Miracle-dz/UniFAR-FTUs huggingface dataset:
Exaggerated in vivo IL-17 responses discriminate recall responses in active TB

Host immune responses at the site of Mycobacterium tuberculosis (Mtb) infection serve to contain the pathogen, but also mediate the pathogenesis of tuberculosis (TB) and onward transmission of infection. Interferon gamma (IFNγ) responses do not discriminate between protection and pathogenicity, but IL-17A/F responses, known to drive pathology in diverse chronic inflammatory diseases, have also been associated with TB pathogenesis in animal models. At the site of in vivo immune recall responses to Mtb modelled by the tuberculin skin test, we show for the first time that active TB in humans is also associated with exaggerated IL-17A/F expression, accumulation of Th17 cells and IL-17A/F bioactivity, including increased neutrophil recruitment and matrix metalloproteinase-1 expression directly implicated in TB pathogenesis. These features discriminate recall responses in patients with active TB from those with cured or latent infection and are also evident at the site of TB disease. Our data support targeting of this pathway in host-directed therapy for TB.
Stereotactic Body Radiotherapy Is Effective in Modifying the Tumor Genome and Tumor Immune Microenvironment in Non-Small Cell Lung Cancer or Lung Metastatic Carcinoma

Background and Purpose To directly reveal the change in genome mutation, RNA transcript of tumor cells, and tumor microenvironment (TME) after stereotactic body radiotherapy (SBRT) in paired human lung tumor specimens. Materials and Methods Paired tumor samples were collected from 10 patients with non-small cell lung cancer (NSCLC) or lung metastatic carcinoma within a week before and after SBRT. DNA and RNA of tumor tissues was extracted from the paired samples. Whole-exome and RNA sequencing assays were performed by next-generation sequencing. Gene mutation, genomic expression, T-cell receptor (TCR) repertoire, and profiling of tumor-infiltrating immune cells were analyzed through bioinformatics analysis in paired tumor samples. CD8+ T-cell infiltration and PD-L1 expressions were detected by immunostaining in tumor tissues. Results The diversity of TCR repertoire and PD-L1 expression increased significantly in the TME, and the most enriched term of the gene ontology analysis was the immune response gene after receiving SBRT. SBRT induced neo-mutation of genes in tumor cells but did not increase tumor mutation burden in tumor tissues. TME displayed complex immune cell changes and infiltration and expression of immune-regulating factors such as C-X-C motif chemokine (CXCL) 10, CXCL16, interferons (IFNs), and IFN receptors. CD8+ T-cells in tumor tissues did not improve significantly after SBRT while the infiltrating TH1 and TH2 cells decreased remarkably. Conclusion SBRT improved the TCR repertoire diversity and PD-L1 expression in the TME and induced neo-mutation of genes in tumor cells but did not increase CD8+ T-cell infiltration and IFN expression in the tumor tissue within a week.
Effect of Forage Moringa oleifera L. (moringa) on Animal Health and Nutrition and Its Beneficial Applications in Soil, Plants and Water Purification

Moringa oleifera L. (moringa) is known as one of the most useful multipurpose plants. It can be effectively utilized as a natural biopesticide and inhibitor of several plant pathogens. Thus, it can be included in integrated pest management strategies. Moringa and its products have different uses in many agricultural systems. The use of moringa as a crop enhancer is an eco-friendly way of improving crop yields at the lowest possible cost. This inexpensive increase in productivity can contribute to meeting some of the food needs in some parts of the world as the global population increases and poverty rates rise. One of the most important characteristics of moringa is that it has high biological and nutritional values and can be used as animal feed, green fertilizer, medicine, biopesticide and in seed production. Moringa has been characterized as a potentially useful animal feed owing to its high content of protein, carotenoids, several minerals and vitamins (such as iron and ascorbic acid) and certain phytochemicals (kaempferitrin, isoquercitrin, rhamnetin, kaempferol and quercetin). This review aims to provide more knowledge about the nature, nutritional value, phytochemicals and uses of Moringa oleifera as a promising material in the fields of soil and plant management, water treatment, as well as animal and poultry production.
Top-Down Inference in the Auditory System: Potential Roles for Corticofugal Projections

