Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of Dietary Seaweed Supplementation in Cows on Milk Macrominerals, Trace Elements and Heavy Metal Concentrations

This study investigated the effect of seaweed supplementation in dairy cow diets on milk yield, basic composition, and mineral concentrations. Thirty-seven Icelandic cows were split into three diet treatments: control (CON, no seaweed), low seaweed (LSW, 0.75% concentrate dry matter (DM), 13–40 g/cow/day), and high seaweed (HSW, 1.5% concentrate DM, 26–158 g/cow/day). Cows were fed the same basal diet of grass silage and concentrate for a week, and then were introduced to the assigned experimental diets for 6 weeks. The seaweed mix of 91% Ascophyllum nodosum: 9% Laminaria digitata (DM basis), feed, and milk samples were collected weekly. Data were analyzed using a linear mixed effects model, with diet, week, and their interaction as fixed factors, cow ID as random factor, and the pre-treatment week data as a covariate. When compared with CON milk, LSW and HSW milk had, respectively, less Se (−1.4 and −3.1 μg/kg milk) and more I (+744 and +1649 μg/kg milk), while HSW milk also had less Cu (−11.6 μg/kg milk) and more As (+0.17 μg/kg milk) than CON milk. The minimal changes or concentrations in milk for Se, Cu, and As cannot be associated with any effects on consumer nutrition, but care should be taken when I-rich seaweed is fed to cows to avoid excessive animal I supply and milk I concentrations.
A KRT71 Loss-of-Function Variant Results in Inner Root Sheath Dysplasia and Recessive Congenital Hypotrichosis of Hereford Cattle

Genodermatoses, such as heritable skin disorders, mostly represent Mendelian conditions. Congenital hypotrichosis (HY) characterize a condition of being born with less hair than normal. The purpose of this study was to characterize the clinicopathological phenotype of a breed-specific non-syndromic form of HY in Hereford cattle and to identify the causative genetic variant for this recessive disorder. Affected calves showed a very short, fine, wooly, kinky and curly coat over all parts of the body, with a major expression in the ears, the inner part of the limbs, and in the thoracic-abdominal region. Histopathology showed a severely altered morphology of the inner root sheath (IRS) of the hair follicle with abnormal Huxley and Henle’s layers and severely dysplastic hair shafts. A genome-wide association study revealed an association signal on chromosome 5. Homozygosity mapping in a subset of cases refined the HY locus to a 690 kb critical interval encompassing a cluster of type II keratin encoding genes. Protein-coding exons of six positional candidate genes with known hair or hair follicle function were re-sequenced. This revealed a protein-changing variant in the KRT71 gene that encodes a type II keratin specifically expressed in the IRS of the hair follicle (c.281delTGTGCCCA; p.Met94AsnfsX14). Besides obvious phenocopies, a perfect concordance between the presence of this most likely pathogenic loss-of-function variant located in the head domain of KRT71 and the HY phenotype was found. This recessive KRT71-related form of hypotrichosis provides a novel large animal model for similar human conditions. The results have been incorporated in the Online Mendelian Inheritance in Animals (OMIA) database (OMIA 002114-9913).
Composting of Calotropis gigantea Leaves In Presence of Sheep Dung

Calotropis gigantea is a plant grown almost everywhere and has no economic use. Leaves of Calotropis gigantea plants were composted with sheep dung. Composting conditions were maintained and samples were withdrawn at 30, 60 and 90 days of composting and analysed for pH, electrical conductivity, Ca 2+ , Mg 2+ , Cl 1, total organic carbon, total nitrogen, available phosphorus and available potassium. Results show that contents of these parameters changes with time and at 90 days nutrient rich compost is obtained with decreased concentration of chloride.
Association between CYP3A5 Polymorphism and Statin-Induced Adverse Events: A Systemic Review and Meta-Analysis

