Opening Access To Practice-based Evidence in Clinical Decision Support Systems with Natural Query Language

Evidence-based medicine can be effective only if constantly tested against errors in medical practice. Clinical record database summarization supported by a machine allows allow to detect anomalies and therefore help detect the errors in early phases of care. Summarization system is a part of Clinical Decision Support Systems however it cannot be used directly by the stakeholder as long as s/he is not able to query the clinical record database. Natural Query Languages allow opening access to data for clinical practitioners, that usually do not have knowledge about articial query languages. Results: We have developed general purpose reporting system called Ask Data Anything (ADA) that we applied to a particular CDSS implementation. As a result, we obtained summarization system that opens the access for these of clinical researchers that were excluded from the meaningful summary of clinical records stored in a given clinical database. The most significant part of the component - NQL parser - is a hybrid of Controlled Natural Language (CNL) and pattern matching with a prior error repair phase. Equipped with reasoning capabilities due to the intensive use of semantic technologies, our hybrid approach allows one to use very simple, keyword-based (even erroneous) queries as well as complex CNL ones with the support of a predictive editor. By using ADA sophisticated summarizations of clinical data are produced as a result of NQL query execution. In this paper, we will present the main ideas underlying ADA component in the context of CDSS

Hot Start PCR with heat-activatable primers: a novel approach for improved PCR performance

The polymerase chain reaction (PCR) is widely used for applications which require a high level of specificity and reliability, such as genetic testing, clinical diagnostics, blood screening, forensics and biodefense. Great improvements to PCR performance have been achieved by the use of Hot Start activation strategies that aim to prevent DNA polymerase extension until more stringent, higher temperatures are reached. Herein we present a novel Hot Start activation approach in PCR where primers contain one or two thermolabile, 4-oxo-1-pentyl (OXP) phosphotriester (PTE) modification groups at 3′-terminal and 3′-penultimate internucleotide linkages. Studies demonstrated that the presence of one or more OXP PTE modifications impaired DNA polymerase primer extension at the lower temperatures that exist prior to PCR amplification. Furthermore, incubation of the OXP-modified primers at elevated temperatures was found to produce the corresponding unmodified phosphodiester (PDE) primer, which was then a suitable DNA polymerase substrate. The OXP-modified primers were tested in conventional PCR with endpoint detection, in one-step reverse transcription (RT)–PCR and in real-time PCR with SYBR Green I dye and Taqman® probe detection. When OXP-modified primers were used as substitutes for unmodified PDE primers in PCR, significant improvement was observed in the specificity and efficiency of nucleic acid target amplification

Structural evidence of the species dependent albumin binding of the modified cyclic phosphatidic acid with cytotoxic properties

Cyclic phosphatidic acids (cPAs) are naturally occurring, very active signalling molecules, which are involved in several pathological states, such as cancer, diabetes or obesity. As molecules of highly lipidic character found in the circulatory system, cPAs are bound and transported by the main extracellular lipid binding protein–serum albumin. Here, we present the detailed interactions between human serum albumin (HSA) and equine serum albumin (ESA) with a derivative of cPA, 1-O-myristoyl-sn-glycerol-2,3-cyclic phosphorodithioate (Myr-2S-cPA). Initial selection of the ligand used for the structural study was made by the analysis of the therapeutically promising properties of the sulfur containing analogues of cPA in respect to the unmodified lysophospholipids (LPLs). Substitution of one or two non-bridging oxygen atoms in the phosphate group with one or two sulfur atoms increases the cytotoxic effect of cPAs up to 60% on the human prostate cancer (PC) cells. Myr-2S-cPA reduces cancer cell viability in a dose-dependent manner, with IC(50) value of 29.0 μM after 24 h incubation, which is almost 30% lower than IC(50) of single substituted phosphorothioate cPA. Although, the structural homology between HSA and ESA is big, their crystal complexes with Myr-2S-cPA demonstrate significantly different mode of binding of this LPL analogue. HSA binds three molecules of Myr-2S-cPA, whereas ESA only one. Moreover, none of the identified Myr-2S-cPA binding sites overlap in both albumins