Miracle-dz/UniFAR-FTUs huggingface dataset:
Enhancement of Antiviral Activity of Human Alpha-Defensin 5 against Herpes Simplex Virus 2 by Arginine Mutagenesis at Adaptive Evolution Sites

ABSTRACT Herpes simplex virus 2 (HSV-2) infection is still one of the common causes of sexually transmitted diseases worldwide. The prevalence of HSV strains resistant to traditional nucleoside antiviral agents has led to the development of novel antiviral drugs. Human alpha-defensin 5 (HD5), a kind of endogenous antimicrobial peptide expressed in the epithelia of the small intestine and urogenital tract, displays natural antiviral activity. Based on arginine-rich features and adaptive evolution characteristics of vertebrate defensins, we conducted a screen for HD5 derivatives with enhanced anti-HSV-2 activity by a single arginine substitution at the adaptive evolution sites. Cell protection assay and temporal antiviral studies showed that HD5 and its mutants displayed affirmatory but differential anti-HSV-2 effects in vitro by inhibiting viral adhesion and entry. Inspiringly, the E21R-HD5 mutant had significantly higher antiviral activity than natural HD5, which is possibly attributed to the stronger binding affinity of the E21R-HD5 mutant with HSV-2 capsid protein gD, indicating that E21R mutation can increase the anti-HSV-2 potency of HD5. In a mouse model of lethal HSV-2 infection, prophylactic and/or therapeutic treatment with E21R-HD5 via intravaginal instillation remarkably alleviated the symptoms and delayed disease progress and resulted in about a 1.5-fold-higher survival rate than in the HD5 group. Furthermore, the E21R variant exhibited a 2-fold-higher antiviral potency against HIV-1 over parental HD5 in vitro. This study demonstrates that arginine mutagenesis at appropriate evolution sites may significantly enhance the antiviral activity of HD5, which also paves a facile way to search for potent antiviral drugs based on natural antimicrobial peptides.
Ecoepidemiology and Complete Genome Comparison of Different Strains of Severe Acute Respiratory Syndrome-Related Rhinolophus Bat Coronavirus in China Reveal Bats as a Reservoir for Acute, Self-Limiting Infection That Allows Recombination Events

ABSTRACT Despite the identification of severe acute respiratory syndrome-related coronavirus (SARSr-CoV) in Rhinolophus Chinese horseshoe bats (SARSr-Rh-BatCoV) in China, the evolutionary and possible recombination origin of SARSr-CoV remains undetermined. We carried out the first study to investigate the migration pattern and SARSr-Rh-BatCoV genome epidemiology in Chinese horseshoe bats during a 4-year period. Of 1,401 Chinese horseshoe bats from Hong Kong and Guangdong, China, that were sampled, SARSr-Rh-BatCoV was detected in alimentary specimens from 130 (9.3%) bats, with peak activity during spring. A tagging exercise of 511 bats showed migration distances from 1.86 to 17 km. Bats carrying SARSr-Rh-BatCoV appeared healthy, with viral clearance occurring between 2 weeks and 4 months. However, lower body weights were observed in bats positive for SARSr-Rh-BatCoV, but not Rh-BatCoV HKU2. Complete genome sequencing of 10 SARSr-Rh-BatCoV strains showed frequent recombination between different strains. Moreover, recombination was detected between SARSr-Rh-BatCoV Rp3 from Guangxi, China, and Rf1 from Hubei, China, in the possible generation of civet SARSr-CoV SZ3, with a breakpoint at the nsp16/spike region. Molecular clock analysis showed that SARSr-CoVs were newly emerged viruses with the time of the most recent common ancestor (tMRCA) at 1972, which diverged between civet and bat strains in 1995. The present data suggest that SARSr-Rh-BatCoV causes acute, self-limiting infection in horseshoe bats, which serve as a reservoir for recombination between strains from different geographical locations within reachable foraging range. Civet SARSr-CoV is likely a recombinant virus arising from SARSr-CoV strains closely related to SARSr-Rh-BatCoV Rp3 and Rf1. Such frequent recombination, coupled with rapid evolution especially in ORF7b/ORF8 region, in these animals may have accounted for the cross-species transmission and emergence of SARS.
Exosome-Mediated Intercellular Communication between Hepatitis C Virus-Infected Hepatocytes and Hepatic Stellate Cells

