Miracle-dz/UniFAR-FTUs huggingface dataset:
Symptomatic Atherosclerotic Non-acute Intracranial Vertebral Artery Total Occlusion: Clinical Features, Imaging Characteristics, Endovascular Recanalization, and Follow-up Outcomes

Background and Objectives: Previous studies on symptomatic atherosclerotic non-acute intracranial vertebral artery total occlusion that was refractory to medical therapy are rare. We aimed to assess the clinical features, imaging characteristics, endovascular treatment feasibility and follow-up outcomes of patients with this condition. Methods: Data from consecutive patients who had symptomatic atherosclerotic non-acute intracranial vertebral artery total occlusion and underwent endovascular recanalization from February 2016 to April 2020 were retrospectively collected in our prospective database. Clinical, imaging, procedural, and follow-up data were collected and analyzed. Results: Thirty-one patients, predominantly males, were enrolled in this study. These patients presented with recurrent/progressive stroke in the posterior circulation despite aggressive medical therapy. Angiographic analysis revealed asymmetric vertebral arteries due to unilateral hypoplasia and intracranial vertebral artery total occlusions in the dominant vertebral arteries, which were characterized by long lesion length and high clot burden. Multiple infarctions and perfusion defects in the posterior circulation were demonstrated by diffusion-weighted imaging and arterial spin labeling, respectively. Successful endovascular recanalization was achieved in 87.1% of the patients. Over a median clinical follow-up duration of 11.0 months, 74.1% of patients with successful recanalization achieved favorable clinical outcomes (mRS score ≤2). Conclusion: Symptomatic atherosclerotic non-acute intracranial vertebral artery total occlusion attributable to hypoperfusion is characterized by recurrent/progressive ischemic events, dominant intracranial vertebral artery total occlusion, long lesion length, and high clot burden. Endovascular recanalization of the dominant intracranial vertebral artery occlusion appears to be a feasible treatment for these patients.
GENETIC CHARACTERIZATION OF EGYPTIAN NEWCASTLE DISEASE VIRUS STRAINS ISOLATED FROM FLOCKS VACCINATED AGAINST NEWCASTLE DISEASE VIRUS, 2014-2015

In the present study, forty-five chicken flocks suspected to be infected with Newcastle disease virus (NDV) in Sharkia Governorate were submitted for clinical and postmortem examination as well as virus isolation and sero-molecular identification. Forty samples were positive for hemagglutinating viruses, 15/40 (37.5%) were confirmed positive isolates against NDV antiserum, 12/40 (30%) were positive isolates against both NDV and AIV (H5) antisera and 9/40 (22.5%) were positive against AIV antiserum using serological identification. Twenty-seven NDV isolates were confirmed positive by molecular identification; twelve of them were confirmed as virulent NDV strains using specific primers. A fragment of 766-bp comprising the 3' end of the M gene and the 5' end of the F gene was sequenced from four amplified products, revealing that these isolates carried the 112RRQKRF117 motif, which is characteristic of virulent strains. The investigated strains were clustered with a class II genotype VIId with large genetic distance with the LaSota strain. This is alarming given the potential evolution of different virulent NDVs and may explain the circulation of these virulent strains among Egyptian poultry farms despite the application of intensive vaccination programs. Key words: Sharkia; NDV; genotype VIId; poultry; PCR
Irisin Protects Against Motor Dysfunction of Rats with Spinal Cord Injury via Adenosine 5'-Monophosphate (AMP)-Activated Protein Kinase-Nuclear Factor Kappa-B Pathway

The aim of the present research was to investigate the effects of irisin, a skeletal muscle-derived myokine, on spinal cord injury (SCI) in rats and explore the possible mechanisms. SCI model was constructed in male SD rats. The effects of irisin on SCI rats were assessed via behavior tests including Basso, Beattie, and Bresnahan (BBB) scoring method and inclined plane test, followed by histomorphology tests including HE staining, Nissl staining, and transmission electron microscope examination. Biochemical analyses including PCR, Western blots and ELISA were employed to further evaluate the changes at molecular level of SCI rats. In addition, lipopolysaccharide (LPS)-induced cell damage model was established in PC12 cells to verify the mechanism of irisin’s effect on nerve cells in vitro. Results showed that the BBB score and the angle of incline significantly decreased after SCI surgery, however, chronic irisin treatment improved SCI-induced motor dysfunction. HE and Nissl staining assays showed that SCI surgery induced histological injury of spinal cord, which could be reversed by irisin treatment. Morphological abnormality of nerve cells caused by SCI also could be alleviated by irisin. Further biochemical analyses showed that irisin inhibited SCI-induced overexpression of Interleukin-1β (IL-1β), Interleukin- 6 (IL-6), tumor necrosis factor alpha (TNF-α), inducible nitricoxidesynthase (iNOS) and Cyclooxygenase-2 (COX-2)], as well as nuclear factor kappa-B (NF-κB)p65 in rats, and the positive function of irisin could be reversed by Compound C treatment. In our in vitro study, LPS-induced declines of cell viability and neurite length of PC12 cell were inhibited by irisin treatment, and irisin inhibited LPS-induced overexpression of NF-κBp65, IL-1β, IL-6, TNF-α, iNOS and COX-2. These changes could be reversed by activated protein kinase (AMPK) siRNA pre-treatment. Taken together, irisin could protect the rats from SCI, and its protection is associated with the regulation of adenosine 5'-monophosphate-activated protein kinase (AMPK)- NF-κB signaling pathway.
Cutibacterium acnes Phylotype I and II Strains Interact Differently With Human Skin Cells

