The availability of scientific bibliographies through online databases provides a rich source of information for scientists to support their research. However, the risk of this pervasive availability is that an individual researcher may fail to find relevant information that is outside the direct scope of interest. Following Swanson's ABC model of disjoint but complementary structures in the biomedical literature, we have developed a discovery support tool to systematically analyze the scientific literature in order to generate novel and plausible hypotheses. In this case report, we employ the system to find potentially new target diseases for the drug thalidomide. We find solid bibliographic evidence suggesting that thalidomide might be useful for treating acute pancreatitis, chronic hepatitis C, Helicobacter pylori-induced gastritis, and myasthenia gravis. However, experimental and clinical evaluation is needed to validate these hypotheses and to assess the trade-off between therapeutic benefits and toxicities.

In acute myeloid leukemia (AML), several signaling pathways such as the phosphatidylinositol-3-kinase/AKT and the mammalian target of rapamycin (PI3K/AKT/mTOR) pathway are deregulated and constitutively activated as a consequence of genetic and cytogenetic abnormalities. We tested the effectiveness of PI3K/AKT/mTOR-targeting therapies and tried to identify alterations that associate with treatment sensitivity. By analyzing primary samples and cell lines, we observed a wide range of cytotoxic activity for inhibition of AKT (MK-2206), mTORC1 (rapamycin) and PI3K/mTORC1/2 (BEZ-235) with a high sensitivity of cells carrying an MLL rearrangement. In vivo PI3K/mTOR inhibition delayed tumor progression, reduced tumor load and prolonged survival in an MLL-AF9(+)/FLT3-ITD(+) xenograft mouse model. By performing targeted amplicon sequencing in 38 MLL-AF9(+) and 125 cytogenetically normal AML patient samples, we found a high additional mutation rate for genes involved in growth factor signaling in 79% of all MLL-AF9(+) samples, which could lead to a possible benefit of this cohort. PI3K/mTOR inhibition for 24 h led to the cross-activation of the ERK pathway. Further in vitro studies combining PI3K/mTOR and ERK pathway inhibition revealed highly synergistic effects in apoptosis assays. Our data implicate a possible therapeutic benefit of PI3K/mTOR inhibition in the MLL-mutated subgroup. Inhibiting rescue pathways could improve the therapeutic efficacy of PI3K-targeted therapies in AML.

he Blood Products Advisory Committee of the Food and Drug Administration (FDA) recently recommended the approval of the use of solvent T and detergent treatment for fresh-frozen plasma (FFP). The FDA is expected to issue soon a license to VI.Technologies, Inc. (VITEX, New York, NY) to produce solventldetergent (SD)-treated plasma (SD plasma). Because an estimated 2 million units of plasma are transfused in the United States each year, the availability of an alternative blood component will likely have a significant impact on physician practices and on the supply of, and demand for, FFP This report reviews issues surrounding the development of SD technologies for use in virus inactivation, current clinical data relevant to the use of SD plasma, and answers to some commonly asked questions. The review is intended not to establish a standard or requirement for the use of FFP or SD plasma, but to provide background information for medical staffs as they consider transfusion alternatives. Development of guidelines or standards for voluntary compliance will require additional clinical data.Currently, most FFP is prepared in blood centers as a by-product of whole-blood processing, although FFP can also be prepared by plasmapheresis. FFP is a relatively safe biologic; its overall risk is estimated at 7.5 adverse events per 10,000 units transfused and 3.7 adverse events per 1,000 ABBREVIATIONS: AHF = anti-hemophilic factor; FDA = Food and Drug Administration; FFP = fresh-frozen plasma; HAV = hepatitis A virus; HBV = hepatitis B virus; HCV = hepatitis C virus; HIV = human immunodeficiency virus; IU = International units; SD = solventldetergent (treatment); TNBP = tri(n-buty1)phosphate; lTP = thrombotic thrombocytopenic purpura.From the American Association of Blood Banks Ad Hoc Committee on SolventlDetergent-Treated Plasma.

Compared with hetastarch (HS), the low molecular weight analog pentastarch (PS) has been reported to be equally effective for granulocyte collection by centrifugal leukapheresis, to result in fewer adverse donor reactions (ADR), and to have a more rapid elimination profile. We prospectively compared the granulocyte collection efficiency (GCE), granulocyte yield, and ADR in 72 randomly paired granulocytapheresis procedures from 36 volunteer donors using the model CS-3000 Plus Blood Cell Separator (CS) and either PS or HS as the sedimenting agent. Paired collections from each donor allowed us to compare the two agents directly while controlling for intrinsic donor differences. In 33 of 36 (92%) donors, HS procedures were significantly more efficient than PS procedures (P < .001). As an average, HS collections yielded 2.3 +/- 0.67 x 10(10) granulocytes at 58% +/- 8.8% GCE, whereas PS procedures resulted in 1.4 +/- 0.76 x 10(10) granulocytes at 33% +/- 15% GCE. No starch-induced ADR were seen with either agent. For granulocyte harvests using the CS, (1) in most donors, using HS as the red blood cell sedimenting agent during centrifugal leukapheresis results in significantly higher (nearly twofold) GCE and larger granulocyte yields in comparison with using PS, (2) ADR were not observed with either agent, and (3) the potential benefit of more rapid PS elimination should be balanced against significantly lower granulocyte yields.

Literature‐based discovery has resulted in new knowledge. In the biomedical context, Don R. Swanson has generated several literature‐based hypotheses that have been corroborated experimentally and clinically. In this paper, we propose a two‐step model of the discovery process in which hypotheses are generated and subsequently tested. We have implemented this model in a Natural Language Processing system that uses biomedical Unified Medical Language System (UMLS) concepts as its unit of analysis. We use the semantic information that is provided with these concepts as a powerful filter to successfully simulate Swanson's discoveries of connecting Raynaud's disease with fish oil and migraine with a magnesium deficiency.