Miracle-dz/UniFAR-FTUs huggingface dataset:
Simultaneous Optimization of Oral and Transdermal Nanovesicles for Bioavailability Enhancement of Ivabradine Hydrochloride

Purpose Ivabradine hydrochloride is selective pacemaker current (If) ion channel inhibitor used in case of chronic heart failure (CHF) with superior efficacy and lower side effects than most β-blockers. However, the drug suffers from low bioavailability (≈40%) due to extensive first-pass metabolism. Hence, this work aims to formulate nanovesicular platforms to enhance their bioavailability both orally and transdermally. Materials and Methods A central composite face-centered design was employed to formulate the nanovesicles, both phosphatidylcholine: drug ratio and percentage of pluronic F68 were used as independent variables. The nine developed formulae were characterized in terms of vesicle size (nm), polydispersity index, zeta potential (mV), entrapment efficiency (%). Decreasing vesicle size, increasing negative value of the zeta potential, and increasing entrapment efficiency were the chosen constraints to optimize the engineered nanovesicles. The candidate formula was subjected to further investigation including lyophilization, loading into carbopol gel, in vitro release, imaging with a transmission electron microscope, histopathological examination, in vitro cytotoxicity study and in vivo pharmacokinetics. Results The optimized nanovesicular formula was composed of lipid: drug ratio of 3.91:1 and 100% pluronic as a stabilizer. It has particle size, zeta potential and entrapment efficiency of 337.6 nm, −40.5 mV and 30.5, respectively. It was then lyophilized in the presence of 5% trehalose as a cryoprotectant, dispersed in 0.5% carbopol to develop the transdermal gel. The two different forms of the candidate formula (lyophilized and gel form) displayed sustained drug release in comparison to drug solution. The histopathological and cytotoxicity studies showed that the optimized formula was safe and highly biocompatible. The pharmacokinetics parameters measured declared a higher Cmax and half-life of both formulae in comparison to market product (Procoralan®) with a 2.54- and 1.85-folds increase in bioavailability, respectively. Conclusion Hence, the developed nanovesicles can be reported as the first nanoplatforms to be used for simultaneous ivabradine delivery by both oral and topical routes with enhanced oral and transdermal drug delivery. The developed nanoplatforms hence can be further used to formulate other drugs that suffer from low bioavailability due to extensive first-pass metabolism.
The Role of Prevention in Reducing the Economic Impact of ME/CFS in Europe: A Report from the Socioeconomics Working Group of the European Network on ME/CFS (EUROMENE)

This report addresses the extent to which there may be scope for preventive programmes for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), and, if so, what economic benefits may accrue from the implementation of such programmes. We consider the economic case for prevention programmes, whether there is scope for preventive programmes for ME/CFS, and what are the health and economic benefits to be derived from the implementation of such programmes. We conclude that there is little scope for primary prevention programmes, given that ME/CFS is attributable to a combination of host and environmental risk factors, with host factors appearing to be most prominent, and that there are few identified modifiable risk factors that could be the focus of such programmes. The exception is in the use of agricultural chemicals, particularly organophosphates, where there is scope for intervention, and where Europe-wide programmes of health education to encourage safe use would be beneficial. There is a need for more research on risk factors for ME/CFS to establish a basis for the development of primary prevention programmes, particularly in respect of occupational risk factors. Secondary prevention offers the greatest scope for intervention, to minimise diagnostic delays associated with prolonged illness, increased severity, and increased costs.
CALIPSO observations of the dependence of homo- andheterogeneous ice nucleation in cirrus clouds on latitude, seasonand surface condition

