Comparing the DNA-damage RBE of intraoperative and conventional electron beams using a hybrid simulation approach.

PURPOSE: Employing electron beam for radiotherapy purposes now has been established as one of the standard cancer treatment modalities. Both dedicated intraoperative and conventional electron beams can be employed in patient irradiation. Due to the differences between accelerating structure and electron beam delivery of dedicated intraoperative radiotherapy (IORT) machines and conventional ones, the initial energy spectra of the produced electron beam by these machines may be different. Accordingly, this study aims to evaluate whether these spectral differences can affect the relevant relative biological effectiveness (RBE) values of intraoperative and conventional electron beams. MATERIALS AND METHODS: A hybrid Monte Carlo simulation approach was considered. At first, the head LIAC12 machine (as an IORT accelerator) and Varian 2100C/D (as a conventional accelerator) were simulated by MCNPX code and electron energy spectra at different depths and off-axis distances were scored for two nominal electron energies of 6 and 12 MeV at the field sizes of 6 and 10 cm. Then, the calculated spectra were imported to MCDS code to estimate the induced DNA-damage RBE values. Finally, the obtained RBE values for intraoperative and conventional electron beams were compared together. RESULTS: The results showed that the RBE values of the intraoperative electron beam are superior to those obtained for conventional electron beam at the same energy/field size combination. Variations of the depth can regularly affect the RBE value for both conventional and intraoperative electron beams, while no ordered variation trend was observed for RBE with changing the off-axis distance. Variations of electron energy and field size can also influence the RBE value for both types of studied electron beams. CONCLUSIONS: From the results, it can be concluded the structural differences between the dedicated IORT and conventional Linacs can lead to distinct initial electron energy spectra for intraoperative and conventional electron beams. These physical differences can finally lead to different RBE values for intraoperative and conventional electron beams at the same energy and field size.

Text mining applications to support health library practice: A case study on marijuana legalization Twitter analytics.

BACKGROUND: Twitter is rich in data for text and data analytics research, with the ability to capture trends. OBJECTIVES: This study examines Canadian tweets on marijuana legalization and terminology used. Presented as a case study, Twitter analytics will demonstrate the varied applications of how this kind of research method may be used to inform library practice. METHODS: Twitter API was used to extract a subset of tweets using seven relevant hashtags. Using open-source programming tools, the sampled tweets were analysed between September to November 2018, identifying themes, frequently used terms, sentiment, and co-occurring hashtags. RESULTS: More than 1,176,000 tweets were collected. The most popular hashtag co-occurrence, two hashtags appearing together, was #cannabis and #CdnPoli. There was a high variance in the sentiment analysis of all collected tweets but most scores had neutral sentiment. DISCUSSION: The case study presents text-mining applications relevant to help make informed decisions in library practice through service analysis, quality analysis, and collection analysis. CONCLUSIONS: Findings from sentiment analysis may determine usage patterns from users. There are several ways in which libraries may use text mining to make evidence-informed decisions such as examining all possible terminologies used by the public to help inform comprehensive evidence synthesis projects and build taxonomies for digital libraries and repositories.

Domino protocol for the synthesis of diversely functionalized derivatives of a novel fused pentacyclic antioxidant/anticancer fluorescent scaffold: Pyrazolo[5'',1'':2',3']pyrimido[4',5':5,6][1,4]thiazino[2,3-b]quinoxaline.

Rising to the challenge of formidable multi-step reaction needed for the synthesis of polycyclic compounds, an efficient one-pot two-step procedure for the synthesis of densely functionalized novel pyrazolo[5″,1'':2',3']pyrimido[4',5':5,6] [1,4]thiazino[2,3-b]quinoxalines from synthetically accessible starting materials 6-bromo-7-chloro-3-cyano-2-(ethylthio)-5-methylpyrazolo[1,5-a]pyrimidine, 3-aminoquinoxaline-2-thiol and some readily accessible alkyl halides was established. The domino reaction pathway involves cyclocondensation/N-alkylation sequence in K2CO3/N,N-dimethyl formamide under heating condition. DPPH free radical scavenging activity of all synthesized pyrazolo[5″,1'':2',3']pyrimido[4',5':5,6][1,4]thiazino[2,3-b]quinoxalines was evaluated to determine their antioxidant potentials. IC50 values were recorded in the range of 29-71 µM. N-benzyl substituted derivative represented the most effective antioxidant activity as well as antiproliferative activity against MCF-7 cells. Moreover, fluorescence in solution for these compounds exhibited strong red emission in the visible region (λflu. = 536-558 nm) with good to excellent quantum yields (61-95%). Due to their interesting fluorescence properties, these novel pentacyclic fluorophores can be used as fluorescent markers and probes for studies in biochemistry and pharmacology.

