Miracle-dz/UniFAR-FTUs huggingface dataset:
Emerging Treatment Options for Multi-Drug-Resistant Bacterial Infections

Antimicrobial resistance (AMR) remains one of the top public health issues of global concern. Among the most important strategies for AMR control there is the correct and appropriate use of antibiotics, including those available for the treatment of AMR pathogens. In this article, after briefly reviewing the most important and clinically relevant multi-drug-resistant bacteria and their main resistance mechanisms, we describe the emerging antimicrobial options for both MDR Gram-positive cocci and Gram-negative bacilli, including recently marketed agents, molecules just approved or under evaluation and rediscovered older antibiotics that have regained importance due to their antimicrobial spectrum. Specifically, emerging options for Gram-positive cocci we reviewed include ceftaroline, ceftobiprole, tedizolid, dalbavancin, and fosfomycin. Emerging treatment options for Gram-negative bacilli we considered comprise ceftolozane-tazobactam, ceftazidime-avibactam, meropenem-vaborbactam, imipenem-relebactam, aztreonam-avibactam, minocycline, fosfomycin, eravacycline, plazomicin, and cefiderocol. An exciting scenario is opening today with the long awaited growing availability of novel molecules for the treatment of AMR bacteria. Knowledge of mechanisms of action and resistance patterns allows physicians to increasingly drive antimicrobial treatment towards a precision medicine approach. Strict adherence to antimicrobial stewardship practices will allow us to preserve the emerging antimicrobials for our future.
Endocrine-Disrupting Chemicals and Early Puberty in Girls

In recent decades, pubertal onset in girls has been considered to occur at an earlier age than previously. Exposure to endocrine-disrupting chemicals (EDCs) has been associated with alterations in pubertal timing, with several reports suggesting that EDCs may have a role in the secular trend in pubertal maturation, at least in girls. However, relevant studies give inconsistent results. On the other hand, the majority of girls with idiopathic precocious or early puberty present the growth pattern of constitutional advancement of growth (CAG), i.e., growth acceleration soon after birth. Herein, we show that the growth pattern of CAG is unrelated to exposure to endocrine-disrupting chemicals and is the major determinant of precocious or early puberty. Presented data suggest that EDCs, at most, have a minor effect on the timing of pubertal onset in girls.
Stress Modifies the Expression of Glucocorticoid-Responsive Genes by Acting at Epigenetic Levels in the Rat Prefrontal Cortex: Modulatory Activity of Lurasidone

Epigenetics is one of the mechanisms by which environmental factors can alter brain function and may contribute to central nervous system disorders. Alterations of DNA methylation and miRNA expression can induce long-lasting changes in neurobiological processes. Hence, we investigated the effect of chronic stress, by employing the chronic mild stress (CMS) and the chronic restraint stress protocol, in adult male rats, on the glucocorticoid receptor (GR) function. We focused on DNA methylation specifically in the proximity of the glucocorticoid responsive element (GRE) of the GR responsive genes Gadd45β, Sgk1, and Gilz and on selected miRNA targeting these genes. Moreover, we assessed the role of the antipsychotic lurasidone in modulating these alterations. Chronic stress downregulated Gadd45β and Gilz gene expression and lurasidone normalized the Gadd45β modification. At the epigenetic level, CMS induced hypermethylation of the GRE of Gadd45β gene, an effect prevented by lurasidone treatment. These stress-induced alterations were still present even after a period of rest from stress, indicating the enduring nature of such changes. However, the contribution of miRNA to the alterations in gene expression was moderate in our experimental conditions. Our results demonstrated that chronic stress mainly affects Gadd45β expression and methylation, effects that are prolonged over time, suggesting that stress leads to changes in DNA methylation that last also after the cessation of stress procedure, and that lurasidone is a modifier of such mechanisms.
Self-Perception of the Knee Is Associated with Joint Motion during the Loading Response in Individuals with Knee Osteoarthritis: A Pilot Cross-Sectional Study