Abstract. There are two fundamental mechanisms through which cirrus clouds form; homo- and heterogeneous ice nucleation (henceforth hom and het). The relative contribution of each mechanism to ice crystal production often determines the microphysical and radiative properties of a cirrus cloud. A new satellite remote sensing method is described in this study to estimate cirrus cloud ice particle number concentration and the relative contribution of hom and het to cirrus cloud formation as a function of altitude, latitude, season and surface type (e.g. land vs. ocean). This method uses co-located observations from the Infrared Imaging Radiometer (IIR) and from the CALIOP (Cloud and Aerosol Lidar with Orthogonal Polarization) lidar aboard the CALIPSO (Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observation) polar orbiting satellite, employing IIR channels at 10.6 μm and 12.05 μm. The method is applied here to single-layered clouds of visible optical depth between about 0.3 and 3. Two years of Version 3 data have been analyzed for the years 2008 and 2013, with each season characterized in terms of 532 nm cirrus cloud centroid altitude and temperature, the cirrus cloud ice particle number concentration, effective diameter, layer-average ice water content and visible optical depth. Using a conservative criterion for hom cirrus, on average, the sampled cirrus clouds formed through hom occur about 43 % of the time in the Arctic and 50 % of the time in the Antarctic, and during winter at mid-latitudes in the Northern Hemisphere, hom cirrus occur 37 % of the time. Elsewhere (and during other seasons in the Northern Hemisphere mid-latitudes), this hom cirrus fraction is lower. Processes that could potentially explain these observations are discussed, as well as the potential relevancy of these results to ice nucleation studies, climate modeling and jet-stream dynamics.
Biological Properties and Genetic Characterization of Novel Low Pathogenic H7N3 Avian Influenza Viruses Isolated from Mallard Ducks in the Caspian Region, Dagestan, Russia

Avian influenza viruses (AIVs) are maintained in wild bird reservoirs, particularly in mallard ducks and other waterfowl. Novel evolutionary lineages of AIV that arise through genetic drift or reassortment can spread with wild bird migrations to new regions, infect a wide variety of resident bird species, and spillover to domestic poultry. The vast continental reservoir of AIVs in Eurasia harbors a wide diversity of influenza subtypes, including both highly pathogenic (HP) and low pathogenic (LP) H7 AIV. The Caspian Sea region is positioned at the intersection of major migratory flyways connecting Central Asia, Europe, the Black and Mediterranean Sea regions and Africa and holds a rich wetland and avian ecology. To understand genetic reservoirs present in the Caspian Sea region, we collected 559 cloacal swabs from Anseriformes and other species during the annual autumn migration periods in 2017 and 2018. We isolated two novel H7N3 LPAIV from mallard ducks whose H7 hemagglutinin (HA) gene was phylogenetically related to contemporaneous strains from distant Mongolia, and more closely Georgia and Ukraine, and predated the spread of this H7 LPAIV sublineage into East Asia in 2019. The N3 neuraminidase gene and internal genes were prototypical of AIV widely dispersed in wild bird reservoirs sampled along flyways connected to the Caspian region. The polymerase and nucleoprotein segments clustered with contemporaneous H5 HPAI (clade 2.3.4.4b) isolates, suggesting the wide dispersal of H7 LPAIV and the potential of this subtype for reassortment. These findings highlight the need for deeper surveillance of AIV in wild birds to better understand the extent of infection spread and evolution along spatial and temporal flyways in Eurasia.
A Moderate Reduction of Dietary Crude Protein Provide Comparable Growth Performance and Improve Metabolism via Changing Intestinal Microbiota in Sushan Nursery Pigs

Simple Summary Dietary protein is an important source of amino acids for livestock, while excess protein consumption and an imbalance of amino acids in the diet result in increased feed costs and an increased risk of diarrhea, caused by the proliferation of pathogenic bacteria. Therefore, we investigated whether a diet with a moderate reduction of crude protein levels, supplemented with crystalline amino acids, could alleviate these problems. The results showed that a moderate reduction in the dietary protein level can provide similar growth performance and improve metabolism, due to the improvement of intestinal microbiota, compared with high protein feed in Sushan nursery pigs. These findings present new insights into the role of microorganisms in metabolism, and point to a potential nutrition strategy for indigenous pig production. Abstract In this paper, we investigated the effects of a diet with a moderate reduction of dietary crude protein (CP) level, supplemented with five crystalline amino acids (Lys, Met, Thr, Try, and Val), on the growth, metabolism, and fecal microbiota of Sushan nursery pigs. Seventy Sushan nursery pigs with an average body weight of 19.56 ± 0.24 kg were randomly allocated to two experimental dietary treatments: 18% CP (high protein; group HP), and 15% CP (low protein; group LP). We found that the differences in the two diets had no significant effect on the growth performance of Sushan nursery pigs. Nursery pigs on the 15% CP diet showed significantly improved protein, amino acid, and energy utilization. Furthermore, the LP diet cloud optimized the gut microflora composition to some extent. The functional structure of bacterial communities implied improved metabolic capabilities in group LP. Additionally, correlation analysis between fecal microbiota and metabolic profiles confirmed that the increase of beneficial bacterial in the feces was beneficial to the health and metabolism of the nursery pigs. In conclusion, a moderate reduction in the dietary protein level can improve growth and metabolism due to the improvement of intestinal microbiota in Sushan nursery pigs. This finding could provide useful reference data for the application of a different nutrition strategy in indigenous pig production.
Molecular Characterization of Staphylococcus aureus Obtained from Blood Cultures of Paediatric Patients Treated in a Tertiary Care Hospital in Mexico

