Using semantic clustering to support situation awareness on Twitter: The case of World Views

In recent years, situation awareness has been recognised as a critical part of effective decision making, in particular for crisis management. One way to extract value and allow for better situation awareness is to develop a system capable of analysing a dataset of multiple posts, and clustering consistent posts into different views or stories (or, world views). However, this can be challenging as it requires an understanding of the data, including determining what is consistent data, and what data corroborates other data. Attempting to address these problems, this article proposes Subject-Verb-Object Semantic Suffix Tree Clustering (SVOSSTC) and a system to support it, with a special focus on Twitter content. The novelty and value of SVOSSTC is its emphasis on utilising the Subject-Verb-Object (SVO) typology in order to construct semantically consistent world views, in which individuals---particularly those involved in crisis response---might achieve an enhanced picture of a situation from social media data. To evaluate our system and its ability to provide enhanced situation awareness, we tested it against existing approaches, including human data analysis, using a variety of real-world scenarios. The results indicated a noteworthy degree of evidence (e.g., in cluster granularity and meaningfulness) to affirm the suitability and rigour of our approach. Moreover, these results highlight this article's proposals as innovative and practical system contributions to the research field

Endoperoxide antimalarials: development, structural diversity and pharmacodynamic aspects with reference to 1,2,4-trioxane-based structural scaffold

Mithun Rudrapal, Dipak Chetia Department of Pharmaceutical Sciences, Dibrugarh University, Dibrugarh, India Abstract: Malaria disease continues to be a major health problem worldwide due to the emergence of multidrug-resistant strains of Plasmodium falciparum. In recent days, artemisinin (ART)-based drugs and combination therapies remain the drugs of choice for resistant P. falciparum malaria. However, resistance to ART-based drugs has begun to appear in some parts of the world. Endoperoxide compounds (natural/semisynthetic/synthetic) representing a huge number of antimalarial agents possess a wide structural diversity with a desired antimalarial effectiveness against resistant P. falciparum malaria. The 1,2,4-trioxane ring system lacking the lactone ring that constitutes the most important endoperoxide structural scaffold is believed to be the key pharmacophoric moiety and is primarily responsible for the pharmacodynamic potential of endoperoxide-based antimalarials. Due to this reason, research into endoperoxide, particularly 1,2,4-trioxane-, 1,2,4-trioxolane- and 1,2,4,5-teraoxane-based scaffolds, has gained significant interest in recent years for developing antimalarial drugs against resistant malaria. In this paper, a comprehensive effort has been made to review the development of endoperoxide antimalarials from traditional antimalarial leads (natural/semisynthetic) and structural diversity of endoperoxide molecules derived from 1,2,4-trioxane-, 1,2,4-trioxolane- and 1,2,4,5-teraoxane-based structural scaffolds, including their chimeric (hybrid) molecules, which are newer and potent antimalarial agents. Keywords: endoperoxide, structural diversity, 1,2,4-trioxane, pharmacophore, pharmacodynamic, antimalaria

Design, molecular docking, drug-likeness, and molecular dynamics studies of 1,2,4-trioxane derivatives as novel Plasmodium falciparum falcipain-2 (FP-2) inhibitors

Despite significant progress made in drug discovery and development over the past few decades, malaria remains a life-threatening infectious disease across the globe. Because of the widespread emergence of drug-resistant strains of Plasmodium falciparum, the clinical utility of existing drug therapies including Artemisinin-based Combination Therapies (ACTs) in the treatment of malaria has been increasingly limited. It has become a serious health concern which, therefore, necessitates the development of novel drug molecules and/or alternative therapies to combat, particularly resistant P. falciparum. The objective of the present study was to develop 1,2,4-trioxane derivatives as novel antimalarial agents that would be effective against resistant P. falciparum. In our study, 15 new trioxane derivatives were designed by molecular modification of the 1,2,4-trioxane scaffold as possible antimalarial agents. Molecular modeling studies of trioxane derivatives were performed based on the CADD approach using Biovia Discovery Studio (DS) 2018 software. The protein-ligand docking study was performed against P. falciparum falcipain 2 (FP-2) using the simulation-based docking protocol LibDock by the flexible docking method. The assessment of drug-likeness, ADMET properties, and toxicity was also performed. Furthermore, the compounds CC3 and CC7, which showed the best binding affinity against the target P. falciparum FP-2, were investigated by molecular dynamics (MD) simulation studies followed by the calculation of MM-PBSA binding free energy of protein-ligand complexes using DS 2020. Results of the docking study showed that among the 15 compounds, three trioxane derivatives were found to possess promising binding affinity with LibDock scores ranging from 117.16 to 116.90. Drug-likeness, ADMET, and toxicity properties were found to be satisfactory for all the compounds. Among the 15 compounds, two compounds, namely CC3 and CC7, showed the highest binding affinity against FP-2 with LibDock score of 117.166 and 117.200, respectively. The Libdock score of the co-crystal inhibitor was 114.474. MD studies along with MM-PBSA calculations of binding energies further confirmed the antimalarial potential of the compounds CC3 and CC7, with the formation of well-defined and stable receptor-ligand interactions against the P. falciparum FP-2 enzyme. Additionally, the selectivity of trioxane hits identified as potential inhibitors of P. falciparum cysteine protease FP-2 was determined on human cysteine proteases such as cathepsins (Cat K and Cat L), which are host homologous. Finally, it was concluded that the newly designed 1,2,4-trioxane derivatives can be further studied for in vitro and in vivo antimalarial activities for their possible development as potent antimalarial agents effective against resistant P. falciparu