Small knee flexion motion is a characteristic of gait in individuals with knee osteoarthritis. This study examined the relationship between knee flexion excursion in loading response and knee self-perception in individuals with knee osteoarthritis. Twenty-one individuals with knee osteoarthritis participated in this study. Knee flexion excursions in loading response while walking at a comfortable and a fast-walking speed were measured using an inertial measurement unit-based motion capture system. The degree of knee perceptual impairment was evaluated using the Fremantle Knee Awareness Questionnaire (FreKAQ). The relationships between the FreKAQ score and gait variables and knee function were evaluated by calculating the correlation coefficient. The unique contributions of knee self-perception and muscle strength to knee flexion excursion in loading response were analyzed using hierarchical linear regression. Knee self-perception was significantly correlated with pain during walking, muscle strength and knee flexion excursion at fast speed. In the fast speed condition only, impaired knee self-perception was inversely proportional to knee flexion excursion and accounted for 21.8% of the variance in knee flexion excursion. This result suggests that impaired self-perception of the knee may help to explain the decrease in the knee flexion excursion in the loading response in individuals with knee osteoarthritis.
Mycobacterium microti Infection in Red Foxes in France

Mycobacterium microti, member of the Mycobacterium tuberculosis, complex is known to interfere in the screening and diagnosis of bovine tuberculosis. This pathogen is increasingly detected in the frame of surveillance programs for tuberculosis in livestock and wildlife. Recently, red foxes (Vulpes vulpes) were found infected by Mycobacterium bovis in four French endemic areas. M. microti infection was concomitantly found during this investigation. Rates of infection by M. microti and M. bovis are not different except in one of the four areas (lower prevalence for M. microti in Charente). As for M. bovis infection, none of the infected foxes presented gross TB-like lesions. Infection of red foxes by M. microti seems to occur by ingestion of contaminated food, as mesenteric lymph nodes are mostly infected albeit no fecal excretion could be detected. Red foxes appear to be susceptible to Mycobacterium microti infection but seem to play a role of dead-end host for the transmission of this bacillus.
Hemolytic Activity, Cytotoxicity, and Antimicrobial Effects of Human Albumin- and Polysorbate-80-Coated Silver Nanoparticles

In this study, we aimed to develop a technique for colloidal silver nanoparticle (AgNP) modification in order to increase their stability in aqueous suspensions. For this purpose, 40-nm spherical AgNPs were modified by the addition of either human albumin or Tween-80 (Polysorbate-80). After detailed characterization of their physicochemical properties, the hemolytic activity of the nonmodified and modified AgNPs was investigated, as well as their cytotoxicity and antimicrobial effects. Both albumin- and Tween-80-coated AgNPs demonstrated excellent stability in 0.9% sodium chloride solution (>12 months) compared to nonmodified AgNPs, characterized by their rapid precipitation. Hemolytic activity of nonmodified and albumin-coated AgNPs was found to be minimal, while Tween-80-modified AgNPs produced significant hemolysis after 1, 2, and 24 h of incubation. In addition, both native and Tween-80-covered AgNPs showed dose-dependent cytotoxic effects on human adipose-tissue-derived mesenchymal stem cells. The albumin-coated AgNPs showed minimal cytotoxicity. The antimicrobial effects of native and albumin-coated AgNPs against S. aureus, K. pneumonia, P. aeruginosa, Corynebacterium spp. , and Acinetobacter spp. were statistically significant. We conclude that albumin coating of AgNPs significantly contributes to improve stability, reduce cytotoxicity, and confers potent antimicrobial action.
Lorenz Plot Analysis in Dogs with Sinus Rhythm and Tachyarrhythmias

