sickness indices by monitoring changes of behaviors in rats under rotation stimulation. METHOD: SD rats were stimulated by Crampton model with different time courses. Pica or kaolin consumption (KC), conditioned taste aversion (CTA) or saccharine water ingestion (SWI), 2 h food ingestion (2hFI), and open-field test (OFT) scores were observed. RESULT: Apparent changes of the four indices were observed after rotation stimulation. SWI, OFT scores and 2hFI decreased exponentially with increase of duration of the motion stimulation. KC increased linearly with the increase of time within 12 h stimulation. After 18 h stimulation, KC decreased to a level even lower than that after 6 or 12 h stimulation. The adjusted correlation between changes of the indices and duration of stimulation within 12 h are: 0.94 for KC, 0.54 for SWI, 0.44 for 2hFI and 0.34 for OFT. The maximum efficiency of the four indices appeared at 6-hour stimulation: 70% for KC, 90% for SWI, 80% for 2hFI and 95% for OFT. CONCLUSION: It is found that pica and CTA were more specific than the other indices. They may serve as primary indices and can be combined with the secondary indices such as 2hFI or OFT. Six hours is the optimal duration of stimulation by Crampton model for rotation sickness studies.

Distinct requirements for the naturally occurring splice forms Stat4alpha and Stat4beta in IL-12 responses.

Signal transducer and activator of transcription (Stat)4 is a signaling molecule required for normal responses to interleukin-12 (IL-12) and is critically involved in inflammatory responses. We have isolated an alternatively spliced isoform of Stat4, termed Stat4beta, which lacks 44 amino acids at the C-terminus, encompassing the putative transcriptional activation domain. To assess the in vivo roles of these Stat4 isoforms, we generated transgenic Stat4-deficient mice expressing Stat4alpha or Stat4beta. Our results indicate that T-cell-specific expression of Stat4alpha or Stat4beta can mediate many aspects of IL-12 signaling including the differentiation of Th1 cells. However, Stat4alpha is required for normal levels of IL-12-induced interferon-gamma production from Th1 cells. Microarray analysis identified 98 genes induced by both Stat4 isoforms, 32 genes induced only by Stat4alpha and 29 genes induced only by Stat4beta. Some induced genes correlate with specific functions including the ability of Stat4beta, but not Stat4alpha, to mediate IL-12-stimulated proliferation. Thus, Stat4alpha and Stat4beta have distinct roles in mediating responses to IL-12.

A cytoskeleton-like role for the bacterial cell wall during engulfment of the Bacillus subtilis forespore.

A hallmark of bacterial endospore formation is engulfment, during which the membrane of one cell (the mother cell) migrates around the future spore, enclosing it in the mother cell cytoplasm. Bacteria lack proteins required for eukaryotic phagocytosis, and previously proteins required for membrane migration remained unidentified. Here we provide cell biological and genetic evidence that three membrane proteins synthesized in the mother cell are required for membrane migration as well as for earlier steps in engulfment. Biochemical studies demonstrate that one of these proteins, SpoIID, is a cell wall hydrolase, suggesting that membrane migration in bacteria can be driven by membrane-anchored cell wall hydrolases. We propose that the bacterial cell wall plays a role analogous to that of the actin and tubulin network of eukaryotic cells, providing a scaffold along which proteins can move.