Synthesis, molecular docking and dynamics studies of pyridazino[4,5-b]quinoxalin-1(2H)-ones as targeting main protease of COVID-19.

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has created a crisis in public health. Because, the 3CLpro, the main protease of SARS-CoV-2, possesses a critical role in coronavirus replication, many efforts have been devoted to developing various inhibitors to prevent the fast spread of COVID-19. In the current work, a number of various pyridazino[4,5-b]quinoxalin-1(2H)-one derivatives bearing thiadiazine and thiadiazole fragments has been prepared via a straightforward and practical strategy involving the reaction of 2-(ethoxycarbonyl)-3-formylquinoxaline 1,4-dioxide with thiocarbohydrazide under reflux conditions. To determine the bioavailability of pyridazino[4,5-b]quinoxalin-1(2H)-one derivatives, Lipinski's rule of five has been carried out. Regarding this rule, none of the synthesized compounds exhibit any deviation from Lipinski's rule of five. Furthermore, molecular docking and molecular dynamics approaches have been implemented to figure out the potential interactions of products with SARS-CoV-2 main protease. The outcomes of molecular docking studies demonstrate that the phenyl and nitrophenyl substituted pyridazino[4,5-b]quinoxalin-1(2H)-one show the lowest binding affinity among the other compounds, indicating a favorable orientation in the active site of the chymotrypsin-like cysteine protease. In addition, the MD simulation performed to evaluate the stability of the protein-ligand complex represents that the average binding energy of the nitrophenyl complex is less than that of the phenyl complex. Therefore, according to the in silico results, the inhibitory effect of the nitrophenyl complex is more significant than the phenyl complex.Communicated by Ramaswamy H. Sarma.

Natural halloysite nanotubes as an efficient catalyst in strecker reaction: the synthesis of α-amino nitriles under solvent-free conditions.

In this work, a green and cost-effective method based on halloysite as natural catalyst for the synthesis of α-amino nitriles via Strecker three-component reaction is introduced. The chemical and physical structure of natural halloysite has characterized thoroughly, and then the effect of different parameters such as the amount of catalyst, solvent, and temperature was optimized in the synthesis of 2-phenyl-2-(phenylamino)acetonitrile as the model reaction. Then, various substituted benzaldehydes and anilines were converted to the desired α-amino nitriles under the optimized conditions. Electronic properties of substituents on aldehydes and aromatic amines have been affected the reaction efficiency. For all substrates, good to excellent yields of the corresponding α-amino nitriles were obtained under solvent-free conditions at room temperature. The catalyst has been recovered and reused five times in successive Strecker reaction.

Pyrido[1,2-e]purine: Design and Synthesis of Appropriate Inhibitory Candidates against the Main Protease of COVID-19.

A series of tricyclic and polycyclic pyrido[1,2-e]purine derivatives were designed and synthesized via a two-step, one-pot reaction of 2,4-dichloro-5-amino-6-methylpyrimidine with pyridine under reflux conditions. Various derivatives of pyrido[1,2-e]purine were also synthesized by substituting the chlorine atom with secondary amines. After careful physiochemical and pharmacokinetic predictions, the inhibitory effects of the synthesized compounds against the main protease of SARS-CoV-2 have been evaluated by molecular docking and molecular dynamics approaches. The in silico results revealed that among all of the studied compounds, the morpholine/piperidine-substituted pyrido[1,2-e]purine derivatives are the best candidates as effective inhibitors of SARS-CoV-2.

An efficient and green one-pot synthesis of tetrahydrobenzo[a]xanthenes, 1,8-dioxo-octahydroxanthenes and dibenzo[a,j]xanthenes by Fe3O4@Agar-Ag as nanocatalyst.