Simple Summary The Lorenz plot (LP) is a geometrical method to assess the dynamics of heart rate variability. It consists of a two-dimensional Cartesian coordinate system derived from electrocardiographic monitoring, in which each recorded R-R interval is plotted as a function of the previous R-R interval, and the values of each pair of successive R-R interval define a dot in the plot. The resultant clusters of dots can be evaluated quantitatively and qualitatively, and categorized into distinct geometrical patterns. In humans, several studies have demonstrated that the analysis of LP patterns (LPPs) has the potential to speed-up and improve the accuracy of arrhythmia detection and differentiation, especially in patients with tachyarrhythmias. As data on LP analysis are limited in dogs, this study describes the graphic features of LP derived from Holter recordings obtained in dogs with sinus rhythm and tachyarrhythmias, and analyzes the usefulness of LPP recognition in this species. We sought to evaluate if distinct cardiac rhythms imprint distinct and reproducible LPPs in dogs, as previously described in humans, and if each LLP can be used as a sensitive and specific indicator of a particular cardiac rhythm in this species. Abstract The Lorenz plot (LP), a graphical representation of heart rate variability, has been poorly studied in dogs to date. The present study aimed to describe the graphic features of LP in dogs with sinus rhythm (SR) and tachyarrhythmias, and to analyze the usefulness of its pattern recognition. One hundred and nineteen canine Holter recordings were retrospectively evaluated. Cardiac rhythms were classified as: SR; SR with frequent (>100) premature ectopies (atrial, SR-APCs; ventricular, SR-VPCs; atrial and ventricular, SR-APCs-VPCs); atrial fibrillation (AF); and AF with frequent VPCs (AF-VPCs). Lorenz plots were studied qualitatively and quantitatively, and classified by distinct LP patterns (LPPs). Repeatability and reproducibility of LPP classification and diagnostic value were determined. Recordings included: 48 SR, 9 SR-APCs, 35 SR-VPCs, 5 SR-APCs-VPCs, 4 AF, and 18 AF-VPCs. Ten LPPs were identified: comet (n = 12), torpedo (n = 3), Y-shaped (n = 6), diamond (n = 10), diamond with a central silent zone (n = 17), double side-lobe (DSL) (n = 47), triple side-lobe (n = 1), quadruple side-lobe (n = 2), fan (n = 18), and fan with DSL (n = 3). Repeatability and reproducibility of LPP classification were excellent. The DSL pattern was both highly sensitive (91.3%) and specific (94.5%) for SR with frequent premature ectopies, either APCs, or VPCs, or both. The remaining LPPs had lower diagnostic value (high specificity but low sensitivity). Distinct rhythms imprint distinct and reproducible LPPs in dogs. The majority of canine LPPs are specific but insensitive indicators of SR and tachyarrhythmias.
Chimeric Antigen Receptor (CAR) T Cell Therapy for Metastatic Melanoma: Challenges and Road Ahead

Metastatic melanoma is the most aggressive and difficult to treat type of skin cancer, with a survival rate of less than 10%. Metastatic melanoma has conventionally been considered very difficult to treat; however, recent progress in understanding the cellular and molecular mechanisms involved in the tumorigenesis, metastasis and immune escape have led to the introduction of new therapies. These include targeted molecular therapy and novel immune-based approaches such as immune checkpoint blockade (ICB), tumor-infiltrating lymphocytes (TILs), and genetically engineered T-lymphocytes such as chimeric antigen receptor (CAR) T cells. Among these, CAR T cell therapy has recently made promising strides towards the treatment of advanced hematological and solid cancers. Although CAR T cell therapy might offer new hope for melanoma patients, it is not without its shortcomings, which include off-target toxicity, and the emergence of resistance to therapy (e.g., due to antigen loss), leading to eventual relapse. The present review will not only describe the basic steps of melanoma metastasis, but also discuss how CAR T cells could treat metastatic melanoma. We will outline specific strategies including combination approaches that could be used to overcome some limitations of CAR T cell therapy for metastatic melanoma.
Impact of Cold Storage on Bioactive Compounds and Their Stability of 36 Organically Grown Beetroot Genotypes

In order to exploit the functional properties of fresh beetroot all year round, maintaining the health-benefiting compounds is the key factor. Thirty-six beetroot genotypes were evaluated regarding their content of total dry matter, total phenolic compounds, betalain, nitrate, and total soluble sugars directly after harvest and after cold storage periods of one and four months. Samples were collected from two field experiments, which were conducted under organic conditions in Southwestern Germany in 2017 and 2018. The outcome of this study revealed a significant influence of genotype (p < 0.05) on all measured compounds. Furthermore, significant impacts were shown for storage period on total dry matter content, nitrate, and total phenolic compounds. The medians of nitrate content based on the genotypes studied within the experiment ranged between 4179 ± 1267–20,489 ± 2988 mg kg−1 DW (dry weight), and that for the total phenolic compounds varied between 201.45 ± 13.13 mg GAE 100 g−1 DW and 612.39 ± 40.58 mg GAE 100 g−1 DW (milligrams of gallic acid equivalents per 100 g of dry weight). According to the significant influence of the interactions of storage period and genotype on total soluble sugars and betalain, the decrease or increase in the content of the assessed compounds during the cold storage noted to be genotype-specific. Therefore, to benefit beetroots with retained quality for an extended time after harvest, selection of the suitable genotype based on the intended final use is recommended.
Male-Biased microRNA Discovery in the Pea Aphid

