Differential methylation of circulating free DNA assessed through cfMeDiP as a new tool for breast cancer diagnosis and detection of BRCA1/2 mutation.

Background: Recent studies have highlighted the importance of the cell-free DNA (cfDNA) methylation profile in detecting breast cancer (BC) and its different subtypes. We investigated whether plasma cfDNA methylation, using cell-free Methylated DNA Immunoprecipitation and High-Throughput Sequencing (cfMeDIP-seq), may be informative in characterizing breast cancer in patients with BRCA1/2 germline mutations for early cancer detection and response to therapy.

Methods: We enrolled 23 BC patients with germline mutation of BRCA1 and BRCA2 genes, 19 healthy controls without BRCA1/2 mutation, and two healthy individuals who carried BRCA1/2 mutations.

Computer-aided drug repurposing to tackle antibiotic resistance based on topological data analysis.

The progressive emergence of antimicrobial resistance has become a global health problem in need of rapid solution. Research into new antimicrobial drugs is imperative. Drug repositioning, together with computational mathematical prediction models, could be a fast and efficient method of searching for new antibiotics.

A variational algorithm to detect the clonal copy number substructure of tumors from scRNA-seq data.

Single-cell RNA sequencing is the reference technology to characterize the composition of the tumor microenvironment and to study tumor heterogeneity at high resolution. Here we report Single CEll Variational ANeuploidy analysis (SCEVAN), a fast variational algorithm for the deconvolution of the clonal substructure of tumors from single-cell RNA-seq data. It uses a multichannel segmentation algorithm exploiting the assumption that all the cells in a given copy number clone share the same breakpoints.

Synthesis of Quinolones and Zwitterionic Quinolonate Derivatives with Broad-Spectrum Antibiotic Activity.

Quinolones are one of the most extensively used therapeutic families of antibiotics. However, the increase in antibiotic-resistant bacteria has rendered many of the available compounds useless. After applying our prediction model of activity against to a library of 1000 quinolones, two quinolones were selected to be synthesized.

New Pharmacokinetic and Microbiological Prediction Equations to Be Used as Models for the Search of Antibacterial Drugs.

Currently, the development of resistance of bacteria is one of the most important health problems worldwide. Consequently, there is a growing urge for finding new compounds with antibacterial activity. Furthermore, it is very important to find antibacterial compounds with a good pharmacokinetic profile too, which will lead to more efficient and safer drugs.

Virtual Combinatorial Chemistry and Pharmacological Screening: A Short Guide to Drug Design.

Traditionally, drug development involved the individual synthesis and biological evaluation of hundreds to thousands of compounds with the intention of highlighting their biological activity, selectivity, and bioavailability, as well as their low toxicity. On average, this process of new drug development involved, in addition to high economic costs, a period of several years before hopefully finding a drug with suitable characteristics to drive its commercialization. Therefore, the chemical synthesis of new compounds became the limiting step in the process of searching for or optimizing leads for new drug development.

Monitoring Weeder Robots and Anticipating Their Functioning by Using Advanced Topological Data Analysis.

The present paper aims at analyzing the topological content of the complex trajectories that weeder-autonomous robots follow in operation. We will prove that the topological descriptors of these trajectories are affected by the robot environment as well as by the robot state, with respect to maintenance operations. Most of existing methodologies enabling efficient diagnosis are based on the data analysis, and in particular on some statistical quantities derived from the data.

Circadian PERformance in breast cancer: a germline and somatic genetic study of PER3 polymorphisms and gene co-expression.

Polymorphisms in the PER3 gene have been associated with several human disease phenotypes, including sleep disorders and cancer. In particular, the long allele of a variable number of tandem repeat (VNTR) polymorphism has been previously linked to an increased risk of breast cancer. Here we carried out a combined germline and somatic genetic analysis of the role of the PER3 polymorphism in breast cancer.

Transcriptomic and Genetic Associations between Alzheimer's Disease, Parkinson's Disease, and Cancer.

Alzheimer's (AD) and Parkinson's diseases (PD) are the two most prevalent neurodegenerative disorders in human populations. Epidemiological studies have shown that patients suffering from either condition present a reduced overall risk of cancer than controls (i.e.

Real-Time Path Planning Based on Harmonic Functions under a Proper Generalized Decomposition-Based Framework.

