Endogenous relapse and exogenous reinfection in recurrent pulmonary tuberculosis: A retrospective study revealed by whole genome sequencing

BackgroundTuberculosis may reoccur due to reinfection or relapse after initially successful treatment. Distinguishing the cause of TB recurrence is crucial to guide TB control and treatment. This study aimed to investigate the source of TB recurrence and risk factors related to relapse in Hunan province, a high TB burden region in southern China.MethodsA population-based retrospective study was conducted on all culture-positive TB cases in Hunan province, China from 2013 to 2020. Phenotypic drug susceptibility testing and whole-genome sequencing were used to detect drug resistance and distinguish between relapse and reinfection. Pearson chi-square test and Fisher exact test were applied to compare differences in categorical variables between relapse and reinfection. The Kaplan–Meier curve was generated in R studio (4.0.4) to describe and compare the time to recurrence between different groups. p < 0.05 was considered statistically significant.ResultsOf 36 recurrent events, 27 (75.0%, 27/36) paired isolates were caused by relapse, and reinfection accounted for 25.0% (9/36) of recurrent cases. No significant difference in characteristics was observed between relapse and reinfection (all p > 0.05). In addition, TB relapse occurs earlier in patients of Tu ethnicity compared to patients of Han ethnicity (p < 0.0001), whereas no significant differences in the time interval to relapse were noted in other groups. Moreover, 83.3% (30/36) of TB recurrence occurred within 3 years. Overall, these recurrent TB isolates were predominantly pan-susceptible strains (71.0%, 49/69), followed by DR-TB (17.4%, 12/69) and MDR-TB (11.6%, 8/69), with mutations mainly in codon 450 of the rpoB gene and codon 315 of the katG gene. 11.1% (3/27) of relapse cases had acquired new resistance during treatment, with fluoroquinolone resistance occurring most frequently (7.4%, 2/27), both with mutations in codon 94 of gyrA.ConclusionEndogenous relapse is the main mechanism leading to TB recurrences in Hunan province. Given that TB recurrences can occur more than 4 years after treatment completion, it is necessary to extend the post-treatment follow-up period to achieve better management of TB patients. Moreover, the relatively high frequency of fluoroquinolone resistance in the second episode of relapse suggests that fluoroquinolones should be used with caution when treating TB cases with relapse, preferably guided by DST results

A Novel High-Throughput Vaccinia Virus Neutralization Assay and Preexisting Immunity in Populations from Different Geographic Regions in China

Background: Pre-existing immunity to Vaccinia Tian Tan virus (VTT) resulting from a large vaccination campaign against smallpox prior to the early 1980s in China, has been a major issue for application of VTT-vector based vaccines. It is essential to establish a sensitive and high-throughput neutralization assay to understand the epidemiology of Vaccinia-specific immunity in current populations in China. Methodology/Principal Findings: A new anti-Vaccinia virus (VACV) neutralization assay that used the attenuated replication-competent VTT carrying the firefly luciferase gene of Photinus pyralis (rTV-Fluc) was established and standardized for critical parameters that included the choice of cell line, viral infection dose, and the infection time. The current study evaluated the maintenance of virus-specific immunity after smallpox vaccination by conducting a non-randomized, crosssectional analysis of antiviral antibody-mediated immune responses in volunteers examined 30–55 years after vaccination. The rTV-Fluc neutralization assay was able to detect neutralizing antibodies (NAbs) against Vaccinia virus without the ability to differentiate strains of Vaccinia virus. We showed that the neutralizing titers measured by our assay were similar to those obtained by the traditional plaque reduction neutralization test (PRNT). Using this assay, we found a low prevalence of NAb to VTT (7.6%) in individuals born before 1980 from Beijing and Anhui provinces in China, and when present, anti-VTT NAb titers were low. No NAbs were detected in all 222 samples from individuals born after 1980. There was no significan

