Estimates of Japanese Encephalitis mortality and morbidity: A systematic review and modeling analysis

BackgroundJapanese Encephalitis (JE) is known for its high case fatality ratio (CFR) and long-term neurological sequelae. Over the years, efforts in JE treatment and control might change the JE fatality risk. However, previous estimates were from 10 years ago, using data from cases in the 10 years before this. Estimating JE disease severity is challenging because data come from countries with different JE surveillance systems, diagnostic methods, and study designs. Without precise and timely JE disease severity estimates, there is continued uncertainty about the JE disease burden and the effect of JE vaccination.MethodologyWe performed a systematic review to collate age-stratified JE fatality and morbidity data. We used a stepwise model selection with BIC as the selection criteria to identify JE CFR drivers. We used stacked regression, to predict country-specific JE CFR from 1961 to 2030. JE morbidity estimates were grouped from similar study designs to estimate the proportion of JE survivors with long-term neurological sequelae.Principal findingsWe included 82 and 50 peer-reviewed journal articles published as of March 06 2021 for JE fatality and morbidity with 22 articles in both analyses. Results suggested overall JE CFR estimates of 26% (95% CI 22, 30) in 1961–1979, 20% (95% CI 17, 24) in 1980–1999, 14% (95% CI 11, 17) in 2000–2018, and 14% (95% CI 11, 17) in 2019–2030. Holding other variables constant, we found that JE fatality risk decreased over time (OR: 0.965; 95% CI: 0.947–0.983). Younger JE cases had a slightly higher JE fatality risk (OR: 1.012; 95% CI: 1.003–1.021). The odds of JE fatality in countries with JE vaccination is 0.802 (90% CI: 0.653–0.994; 95% CI: 0.62–1.033) times lower than the odds in countries without JE vaccination. Ten percentage increase in the percentage of rural population to the total population was associated with 15.35% (95% CI: 7.71, 22.57) decrease in JE fatality odds. Ten percentage increase in population growth rate is associated with 3.71% (90% CI: 0.23, 7.18; 95% CI: -0.4, 8.15) increase in JE fatality odds. Adjusting for the effect of year, rural population percent, age of JE cases, and population growth rate, we estimated that there was a higher odds of JE fatality in India compared to China. (OR: 5.46, 95% CI: 3.61–8.31). Using the prediction model we found that, in 2000–2018, Brunei, Pakistan, and Timor-Leste were predicted to have the highest JE CFR of 20%. Bangladesh, Guam, Pakistan, Philippines, and Vietnam had projected JE CFR over 20% for after 2018, whereas the projected JE CFRs were below 10% in China, Indonesia, Cambodia, Myanmar, Malaysia, and Thailand. For disability, we estimated that 36% (min-max 0–85) JE patients recovered fully at hospital discharge. One year after hospital discharge, 46% (min-max 0%-97%) JE survivors were estimated to live normally but 49% (min-max 3% - 86%)till had neurological sequelae.ConclusionJE CFR estimates were lower than 20% after 2000. Our study provides an updated estimation of CFR and proportion of JE cases with long-term neurological sequelae that could help to refine cost-benefit assessment for JE control and elimination programs.     

Positional behavior and canopy use of black snub-nosed monkeys Rhinopithecus strykeri in the Gaoligong Mountains,Yunnan, China

Studies on positional behavior and canopy use are essential for understanding how arboreal animals adapt their morphological characteristics and behaviors to the challenges of their environment. This study explores canopy and substrate use along with positional behavior in adult black snub-nosed monkeys Rhinopithecus strykeri, an endemic, critically endangered primate species in Gaoligong Mountains, southwest China. Using continuous focal animal sampling, we collected data over a 52-month period and found that R. strykeri is highly arboreal primarily using the high layers of the forest canopy (15–30 m), along with the terminal zone of tree crowns (52.9%), medium substrates (41.5%), and oblique substrates (56.8%). We also found sex differences in canopy and substrate use. Females use the terminal zones (56.7% versus 40.4%), small/medium (77.7% versus 60.1%), and oblique (59.9% versus 46.5%) substrates significantly more than males. On the other hand, males spend more time on large/very large (39.9% versus 22.3%) and horizontal (49.7% versus 35.2%) substrates. Whereas both sexes mainly sit (84.7%), and stand quadrupedally (9.1%), males stand quadrupedally (11.5% versus 8.3%), and bipedally (2.9% versus 0.8%) more often than females. Clamber, quadrupedalism, and leap/drop are the main locomotor modes for both sexes. Rhinopithecus strykeri populations never enter canopies of degenerated secondary forest and mainly use terminal branches in the middle and upper layers of canopies in intact mid-montane moist evergreen broadleaf forest and hemlock coniferous broadleaf mixed forests across their habitat.     