Purpose: Cytochrome P450 (CYP) is involved in the metabolism of statins; CYP3A5 is the main enzyme responsible for lipophilic statin metabolism. However, the evidence of the association between CYP3A5*3 polymorphism and the risk of statin-induced adverse events remains unclear. Therefore, this study aimed to perform a systematic review and meta-analysis to investigate the relationship between the CYP3A5*3 polymorphism and the risk of statin-induced adverse events. Methods: The PubMed, Web of Science, and EMBASE databases were searched for qualified studies published until August 2020. Observational studies that included the association between statin-induced adverse events and the CYP3A5*3 polymorphism were reviewed. The odds ratios (ORs) and 95% confidence intervals (CIs) were evaluated to assess the strength of the relationship. The Mantel–Haenszel method was used to provide the pooled ORs. Heterogeneity was estimated with I2 statistics and publication bias was determined by Begg’s and Egger’s test of the funnel plot. Data analysis was performed using Review Manager (version 5.4) and R Studio (version 3.6). Results: In total, data from 8 studies involving 1614 patients were included in this meta-analysis. The CYP3A5*3 polymorphism was found to be associated with the risk of statin-induced adverse events (*3/*3 vs. *1/*1 + *1/*3: OR = 1.40, 95% CI = 1.08–1.82). For myopathy, the pooled OR was 1.30 (95% CI: 0.96–1.75). The subgroup analysis of statin-induced myopathy revealed a trend, which did not achieve statistical significance. Conclusions: This meta-analysis demonstrated that the CYP3A5*3 polymorphism affected statin-induced adverse event risk. Therefore, CYP3A5 genotyping may be useful to predict statin toxicity.
Eradication of Candida albicans Biofilm Viability: In Vitro Combination Therapy of Cationic Carbosilane Dendrons Derived from 4-Phenylbutyric Acid with AgNO3 and EDTA

Candida albicans is a human pathogen of significant clinical relevance. This pathogen is resistant to different drugs, and most clinical antifungals are not effective against the prevention and treatment of C. albicans infections. As with other microorganisms, it can produce biofilms that serve as a barrier against antifungal agents and other substances, contributing to infection in humans and environmental tolerance of this microorganism. Thus, resistances and biofilm formation make treatment difficult. In addition, the complete eradication of biofilms in implants, catheters and other medical devices, is challenging and necessary to prevent relapses of candidemia. Therefore, it is a priority to find new molecules or combinations of compounds with anti-Candida biofilm activity. Due to the difficulty of treating and removing biofilms, the aim of this study was to evaluate the in vitro ability of different generation of cationic carbosilane dendrons derived from 4-phenylbutyric acid, ArCO2Gn(SNMe3I)m, to eradicate C. albicans biofilms. Here, we assessed the antifungal activity of the second generation dendron ArCO2G2(SNMe3I)4 against C. albicans cells and established biofilms since it managed to seriously damage the membrane. In addition, the combinations of the second generation dendron with AgNO3 or EDTA eradicated the viability of biofilm cells. Alterations were observed by scanning electron microscopy and cytotoxicity was assessed on HeLa cells. Our data suggest that the dendritic compound ArCO2G2(SNMe3I)4 could represent an alternative to control the infections caused by this pathogen.
Predicting Hemodynamic Failure Development in PICU Using Machine Learning Techniques

The present work aims to identify the predictors of hemodynamic failure (HF) developed during pediatric intensive care unit (PICU) stay testing a set of machine learning techniques (MLTs), comparing their ability to predict the outcome of interest. The study involved patients admitted to PICUs between 2010 and 2020. Data were extracted from the Italian Network of Pediatric Intensive Care Units (TIPNet) registry. The algorithms considered were generalized linear model (GLM), recursive partition tree (RPART), random forest (RF), neural networks models, and extreme gradient boosting (XGB). Since the outcome is rare, upsampling and downsampling algorithms have been applied for imbalance control. For each approach, the main performance measures were reported. Among an overall sample of 29,494 subjects, only 399 developed HF during the PICU stay. The median age was about two years, and the male gender was the most prevalent. The XGB algorithm outperformed other MLTs in predicting HF development, with a median ROC measure of 0.780 (IQR 0.770–0.793). PIM 3, age, and base excess were found to be the strongest predictors of outcome. The present work provides insights for the prediction of HF development during PICU stay using machine-learning algorithms.
Pharmaceutical Formulations with P-Glycoprotein Inhibitory Effect as Promising Approaches for Enhancing Oral Drug Absorption and Bioavailability

