Miracle-dz/UniFAR-FTUs huggingface dataset:
A Victorivirus and Two Novel Mitoviruses Co-Infected the Plant Pathogen Nigrospora oryzae

Three dsRNAs, in sizes of approximately 2.5–5 kbp, were detected in the plant pathogenic fungus Nigrospora oryzae strain CS-7.5-4. Genomic analysis showed that the 5.0 kb dsRNA was a victorivirus named as Nigrospora oryzae victorivirus 2 (NoRV2). The genome of NoRV2 was 5166 bp in length containing two overlapping open reading frames (ORFs), ORF1 and ORF2. ORF1 was deduced to encode a coat protein (CP) showing homology to the CPs of viruses belonging to the Totiviridae family. The stop codon of ORF1 and the start codon of ORF2 were overlapped by the tetranucleotide sequence AUGA. ORF2 was predicted to encode an RNA-dependent RNA polymerase (RdRp), which was highly similar to the RdRps of victoriviruses. Virus-like particle examination demonstrated that the genome of NoRV2 was solely encapsidated by viral particles with a diameter of approximately 35 nm. The other two dsRNAs that were less than 3.0 kb were predicted to be the genomes of two mitoviruses, named as Nigrospora oryzae mitovirus 1 (NoMV1) and Nigrospora oryzae mitovirus 2 (NoMV2). Both NoMV1 and NoMV2 were A-U rich and with lengths of 2865 and 2507 bp, respectively. Mitochondrial codon usage inferred that each of the two mitoviruses contains a major large ORF encoding a mitoviral RdRp. Horizontal transfer experiments showed that the NoMV1 and NoMV2 could be cotransmitted horizontally via hyphal contact to other virus-free N. oryzae strains and causes phenotypic change to the recipient, such as an increase in growth rate. This is the first report of mitoviruses in N. oryzae.
Novel Protein-Based Pneumococcal Vaccines: Assessing the Use of Distinct Protein Fragments Instead of Full-Length Proteins as Vaccine Antigens

Non-serotype-specific protein-based pneumococcal vaccines have received extensive research focus due to the limitations of polysaccharide-based vaccines. Pneumococcal proteins (PnPs), universally expressed among serotypes, may induce broader immune responses, stimulating humoral and cellular immunity, while being easier to manufacture and less expensive. Such an approach has raised issues mainly associated with sequence/level of expression variability, chemical instability, as well as possible undesirable reactogenicity and autoimmune properties. A step forward employs the identification of highly-conserved antigenic regions within PnPs with the potential to retain the benefits of protein antigens. Besides, their low-cost and stable construction facilitates the combination of several antigenic regions or peptides that may impair different stages of pneumococcal disease offering even wider serotype coverage and more efficient protection. This review discusses the up-to-date progress on PnPs that are currently under clinical evaluation and the challenges for their licensure. Focus is given on the progress on the identification of antigenic regions/peptides within PnPs and their evaluation as vaccine candidates, accessing their potential to overcome the issues associated with full-length protein antigens. Particular mention is given of the use of newer delivery system technologies including conjugation to Toll-like receptors (TLRs) and reformulation into nanoparticles to enhance the poor immunogenicity of such antigens.
Correlation Between Violence and Antipsychotic Dosage in Schizophrenia: A Secondary Analysis of The Clinical Antipsychotic Trials for Intervention Effectiveness (CATIE) Dataset

Abstract Introduction Violent behavior is more common in individuals with schizophrenia, compared to the general population. Studies suggest higher psychotic symptoms are predictive of greater violent behavior. On the other hand, violent behaviors are reduced with antipsychotic treatment. However, the relationship between antipsychotic dosage and violence has not been studied to date. Thus, we aimed to determine if there exists an association between antipsychotic dosage and violence scores and whether the maximum violence would be predictive of the final antipsychotic dosage. We hypothesized that the violence scores at the final assessment in the Clinical Antipsychotic Trials for Intervention Effectiveness (CATIE) would be correlated with the corresponding drug dosage and the maximum violence severity score would be predictive of the final dosage. Methods Antipsychotic dosage at the end of the trial was converted into defined daily dosage and chlorpromazine equivalents (CPZe). Final and maximum violence sum scores were analyzed from the final violence assessment interviews. Spearman’s rank-order correlation and linear regression analyses were used to analyze the relationship between the violence scores and standardized antipsychotic dosages. Results The analysis was on 952 individuals with schizophrenia. There was a significant association between maximum violence severity score and the final CPZe dosage (p=0.049). Exploratory analysis of age and ethnicity revealed younger non-white individuals to be at a higher risk of engaging in violent activities. Discussion Violence in schizophrenia is associated with poor illness course. Further studies focusing on violence in younger non-white individuals are warranted.
Effect of breast myopathies on quality and microbial shelf life of broiler meat.

