Influenza viruses are responsible for millions of cases globally and significantly threaten public health. Since pandemic and zoonotic influenza viruses have emerged in the last 20 years and some of the viruses have resulted in high mortality in humans, a universal influenza vaccine is needed to provide comprehensive protection against a wide range of influenza viruses. Current seasonal influenza vaccines provide strain-specific protection and are less effective against mismatched strains. The rapid antigenic drift and shift in influenza viruses resulted in time-consuming surveillance and uncertainty in the vaccine protection efficacy. Most recent universal influenza vaccine studies target the conserved antigen domains of the viral surface glycoproteins and internal proteins to provide broader protection. Following the development of advanced vaccine technologies, several innovative strategies and vaccine platforms are being explored to generate robust cross-protective immunity. This review provides the latest progress in the development of universal influenza vaccines.

Avian influenza virus (AIV) can cause severe diseases in poultry worldwide. H6N1 AIV was the dominant enzootic subtype in 1985 in the chicken farms of Taiwan until the initial outbreak of a low pathogenic avian influenza (LPAI) H5N2 virus in 2003; thereafter, this and other LPAIs have been sporadically detected. In 2015, the outbreak of three novel H5Nx viruses of highly pathogenic avian influenza (HPAI) emerged and devastated Taiwanese chicken and waterfowl industries. The mechanism of variation in pathogenicity among these viruses is unclear; but, in light of the many biological functions of viral non-structural protein 1 (NS1), including interferon (IFN) antagonist and host range determinant, we hypothesized that NS genetic diversity contributes to AIV pathogenesis. To determine the impact of NS1 variants on viral infection dynamics, we established a reverse genetics system with the genetic backbone of the enzootic Taiwanese H6N1 for generation of reassortant AIVs carrying exogenous NS segments of three different Taiwanese H5N2 strains. We observed distinct cellular distributions of NS1 among the reassortant viruses. Moreover, exchange of the NS segment significantly influenced growth kinetics and induction of cytokines [IFN-α, IFN-β, and tumor necrosis factor alpha (TNF-α)] in an NS1-and host-specific manner. The impact of NS1 variants on viral replication appears related to their synergic effects on viral RNA-dependent RNA polymerase activity and IFN response. With these approaches, we revealed that NS1 is a key factor responsible for the diverse characteristics of AIVs in Taiwan.

An adenoviral (AdV)-based vector system is a promising platform for vaccine development and gene therapy applications. Administration of an AdV vector elicits robust innate immunity, leading to the development of humoral and cellular immune responses against the vector and the transgene antigen, if applicable. The use of high doses (1011–1013 virus particles) of an AdV vector, especially for gene therapy applications, could lead to vector toxicity due to excessive levels of innate immune responses, vector interactions with blood factors, or high levels of vector transduction in the liver and spleen. Additionally, the high prevalence of AdV infections in humans or the first inoculation with the AdV vector result in the development of vector-specific immune responses, popularly known as preexisting vector immunity. It significantly reduces the vector efficiency following the use of an AdV vector that is prone to preexisting vector immunity. Several approaches have been developed to overcome this problem. The utilization of rare human AdV types or nonhuman AdVs is the primary strategy to evade preexisting vector immunity. The use of heterologous viral vectors, capsid modification, and vector encapsulation are alternative methods to evade vector immunity. The vectors can be optimized for clinical applications with comprehensive knowledge of AdV vector immunity, toxicity, and circumvention strategies.

CCL17, a chemotactic cytokine produced by macrophages, is known to promote inflammatory and fibrotic effects in multiple organs, but its role in mediating renal fibrosis is unclear. In our study cohort of 234 chronic kidney disease (CKD) patients and 65 healthy controls, human cytokine array analysis revealed elevated CCL17 expression in CKD that correlated negatively with renal function. The area under the receiver operating characteristic curve of CCL17 to predict the development of CKD stages 3b–5 was 0.644 (p < 0.001), with the optimal cut-off value of 415.3 ng/mL. In vitro over-expression of CCL17 in HK2 cells had no effect on cell viability, but increased cell motility and the expression of α-SMA, vimentin and collagen I, as shown by western blot analysis. In a unilateral ureteral obstruction (UUO) mouse model, we observed significantly increased interstitial fibrosis and renal tubule dilatation by Masson’s Trichrome and H&E staining, and markedly increased expression of CCL17, vimentin, collagen I, and α-SMA by IHC stain, qRTPCR, and western blotting. CCL17 induced renal fibrosis by promoting the epithelial-mesenchymal transition, resulting in ECM accumulation. CCL17 may be a useful biomarker for predicting the development of advanced CKD.