P-glycoprotein (P-gp) is crucial in the active transport of various substrates with diverse structures out of cells, resulting in poor intestinal permeation and limited bioavailability following oral administration. P-gp inhibitors, including small molecule drugs, natural constituents, and pharmaceutically inert excipients, have been exploited to overcome P-gp efflux and enhance the oral absorption and bioavailability of many P-gp substrates. The co-administration of small molecule P-gp inhibitors with P-gp substrates can result in drug–drug interactions and increased side effects due to the pharmacological activity of these molecules. On the other hand, pharmaceutically inert excipients, including polymers, surfactants, and lipid-based excipients, are safe, pharmaceutically acceptable, and are not absorbed from the gut. Notably, they can be incorporated in pharmaceutical formulations to enhance drug solubility, absorption, and bioavailability due to the formulation itself and the P-gp inhibitory effects of the excipients. Different formulations with inherent P-gp inhibitory activity have been developed. These include micelles, emulsions, liposomes, solid lipid nanoparticles, polymeric nanoparticles, microspheres, dendrimers, and solid dispersions. They can bypass P-gp by different mechanisms related to their properties. In this review, we briefly introduce P-gp and P-gp inhibitors, and we extensively summarize the current development of oral drug delivery systems that can bypass and inhibit P-gp to improve the oral absorption and bioavailability of P-gp substrates. Since many drugs are limited by P-gp-mediated efflux, this review is helpful for designing suitable formulations of P-gp substrates to enhance their oral absorption and bioavailability.
Comprehensive Analysis of Chemotherapeutic Agents That Induce Infectious Neutropenia

Chemotherapy-induced neutropenia (CIN) has been associated with a risk of infections and chemotherapy dose reductions and delays. The chemotherapy regimen remains one of the primary determinants of the risk of neutropenia, with some regimens being more myelotoxic than others. Although a number of clinical trials have currently highlighted the risk of CIN with each chemotherapy regimen, only a few ones have comprehensively examined the risk associated with all chemotherapeutic agents. Therefore, this study aimed to investigate the risk factors and characteristics of CIN caused by each neoplastic agent using data from the large voluntary reporting Food and Drug Administration Adverse Event Reporting System database. Initially, univariate analysis showed that an age ≥ 65 years, the female sex, and treatment with chemotherapeutic agents were factors that caused CIN. Then, cluster and component analyses showed that cytotoxic agents (i.e., alkylating agents, antimetabolic agents, antineoplastic antibiotics, platinating agents, and plant-derived alkaloids) were associated with infection following neutropenia. This comprehensive analysis comparing CIN risk suggests that elderly or underweight patients treated with cytotoxic drugs require particularly careful monitoring.
New Data on Organization and Spatial Localization of B-Chromosomes in Cell Nuclei of the Yellow-Necked Mouse Apodemus flavicollis

The gene composition, function and evolution of B-chromosomes (Bs) have been actively discussed in recent years. However, the additional genomic elements are still enigmatic. One of Bs mysteries is their spatial organization in the interphase nucleus. It is known that heterochromatic compartments are not randomly localized in a nucleus. The purpose of this work was to study the organization and three-dimensional spatial arrangement of Bs in the interphase nucleus. Using microdissection of Bs and autosome centromeric heterochromatic regions of the yellow-necked mouse (Apodemus flavicollis) we obtained DNA probes for further two-dimensional (2D)- and three-dimensional (3D)- fluorescence in situ hybridization (FISH) studies. Simultaneous in situ hybridization of obtained here B-specific DNA probes and autosomal C-positive pericentromeric region-specific probes further corroborated the previously stated hypothesis about the pseudoautosomal origin of the additional chromosomes of this species. Analysis of the spatial organization of the Bs demonstrated the peripheral location of B-specific chromatin within the interphase nucleus and feasible contact with the nuclear envelope (similarly to pericentromeric regions of autosomes and sex chromosomes). It is assumed that such interaction is essential for the regulation of nuclear architecture. It also points out that Bs may follow the same mechanism as sex chromosomes to avoid a meiotic checkpoint.
Modeling of CCR5 Recognition by HIV-1 gp120: How the Viral Protein Exploits the Conformational Plasticity of the Coreceptor