Agar-coated Fe3O4 nanoparticles (Fe3O4@agar) were prepared simply through in situ co-precipitation of Fe2+ and Fe3+ ions via NH4OH in an aqueous solution of Agar. Coating of Ag+ ions on the surface of the latter followed by mild reduction of Ag+ with NaBH4 gives Fe3O4@Agar-Ag NPs. The magnetic Fe3O4@Agar-Ag nanocatalyst was characterized thoroughly by FT-IR, XRD, SEM, TEM, VSM, EDX, TGA, and ICP analyses. Its catalytic activity was assessed in the synthesis of 12-aryl-8,9,10,12-tetrahydrobenzo[a]xanthene-11-one, 14-aryl-14H-dibenzo[a,j]xanthenes, and 1,8-dioxo-octahydroxanthene derivatives through a one-pot condensation of dimedone, 2-naphthol, and aryl aldehydes in EtOH. This novel method represents lots of advantages compared to the previous researches, such as avoiding the toxic catalysts, easy method for isolation of the products, satisfying yields, totally clean conditions, and simplicity of the methodology. This catalytic system is attributed to an eco-friendly process, high catalytic activity, and facility of recovery using an external magnet. A novel and magnetically recyclable catalyst known as Fe3O4@Agar-Ag NPs as a heterogeneous catalyst were synthesized by a simple method. Using this facile, efficient, and eco-friendly Nanocomposite, for the different models of xanthene reaction was represented.

A Dimroth rearrangement approach for the synthesis of selenopheno[2,3-e][1,2,4]triazolo[1,5-c]pyrimidines with cytotoxic activity on breast cancer cells.

New selenopheno[2,3-e][1,2,4]triazolo[1,5-c]pyrimidine derivatives have been synthesized via Dimroth rearrangement by cyclocondensation of 7-cyano-4-hydrazinyl-6-(pyrrolidin-1-yl)selenopheno[3,2-d]pyrimidine with electrophilic carbons of either orthoesters in acetic acid or carbon disulfide in pyridine followed by S-alkylation. All the newly synthesized products have been structurally elucidated. The in vitro anticancer screening of the tricyclic Se-containing heterocycles was accomplished against human breast carcinoma MCF-7 cancerous cell line and L929 cells. Anticancer results revealed that the S-hexyl-substituted compound with an IC50 value of 158.9 µM in 72 h was foremost among others in cytotoxic potency. In the following order, S-pentyl and S-ethyl-substituted derivatives with IC50 values of 216.1 and 396.5 µM were second and third efficient compounds as in anticancer activity, respectively. The inhibitory effects of the mentioned compounds were less on the growth of L929 cells.

Dimroth rearrangement-based synthesis of novel derivatives of [1,3]selenazolo[5,4-e][1,2,4]triazolo[1,5-c]pyrimidine as a new class of selenium-containing heterocyclic architecture.

As a part of our ongoing endeavor towards developing novel heterocyclic architectures, a number of novel Se-containing tricyclic heterocycles of the type [1,3]selenazolo[5,4-e][1,2,4]triazolo[1,5-c]pyrimidine have been synthesized through heteroannulation of a newly produced hydrazino derivative of selenazolo[4,5-d]pyrimidine with either orthoesters or carbon disulfide in pyridine followed by S-alkylation. Moreover, the multistep protocol employed in this investigation provides a new insight into the Dimroth rearrangement in both acidic and basic media as a means for the cyclocondensation of triazole on the selenazolopyrimidine framework leading to selenazolotriazolopyrimidines. The synthesis of new derivatives of novel selenazolotriazolopyrimidines via Dimroth rearrangement in both acidic and basic media is presented.

A magnetic copper organic framework material as an efficient and recyclable catalyst for the synthesis of 1,2,3-triazole derivatives.

In this study, a core-shell magnetic metal organic framework (MOF) catalyst was introduced based on Fe3O4 magnetic nanoparticles (MNPs) and copper organic frameworks. In this catalyst, Fe3O4 MNPs have been coated with MOFs in which copper was the inorganic nodes and 1,3,5-benzenetricarboxylic acid was the organic linkers. Then, the core-shell structures and catalytic efficiency have been confirmed properly and completely with various analyses such as FT-IR, TEM, SEM, TEM mapping, SEM mapping, EDX, PXRD, TGA, ICP and VSM. The Cu moieties in MOF and shell structures can catalyze the synthesis of 1,2,3-triazole derivatives with good to excellent yields in the presence of water as a green solvent. Moreover, this catalyst showed the high reusability due to the super paramagnetic properties.

Challenges with organization, discoverability and access in Canadian open health data repositories.

