Explore the vast range of titles available.

The effectiveness of inactivated SARS-CoV-2 vaccines against the Delta variant, which has been associated with greater transmissibility and virulence, remains unclear. We conducted a test-negative case-control study to explore the vaccine effectiveness (VE) in real-world settings. We recruited participants aged 18-59 years who consisted of SARS-CoV-2 test-positive cases (n = 74) and test-negative controls (n = 292) during the outbreak of the Delta variant in May 2021 in Guangzhou city, China. Vaccination status was compared to estimate The VE of SARS-CoV-2 inactivated vaccines. A single dose of inactivated SARS-CoV-2 vaccine yielded the VE of only 13.8%. After adjusting for age and sex, the overall VE for two-dose vaccination was 59.0% (95% confidence interval: 16.0% to 81.6%) against coronavirus disease 2019 (COVID-19) and 70.2% (95% confidence interval: 29.6-89.3%) against moderate COVID-19 and 100% against severe COVID-19 which might be overestimated due to the small sample size. The VE of two-dose vaccination against COVID-19 reached 72.5% among participants aged 40-59 years, and was higher in females than in males against COVID-19 and moderate diseases. While single dose vaccination was not sufficiently protective, the two-dose dosing scheme of the inactivated vaccines was effective against the Delta variant infection in real-world settings, with the estimated efficacy exceeding the World Health Organization minimal threshold of 50%.

As of June 8, 2020, the global reported number of COVID-19 cases had reached more than 7 million with over 400 000 deaths. The household transmissibility of the causative pathogen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains unclear. We aimed to estimate the secondary attack rate of SARS-CoV-2 among household and non-household close contacts in Guangzhou, China, using a statistical transmission model. In this retrospective cohort study, we used a comprehensive contact tracing dataset from the Guangzhou Center for Disease Control and Prevention to estimate the secondary attack rate of COVID-19 (defined as the probability that an infected individual will transmit the disease to a susceptible individual) among household and non-household contacts, using a statistical transmission model. We considered two alternative definitions of household contacts in the analysis: individuals who were either family members or close relatives, such as parents and parents-in-law, regardless of residential address, and individuals living at the same address regardless of relationship. We assessed the demographic determinants of transmissibility and the infectivity of COVID-19 cases during their incubation period. Between Jan 7, 2020, and Feb 18, 2020, we traced 195 unrelated close contact groups (215 primary cases, 134 secondary or tertiary cases, and 1964 uninfected close contacts). By identifying households from these groups, assuming a mean incubation period of 5 days, a maximum infectious period of 13 days, and no case isolation, the estimated secondary attack rate among household contacts was 12·4% (95% CI 9·8–15·4) when household contacts were defined on the basis of close relatives and 17·1% (13·3–21·8) when household contacts were defined on the basis of residential address. Compared with the oldest age group (≥60 years), the risk of household infection was lower in the youngest age group (<20 years; odds ratio [OR] 0·23 [95% CI 0·11–0·46]) and among adults aged 20–59 years (OR 0·64 [95% CI 0·43–0·97]). Our results suggest greater infectivity during the incubation period than during the symptomatic period, although differences were not statistically significant (OR 0·61 [95% CI 0·27–1·38]). The estimated local reproductive number (R) based on observed contact frequencies of primary cases was 0·5 (95% CI 0·41–0·62) in Guangzhou. The projected local R, had there been no isolation of cases or quarantine of their contacts, was 0·6 (95% CI 0·49–0·74) when household was defined on the basis of close relatives. SARS-CoV-2 is more transmissible in households than SARS-CoV and Middle East respiratory syndrome coronavirus. Older individuals (aged ≥60 years) are the most susceptible to household transmission of SARS-CoV-2. In addition to case finding and isolation, timely tracing and quarantine of close contacts should be implemented to prevent onward transmission during the viral incubation period. US National Institutes of Health, Science and Technology Plan Project of Guangzhou, Project for Key Medicine Discipline Construction of Guangzhou Municipality, Key Research and Development Program of China.

