Mining Relational Paths in Integrated Biomedical Data

Much life science and biology research requires an understanding of complex relationships between biological entities (genes, compounds, pathways, diseases, and so on). There is a wealth of data on such relationships in publicly available datasets and publications, but these sources are overlapped and distributed so that finding pertinent relational data is increasingly difficult. Whilst most public datasets have associated tools for searching, there is a lack of searching methods that can cross data sources and that in particular search not only based on the biological entities themselves but also on the relationships between them. In this paper, we demonstrate how graph-theoretic algorithms for mining relational paths can be used together with a previous integrative data resource we developed called Chem2Bio2RDF to extract new biological insights about the relationships between such entities. In particular, we use these methods to investigate the genetic basis of side-effects of thiazolinedione drugs, and in particular make a hypothesis for the recently discovered cardiac side-effects of Rosiglitazone (Avandia) and a prediction for Pioglitazone which is backed up by recent clinical studies

Pharmacokinetics and Safety of Fluconazole in Young Infants Supported with Extracorporeal Membrane Oxygenation

Candida infections are a leading cause of infectious disease-related death in infants supported with extracorporeal membrane oxygenation (ECMO). The ECMO circuit can alter drug pharmacokinetics (PK), thus standard fluconazole dosing in children on ECMO may result in suboptimal drug exposure. This study determined the PK of fluconazole in infants on ECMO

Effects of Visible Light on Gas Sensors: From Inorganic Resistors to Molecular Material-Based Heterojunctions

In the last two decades, many research works have been focused on enhancing the properties of gas sensors by utilising external triggers like temperature and light. Most interestingly, the light-activated gas sensors show promising results, particularly using visible light as an external trigger that lowers the power consumption as well as improves the stability, sensitivity and safety of the sensors. It effectively eliminates the possible damage to sensing material caused by high operating temperature or high energy light. This review summarises the effect of visible light illumination on both chemoresistors and heterostructure gas sensors based on inorganic and organic materials and provides a clear understanding of the involved phenomena. Finally, the fascinating concept of ambipolar gas sensors is presented, which utilised visible light as an external trigger for inversion in the nature of majority charge carriers in devices. This review should offer insight into the current technologies and offer a new perspective towards future development utilising visible light in light-assisted gas sensors

Statistical modeling and optimization of cellulase production by Bacillus licheniformis NCIM 5556 isolated from the hot spring, Maharashtra, India

Cellulase shows great interest in the field of organic acids, and biotechnology industries. Cellulase-producing thermophilic bacteria was isolated from West Coast hot spring (Rajapur, Ratnagiri District of Maharashtra (Lat. 16°38′42″N; long. 73°31′53″E) and identified as Bacillus licheniformis. Out of seven variables in the cellulase production medium, four variables such as carboxy methyl cellulose (CMC), calcium chloride, Tween-20, and temperature were screened through Plackett–Burman design and further optimized through response surface methodology (RSM) for higher cellulase production. The optimal conditions were found to be CMC, 19.21 g/L, CaCl2·6H2O, 25.06 mg/L, Tween-20, 2.96 mL/L and temperature 43.35 °C. The high cellulase production 42.99 IU/mL was achieved in a 7 L scale bio fermenter using optimal conditions. A 3 fold increase in cellulase production was achieved by RSM model. These methods have proven suitable to optimize cellulase production by a thermophilic Bacillus

A simple and selective liquid chromatography- tandem mass spectrometry method for determination of ε-aminocaproic acid in human plasma

Understanding the clinical pharmacology of the antifibrinolytic drug epsilon-aminocaproic acid (EACA) is critical for rational drug administration in children. The aim of this study is to develop a reliable assay for the determination of EACA in human plasma. We describe a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) assay for EACA in human plasma. Sample preparation involved plasma dilution (1:2040), followed by reversed-phase chromatographic separation and selective detection using tandem mass spectrometry. EACA had a linear range of 1 - 250 μg/mL. The intraday precision based on the standard deviation of replicates of quality control samples ranged from 4.7 to 10.4% and the accuracy ranged from 92-106%. The interday precision ranged from 4.6 to 9.8% and the accuracy ranged from 95-103%. Stability studies showed that EACA was stable during the conditions for sample preparation and storage. The described method is robust and successfully employed for clinical studies of EACA in childre

A sensitive and selective liquid chromatography/tandem mass spectrometry method for quantitative analysis of efavirenz in human plasma.

