Single-stranded RNA adjuvant enhances the efficacy of 10-valent human papilloma virus-like particle vaccine.

Following the development of various types of vaccines, the use of adjuvants to boost vaccine efficacy has become a focus of research. Aluminum hydroxide (alum), the most commonly used adjuvant, induces a certain immune response and ensures safety in human trials. However, alum mainly induces only a Th2 response; its Th1 response is weak. Thus, we previously developed a single-stranded ribose nucleic acid (ssRNA) adjuvant that induces a Th1 response through toll-like receptors. Here, we explored whether 10-valent human papilloma virus (HPV)-like particle (VLP) vaccine formulated with ssRNA adjuvant and alum helped to enhance immune response and maintained memory response. The mice were immunized intramuscularly twice at 2 week intervals and were inoculated 4 days after the second boost (after about 1 year). The antibody response and T cell activation were measured by Elispot, ELISA using harvested serum and splenocytes. The 10-valent HPV VLP vaccine formulated with ssRNA adjuvant and alum increased the antigen-specific immune response more than alum used alone. It increased each type-specific IgG1/IgG2a titer, and antigen-specific IFN-γ cells. Furthermore, the ssRNA adjuvant with alum induced memory response. In memory response, each type-specific IgG1/IgG2c, IFN-γ, and IL-6 cytokine, and neutralizing antibodies were increased by the ssRNA adjuvant with alum. Overall, the ssRNA adjuvant with alum induced memory responses and balanced Th1/Th2 responses. The ssRNA adjuvant and alum may help to enhance prophylactic vaccine efficacy.

Short-Term Event Prediction in the Operating Room (STEP-OP) of Five-Minute Intraoperative Hypotension Using Hybrid Deep Learning: Retrospective Observational Study and Model Development.

BACKGROUND: Intraoperative hypotension has an adverse impact on postoperative outcomes. However, it is difficult to predict and treat intraoperative hypotension in advance according to individual clinical parameters. OBJECTIVE: The aim of this study was to develop a prediction model to forecast 5-minute intraoperative hypotension based on the weighted average ensemble of individual neural networks, utilizing the biosignals recorded during noncardiac surgery. METHODS: In this retrospective observational study, arterial waveforms were recorded during noncardiac operations performed between August 2016 and December 2019, at Seoul National University Hospital, Seoul, South Korea. We analyzed the arterial waveforms from the big data in the VitalDB repository of electronic health records. We defined 2s hypotension as the moving average of arterial pressure under 65 mmHg for 2 seconds, and intraoperative hypotensive events were defined when the 2s hypotension lasted for at least 60 seconds. We developed an artificial intelligence-enabled process, named short-term event prediction in the operating room (STEP-OP), for predicting short-term intraoperative hypotension. RESULTS: The study was performed on 18,813 subjects undergoing noncardiac surgeries. Deep-learning algorithms (convolutional neural network [CNN] and recurrent neural network [RNN]) using raw waveforms as input showed greater area under the precision-recall curve (AUPRC) scores (0.698, 95% CI 0.690-0.705 and 0.706, 95% CI 0.698-0.715, respectively) than that of the logistic regression algorithm (0.673, 95% CI 0.665-0.682). STEP-OP performed better and had greater AUPRC values than those of the RNN and CNN algorithms (0.716, 95% CI 0.708-0.723). CONCLUSIONS: We developed STEP-OP as a weighted average of deep-learning models. STEP-OP predicts intraoperative hypotension more accurately than the CNN, RNN, and logistic regression models. TRIAL REGISTRATION: ClinicalTrials.gov NCT02914444; https://clinicaltrials.gov/ct2/show/NCT02914444.

Cloning and expression of a prion protein (PrP) gene from Korean bovine (Bos taurus coreanae) and production of rabbit anti-bovine PrP antibody.

A PrP gene, from a Korean bovine, exhibiting a nonsense and a missense polymorphism respectively at nucleotides 576 and 652 has been cloned. The latter resulted in Glu to Lys substitution at amino acid residue 218. After expression and purification of the recombinant bovine PrP (recBoPrP) with Glu218Lys substitution, a polyclonal antibody against this protein was raised. ELISA and Western blot analysis suggested that the recBoPrP obtained in this study had a unique conformation not presented in native PrP(C), and the polyclonal antibody recognized PrP in a conformation dependent manner. These reagents will be valuable tools for studying PrP conformation.