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Approximate 70% of cobra venom is composed of cytotoxin (CTX), which is responsible for the dermonecrotic symptoms of cobra envenomation. However, CTX is generally low in immunogenicity, and the antivenom is ineffective in attenuating its in vivo toxicity. Furthermore, little is known about its epitope properties for empirical antivenom therapy. This study aimed to determine the epitope sequences of CTX using the immunoinformatic analyses and epitope-omics profiling. A conserved CTX was used in this study to determine its T-cell and B-cell epitope sequences using immunoinformatic tools and molecular docking simulation with different Human Leukocyte Antigens (HLAs). The potential T-cell and B-cell epitopes were 'KLVPLFY,' 'CPAGKNLCY,' 'MFMVSTPTK,' and 'DVCPKNSLL.' Molecular docking simulations disclosed that the HLA-B62 supertype exhibited the greatest binding affinity towards cobra venom cytotoxin. The namely L7, G18, K19, N20, M25, K33, V43, C44, K46, N47, and S48 of CTX exhibited prominent intermolecular interactions with HLA-B62. The multi-enzymatic-limited-digestion/liquid chromatography-mass spectrometry (MELD/LC–MS) also revealed three potential epitope sequences as 'LVPLFYK,' 'MFMVS,' and 'TVPVKR'. From different epitope mapping approaches, we concluded four potential epitope sites of CTX as 'KLVPLFYK', 'AGKNL', 'MFMVSTPKVPV' and 'DVCPKNSLL'. Site-directed mutagenesis of these epitopes confirmed their locations at the functional loops of CTX. These epitope sequences are crucial to CTX's structural folding and cytotoxicity. The results concluded the epitopes that resided within the functional loops constituted potential targets to fabricate synthetic epitopes for CTX-targeted antivenom production. [ABSTRACT FROM AUTHOR]

Vaccine-induced neutralizing antibodies (nAbs) are key biomarkers considered to be associated with vaccine efficacy. In United States government-sponsored phase 3 efficacy trials of COVID-19 vaccines, nAbs are measured by two different validated pseudovirus-based SARS-CoV-2 neutralization assays, with each trial using one of the two assays. Here we describe and compare the nAb titers obtained in the two assays. We observe that one assay consistently yielded higher nAb titers than the other when both assays were performed on the World Health Organization's anti-SARS-CoV-2 immunoglobulin International Standard, COVID-19 convalescent sera, and mRNA-1273 vaccinee sera. To overcome the challenge this difference in readout poses in comparing/combining data from the two assays, we evaluate three calibration approaches and show that readouts from the two assays can be calibrated to a common scale. These results may aid decision-making based on data from these assays for the evaluation and licensure of new or adapted COVID-19 vaccines. [ABSTRACT FROM AUTHOR]

