Epidemiology of Angiostrongylus cantonensis and eosinophilic meningitis in the People's Republic of China

Background: Human eosinophilic meningitis is mainly caused by the rat lungworm Angiostrongylus cantonensis, especially in tropical and subtropical regions. Since the mid-1940s, more than 2800 cases of eosinophilic meningitis have been reported in at least 30 countries. Of note, A. cantonensis is one of a few helminths that can cause an outbreak within a short time period (usually within 2 weeks). Fatal cases, particular among young children, have been reported in heavily infected subjects. Eosinophilic meningitis is paradoxically an emerging infectious disease in the People¡¯s Republic of China (P.R. China). Indeed, while the rat lungworm was discovered in Guangzhou (formerly Canton) in 1933, there were only few cases reported until the mid 1990s. However, the biological invasion of two exotic snail species, namely the African land snail Achatina fulica and the South American freshwater snail Pomacea spp., drove the emergence of this disease. Thus far, more than three-quarter of human cases could definitely be related to the consumption of these snail species, particularly Pomacea spp. The seven outbreaks that occurred between 1997 and 2006 in P.R. China were all attributed to these two invasive snail species. Due to the emergence of eosinophilic meningitis and the issue of outbreaks that occurred at a growing frequency in P.R. China, there as a felt need to deepen our understanding of the epidemiology and control of this disease. Although several small-scale surveys pertaining to A. cantonensis had been carried out in P.R. China, the exact distribution of the parasite, and the invasive snail species that act as intermediate hosts remained to be determined. Goal and objectives: The overarching goal of this thesis is to improve our knowledge on the epidemiology of A. cantonensis and eosinophilic meningitis in P.R. China. There are six specific and interlinked objectives: (i) to identify the control priorities in eosinophilic meningitis by observing and analyzing outbreaks; (ii) to reveal the geographical distribution of A. cantonensis and to identify the major intermediate hosts; (iii) to characterize the mitochondrial (mt) genome of A. cantonensis and its close relative A. costaricensis in order to identify genetic marker that might give rise to novel diagnostic assays and population genetic studies; (iv) to evaluate the intraspecific differentiation of A. cantonensis and explore the potential dynamic scenarios in P.R. China; (v), to assess the genetic diversity of the invasive snail species Pomacea spp. and explore potential spread scenarios; and (vi) to assess the interplay between invasive snails, climate change and transmission dynamics. Methodology and principal findings: In 2008, we had the opportunity to study an outbreak of angiostrongyliasis that occurred in Dali due to the consumption of Pomacea spp. We found a prolonged period (8 months) of this outbreak with the peak occurring in February 2008, owing to a traditional festival. Only 11 out of 33 patients with complete data records were categorized into clinically diagnosed cases, whereas the others were grouped into suspected cases according to the existing diagnosis criteria. None of the patients was parasitologically diagnosed. Some important information for diagnosis was missing, which reflected the ignorance of clinicians on this disease. The existing diagnosis criteria for clinically diagnosed case requested an elevated eosinophil count both in peripheral blood and in cerebrospinal fluid (CSF), which was rather restrict. Interestingly, not all patients simultaneously experienced a marked change in eosinophil count, both in peripheral blood and CSF. Our findings called for further standardization of diagnosis and generalization of the clinical criteria. Surveillance system in endemic areas should be established for both security of snail food and human cases in hospitals. We had access to data obtained from the first national survey pertaining to A. cantonensis which was implemented using a geographical grid sampling approach. Our results showed that the rat lungworm was endemic in 59 of the 164 surveyed counties (36.0%), which represented seven south provinces in the mainland of P.R. China. Two of these provinces were newly confirmed. Two invasive snail species were identified as the key intermediate hosts. On average, the prevalence of A. cantonensis among A. fulica and Pomacea spp. was 13.4% and 6.8%, respectively. The prevalence among other terrestrial mollusks range from 0.3% (snail) to 6.5% (slugs), while that among freshwater snails was only 0.05%. Pomacea snails were found in 11 provinces, whereas A. fulica was encountered in six provinces. The complete mt genomes of A. cantonensis and A. costaricensis are 13,497 bp and 13,585 bp in