Purpose Staphylococcus aureus is one of the main causative agents of hospital-acquired (HA) infections. In Mexico, information about the characteristics of clinical S. aureus isolates is limited. Our aim was to characterize S. aureus strains obtained from blood cultures of paediatric patients treated in a tertiary care hospital. Materials and Methods We analysed 249 S. aureus isolates over the period from 2006 to 2019, and their resistance profiles were determined. The isolates were classified into methicillin-resistant S. aureus (MRSA) or methicillin-sensitive S. aureus (MSSA). Staphylococcal cassettes chromosome mec (SCCmec) were detected. Virulence genes (cna, clfA, clfB, eta, etb, fnbA, fnbB, hla, pvl, sec, and tsst) were amplified, and their clonal relationships were established by pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST) and clonal complex (CC) typing. We reviewed one hundred medical files to collect clinical information. Results Thirty-eight percent of the isolates were MRSA and showed an expanded profile of resistance to other non-beta-lactam antibiotics, while MSSA strains presented a reduced resistance profile. SCCmec-II was the most frequent element (86.3%). Eight virulence factors were detected in MSSA and six in MRSA. The pvl gene was detected in four MRSA-SCCmec-IV isolates (P≤0.0001). MRSA isolates were distributed among 14 clones and were classified into 15 sequence types (ST); the most frequent was ST1011 (17%). The most common CC in MRSA was CC5 (69%, P≤0.0001), and in MSSA, it was CC30 (30%, P≤0.0001). Eighty-seven percent of MRSA isolates were HA-MRSA, and 13% were community-acquired MRSA (CA-MRSA). Of 21 HA-MRSA isolates, 17 had SCCmec-II, while two CA-MRSA isolates had SCCmec-IV. Of MSSA isolates, 77% were derived from HA infections and 23% from CA infections. Conclusion MSSA isolates had more virulence factors. MRSA isolates were resistant to more non-beta-lactam antibiotics, and those with SCCmec-IV expressed a greater variety of virulence factors. Most S. aureus isolates belonged to CC5.
Narcissism and Exercise Addiction: The Mediating Roles of Exercise-Related Motives

The present research examined whether the associations that narcissistic personality features had with exercise addiction were mediated by particular motives for engaging in exercise in a large Israeli community sample (N = 2629). The results revealed that each aspect of narcissism was positively associated with exercise addiction. Narcissistic admiration and narcissistic rivalry had similar positive indirect associations with exercise addiction through the interpersonal motive for exercise. However, these aspects of narcissism diverged in their indirect associations with exercise addiction through psychological motives, body-related motives, and fitness motives for exercise such that these indirect associations were positive for narcissistic admiration but negative for narcissistic rivalry. Narcissistic vulnerability had positive indirect associations with exercise addiction through body-related motives and fitness motives that were similar to those observed for narcissistic admiration. These results suggest that exercise-related motives may play important roles in the associations that narcissistic personality features have with exercise addiction. The discussion will focus on the implications of these results for understanding the complex connections between narcissism and exercise addiction.
Is Smiling the Key? Machine Learning Analytics Detect Subtle Patterns in Micro-Expressions of Infants with ASD