Acne vulgaris is one of the most common skin disorders and affects the pilosebaceous units. Although the exact pathogenesis of acne is still unknown, Cutibacterium acnes (formerly known as Propionibacterium acnes) is considered one of the key contributing factors. In fact, a significant association exists between C. acnes strains belonging to phylotype I and acne. However, there is still heavy debate on the exact role of C. acnes in acne and its behavior in the pilosebaceous unit, and more specifically its interactions with the human skin cells. In this study, key elements of the host-pathogen interaction were studied for a collection of C. acnes strains, belonging to phylotype I and II, including association with HaCaT keratinocytes and SZ95 sebocytes, the effect of C. acnes on keratinocyte tight junctions in a HaCaT monoculture and in an additional keratinocyte-sebocyte co-culture model, and C. acnes invasion through the keratinocyte cell layer. Our data showed association of all C. acnes strains to both skin cell lines, with a significantly higher association of type I strains compared to type II strains. Microscopic imaging and western blot analysis of the tight junction protein ZO-1, together with transepithelial electrical resistance (TEER) measurements revealed an initial induction of keratinocyte tight junctions after 24 h infection but a degradation after 48 h, demonstrating a decline in cell lining integrity during infection. Subsequently, C. acnes was able to invade after 48 h of infection, although invasion frequency was significantly higher for type II strains compared to type I strains.
Darwinian dynamics over recurrent neural computations for combinatorial problem solving

Efficient search in enormous combinatorial spaces is an essential component of intelligence. Humans, for instance, are often found searching for optimal action sequences, linguistic structures and causal explanations. Is there any computational domain that provides good-enough and fast-enough solutions to such a diverse set of problems, yet can be robustly implemented over neural substrates? Based on previous accounts, we propose that a Darwinian process, operating over sequential cycles of imperfect copying and selection of informational patterns, is a promising candidate. It is, in effect, a stochastic parallel search that i) does not need local gradient-like information and ii) redistributes its computational resources from globally bad to globally good solution candidates automatically. Here we demonstrate these concepts in a proof-of-principle model based on dynamical output states of reservoir computers as units of evolution. We show that a population of reservoir computing units, arranged in one or two-dimensional topologies, is capable of maintaining and continually improving upon existing solutions over rugged combinatorial reward landscapes. We also provide a detailed analysis of how neural quantities, such as noise and topology, translate to evolutionary ones, such as mutation rate and population structure. We demonstrate the existence of a sharp error threshold, a neural noise level beyond which information accumulated by an evolutionary process cannot be maintained. We point at the importance of neural representation, akin to genotype-phenotype maps, in determining the efficiency of any evolutionary search in the brain. Novel analysis methods are developed, including neural firing pattern phylogenies that display the unfolding of the process.
Nitrate inhibits nodule organogenesis through inhibition of cytokinin biosynthesis in Lotus japonicus

Legumes balance nitrogen acquisition from soil nitrate with symbiotic nitrogen fixation. Nitrogen fixation requires establishment of a new organ, which is a cytokinin dependent developmental process in the root. We found cytokinin biosynthesis is a central integrator, balancing nitrate signalling with symbiotic acquired nitrogen. Low nitrate conditions provide a permissive state for induction of cytokinin by symbiotic signalling and thus nodule development. In contrast, high nitrate is inhibitory to cytokinin accumulation and nodule establishment in the root zone susceptible to nodule formation. This reduction of symbiotic cytokinin accumulation was further exacerbated in cytokinin biosynthesis mutants, which display hypersensitivity to nitrate inhibition of nodule development, maturation and nitrogen fixation. Consistent with this, cytokinin application can rescue nodulation and nitrogen fixation of biosynthesis mutants in a concentration dependent manner. These inhibitory impacts of nitrate on symbiosis occur in a Nlp1 and Nlp4 dependent manner and contrast with the positive influence of nitrate on cytokinin biosynthesis that occurs in non-symbiotic species. Altogether this shows that legumes, as exemplified by Lotus japonicus, have evolved a different cytokinin response to nitrate compared to non-legumes. One sentence summary Cytokinin biosynthesis is suppressed by nitrate in Lotus japonicus, providing a mechanism for nitrate inhibition of symbiotic nodule organogenesis.
Genome-wide analysis of long noncoding RNAs, 24-nt siRNAs, DNA methylation and H3K27me3 marks in Brassica rapa and related species