ABSTRACT Fibrogenic pathways in the liver are principally regulated by activation of hepatic stellate cells (HSC). Fibrosis is associated with chronic hepatitis C virus (HCV) infection, although the mechanism is poorly understood. HSC comprise the major population of nonparenchymal cells in the liver. Since HCV does not replicate in HSC, we hypothesized that exosomes secreted from HCV-infected hepatocytes activate HSC. Primary or immortalized human hepatic stellate (LX2) cells were exposed to exosomes derived from HCV-infected hepatocytes (HCV-exo), and the expression of fibrosis-related genes was examined. Our results demonstrated that HCV-exo internalized to HSC and increased the expression of profibrotic markers. Further analysis suggested that HCV-exo carry miR-19a and target SOCS3 in HSC, which in turn activates the STAT3-mediated transforming growth factor β (TGF-β) signaling pathway and enhances fibrosis marker genes. The higher expression of miR-19a in exosomes was also observed from HCV-infected hepatocytes and in sera of chronic HCV patients with fibrosis compared to healthy volunteers and non-HCV-related liver disease patients with fibrosis. Together, our results demonstrated that miR-19a carried through the exosomes from HCV-infected hepatocytes activates HSC by modulating the SOCS-STAT3 axis. Our results implicated a novel mechanism of exosome-mediated intercellular communication in the activation of HSC for liver fibrosis in HCV infection. IMPORTANCE HCV-associated liver fibrosis is a critical step for end-stage liver disease progression. However, the molecular mechanisms for hepatic stellate-cell activation by HCV-infected hepatocytes are underexplored. Here, we provide a role for miR-19a carried through the exosomes in intercellular communication between HCV-infected hepatocytes and HSC in fibrogenic activation. Furthermore, we demonstrate the role of exosomal miR-19a in activation of the STAT3–TGF-β pathway in HSC. This study contributes to the understanding of intercellular communication in the pathogenesis of liver disease during HCV infection.
RoBA Multiplier: A Rounding-Based Approximate Multiplier for High-Speed yet Energy-Efficient Digital Signal Processing

In this paper, we propose an approximate multiplier that is high speed yet energy efficient. The approach is to round the operands to the nearest exponent of two. This way the computational intensive part of the multiplication is omitted improving speed and energy consumption at the price of a small error. The proposed approach is applicable to both signed and unsigned multiplications. We propose three hardware implementations of the approximate multiplier that includes one for the unsigned and two for the signed operations. The efficiency of the proposed multiplier is evaluated by comparing its performance with those of some approximate and accurate multipliers using different design parameters. In addition, the efficacy of the proposed approximate multiplier is studied in two image processing applications, i.e., image sharpening and smoothing.
Radioactive Isotopes in Medicine and Biology: Medicine.

Radioactive Isotopes in Medicine and Biology: Basic Physics and Instrumentation. By Edith H. Ouimby, ScD, and Sergei Feitelberg, MD. Price, $8. Pp 343. Lea & Febiger, Publishers, 600 S Washington Sq. Philadelphia 6, 1963. Any author who prepares a book on the clinical use of radioisotopes finds difficulty in defining the subject and in choosing areas for emphasis. The several texts available illustrate these problems. There is no agreement on the amount of basic physics needed by, or acceptable to, the practicing physician. To what extent should he simply follow a cookbook plan in using isotopes, and if this is what he is to do, why not turn it all over to a technician? Some of the texts include an extensive coverage of thyroid physiology and thyroid disease. This is perhaps logical in view of the important usefulness of radioiodine; yet it is, in a way, inconsistent. We do not
Rift Valley Fever Virus Strain MP-12 Enters Mammalian Host Cells via Caveola-Mediated Endocytosis