length, respectively. Hence, these two closely related nematodes have the smallest mt genomes in the class of Chromadorea characterized thus far. Overall nucleotide identity of these two mt genomes was 81.6%, with a range from 77.7% to 87.1% in individual gene pairs. These findings provide a sound basis for screening potential genetic markers for diagnosis and further in-depth population genetic studies. The mt genome-wide analysis identified three major gene arrangement patterns from 48 nematode mt genomes. The gene arrangement, coupled with a phylogenetic tree based on concatenated amino acid sequence, supported a closer relationship between Ascaridida and Strongylida rather than Spirurida, which is inconsistent with findings of previous studies according to the nuclear small ribosomal subunit DNA. A. cantonensis specimens obtained from 33 collection sites were used to study the intraspecific differentiation based on the mitochondrial nad1 gene. A total of 73 haplotypes of A. cantonensis were identified from 143 sequences, which resulted in seven distinctive clades (Mainland, Hainan, Sanya, Tiane, Nanao, Zixing and Thailand). Geographical distance and natural isolation played a role in the spatial distribution of these clades, which supported the Southeast Asian origin from a molecular point of view. A considerable haplotype invasion was noted, which indicated the impact of human activities on biodiversity. The potential invasion routes for the clades Hainan, Sanya and Tiane were inferred based on a network analysis. The conflict between the presumptive origin of the clades Hainan and Tiane and those of the clades Nanao and Sanya call for further research. A total of 523 sequences of mt gene cox1 of Pomacea spp. were obtained from 56 collection sites. Twenty-five haplotypes were identified with an overall diversity of 0.702, which was higher than those observed in previous studies. From a global point of view, only five out of 98 haplotypes, which were determined by the currently 228 available sequences in GenBank as well as the 523 sequences described in the present thesis, were shared between introduced (Southeast Asia) and native (South America) ranges. The 98 haplotypes were clustered into 10 groups. Six groups occurred in the mainland of P.R. China, among only two can be traced back to the South Americas, whereas were two also occurred in other countries in Southeast Asia. The remaining two groups only occurred in P.R. China. A phylogenetic analysis showed that two species (i.e. P. canaliculata and P. insularum) coexist in the mainland of P.R. China, although the phylogenetic position of group B is still pending. The definite spread route of this snail species was not determined, but the increased diversity in single collection sites indicated multiple and secondary introductions. Finally, we developed a biology-driven model to determined potential impacts of climate change on the distribution of Pomacea spp., and hence the transmission of A. cantonensis. Mean January temperature and snail generation intensity (generation number) were identified as key factors determining the distribution of Pomacea spp.. The model predicted an increase of 56.9% for the ¡®spread¡¯ and a decrease of 40.9% for the ¡®establishment¡¯ regions (¡®spread¡¯ and ¡®establishment¡¯ defined according to the aforementioned national sampling survey) by the 2030s relative to the present day. Key determinants of A. cantonensis transmission were identified as the generation intensity in the intermediate host, the longevity of A. cantonensis-infected rats and the dormant period of Pomacea spp. Importantly, transmission of A. cantonensis occurs only in areas where the snail¡¯s dormant period is below 173.2 days. The potential endemic area of A. cantonensis was predicted to double by the 2030s relative to the present day. Conclusions/significance: Outbreaks of eosinophilic meningitis are of particular and growing concern in P.R. China. Standardization and generalization of diagnosis and treatment are therefore urgently required to be better equipped for future outbreaks. The first national survey deepened our understanding of the distribution of A. cantonensis and two invasive snail species that have been identified as the key intermediate hosts. Our in-depth population genetic studies of A. cantonensis revealed that human activities changed the original distribution and might have facilitated long-distance dispersal. The well divergent clades implied that the mt genes are promising candidates for novel diagnostic markers and population genetic studies. Our research also showed that two species of Pomacea coexist in P.R. China. The current distribution indicated multiple and secondary introductions. Although the definite role of these snail in the current distribution pattern of A. cantonensis is not clear, the potential impact is considerable in a future warmer P.R. China