Time is a key factor to consider in Autism Spectrum Disorder. Detecting the condition as early as possible is crucial in terms of treatment success. Despite advances in the literature, it is still difficult to identify early markers able to effectively forecast the manifestation of symptoms. Artificial intelligence (AI) provides effective alternatives for behavior screening. To this end, we investigated facial expressions in 18 autistic and 15 typical infants during their first ecological interactions, between 6 and 12 months of age. We employed Openface, an AI-based software designed to systematically analyze facial micro-movements in images in order to extract the subtle dynamics of Social Smiles in unconstrained Home Videos. Reduced frequency and activation intensity of Social Smiles was computed for children with autism. Machine Learning models enabled us to map facial behavior consistently, exposing early differences hardly detectable by non-expert naked eye. This outcome contributes to enhancing the potential of AI as a supportive tool for the clinical framework.
50th Anniversary Perspective: Functional Nanoparticles from the Solution Self-Assembly of Block Copolymers

This Perspective outlines recent advances concerning the formation and potential uses of block copolymer micelles, a class of soft-matter-based nanoparticles of growing importance. As a result of rapidly expanding interest since the mid-1990s, substantial advances have been reported in terms of the development of morphological diversity, structural complexity, control over micelle dimensions, scale-up, and applications in a range of areas from nanocomposites to nanomedicine.
Complete mitochondrial DNA sequence of the Psammocora profundacella (Scleractinia, Psammocoridae): mitogenome characterisation and phylogenetic implications

Abstract Complete mitochondrial DNA sequence data have played a significant role in phylogenetic and evolutionary studies of scleractinian corals. In this study, the complete mitogenome of Psammocora profundacella Gardiner, 1898, collected from Guangdong Province, China, was sequenced by next-generation sequencing for the first time. Psammocora profundacella is the first species for which a mitogenome has been sequenced in the family Psammocoridae. The length of its assembled mitogenome sequence was 16,274 bp, including 13 protein-coding genes, two tRNAs and two rRNAs. Its gene content and gene order were consistent with the other Scleractinia species. All genes were encoded on the H strand and the GC content of the mitochondrial genome was 30.49%. Gene content and order were consistent with the other Scleractinia species. Based on 13 protein-coding genes, Maximum Likelihood phylogenetic analysis showed that P. profundacella belongs to the “Robust” clade. Mitochondrial genome data provide important molecular information for understanding the phylogeny of stony corals. More variable markers and additional species should be sequenced to confirm the evolutionary relationships of Scleractinia in the future.
The Human 2-Cys Peroxiredoxins form Widespread, Cysteine-Dependent- and Isoform-Specific Protein-Protein Interactions

Redox signaling is controlled by the reversible oxidation of cysteine thiols, a post-translational modification triggered by H2O2 acting as a second messenger. However, H2O2 actually reacts poorly with most cysteine thiols and it is not clear how H2O2 discriminates between cysteines to trigger appropriate signaling cascades in the presence of dedicated H2O2 scavengers like peroxiredoxins (PRDXs). It was recently suggested that peroxiredoxins act as peroxidases and facilitate H2O2-dependent oxidation of redox-regulated proteins via disulfide exchange reactions. It is unknown how the peroxiredoxin-based relay model achieves the selective substrate targeting required for adequate cellular signaling. Using a systematic mass-spectrometry-based approach to identify cysteine-dependent interactors of the five human 2-Cys peroxiredoxins, we show that all five human 2-Cys peroxiredoxins can form disulfide-dependent heterodimers with a large set of proteins. Each isoform displays a preference for a subset of disulfide-dependent binding partners, and we explore isoform-specific properties that might underlie this preference. We provide evidence that peroxiredoxin-based redox relays can proceed via two distinct molecular mechanisms. Altogether, our results support the theory that peroxiredoxins could play a role in providing not only reactivity but also selectivity in the transduction of peroxide signals to generate complex cellular signaling responses.
Cerebral Apolipoprotein D Exits the Brain and Accumulates in Peripheral Tissues

