Automatic Finding Trapezoidal Membership Functions in Mining Fuzzy Association Rules Based on Learning Automata

Association rule mining is an important data mining technique used for discovering relationships among all data items. Membership functions have a significant impact on the outcome of the mining association rules. An important challenge in fuzzy association rule mining is finding an appropriate membership functions, which is an optimization issue. In the most relevant studies of fuzzy association rule mining, only triangle membership functions are considered. This study, as the first attempt, used a team of continuous action-set learning automata (CALA) to find both the appropriate number and positions of trapezoidal membership functions (TMFs). The spreads and centers of the TMFs were taken into account as parameters for the research space and a new approach for the establishment of a CALA team to optimize these parameters was introduced. Additionally, to increase the convergence speed of the proposed approach and remove bad shapes of membership functions, a new heuristic approach has been proposed. Experiments on two real data sets showed that the proposed algorithm improves the efficiency of the extracted rules by finding optimized membership functions

Random survival forest in determination of important risk factors on overall survival and disease-free survival in gastric cancer patients

Objective: Although the incidence of stomach cancer is decreasing in the world, its incidence is still high in Iran. Despite different treatments for cancer, disease recurrence, and death may occur in some patients. Various factors affect survival and recurrence after treatment. This study aims to identify factors affecting overall survival (OS) and disease-free survival (DFS) in patients with gastric cancer (GC) using a random survival forest (RSF). Patients and Methods: In this retrospective study, 553 patients with GC, diagnosed between 2010 and 2018 in Kurdistan province in the west of Iran, were assessed. Important factors of OS and DFS were identified using the COX model and RSF. Analysis of data was implemented by R free software version 3.5.3. Results: The mean (Standard Deviation(SD)) age of patients was 66.99 (13.3) years. The median of OS and DFS was 18 and 37.5 months, respectively. Using RSF, the important affected factors on OS were tumor grade, stage, age, recurrence, surgery, and metastasis, respectively. Also according to the RSF model, stage, tumor grade, radiotherapy, tumor site, surgery, and age were the important risk factors for DFS. Based on the prediction error criterion, the random survival forest performed well in predicting disease-free survival. meanwhile, both RSF and Cox models had the same performance in predicting overall survival. Conclusions: Due to the relationship between tumor grade, disease stage and age, the random survival forest identified these variables as important variables in predicting both outcomes, although the Cox model was not able to detect these factors, which indicates better performance of RSF

Cardiac abnormalities due to multisystem inflammatory syndrome temporally associated with Covid-19 among children: A systematic review and meta-analysis

Background: Cardiac defects due to multisystem inflammatory syndrome in children (MIS-C) have been abundantly reported leading high morbidity among children affected by Covid-19. We aimed to systematically assess the incidence of such cardiac abnormalities due to MIS-C in children suffering Covid-19. Methods: The manuscript databases including Medline, Web of knowledge, Google scholar, Scopus, and Cochrane were deeply searched by the two blinded investigators for all eligible studies based on the relevant keywords. The risk of bias for each study was assessed according to QUADAS-2 tool. Statistical analysis was performed using the Comprehensive Meta Analysis (CMA) software. Results: In final, 21 articles (including 916 children) were eligible for the final analysis that all yielded good quality and none of the citation was determined to have high risk of bias. Considering studies focusing different cardiac abnormalities related to MIS-C yielded a pooled prevalence of 38.0 for significant left ventricular dysfunction, 20.0 for coronary aneurism or dilatation, 28.1 for ECG abnormalities or cardiac arrhythmias, 33.3 for raised serum troponin level and 43.6 for raised proBNP/BNP level. Conclusion: Although cardiac abnormalities among children suffering Covid-19 are uncommon, in the context of the MIS-C can be common and therefore potentially serious and life threatening. © 202

Management of new onset loss of sense of smell during the COVID-19 pandemic - BRS Consensus Guidelines

OBJECTIVES: The primary aim of the study is to provide recommendations for the investigation and management of patients with new onset loss of sense of smell during the COVID-19 pandemic. DESIGN: After undertaking a literature review, we used the RAND/UCLA methodology with a multi-step process to reach consensus about treatment options, onward referral, and imaging. SETTING AND PARTICIPANTS: An expert panel consisting of 15 members was assembled. A literature review was undertaken prior to the study and evidence was summarised for the panellists. MAIN OUTCOME MEASURES: The panel undertook a process of ranking and classifying appropriateness of different investigations and treatment options for new onset loss of sense of smell during the COVID-19 pandemic. Using a 9-point Likert scale, panellists scored whether a treatment was: Not recommended, optional, or recommended. Consensus was achieved when more than 70% of responses fell into the category defined by the mean. RESULTS: Consensus was reached on the majority of statements after 2 rounds of ranking. Disagreement meant no recommendation was made regarding one treatment, using Vitamin A drops. Alpha-lipoic acid was not recommended, olfactory training was recommended for all patients with persistent loss of sense of smell of more than 2 weeks duration, and oral steroids, steroid rinses, and omega 3 supplements may be considered on an individual basis. Recommendations regarding the need for referral and investigation have been made. CONCLUSION: This study identified the appropriateness of olfactory training, different medical treatment options, referral guidelines and imaging for patients with COVID-19-related loss of sense of smell. The guideline may evolve as our experience of COVID-19 develops