It has become widely accepted that humans use contextual information to infer the meaning of ambiguous acoustic signals. In speech, for example, high-level semantic, syntactic, or lexical information shape our understanding of a phoneme buried in noise. Most current theories to explain this phenomenon rely on hierarchical predictive coding models involving a set of Bayesian priors emanating from high-level brain regions (e.g., prefrontal cortex) that are used to influence processing at lower-levels of the cortical sensory hierarchy (e.g., auditory cortex). As such, virtually all proposed models to explain top-down facilitation are focused on intracortical connections, and consequently, subcortical nuclei have scarcely been discussed in this context. However, subcortical auditory nuclei receive massive, heterogeneous, and cascading descending projections at every level of the sensory hierarchy, and activation of these systems has been shown to improve speech recognition. It is not yet clear whether or how top-down modulation to resolve ambiguous sounds calls upon these corticofugal projections. Here, we review the literature on top-down modulation in the auditory system, primarily focused on humans and cortical imaging/recording methods, and attempt to relate these findings to a growing animal literature, which has primarily been focused on corticofugal projections. We argue that corticofugal pathways contain the requisite circuitry to implement predictive coding mechanisms to facilitate perception of complex sounds and that top-down modulation at early (i.e., subcortical) stages of processing complement modulation at later (i.e., cortical) stages of processing. Finally, we suggest experimental approaches for future studies on this topic.
Protein Kinase R Restricts the Intracellular Survival of Mycobacterium tuberculosis by Promoting Selective Autophagy

Tuberculosis (TB) is a deadly infectious lung disease caused by the pathogenic bacterium Mycobacterium tuberculosis (Mtb). The identification of macrophage signaling proteins exploited by Mtb during infection will enable the development of alternative host-directed therapies (HDT) for TB. HDT strategies will boost host immunity to restrict the intracellular replication of Mtb and therefore hold promise to overcome antimicrobial resistance, a growing crisis in TB therapy. Protein Kinase R (PKR) is a key host sensor that functions in the cellular antiviral response. However, its role in defense against intracellular bacterial pathogens is not clearly defined. Herein, we demonstrate that expression and activation of PKR is upregulated in macrophages infected with Mtb. Immunological profiling of human THP-1 macrophages that overexpress PKR (THP-PKR) showed increased production of IP-10 and reduced production of IL-6, two cytokines that are reported to activate and inhibit IFNγ-dependent autophagy, respectively. Indeed, sustained expression and activation of PKR reduced the intracellular survival of Mtb, an effect that could be enhanced by IFNγ treatment. We further demonstrate that the enhanced anti-mycobacterial activity of THP-PKR macrophages is mediated by a mechanism dependent on selective autophagy, as indicated by increased levels of LC3B-II that colocalize with intracellular Mtb. Consistent with this mechanism, inhibition of autophagolysosome maturation with bafilomycin A1 abrogated the ability of THP-PKR macrophages to limit replication of Mtb, whereas pharmacological activation of autophagy enhanced the anti-mycobacterial effect of PKR overexpression. As such, PKR represents a novel and attractive host target for development of HDT for TB, and our data suggest value in the design of more specific and potent activators of PKR.
Flexible Virtual Reality System for Neurorehabilitation and Quality of Life Improvement

As life expectancy is mostly increasing, the incidence of many neurological disorders is also constantly growing. For improving the physical functions affected by a neurological disorder, rehabilitation procedures are mandatory, and they must be performed regularly. Unfortunately, neurorehabilitation procedures have disadvantages in terms of costs, accessibility and a lack of therapists. This paper presents Immersive Neurorehabilitation Exercises Using Virtual Reality (INREX-VR), our innovative immersive neurorehabilitation system using virtual reality. The system is based on a thorough research methodology and is able to capture real-time user movements and evaluate joint mobility for both upper and lower limbs, record training sessions and save electromyography data. The use of the first-person perspective increases immersion, and the joint range of motion is calculated with the help of both the HTC Vive system and inverse kinematics principles applied on skeleton rigs. Tutorial exercises are demonstrated by a virtual therapist, as they were recorded with real-life physicians, and sessions can be monitored and configured through tele-medicine. Complex movements are practiced in gamified settings, encouraging self-improvement and competition. Finally, we proposed a training plan and preliminary tests which show promising results in terms of accuracy and user feedback. As future developments, we plan to improve the system’s accuracy and investigate a wireless alternative based on neural networks.
Effect of intraocular pressure lowering on the capillary density of optic nerve head and retinal nerve fiber layer in patients with glaucoma

