Infer Implicit Contexts in Real-time Online-to-Offline Recommendation

Understanding users' context is essential for successful recommendations, especially for Online-to-Offline (O2O) recommendation, such as Yelp, Groupon, and Koubei. Different from traditional recommendation where individual preference is mostly static, O2O recommendation should be dynamic to capture variation of users' purposes across time and location. However, precisely inferring users' real-time contexts information, especially those implicit ones, is extremely difficult, and it is a central challenge for O2O recommendation. In this paper, we propose a new approach, called Mixture Attentional Constrained Denoise AutoEncoder (MACDAE), to infer implicit contexts and consequently, to improve the quality of real-time O2O recommendation. In MACDAE, we first leverage the interaction among users, items, and explicit contexts to infer users' implicit contexts, then combine the learned implicit-context representation into an end-to-end model to make the recommendation. MACDAE works quite well in the real system. We conducted both offline and online evaluations of the proposed approach. Experiments on several real-world datasets (Yelp, Dianping, and Koubei) show our approach could achieve significant improvements over state-of-the-arts. Furthermore, online A/B test suggests a 2.9% increase for click-through rate and 5.6% improvement for conversion rate in real-world traffic. Our model has been deployed in the product of "Guess You Like" recommendation in Koubei.Comment: 9 pages,KDD,KDD201

Interleukin-17 Contributes to the Pathogenesis of Autoimmune Hepatitis through Inducing Hepatic Interleukin-6 Expression

T helper cells that produce IL-17 (Th17 cells) have recently been identified as the third distinct subset of effector T cells. Emerging data suggests that Th17 cells play an important role in the pathogenesis of many liver diseases by regulating innate immunity, adaptive immunity, and autoimmunity. In this study, we examine the role and mechanism of Th17 cells in the pathogenesis of autoimmune hepatitis (AIH). The serum levels of IL-17 and IL-23, as well as the frequency of IL-17+ cells in the liver, were significantly elevated in patients with AIH, compared to other chronic hepatitis and healthy controls. The hepatic expressions of IL-17, IL-23, ROR-γt, IL-6 and IL-1β in patients with AIH were also significantly increased and were associated with increased inflammation and fibrosis. IL-17 induces IL-6 expression via the MAPK signaling pathway in hepatocytes, which, in turn, may further stimulate Th17 cells and forms a positive feedback loop. In conclusion, Th17 cells are key effector T cells that regulate the pathogenesis of AIH, via induction of MAPK dependent hepatic IL-6 expression. Blocking the signaling pathway and interrupting the positive feedback loop are potential therapeutic targets for autoimmune hepatitis

Image_2_Efficacy and safety of novel carbapenem–β-lactamase inhibitor combinations: Results from phase II and III trials.tif

ObjectivesThe addition of novel β-lactamase inhibitors to carbapenems restores the activity against multidrug-resistant Gram-negative bacteria. The aim of this study was to summarize the evidence on the efficacy and safety of novel carbapenem–β-lactamase inhibitor combinations.MethodsWe conducted a meta-analysis of clinical trials comparing novel carbapenem–β-lactamase inhibitor combinations with comparators to assess the clinical and microbiological responses, mortality, and adverse events (AEs).ResultsA total of 1,984 patients were included. The pooled risk ratios (RRs) of clinical cure, microbiological eradication, all-cause mortality, and 28-day mortality were 1.11 (95% CI: 0.98–1.26), 0.98 (95% CI: 0.82–1.16), 0.90 (95% CI: 0.49–0.94), and 0.68 (95% CI: 0.49–0.94) between the novel carbapenem–β-lactamase inhibitor combinations and control groups. Sensitivity analysis revealed that the phase II trial of imipenem–cilastatin/relebactam (ICR) against complicated urinary tract infections could be the most important factor of heterogeneity for the microbiological response. The therapeutic effect of novel carbapenem–β-lactamase inhibitor combinations was better in meropenem–vaborbactam (MEV), phase III trials, and number of patients less than 200. The RRs of AEs from any cause and serious adverse events (SAEs) for patients receiving novel carbapenem–β-lactamase inhibitor combinations were 0.98 (95% CI: 0.93–1.04) and 1.01 (95% CI: 0.75–1.36), respectively.ConclusionsICR and MEV were superior to comparators for clinical cure and survival rate in the treatment of complicated infections, and both were as tolerable as the comparators.</p

