A Randomized, Double-Blind, Controlled Phase III Clinical Trial to Evaluate the Immunogenicity and Safety of a Lyophilized Human Rabies Vaccine (Vero Cells) in Healthy Participants Aged 10-60 Years Following Essen and Zagreb Vaccination Procedures.

OBJECTIVE: In this paper, we aim to show that the immunogenicity of the lyophilized human rabies vaccine (Vero cells) (investigational vaccine) developed by Dalian Aleph Biomedical Co., Ltd. in healthy participants aged 10-60 years old is non-inferior to the lyophilized PVRV (positive control) manufactured by Liaoning Chengda Biotechnology Co., Ltd. (Shenyang, China), and that its safety is clinically acceptable. METHOD: A total of 2776 participants were enrolled in this study and divided into four groups: a five-dose test group, a five-dose control group, a four-dose test group, and a four-dose control group. The patients in the four-dose groups (Zagreb) were vaccinated on Days 0 (two doses), 7 (one dose), and 21 (one dose), and those in the five-dose groups (Essen) were vaccinated on Days 0, 3, 7, 14, and 28 (one dose each). The rabies-virus-neutralizing antibody assay with the RFFIT was used to assess the immunogenicity, and the adverse events (AEs) and serious adverse events (SAEs) were identified and collated. RESULTS: The positive seroconversion rate was up to 100% on Days 14 and 35/42 after vaccination following any procedures in pre-immunization antibody-negative participants, and the positive seroconversion rate and geometric mean concentration (GMC) of the test groups (Zagreb and Essen vaccination procedures) was not inferior to that of the control groups. On Day 7 after vaccination, the immunogenicity of the Zagreb procedure with two doses of the vaccine on Day 0 was superior to the Essen procedure with one dose of vaccine, that is, the former had a higher seroconversion rate and RVNA titer. The non-inferiority criterion of immunogenicity was met for the whole population, the population aged 10-18 years and ≥18 years, and the pre-immunization antibody-positive population. The incidences of all AEs, solicited AEs, and unsolicited AEs in both groups were not statistically significant, and no vaccination-related SAEs were observed. CONCLUSION: The investigated vaccine is safe, its immunogenicity is non-inferior to that of the control vaccine, and the efficacy of the Zagreb procedure is superior to that of the Essen procedure 7 days after the first dose.

Polysaccharides from Fu brick tea ameliorate obesity by modulating gut microbiota and gut microbiota-related short chain fatty acid and amino acid metabolism.

Fu brick tea (FBT) is a traditional tea manufactured by solid-state fermentation of tea leaves (Camellia sinensis). Although anti-obesity effects have been reported for FBT, the associated role of FBT polysaccharides (PSs) and the underlying mechanisms remain unknown. In this study, we found that FBTPSs inhibited obesity, hyperlipidemia, and inflammation; improved intestinal barrier function; and alleviated gut microbiota dysbiosis in high-fat diet-fed rats. Akkermansia muciniphila, Bacteroides, Parasutterella, Desulfovibrio, and Blautia were the core microbes regulated by FBTPSs. FBTPSs regulated the production of gut microbiota-related metabolites, including short-chain fatty acids (SCFAs), branched-chain amino acids, and aromatic amino acids throughout the development of obesity, and regulated the SCFA-GPR signaling pathway. FBTPS-treated fecal microbiota transplant ameliorated obesity, alleviated gut microbiota dysbiosis, and improved gut microbiota-associated metabolites, suggesting that the anti-obesity effect of FBTPSs was gut microbiota-dependent. FBTPSs may serve as novel prebiotic agents for the treatment of obesity and dysbiosis of gut microbiota.

Analysis of segmentation of lung parenchyma based on deep learning methods.

Precise segmentation of lung parenchyma is essential for effective analysis of the lung. Due to the obvious contrast and large regional area compared to other tissues in the chest, lung tissue is less difficult to segment. Special attention to details of lung segmentation is also needed. To improve the quality and speed of segmentation of lung parenchyma based on computed tomography (CT) or computed tomography angiography (CTA) images, the 4th International Symposium on Image Computing and Digital Medicine (ISICDM 2020) provides interesting and valuable research ideas and approaches. For the work of lung parenchyma segmentation, 9 of the 12 participating teams used the U-Net network or its modified forms, and others used the methods to improve the segmentation accuracy include attention mechanism, multi-scale feature information fusion. Among them, U-Net achieves the best results including that the final dice coefficient of CT segmentation is 0.991 and the final dice coefficient of CTA segmentation is 0.984. In addition, attention U-Net and nnU-Net network also performs well. In this paper, the methods chosen by 12 teams from different research groups are evaluated and their segmentation results are analyzed for the study and references to those involved.

Characteristics and related factors of emergency department visits, readmission, and hospital transfers of inpatients under a DRG-based payment system: A nationwide cohort study.