Purpose: To evaluate the effect of IOP lowering on the capillary density of optic nerve head and retinal nerve fiber layer in patients with primary open angle glaucoma. Methods: Twenty eyes of 14 glaucomatous patients and 15 eyes of nine normal patients were enrolled. The most appropriate hypotonic treatment was applied to every patient. A HD Angio Disc 4.5 scan (Avanti-AngioVue) was performed at baseline and after a month in the glaucomatous eyes. The following parameters were analyzed: Radial Papillary Capillaries (RPC) density, inside disc, peripapillary, superior-hemi, inferior-hemi, quadrants, and peripapillary, hemi-superior, hemi-inferior, and quadrants RNFL thickness. Optic nerve head analysis was also evaluated. In addition, the RPC density and the RNFL were assessed in the eight sectors provided by the software. Results: The RPC density did not significantly change after IOP reduction (p > 0.05). The inferior-temporal (p = 0.005) and inferior-nasal sectors (p < 0.001) showed a greater capillary density than the respective superior sectors in healthy eyes. In contrast in the glaucomatous eyes, the superior-nasal exhibited greater capillary density with respect to the inferior-nasal sectors. The aggregate RPC density of the inferior sectors was greater than the superior ones in the control group (p < 0.001). An improvement of the average disc area (p = 0.01) and the average cup volume (p = 0.059) were also observed along with increased RNFL thickness at different locations (all, p < 0.05) after IOP lowering therapy was initiated. Conclusion: The glaucomatous eyes presented rarefaction of the radial papillary capillaries density in the inferior sectors, but no significant changes in the density after IOP-lowering medications.
Marangoni effects on the motion of an expanding or contracting bubble pinned at a submerged tube tip

This work studies the motion of an expanding or contracting bubble pinned at a submerged tube tip and covered with an insoluble Volmer surfactant. The motion is driven by constant flow rate Q into or out of the tube tip. The purpose is to examine two central assumptions commonly made in the bubble and drop methods for measuring dynamic surface tension, those of uniform surfactant concentration and of purely radial flow. Asymptotic solutions are obtained in the limit of the capillary number Ca→0 with the Reynolds number Re=o(Ca−1, non-zero Gibbs elasticity (G), and arbitrary Bond number (Bo). (Ca=μQ/a2σc, where μ is the liquid viscosity, a is the tube radius, and σc is the clean surface tension.) This limit is relevant to dynamic-tension experiments, and gives M→∞, where M=G/Ca is the Marangoni number. We find that in this limit the deforming bubble at each instant in time takes the static shape. The surfactant distribution is uniform, but its value varies with time as the bubble area changes. To maintain a uniform distribution at all times, a tangential flow is induced, the magnitude of which is more than twice that in the clean case. This is in contrast to the surface-immobilizing effect of surfactant on an isolated translating bubble. These conclusions are confirmed by a boundary integral solution of Stokes flow valid for arbitrary Ca, G and Bo. The uniformity in surfactant distribution validates the first assumption in the bubble and drop methods, but the enhanced tangential flow contradicts the second.
Dose‐escalation study of vemurafenib with sorafenib or crizotinib in patients with BRAF‐mutated advanced cancers

BRAF inhibitors are effective in melanoma and other cancers with BRAF mutations; however, patients ultimately develop therapeutic resistance through the activation of alternative signaling pathways such as RAF/RAS or MET. The authors hypothesized that combining the BRAF inhibitor vemurafenib with either the multikinase inhibitor sorafenib or the MET inhibitor crizotinib could overcome therapeutic resistance.
Involvement of Essential Signaling Cascades and Analysis of Gene Networks in Diabesity