Trastuzumab is the backbone of HER2-directed gastric cancer therapy, but poor patient response due to insufficient cell sensitivity and drug resistance remains a clinical challenge. Here, we report that HER2 is involved in cell mitotic promotion for tumorigenesis by hyperactivating a crucial HER2-SHCBP1-PLK1 axis that drives trastuzumab sensitivity and is targeted therapeutically. SHCBP1 is an Shc1-binding protein but is detached from scaffold protein Shc1 following HER2 activation. Released SHCBP1 responds to HER2 cascade by translocating into the nucleus following Ser273 phosphorylation, and then contributing to cell mitosis regulation through binding with PLK1 to promote the phosphorylation of the mitotic interactor MISP. Meanwhile, Shc1 is recruited to HER2 for MAPK or PI3K pathways activation. Also, clinical evidence shows that increased SHCBP1 prognosticates a poor response of patients to trastuzumab therapy. Theaflavine-3, 3’-digallate (TFBG) is identified as an inhibitor of the SHCBP1-PLK1 interaction, which is a potential trastuzumab sensitizing agent and, in combination with trastuzumab, is highly efficacious in suppressing HER2-positive gastric cancer growth. These findings suggest an aberrant mitotic HER2-SHCBP1-PLK1 axis underlies trastuzumab sensitivity and offer a new strategy to combat gastric cancer. Resistance to Trastuzumab in HER2 gastric cancer patients remains a clinical challenge. In this study, the authors demonstrate that HER2 promotes tumorigenesis in gastric cancer by regulating mitotic progression through a Shc1-SHCBP1-PLK1-MISP axis and they identify a compound, TFBG, able to disrupt SHCBP1/PLK1 interaction and to synergize with trastuzumab.

In this paper, we propose a novel Deep Reinforcement Learning (DRL) algorithm which can navigate non-holonomic robots with continuous control in an unknown dynamic environment with moving obstacles. We call the approach MK-A3C (Memory and Knowledge-based Asynchronous Advantage Actor-Critic) for short. As its first component, MK-A3C builds a GRU-based memory neural network to enhance the robot’s capability for temporal reasoning. Robots without it tend to suffer from a lack of rationality in face of incomplete and noisy estimations for complex environments. Additionally, robots with certain memory ability endowed by MK-A3C can avoid local minima traps by estimating the environmental model. Secondly, MK-A3C combines the domain knowledge-based reward function and the transfer learning-based training task architecture, which can solve the non-convergence policies problems caused by sparse reward. These improvements of MK-A3C can efficiently navigate robots in unknown dynamic environments, and satisfy kinetic constraints while handling moving objects. Simulation experiments show that compared with existing methods, MK-A3C can realize successful robotic navigation in unknown and challenging environments by outputting continuous acceleration commands.

Desulfovibrio (DSV) is frequently found in the human intestine but limited knowledge is available regarding the relationship between DSV and host health. In this study, we analyzed large-scale cohort data from the Guangdong Gut Microbiome Project to study the ecology of DSV and the associations of DSV and host health parameters. Phylogenetic analysis showed that Desulfovibrio piger might be the most common and abundant DSV species in the GGMP. Predominant sub-OTUs of DSV were positively associated with bacterial community diversity. The relative abundance of DSV was positively correlated with beneficial genera, including Oscillospira , Coprococcus , Ruminococcus , Akkermansia, Roseburia , Faecalibacterium , and Bacteroides , and was negatively associated with harmful genera, such as Clostridium , Escherichia , Klebsiella , and Ralstonia. Moreover, the relative abundance of DSV was negatively correlated with body mass index, waist size, triglyceride levels, and uric acid levels. This suggests that DSV is associated with healthy hosts in some human populations.

Methimazole and propylthiouracil are the most common antithyroid drugs. We assessed the safety signals associated with methimazole and propylthiouracil by data mining the FDA pharmacovigilance database. Data were retrieved from the FAERS database from the 1st quarter of 2004 through the 4th quarter of 2023. A disproportionate analysis of reporting advantage ratios was used to assess potential associations between adverse events and methimazole/propylthiouracil. A total of 17,379,609 reports were extracted, of which 5,317 cases of methimazole and 1,761 cases of propylthiouracil were classified as primary suspect reports. After combining the same primary ID, 1586 patients with methimazole and 446 patients with propylthiouracil were retained. We observed 8 categories of SOCs with a reported number ≥ 30 for methimazole and 12 categories of SOCs with a reported number ≥ 10 for propylthiouracil. The median time to adverse events in patients with methimazole was 31 days, with an interquartile range of 31-74 days. The median time to adverse events in patients with propylthiouracil was 90 days, with an interquartile range was 20-388.5 days. Our study provided a more in-depth and extensive understanding of adverse events that may be associated with methimazole and propylthiouracil, which will help to reduce the risk of adverse events in the clinical treatment of methimazole and propylthiouracil.