Understanding the nature and determinants of store loyalty in China

Store loyalty is confirmed to be important for retailers as it can help them gain and retain a competitive advantage over their counterparts. Researchers suggest that to achieve store loyalty the retailer needs to cope with competition from both the task environment and the institutional environment. The task environment may require the retailer to provide merchandise of good quality and price and with a broad range of choice. In the institutional environment, consumers may develop diversified requirements towards a specific store where they conduct their shopping because they have diversified roles in society, e.g., as an employee, a member of the community, and/or as a religious believer. To meet challenges from the institutional environment, a store may donate to the community or ensure a good working environment for employees. According to institutional theory, once these rules are followed consumers perceive the store to be legitimate in the current institutional environment. This is referred as organizational legitimacy. Therefore, it is suggested that the consumers will support the store. This argument builds a solid foundation for the current research. It signifies the importance of institutional environment for establishing store loyalty. The current research further explores the influence of the institutional environment on store loyalty. According to institutional theory, the development of institutions is history-based and context-specific. Stakeholders based in different institutional environments may develop different institutional requirements. Therefore, it is necessary to investigate specific institutional requirements within their specific institutional environments. Furthermore, the formulation of organizational legitimacy can be categorized at a collective level or an individual level. Past research has explored the formulation of organizational legitimacy on the collective level. The individual level needs to be explored because it can influence the establishment of organizational legitimacy on the collective level. Finally, institutional theory also suggests that international companies will face many more challenges from the institutional environment when they expand into overseas markets. These three facets construct the three angles for the current research. Past research suggests that performative actions (measured by store image), and symbolic actions (measured by corporate social responsibility), can be employed to satisfy both the requirements of task environment and institutional environment, then to formulate organizational legitimacy, and then store loyalty. In the current research the influence of performative actions and symbolic actions on organizational legitimacy are explored from the abovementioned three facets. Firstly, the specific requirements of performative actions and symbolic actions in the specific context are investigated. The Chinese retail market is chosen as the investigation context due to its attractiveness in the international retail market. Secondly, the performative and symbolic actions influencing the formulation of organizational legitimacy on the individual level are explored. Thirdly, whether consumers in the host country develop higher requirements of performative and symbolic actions towards international retailers compared with local retailers is investigated. From the qualitative research, the consumers’ performative and institutional requirements towards the store operated by foreign or domestic retailers in the specific context are investigated, i.e., the Chinese retail market. Face-to-face in-depth interviews were conducted with 20 Chinese consumers from Ningbo (a city located in Eastern part of China). The results show that the respondents have clear economic and institutional requirements regarding stores operated by foreign or domestic retailers. From the economic perspective, store location, merchandise (assortment, price, and quality), store environment, and service are the focus. Interviewees also show their interest concerning the institutional actions taken by the store. They expect a store to show concern about the provision of a good working environment and equal payment for employees, donations they make to charity, and assurance of fair trade with local suppliers. For the second facet, questionnaires delivered to respondents from Ningbo resulted in the collection of 607 useful questionnaires. The statistical software Smart PLS is employed to analyse the data. The results show that individual consumers develop instrument evaluation towards the performative and symbolic actions of a store. Also, the consumer evaluates the symbolic actions from relational-moral perspectives. Both the instrumental evaluation and the relational-moral evaluation help the store achieve the perceived organizational legitimacy on the individual level and then the store loyalty. This signifies that the consumer may evaluate whether the store can bring economic benefits, efficiency, and so on. It is also important that the strategies of a store make consumers feel respected and reach their moral standards. It is suggested that the formulation of perceived organizational legitimacy on the individual level will influence the formulation of perceived organizational legitimacy on the collective level. As a result, the store needs to pay attention to the how its strategies, such as performative and symbolic actions, are evaluated by the individual consumer because it may influence the support of the group of consumers’ judgement towards the store. To achieve the third research goal, the data collected from the questionnaire are also investigated by multigroup analysis. The data are split into two groups, those consumers who show loyalty towards the store operated by domestic retailers or those who demonstrate loyalty to foreign retailers. The significant differentiations between the two groups show that consumers have higher instrumental evaluation towards the performative actions of a store operated by international retailers. For the store run by the international retailers, instrumental evaluation plays a more important role in formulating the perceived organizational legitimacy on the individual consumer. Other relationships within the conceptual framework reveal no significant differentiations between the two groups. This implies that the liability of foreignness from the institutional environment does not have significant influence on the international expansion of international retailers in the current research context. International retailers have not faced more institutional challenges from consumers in their host countries. Part of the reason for this is because the research is based on the grocery industry in which consumers show more concern about efficiency. Furthermore, it is possible that the institutional actions taken by international retailers are good enough to conquer the problem of the liability of foreignness. On the contrary, stores run by international retailers win consumers’ support by better performative actions compared with those of stores operated by domestic retailers