A Broad Learning Approach for Context-Aware Mobile Application Recommendation

With the rapid development of mobile apps, the availability of a large number of mobile apps in application stores brings challenge to locate appropriate apps for users. Providing accurate mobile app recommendation for users becomes an imperative task. Conventional approaches mainly focus on learning users' preferences and app features to predict the user-app ratings. However, most of them did not consider the interactions among the context information of apps. To address this issue, we propose a broad learning approach for \textbf{C}ontext-\textbf{A}ware app recommendation with \textbf{T}ensor \textbf{A}nalysis (CATA). Specifically, we utilize a tensor-based framework to effectively integrate user's preference, app category information and multi-view features to facilitate the performance of app rating prediction. The multidimensional structure is employed to capture the hidden relationships between multiple app categories with multi-view features. We develop an efficient factorization method which applies Tucker decomposition to learn the full-order interactions within multiple categories and features. Furthermore, we employ a group $\ell_{1}-$norm regularization to learn the group-wise feature importance of each view with respect to each app category. Experiments on two real-world mobile app datasets demonstrate the effectiveness of the proposed method

A Numerical Investigation of the Sparkjet Actuator in Multiple-shot Mode

AbstractComputational simulations were performed in multiple-shot mode to investigate the effects of the boundary conditions and the deposition energy on the performance of the Sparkjet actuator. The user define function (UDF) was applied in the source term of the energy equation to imitate the very arc current discharges which produce the synthetic flow. The method of numerical simulation is verified by the existing experimental and analytical data. Two parameters including the integration mass and momentum are defined to evaluate the performance of the Sparkjet actuator. The simulation results show that Sparkjet flow is more affected by the boundary conditions of the external walls of the cavity and its deposition energy. The performance of Sparkjet actuator drops with the increase of operation cycle when the wall of cavity is adiabatic. When the temperature of wall of cavity is constant, the integration mass and momentum during the exhaling stage decrease with the increase of temperature. The performance of actuator decreases with the increase of heat transfer coefficient when the wall of cavity is set to be coupled with effect of radiation and convection. The performance of actuator increases with increase of deposition energy

The Modeling of Interval-Valued Time Series Using Possibility Measure-Based Encoding-Decoding Mechanism

Interval-valued time series (ITS) is a collection of interval-valued data whose entires are ordered by time. The modeling of ITS is an ongoing issue pursued by many researchers. There are diverse ITS models showing better performance. This paper proposes a new ITS model using possibility measure-based encoding-decoding mechanism involved in fuzzy theory. The proposed model consists of four modules, say, linguistic variable generation module, encoding module, inference module and decoding module. The linguistic variable generation module can provide a series of linguistic variables expressed in fuzzy sets used to described dynamic characteristics of ITS. The encoding module encodes ITS into some embedding vectors with semantics with the aid of possibility measure and linguistic variables formed by linguistic variable generation module. The inference module uses artificial neural network to capture relationship implied in those embedding vectors with semantic. The decoding module decodes for the outputs of the inference module to produce the output of linguistic and interval formats by using the possibility measure-based encoding-decoding mechanism. In comparison with existing ITS models, the proposed model can not only produce the output of linguistic format, but also exhibit better numeric performance

New insights into fibrotic signaling in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) mostly occurs in the background of liver fibrosis, and activated hepatic stellate cells (HSCs) exist in HCC tissues and adjacent tissues. HSC activation is involved throughout the development of HCC precancerous lesions, which has gradually attracted the attention of related researchers. In addition, HCC can promote the activation of HSCs, which in turn accelerates the occurrence and development of HCC by promoting tumor angiogenesis. In this review, we reviewed 264 studies from PubMed and ScienceDirect to summarize and analyze current significant fibrotic signaling in HCC. As a result, we found 10 fibrotic signaling pathways that are closely related to the activation, proliferation, invasion, migration, and promotion of apoptosis of HCC cells. In addition, we found that crosstalk between various fibrotic signaling pathways of HCC, hypoxia-induced energy metabolic reprogramming of HCC cells, matrix stiffness and stemness of HCC cells, and ferroptosis of HCC cells and HSCs are the latest research hotspots. Furthermore, related drugs that have been found to target these 10 fibrotic signaling pathways of HCC are listed. Our study provides a new reference for developing anti-HCC drugs

Towards integrated surveillance-response systems for the prevention of future pandemics

Most human pathogens originate from non-human hosts and certain pathogens persist in animal reservoirs. The transmission of such pathogens to humans may lead to self-sustaining chains of transmission. These pathogens represent the highest risk for future pandemics. For their prevention, the transmission over the species barrier - although rare - should, by all means, be avoided. In the current COVID-19 pandemic, surprisingly though, most of the current research concentrates on the control by drugs and vaccines, while comparatively little scientific inquiry focuses on future prevention. Already in 2012, the World Bank recommended to engage in a systemic One Health approach for zoonoses control, considering integrated surveillance-response and control of human and animal diseases for primarily economic reasons. First examples, like integrated West Nile virus surveillance in mosquitos, wild birds, horses and humans in Italy show evidence of financial savings from a closer cooperation of human and animal health sectors. Provided a zoonotic origin can be ascertained for the COVID-19 pandemic, integrated wildlife, domestic animal and humans disease surveillance-response may contribute to prevent future outbreaks. In conclusion, the earlier a zoonotic pathogen can be detected in the environment, in wildlife or in domestic animals; and the better human, animal and environmental surveillance communicate with each other to prevent an outbreak, the lower are the cumulative costs