Introduction: Open health data provides healthcare professionals, biomedical researchers and the general public with access to health data which has the potential to improve healthcare delivery and policy. The challenge is to create and implement appropriate metadata, or structured data about the data, to ensure that data are easy to discover, access and re-use. The goal of this study is to identify, evaluate and compare Canadian open health data repositories for their searching, browsing and navigation functionalities, the richness of their metadata description practices, and their metadata-based filtering mechanisms. Methods: Metadata-based search and browsing was evaluated in addition to the number and nature of metadata elements. Six Canadian open health data repositories across national, provincial and institutional levels were evaluated. Data collected using verbatim text recording was evaluated using an analytical framework based on the 2019 Dataverse North Metadata Best Practices guide and 2019 Data Citation Implementation Project roadmap. Results: All repositories required filtering to access "open health data." All repositories included 'subject' facets for filtering, and 'title' and 'description' on the Results List. Use case evaluations suggest improvements including advanced search, health-specific search terms, records for all repositories, and links to related publications. Discussion: Consistent use of 'title' and 'description' suggests that an interoperable interface is possible. Inconsistencies in records indicate the need for explicit, easy to find mechanisms to access metadata in repositories. The analytical framework represents first draft guidelines for metadata creation and implementation to improve organization, discoverability, and access to Canadian open health data.

Step Forward to Stronger Neutral Organic Superbases: Fused Troponimines.

In this study, using a computational approach, we are pursuing to find a proper answer about the possible application of fused TIs as superbases through the calculation and discussion of standard thermochemistry parameters, like gas-phase basicity (GB) and proton affinity (PA). In some studied cases, the role of aromaticity/antiaromaticity fluctuations supposed to be more important than mesomeric effects. In this sense, nucleus-independent chemical shift (NICS) and anisotropy of the induced current density (ACID) were utilized in this study to probe into the aromaticity-related parameters of the proposed molecules. Results revealed the highest GB/PA values for the molecules having cyclobutadiene in between two troponimines. Additional investigation was performed into the other candidates of cyclobutadiene-fused troponimines by substituting several electron donors along with the changing position of donors. Some novel superbases offered record-holding GB/PA values so that PA magnitudes higher than 300 kcal mol-1 are now feasible for nonphosphorous neutral organic superbases (NOS).

The effect of solvation in torquoselectivity: ring opening of monosubstituted cyclobutenes.

The paradigmatic electrocyclic ring opening of monosubstituted cyclobutenes has been used to diagnose possible solvation effects tuning the torquoselectivity observed in these reactions. This kind of selectivity in electrocyclic reactions is mostly due to strong orbital interactions, particularly when they involve powerful electron donors and acceptors, which also combine with usually milder steric effects. Orbital interactions are established between the cleaving C-C bond and the HOMO/LUMO of the EDG/EWG substituent. This implies that the larger torquoselectivity-featuring substrates may also suffer stronger solvation effects due to the higher polarity imposed by the substituent. This premise is tested and the source of solvation effects as a consequence of substitution analyzed.

Synthesis, X-ray and Fluorescence Characteristics of Pyrimido[5,4-e]thiazolo[3,2-a]pyrimidine as a Novel Heterocyclic System.

Derivatives of a new heterocyclic system, pyrimido[5,4-e]thiazolo[3,2-a]pyrimidine 3, were prepared by sequential treatment of ethyl 4-chloro-2-(methylthio)pyrimidine-5-carboxylate 1 with 4,5-dihydrothiazol-2-amine 2 and various secondary amines. Single crystal X-ray analysis confirmed the structure of the regioisomer 3. The photophysical characterization of these new compounds was performed by UV/VIS absorption and fluorescence emission spectroscopy. Out of six derivatives studied, only four products 4a-d showed relatively strong fluorescence intensity. The relevant photophysical parameters for all derivatives in this series, including quantum yields and Stokes shifts for the best fluorophores are given.

Synthesis, characterization and in vitro anticancer evaluations of two novel derivatives of deferasirox iron chelator.

Iron (Fe) chelation therapy was initially designed to alleviate the toxic effects of excess Fe evident in Fe-overload diseases. However, the novel toxicological properties of some Fe chelator-metal complexes have shifted significant attention to their application in cancer chemotherapy. The present study investigates the new role of deferasirox as an anticancer agent due to its ability to chelate with iron. Because of aminoacids antioxidant effect, deferasirox and its two novel amino acid derivatives have been synthesized through the treatment of deferasirox with DCC as well as glycine or phenylalanine methyl ester. All new compounds have been characterized by elemental analysis, FT-IR NMR and mass spectrometry. Therefore, the cytotoxicity of these compounds was screened for antitumor activity against some cell lines using cisplatin as a comparative standard by MTT assay and Flow cytometry. The impact of iron in the intracellular generation of reactive oxygen species was assessed on HT29 and MDA-MB-231 cells. The potential of the synthesized iron chelators for their efficacy to protect cells against model oxidative injury induced was compared. The reactive oxygen species intracellular fluorescence intensity were measured and the result showed that the reactive oxygen species intensity after iron incubation increased while after chelators incubation the reactive oxygen species intensity were decreased significantly. Besides, the effect of the synthesized compounds on mouse fibroblast cell line (L929) was simultaneously evaluated as control. The pharmacological results showed that deferasirox and its two novel aminoacid derivatives were potent anticancer agents.