The outcomes of patients with incident kidney failure who start hemodialysis are influenced by several factors. Whether hemodialysis facility characteristics are associated with patient outcomes is unclear. We included adults diagnosed as having kidney failure requiring hemodialysis during January 1, 2001 to December 31, 2013 from the Taiwan National Health Insurance Research Database to perform this retrospective cohort study. The exposures included different sizes and levels of hemodialysis facilities. The outcomes were all-cause mortality, cardiovascular death, infection-related death, hospitalization, and kidney transplantation. During 2001–2013, we identified 74,406 patients and divided them in to three groups according to the facilities where they receive hemodialysis: medical center (n = 8263), non-center hospital (n = 40,008), and clinic (n = 26,135). The multivariable Cox model demonstrated that a larger facility size was associated with a low mortality risk (hazard ratio [HR] 0.991, 95% confidence interval [95% CI] 0.984–0.998; every 20 beds per facility). Compared with medical centers, patients in non-center hospitals and clinics had higher mortality risks (HR 1.13, 95% CI 1.09–1.17 and HR 1.11, 95% CI 1.06–1.15, respectively). Patients in medical centers and non-center hospitals had higher risk of hospitalization (subdistribution HR [SHR] 1.11, 95% CI 1.10–1.12 and SHR 1.22, 95% CI 1.21–1.23, respectively). Patients in medical centers had the highest rate of kidney transplantation among the three groups. In patients with incident kidney failure, a larger hemodialysis facility size was associated with lower mortality. Overall, medical center patients had a lower mortality rate and higher transplantation rate, whereas clinic patients had a lower hospitalization risk. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is a common complication in acute heart failure (AHF) and is associated with prolonged hospitalization and increased mortality. The aim of this study was to externally validate existing prediction models of AKI in patients with AHF. Data for 10,364 patients hospitalized for acute heart failure between 2008 and 2018 were extracted from the Chang Gung Research Database and analysed. The primary outcome of interest was AKI, defined according to the KDIGO definition. The area under the receiver operating characteristic (AUC) curve was used to assess the discrimination performance of each prediction model. Five existing prediction models were externally validated, and the Forman risk score and the prediction model reported by Wang et al. showed the most favourable discrimination and calibration performance. The Forman risk score had AUCs for discriminating AKI, AKI stage 3, and dialysis within 7 days of 0.696, 0.829, and 0.817, respectively. The Wang et al. model had AUCs for discriminating AKI, AKI stage 3, and dialysis within 7 days of 0.73, 0.858, and 0.845, respectively. The Forman risk score and the Wang et al. prediction model are simple and accurate tools for predicting AKI in patients with AHF. [ABSTRACT FROM AUTHOR]

With ageing populations, new elderly end-stage kidney disease (ESKD) cases rise. Unlike younger patients, elderly ESKD patients are less likely to undergo kidney transplant, and therefore the decision of receiving peritoneal dialysis (PD) and hemodialysis (HD) is more crucial. A total of 36,852 patients, aged more than 65, who were newly diagnosed with ESKD and initiated renal replacement therapy between 2013 and 2019 were identified. These patients were categorized into two groups: the PD group and the HD group according to their long-term renal replacement treatment. After propensity score matching, the PD group (n = 1628) displayed a lower incidence of major adverse cardiac and cerebrovascular events (MACCE) (10.09% vs. 13.03%, hazard ratio (HR): 0.74, 95% confidence interval (CI): 0.66–0.83), malignancy (1.23% vs. 2.14%, HR: 0.55, 95% CI: 0.40–0.76), and MACCE-associated mortality (1.35% vs. 2.25%, HR: 0.62, 95% CI: 0.46–0.84) compared to the HD group (n = 6512). However, the PD group demonstrated a higher rate of infection (34.09% vs. 24.14%, HR: 1.28, 95% CI: 1.20–1.37). The risks of all-cause mortality and infection-associated mortality were not different. This study may provide valuable clinical information to assist elderly ESKD patients to choose HD or PD as their renal replacement therapy. [ABSTRACT FROM AUTHOR]

In this work, 4-layered SiO2/Bi2Te3/SiO2/Cu film structures were designed and fabricated and the optical properties investigated in the wavelength region of 250-1200 nm for their promising applications for direct solar-thermal-electric conversion. A typical 4-layered film sample with the structure SiO2 (66.6 nm)/Bi2Te3 (7.0 nm)/SiO2 (67.0 nm)/Cu (>100.0 nm) was deposited on a Si or K9-glass substrate by magnetron sputtering. The experimental results agree well with the simulated ones showing an average optical absorption of 96.5%, except in the shorter wavelength region, 250-500 nm, which demonstrates the superior absorption property of the 4-layered film due to the randomly rough surface of the Cu layer resulting from the higher deposition power. The high reflectance of the film structure in the long wavelength region of 2-20 μm will result in a low thermal emittance, 0.064 at 600 K. The simpler 4-layered structure with the thermoelectric Bi2Te3 used as the absorption layer may provide a straightforward way to obtain solar-thermal-electric conversion more efficiently through future study. [ABSTRACT FROM AUTHOR]