High-performance liquid chromatography–tandem mass spectrometry in the identification and determination of phase I and phase II drug metabolites

Applications of tandem mass spectrometry (MS/MS) techniques coupled with high-performance liquid chromatography (HPLC) in the identification and determination of phase I and phase II drug metabolites are reviewed with an emphasis on recent papers published predominantly within the last 6 years (2002–2007) reporting the employment of atmospheric pressure ionization techniques as the most promising approach for a sensitive detection, positive identification and quantitation of metabolites in complex biological matrices. This review is devoted to in vitro and in vivo drug biotransformation in humans and animals. The first step preceding an HPLC-MS bioanalysis consists in the choice of suitable sample preparation procedures (biomatrix sampling, homogenization, internal standard addition, deproteination, centrifugation, extraction). The subsequent step is the right optimization of chromatographic conditions providing the required separation selectivity, analysis time and also good compatibility with the MS detection. This is usually not accessible without the employment of the parent drug and synthesized or isolated chemical standards of expected phase I and sometimes also phase II metabolites. The incorporation of additional detectors (photodiode-array UV, fluorescence, polarimetric and others) between the HPLC and MS instruments can result in valuable analytical information supplementing MS results. The relation among the structural changes caused by metabolic reactions and corresponding shifts in the retention behavior in reversed-phase systems is discussed as supporting information for identification of the metabolite. The first and basic step in the interpretation of mass spectra is always the molecular weight (MW) determination based on the presence of protonated molecules [M+H]+ and sometimes adducts with ammonium or alkali-metal ions, observed in the positive-ion full-scan mass spectra. The MW determination can be confirmed by the [M-H]- ion for metabolites providing a signal in negative-ion mass spectra. MS/MS is a worthy tool for further structural characterization because of the occurrence of characteristic fragment ions, either MSn analysis for studying the fragmentation patterns using trap-based analyzers or high mass accuracy measurements for elemental composition determination using time of flight based or Fourier transform mass analyzers. The correlation between typical functional groups found in phase I and phase II drug metabolites and corresponding neutral losses is generalized and illustrated for selected examples. The choice of a suitable ionization technique and polarity mode in relation to the metabolite structure is discussed as well

Role of Biotransformation Studies in Minimizing Metabolism-Related Liabilities in Drug Discovery

Metabolism-related liabilities continue to be a major cause of attrition for drug candidates in clinical development. Such problems may arise from the bioactivation of the parent compound to a reactive metabolite capable of modifying biological materials covalently or engaging in redox-cycling reactions leading to the formation of other toxicants. Alternatively, they may result from the formation of a major metabolite with systemic exposure and adverse pharmacological activity. To avert such problems, biotransformation studies are becoming increasingly important in guiding the refinement of a lead series during drug discovery and in characterizing lead candidates prior to clinical evaluation. This article provides an overview of the methods that are used to uncover metabolism-related liabilities in a pre-clinical setting and offers suggestions for reducing such liabilities via the modification of structural features that are used commonly in drug-like molecules

Advances in structure elucidation of small molecules using mass spectrometry

The structural elucidation of small molecules using mass spectrometry plays an important role in modern life sciences and bioanalytical approaches. This review covers different soft and hard ionization techniques and figures of merit for modern mass spectrometers, such as mass resolving power, mass accuracy, isotopic abundance accuracy, accurate mass multiple-stage MS(n) capability, as well as hybrid mass spectrometric and orthogonal chromatographic approaches. The latter part discusses mass spectral data handling strategies, which includes background and noise subtraction, adduct formation and detection, charge state determination, accurate mass measurements, elemental composition determinations, and complex data-dependent setups with ion maps and ion trees. The importance of mass spectral library search algorithms for tandem mass spectra and multiple-stage MS(n) mass spectra as well as mass spectral tree libraries that combine multiple-stage mass spectra are outlined. The successive chapter discusses mass spectral fragmentation pathways, biotransformation reactions and drug metabolism studies, the mass spectral simulation and generation of in silico mass spectra, expert systems for mass spectral interpretation, and the use of computational chemistry to explain gas-phase phenomena. A single chapter discusses data handling for hyphenated approaches including mass spectral deconvolution for clean mass spectra, cheminformatics approaches and structure retention relationships, and retention index predictions for gas and liquid chromatography. The last section reviews the current state of electronic data sharing of mass spectra and discusses the importance of software development for the advancement of structure elucidation of small molecules

ICAR: endoscopic skull‐base surgery

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