Simple Summary Males and females develop from a genome that is largely similar, yet the sexes have dramatically different traits. How this happens has driven interest in the role of epigenetic mechanisms—i.e., changes in gene function that are not due to changes in the DNA—in regulating sexual dimorphisms. Our focus here is on differences between the sexes in one epigenetic mechanism, the downregulation of gene expression by small RNAs called microRNAs. Typical genomes code for hundreds of microRNAs and each one can target many protein-coding RNAs, ultimately causing them to produce fewer protein copies. Here, we focus on microRNAs in male versus female pea aphids. We use small RNA sequence data to identify all the microRNAs in the pea aphid genome and to find microRNAs that are highly biased towards expression in males. This work is foundational for future studies of the epigenetic basis of sex differences in the pea aphid. Abstract Epigenetic mechanisms modulate gene expression levels during development, shaping how a single genome produces a diversity of phenotypes. Here, we begin to explore the epigenetic regulation of sexual dimorphism in pea aphids (Acyrthosiphon pisum) by focusing on microRNAs. Previous analyses of microRNAs in aphids have focused solely on females, so we performed deep sequencing of a sample containing early-stage males. We used this sample, plus samples from Genbank, to find 207 novel pea aphid microRNA coding loci. We localized microRNA loci to a chromosome-level assembly of the pea aphid genome and found that those on the X chromosome have lower overall expression compared to those on autosomes. We then identified a set of 19 putative male-biased microRNAs and found them enriched on the X chromosome. Finally, we performed protein-coding RNA-Seq of first instar female and male pea aphids to identify genes with lower expression in males. 10 of these genes were predicted targets of the 19 male-biased microRNAs. Our study provides the most complete set of microRNAs in the pea aphid to date and serves as foundational work for future studies on the epigenetic control of sexual dimorphism.
Terahertz Photoconductivity Spectra of Electrodeposited Thin Bi Films

Electron dynamics in the polycrystalline bismuth films were investigated by measuring emitted terahertz (THz) radiation pulses after their photoexcitation by tunable wavelength femtosecond duration optical pulses. Bi films were grown on metallic Au, Pt, and Ag substrates by the electrodeposition method with the Triton X-100 electrolyte additive, which allowed us to obtain more uniform films with consistent grain sizes on any substrate. It was shown that THz pulses are generated due to the spatial separation of photoexcited electrons and holes diffusing from the illuminated surface at different rates. The THz photoconductivity spectra analysis has led to a conclusion that the thermalization of more mobile carriers (electrons) is dominated by the carrier–carrier scattering rather than by their interaction with the lattice.
A Systematic Review on the Role of SIRT1 in Duchenne Muscular Dystrophy

Duchenne muscular dystrophy (DMD) is a muscular disease characterized by progressive muscle degeneration. Life expectancy is between 30 and 50 years, and death is correlated with cardiac or respiratory complications. Currently, there is no cure, so there is a great interest in new pharmacological targets. Sirtuin1 (SIRT1) seems to be a potential target for DMD. In muscle tissue, SIRT1 exerts anti-inflammatory and antioxidant effects. The aim of this study is to summarize all the findings of in vivo and in vitro literature studies about the potential role of SIRT1 in DMD. A systematic literature search was performed according to PRISMA guidelines. Twenty-three articles satisfied the eligibility criteria. It emerged that SIRT1 inhibition led to muscle fragility, while conversely its activation improved muscle function. Additionally, resveratrol, a SIRT1 activator, has brought beneficial effects to the skeletal, cardiac and respiratory muscles by exerting anti-inflammatory activity that leads to reduced myofiber wasting.
Effects of the COVID-19 Pandemic on Mental Health in Peru: Psychological Distress