PYRIMIDOOXADIAZINE AND TRIAZOLOPYRIMIDOOXADIAZINE DERIVATIVES: SYNTHESIS AND CYTOTOXIC EVALUATION IN HUMAN CANCER CELL LINES.

In vitro antiproliferative activities of some pyrimido[4,5-e][1,3,4]oxadiazine and [1,2,4]triazolo[4',3':1,2]pyrimido[4,5-e][1,3,4]oxadiazine derivatives were examined in human malignant cancer cell lines. All synthesized compounds inhibited the growth of malignant cells in a dose dependent manner, but among them 1,5,7-trimethyl-3-phenyl-1H-[1,2,4]triazolo[4',3':1,2]pyrimido[4,5-e][1,3,4]oxadiazine and [(1,5-dimethyl-3-phenyl-1H-[1,2,4]triazolo[4',3':1,2]pyrimido[4,5-e][1,3,4]oxadiazin-7-yl)sulfanyl]acetonitrile, both with triazole moiety, were found to be more effective than other compounds; they also induced a sub-G1 peak in the flow cytometry histogram of treated cells compared to controls, indicating that apoptotic cell death is involved in toxicity they induce. The results showed that compounds with triazole moiety fused to pyrimido[4,5-e] [1,3,4]oxadiazine derivatives are more active than those bearing chlorine or pyrrolidine groups at C-7 position.

Structure and vibrational analysis of methyl 3-amino-2-butenoate.

The molecular structure and vibrational spectra of methyl 3-(amino)-2-butenoate (MAB) and its deuterated analogous, D(3)MAB, were investigated using density functional theory (DFT) calculations. The geometrical parameters and harmonic vibrational wavenumbers of MAB and D(3)MAB were obtained at the B3LYP/6-311++G(d,p) level. The calculated vibrational wavenumbers were compared with the corresponding experimental results. The assignment of the IR and Raman spectra of MAB and D(3)MAB was facilitated by calculating the anharmonic wavenumbers at the B3LYP/6-311G(d,p) level as well as recording and calculating the MAB spectra in CCl(4) solution. The assigned normal modes were compared with a similar molecule, 4-amino-3-penten-2-one (APO). The theoretical results were in good agreement with the experimental data. All theoretical and experimental results indicate that substitution of a methyl group with a methoxy group considerably weakens the intramolecular hydrogen bond and reduces the π-electron delocalization in the chelated ring system. The IR spectra also indicate that in the solid state, MAB is not only engaged in an intramolecular hydrogen bond, but also forms an intermolecular hydrogen bond. However, the intermolecular hydrogen bond will be removed in dilute CCl(4) solution.

Health information support provided by professional associations in Canada.

BACKGROUND: Healthcare practitioners in Alberta and across Canada have varying levels of access to information resources depending on their institutional and professional affiliations, yet access to current health information is critical for all. OBJECTIVES: To determine what information resources and services are provided by Albertan and Canadian professional health associations to their members. METHODS: Representatives of professional colleges and associations were interviewed regarding information resources and services offered to members and perceptions of their members' information needs. RESULTS: National-level associations are more likely to provide resources than provincial ones. There is a clear distinction between colleges and associations in terms of information offered: colleges provide regulatory information, while associations are responsible for provision of clinical information resources. Only half of the associations interviewed provide members with access to licensed databases, with cost being a major barrier. CONCLUSIONS: There is considerable variation in the number of electronic resources and the levels of information support provided by professional health associations in Alberta and Canada. Access and usage vary among the health professions. National licensing of resources or creation of a portal linking to freely available alternatives are potential options for increasing access and awareness.

Molecular iodine promoted synthesis of new pyrazolo[3,4-d]pyrimidine derivatives as potential antibacterial agents.

Iodocyclization of 5-amino-1-(2,4-dinitrophenyl)-1H-4-pyrazolcarboxamides with aromatic aldehydes gave a new series of pyrazolo[3,4-d]pyrimidine derivatives in a single step and their antibacterial activity comparable to Streptomycin as reference drug was evaluated.