GenClust: A genetic algorithm for clustering gene expression data

BACKGROUND: Clustering is a key step in the analysis of gene expression data, and in fact, many classical clustering algorithms are used, or more innovative ones have been designed and validated for the task. Despite the widespread use of artificial intelligence techniques in bioinformatics and, more generally, data analysis, there are very few clustering algorithms based on the genetic paradigm, yet that paradigm has great potential in finding good heuristic solutions to a difficult optimization problem such as clustering. RESULTS: GenClust is a new genetic algorithm for clustering gene expression data. It has two key features: (a) a novel coding of the search space that is simple, compact and easy to update; (b) it can be used naturally in conjunction with data driven internal validation methods. We have experimented with the FOM methodology, specifically conceived for validating clusters of gene expression data. The validity of GenClust has been assessed experimentally on real data sets, both with the use of validation measures and in comparison with other algorithms, i.e., Average Link, Cast, Click and K-means. CONCLUSION: Experiments show that none of the algorithms we have used is markedly superior to the others across data sets and validation measures; i.e., in many cases the observed differences between the worst and best performing algorithm may be statistically insignificant and they could be considered equivalent. However, there are cases in which an algorithm may be better than others and therefore worthwhile. In particular, experiments for GenClust show that, although simple in its data representation, it converges very rapidly to a local optimum and that its ability to identify meaningful clusters is comparable, and sometimes superior, to that of more sophisticated algorithms. In addition, it is well suited for use in conjunction with data driven internal validation measures and, in particular, the FOM methodology

Immersion Ultrasound Therapy in Combination with Manual Therapy in the Treatment of Ischemic Digital Ulcers in Systemic Sclerosis

Background and Objectives: Digital ulcers (DUs) are the most common complication in patients with Systemic Sclerosis (SSc). They cause pain with hand dysfunction and negatively impact activities of daily and working life. Our study aims to evaluate the efficacy of a combined treatment of manual therapy and ultrasound therapy in SSc patients with ischemic DU (IDU) compared to manual therapy alone. Materials and Methods: We conducted a before-and-after study (non-randomized study). We enrolled a consecutive series of IDU patients undergoing rehabilitation treatment and divided them into two groups: a treatment group consisting of patients undergoing a combination of manual therapy and US water immersion and a standard care group consisting of patients subjected to manual therapy alone. At the time of the first visit (T0) and at the end of the 4-week rehabilitation period (T1), we evaluated functional capacity, pain intensity, ulcer evolution, and quality of life. Results: In the treatment group, we observed a statistically significant improvement in the functional capacity of the hand (DHI: 28.15 11.0 vs. 19.05 8.83; p < 0.05), pain (NRS: 5.55 1.2 vs. 2.9 1.09; p < 0.05), and PSST score (24.4 4.0 vs. 16.2 2.36; p < 0.05). In the standard care group, we observed a statistically significant improvement only for the functional capacity of the hand (DHI: 28.85 9.72 vs. 22.7 7.68; p < 0.05). Finally, from the comparison between the treatment group and the standard care group, we observed statistically significant improvements in pain (2.9 1.09 vs. 4.5 1.07; p < 0.05) and in the PSST scale (16.2 2.36 vs. 20.4 4.02; p < 0.05). Furthermore, at the end of treatment in the treatment group, 15 ulcers (62.5%) were completely healed, while in the standard care group, only 3 ulcers were completely healed (14.3%). Conclusions: Combined treatment with manual therapy and ultrasound therapy appears to be useful in the management of IDU in patients with scleroderma

Positive effects of tomato paste on vascular function after a fat meal in male healthy subjects

Tomato consumption has been recently associated with a reduced incidence of cardiovascular disease (CVD). The aim of this study was to test whether a seven-day period of tomato paste pur\ue8e (tomato paste, TP) supplementation could improve some haemodynamic parameters in healthy volunteers before and after a standardized fat meal (FM)

MEDIATE - Molecular DockIng at homE: Turning collaborative simulations into therapeutic solutions

IntroductionCollaborative computing has attracted great interest in the possibility of joining the efforts of researchers worldwide. Its relevance has further increased during the pandemic crisis since it allows for the strengthening of scientific collaborations while avoiding physical interactions. Thus, the E4C consortium presents the MEDIATE initiative which invited researchers to contribute via their virtual screening simulations that will be combined with AI-based consensus approaches to provide robust and method-independent predictions. The best compounds will be tested, and the biological results will be shared with the scientific community.Areas coveredIn this paper, the MEDIATE initiative is described. This shares compounds' libraries and protein structures prepared to perform standardized virtual screenings. Preliminary analyses are also reported which provide encouraging results emphasizing the MEDIATE initiative's capacity to identify active compounds.Expert opinionStructure-based virtual screening is well-suited for collaborative projects provided that the participating researchers work on the same input file. Until now, such a strategy was rarely pursued and most initiatives in the field were organized as challenges. The MEDIATE platform is focused on SARS-CoV-2 targets but can be seen as a prototype which can be utilized to perform collaborative virtual screening campaigns in any therapeutic field by sharing the appropriate input files

