Multicentre oncology clinical trials in primary health care in Cuba: evaluation of programme implementation in Villa Clara Province, 2010-2020.

Background: The Center of Molecular Immunology of Cuba has developed a programme for the conducting of multicentre oncology clinical trials in primary healthcare centres since 2009.

Aim: To evaluate the ability to conduct oncology clinical trials in primary health care.

Design & Setting: A longitudinal, prospective, analytical study was developed between July 2010 and August 2020 in the Villa Clara province.

Reactivity of Binary Construction and Demolition Waste Mix as Supplementary Cementitious Materials.

Calcareous and siliceous CDW wastes from concrete and glass wastes when mixed in binary mixtures has been analyzed in this study. Fine CDW fractions (<5 mm) of different sorts are selected: siliceous waste (HsT), calcareous waste (HcG) and laminated glass waste. The binary mixtures HsT/glass and HcG/glass at mix-proportions of 1:1, 2:1 and 1:2, respectively, are analyzed with a range of characterization techniques (XRD, TG/DTA, SEM-EDX, NMR, FT-IR) in the pure pozzolan/lime system over a reaction time of 90 days.

New Parameter of the Second Half of the P-Wave, P-Wave Duration, and Atrial Conduction Times Predict Atrial Fibrillation during Electrophysiological Studies.

Objective: Several P-wave parameters reflect atrial conduction characteristics and have been used to predict atrial fibrillation (AF). The aim of this study was to determine the relationship between maximum P-wave duration (PMax) and new P-wave parameters, with atrial conduction times (CT), and to assess their predictive value of AF during electrophysiological studies (AF-EPS).

Subjects And Methods: This was a cross-sectional study in 153 randomly selected patients aged 18-70 years, undergoing EPS.

Quantitative Comparison of Binary Mix of Agro-Industrial Pozzolanic Additions for Elaborating Ternary Cements: Kinetic Parameters.

In this research work, the quantitative characterization of a binary blend comprised of two pozzolans (sugar cane straw (SCSA)-sugar cane bagasse ashes (SCBA), bamboo leaf ash (BLAsh)-SCBA and paper sludge (PS)-fly ash (FA)) taking into account the calculated values of the kinetic parameters of the reaction in the pozzolan/calcium hydroxide system is shown. The paper shows the most significant and important results obtained by the authors in the quantitative assessment (calculation of kinetic parameters) of the pozzolanic reaction of different mixtures of pozzolanic materials that are residues from agriculture or industrial processes. This allows a direct and rigorous comparison of the pozzolanic activity of the binary combinations of materials.

Development of Bioinspired Functional Chitosan/Cellulose Nanofiber 3D Hydrogel Constructs by 3D Printing for Application in the Engineering of Mechanically Demanding Tissues.

Soft tissues are commonly fiber-reinforced hydrogel composite structures, distinguishable from hard tissues by their low mineral and high water content. In this work, we proposed the development of 3D printed hydrogel constructs of the biopolymers chitosan (CHI) and cellulose nanofibers (CNFs), both without any chemical modification, which processing did not incorporate any chemical crosslinking. The unique mechanical properties of native cellulose nanofibers offer new strategies for the design of environmentally friendly high mechanical performance composites.

Long-term Cognitive Network-based architecture for multi-label classification.

This paper presents a neural system to deal with multi-label classification problems that might involve sparse features. The architecture of this model involves three sequential blocks with well-defined functions. The first block consists of a multilayered feed-forward structure that extracts hidden features, thus reducing the problem dimensionality.

Assessing mineral profiles for rice flour fraud detection by principal component analysis based data fusion.

The present work proposes to detect adulteration in rice flour using mineral profiles. Eighty-seven flour samples from two rice kinds (Indica and Japonica) plus thirty adulterated flour samples were analyzed by ICP OES. After obtaining the quantitative elemental fingerprint of the samples, PCA and LDA were applied.

Biodegradation of Crystalline Cellulose Nanofibers by Means of Enzyme Immobilized-Alginate Beads and Microparticles.

Recent advances in nanocellulose technology have revealed the potential of crystalline cellulose nanofibers to reinforce materials which are useful for tissue engineering, among other functions. However, the low biodegradability of nanocellulose can possess some problems in biomedical applications. In this work, alginate particles with encapsulated enzyme cellulase extracted from were prepared for the biodegradation of crystalline cellulose nanofibers, which carrier system could be incorporated in tissue engineering biomaterials to degrade the crystalline cellulose nanoreinforcement in situ and on-demand during tissue regeneration.

