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Quantitative structurereactivity relationships (QSRRs) were investigated for the estimation of the Mayr nucleophilicity parameter N using data sets with 218 nucleophiles (solvent: CH2Cl2) and 88 compounds (solvent: MeCN) extracted from the Mayr's Database of Reactivity Parameters. The best predictions were observed for consensus models of random forests and associative neural networks, trained with empirical 2D and 3D CDK molecular descriptors, which yielded RMSE of 1.54 and 1.97 for independent test sets of the two solvent data sets, respectively. Compounds with silicon atoms were more difficult to predict, as well as classes of compounds with a reduced number of examples in the training set. The models' predictions were consistently more accurate than estimations simply based on the average of the N parameter within the class of the query compound. The possibility of calculating rate constants using the obtained models was also explored. [ABSTRACT FROM AUTHOR]

Spectra-structure relationships were investigated for estimating the anomeric configuration, residues and type of linkages of linear and branched trisaccharides using 13C-NMR chemical shifts. For this study, 119 pyranosyl trisaccharides were used that are trimers of the a or b anomers of D-glucose, D-galactose, D-mannose, L-fucose or L-rhamnose residues bonded through a or b glycosidic linkages of types 1→2, 1→3, 1→4, or 1→6, as well as methoxylated and/or N-acetylated amino trisaccharides. Machine learning experiments were performed for: (1) classification of the anomeric configuration of the first unit, second unit and reducing end; (2) classification of the type of first and second linkages; (3) classification of the three residues: reducing end, middle and first residue; and (4) classification of the chain type. Our previously model for predicting the structure of disaccharides was incorporated in this new model with an improvement of the predictive power. The best results were achieved using Random Forests with 204 di- and trisaccharides for the training set-it could correctly classify 83%, 90%, 88%, 85%, 85%, 75%, 79%, 68% and 94% of the test set (69 compounds) for the nine tasks, respectively, on the basis of unassigned chemical shifts. [ABSTRACT FROM AUTHOR]

Abstract: A machine learning approach was explored for the prediction of the anomeric configuration, residues, and type of linkages of disaccharides using 13C NMR chemical shifts. For this study, 154 pyranosyl disaccharides were used that are dimers of the α or β anomers of d-glucose, d-galactose or d-mannose residues bonded through α or β glycosidic linkages of types 1→2, 1→3, 1→4, or 1→6, as well as methoxylated disaccharides. The 13C NMR chemical shifts of the training set were calculated using the casper (Computer Assisted SPectrum Evaluation of Regular polysaccharides) program, and chemical shifts of the test set were experimental values obtained from the literature. Experiments were performed for (1) classification of the anomeric configuration, (2) classification of the type of linkage, and (3) classification of the residues. Classification trees could correctly classify 67%, 74%, and 38% of the test set for the three tasks, respectively, on the basis of unassigned chemical shifts. The results for the same experiments using Random Forests were 93%, 90%, and 68%, respectively. [Copyright &y& Elsevier]

The representation of metabolic reactions strongly relies on visualization, which is a major barrier for blind users. The NavMol software renders the communication and interpretation of molecular structures and reactions accessible by integrating chemoinformatics and assistive technology. NavMol 3.0 provides a molecular editor for metabolic reactions. The user can start with templates of reactions and build from such cores. Atom-to-atom mapping enables changes in the reactants to be reflected in the products (and vice-versa) and the reaction centres to be automatically identified. Blind users can easily interact with the software using the keyboard and textto- speech technology. [ABSTRACT FROM AUTHOR]

The risk of methicillin-resistant Staphylococcus aureus (MRSA) infection is increasing in both the developed and developing countries. New approaches to overcome this problem are in need. A ligand-based strategy to discover new inhibiting agents against MRSA infection was built through exploration of machine learning techniques. This strategy is based in two quantitative structure–activity relationship (QSAR) studies, one using molecular descriptors (approach A) and the other using descriptors (approach B). In the approach A, regression models were developed using a total of 6645 molecules that were extracted from the ChEMBL, PubChem and ZINC databases, and recent literature. The performance of the regression models was successfully evaluated by internal and external validation, the best model achieved R2 of 0.68 and RMSE of 0.59 for the test set. In general natural product (NP) drug discovery is a time-consuming process and several strategies for dereplication have been developed to overcome this inherent limitation. In the approach B, we developed a new NP drug discovery methodology that consists in frontloading samples with 1D NMR descriptors to predict compounds with antibacterial activity prior to bioactivity screening for NPs discovery. The NMR QSAR classification models were built using 1D NMR data (1H and 13C) as descriptors, from crude extracts, fractions and pure compounds obtained from actinobacteria isolated from marine sediments collected off the Madeira Archipelago. The overall predictability accuracies of the best model exceeded 77% for both training and test sets. [ABSTRACT FROM AUTHOR]

The article offers information on several online application programs which can help blind students in processing molecular structures. It mentions the BrailChem Web Service which navigation is designed particularly for people with visual disorders. It cites the Kekule program which offers information about the presence of bonds, substructures and atoms. It also notes the MOLinsight Web portal which provides efficient navigation experience for students.