To evaluate the impact of emerging myopathies on meat quality and microbial shelf life, 48 normal, 48 white striped (WS), and 48 wooden breasts (WB) were stored for 11 d at 4°C aerobically and analyzed at 24, 72, 120, 168, 216, and 264 h post-mortem. Normal breasts showed lower (P < 0.001) redness index (-0.88 vs. -0.41 and -0.43) and cooking losses (22.0 vs. 23.8 vs. 26.9%) than those of WS and WB meat. Normal and WS breasts exhibited higher protein content than that in WB meat (23.9 and 23.2 vs. 21.4%; P < 0.001). Normal meat also had a lower ether extract content than that in WB meat (1.09 vs. 1.88%; P < 0.001), with intermediate values for WS meat. Normal breasts exhibited higher saturated fatty acid (FA) rate (31.3 vs. 28.0% of total FA on average) and lower unsaturated FA rate (68.7 vs. 72.0%) than those in WS and WB meat (P < 0.001). Differences were mainly due to polyunsaturated FA (30.5% in normal vs. 35.3 and 35.4% in WS and WB meat; P < 0.001). Normal breasts had higher initial total viable count (TVC) and a shorter TVC lag phase than those of WS and WB meat (46.3 vs. 85.2 and 77.8 h). The microbial shelf life threshold (7 log10 CFU TVC/g) was achieved first in normal (130 h) and then in WS (149 h) and WB (192 h) meat. TVC and Pseudomonas spp. counts were significantly higher in normal than those in the affected breasts between 72 and 216 h of storage. Enterobacteriaceae spp. and lactic acid bacteria counts were significantly higher in normal meat, lower in WB meat, and intermediate in WS meat until 216 h. All differences in microbial targets across meat types disappeared by 264 h of storage. Further studies are necessary to elucidate the factors and the mechanisms that may modulate microbial growth and composition during storage in broiler breast meat affected by myopathies.
The CD98 Heavy Chain Is a Marker and Regulator of Head and Neck Squamous Cell Carcinoma Radiosensitivity

Purpose: The heavy chain of the CD98 protein (CD98hc) is encoded by the SLC3A2 gene. Together with the light subunit LAT1, CD98hc constitutes a heterodimeric transmembrane amino acid transporter. High SLC3A2 mRNA expression levels are associated with poor prognosis in patients with head and neck squamous cell carcinoma (HNSCC) treated with radiochemotherapy. Little is known regarding the CD98hc protein–mediated molecular mechanisms of tumor radioresistance. Experimental Design: CD98hc protein expression levels were correlated with corresponding tumor control dose 50 (TCD50) in HNSCC xenograft models. Expression levels of CD98hc and LAT1 in HNSCC cells were modulated by siRNA or CRISPR/Cas9 gene editing. HNSCC cell phenotypes were characterized by transcription profiling, plasma membrane proteomics, metabolic analysis, and signaling pathway activation. Expression levels of CD98hc and LAT1 proteins were examined by IHC analysis of tumor tissues from patients with locally advanced HNSCC treated with primary radiochemotherapy (RCTx). Primary endpoint was locoregional tumor control (LRC). Results: High expression levels of CD98hc resulted in an increase in mTOR pathway activation, amino acid metabolism, and DNA repair as well as downregulation of oxidative stress and autophagy. High expression levels of CD98hc and LAT1 proteins were significantly correlated and associated with an increase in radioresistance in HNSCC in vitro and in vivo models. High expression of both proteins identified a poor prognosis subgroup in patients with locally advanced HNSCC after RCTx. Conclusions: We found that CD98hc-associated signaling mechanisms play a central role in the regulation of HNSCC radioresistance and may be a promising target for tumor radiosensitization.
Predictors of positive surgical margins in patients undergoing partial nephrectomy: A large single-center experience.