Understanding the nature and determinants of store loyalty in China

Store loyalty is confirmed to be important for retailers as it can help them gain and retain a competitive advantage over their counterparts. Researchers suggest that to achieve store loyalty the retailer needs to cope with competition from both the task environment and the institutional environment. The task environment may require the retailer to provide merchandise of good quality and price and with a broad range of choice. In the institutional environment, consumers may develop diversified requirements towards a specific store where they conduct their shopping because they have diversified roles in society, e.g., as an employee, a member of the community, and/or as a religious believer. To meet challenges from the institutional environment, a store may donate to the community or ensure a good working environment for employees. According to institutional theory, once these rules are followed consumers perceive the store to be legitimate in the current institutional environment. This is referred as organizational legitimacy. Therefore, it is suggested that the consumers will support the store. This argument builds a solid foundation for the current research. It signifies the importance of institutional environment for establishing store loyalty. The current research further explores the influence of the institutional environment on store loyalty. According to institutional theory, the development of institutions is history-based and context-specific. Stakeholders based in different institutional environments may develop different institutional requirements. Therefore, it is necessary to investigate specific institutional requirements within their specific institutional environments. Furthermore, the formulation of organizational legitimacy can be categorized at a collective level or an individual level. Past research has explored the formulation of organizational legitimacy on the collective level. The individual level needs to be explored because it can influence the establishment of organizational legitimacy on the collective level. Finally, institutional theory also suggests that international companies will face many more challenges from the institutional environment when they expand into overseas markets. These three facets construct the three angles for the current research. Past research suggests that performative actions (measured by store image), and symbolic actions (measured by corporate social responsibility), can be employed to satisfy both the requirements of task environment and institutional environment, then to formulate organizational legitimacy, and then store loyalty. In the current research the influence of performative actions and symbolic actions on organizational legitimacy are explored from the abovementioned three facets. Firstly, the specific requirements of performative actions and symbolic actions in the specific context are investigated. The Chinese retail market is chosen as the investigation context due to its attractiveness in the international retail market. Secondly, the performative and symbolic actions influencing the formulation of organizational legitimacy on the individual level are explored. Thirdly, whether consumers in the host country develop higher requirements of performative and symbolic actions towards international retailers compared with local retailers is investigated. From the qualitative research, the consumers’ performative and institutional requirements towards the store operated by foreign or domestic retailers in the specific context are investigated, i.e., the Chinese retail market. Face-to-face in-depth interviews were conducted with 20 Chinese consumers from Ningbo (a city located in Eastern part of China). The results show that the respondents have clear economic and institutional requirements regarding stores operated by foreign or domestic retailers. From the economic perspective, store location, merchandise (assortment, price, and quality), store environment, and service are the focus. Interviewees also show their interest concerning the institutional actions taken by the store. They expect a store to show concern about the provision of a good working environment and equal payment for employees, donations they make to charity, and assurance of fair trade with local suppliers. For the second facet, questionnaires delivered to respondents from Ningbo resulted in the collection of 607 useful questionnaires. The statistical software Smart PLS is employed to analyse the data. The results show that individual consumers develop instrument evaluation towards the performative and symbolic actions of a store. Also, the consumer evaluates the symbolic actions from relational-moral perspectives. Both the instrumental evaluation and the relational-moral evaluation help the store achieve the perceived organizational legitimacy on the individual level and then the store loyalty. This signifies that the consumer may evaluate whether the store can bring economic benefits, efficiency, and so on. It is also important that the strategies of a store make consumers feel respected and reach their moral standards. It is suggested that the formulation of perceived organizational legitimacy on the individual level will influence the formulation of perceived organizational legitimacy on the collective level. As a result, the store needs to pay attention to the how its strategies, such as performative and symbolic actions, are evaluated by the individual consumer because it may influence the support of the group of consumers’ judgement towards the store. To achieve the third research goal, the data collected from the questionnaire are also investigated by multigroup analysis. The data are split into two groups, those consumers who show loyalty towards the store operated by domestic retailers or those who demonstrate loyalty to foreign retailers. The significant differentiations between the two groups show that consumers have higher instrumental evaluation towards the performative actions of a store operated by international retailers. For the store run by the international retailers, instrumental evaluation plays a more important role in formulating the perceived organizational legitimacy on the individual consumer. Other relationships within the conceptual framework reveal no significant differentiations between the two groups. This implies that the liability of foreignness from the institutional environment does not have significant influence on the international expansion of international retailers in the current research context. International retailers have not faced more institutional challenges from consumers in their host countries. Part of the reason for this is because the research is based on the grocery industry in which consumers show more concern about efficiency. Furthermore, it is possible that the institutional actions taken by international retailers are good enough to conquer the problem of the liability of foreignness. On the contrary, stores run by international retailers win consumers’ support by better performative actions compared with those of stores operated by domestic retailers

Robust Control of Disturbed Fractional-Order Economical Chaotic Systems with Uncertain Parameters

This paper focuses on the robust control of fractional-order economical chaotic system (FOECS) with parametric uncertainties and external disturbances. The dynamical behavior of FOECS is studied by numerical simulation, and circuit implementations of FOECS are also given. Based on fractional-order Lyapunov stability theorems, a robust adaptive controller, which can guarantee that all signals remain bounded and the tracking error tends to a small region, is designed. The proposed method can be used to control a large range of fractional-order systems with system uncertainties. Fractional-order adaptation laws are constructed to update the estimation of adaptive parameters. Finally, the robustness and effectiveness of our control method are indicated by simulation results