Citronellal as a Promising Candidate for Alzheimer’s Disease Treatment: A Comprehensive Study on In Silico and In Vivo Anti-Acetylcholine Esterase Activity

One of the primary therapeutic approaches for managing Alzheimer’s disease (AD) involves the modulation of Acetylcholine esterase (AChE) activity to elevate acetylcholine (ACh) levels inside the brain. The current study employed computational chemistry approaches to evaluate the inhibitory effects of CTN on AChE. The docking results showed that Citronellal (CTN) and standard Donepezil (DON) have a binding affinity of −6.5 and −9.2 Kcal/mol, respectively, towards AChE. Further studies using molecular dynamics (MD) simulations were carried out on these two compounds. Binding free energy calculations and ligand-protein binding patterns suggested that CTN has a binding affinity of −12.2078. In contrast, DON has a much stronger binding relationship of −47.9969, indicating that the standard DON has a much higher binding affinity than CTN for AChE. In an in vivo study, Alzheimer-type dementia was induced in mice by scopolamine (1.5 mg/kg/day i.p) for 14 days. CTN was administered (25 and 50 mg/kg. i.p) along with scopolamine (SCO) administration. DON (0.5 mg/kg orally) was used as a reference drug. CTN administration significantly improved the mice’s behavior as evaluated by the Morris water maze test, evident from decreased escape latency to 65.4%, and in the CPS test, apparent from reduced escape latency to 69.8% compared to the positive control mice. Moreover, CTN significantly increased the activities of antioxidant enzymes such as catalase and superoxide dismutase (SOD) compared to SCO. Furthermore, CTN administration significantly decreased SCO-induced elevated AChE levels in mice. These results were supported by histopathological and in silico molecular docking studies. CTN may be a potential antioxidant and neuroprotective supplement

Atorvastatin ascorbic acid cocrystal strategy to improve the safety and efficacy of atorvastatin

The study was aimed to investigate the effect of dissolution enhancement on the hypolipidemic effect and hepatotoxicity of the drug in hyperlipidemic rats. Atorvastatin ascorbic acid cocrystals were prepared by phase solution methods and characterized by Fourier transformation infrared spectroscopy, differential scanning calorimetry, scanning electron microscopy, X-Ray powder diffraction. Results of characterization confirmed that atorvastatin ascorbic acid cocrystals exhibited particle size was 221 nm. In in vitro study, results of dissolution test showed that the release of atorvastatin was increased to 1.6 folds. From In vivo study results, it was observed that in atorvastatin ascorbic acid cocrystals treated rats, serum total cholesterol, triglycerides, liver transaminase levels were significantly decreased, and liver glutathione activity was increased. In conclusion, atorvastatin ascorbic acid cocrystals therapy exhibited less hepatotoxicity in presence of ascorbic acid when compared to atorvastatin alone therapy and also the efficacy of therapy was improved

Sementes de feijão submetidas a ciclos e períodos de hidratação-secagem Bean seeds subjected to hydration-dehydration cycles and periods

A técnica de hidratação-secagem pode ocasionar alterações fisiológicas e bioquímicas em sementes de feijão e afetar sua qualidade fisiológica. Sementes do cultivar Carioca foram submetidas a tratamentos de hidratação-secagem por 6, 12 e 24 horas com três ciclos de hidratação, com o objetivo de avaliar os efeitos causados por períodos e ciclos de hidratação-secagem na qualidade fisiológica das sementes. O delineamento experimental utilizado foi inteiramente casualizado, com quatro repetições, analisado estatisticamente em esquema fatorial 3 x 3 com uma testemunha absoluta. Para a primeira contagem da germinação, os tratamentos de períodos combinados com ciclos de hidratação-secagem, apresentaram superioridade em relação ao tratamento testemunha. Na avaliação de grupos de proteínas, as concentrações de globulinas e prolaminas nas sementes submetidas aos tratamentos, foram significativamene superiores a testemunha. Os cátions (Ca, Mg e K) lixiviados para solução de embebição das sementes tiveram comportamento semelhante à condutividade elétrica das mesmas.<br>The hydration-dehydration technique may cause physiological and biochemical modifications in bean seeds, affecting their physiological quality. Seeds cv. Carioca were submitted to hydration-dehydration treatments for 6, 12 and 24 hours with three hydration cycles. The objective was evaluate the effects caused by hydration-dehydration treatments on bean seed physiological quality. The experimental design was completely randomized, with four replications, 3 x 3 factorial, with an absolute control. At the first germination count the hydration-dehydration duration and cycle treatments were superior in relation to the control. Regarding the protein fractions the treated seed globulin and prolamin concentrations increased significantly as compared to the controls. The leached cations (Ca, Mg and K) in the seed imbibition solution had a similar behaviour in relation to the electrolytic leakage