(1) Aims: Diabesity, defined as diabetes occurring in the context of obesity, is a serious health problem that is associated with an increased risk of premature heart attack, stroke, and death. To date, a key challenge has been to understand the molecular pathways that play significant roles in diabesity. In this study, we aimed to investigate the genetic links between diabetes and obesity in diabetic individuals and highlight the role(s) of shared genes in individuals with diabesity. (2) Methods: The interactions between the genes were analyzed using the Search Tool for the Retrieval of Interacting Genes (STRING) tool after the compilation of obesity genes associated with type 1 diabetes (T1D), type 2 diabetes (T2D), and maturity-onset diabetes of the young (MODY). Cytoscape plugins were utilized for enrichment analysis. (3) Results: We identified 546 obesity genes that are associated with T1D, T2D, and MODY. The network backbone of the identified genes comprised 514 nodes and 4126 edges with an estimated clustering coefficient of 0.242. The Molecular Complex Detection (MCODE) generated three clusters with a score of 33.61, 16.788, and 6.783, each. The highest-scoring nodes of the clusters were AGT, FGB, and LDLR genes. The genes from cluster 1 were enriched in FOXO-mediated transcription of oxidative stress, renin secretion, and regulation of lipolysis in adipocytes. The cluster 2 genes enriched in Src homology 2 domain-containing (SHC)-related events triggered by IGF1R, regulation of lipolysis in adipocytes, and GRB2: SOS produce a link to mitogen-activated protein kinase (MAPK) signaling for integrins. The cluster 3 genes ere enriched in IGF1R signaling cascade and insulin signaling pathway. (4) Conclusion: This study presents a platform to discover potential targets for diabesity treatment and helps in understanding the molecular mechanism.
Cyclic RGD Peptide Targeting Coated Nano Drug Co-Delivery System for Therapeutic Use in Age-Related Macular Degeneration Disease

Vascular endothelial growth factor (VEGF) expression increased significantly in the pathogenesis of age-related macular degeneration, which induced the formation of pathological blood vessels. Dexamethasone is an exogenous anti-angiogenic drug while bevacizumab is an endogenous anti-angiogenic drug. They both have been widely used in ophthalmology. However, independent administration is not enough to completely block the development of choroidal neovascularization (CNV), and the number of eyes vitreous injections is limited. Reasonable combination of drugs may produce significantly better therapeutic effect than single drug treatment. The cyclic RGD (cRGD) peptide has a particularly high affinity with retinal pigment epithelial cells, where VEGF secretes from. In this study, we prepared nanoparticles of bevacizumab and dexamethasone with cRGD peptide as the target (aBev/cRGD-DPPNs). The particle size of the aBev/cRGD-DPPNs was 213.8 ± 1.5 nm, SEM results showed that the nano-carriers were well dispersed and spherical. The cell uptake study demonstrated the selectivity of the aBev/cRGD-DPPN to ARPE-19 with αVβ3 over expressed. The aBev/cRGD-DPPNs had a better apoptosis induction effect and an obvious inhibitory effect on migration, invasion, and capillary-like structures formation of human umbilical vein epithelial cells. The fluorescein fundus angiography study, immunohistochemistry and histopathological evaluation showed the aBev/cRGD-DPPNs greatly reduced the development of CNV on a rabbit model.
EVALUATION ABILITY OF DIFFERENT BARADA RIVER MICROCOCCUS SPP. STRAIN TO BIOREMEDIATION OF HYDROCARBONS