OBJECTIVE To identify preoperative factors that predict positive surgical margins in partial nephrectomy. MATERIAL AND METHODS Using our institutional partial nephrectomy database, we investigated the patients who underwent partial nephrectomy for malignant tumors between January 2011 and December 2015. Patient, tumor, surgeon characteristics were compared by surgical margin status. Multivariable logistic regression was used to identify independent predictors of positive surgical margins. RESULTS A total of 1025 cases were available for analysis, of which 65 and 960 had positive and negative surgical margins, respectively. On univariate analysis, positive margins were associated with older age (64.3 vs. 59.6, p<0.01), history of prior ipsilateral kidney surgery (13.8% vs. 5.6%, p<0.01), lower preoperative eGFR (74.7 mL/min/1.73 m2 vs. 81.2 mL/min/1.73 m2, p=0.01), high tumor complexity (31.8% vs. 19.0%, p=0.03), hilar tumor location (23.1% vs. 12.5%, p=0.01), and lower surgeon volume (p<0.01). Robotic versus open approach was not associated with the risk of positive margins (p=0.79). On multivariable analysis, lower preoperative eGFR, p=0.01), hilar tumor location (p=0.01), and lower surgeon volume (p<0.01) were found to be independent predictors of positive margins. CONCLUSION In our large institutional series of partial nephrectomy cases, patient, tumor, and surgeon factors influence the risk of positive margins. Of these, surgeon volume is the single most important predictor of surgical margin status, indicating that optimal oncological outcomes are best achieved by high-volume surgeons.
Hydrogen Indirectly Suppresses Increases in Hydrogen Peroxide in Cytoplasmic Hydroxyl Radical-Induced Cells and Suppresses Cellular Senescence

Bacteria inhabiting the human gut metabolize microbiota-accessible carbohydrates (MAC) contained in plant fibers and subsequently release metabolic products. Gut bacteria produce hydrogen (H2), which scavenges the hydroxyl radical (•OH). Because H2 diffuses within the cell, it is hypothesized that H2 scavenges cytoplasmic •OH (cyto •OH) and suppresses cellular senescence. However, the mechanisms of cyto •OH-induced cellular senescence and the physiological role of gut bacteria-secreted H2 have not been elucidated. Based on the pyocyanin-stimulated cyto •OH-induced cellular senescence model, the mechanism by which cyto •OH causes cellular senescence was investigated by adding a supersaturated concentration of H2 into the cell culture medium. Cyto •OH-generated lipid peroxide caused glutathione (GSH) and heme shortage, increased hydrogen peroxide (H2O2), and induced cellular senescence via the phosphorylation of ataxia telangiectasia mutated kinase serine 1981 (p-ATMser1981)/p53 serine 15 (p-p53ser15)/p21 and phosphorylation of heme-regulated inhibitor (p-HRI)/phospho-eukaryotic translation initiation factor 2 subunit alpha serine 51 (p-eIF2α)/activating transcription factor 4 (ATF4)/p16 pathways. Further, H2 suppressed increased H2O2 by suppressing cyto •OH-mediated lipid peroxide formation and cellular senescence induction via two pathways. H2 produced by gut bacteria diffuses throughout the body to scavenge cyto •OH in cells. Therefore, it is highly likely that gut bacteria-produced H2 is involved in intracellular maintenance of the redox state, thereby suppressing cellular senescence and individual aging. Hence, H2 produced by intestinal bacteria may be involved in the suppression of aging.
Commentary on: Glaucoma drainage devices: Boon or bane

In refractory glaucoma or conditions resulting in extensive conjunctival scarring, such as previously failed glaucoma filtering procedures, trauma, or previous ocular surgery, trabeculectomy has a notoriously poor success rate. In such situations, glaucoma drainage devices (GDDs) appear to be a better choice[1,2] because they create an alternate pathway by shunting aqueous from the anterior chamber to an equatorial plate through a long tube resulting in a posterior bleb. [3]
Homocysteine: A Potential Biomarker for Diabetic Retinopathy

Diabetic retinopathy (DR) is the most common cause of blindness in people under the age of 65. Unfortunately, the current screening process for DR restricts the population that can be evaluated and the disease goes undetected until irreversible damage occurs. Herein, we aimed to evaluate homocysteine (Hcy) as a biomarker for DR screening. Hcy levels were measured by enzyme-linked immuno sorbent assay (ELISA) and immunolocalization methods in the serum, vitreous and retina of diabetic patients as well as in serum and retina of different animal models of DM representing type 1 diabetes (streptozotocin (STZ) mice, Akita mice and STZ rats) and db/db mice which exhibit features of human type 2 diabetes. Our results revealed increased Hcy levels in the serum, vitreous and retina of diabetic patients and experimental animal models of diabetes. Moreover, optical coherence tomography (OCT) and fluorescein angiography (FA) were used to evaluate the retinal changes in mice eyes after Hcy-intravitreal injection into normal wild-type (WT) and diabetic (STZ) mice. Hcy induced changes in mice retina which were aggravated under diabetic conditions. In conclusion, our data reported Hcy as a strong candidate for use as a biomarker in DR screening. Targeting the clearance of Hcy could also be a future therapeutic target for DR.
Deep Convolutional Neural Networks for Heart Sound Segmentation

