Analyzer Control System (ACS)-A Software Package for Mass Spectrometer System Operation, Trouble Shooting and Protyping

No abstract availabl

N-(4-[18F]fluorobenzyl)cholylglycine, a novel tracer for PET of enterohepatic circulation of bile acids: radiosynthesis and proof-of-concept studies in rats

Enterohepatic circulation (EHC) of conjugated bile acids is an important physiological process crucial for regulation of intracellular concentrations of bile acids and their function as detergents and signal carriers. Only few bile acid-derived imaging agents have been synthesized and hitherto none have been evaluated for studies of EHC. We hypothesized that N-(4-[F]fluorobenzyl)cholylglycine ([F]FBCGly), a novel fluorine-18 labeled derivative of endogenous cholylglycine, would be a suitable tracer for PET of the EHC of conjugated bile acids, and we report here a radiosynthesis of [F]FBCGly and a proof-of-concept study by PET/MR in rats.A radiosynthesis of [F]FBCGly was developed based on reductive alkylation of glycine with 4-[F]fluorobenzaldehyde followed by coupling to cholic acid. [F]FBCGly was investigated in vivo by dynamic PET/MR in anesthetized rats; untreated or treated with cholyltaurine or rifampicin. Possible in vivo metabolites of [F]FBCGly were investigated by analysis of blood and bile samples, and the stability of [F]FBCGly towards enzymatic de-conjugation by Cholylglycine Hydrolase was tested in vitro.[F]FBCGly was produced with a radiochemical purity of 96% ± 1% and a non-decay corrected radiochemical yield of 1.0% ± 0.3% (mean ± SD; n = 12). PET/MR studies showed that i.v.-administrated [F]FBCGly underwent EHC within 40-60 min with a rapid transhepatic transport from blood to bile. In untreated rats, the radioactivity concentration of [F]FBCGly was approximately 15 times higher in bile than in liver tissue. Cholyltaurine and rifampicin inhibited the biliary secretion of [F]FBCGly. No fluorine-18 metabolites of [F]FBCGly were observed.We have developed a radiosynthesis of a novel fluorine-18 labeled bile acid derivative, [F]FBCGly, and shown by PET/MR that [F]FBCGly undergoes continuous EHC in rats without metabolizing. This novel tracer may prove useful in PET studies on the effect of drugs or diseases on the EHC of conjugated bile acids

Determining T2 relaxation time and stroke onset relationship in ischaemic stroke within apparent diffusion coefficient-defined lesions. A user-independent method for quantifying the impact of stroke in the human brain

Background and objective:In hyperacute ischaemic stroke, T2 of cerebral water increases with time. Quantifying this change may be informative of the extent of tissue damage and onset time. Our objective was to develop a user-unbiased method to measure the effect of cerebral ischaemia on T2 to study stroke onset time-dependency in human acute stroke lesions. Methods:Six rats were subjected to permanent middle cerebral occlusion to induce focal ischaemia, and a consecutive cohort of acute stroke patients (n=38) were recruited within 9 hours from symptom onset. T1-weighted structural, T2 relaxometry, and diffusion MRI for apparent diffusion coefficient (ADC) were acquired. Ischaemic lesions were defined as regions of lowered ADC. The median T2 difference (ΔT2) between lesion and contralateral non-ischaemic control region was determined by the newly-developed spherical reference method, and data compared to that obtained by the mirror reference method. Linear regressions and receiver operating characteristics (ROC) were compared between the two methods. Results:ΔT2 increases linearly in rat brain ischaemia by 1.9 ± 0.8 ms/h during the first 6 hours, as determined by the spherical reference method. In patients, ΔT2 linearly increases by 1.6 ± 1.4 and 1.9 ± 0.9 ms/h in the lesion, as determined by the mirror reference and spherical reference method, respectively. ROC analyses produced areas under the curve of 0.83 and 0.71 for the spherical and mirror reference methods, respectively. Conclusions:Data from the spherical reference method showed that the median T2 increase in the ischaemic lesion is correlated with stroke onset time in a rat as well as in a human patient cohort, opening the possibility of using the approach as a timing tool in clinics.</p

Household food insecurity and childhood overweight in Jamaica and Québec: a gender-based analysis