A selective and a highly sensitive method for the determination of the non-nucleoside reverse transcriptase inhibitor (NNRTI), efavirenz, in human plasma has been developed and fully validated based on high performance liquid chromatography tandem mass spectrometry (LC-MS/MS). Sample preparation involved protein precipitation followed by one to one dilution with water. The analyte, efavirenz was separated by high performance liquid chromatography and detected with tandem mass spectrometry in negative ionization mode with multiple reaction monitoring. Efavirenz and ¹³C₆-efavirenz (Internal Standard), respectively, were detected via the following MRM transitions: m/z 314.20243.90 and m/z 320.20249.90. A gradient program was used to elute the analytes using 0.1% formic acid in water and 0.1% formic acid in acetonitrile as mobile phase solvents, at a flow-rate of 0.3 mL/min. The total run time was 5 min and the retention times for the internal standard (¹³C₆-efavirenz) and efavirenz was approximately 2.6 min. The calibration curves showed linearity (coefficient of regression, r>0.99) over the concentration range of 1.0-2,500 ng/mL. The intraday precision based on the standard deviation of replicates of lower limit of quantification (LLOQ) was 9.24% and for quality control (QC) samples ranged from 2.41% to 6.42% and with accuracy from 112% and 100-111% for LLOQ and QC samples. The inter day precision was 12.3% and 3.03-9.18% for LLOQ and quality controls samples, and the accuracy was 108% and 95.2-108% for LLOQ and QC samples. Stability studies showed that efavirenz was stable during the expected conditions for sample preparation and storage. The lower limit of quantification for efavirenz was 1 ng/mL. The analytical method showed excellent sensitivity, precision, and accuracy. This method is robust and is being successfully applied for therapeutic drug monitoring and pharmacokinetic studies in HIV-infected patients

Quantitative changes in gait parameters after central corpectomy for cervical spondylotic myelopathy

Object: In this study, quantitative gait analysis is used to describe the changes in the kinematic and kinetic parameters of gait after central corpectomy in patients with cervical spondylotic myelopathy (CSM). Methods: Six men with CSM that was categorized preoperatively as Nurick Grade 3 or 4 were assessed using quantitative gait analysis. The values of various kinematic and kinetic parameters, physiological cost index, and range of motion (ROM) in the lower-limb joints were computed preoperatively as well as at follow-up review 12 months or more postoperatively. Patients also received scores based on the Nurick and Japanese Orthopaedic Association (JOA) lower-limb functional scales pre- and postoperatively. The mean Nurick grade improved from 3.3 to 2 (p = 0.02) and the mean JOA lower-limb score improved from 4.2 to 6 (p = 0.02). The forward ground reaction force showed a statistically significant increase from 10.8 ± 4.1% body weight to 12.1 ± 3.6% body weight (p = 0.04). There was a significant improvement in the ROM at the knees, from 48.6 ± 7.7° to 54.2 ± 5.2°(p = 0.03). There was an increase in the mean walking speed, stride length, percentage of single-limb support time, vertical and backward ground reaction forces, and ROM at the hips in the postoperative gait analysis. These results indicate an improved stability of gait as well as greater flexibility in the knee after decompression of the spinal cord. These changes correlated with an improvement in the functional status of patients with CSM after central corpectomy. Conclusions: Gait analysis can be used as a quantitative tool in the pre- and postoperative evaluation of patients with CSM

π-Extended Porphyrin–Phthalocyanine Heterojunction Devices Exhibiting High Ammonia Sensitivity with a Remarkable Light Effect

International audienc

Liquid Chromatography-Tandem Mass Spectrometry Assays for Therapeutic Drug Monitoring of Cefepime

With the development and growth of multi-drug resistance organisms, therapeutic drug monitoring (TDM) has become an increasingly common tool to assure the efficacy and safety of antimicrobial therapy. The requirement for TDM has not routinely extended to cephalosporins, such as cefepime, due to their wide therapeutic window. However, the implementation of TDM for cefepime is becoming increasingly important as many Gram-negative bacteria have adapted mechanisms that increase resistance to antimicrobials and therefore require higher concentrations of cefepime for bacterial eradication. Additionally, pharmacokinetic variability and difficulty in treating patients, especially those who are critically ill or those with renal dysfunction, necessitate TDM to ensure optimal cefepime concentrations. This review aims to assess and evaluate the techniques currently utilized to quantify cefepime in both plasma and serum in terms of usefulness for feasible and readily adaptable bedside cefepime TDM

Molecular Engineering of Silicon Phthalocyanine to Improve the Charge Transport and Ammonia Sensing Properties of Organic Heterojunction Gas Sensors

Abstract Novel organic heterostructures fabricated with a bilayer consisting of an axially substituted silicon phthalocyanine (R2‐SiPc) derivative and lutetium bis‐phthalocyanine (LuPc2) are investigated for their ammonia sensing properties. Surface and microstructure characterization of the heterostructure films reveal either compact or highly porous surface topography in (345F)2‐SiPc and Cl2‐SiPc‐based heterostructures, while electrical characterization reveals a strong influence of the axial substituent in R2‐SiPc on NH3 sensing capabilities. Electrical characterization further demonstrates an apparent energy barrier for interfacial charge transport, which is higher in the (345F)2‐SiPc/LuPc2 heterojunction device. In‐depth charge transport studies by impedance spectroscopy further reveal a resistive interface in (345F)2‐SiPc/LuPc2 and faster bulk and interfacial charge transport in Cl2‐SiPc/LuPc2 heterojunction devices. Different interfacial charge transport capabilities and surface topographies affect NH3 sensing properties of the two heterojunction devices, in which (345F)2‐SiPc/LuPc2 reveals a fast and non‐linear response with a limit of detection (LOD) of 310 ppb, while Cl2‐SiPc/LuPc2 exhibits a slow, and linear response to NH3 with LOD of 100 ppb. Finally, different metrological parameters of the two sensors are correlated to the respective gas‐material interactions, in which adsorption and diffusion regimes are modulated by the surface topography and hydrophobicity of the sensing layer