The chemokine receptor CCR5 is a key player in HIV-1 infection. The cryo-EM 3D structure of HIV-1 envelope glycoprotein (Env) subunit gp120 in complex with CD4 and CCR5 has provided important structural insights into HIV-1/host cell interaction, yet it has not explained the signaling properties of Env nor the fact that CCR5 exists in distinct forms that show distinct Env binding properties. We used classical molecular dynamics and site-directed mutagenesis to characterize the CCR5 conformations stabilized by four gp120s, from laboratory-adapted and primary HIV-1 strains, and which were previously shown to bind differentially to distinct CCR5 forms and to exhibit distinct cellular tropisms. The comparative analysis of the simulated structures reveals that the different gp120s do indeed stabilize CCR5 in different conformational ensembles. They differentially reorient extracellular loops 2 and 3 of CCR5 and thus accessibility to the transmembrane binding cavity. They also reshape this cavity differently and give rise to different positions of intracellular ends of transmembrane helices 5, 6 and 7 of the receptor and of its third intracellular loop, which may in turn influence the G protein binding region differently. These results suggest that the binding of gp120s to CCR5 may have different functional outcomes, which could result in different properties for viruses.
Beneficial Outcomes of Omega-6 and Omega-3 Polyunsaturated Fatty Acids on Human Health: An Update for 2021

Oxidative stress and inflammation have been recognized as important contributors to the risk of chronic non-communicable diseases. Polyunsaturated fatty acids (PUFAs) may regulate the antioxidant signaling pathway and modulate inflammatory processes. They also influence hepatic lipid metabolism and physiological responses of other organs, including the heart. Longitudinal prospective cohort studies demonstrate that there is an association between moderate intake of the omega-6 PUFA linoleic acid and lower risk of cardiovascular diseases (CVDs), most likely as a result of lower blood cholesterol concentration. Current evidence suggests that increasing intake of arachidonic acid (up to 1500 mg/day) has no adverse effect on platelet aggregation and blood clotting, immune function and markers of inflammation, but may benefit muscle and cognitive performance. Many studies show that higher intakes of omega-3 PUFAs, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are associated with a lower incidence of chronic diseases characterized by elevated inflammation, including CVDs. This is because of the multiple molecular and cellular actions of EPA and DHA. Intervention trials using EPA + DHA indicate benefit on CVD mortality and a significant inverse linear dose–response relationship has been found between EPA + DHA intake and CVD outcomes. In addition to their antioxidant and anti-inflammatory roles, omega-3 fatty acids are considered to regulate platelet homeostasis and lower risk of thrombosis, which together indicate their potential use in COVID-19 therapy.
Fungal Endophytic Community and Diversity Associated with Desert Shrubs Driven by Plant Identity and Organ Differentiation in Extremely Arid Desert Ecosystem

Despite desert ecosystem being crucial to our understanding of natural geography, species evolution and global climate change, there is limited information on the dynamics of their composition and the diversity of endophytic fungi communities driven by plant identity and organ differentiation. Here, an extensive investigation of endophytic fungal microbiome in root, stem, and leaf organs associated with five xerophyte shrubs in an extremely arid desert, Northwest China, were examined. The fungal community dominated by Dothideomycetes and Pleosporales. Shrub species strongly drive the niche-based processes of endophytic fungi across the root, stem and leaf compartments. The diversity and composition of endophytic fungi in stem showed higher variability among plant species than leaf and root. The fungal communities in root libraries were more diverse and exhibited a remarkable differentiation of community composition. We further demonstrated the significant host preferences and tissue specificity of desert endophytic fungi, and unique specific taxa were also observed. The co-occurrence network revealed the coexistence of fungal endophytes in arid desert, and the root fungal network harbored the highest interspecies connectivity. Members of Pleosporales were the most common keystone species in the root fungal network. This is the first report of mycobiota in both plant species and organ differentiation in an extremely arid desert ecosystem.
Liquid Lipids Act as Polymorphic Modifiers of Tristearin-Based Formulations Produced by Melting Technologies