Computational cluster validation for microarray data analysis: experimental assessment of Clest, Consensus Clustering, Figure of Merit, Gap Statistics and Model Explorer

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Controlling nutritional status score predicts 2-year outcomes in elderly patients admitted for acute heart failure

BackgroundHeart failure (HF) is a major cause of death among the elderly. Its prevalence increases dramatically with age. The prevalence of malnourished subjects is high in hospitalized elderly patients. We aimed to investigate the prognostic role of malnutrition, assessed by controlling nutritional status (CONUT) score, on adverse clinical outcomes in the elderly admitted for acute HF.MethodsWe enrolled 293 patients (mean age 84 years; 48% men) consecutively admitted for acute HF to the Internal Medicine or Geriatrics Divisions at the 'IRCCS Sacro Cuore-Don Calabria' Hospital of Negrar (Verona, Italy) from 2013 to 2015. We predicted the risk of all-cause death, re-hospitalizations for HF and non-HF causes, and the composite of all-cause death or hospitalizations over 2-year follow-up. Patients were divided into four groups according to CONUT score: normal-CONUT (0-1; n = 30); mild-CONUT (2-3; n = 56); moderate-CONUT (4-7; n = 171); and severe-CONUT (>= 8; n = 36).ResultsHigher CONUT scores were associated with older age and lower entry blood pressures. No difference in hemodynamics was noted at the discharge. Kaplan-Meier curves showed a significant association between worsening CONUT scores and risk of all-cause death (p < 0.01), re-hospitalizations (p < 0.01), or both (p < 0.001). Cox regression analysis revealed these significant associations persisted after adjustment for age, sex, pre-existing cardiovascular disease, diabetes, chronic kidney disease, heart rate, systolic blood pressure, and plasma brain natriuretic peptide levels at discharge (all-cause mortality HR = 1.29 (1.00-1.66), p = 0.049; hospitalization for HF HR = 1.36 (1.03-1.81), p = 0.033; hospitalization for non-HF HR = 1.38 (1.03-1.86), p = 0.034; composite outcome HR = 1.33 (1.07-1.64), p = 0.01).ConclusionsMalnutrition, assessed by the CONUT score, is common among elderly patients admitted for acute HF and is strongly related to increased long-term risk of all-cause death and re-hospitalizations

Non-alcoholic fatty liver disease and increased risk of all-cause mortality in elderly patients admitted for acute heart failure

Nonalcoholic fatty liver disease (NAFLD) is an emerging risk factor for incident heart failure (HF). It is currently unknown whether NAFLD predicts all-cause mortality in patients admitted for acute HF. We aimed to assess whether NAFLD and its severity (diagnosed by ultrasonography and non-invasive fibrosis biomarkers) were associated with increased all-cause mortality in this particularly high-risk patient population

Expanding the genetic and phenotypic spectrum of CHD2-related disease: From early neurodevelopmental disorders to adult-onset epilepsy

CHD2 encodes the chromodomain helicase DNA-binding protein 2, an ATP-dependent enzyme that acts as a chromatin remodeler. CHD2 pathogenic variants have been associated with various early onset phenotypes including developmental and epileptic encephalopathy, self-limiting or pharmacoresponsive epilepsies and neurodevelopmental disorders without epilepsy. We reviewed 84 previously reported patients carrying 76 different CHD2 pathogenic or likely pathogenic variants and describe 18 unreported patients carrying 12 novel pathogenic or likely pathogenic variants, two recurrent likely pathogenic variants (in two patients each), three previously reported pathogenic variants, one gross deletion. We also describe a novel phenotype of adult-onset pharmacoresistant epilepsy, associated with a novel CHD2 missense likely pathogenic variant, located in an interdomain region. A combined review of previously published and our own observations indicates that although most patients (72.5%) carry truncating CHD2 pathogenic variants, CHD2-related phenotypes encompass a wide spectrum of conditions with developmental delay/intellectual disability (ID), including prominent language impairment, attention deficit hyperactivity disorder and autistic spectrum disorder. Epilepsy is present in 92% of patients with a median age at seizure onset of 2 years and 6 months. Generalized epilepsy types are prevalent and account for 75.5% of all epilepsies, with photosensitivity being a common feature and adult-onset nonsyndromic epilepsy a rare presentation. No clear genotype-phenotype correlation has emerged