ABSTRACT Rift Valley fever virus (RVFV) is a zoonotic pathogen capable of causing serious morbidity and mortality in both humans and livestock. The lack of efficient countermeasure strategies, the potential for dispersion into new regions, and the pathogenesis in humans and livestock make RVFV a serious public health concern. The receptors, cellular factors, and entry pathways used by RVFV and other members of the family Bunyaviridae remain largely uncharacterized. Here we provide evidence that RVFV strain MP-12 uses dynamin-dependent caveola-mediated endocytosis for cell entry. Caveolae are lipid raft domains composed of caveolin (the main structural component), cholesterol, and sphingolipids. Caveola-mediated endocytosis is responsible for the uptake of a wide variety of host ligands, as well as bacteria, bacterial toxins, and a number of viruses. To determine the cellular entry mechanism of RVFV, we used small-molecule inhibitors, RNA interference (RNAi), and dominant negative (DN) protein expression to inhibit the major mammalian cell endocytic pathways. Inhibitors and RNAi specific for macropinocytosis and clathrin-mediated endocytosis had no effect on RVFV infection. In contrast, inhibitors of caveola-mediated endocytosis, and RNAi targeted to caveolin-1 and dynamin, drastically reduced RVFV infection in multiple cell lines. Expression of DN caveolin-1 also reduced RVFV infection significantly, while expression of DN EPS15, a protein required for the assembly of clathrin-coated pits, and DN PAK-1, an obligate mediator of macropinocytosis, had no significant impact on RVFV infection. These results together suggest that the primary mechanism of RVFV MP-12 uptake is dynamin-dependent, caveolin-1-mediated endocytosis.
Validity and Reliability of the Vestibular/Ocular Motor Screening and Associations With Common Concussion Screening Tools

Background: Sustaining a concussion commonly results in vestibular impairments that may be associated with balance deficits. To screen for vestibular impairments after a concussion, the Vestibular/Ocular Motor Screening (VOMS) tool was developed. The relationship between the VOMS and other concussion screening tools, such as the Balance Error Scoring System (BESS) and King-Devick (K-D), have not been explored. Hypotheses: (1) VOMS would provide reliable results and not provoke symptoms in healthy adolescents and (2) VOMS test items would measure related aspects of vestibular function that are not measured through the BESS or K-D. Study Design: Cross-sectional, descriptive. Level of Evidence: Level 4. Methods: A total of 105 healthy adolescents (53 male, 52 female; mean age, 15.4 years) completed the VOMS, BESS, and K-D tests. A subsample of 21 adolescents (16 male, 5 female; mean age, 15.5 years) completed the VOMS twice. Results: The median total symptom score for all 7 VOMS items was 0 (0-5). The majority of the individual VOMS test items total symptom scores demonstrated a significant correlation with each other (rs = 0.25-0.66, P < 0.02). The individual VOMS items did not demonstrate a significant relationship to the BESS or K-D. VOMS items demonstrated high agreement in total symptom scores between testing trials, with near point convergence (NPC) distance demonstrating an intraclass correlation coefficient (ICC) of 0.95 (95% CI, 0.89-0.98; P < 0.001). The MDC95 (minimal detectable change with 95 confidence) for NPC distance was 4 cm. Conclusion: The VOMS did not provoke vestibular symptoms in healthy adolescents. The VOMS items measured unique aspects of vestibular function other than those measured by the BESS or K-D with good reliability. Clinical Relevance: Clinicians should consider implementing the VOMS as part of a comprehensive concussion assessment if vestibular impairment is suspected. If NPC distance is measured twice, a difference of >4 cm would be considered real change outside of measurement error.
Prevalence of Diabetes Mellitus in Newly Admitted Undergraduates of Olabisi Onabanjo University, Nigeria

The prevalence of diabetes mellitus was studied in newly admitted undergraduates of Olabisi Onabanjo University. A total of 2,421 apparently healthy young adults (undergraduates) were randomly selected from the newly admitted undergraduates who registered in a session (period of 9 months) in Olabisi Onabanjo University Health Centre, Ago-Iwoye. These subjects were screened biochemically for diabetes mellitus, by carrying out urinalysis as well as capillary blood glucose estimation using the standard glucometer. The 1997 World Health Organization criteria for diagnosis of diabetes mellitus was used. The overall prevalence of diabetes mellitus was 3.47%. Generally the prevalence increases with age among the study population. There was no statistically significant difference between the sexes (Male/Female = 2.9% - 4.2%). Key words: Prevalence, Diabetes Mellitus, University Health Centre, Newly admitted undergraduates. Nigerian Medical Practitioner Vol.47(3) 2005: 26-28
Mechanistic Study of Broadly Neutralizing Human Monoclonal Antibodies against Dengue Virus That Target the Fusion Loop

