Na Hong

The replication of positive-strand RNA viral genomes involves various cis-acting RNA sequences. Generally, regulatory RNA sequences are present at or near genomic termini; however, internal replication elements (IREs) also exist. Here we report the structural and functional characterization of an IRE present in the readthrough portion of the p92 polymerase gene of Tomato bushy stunt virus. Analysis of this element in the context of a noncoding defective interfering RNA revealed a functional core structure composed of two noncontiguous segments of sequence that interact with each other to form an extended helical conformation. IRE activity required maintenance of several base-paired sections as well as two distinct structural features: (i) a short, highly conserved segment that can potentially form two different and mutually exclusive structures and (ii) an internal loop that contains a critical CC mismatch. The IRE was also shown to play an essential role within the context of the viral genome. In vivo analysis with novel RNA-based temperature-sensitive genomic mutants and translationally active subgenomic viral replicons revealed the following about the IRE: (i) it is active in the positive strand, (ii) it is dispensable late in the viral RNA replication process, and (iii) it is functionally inhibited by active translation over its sequence. Together, these results suggest that IRE activity is required in the cytosol at an early step in the viral replication process, such as template recruitment and/or replicase complex assembly.

Several parameters of preoperative complete blood count (CBC) and inflammation-associated blood cell markers derived from them have been reported to correlate with prognosis in patients with epithelial ovarian cancer (EOC), but their prognostic importance and optimal cutoffs are still needed be elucidated. Clinic/pathological parameters, 5-year follow-up data and preoperative CBC parameters were obtained retrospectively in 654 EOC patients underwent primary surgery at Mayo Clinic. Cutoffs for neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) were optimized by receiver operating characteristic (ROC) curve. Prognostic significance for overall survival (OS) and recurrence free survival (RFS) were determined by Cox proportional hazards models and Kaplan-Meier method. Associations of RDW and NLR with clinic/pathological parameters were analyzed using non-parametric tests. RDW with cutoff 14.5 and NLR with cutoff 5.25 had independent prognostic significance for OS, while combined RDW and NLR scores stratified patients into low (RDW-low and NLR-low), intermediate (RDW-high or NLR-high) and high risk (RDW-high and NLR-high) groups, especially in patients with high-grade serous ovarian cancer (HGSOC). Moreover, high NLR was associated with poor RFS as well. Elevated RDW was strongly associated with age, whereas high NLR was strongly associated with stage, preoperative CA125 level and ascites at surgery.

ABSTRACT Background With the outbreak of coronavirus disease 2019 (COVID-19), a sudden case increase in late February 2020 led to deep concern globally. Italy, South Korea, Iran, France, Germany, Spain, the US and Japan are probably the countries with the most severe outbreaks. Collecting epidemiological data and predicting epidemic trends are important for the development and measurement of public intervention strategies. Epidemic prediction results yielded by different mathematical models are inconsistent; therefore, we sought to compare different models and their prediction results to generate objective conclusions. Methods We used the number of cases reported from January 23 to March 20, 2020, to estimate the possible spread size and peak time of COVID-19, especially in 8 high-risk countries. The logistic growth model, basic SEIR model and adjusted SEIR model were adopted for prediction. Given that different model inputs may infer different model outputs, we implemented three model predictions with three scenarios of epidemic development. Results When comparing all 8 countries’ short-term prediction results and peak predictions, the differences among the models were relatively large. The logistic growth model estimated a smaller epidemic size than the basic SERI model did; however, once we added parameters that considered the effects of public health interventions and control measures, the adjusted SERI model results demonstrated a considerably rapid deceleration of epidemic development. Our results demonstrated that contact rate, quarantine scale, and the initial quarantine time and length are important factors in controlling epidemic size and length. Conclusions We demonstrated a comparative assessment of the predictions of the COVID-19 outbreak in eight high-risk countries using multiple methods. By forecasting epidemic size and peak time as well as simulating the effects of public health interventions, the intent of this paper is to help clarify the transmission dynamics of COVID-19 and recommend operation suggestions to slow down the epidemic. It is suggested that the quick detection of cases, sufficient implementation of quarantine and public self-protection behaviors are critical to slow down the epidemic.