Neutralizing antibodies against adenovirus type 2 in normal and HIV-1-infected subjects: Implications for use of Ad2 vectors in vaccines

Pre-existing neutralizing antibodies (NAbs) directed against vaccine vectors have attracted considerable research attention. Therefore, our aim was to establish a high-throughput economical neutralization assay to investigate the epidemiology of adenovirus type 2 (Ad2)-specific immunity in China and developed countries, including in a Chinese Human immunodeficiency virus (HIV)-1-infected population, and to guide the application of Ad2-vectored vaccines. We established a FluoroSpot-based anti-Ad2-virus neutralization assay using a recombinant replication-deficient Ad2 that expresses enhanced green fluorescent protein and standardized the critical parameters, including the choice of cell line, cell concentration, viral infective dose, and incubation time. The sera of 561 healthy individuals from China and developed countries and from 230 HIV-1-infected Chinese individuals were screened with this assay for Nabs against Ad2. The prevalence of anti-Ad2 NAbs was high in both China (92.2%) and developed countries (86.9%). Of the Ad2-seropositive individuals, 64.6% in China and 77.4% in developed countries had high NAb titers (> 810). The frequency of anti-Ad2 NAbs was higher in Anhui (97.5%) than in Beijing (88.7%). Their prevalence differed significantly according to age in Beijing, but not in Anhui Province, but by sex in neither province. Ad2 seroprevalence was as high among HIV-1-infected individuals (88.7%) as among healthy individuals (92.2%) in China. In conclusion, a simple, intuitive, high-throughput, economical fluorescence-based neutralization assay was developed to determine anti-Ad2 NAbs titers. Ad2 exposure was high in both healthy and HIV-1-infected populations in China, so vectors based on Ad2 may be inappropriate for human vaccines

Exposure to legacy and novel perfluoroalkyl substance disturbs the metabolic homeostasis in pregnant women and fetuses: A metabolome-wide association study

Background: Perfluoroalkyl substances (PFASs) exist extensively and several of these have been verified to be toxic. Prenatal exposure to PFASs has attracted much attention. Metabolome-wide association analyses can be used to explore the toxicity mechanisms of PFASs by identifying associated biomarkers. Objectives: To evaluate associations between the metabolites in maternal and cord serum and internal exposure to several common PFASs. Methods: Paired maternal and cord serum samples were collected from 84 pregnant women who gave birth between 2015 and 2016. Seven legacy and two novel PFASs were measured. A nontarget metabolomic method and an iterative metabolite annotation based on metabolic pathways were applied to characterize the metabolic profiles. Linear regression adjusted with the false discovery rate and covariates was used to indicate the associations. Results: A total of 279 features in maternal serum and 338 features in cord serum were identified as metabolites associated with PFAS exposure. Perfluorooctanoic acid (PFOA) and perfluorohexane sulfonic acid (PFHxS) were two PFASs associated with more metabolites, while the two novel chlorinated polyfluorinated ether sulfonic acids (Cl-PFESAs) showed less relevance to the metabolome. With pathway enrichment analysis, we found that three fatty acid metabolisms and retinol metabolism were correlated with PFAS exposure in maternal blood, and that sterol metabolism showed the correlation in both maternal serum and cord serum. Conclusions: We identified metabolites and pathways in pregnant women and fetuses associated with the exposure to several PFAS, indicating a promising application for metabolome-wide association studies. Additional research is needed to confirm causation

Spatial-temporal variations of spring drought based on spring-composite index values for the Songnen Plain, Northeast China

National Natural Science Foundation of China 41201568；CAS KZCX2-YW-Q06-1<p class="FR_field"> A spring-composite index (s-CI) is proposed in this study that involves slightly altering the use of the accumulated precipitation from the composite index (CI) comparing the value with other three commonly used indices (standardized precipitation index, SPI; self-calibrated Palmer drought severity index, sc-PDSI; and CI). In addition, the spatial-temporal variation of the s-CI in the Songnen Plain (SNP) was investigated using the Mann-Kendall test and empirical orthogonal function (EOF) methods. The results indicated that the proposed s-CI could identify most drought events in 1990s and 2000s and performed relatively better than SPI, sc-PDSI, and CI in this region. Compared with the other three indices, the s-CI had a higher correlation with relative soil moisture in April and May. The recent spring droughts (2000s) were the most severe in April or May. The weather was drier in May compared with April in the 1980s, whereas the weather was wetter in May than in April in the 1960s and 1970s. Moreover, the spatial patterns of the first EOFs for both April and May indicated an obviously east-west gradient in the SNP, whereas the second EOFs displayed north-south drought patterns. The proposed index is particularly suitable for detecting, monitoring, and exploring spring droughts in the Songnen Plain under global warming.</p