p53 Degradation by a Coronavirus Papain-like Protease Suppresses Type I Interferon Signaling

Infection by human coronaviruses is usually characterized by rampant viral replication and severe immunopathology in host cells. Recently, the coronavirus papain-like proteases (PLPs) have been identified as suppressors of the innate immune response. However, the molecular mechanism of this inhibition remains unclear. Here, we provide evidence that PLP2, a catalytic domain of the nonstructural protein 3 of human coronavirus NL63 (HCoV-NL63), deubiquitinates and stabilizes the cellular oncoprotein MDM2 and induces the proteasomal degradation of p53. Meanwhile, we identify IRF7 (interferon regulatory factor 7) as a bona fide target gene of p53 to mediate the p53-directed production of type I interferon and the innate immune response. By promoting p53 degradation, PLP2 inhibits the p53-mediated antiviral response and apoptosis to ensure viral growth in infected cells. Thus, our study reveals that coronavirus engages PLPs to escape from the innate antiviral response of the host by inhibiting p53-IRF7-IFNβ signaling.     

Application of Multiple Imputation for Missing Values in Three-Way Three-Mode Multi-Environment Trial Data

It is a common occurrence in plant breeding programs to observe missing values in three-way three-mode multi-environment trial (MET) data. We proposed modifications of models for estimating missing observations for these data arrays, and developed a novel approach in terms of hierarchical clustering. Multiple imputation (MI) was used in four ways, multiple agglomerative hierarchical clustering, normal distribution model, normal regression model, and predictive mean match. The later three models used both Bayesian analysis and non-Bayesian analysis, while the first approach used a clustering procedure with randomly selected attributes and assigned real values from the nearest neighbour to the one with missing observations. Different proportions of data entries in six complete datasets were randomly selected to be missing and the MI methods were compared based on the efficiency and accuracy of estimating those values. The results indicated that the models using Bayesian analysis had slightly higher accuracy of estimation performance than those using non-Bayesian analysis but they were more time-consuming. However, the novel approach of multiple agglomerative hierarchical clustering demonstrated the overall best performances.     

Characteristic morphology of intracellular microcolonies of Legionella oakridgensis OR-10

Legionella oakridgensis occasionally causes pneumonia in humans. We report here the characteristic morphology of intracellular microcolonies of L. oakridgensis OR-10 in infected epithelial cells. By light microscopy after Gimenez staining, the bacteria showed serpentine-like chain, disk-like conglomerate, and granular forms when they grew intracellularly in Vero cells, HeLa cells, and A549 cells. In a time-lapse study, we observed the progressive change from a serpentine-like chain form to a conglomerate form in Vero cells. Transmission electron microscopy showed that L. oakridgensis OR-10 proliferated both inside membrane structures and in the cytoplasm. Such highly serpentine chain growth has not been reported in any intracellular bacteria. Furthermore, these results imply that L. oakridgensis OR-10 may be proliferating inside the endoplasmic reticulum.     

Laccase-mediated system pretreatment to enhance the effect of hydrogen peroxide bleaching of cotton fabric

This study evaluates the bleaching efficiency of the hydrogen peroxide bleaching process combined with laccase-mediated system pretreatment (LMS-HPBP) in the treatment of scoured cotton fabric. By changing the factors of laccase-mediated system pretreatment and the hydrogen peroxide bleaching process and examining the subsequent whiteness value and retained tensile strength of the samples, we find three LMS-HPBP processes that are more environment friendly than the conventional hydrogen peroxide bleaching process (CHPBP): (i) bleaching with lower dosage of hydrogen peroxide; (ii) bleaching at reduced temperature; (iii) bleaching for shortened duration. Whiteness, retained tensile strength and K/S values of cotton fabric samples treated by i-iii processes were similar to or higher than those by CHPBP. X-ray diffraction (XRD) analysis also demonstrated that the three processes rendered fabric of both lower crystallinity and bigger crystallite size than those by CHPBP. In addition, the "green" short-flow process was developed to treat cotton fabric and the results obtained shows this method is feasible as a new energy-saving process.