ABSTRACT There are no available vaccines for dengue, the most important mosquito-transmitted viral disease. Mechanistic studies with anti-dengue virus (DENV) human monoclonal antibodies (hMAbs) provide a rational approach to identify and characterize neutralizing epitopes on DENV structural proteins that can serve to inform vaccine strategies. Here, we report a class of hMAbs that is likely to be an important determinant in the human humoral response to DENV infection. In this study, we identified and characterized three broadly neutralizing anti-DENV hMAbs: 4.8A, D11C, and 1.6D. These antibodies were isolated from three different convalescent patients with distinct histories of DENV infection yet demonstrated remarkable similarities. All three hMAbs recognized the E glycoprotein with high affinity, neutralized all four serotypes of DENV, and mediated antibody-dependent enhancement of infection in Fc receptor-bearing cells at subneutralizing concentrations. The neutralization activities of these hMAbs correlated with a strong inhibition of virus-liposome and intracellular fusion, not virus-cell binding. We mapped epitopes of these antibodies to the highly conserved fusion loop region of E domain II. Mutations at fusion loop residues W101, L107, and/or G109 significantly reduced the binding of the hMAbs to E protein. The results show that hMAbs directed against the highly conserved E protein fusion loop block viral entry downstream of virus-cell binding by inhibiting E protein-mediated fusion. Characterization of hMAbs targeting this region may provide new insights into DENV vaccine and therapeutic strategies.
Eye Injuries in High School and Collegiate Athletes

Background: Although eye injuries constitute a small percentage of high school and college sports injuries, they have the potential to be permanently debilitating. Hypothesis: Eye injury rates will vary by sport, sex, and between the high school and college age groups. Study Design: Descriptive epidemiology study. Level of Evidence: Level 3. Methods: Data from eye injury reports in high school and college athletes were obtained from the National High School Sports-Related Injury Surveillance System, High School Reporting Information Online (HS RIO) database over a 10-year span (2005-2006 through 2014-2015 school years) and the National Collegiate Athletic Association (NCAA) Injury Surveillance Program (ISP) over an 11-year span (2004-2005 through 2014-2015 school years). Injury rates per 100,000 athlete-exposures (AEs), injury rate ratios (RRs), and 95% CIs were calculated. Distributions of eye injuries by diagnosis, mechanism, time loss, and surgery needs were also examined. Results: A total of 237 and 273 eye injuries were reported in the HS RIO and the NCAA ISP databases, respectively. The sports with the highest eye injury rates (per 100,000 AEs) for combined high school and college athletes were women’s basketball (2.36), women’s field hockey (2.35), men’s basketball (2.31), and men’s wrestling (2.07). Overall eye injury rates at the high school and college levels were 0.68 and 1.84 per 100,000 AEs, respectively. Eye injury rates were higher in competition than practice in high school (RR, 3.47; 95% CI, 2.69-4.48) and college (RR, 3.13; 95% CI, 2.45-3.99). Most injuries were contusions (high school, 35.9%; college, 33.3%) and due to contact (high school, 89.9%; college, 86.4%). Only a small percentage of injuries resulted in time loss over 21 days (high school, 4.2%; college, 3.0%). Conclusion: Eye injury rates and patterns vary by sport, sex, and between the high school and college age groups. Although severe injuries do occur, most eye injuries sustained by high school and college athletes are minor, with limited time loss and full recovery. Clinical Relevance: Additional focus needs to be placed on preventing eye injuries at the collegiate level in women’s and men’s basketball, women’s field hockey, and men’s wrestling.
Cumulative Effects of Concussion History on Baseline Computerized Neurocognitive Test Scores: Systematic Review and Meta-analysis