OBJECTIVES: Taiwan has implemented the Diagnosis Related Groups (DRGs) since 2010, and the quality of care under the DRG-Based Payment System is concerned. This study aimed to examine the characteristics, related factors, and time distribution of emergency department (ED) visits, readmission, and hospital transfers of inpatients under the DRG-Based Payment System for each Major Diagnostic Category (MDC). METHODS: We conducted a retrospective cohort study using data from the National Health Insurance Research Database (NHIRD) from 2012 to 2013 in Taiwan. Multilevel logistic regression analysis was used to examine the factors related to ED visits, readmissions, and hospital transfers of patients under the DRG-Based Payment System. RESULTS: In this study, 103,779 inpatients were under the DRG-Based Payment System. Among these inpatients, 4.66% visited the ED within 14 days after their discharge. The factors associated with the increased risk of ED visits within 14 days included age, lower monthly salary, urbanization of residence area, comorbidity index, MDCs, and hospital ownership (p < 0.05). In terms of MDCs, Diseases and Disorders of the Kidney and Urinary Tract (MDC11) conferred the highest risk of ED visits within 14 days (OR = 4.95, 95% CI: 2.69-9.10). Of the inpatients, 6.97% were readmitted within 30 days. The factors associated with the increased risk of readmission included gender, age, lower monthly salary, comorbidity index, MDCs, and hospital ownership (p < 0.05). In terms of MDCs, the inpatients with Pregnancy, Childbirth and the Puerperium (MDC14) had the highest risk of readmission within 30 days (OR = 20.43, 95% CI: 13.32-31.34). Among the inpatients readmitted within 30 days, 75.05% of them were readmitted within 14 days. Only 0.16% of the inpatients were transferred to other hospitals. CONCLUSION: The study shows a significant correlation between Major Diagnostic Categories in surgery and ED visits, readmission, and hospital transfers. The results suggested that the main reasons for the high risk may need further investigation for MDCs in ED visits, readmissions, and hospital transfers.

Tea consumption and colorectal cancer risk: a meta-analysis of prospective cohort studies.

PURPOSE: Data from in vitro and animal studies support the preventive effect of tea (Camellia sinensis) against colorectal cancer. Further, many epidemiologic studies evaluated the association between tea consumption and colorectal cancer risk, but the results were inconsistent. We conducted a meta-analysis of prospective cohort studies to systematically assess the association between tea consumption and colorectal cancer risk. METHODS: A comprehensive literature review was conducted to identify the related articles by searching PubMed and Embase up to June, 2019. Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated using a fixed effect model. RESULTS: Twenty cohort articles were included in the present meta-analysis involving 2,068,137 participants and 21,437 cases. The combined RR of colorectal cancer for the highest vs. lowest tea consumption was determined to 0.97 (95% CI 0.94-1.01) with marginal heterogeneity (I2 = 24.0%, P = 0.093) among all studies. This indicated that tea consumption had no significant association with colorectal cancer risk. Stratified analysis showed that no significant differences were found in all subgroups. We further conducted the gender-specific meta-analysis for deriving a more precise estimation. No significant association was observed between tea consumption and colorectal cancer risk in male (combined RR = 0.97; 95% CI 0.90-1.04). However, tea consumption had a marginal significant inverse impact on colorectal cancer risk in female (combined RR = 0.93; 95% CI 0.86-1.00). Further, we found a stronger inverse association between tea consumption and risk of colorectal cancer among the female studies with no adjustment of coffee intake (RR: 0.90; 95% CI 0.82-1.00, P < 0.05) compared to the female studies that adjusted for coffee intake (RR = 0.97; 95% CI 0.87-1.09, P > 0.05). CONCLUSIONS: Our finding indicates that tea consumption has no significant impact on the colorectal cancer risk in both genders combined, but gender-specific meta-analysis shows that tea consumption has a marginal significant inverse impact on colorectal cancer risk in female.

Vaccination of advanced hepatocellular carcinoma patients with tumor lysate-pulsed dendritic cells: a clinical trial.

Hepatocellular carcinoma (HCC) is a common and rapidly progressing malignancy. Current treatment options for advanced HCC are limited. This clinical study of dendritic cell (DC)-based immunotherapy for HCC enrolled 31 patients with advanced HCC. DCs, propagated from peripheral blood monocytes, were pulsed with autologous tumor lysates to treat HCC. The first 14 patients underwent pulsed therapy with five courses of DC vaccination intravenously at weekly intervals. The other 17 patients underwent monthly boost vaccinations after the initial pulsed therapy. Among the 31 patients, 4 (12.9%) exhibited partial response to DC vaccination. Seventeen patients (54.8%) had stable disease. Ten patients (32.3%) had progressive disease. The overall 1-year survival rate of all 31 patients was 40.1 +/- 9.1%. The patients treated with pulsed and boosted therapy had better 1-year survival rates than those treated by pulsed therapy alone (63.3 +/- 12.0% vs. 10.7 +/- 9.4%; P < 0.001). In this trial, DC vaccinations for advanced HCC were safe. Liver function tests showed no difference before and after DC vaccinations. The results of this clinical trial indicate that DC vaccination is a safe treatment for HCC. Pulsed DC vaccination followed by boosters can provide better clinical survival for advanced HCC patients than pulsed DC vaccination only. Further studies are needed to increase the efficacy of this therapeutic approach.

Age distribution for T cell reactivity to vaccinia virus in a healthy population.

The potential for bioterrorism involving smallpox has led to a debate about the durability of protective immunity against smallpox from vaccination. By assessing the T cell reactivity to vaccinia virus in a healthy population, we show that subjects who were vaccinated within the past 3 decades and who have a visible vaccination scar had remarkable T cell reactivity. However, person who were vaccinated within the past 3 decades but who do not have a scar and those who were vaccinated >4 decades ago had responses as low as those in unvaccinated subjects. Thus, we estimate that the significant T cell memory response to vaccinia virus from successful vaccination may persist for only 20-30 years. Furthermore, we found the vaccinia-specific cellular immunity could be easily assessed by determination of the frequencies of vaccinia-specific CD69 expression on T cell subsets. These data may help in the development of public health strategies to counter bioterrorism threats associated with smallpox.