This pandemic has been classified as a “psychological pandemic” that produces anxiety, depression, post-traumatic stress disorder, and sleep disorders. As the mental health effects of the Coronavirus Disease 2019 (COVID-19), caused by SARS-CoV-2, continue to unfold, there are still large knowledge gaps about the variables that predispose individuals to, or protect individuals against the disease. However, there are few publications on the effects of the COVID-19 pandemic on the mental health of citizens in Latin American countries. In this study, the effects that COVID-19 had on citizens of Peru have been described. For this, 1699 questionnaires, collected between 2 April and 2 September 2020, were analyzed. Descriptive, bivariate analysis was performed with odds ratio (OR) calculations and a data mining methodology. Sociodemographic variables (from the General Health Questionnaire), health conditions and perception, symptoms, and variables related to contact and preventive measures regarding COVID-19 were analyzed. As compared to other countries, less affectation of mental health and increased use of preventive measures were observed. It has been suggested that the country’s precarious health system and poverty rates prior to the pandemic may justify higher mortality figures in Peru than in other Latin American countries, despite prompt action for its containment and compliance with the protective measures. Psychological distress had a greater incidence in women, young people, people without a partner, and people without university studies. The most significant conditioning variables were self-perceived health status, headache or muscle pain over the past 14 days, level of studies, and age. The extensive use of preventive measures against COVID-19 is in line with the strict legislative measures taken, and this is, in turn, in line with other countries when looking at the lower effect on mental health, but contrary when focusing on the high lethality identified. The need to include the economy or availability and quality of healthcare in future studies arises, as well as the suitability to analyze the cause for differences between countries.
Integration of Dental Implants in Conjunction with EDTA-Conditioned Dentin Grafts: An Experimental Study

This study was undertaken to investigate the integration of titanium micro-implants installed in conjunction with previously dentin-grafted areas and to study the morphological appearance, mineral content, and healing pattern of xenogenic EDTA-conditioned dentin blocks and granules grafted to cavities in the tibial bone of rabbits. Demineralized and non-demineralized dentin blocks and granules from human premolars were implanted into cavities prepared on the lateral aspects of the tibias of rabbits. After a healing period of six months, micro-implants were installed at each surgical site. Histological examinations were carried out after 24 weeks. Characterization of the EDTA-conditioned dentin blocks was performed by means of light microscopy, dental X-rays, scanning electron microscopy, and energy dispersive X-ray analysis (EDX). No implants were found to be integrated in direct contact with the dentin particles or blocks. On the EDTA-conditioned dentin surface, the organic marker elements C and N dominated, as revealed by EDX. The hydroxyapatite constituents Ca and P were almost absent on the dentin surface. No statistically significant difference was observed between the EDTA-conditioned and non-demineralized dentin, as revealed by BIC and BA. The bone-inductive capacity of the dentin material seemed limited, although demineralization by means of EDTA indicated higher BIC and BA values in conjunction with the installed implants in the area. A 12 h EDTA treatment did not fully decalcify the grafts, as revealed by X-ray analysis.
Potential Applications of Chitosan-Based Nanomaterials to Surpass the Gastrointestinal Physiological Obstacles and Enhance the Intestinal Drug Absorption

The small intestine provides the major site for the absorption of numerous orally administered drugs. However, before reaching to the systemic circulation to exert beneficial pharmacological activities, the oral drug delivery is hindered by poor absorption/metabolic instability of the drugs in gastrointestinal (GI) tract and the presence of the mucus layer overlying intestinal epithelium. Therefore, a polymeric drug delivery system has emerged as a robust approach to enhance oral drug bioavailability and intestinal drug absorption. Chitosan, a cationic polymer derived from chitin, and its derivatives have received remarkable attention to serve as a promising drug carrier, chiefly owing to their versatile, biocompatible, biodegradable, and non-toxic properties. Several types of chitosan-based drug delivery systems have been developed, including chemical modification, conjugates, capsules, and hybrids. They have been shown to be effective in improving intestinal assimilation of several types of drugs, e.g., antidiabetic, anticancer, antimicrobial, and anti-inflammatory drugs. In this review, the physiological challenges affecting intestinal drug absorption and the effects of chitosan on those parameters impacting on oral bioavailability are summarized. More appreciably, types of chitosan-based nanomaterials enhancing intestinal drug absorption and their mechanisms, as well as potential applications in diabetes, cancers, infections, and inflammation, are highlighted. The future perspective of chitosan applications is also discussed.