Long noncoding RNAs (lncRNAs) are RNA fragments that generally do not code for a protein but are involved in epigenetic gene regulation. In this study, lncRNAs of Brassica rapa were classified into long intergenic noncoding RNAs, natural antisense RNAs, and intronic noncoding RNAs and their expression were analyzed in relation to genome-wide 24-nt small interfering RNAs (siRNAs), DNA methylation, and histone H3 lysine 27 trimethylation marks (H3K27me3). More than 65% of the lncRNAs analyzed consisted of one exon, and more than 55% overlapped with inverted repeat regions (IRRs). Overlap of lncRNAs with IRRs or genomic regions encoding for 24-nt siRNAs resulted in increased DNA methylation levels and when both were present, there were further increase in DNA methylation levels. LncRNA did not overlap greatly with H3K27me3 marks, but the expression level of intronic noncoding RNAs that did coincide with H3K27me3 marks was higher than without H3K27me3 marks. The Brassica genus comprises important vegetables and oil seed crops grown across the world. Brassica rapa is a diploid (AA genome) thought to be one of the ancestral species of both B. juncea (AABB genome) and B. napus (AACC) through genome merging (allotetrapolyploidization). Complex genome restructuring and epigenetic alterations are thought to be involved in these allotetrapolyploidization events, but the detailed mechanism is not known. Comparison of lncRNAs between B. rapa and B. nigra, B. oleracea, B. juncea, and B. napus showed the highest conservation with B. oleracea. This study presents a comprehensive analysis of the epigenome structure of the B. rapa at multi-epigenetic levels (siRNAs, DNA methylation, H3K27me3, and lncRNAs) and offers insights into the function of lncRNA in the Brassica genus.
Derivation of predator functional responses using a mechanistic approach in a natural system

The functional response is central to our understanding of any predator–prey system as it establishes the link between trophic levels. Most functional responses are evaluated using phenomenological models linking predator acquisition rate and prey density. However, our ability to measure functional responses using such an approach is often limited in natural systems and the use of inaccurate functions can profoundly affect the outcomes of population and community models. Here, we develop a mechanistic model based on extensive data to assess the functional response of a generalist predator, the arctic fox (Vulpes lagopus), to various tundra prey species (lemmings and the nests of geese, passerines and sandpipers). We found that predator acquisition rates derived from the mechanistic model were consistent with field observations. Although sigmoidal functional responses were previously used to model fox-prey population dynamics, none of our simulations resulted in a saturating response in all prey species. Our results highlight the importance of predator searching components in predator-prey interactions, especially predator speed, while predator acquisition rates were not limited by handling processes. By combining theory with field observations, our study provides evidences that predator acquisition rate is not systematically limited at the highest prey densities observed in a natural system. We reinforce the idea that functional response categories, typically types I, II, and III, should be considered as particular cases along a continuum. Specific functions derived with a mechanistic approach for a range of densities observed in natural communities should improve our ability to model and understand predator-prey systems.
In-vivo histology of iron and myelin in the brain using magnetic susceptibility source separation in MRI

Obtaining a histological fingerprint from the in-vivo brain has been a long-standing target of magnetic resonance imaging (MRI). In particular, non-invasive imaging of iron and myelin, which are involved in normal brain functions and are histopathological hallmarks in a few neurodegenerative diseases, has practical utilities in neuroscience and medicine. Here, we propose a biophysical model that describes the individual contribution of iron and myelin to MRI signals via their difference in magnetic susceptibility (i.e., paramagnetic iron vs. diamagnetic myelin). Using this model, we develop a method, χ-separation, that generates the voxel-wise distributions of iron and myelin. The method is validated using computer simulation and phantom experiments, and applied to ex-vivo and in-vivo brains. The results delineate the well-known histological features of iron and myelin in the specimen (e.g., co-localization of iron and myelin in Gennari line), healthy volunteers (e.g., myelin-lacking and iron-rich pulvinar), and multiple sclerosis patients (e.g., demyelinated iron-rim lesion). This new in-vivo histology technology, taking less than 20 min, may serve as a practical tool for exploring the microstructural information of the brain.
The spatial-temporal dynamics of respiratory syncytial virus infections across the east-west coasts of Australia during 2016-17