Context: It is unclear whether individuals with a history of single or multiple clinically recovered concussions exhibit worse cognitive performance on baseline testing compared with individuals with no concussion history. Objective: To analyze the effects of concussion history on baseline neurocognitive performance using a computerized neurocognitive test. Data sources: PubMed, CINAHL, and psycINFO were searched in November 2015. The search was supplemented by a hand search of references. Study Selection: Studies were included if participants completed the Immediate Post-concussion Assessment and Cognitive Test (ImPACT) at baseline (ie, preseason) and if performance was stratified by previous history of single or multiple concussions. Study Design: Systematic review and meta-analysis. Level of Evidence: Level 2. Data Extraction: Sample size, demographic characteristics of participants, as well as performance of participants on verbal memory, visual memory, visual-motor processing speed, and reaction time were extracted from each study. Results: A random-effects pooled meta-analysis revealed that, with the exception of worsened visual memory for those with 1 previous concussion (Hedges g = 0.10), no differences were observed between participants with 1 or multiple concussions compared with participants without previous concussions. Conclusion: With the exception of decreased visual memory based on history of 1 concussion, history of 1 or multiple concussions was not associated with worse baseline cognitive performance.
HBZ Stimulates Brain-Derived Neurotrophic Factor/TrkB Autocrine/Paracrine Signaling To Promote Survival of Human T-Cell Leukemia Virus Type 1-Infected T Cells

ABSTRACT Brain-derived neurotrophic factor (BDNF) is a neurotrophin that promotes neuronal proliferation, survival, and plasticity. These effects occur through autocrine and paracrine signaling events initiated by interactions between secreted BDNF and its high-affinity receptor, TrkB. A BDNF/TrkB autocrine/paracrine signaling loop has additionally been implicated in augmenting the survival of cells representing several human cancers and is associated with poor patient prognosis. Adult T-cell leukemia (ATL) is a fatal malignancy caused by infection with the complex retrovirus human T-cell leukemia virus type 1 (HTLV-1). In this study, we found that the HTLV-1-encoded protein HBZ activates expression of BDNF, and consistent with this effect, BDNF expression is elevated in HTLV-1-infected T-cell lines compared to uninfected T cells. Expression of TrkB is also higher in HTLV-1-infected T-cell lines than in uninfected T cells. Furthermore, levels of both BDNF and TrkB mRNAs are elevated in peripheral blood mononuclear cells (PBMCs) from ATL patients, and ATL patient sera contain higher concentrations of BDNF than sera from noninfected individuals. Finally, chemical inhibition of TrkB signaling increases apoptosis in HTLV-1-infected T cells and reduces phosphorylation of glycogen synthase kinase 3β (GSK-3β), a downstream target in the signaling pathway. These results suggest that HBZ contributes to an active BDNF/TrkB autocrine/paracrine signaling loop in HTLV-1-infected T cells that enhances the survival of these cells. IMPORTANCE Infection with human T-cell leukemia virus type 1 (HTLV-1) can cause a rare form of leukemia designated adult T-cell leukemia (ATL). Because ATL patients are unresponsive to chemotherapy, this malignancy is fatal. As a retrovirus, HTLV-1 integrates its genome into a host cell chromosome in order to utilize host factors for replication and expression of viral proteins. However, in infected cells from ATL patients, the viral genome is frequently modified to block expression of all but a single viral protein. This protein, known as HBZ, is therefore believed to modulate cellular pathways necessary for the leukemic state and the chemotherapeutic resistance of the cell. Here we provide evidence to support this hypothesis. We found that HBZ promotes a BDNF/TrkB autocrine/paracrine signaling pathway that is known to enhance the survival and chemotherapeutic resistance of other types of cancer cells. It is possible that inhibition of this pathway may improve treatments for ATL.
Using Incident Reports to Identify Vulnerabilities: A Case Study in Radiation Therapy

As mandatory reporting of health care incidents becomes more prevalent, the need for effective strategies for analyzing historical reports to identify vulnerabilities is increasingly important. For this project, the research team reviewed existing event narratives collected by the U.S. Nuclear Regulatory Commission (NRC) that described errors with the use of nuclear byproducts in four medical treatment modalities: gamma knife stereotactic radiosurgery, high dose rate brachytherapy, low dose rate brachytherapy, and interstitial brachytherapy. This analysis had three levels: identification of possible system vulnerabilities based on historical data, analysis of event data for trends over time and for each treatment modality, and comparison of the suggested corrective actions with the implemented corrective actions for each event. The research team identified types of errors that were more prevalent with each treatment modality, along with discrepancies between suggested corrective actions and the implemented corrective actions. This project is a case study illustrating strategies for extracting valuable information from incident-reporting databases.