Influencing Factors Study of the Variable Speed Scroll Compressor with EVI Technology

Heating capacity of general air-condition system at low ambient temperature has been heavily attenuated. To solve the problem stated, the variable speed Scroll compressor with enhanced vapor injection (EVI) becomes the focus of the study in recent years. Influencing factors of the capacity and energy efficiency of the scroll compressor with EVI technology have been introduced in paper, including the area of Supplementary channel, the parameters of orbiting and fixed scroll profile, the position and number of Supplementary inlet. The different scheme of prototype is tested and the effect of the scheme is compared and analyzed. With the vapor injected into compress chambers, the Gas forces of working chambers change, and the characteristics of gas force about the scroll compressor with EVI Technology have also been analyzed

Emerging Angiostrongyliasis in Mainland China

Our review of angiostrongyliasis in China found that the disease is emerging as a result of changes in food consumption habits and long-distance transportation of food. Enhanced understanding of angiostrongyliasis epidemiology, increased public awareness about the risks associated with eating raw food, and enhanced food safety measures are needed

High mobility group box 1 promotes radioresistance in esophageal squamous cell carcinoma cell lines by modulating autophagy

Resistance to radiotherapy results in relapse and treatment failure in locally advanced esophageal squamous cell carcinoma (ESCC). High mobility group box 1 (HMGB1) is reported to be associated with the radioresistance in bladder and breast cancer. However, the role of HMGB1 in the radiotherapy response in ESCC has not been fully elucidated. Here, we investigated the role of HMGB1 to radioresistance in ESCC clinical samples and cell lines. We found that HMGB1 expression was associated with tumor recurrence after postoperative radiotherapy in locally advanced ESCC patients. HMGB1 knockdown in ESCC cells resulted in increased radiosensitivity both in vitro and in vivo. Autophagy level was found depressed in HMGB1 inhibition cells and activation of autophagy brought back cell's radioresistance. Our results demonstrate that HMGB1 activate autophagy and consequently promote radioresistance. HMGB1 may be used as a predictor of poor response to radiotherapy in ESCC patients. Our finding also highlights the importance of the utility of HMGB1 in ESCC radiosensitization.Peer reviewe

Increasing the Environmental Sustainability of Greenhouse Vegetable Production by Combining Biochar Application and Drip Fertigation—Effects on Soil N2_{2}O Emissions and Carbon Sequestrations

Drip fertigation with reduced fertilizer and water inputs has been widely used in greenhouse vegetable production in China. However, farmers usually do not apply additional organic material with a high carbon content, although soil organic carbon (SOC) concentrations are mostly below the optimum level for vegetable production. Returning straw or biochar to fields is an effective strategy for sustainability and environmental friendliness. We tested whether drip fertigation, (DIF) combined with maize straw (DIF+S) or biochar (DIF+BC), is a suitable option to improve SOC sequestration over eight growing seasons, and how these options affect soil N$_{2}$O emissions and yields or partial factor productivity of applied N (PFP$_{N}$) of crops over three growing seasons. During the winter–spring growing season, DIF+BC significantly reduced soil N$_{2}$O emission by 61.2% and yield-scaled N$_{2}$O emission by 62.4%, while increasing the tomato yield and PFP$_{N}$ compared with DIF. Straw incorporation had similar trends but without significant effects. Conversely, straw and biochar incorporation increased N$_{2}$O emission during the autumn–winter season. The structural equation model indicated N$_{2}$O emission was dominantly driven by soil NH$_{4}$$^{+}$-N concentration, temperature and moisture. The N$_{2}$O emission factor decreased significantly with increased PFP$_{N}$. Moreover, the contribution of biochar to the increased SOC was approximately 78%, which was four times higher than that of straw incorporation. Overall, the results highlighted the potential of drip fertigation with biochar incorporation to mitigate N$_{2}$O emissions, improve PFP$_{N}$ and significantly increase SOC storage, which could all contribute to maintaining environmental sustainability and soil quality of greenhouse vegetable production