Despite the growing interest in lipid-based formulations, their polymorphism is still a challenge in the pharmaceutical industry. Understanding and controlling the polymorphic behavior of lipids is a key element for achieving the quality and preventing stability issues. This study aims to evaluate the impact of different oral-approved liquid lipids (LL) on the polymorphism, phase transitions and structure of solid lipid-based formulations and explore their influence on drug release. The LL investigated were isopropyl myristate, ethyl oleate, oleic acid, medium chain trigycerides, vitamin E acetate, glyceryl monooleate, lecithin and sorbitane monooleate. Spray-congealing was selected as an example of a melting-based solvent-free manufacturing method to produce microparticles (MPs) of tristearin (Dynasan®118). During the production process, tristearin MPs crystallized in the metastable α-form. Stability studied evidenced a slow phase transition to the stable β-polymorph overtime, with the presence of the α-form still detected after 60 days of storage at 25 °C. The addition of 10% w/w of LL promoted the transition of tristearin from the α-form to the stable β-form with a kinetic varying from few minutes to days, depending on the specific LL. The combination of various techniques (DSC, X-ray diffraction analysis, Hot-stage polarized light microscopy, SEM) showed that the addition of LL significantly modified the crystal structure of tristearin-based formulations at different length scales. Both the polymorphic form and the LL addition had a strong influence on the release behavior of a model hydrophilic drug (caffeine). Overall, the addition of LL can be considered an interesting approach to control triglyceride crystallization in the β-form. From the industrial viewpoint, this approach might be advantageous as any polymorphic change will be complete before storage, hence enabling the production of stable lipid formulations.
Physicochemical and Microstructural Characterization of Whey Protein Films Formed with Oxidized Ferulic/Tannic Acids

Protein-based biodegradable packaging films are of environmental significance. The effect of oxidized ferulic acid (OFA)/tannic acid (OTA) on the crosslinking and film-forming properties of whey protein isolate (WPI) was investigated. Both of the oxidized acids induced protein oxidation and promoted WPI crosslinking through the actions of quinone carbonyl and protein sulfhydryl, and amino groups. OTA enhanced the tensile strength (from 4.5 MPa to max 6.7 MPa) and stiffness (from 215 MPa to max 376 MPa) of the WPI film, whereas OFA significantly increased the elongation at break. The water absorption capability and heat resistance of the films were greatly improved by the addition of OTA. Due to the original color of OTA, the incorporation of OTA significantly reduced light transmittance of the WPI film (λ 200–600 nm) as well as the transparency, whereas no significant changes were induced by the OFA treatment. Higher concentrations of OTA reduced the in vitro digestibility of the WPI film, while the addition of OFA had no significant effect. Overall, these two oxidized polyphenols promoted the crosslinking of WPI and modified the film properties, with OTA showing an overall stronger efficacy than OFA due to more functional groups available.
Response of Controlled Cell Load Biofilms to Cold Atmospheric Plasma Jet: Evidence of Extracellular Matrix Contribution

Aim: Study of the biocidal effect of a cold atmospheric-pressure plasma in ambient air on single-species bacterial biofilms with controlled cell density, characterized by different extracellular matrices. Methods and results: Two bacterial strains were chosen to present different Gram properties and contrasted extracellular matrices: Pseudomonas aeruginosa ATCC 15442 (Gram-negative), and Leuconostoc citreum NRRL B-1299 (Gram-positive). P. aeruginosa biofilm exhibits a complex matrix, rich in proteins while L. citreum presents the specificity to produce glucan-type exopolysaccharides when grown in the presence of sucrose. Plasma was applied on both surface-spread cells and 24-h grown biofilms with controlled cell loads over 5, 10, or 20 min. Surface-spread bacteria showed a time dependent response, with a maximal bacterial reduction of 2.5 log after 20 min of treatment. On the other hand, in our experimental conditions, no bactericidal effect could be observed when treating biofilms of P. aeruginosa and glucan-rich L. citreum. Conclusions: For biofilms presenting equivalent cell loads, the response to plasma treatment seemed to depend on the properties of the extracellular matrix characterized by infrared spectroscopy, scanning electron microscopy, or dry weight. Significance and impact of study: Both cell load standardization and biofilm characterization are paramount factors to consider the biocide effect of plasma treatments. The extracellular matrix could affect the plasma efficacy by physical and/or chemical protective effects.