This paper presents a real-time global path planning method for mobile robots using harmonic functions, such as the Poisson equation, based on the Proper Generalized Decomposition (PGD) of these functions. The main property of the proposed technique is that the computational cost is negligible in real-time, even if the robot is disturbed or the goal is changed. The main idea of the method is the off-line generation, for a given environment, of the whole set of paths from any start and goal configurations of a mobile robot, namely the computational vademecum, derived from a harmonic potential field in order to use it on-line for decision-making purposes.

Molecular Topology for the Search of New Anti-MRSA Compounds.

The variability of methicillin-resistant (MRSA), its rapid adaptive response against environmental changes, and its continued acquisition of antibiotic resistance determinants have made it commonplace in hospitals, where it causes the problem of multidrug resistance. In this study, we used molecular topology to develop several discriminant equations capable of classifying compounds according to their anti-MRSA activity. Topological indices were used as structural descriptors and their relationship with anti-MRSA activity was determined by applying linear discriminant analysis (LDA) on a group of quinolones and quinolone-like compounds.

A COVID-19 Drug Repurposing Strategy through Quantitative Homological Similarities Using a Topological Data Analysis-Based Framework.

Since its emergence in March 2020, the SARS-CoV-2 global pandemic has produced more than 116 million cases and 2.5 million deaths worldwide. Despite the enormous efforts carried out by the scientific community, no effective treatments have been developed to date.

Tree-Based QSAR Model for Drug Repurposing in the Discovery of New Antibacterial Compounds Against .

Drug repurposing appears as an increasing popular tool in the search of new treatment options against bacteria. In this paper, a tree-based classification method using Linear Discriminant Analysis (LDA) and discrete indexes was used to create a QSAR (Quantitative Structure-Activity Relationship) model to predict antibacterial activity against Escherichia coli. The model consists on a hierarchical decision tree in which a discrete index is used to divide compounds into groups according to their values for said index in order to construct probability spaces.

Adaptive one-class Gaussian processes allow accurate prioritization of oncology drug targets.

Motivation: The cost of drug development has dramatically increased in the last decades, with the number new drugs approved per billion US dollars spent on R&D halving every year or less. The selection and prioritization of targets is one the most influential decisions in drug discovery. Here we present a Gaussian Process model for the prioritization of drug targets cast as a problem of learning with only positive and unlabeled examples.

Molecular Topology for the Discovery of New Broad-Spectrum Antibacterial Drugs.

In this study, molecular topology was used to develop several discriminant equations capable of classifying compounds according to their antibacterial activity. Topological indices were used as structural descriptors and their relation to antibacterial activity was determined by applying linear discriminant analysis (LDA) on a group of quinolones and quinolone-like compounds. Four equations were constructed, named DF1, DF2, DF3, and DF4, all with good statistical parameters such as Fisher-Snedecor's F (over 25 in all cases), Wilk's lambda (below 0.

Topological index as a factor determining the antibacterial activity of quinolones against .

Due to antibiotic resistance and the lack of investment in antimicrobial R&D, quantitative structure-activity relationship (SAR) methods appear as an ideal approach for the discovery of new antibiotics. Molecular topology and linear discriminant analysis were used to construct a model to predict activity against . This model establishes new SARs, of which, molecular size and complexity (), stand out for their discriminant power.

New solvent options for assays in the larvae model.

Experimentation in mammals is a long and expensive process in which ethical aspects must be considered, which has led the scientific community to develop alternative models such as that of . This model is a cost and time effective option to act as a filter in the drug discovery process. The main limitation of this model is the lack of variety in the solvents used to administer compounds, which limits the compounds that can be studied using this model.

Long term patient satisfaction and quality of life with AMS700CX inflatable penile prosthesis.

Objective: Penile prosthesis implantation is the solution of choice in patients who have failed or present contraindication to the use of all conservative treatment for erectile dysfunction (ED). Overall, satisfaction rates are high, with more than 80% of patients and partners fully satisfied with cosmetic and functional result of surgery. Chronic postoperative pain, penile shortening, soft or hyposensitive glans, pencil like penis syndrome and difficulty to cycle the device represent the most common causes of patient's dissatisfaction.

The use of "LAST" operation in high risk patient.

Background: The LAST operation, in spite of few drawbacks, represents a good option for single Left Anterior Descending (LAD) revascularization. This procedure does not allow multivessel revascularization, where hybrid procedure have been previous described. We report preliminary experience with the LAST operation performed in high risk patients.

Geobacillus toebii subsp. decanicus subsp. nov., a hydrocarbon-degrading, heavy metal resistant bacterium from hot compost.

A thermophilic, spore-forming bacterial strain L1(T) was isolated from hot compost "Pomigliano Environment" s.p.a.