Jump Point Search (JPS) is a well known symmetry-breaking algorithm that can substantially improve performance for grid-based optimal pathfinding. When the input grid is static further speedups can be obtained by combining JPS with goal bounding techniques such as Geometric Containers (instantiated as Bounding Boxes) and Compressed Path Databases. Two such methods, JPS+BB and Two-Oracle Path PlannING (Topping), are currently among the fastest known approaches for computing shortest paths on grids. The principal drawback for these algorithms is the overhead costs: each one requires an all-pairs precomputation step, the running time and subsequent storage costs of which can be prohibitive. In this work we consider an alternative approach where we precompute and store goal bounding data only for grid cells which are also jump points. Since the number of jump points is usually much smaller than the total number of grid cells, we can save up to orders of magnitude in preprocessing time and space. Considerable precomputation savings do not necessarily mean performance degradation. For a second contribution we show how canonical orderings, partial expansion strategies and enhanced intermediate pruning can be leveraged to improve online query performance despite a reduction in preprocessed data. The combination of faster preprocessing and stronger online reasoning leads to three new and highly performant algorithms: JPS+BB+ and Two-Oracle Pathfinding Search (TOPS) based on search, and Topping+ based on path extraction. We give a theoretical analysis showing that each method is complete and optimal. We also report convincing gains in a comprehensive empirical evaluation that includes almost all current and cutting-edge algorithms for grid-based pathfinding.

To investigate the level of screen time and gross motor movement level and the correlation between them in left-behind children aged 3 to 6 years old in China. A randomized whole-group sampling method was used to study 817 left-behind children aged 3-6 years in 15 kindergartens in Xiangcheng city, Henan province. The third version of the Test of Gross Motor Development (TGMD-3) was used to test the children's gross motor movement level, and the screen time questionnaire was used to test the children's screen time level. The relationship between the two and the indicators was explored using Pearson's two-sided correlation and multilevel regression. The average daily screen time of left-behind children aged 3-6 years old increased with age, and the reporting rate of >2 h/d ranged from 22.43% to 33.73%; gross motor movement of left-behind children aged 3-6 years old increased with age, with significant differences between age (p<0.05). There was a low to moderate negative correlation (r = -0.133 to -0.354, p<0.05) between screen time and gross motor movement in children aged 3-6 years, and multiple regression analysis showed that screen time was predictive of gross motor movement in children (p<0.05), with an explanation rate of 21.4%. There is a correlation between screen time and gross motor movement development in children aged 3-6 years old left behind, and the gross motor movement ability of children aged 3-6 years old can be developed by reducing screen time and increasing physical activity.

An effective method for separating and purifying critical saponins (polyphyllin II and polyphyllin VII) from a Paris polyphylla var. yunnanensis extract was developed in this study which was environmentally friendly and economical. Static adsorption kinetics, thermodynamics, and the dynamic adsorption-desorption of macroporous resins were investigated, and then the conditions of purification and separation were optimized by fitting with an adsorption thermodynamics equation and a kinetic equation. Effective NKA-9 resin from seven macroporous resins was screened out to separate and purify the two saponins. The static adsorption and dynamic adsorption were chemical and physical adsorption dual-processes on the NKA-9 resin. Under the optimum parameters, the contents of polyphyllin II and polyphyllin VII in the product were 17.3-fold and 28.6-fold those in plant extracts, respectively. The total yields of the two saponins were 93.16%. This research thus provides a theoretical foundation for the large-scale industrial production of the natural drugs polyphyllin II and polyphyllin VII.

Urolithiasis is a common urological disease with increasing prevalence and high recurrence rates around the world. Numerous studies have indicated reactive oxygen species (ROS) and oxidative stress (OS) were crucial pathogenic factors in stone formation. Dietary polyphenols are a large group of natural antioxidant compounds widely distributed in plant-based foods and beverages. Their diverse health benefits have attracted growing scientific attention in recent decades. Many literatures have reported the effectiveness of dietary polyphenols against stone formation. The antiurolithiatic mechanisms of polyphenols have been explained by their antioxidant potential to scavenge free radicals and ROS, modulate the expression and the activity of endogenous antioxidant and prooxidant enzymes, regulate signaling pathways associated with OS, and maintain cell morphology and function. In this review, we first describe OS and its pathogenic effects in urolithiasis and summarize the classification and sources of dietary polyphenols. Then, we focus on the current evidence defining their antioxidant potential against stone formation and put forward challenges and future perspectives of dietary polyphenols. To conclude, dietary polyphenols offer potential applications in the treatment and prevention of urolithiasis.