Table_1_Efficacy and safety of novel carbapenem–β-lactamase inhibitor combinations: Results from phase II and III trials.pdf

ObjectivesThe addition of novel β-lactamase inhibitors to carbapenems restores the activity against multidrug-resistant Gram-negative bacteria. The aim of this study was to summarize the evidence on the efficacy and safety of novel carbapenem–β-lactamase inhibitor combinations.MethodsWe conducted a meta-analysis of clinical trials comparing novel carbapenem–β-lactamase inhibitor combinations with comparators to assess the clinical and microbiological responses, mortality, and adverse events (AEs).ResultsA total of 1,984 patients were included. The pooled risk ratios (RRs) of clinical cure, microbiological eradication, all-cause mortality, and 28-day mortality were 1.11 (95% CI: 0.98–1.26), 0.98 (95% CI: 0.82–1.16), 0.90 (95% CI: 0.49–0.94), and 0.68 (95% CI: 0.49–0.94) between the novel carbapenem–β-lactamase inhibitor combinations and control groups. Sensitivity analysis revealed that the phase II trial of imipenem–cilastatin/relebactam (ICR) against complicated urinary tract infections could be the most important factor of heterogeneity for the microbiological response. The therapeutic effect of novel carbapenem–β-lactamase inhibitor combinations was better in meropenem–vaborbactam (MEV), phase III trials, and number of patients less than 200. The RRs of AEs from any cause and serious adverse events (SAEs) for patients receiving novel carbapenem–β-lactamase inhibitor combinations were 0.98 (95% CI: 0.93–1.04) and 1.01 (95% CI: 0.75–1.36), respectively.ConclusionsICR and MEV were superior to comparators for clinical cure and survival rate in the treatment of complicated infections, and both were as tolerable as the comparators.</p

Image_1_Efficacy and safety of novel carbapenem–β-lactamase inhibitor combinations: Results from phase II and III trials.tif

ObjectivesThe addition of novel β-lactamase inhibitors to carbapenems restores the activity against multidrug-resistant Gram-negative bacteria. The aim of this study was to summarize the evidence on the efficacy and safety of novel carbapenem–β-lactamase inhibitor combinations.MethodsWe conducted a meta-analysis of clinical trials comparing novel carbapenem–β-lactamase inhibitor combinations with comparators to assess the clinical and microbiological responses, mortality, and adverse events (AEs).ResultsA total of 1,984 patients were included. The pooled risk ratios (RRs) of clinical cure, microbiological eradication, all-cause mortality, and 28-day mortality were 1.11 (95% CI: 0.98–1.26), 0.98 (95% CI: 0.82–1.16), 0.90 (95% CI: 0.49–0.94), and 0.68 (95% CI: 0.49–0.94) between the novel carbapenem–β-lactamase inhibitor combinations and control groups. Sensitivity analysis revealed that the phase II trial of imipenem–cilastatin/relebactam (ICR) against complicated urinary tract infections could be the most important factor of heterogeneity for the microbiological response. The therapeutic effect of novel carbapenem–β-lactamase inhibitor combinations was better in meropenem–vaborbactam (MEV), phase III trials, and number of patients less than 200. The RRs of AEs from any cause and serious adverse events (SAEs) for patients receiving novel carbapenem–β-lactamase inhibitor combinations were 0.98 (95% CI: 0.93–1.04) and 1.01 (95% CI: 0.75–1.36), respectively.ConclusionsICR and MEV were superior to comparators for clinical cure and survival rate in the treatment of complicated infections, and both were as tolerable as the comparators.</p