Objective: To analyze the early results of coronary surgery without cardiopulmonary bypass using the EuroSCORE risk model., Methods: Out of a series of 1104 consecutive patients undergoing CABG during a 20-month period and whose data were prospectively collected, 1083 patients (98.1%) were operated without cardiopulmonary bypass (CPB) and represent the patient population. Mean age was 65.6 +/- 9.9 years (31-90), 23.1% were female, 77.9% hypertensive, 38.0% diabetic, 22.8% had peripheral vascular disease, 73.0% triple-vessel disease, 54.7% previous myocardial infarction and 67.0% were in CCS class III or IV. Three hundred and forty-one patients (31.5%) were operated on urgently. Surgery was performed with the aid of cardiac stabilizers and intracoronary shunts., Results: The mean number of distal anastomoses was 2.9; the left internal mammary artery was used in 99% of patients. In 10 patients (0.9%), conversion to CPB was required, without mortality or morbidity. Sixteen patients (1.5%) had myocardial infarction; mean troponin T and CK-MB at 24 h were 0.20 +/- 0.43 ng/ml and 28.2 +/- 49.9 U/l respectively. Twenty patients (1.8%) had neurologic deficit, 10 (0.9%) required hemofiltration or dialysis, 229 (21%) received blood transfusions and 135 (14.2%) had atrial fibrillation. Median intubation time was 9 h, and median ICU stay was one day. Median hospital stay was 5 days. Twelve patients died in hospital (1.1%). Thirty-day observed mortality and EuroSCORE-predicted mortality were 1.3% and 4.0% respectively (p < 0.01)., Conclusion: Off-pump CAB surgery has become our preferred method in almost all patients undergoing coronary surgery, without compromising completeness of revascularization. Observed mortality was significantly lower than that predicted by EuroSCORE and the incidence of complications was reasonably low considering the population's risk factors.

Objective: To compare 4 methods of myocardial protection in GABG in terms of markers of myocardial ischemia, mortality, morbidity and mid-term results., Material & Methods: Retrospective study of 241 consecutive patients undergoing isolated > 1 CABG using one of 4 methods: off-pump (OFF, n = 108), cardiopulmonary bypass (CPB) and cardioplegia (CARD, n = 66), CPB and beating heart (BEAT, n = 47), or CPB and ventricular fibrillation (FIBR, n = 20). Mean age was 65.7 +/- 9.3 years and mean EuroSCORE was 3.2 +/- 2.3. The groups were similar in terms of age, gender distribution, body mass index, incidence of smoking, hypertension, renal insufficiency, CCS class, ventricular function and mean EuroSCORE. Serial blood samples were collected for CK-MB and troponin T, preoperatively and 1, 6, 12 and 24 hours after the procedure., Results: Mean number of distal anastomoses was 3.27 BEAT, 2.98 CARD, 2.90 FIBR and 2.55 OFF (p < 0.05 OFF vs. the other 3 groups). Six patients died in hospital (2.5%), 2/47 BEAT (4.2%), 1/66 CARD (1.5%), 1/20 FIBR (5.0%), 2/108 (1.9% OFF) (p = 0.1). The incidence of atrial fibrillation, stroke/TIA and blood transfusion and length of stay were similar between groups (p = 0.1) but there was a tendency for increased incidence of Q-wave MI (p = 0.08) in OFF and combined adverse events in FIBR (p = 0.07). At 12 hours postoperatively, CK-MB and troponin T were significantly higher in FIBR than in CARD or OFF (p < 0.05) and at 24 hours, troponin T remained higher in FIBR than in all other groups (p < 0.05). After a mean follow-up of 19 months, no significant difference was observed between groups in mortality or relief of angina., Conclusion: We were unable to demonstrate the superiority of any one revascularization method over another in terms of mortality, morbidity or length of stay. As shown by lower levels of myocardial markers of ischemia, better myocardial protection was obtained with OFF, BEAT and CARD compared to FIBR. Mid-term survival and relief of angina were similar between groups.

Crystalline 1:1 inclusion complexes with beta-cyclodextrin (beta-CD) and the sodium salt of nimesulide (4-nitro-2-phenoxymethanesulfonanilide), and the sodium salt of the derivative 2-phenoxymethanesulfonanilide, have been prepared by co-precipitation from aqueous solution. The presence of true inclusion complexes was supported by elemental analysis, thermogravimetry and powder X-ray diffraction. FTIR and 13C CP MAS NMR spectroscopy confirmed that no chemical modification of the guests occurred upon formation of inclusion complexes. The reaction of the precursors 2-phenoxynitrobenzene and 2-phenoxyaniline with beta-CD was also studied and crystalline inclusion complexes with a 2:1 (host-to-guest) stoichiometry were isolated. The interaction of the different guest species with beta-CD host molecules was studied theoretically by carrying out ab initio calculations. Favourable inclusion geometries were obtained for the four guests mentioned above. On the other hand, it was found that the inclusion of the neutral guests nimesulide and 2-phenoxymethanesulfonanilide was considerably less favourable. This is in agreement with the experimentally observed difficulty in isolating true inclusion complexes containing these guests and beta-CD. The calculated lower stability is attributed to the different steric hindrance arising from the different conformational preferences of neutral and anionic forms.