Diagnosing and reintegrating traceability of infectious diseases via metagenomic next-generation sequencing: Study of a severe case of Rickettsia japonica infection.

Background: In this study, we present a case of Japanese spotted fever (JSF) caused by Rickettsia japonica and use this case to investigate the process of diagnosing and reintegrating traceability of infectious diseases via metagenomic next-generation sequencing (mNGS). Methods: From data relating to epidemiological history, clinical and laboratory examinations, and mNGS sequencing, a diagnosis of severe JSF was concluded. Results: A detailed field epidemiological investigation discovered parasitic Haemaphysalis longicornis from a host animal (dog) in the domicile of the patient, within which R. japonica was detected, along with a diverse array of other potentially pathogenic microorganisms that could cause other infectious diseases. Conclusion: The mNGS provided an efficient method to diagnose JSF infection. This methodology could also be applied to field epidemiological investigations to establish the traceability of infectious diseases.

Trends and focuses of hantavirus researches: a global bibliometric analysis and visualization from 1980 to 2020.

BACKGROUND: There have been worldwide changes in the researches on hantaviruses in the past several decades. Nevertheless, there are few bibliometric analysis studies this field. We aim to evaluate and visualize the research focuses and trends of this field using a bibliometric analysis way to help understand the developmet and future hotspots of this field. MATERIAL AND METHODS: Publications related to hantavirus studies were culled from the Web of Science Core Collection to generate trend analysis. The articles and reviews were re-extracted and Countries, institutions, authors, references and keywords in this field were visually analyzed by using VOSviewer and CiteSpace. RESULTS: A total of 4408 studies were included and the number of publications regarding hantaviruses significantly increased yearly. Three thousand seven hundred sixteen research articles and reviews were retrieved to generate bibliometric analysis. These studies mainly come from 125 countries led by USA and China and 3312 institutions led by the University of Helsinki. Twelve thousand five hundred twenty nine authors were identified and Vaheri A were the most influential author. Journal of Virology was the journal with the most studies and citations. After analysis, Hemorrhagic fever with renal syndrome, Hantavirus cardiopulmonary syndrome, nephropathia epidemica and related genotypes, clinical symptoms and rodents were the most common keywords and developing areas. CONCLUSION: Research on hantavirus is flourishing. Cooperation among different countries and institutions in this field must be strengthened in the future. The ecology and clinical symptoms of new genotypes, the vaccine development and factors that affect host population distribution and density are current and developing areas of study.

Epidemic characteristics and transmission risk prediction of brucellosis in Xi'an city, Northwest China.

Human brucellosis (HB) has re-emerged in China since the mid-1990s, and exhibited an apparent geographic expansion shifted from the traditional livestock regions to the inland areas of China. It is often neglected in non-traditional epidemic areas, posing a serious threat to public health in big cities. We carried out a retrospective epidemiological study in Xi'an, the largest city in northwestern China. It utilizes long-term surveillance data on HB during 2008-2021 and investigation data during 2014-2021. A total of 1989 HB cases were reported in Xi'an, consisting of 505 local cases, i.e., those located in Xi'an and 1,484 non-local cases, i.e., those located in other cities. Significantly epidemiological heterogeneity was observed between them, mainly owing to differences in the gender, occupation, diagnostic delays, and reporting institutions. Serological investigations suggested that 59 people and 1,822 animals (sheep, cattle, and cows) tested positive for brucellosis from 2014 to 2021, with the annual average seroprevalence rates were 1.38 and 1.54%, respectively. The annual animal seroprevalence rate was positively correlated with the annual incidence of non-local HB cases. Multivariate boosted regression tree models revealed that gross domestic product, population density, length of township roads, number of farms, and nighttime lights substantially contributed to the spatial distribution of local HB. Approximately 7.84 million people inhabited the potential infection risk zones in Xi'an. Our study highlights the reemergence of HB in non-epidemic areas and provides a baseline for large and medium-sized cities to identify regions, where prevention and control efforts should be prioritized in the future.

Predicting the Spatial-Temporal Distribution of Human Brucellosis in Europe Based on Convolutional Long Short-Term Memory Network.

Brucellosis is a chronic infectious disease caused by brucellae or other bacteria directly invading human body. Brucellosis presents the aggregation characteristics and periodic law of infectious diseases in temporal and spatial distribution. Taking major European countries as an example, this study established the temporal and spatial distribution sequence of brucellosis, analyzed the temporal and spatial distribution characteristics of brucellosis, and quantitatively predicted its epidemic law by using different traditional or machine learning models. This paper indicates that the epidemic of brucellosis in major European countries has statistical periodic characteristics, and in the same cycle, brucellosis has the characteristics of piecewise trend. Through the comparison of the prediction results of the three models, it is found that the prediction effect of long short-term memory and convolutional long short-term memory models is better than autoregressive integrated moving average model. The first mock exam using Conv layer and data vectorizations predicted that the convolutional long short-term memory model outperformed the traditional long short-term memory model. Compared with the monthly scale, the prediction of the trend stage of brucellosis can achieve better results under the single model prediction. These findings will help understand the development trend and liquidity characteristics of brucellosis, provide corresponding scientific basis and decision support for potential risk assessment and brucellosis epidemic prevention and control, and reduce the loss of life and property.

From Outbreak to Near Disappearance: How Did Non-pharmaceutical Interventions Against COVID-19 Affect the Transmission of Influenza Virus?