Policy of Multisource Drug Products in Latin America: Opportunities and Challenges on the Application of Bioequivalence In Vitro Assays.

Background: The replacement of traditional in vivo bioequivalence studies by in vitro dissolution assays, based on the biopharmaceutical classification system (BCS), has emerged as an important tool for demonstrating the interchangeability of multisource products. This paper summarizes the current implementation of the BCS-based biowaiver for the development of multisource products in Latin America, and identifies several challenges and opportunities for greater convergence and application of BCS regulatory requirements.

Methods: Differences and similarities between the current BCS-based biowaivers' guidelines proposed by two relevant regulatory agencies for the Latin American region (FDA and WHO) and the new ICH harmonization guideline were identified and compared.

Venturicidin A, A Membrane-active Natural Product Inhibitor of ATP synthase Potentiates Aminoglycoside Antibiotics.

Despite the remarkable advances due to the discovery and development of antimicrobials agents, infectious diseases remain the second leading cause of death worldwide. This fact underlines the importance of developing new therapeutic strategies to address the widespread antibiotic resistance, which is the major contributing factor for clinical failures of the current therapeutics. In a screen for antibiotic adjuvants, we identified a natural product from actinomycetes, venturicidin A (VentA), that potentiates the aminoglycoside antibiotic gentamicin against multidrug-resistant clinical isolates of Staphylococcus, Enterococcus, and Pseudomonas aeruginosa.

Perturbation Theory Machine Learning Modeling of Immunotoxicity for Drugs Targeting Inflammatory Cytokines and Study of the Antimicrobial G1 Using Cytometric Bead Arrays.

ChEMBL biological activities prediction for 1-5-bromofur-2-il-2-bromo-2-nitroethene (G1) is a difficult task for cytokine immunotoxicity. The current study presents experimental results for G1 interaction with mouse Th1/Th2 and pro-inflammatory cytokines using a cytometry bead array (CBA). In the test of CBA, the results show no significant differences between the mean values of the Th1/Th2 cytokines for the samples treated with G1 with respect to the negative control, but there are moderate differences for cytokine values between different periods (24/48 h).

Acoustic Breathiness Index for the Japanese-Speaking Population: Validation Study and Exploration of Affecting Factors.

Objectives The purposes of this study were to validate the Acoustic Breathiness Index (ABI) for the Japanese-speaking population and to determine whether it is independent of factors such as sex, age, and perceptual ratings of roughness. Method First, the concurrent validity of the ABI for perceptual breathiness was evaluated on the concatenations of continuous speech and sustained vowels from 288 patients with varying degrees of dysphonia. The diagnostic accuracy was examined on 343 samples with 55 additional normophonic speakers.

In Silico Assessment of ADME Properties: Advances in Caco-2 Cell Monolayer Permeability Modeling.

One of the main goals of in silico Caco-2 cell permeability models is to identify those drug substances with high intestinal absorption in human (HIA). For more than a decade, several in silico Caco-2 models have been made, applying a wide range of modeling techniques; nevertheless, their capacity for intestinal absorption extrapolation is still doubtful. There are three main problems related to the modest capacity of obtained models, including the existence of inter- and/or intra-laboratory variability of recollected data, the influence of the metabolism mechanism, and the inconsistent in vitro-in vivo correlation (IVIVC) of Caco-2 cell permeability.

Integrating theoretical and experimental permeability estimations for provisional biopharmaceutical classification: Application to the WHO essential medicines.

The accuracy of the provisional estimation of the Biopharmaceutics Classification System (BCS) is heavily influenced by the permeability measurement. In this study, several theoretical and experimental models currently employed for BCS permeability classification have been analysed. The experimental models included the in situ rat intestinal perfusion, the ex vivo rat intestinal tissue in an Ussing chamber, the MDCK and Caco-2 cell monolayers, and the parallel artificial membrane (PAMPA).

Computational modeling of human oral bioavailability: what will be next?

The oral route is the most convenient way of administrating drugs. Therefore, accurate determination of oral bioavailability is paramount during drug discovery and development. Quantitative structure-property relationship (QSPR), rule-of-thumb (RoT) and physiologically based-pharmacokinetic (PBPK) approaches are promising alternatives to the early oral bioavailability prediction.