ESKAPE in China: epidemiology and characteristics of antibiotic resistance

ABSTRACTThe escalation of antibiotic resistance and the diminishing antimicrobial pipeline have emerged as significant threats to public health. The ESKAPE pathogens – Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. – were initially identified as critical multidrug-resistant bacteria, demanding urgently effective therapies. Despite the introduction of various new antibiotics and antibiotic adjuvants, such as innovative β-lactamase inhibitors, these organisms continue to pose substantial therapeutic challenges. People’s Republic of China, as a country facing a severe bacterial resistance situation, has undergone a series of changes and findings in recent years in terms of the prevalence, transmission characteristics and resistance mechanisms of antibiotic resistant bacteria. The increasing levels of population mobility have not only shaped the unique characteristics of antibiotic resistance prevalence and transmission within People’s Republic of China but have also indirectly reflected global patterns of antibiotic-resistant dissemination. What’s more, as a vast nation, People’s Republic of China exhibits significant variations in the levels of antibiotic resistance and the prevalence characteristics of antibiotic resistant bacteria across different provinces and regions. In this review, we examine the current epidemiology and characteristics of this important group of bacterial pathogens, delving into relevant mechanisms of resistance to recently introduced antibiotics that impact their clinical utility in China

Characterization of the population structure, drug resistance mechanisms and plasmids of the community-associated Enterobacter cloacae complex in China

Objectives: To investigate the population structure, drug resistance mechanisms and plasmids of community-associated Enterobacter cloacae complex (CA-ECC) isolates in China. Methods: Sixty-two CA-ECC isolates collected from 31 hospitals across China were typed by hsp60 typing and MLST. ESBL and AmpC-overexpression phenotype was determined by double-disc synergy test. Replicon typing and conjugation were performed for plasmid analysis. All ESBL-positive isolates and representative conjugants were subjected to detailed characterization by WGS. Results: Enterobacter hormaechei and Enterobacter kobei were predominant in our collections. MLST distinguished 46 STs with a polyclonal structure. ST591 was the most prevalent clone detected in northern China. Twenty-two isolates (35.5%) were ESBL positive and half of them were E. kobei. ESBL positivity was related to ESBL production (15/22) and to AmpC overexpression (18/22). Core-genome phylogenetic analysis identified intra- and inter-regional dissemination of ESBL-producing E. kobei clones. ESBL producers were exclusively classified as E. hormaechei and E. kobei, and blaCTX-M-3 was the most prevalent ESBL genotype (10/15) detected in four different environments. In the ESBL-positive population, the ESBL producers encoded more drug resistance genes (8-24 genes) by carrying more plasmids (1-3 plasmids) than the non-ESBL-producing isolates, resulting in an inter-group difference in drug susceptibilities. IncHI-type plasmids were prevalent in the ESBL producers (12/15). All IncHI2-type plasmids (n = 11) carried ESBL genes and shared a similar backbone to p09-036813-1A_261 recovered from Salmonella enterica in Canada. Conclusions: The species-specific distribution, species-dependent ESBL mechanism and endemic plasmids identified in our study highlight the necessity for tailored surveillance of CA-ECC in the future

Molecular Epidemiology and Colistin Resistant Mechanism of mcr-Positive and mcr-Negative Clinical Isolated Escherichia coli

Transmissible colistin resistance mediated by the mcr gene has been reported worldwide, but clinical isolates of mcr-negative colistin-resistant Escherichia coli are rarely reported. The aim of this study was to evaluate the mechanism of colistin resistance among mcr-positive and mcr-negative E. coli clinical isolates by performing a molecular epidemiological surveillance. For the first time ever, we show nearly the same isolation ratio for mcr-negative and mcr-positive colistin-resistant clinical isolates (47.5 and 52.5%, respectively), with no demonstrable nosocomial transmission. We provide evidence for the prevalence of the mcr-positive IncX4 plasmid and its high potential for horizontal transfer, with no obvious sequence type (ST) preference. In addition, the minimal inhibitory concentrations (MICs) of colistin of the mcr-negative E. coli isolates were obviously higher than those of mcr-positive isolates. Apart from the usually detected genes, i.e., pmrAB, phoPQ, and mgrB, other genes may be associated with the colistin resistance in mcr-negative E. coli. To the best of our knowledge, this is the first paper to report the molecular epidemiological surveillance and the proper mechanism of colistin resistance in mcr-negative E. coli clinical isolates. Together, the results show that colistin resistance was prevalent not only in the mcr-positive clinical E. coli isolates but also in the mcr-negative isolates