Respiratory syncytial virus (RSV) is an important human respiratory pathogen. In temperate regions a distinct seasonality is observed, where peaks of infections typically occur in early winter, often preceding the annual influenza season. Infections are associated with high rates of morbidity and mortality, and in some populations exceeds that of influenza. Two subtypes, RSV-A and RSV-B, have been described, and molecular epidemiological studies have shown that both viruses mostly co-circulate. This trend also appears to be the case for Australia, however previous genomic studies have been limited to cases from one Eastern state - New South Wales. As such, the broader spatial patterns and viral traffic networks across the continent are not known. Here, we conducted a whole genome study of RSV comparing strains across eastern and western Australia during the period January 2016 to June 2017. In total, 96 new RSV genomes were sequenced, compiled with previously generated data, and examined using a phylodynamic approach. This analysis revealed that both RSV-A and RSV-B strains were circulating, and each subtype was dominated by a single genotype, RSV-A/ON1-like and RSV-B/BA10-like viruses. Some geographical clustering was evident in strains from both states with multiple distinct sub-lineages observed and relatively low mixing across jurisdictions suggesting that endemic transmission was likely seeded from imported, unsampled locations. Overall, the RSV phylogenies reflected a complex pattern of interactions across multiple epidemiological scales from fluid virus traffic across global and regional networks to fine-scale local transmission events.
Memory shapes microbial populations

Correct decision making is fundamental for all living organisms to thrive under environmental changes. The patterns of environmental variation and the quality of available information define the most favourable strategy among multiple options, including sensing and reacting to environmental cues or randomly adopting a phenotypic state. Memory – a phenomenon often associated with, but not restricted to, higher multicellular organisms – can help when temporal correlations exist. How does memory manifest itself in unicellular organisms? Through a combination of deterministic modelling and stochastic simulations, we describe the population-wide fitness consequences of phenotypic memory in microbial populations. Moving beyond binary switching models, our work highlights the need to consider a broader range of switching behaviours when describing microbial adaptive strategies. We show that multiple cellular states capture the empirical observations of lag time distributions, overshoots, and ultimately the phenomenon of phenotypic heterogeneity. We emphasise the implications of our work in understanding antibiotic tolerance, and, in general, survival under fluctuating environments.
A quick and cost-effective method for DNA-free total RNA isolation using magnetic silica beads

Current RNA purification methods widely use silica-based columns that allow quick isolation of high-quality and good quantities of RNA. However, the major limitations include high cost, the requirement of different kits for small RNA isolation, genomic DNA contamination, and not being flexible. Here, we used the in-house RNA isolation reagent (RIR) for cell lysis, followed by RNA precipitation using isopropanol. RNA isolated using the in-house RIR resulted in a similar quantity and quality compared to the commercial TRIzol. Furthermore, the commercial RNA isolation kits with silica-based columns recommend genomic DNA digestion during or after RNA purification, adding time and cost to RNA purification. Here, we developed an optimized in-house protocol for isolating high-quality RNA free of genomic DNA contamination using magnetic silica beads without needing DNase digestion. Additionally, our method purifies total RNA along with the small RNA fraction, including miRNAs, which usually require a separate kit for extraction. Additionally, the RNA prepared with our method was equally suitable for mRNA and miRNA expression analysis using RT-qPCR. Together, the in-house method of RNA isolation using the magnetic silica beads has exhibited comparable or better total RNA extraction compared to commercial kits at a fraction of the cost and across various cells and tissues.
Aberrant peripheral immune responses in acute Kawasaki disease with single-cell sequencing

Kawasaki disease (KD) is the most common cause of acquired heart disease in children in developed countries. Although diverse immune aberrance was reported, a global understanding of immune responses underlying acute KD was lacking. Based on single-cell sequencing, we profiled peripheral blood mononuclear cells from patients with acute KD before and after intravenous immunoglobulin therapy and from healthy controls. Most differentially expressed genes were derived from monocytes, with upregulation of immunoglobulin receptors, complement and receptors and downregulation of MHC class II receptors before therapy. The percentage of B cells was significantly increased before therapy and rapidly returned to normal after therapy. There was also an increased abundance of B-cell receptors with IGHA and IGHG after therapy, accompanied by massive oligoclonal expansion. The percentage of CD8 T cells was remarkably decreased during acute KD, especially the subset of effector memory CD8 T cells. All lymphocyte compartments were characterized by underexpressed interferon response pathways before therapy. The identification of unique innate and adaptive immune responses suggests potential mechanisms underlying pathogenesis and progression of KD.