Background - Childhood overweight is not restricted to developed countries: a number of lower- and middle-income countries are struggling with the double burden of underweight and overweight. Another public health problem that concerns both developing and, to a lesser extent, developed countries is food insecurity. This study presents a comparative gender-based analysis of the association between household food insecurity and overweight among 10-to-11-year-old children living in the Canadian province of Québec and in the country of Jamaica. // Methods - Analyses were performed using data from the 2008 round of the Québec Longitudinal Study of Child Development and the Jamaica Youth Risk and Resiliency Behaviour Survey of 2007. Cross-sectional data were obtained from 1190 10-year old children in Québec and 1674 10-11-year-old children in Jamaica. Body mass index was derived using anthropometric measurements and overweight was defined using Cole's age- and sex-specific criteria. Questionnaires were used to collect data on food insecurity. The associations were examined using chi-square tests and multivariate regression models were used to estimate odds ratios (OR) and 95% confidence intervals. // Results - The prevalence of overweight was 26% and 11% (p < 0.001) in the Québec and Jamaican samples, respectively. In Québec, the adjusted odds ratio for being overweight was 3.03 (95% CI: 1.8-5.0) among children living in food-insecure households, in comparison to children living in food-secure households. Furthermore, girls who lived in food-insecure households had odds of 4.99 (95% CI: 2.4-10.5) for being overweight in comparison to girls who lived in food-secure households; no such differences were observed among boys. In Jamaica, children who lived in food-insecure households had significantly lower odds (OR 0.65, 95% CI: 0.4-0.9) for being overweight in comparison to children living in food-secure households. No gender differences were observed in the relationship between food-insecurity and overweight/obesity among Jamaican children. // Conclusions - Public health interventions which aim to stem the epidemic of overweight/obesity should consider gender differences and other family factors associated with overweight/obesity in both developed and developing countries

Future-proofing and maximizing the utility of metadata: The PHA4GE SARS-CoV-2 contextual data specification package

Background The Public Health Alliance for Genomic Epidemiology (PHA4GE) (https://pha4ge.org) is a global coalition that is actively working to establish consensus standards, document and share best practices, improve the availability of critical bioinformatics tools and resources, and advocate for greater openness, interoperability, accessibility, and reproducibility in public health microbial bioinformatics. In the face of the current pandemic, PHA4GE has identified a need for a fit-for-purpose, open-source SARS-CoV-2 contextual data standard. Results As such, we have developed a SARS-CoV-2 contextual data specification package based on harmonizable, publicly available community standards. The specification can be implemented via a collection template, as well as an array of protocols and tools to support both the harmonization and submission of sequence data and contextual information to public biorepositories. Conclusions Well-structured, rich contextual data add value, promote reuse, and enable aggregation and integration of disparate datasets. Adoption of the proposed standard and practices will better enable interoperability between datasets and systems, improve the consistency and utility of generated data, and ultimately facilitate novel insights and discoveries in SARS-CoV-2 and COVID-19. The package is now supported by the NCBI’s BioSample database

OntoTrek: 3D visualization of application ontology class hierarchies.

An application ontology often reuses terms from other related, compatible ontologies. The extent of this interconnectedness is not readily apparent when browsing through larger textual presentations of term class hierarchies, be it Manchester text format OWL files or within an ontology editor like Protege. Users must either note ontology sources in term identifiers, or look at ontology import file term origins. Diagrammatically, this same information may be easier to perceive in 2 dimensional network or hierarchical graphs that visually code ontology term origins. However, humans, having stereoscopic vision and navigational acuity around colored and textured shapes, should benefit even more from a coherent 3-dimensional interactive visualization of ontology that takes advantage of perspective to offer both foreground focus on content and a stable background context. We present OntoTrek, a 3D ontology visualizer that enables ontology stakeholders-students, software developers, curation teams, and funders-to recognize the presence of imported terms and their domains, ultimately illustrating how projects can capture knowledge through a vocabulary of interwoven community-supported ontology resources

Synthesis and characterisation of indium(iii) bis-thiosemicarbazone complexes: 18 F incorporation for PET imaging

Several structurally related indium chlorido complexes of bis-thiosemicarbazones were prepared, starting from the appropriately substituted bis-thiosemicarbazones, using sodium methoxide in methanol. Detailed NMR studies were conducted to assign the structure including COSY, HSQC, and HMBC techniques. The structures of all indium complexes were solved using single crystal X-ray diffraction. The chlorido ligand was present at the apex of the square pyramidal coordination sphere in all indium complexes. In some complexes, an intermolecular hydrogen bond was present between the chlorine atom and an NH group. Three different indium chlorido complexes were converted into the corresponding fluorido-derivative by a simple halide exchange method using K F. These novel complexes, containing the positron emitting isotope F, may have potential applications in positron emission tomography (PET)