This paper studies the use of deep convolutional neural networks to segment heart sounds into their main components. The proposed methods are based on the adoption of a deep convolutional neural network architecture, which is inspired by similar approaches used for image segmentation. Different temporal modeling schemes are applied to the output of the proposed neural network, which induce the output state sequence to be consistent with the natural sequence of states within a heart sound signal (S1, systole, S2, diastole). In particular, convolutional neural networks are used in conjunction with underlying hidden Markov models and hidden semi-Markov models to infer emission distributions. The proposed approaches are tested on heart sound signals from the publicly available PhysioNet dataset, and they are shown to outperform current state-of-the-art segmentation methods by achieving an average sensitivity of 93.9% and an average positive predictive value of 94% in detecting S1 and S2 sounds.
Transradial versus transfemoral access for anterior circulation mechanical thrombectomy: comparison of technical and clinical outcomes

Background A transradial approach (TRA) is associated with fewer access site complications than a transfemoral technique (TFA). However, there is concern that performing mechanical thrombectomy (MT) via TRA may lead to longer revascularization times and thus worse outcomes. Nonetheless, TRA may confer added benefits in MT since navigation of challenging aortic arch and carotid anatomy is often facilitated by a right radial artery trajectory. Objective To compare outcomes in patients who underwent MT via TRA versus TFA. Methods We performed a retrospective review of our institutional database to identify 51 patients with challenging vascular anatomy who underwent MT for anterior circulation large vessel occlusion between February 2015 and February 2018. Patient characteristics, procedural techniques, and outcomes were recorded. TFA and TRA cohorts were compared. Results Of the 51 patients, 18 (35%) underwent MT via TRA. There were no significant cohort differences in patient characteristics, clot location, or aortic arch type and presence of carotid tortuosity. There were no significant differences in outcomes between the two cohorts, including single-pass recanalization rate (54.5% vs 55.6%, p=0.949) and average number of passes (1.9 vs 1.7, p=0.453). Mean access-to-reperfusion time (61.9 vs 61.1 min, p=0.920), successful revascularization rates (Thrombolysis in Cerebral Infarction score ≥2b 87.9% vs 88.9%, p=1.0) and functional outcomes (modified Rankin Scale score≤2, 39.4% vs 33.3%, p=0.669) were similar between TFA and TRA cohorts, respectively. Conclusions Our results demonstrate equivalence in efficacy and efficiency between TRA and TFA for MT of anterior circulation large vessel occlusion in patients with challenging vascular anatomy. TRA may be better than TFA in well-selected patients undergoing MT.
Haplotype Analysis of Three Common β-Thalassemia Mutations in Syrian Patients

Abstract β-Globin haplotypes were used to investigate the origin of three common β-globin mutations, IVS-I-110 (G>A); HBB: c.93-21G>A, IVS-I-1 (G>A); HBB: c.92 + 1G>A and codon 39 (C>T); HBB: c.118C > T in Syrian patients. Haplotype analysis was done for 49 unrelated patients with β-thalassemia (β-thal) and 20 unrelated healthy subjects by polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP) for the β-globin gene cluster of the following polymorphic restriction sites: HincII 5' to ε, HindIII 5' to Gγ, HindIII 5' to Aγ, HincII in ψβ, HincII 3' to ψβ, AvaII in β, and HinfI 3' to β. The IVS-I-110 mutation was associated with three haplotypes: I [+ – – – – + +] (79.4%), V [+ – – – – + –] (5.9%) and VII [+ – – – – – +] (14.7%), while, the two mutations IVS-I-1 and codon 39 were be linked to a single haplotype V (100.0%) and II [– + + – + + +] (100.0%), respectively. The normal chromosomes (βA/βA) were associated with four haplotypes, I (50.0%), II (7.5%), V (32.5%) and VII (10.0%). In the Syrian population, the IVS-I-110 mutation was associated with multi haplotypes, whereas the IVS-I-1 and codon 39 mutations have a single origin. More studies for the other mutations will be very useful for genetic epidemiological studies in Syria.
The Diversity of Encephalitogenic CD4+ T Cells in Multiple Sclerosis and Its Animal Models

