Induced Pluripotent Stem Cell-Derived Cardiac Progenitors Differentiate to Cardiomyocytes and Form Biosynthetic Tissues.

Induced pluripotent stem cell-derived cardiac progenitors differentiate to cardiomyocytes and form biosynthetic tissues.

PLoS One. 2013; 8(6): e65963
Christoforou N, Liau B, Chakraborty S, Chellapan M, Bursac N, Leong KW

The mammalian heart has little capacity to regenerate, and following injury the myocardium is replaced by non-contractile scar tissue. Consequently, increased wall stress and workload on the remaining myocardium leads to chamber dilation, dysfunction, and heart failure. Cell-based therapy with an autologous, epigenetically reprogrammed, and cardiac-committed progenitor cell source could potentially reverse this process by replacing the damaged myocardium with functional tissue. However, it is unclear whether cardiac progenitor cell-derived cardiomyocytes are capable of attaining levels of structural and functional maturity comparable to that of terminally-fated cardiomyocytes. Here, we first describe the derivation of mouse induced pluripotent stem (iPS) cells, which once differentiated allow for the enrichment of Nkx2-5(+) cardiac progenitors, and the cardiomyocyte-specific expression of the red fluorescent protein. We show that the cardiac progenitors are multipotent and capable of differentiating into endothelial cells, smooth muscle cells and cardiomyocytes. Moreover, cardiac progenitor selection corresponds to cKit(+) cell enrichment, while cardiomyocyte cell-lineage commitment is concomitant with dual expression of either cKit/Flk1 or cKit/Sca-1. We proceed to show that the cardiac progenitor-derived cardiomyocytes are capable of forming electrically and mechanically coupled large-scale 2D cell cultures with mature electrophysiological properties. Finally, we examine the cell progenitors’ ability to form electromechanically coherent macroscopic tissues, using a physiologically relevant 3D culture model and demonstrate that following long-term culture the cardiomyocytes align, and form robust electromechanical connections throughout the volume of the biosynthetic tissue construct. We conclude that the iPS cell-derived cardiac progenitors are a robust cell source for tissue engineering applications and a 3D culture platform for pharmacological screening and drug development studies. HubMed – drug


Extracting drug-drug interaction from the biomedical literature using a stacked generalization-based approach.

PLoS One. 2013; 8(6): e65814
He L, Yang Z, Zhao Z, Lin H, Li Y

Drug-drug interaction (DDI) detection is particularly important for patient safety. However, the amount of biomedical literature regarding drug interactions is increasing rapidly. Therefore, there is a need to develop an effective approach for the automatic extraction of DDI information from the biomedical literature. In this paper, we present a Stacked Generalization-based approach for automatic DDI extraction. The approach combines the feature-based, graph and tree kernels and, therefore, reduces the risk of missing important features. In addition, it introduces some domain knowledge based features (the keyword, semantic type, and DrugBank features) into the feature-based kernel, which contribute to the performance improvement. More specifically, the approach applies Stacked generalization to automatically learn the weights from the training data and assign them to three individual kernels to achieve a much better performance than each individual kernel. The experimental results show that our approach can achieve a better performance of 69.24% in F-score compared with other systems in the DDI Extraction 2011 challenge task. HubMed – drug


Reductions in HIV/STI Incidence and Sharing of Injection Equipment among Female Sex Workers Who Inject Drugs: Results from a Randomized Controlled Trial.

PLoS One. 2013; 8(6): e65812
Strathdee SA, Abramovitz D, Lozada R, Martinez G, Rangel MG, Vera A, Staines H, Magis-Rodriguez C, Patterson TL

We evaluated brief combination interventions to simultaneously reduce sexual and injection risks among female sex workers who inject drugs (FSW-IDUs) in Tijuana and Ciudad Juarez, Mexico during 2008-2010, when harm reduction coverage was expanding rapidly in Tijuana, but less so in Juarez.FSW-IDUs ?18 years reporting sharing injection equipment and unprotected sex with clients within the last month participated in a randomized factorial trial comparing four brief, single-session conditions combining either an interactive or didactic version of a sexual risk intervention to promote safer sex in the context of drug use, and an injection risk intervention to reduce sharing of needles/injection paraphernalia. Women underwent quarterly interviews and testing for HIV, syphilis, gonorrhea, Chlamydia and Trichomonas, blinding interviewers and assessors to assignment. Poisson regression with robust variance estimation and repeated measures ordinal logistic regression examined effects on combined HIV/STI incidence and receptive needle sharing frequency.Of 584 initially HIV-negative FSW-IDUs, retention was ?90%. After 12 months, HIV/STI incidence decreased >50% in the interactive vs. didactic sex intervention (Tijuana:AdjRR:0.38,95% CI:0.16-0.89; Juarez: AdjRR:0.44,95% CI:0.19-0.99). In Juarez, women receiving interactive vs. didactic injection risk interventions decreased receptive needle-sharing by 85% vs. 71%, respectively (p?=?0.04); in Tijuana, receptive needle sharing declined by 95%, but was similar in active versus didactic groups. Tijuana women reported significant increases in access to syringes and condoms, but Juarez women did not.After 12 months in both cities, the interactive sexual risk intervention significantly reduced HIV/STI incidence. Expanding free access to sterile syringes coupled with brief, didactic education on safer injection was necessary and sufficient for achieving robust, sustained injection risk reductions in Tijuana. In the absence of expanding syringe access in Juarez, the injection risk intervention achieved significant, albeit more modest reductions, suggesting that community-level interventions incorporating harm reduction are more powerful than individual-level NCT00840658. HubMed – drug