Apolipoprotein D (ApoD) is a secreted lipocalin associated with neuroprotection and lipid metabolism. In rodent, the bulk of its expression occurs in the central nervous system. Despite this, ApoD has profound effects in peripheral tissues, indicating that neural ApoD may reach peripheral organs. We endeavor to determine if cerebral ApoD can reach the circulation and accumulate in peripheral tissues. Three hours was necessary for over 40% of all the radiolabeled human ApoD (hApoD), injected bilaterally, to exit the central nervous system (CNS). Once in circulation, hApoD accumulates mostly in the kidneys/urine, liver, and muscles. Accumulation specificity of hApoD in these tissues was strongly correlated with the expression of lowly glycosylated basigin (BSG, CD147). hApoD was observed to pass through bEnd.3 blood brain barrier endothelial cells monolayers. However, cyclophilin A did not impact hApoD internalization rates in bEnd.3, indicating that ApoD exit from the brain is either independent of BSG or relies on additional cell types. Overall, our data showed that ApoD can quickly and efficiently exit the CNS and reach the liver and kidneys/urine, organs linked to the recycling and excretion of lipids and toxins. This indicated that cerebral overexpression during neurodegenerative episodes may serve to evacuate neurotoxic ApoD ligands from the CNS.
Ambroxol Treatment Suppresses the Proliferation of Chlamydia pneumoniae in Murine Lungs

Ambroxol (Ax) is used as a mucolytics in the treatment of respiratory tract infections. Ax, at a general dose for humans, does not alter Chlamydia pneumoniae growth in mice. Therefore, we aimed to investigate the potential anti-chlamydial effect of Ax at a concentration four timed higher than that used in human medicine. Mice were infected with C. pneumoniae and 5-mg/kg Ax was administered orally. The number of recoverable C. pneumoniae inclusion-forming units (IFUs) in Ax-treated mice was significantly lower than that in untreated mice. mRNA expression levels of several cytokines, including interleukin 12 (IL-12), IL-23, IL-17F, interferon gamma (IFN-γ), and surfactant protein (SP)-A, increased in infected mice treated with Ax. The IFN-γ protein expression levels were also significantly higher in infected and Ax-treated mice. Furthermore, the in vitro results suggested that the ERK 1/2 activity was decreased, which is essential for the C. pneumoniae replication. SP-A and SP-D treatments significantly decreased the number of viable C. pneumoniae IFUs and significantly increased the attachment of C. pneumoniae to macrophage cells. Based on our results, a dose of 5 mg/kg of Ax exhibited an anti-chlamydial effect in mice, probably an immunomodulating effect, and may be used as supporting drug in respiratory infections caused by C. pneumoniae.
Using a Deep Learning Method and Data from Two-Dimensional (2D) Marker-Less Video-Based Images for Walking Speed Classification

Human body measurement data related to walking can characterize functional movement and thereby become an important tool for health assessment. Single-camera-captured two-dimensional (2D) image sequences of marker-less walking individuals might be a simple approach for estimating human body measurement data which could be used in walking speed-related health assessment. Conventional body measurement data of 2D images are dependent on body-worn garments (used as segmental markers) and are susceptible to changes in the distance between the participant and camera in indoor and outdoor settings. In this study, we propose five ratio-based body measurement data that can be extracted from 2D images and can be used to classify three walking speeds (i.e., slow, normal, and fast) using a deep learning-based bidirectional long short-term memory classification model. The results showed that average classification accuracies of 88.08% and 79.18% could be achieved in indoor and outdoor environments, respectively. Additionally, the proposed ratio-based body measurement data are independent of body-worn garments and not susceptible to changes in the distance between the walking individual and camera. As a simple but efficient technique, the proposed walking speed classification has great potential to be employed in clinics and aged care homes.
Transformation of graphene flakes into carbon nanostructures by γ-irradiation

In this paper the gamma irradiation effect on graphene layers is investigated. A simple method of synthesis from a solid-source bilayer (SiC/Ni) precursor has been used for the production of graphene flakes, both single-layer and multilayer. Samples with graphene flakes on the Ni surface were subjected to gamma irradiation in vacuum and in air under ambient atmospheric conditions. After a dose of 36 kGy, a variety of new carbon structures were observed on the surface of multilayer graphene flakes. This paper summarizes our thorough studies of the special features of these new carbon formations, including our study of the initial film morphology using optical and electron scanning microscopy, micro-Raman spectroscopy, atomic force microscopy and Kelvin probe force microscopy.