The importance of this study is that it is deals with the Barada River pollution with hydrocarbons (crude oil and its derivatives), as well as evaluating the ability of different types of Micrococcus sp. to bioremediation of hydrocarbons. Ten strains of Micrococcus sp. were isolated from the water samples from Barada River in Damascus, and these isolated were classified depending on Bergey's manual to four species: M. luteus, M. lylae, M. flavus, and M. antarcticus. The crude oil dependent growths of these isolates were assessed for 15 days at 30°C by monitoring the gradient fluxes in pH, optical density OD and total viable count TVC in the medium. The result was statistically supported by applying the One-way ANOVA test and the Paired sample t-test. The results showed that activity of species was best at the concentration of 2% of crude oil, and the species of M. lylae was best in dealing with crude oil, although this superiority between species was not supported at the statistical studying. In general, the different species of Micrococcus sp. have a good ability to deal with the different concentrations (1, 2 and 3%) of crude oil. And this supports research which encourages the use of this genus in the bioremediation. This research was indicated to the ability of M. lylae to deal with different concentrations of crude oil, which was not mentioned in previous research
Research on Optimization Scheme of Ship Radar Information Storage Based on Big Data

With the development of marine information technology, ship radar data increases geometrically, and the traditional local server storage architecture has become increasingly unable to meet the requirements of modern ship radar data capacity, so cloud storage has gradually become the mainstream technology of radar data storage. At the same time, because the marine communication network is more vulnerable to external attacks and environmental interference, high-density encryption technology suitable for cloud storage is needed. In this paper, a ship radar cloud storage platform based on big data is studied, and a high-density encryption algorithm CP-ASBE is designed. Finally, simulation is carried out.
Floating countries and corona pandemic: Impact of COVID-19 on stranded Cruise ships

Cruise ships transport a significant number of people in confined spaces over an extended period than other modes of transportation, thereby presenting a unique environment to elevate human-to-human transmitted infections. The overcrowded public rooms, congested accommodations, standard food supplies, and shared sanitary facilities encourage the transmission of infectious diseases by affected persons and through contaminated food, water and surfaces. A novel coronavirus (COVID-19) originating from Wuhan, China in November 2019 spread globally. Unfortunately, Diamond Princess is the first cruise ship on board to have an outbreak of COVID-19 with 3711 passengers and crew members. It began from Yokohama on January 20, 2020, and was supposed to return to Yokohama on February 3 2020. An 80-year-old male passenger, who debarked in Hong Kong on January 25 2020, tested positive for COVID-19 on February 1. Diamond Princess was immediately ordered to stay in the ocean and follow quarantine measures near Yokohama from February 3 onwards. Several other cruise ships such as the Grand Princess, MS Westerdam, Zaandam, etc. had COVID-19 outbreaks onboard. The failure to isolate the crew at the very beginning of quarantine resulted in further transmission of the virus to the passengers and crew. In conclusion, the compact conditions in the cruise ships with high population density amplified the transmission of COVID-19, mainly driven by contact rate and mixing effects.
The flavor of the classic margarita cocktail

The classic Margarita cocktail is made with tequila, orange liqueur, and lime juice. Among other things, this cocktail owes its popularity to its smooth, pleasant, and refreshing flavor. Each of the main ingredients makes its own contribution to the overall perception of this unique flavor. One way to investigate the flavor of a classic Margarita cocktail is to look at the flavor profiles of its ingredients. Tequila, orange, and lime were analyzed as part of the Generessence® program at International Flavors & Fragrances, Inc. Their flavor compositions were determined by gas chromatography-mass spectrometry. Three sample preparation methods were used in the analysis: liquid/liquid extraction, dynamic headspace, and stir bar sorptive extraction (Twister™). The flavor profiles were assessed by combining the results obtained by different sample preparation methods. Each of the main ingredients has been shown to contain few hundred flavor components, indicating that a classic Margarita cocktail flavor is a very complex blend.
Low-Grade Follicular Lymphoma with Highly Unusual Flow Cytometric, FISH, Molecular, and Classical Cytogenetic Results: A Case Report

We present a low-grade follicular lymphoma case with highly unusual ancillary study results. The patient is a 50-year-old female with a 4.3 x 3.8 x 2.2 cm left inguinal mass, from which fine needle aspiration and excisional biopsy specimens were obtained. H&E sections showed effacement of the lymph node architecture by closely packed follicles comprised of mainly centrocytes and without tingible body macrophages. Immunohistochemical stains revealed the follicle cells positive for CD20, PAX5, BCL6, CD10 (weak), and BCL2 (weak), while CD3 highlighted small T lymphocytes mainly in the interfollicular areas.