Biowaiver or Bioequivalence: Ambiguity in Sildenafil Citrate BCS Classification.

The aim of the present study is to contribute to the scientific characterization of sildenafil citrate according to the Biopharmaceutics Classification System, following the World Health Organization (WHO) guidelines for biowaivers. The solubility and intestinal permeability data of sildenafil citrate were collected from literature; however, the experimental solubility studies are inconclusive and its "high permeability" suggests an API in the borderline of BCS Class I and Class II. The pH-solubility profile was determined using the saturation shake-flask method over the pH range of 1.

Collinearity and Sample Coverage Issues in the Objective Measurement of Vocal Quality: The Case of Roughness and Breathiness.

Purpose: The aim of the study was to address the reported inconsistencies in the relationship between objective acoustic measures and perceptual ratings of vocal quality.

Method: This tutorial moves away from the more widely examined problems related to obtaining the perceptual ratings and the acoustic measures and centers in less scrutinized issues regarding the procedure to establish the correspondence. Expressions for the most common measure of association between perceptual and acoustic measures (Pearson's r) are derived using a multiple linear regression model.

Early corticospinal tract damage in prodromal SCA2 revealed by EEG-EMG and EMG-EMG coherence.

Objective: Clinical data suggest early involvement of the corticospinal tract (CST) in spinocerebellar ataxia type 2 (SCA2). Here we tested if early CST degeneration can be detected in prodromal SCA2 mutation carriers by electrophysiological markers of CST integrity.

Methods: CST integrity was tested in 15 prodromal SCA2 mutation carriers, 19 SCA2 patients and 25 age-matched healthy controls, using corticomuscular (EEG-EMG) and intermuscular (EMG-EMG) coherence measures in upper and lower limb muscles.

Fuzzy-Rough Cognitive Networks.

Rough Cognitive Networks (RCNs) are a kind of granular neural network that augments the reasoning rule present in Fuzzy Cognitive Maps with crisp information granules coming from Rough Set Theory. While RCNs have shown promise in solving different classification problems, this model is still very sensitive to the similarity threshold upon which the rough information granules are built. In this paper, we cast the RCN model within the framework of fuzzy rough sets in an attempt to eliminate the need for a user-specified similarity threshold while retaining the model's discriminatory power.

Efficient and biologically relevant consensus strategy for Parkinson's disease gene prioritization.

Background: The systemic information enclosed in microarray data encodes relevant clues to overcome the poorly understood combination of genetic and environmental factors in Parkinson's disease (PD), which represents the major obstacle to understand its pathogenesis and to develop disease-modifying therapeutics. While several gene prioritization approaches have been proposed, none dominate over the rest. Instead, hybrid approaches seem to outperform individual approaches.

QuBiLs-MAS method in early drug discovery and rational drug identification of antifungal agents.

The QuBiLs-MAS approach is used for the in silico modelling of the antifungal activity of organic molecules. To this effect, non-stochastic (NS) and simple-stochastic (SS) atom-based quadratic indices are used to codify chemical information for a comprehensive dataset of 2478 compounds having a great structural variability, with 1087 of them being antifungal agents, covering the broadest antifungal mechanisms of action known so far. The NS and SS index-based antifungal activity classification models obtained using linear discriminant analysis (LDA) yield correct classification percentages of 90.

Harmonization of QSAR Best Practices and Molecular Docking Provides an Efficient Virtual Screening Tool for Discovering New G-Quadruplex Ligands.

Telomeres and telomerase are key players in tumorogenesis. Among the various strategies proposed for telomerase inhibition or telomere uncapping, the stabilization of telomeric G-quadruplex (G4) structures is a very promising one. Additionally, G4 stabilizing ligands also act over tumors mediated by the alternative elongation of telomeres.

Objective measurements of image quality in synchrotron radiation phase-contrast imaging versus digital mammography.

Purpose: Phase-contrast mammography with synchrotron radiation is an innovative X-ray imaging practice that improves the identification of breast lesions. Previous studies have proven the superiority of the mammography images taken in the phase-contrast modality using synchrotron radiation beams as compared with images taken in conventional mammography by subjective analyses. However, to our knowledge, no previous study has compared different acquisition systems in order to quantify this improvement by means of objective robust indicators.