6 research outputs found

    Innovative Integration of Butina Clustering with Ensemble Learning Techniques for the Refined Pharmacophore Modeling of Apelin Receptor Agonists: A High-Impact Computational Approach

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    3D pharmacophore models describe the ligand’s chemical interactions in their bioactive conformation. They offer a simple but sophisticated approach to decipher the chemically encoded ligand information, making them a valuable tool in Drug Design. Our research summarized the key studies for applying 3D pharmacophore models in virtual screening for APJ receptor agonists. Recent advances in clustering algorithms and ensemble methods have enabled classical pharmacophore modeling to evolve into more flexible and knowledge-driven techniques. Butina clustering categorizes molecules based on their structural similarity (indicated by the Tanimoto coefficient) to create a structurally diverse training dataset. The ensemble learning method combines various individual pharmacophore models into a set of pharmacophore models for pharmacophore space optimization in virtual screening. This approach was evaluated on Apelin datasets and afforded good screening performance, as proven by receiver operating characteristic, enrichment factor, Güner-Henry score, and F-measure. Although one of the high-scoring models achieved statistically superior results in each dataset, the ensemble learning method including Voting and Stacking method balanced the shortcomings of each model and passed with close performance measures

    Integration of the Butina algorithm and ensemble learning strategies for the advancement of a pharmacophore ligand-based model : an in silico investigation of apelin agonists

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    Introduction: 3D pharmacophore models describe the ligand's chemical interactions in their bioactive conformation. They offer a simple but sophisticated approach to decipher the chemically encoded ligand information, making them a valuable tool in drug design. Methods: Our research summarized the key studies for applying 3D pharmacophore models in virtual screening for 6,944 compounds of APJ receptor agonists. Recent advances in clustering algorithms and ensemble methods have enabled classical pharmacophore modeling to evolve into more flexible and knowledge-driven techniques. Butina clustering categorizes molecules based on their structural similarity (indicated by the Tanimoto coefficient) to create a structurally diverse training dataset. The learning method combines various individual pharmacophore models into a set of pharmacophore models for pharmacophore space optimization in virtual screening. Results: This approach was evaluated on Apelin datasets and afforded good screening performance, as proven by Receiver Operating Characteristic (AUC score of 0.994 ± 0.007), enrichment factor of (EF1% of 50.07 ± 0.211), Güner-Henry score of 0.956 ± 0.015, and F-measure of 0.911 ± 0.031. Discussion: Although one of the high-scoring models achieved statistically superior results in each dataset (AUC of 0.82; an EF1% of 19.466; GH of 0.131 and F1-score of 0.071), the ensemble learning method including voting and stacking method balanced the shortcomings of each model and passed with close performance measures

    High burden of hepatocellular carcinoma and viral hepatitis in Southern and Central Vietnam: Experience of a large tertiary referral center, 2010 to 2016

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    AimTo examine the largest tertiary referral center in southern and central Vietnam from 2010 to 2016, evaluating epidemiological trends of hepatocellular carcinoma (HCC) and viral hepatitis B-C in this resource-limited setting.MethodsWe extracted data of patients receiving care from Cho Ray Hospital (Ho Chi Minh City), the largest oncology referral center in southern and central Vietnam, from 2010 to 2016. We collected information on patient age, gender, geographic distribution, and disease characteristics including disease stage, tumor biomarker levels [serum alpha-fetoprotein (AFP), AFP-L3 isoform percentage, and prothrombin induced by induced by vitamin K absence-II], and serological testing for hepatitis B virus (HBV) and hepatitis C virus (HCV) infections.ResultsData from 24091 HCC patients were extracted, with sample demographics comprising mostly male (81.8%) and older age (however with 8.5% younger than 40 years old). This patient sample included a geographic catchment population of 56 million people (60% of the country's total population of 92.7 million), derived from 38 provinces and municipalities in Vietnam. Chronic HBV infection was found in 62.3% of cases, and chronic HCV infection in 26.0%. HBV and HCV co-infection was seen in 2.7%. Cirrhosis was found in an estimated 30% to 40% of cases. Nine percent of patients were not found to have chronic viral hepatitis. Twenty three point two percent of the patients had a normal AFP level. A total of 2199 patients were tested with AFP-L3 and PIVKA II over two years, with 57.7% having elevated AFP-L3%, and 88.5% with elevated PIVKA II levels. Over this 7-year period, the incidence of HCC increased, with a large proportion of cases (overall 40.8%) presenting initially an advanced stage, not amendable to surgical or locoregional therapy.ConclusionHCC contributes significant health care burden in southern and central Vietnam, with increasing case volume over this seven-year period. Viral hepatitis likely explains this high HCC prevalence

    Classification and application of metal-based nanoantioxidants in medicine and healthcare

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    Antioxidants play an important role in the prevention of oxidative stress and have been widely used in medicine and healthcare. However, natural antioxidants have several limitations such as low stability, difficult long-term storage, and high cost of large-scale production. Along with significant advances in nanotechnology, nanomaterials have emerged as a promising solution to improve the limitations of natural antioxidants because of their high stability, easy storage, time effectiveness, and low cost. Among various types of nanomaterials exhibiting antioxidant activity, metal-based nanoantioxidants show excellent reactivity because of the presence of an unpaired electron in their atomic structure. In this review, we summarize some novel metal-based nanoantioxidants and classify them into two main categories, namely chain-breaking and preventive antioxidant nanomaterials. In addition, the applications of antioxidant nanomaterials in medicine and healthcare are also discussed. This review provides a deeper understanding of the mechanisms of metal-based nanoantioxidants and a guideline for using these nanomaterials in medicine and healthcare

    A changing picture of shigellosis in southern Vietnam: shifting species dominance, antimicrobial susceptibility and clinical presentation

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    <p>Abstract</p> <p>Background</p> <p>Shigellosis remains considerable public health problem in some developing countries. The nature of <it>Shigellae </it>suggests that they are highly adaptable when placed under selective pressure in a human population. This is demonstrated by variation and fluctuations in serotypes and antimicrobial resistance profile of organisms circulating in differing setting in endemic locations. Antimicrobial resistance in the genus <it>Shigella </it>is a constant threat, with reports of organisms in Asia being resistant to multiple antimicrobials and new generation therapies.</p> <p>Methods</p> <p>Here we compare microbiological, clinical and epidemiological data from patients with shigellosis over three different periods in southern Vietnam spanning14 years.</p> <p>Results</p> <p>Our data demonstrates a shift in dominant infecting species (<it>S. flexneri </it>to <it>S. sonnei</it>) and resistance profile of the organisms circulating in southern Vietnam. We find that there was no significant variation in the syndromes associated with either <it>S. sonnei </it>or <it>S. flexneri</it>, yet the clinical features of the disease are more severe in later observations.</p> <p>Conclusions</p> <p>Our findings show a change in clinical presentation of shigellosis in this setting, as the disease may be now more pronounced, this is concurrent with a change in antimicrobial resistance profile. These data highlight the socio-economic development of southern Vietnam and should guide future vaccine development and deployment strategies.</p> <p>Trial Registration</p> <p>Current Controlled Trials ISRCTN55945881</p
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