Maximizing resource provider service and satisfying user requirements at the same time is a challenging problem in cloud computing environments. The resource provider scheduler can automatically modify the number of resources and usage time of allocation requests. By using rescheduling, resource provider are able to prioritize the most profitable requests dynamically and still satisfy the requirements of the rush requests. In this paper, we propose a novel rescheduling scheme to resolve rush requests with the minimum change in the existing service assignments from graph coloring perspective. We evaluate our proposed scheme under different cloud services task assignment scenarios through computer simulations. The simulation results show that the proposed scheme produces effective contention resolution and better quality-of-service (QoS).

No abstract

Background Various studies have discussed the benefits of applying three-dimensional (3D) techniques, specifically its advantages with respect to ergonomics, feasibility, and the rate of learning achievable in microsurgery training. However, no study has been conducted that compares the operator experience of using two-dimensional (2D) and 3D systems in microsurgical training. The aim of this study is to compare 2D- and 3D-assisted microsurgical training in novices based on anastomosis of chicken femoral arteries. Methods The participants were grouped by previous microsurgical experience. Group A includes novice participants. Group B includes 2D-experienced participants. Group C includes both participants in groups A and B. A questionnaire composed of 10 parameters in the field of image quality, dexterity, ergonomic, and feasibility will be filled out after each participant finished their anastomoses by the 2D and 3D systems. Results The results demonstrated 3D system was scored better on “field of view” (p = 0.004), “less tremor” (p = 0.005), “neck/upper back comfort” (p = 0.043), “lower back comfort” (p = 0.015), “technical feasibility” (p = 0.020), and “educational feasibility” (p = 0.004) in group A (N = 12). In group B (N = 9), 3D system was scored better on “field of view” (p = 0.041) but worse on “image resolution” (p = 0.031). Conclusion With the 3D visualization system for microsurgical anastomosis of chicken femoral model, there are significant improvements in the field of view, stability, ergonomics, and educational value compared with 2D system among all participants. Accordingly, 3D-assisted microsurgery training can be a novel and potential popular training method.

PurposeWe investigated the association between pre-operative anemia and long-term all-cause mortality in patients with vertebral fracture who underwent a vertebroplasty.Materials and methodsWe retrospectively selected patients who were admitted for vertebroplasty for vertebral compression fracture between 2013 and 2020. Patients who had pathologic fractures or had no assessment of bone mineral density were excluded. Relevant information was collected from electronic medical records. Patients’ survival status was confirmed at the end of March 2021. Cox-proportional hazard models were conducted to examine the effects of anemia (&lt;12 g/dL vs. ≥12 g/dL) and pre-operative hemoglobin levels (as a continuous variable) on all-cause mortality with multivariate adjustments.ResultsA total of 167 patients were analyzed (mean age 75.8 ± 9.3 years, male 25.7%). After a median follow-up duration of 2.1 years, pre-operative anemia (hemoglobin &lt;12 g/dL vs. ≥12 g/dL) was independently associated with a higher risk of all-cause mortality (hazard ratio 2.762, 95% CI 1.184 to 6.442, p = 0.019). An increase in pre-operative hemoglobin was associated with a lower risk of all-cause mortality after multivariate adjustment (hazard ratio 0.775, 95% CI 0.606 to 0.991, p = 0.042).ConclusionPre-operative anemia (&lt;12 g/dL) was independently associated with survival outcome among patients with vertebral compression fractures who underwent vertebroplasty. Our findings highlight anemia as a risk factor of long-term mortality in this elderly surgical population.