Autoreactive CD4+ T cells, which target antigens in central nervous system (CNS) myelin, are widely believed to play a critical role in the pathogenesis of multiple sclerosis (MS) in concert with other immune effectors. This theory is supported by data from animal model experiments, genome-wide association studies, and immune profiles of individuals with MS. Furthermore, disease modifying agents that target lymphocytes significantly reduce the rate of MS clinical exacerbations. However, the properties of myelin-reactive CD4+ T cells that are critical for their pathogenic activities are not understood completely. This article reviews the literature on encephalitogenic CD4+ T cells, with an emphasis on T-helper (Th) lineage and cytokine production. An increased understanding of the spectrum of encephalitogenic T cells and how they differ from protective subsets is necessary for the development of the next generation of more effective and safer immunomodulatory therapies customized for individuals with MS and related disorders.
Discussion on critical points for a tailored therapy to cure hepatitis C virus infection

Hepatitis C virus (HCV) infects around 71 million people worldwide and in 2018 it is still a major health problem. Since 2011, anti-HCV therapy with availability of direct-acting antiviral drugs has revolutionized the clinical response and paved the way to eradication strategies. However, despite the high rate of sustained virological response, treatment failure may occur in a limited percentage of patients, possibly due to resistance-associated substitutions (RASs), either emergent or pre-existent even in minority viral populations. Clearly this problem may impair success of eradication strategies. With this background, several questions marks still exist around HCV treatment, including whether pan-genotypic treatments with complete effectiveness in any clinical conditions really exist outside clinical trials, the actual cost-effectiveness of genotyping testing, and utility of RAS detection in viral quasispecies by next generation sequencing approach. In this review, we describe these critical points by discussing recent literature data and our research experience.
The Relationship of Anxiety and Stress With Working Memory Performance in a Large Non-depressed Sample

Clinical anxiety and acute stress caused by major life events have well-documented detrimental effects on cognitive processes, such as working memory (WM). However, less is known about the relationships of state anxiety or everyday stress with WM performance in non-clinical populations. We investigated the associations between these two factors and three WM composites (verbal WM, visuospatial WM, and n-back updating performance) in a large online sample of non-depressed US American adults. We found a trend for a negative association between WM performance and anxiety, but not with stress. Thus, WM performance appears rather robust against normal variation in anxiety and everyday stress.
Semen IgM, IgG1, and IgG3 Differentially Associate With Pro-Inflammatory Cytokines in HIV-Infected Men

Genital inflammation significantly increases the risk for HIV infection. The seminal environment is enriched in pro-inflammatory cytokines and chemokines. Here, we investigated the interplay between semen cytokines and humoral immunity to understand whether the characteristics of semen antibodies are associated with genital inflammation. In 36 HIV-infected and 40 HIV-uninfected mens' semen, HIV-specific antibodies (gp120, gp41, p66, and p24), immunoglobulin (Ig) subclasses, isotypes and cytokines, using multiplex assays, were measured. Semen IgG1, IgG3, and IgM were significantly higher in HIV-infected compared to HIV-uninfected men (p < 0.05). In HIV-uninfected men, pro-inflammatory cytokines IL-6, IL-8, and MCP-1 significantly correlated with IgG1 and total IgG (IgG1+IgG2+IgG3+IgG4) (both r≥0.55; p≤0.001). Total IgG in HIV-infected men correlated to HIV-specific antibodies in the semen irrespective of antiretroviral (ARV) use. In HIV-infected, ARV-treated men, p66 and gp41-specific antibodies were inversely correlated with IL-6 and MIP-1α (both r≥−0.65, p≤0.03). In HIV-infected, ARV-naïve men, p24 and gp120-specific antibodies correlated significantly with pro-inflammatory TNF-α (r≥0.44, p≤0.03), while p24 antibodies correlated significantly with chemokine MIP-1β (r = 0.45; p = 0.02). Local cytokines/chemokines were associated with the mucosal-specific Ig subclasses which likely effect specific antibody functions. Together, these data inform on mucosal-specific immunity that may be elicited in the male genital tract (MGT) in future vaccines and/or combination HIV prevention strategies.