Influenza shares the same putative transmission pathway with coronavirus disease 2019 (COVID-19), and causes tremendous morbidity and mortality annually globally. Since the transmission of COVID-19 in China, a series of non-pharmaceutical interventions (NPIs) against to the disease have been implemented to contain its transmission. Based on the surveillance data of influenza, Search Engine Index, and meteorological factors from 2011 to 2021 in Xi'an, and the different level of emergence responses for COVID-19 from 2020 to 2021, Bayesian Structural Time Series model and interrupted time series analysis were applied to quantitatively assess the impact of NPIs in sequent phases with different intensities, and to estimate the reduction of influenza infections. From 2011 to 2021, a total of 197,528 confirmed cases of influenza were reported in Xi'an, and the incidence of influenza continuously increased from 2011 to 2019, especially, in 2019-2020, when the incidence was up to 975.90 per 100,000 persons; however, it showed a sharp reduction of 97.68% in 2020-2021, and of 87.22% in 2021, comparing with 2019-2020. The highest impact on reduction of influenza was observed in the phase of strict implementation of NPIs with an inclusion probability of 0.54. The weekly influenza incidence was reduced by 95.45%, and an approximate reduction of 210,100 (95% CI: 125,100-329,500) influenza infections was found during the post-COVID-19 period. The reduction exhibited significant variations in the geographical, population, and temporal distribution. Our findings demonstrated that NPIs against COVID-19 had a long-term impact on the reduction of influenza transmission.

The impact of anti-COVID-19 nonpharmaceutical interventions on hand, foot, and mouth disease-A spatiotemporal perspective in Xi'an, northwestern China.

Growing evidence has shown that anti-COVID-19 nonpharmaceutical interventions (NPIs) can support prevention and control of various infectious diseases, including intestinal diseases. However, most studies focused on the short-term mitigating impact and neglected the dynamic impact over time. This study is aimed to investigate the dynamic impact of anti-COVID-19 NPIs on hand, foot, and mouth disease (HFMD) over time in Xi'an City, northwestern China. Based on the surveillance data of HFMD, meteorological and web search data, Bayesian Structural Time Series model and interrupted time series analysis were performed to quantitatively measure the impact of NPIs in sequent phases with different intensities and to predict the counterfactual number of HFMD cases. From 2013 to 2021, a total number of 172,898 HFMD cases were reported in Xi'an. In 2020, there appeared a significant decrease in HFMD incidence (-94.52%, 95% CI: -97.54% to -81.95%) in the first half of the year and the peak period shifted from June to October by a small margin of 6.74% compared to the previous years of 2013 to 2019. In 2021, the seasonality of HFMD incidence gradually returned to the bimodal temporal variation pattern with a significant average decline of 61.09%. In particular, the impact of NPIs on HFMD was more evident among young children (0-3 years), and the HFMD incidence reported in industrial areas had an unexpected increase of 51.71% in 2020 autumn and winter. Results suggested that both direct and indirect NPIs should be implemented as effective public health measures to reduce infectious disease and improve surveillance strategies, and HFMD incidence in Xi'an experienced a significant rebound to the previous seasonality after a prominent decline influenced by the anti-COVID-19 NPIs.

CTCF Expression and Dynamic Motif Accessibility Modulates Epithelial-Mesenchymal Gene Expression.

Epithelial-mesenchymal transition (EMT) and its reversal, mesenchymal-epithelial transition (MET) drive tissue reorganization critical for early development. In carcinomas, processing through EMT, MET, or partial states promotes migration, invasion, dormancy, and metastatic colonization. As a reversible process, EMT is inherently regulated at epigenetic and epigenomic levels. To understand the epigenomic nature of reversible EMT and its partial states, we characterized chromatin accessibility dynamics, transcriptomic output, protein expression, and cellular phenotypes during stepwise reversible EMT. We find that the chromatin insulating protein machinery, including CTCF, is suppressed and re-expressed, coincident with broad alterations in chromatin accessibility, during EMT/MET, and is lower in triple-negative breast cancer cell lines with EMT features. Through an analysis of chromatin accessibility using ATAC-seq, we identify that early phases of EMT are characterized by enrichment for AP-1 family member binding motifs, but also by a diminished enrichment for CTCF binding motifs. Through a loss-of-function analysis, we demonstrate that the suppression of CTCF alters cellular plasticity, strengthening the epithelial phenotype via the upregulation of epithelial markers E-cadherin/CDH1 and downregulation of N-cadherin/CDH2. Conversely, the upregulation of CTCF leads to the upregulation of EMT gene expression and an increase in mesenchymal traits. These findings are indicative of a role of CTCF in regulating epithelial-mesenchymal plasticity and gene expression.

Spatiotemporal association of rapid urbanization and water-body distribution on hemorrhagic fever with renal syndrome: A case study in the city of Xi'an, China.

Hemorrhagic fever with renal syndrome (HFRS) is a zoonosis characterized by clinical features of high fever, hemorrhage, and renal damage. China has the largest number of HFRS cases worldwide, accounting for over 90% of the total reported cases. In this paper, we used surveyed HFRS data and satellite imagery to conduct geostatistical analysis for investigating the associations of rapid urbanization, water bodies, and other factors on the spatiotemporal dynamics of HFRS from year 2005 to 2018 in Xi'an City, Northwest China. The results revealed an evident epidemic aggregation in the incidence of HFRS within Xi'an City with a phenomenal fluctuation in periodic time series. Rapid urbanization was found to greatly affect the HFRS incidence in two different time phases. HFRS caused by urbanization influences farmers to a lesser extent than it does to non-farmers. The association of water bodies with the HFRS incidence rate was found to be higher within the radii of 696.15 m and 1575.39 m, which represented significant thresholds. The results also showed that geomatics approaches can be used for spatiotemporally investigating the HFRS dynamic characteristics and supporting effective allocations of resources to formulate strategies for preventing epidemics.

Spatiotemporal Trends in the Incidence of Gastrointestinal Neoplasms in Wuwei City of Northwestern China From 1995 to 2016: A Hospital-Based Retrospective Observational Study.

OBJECTIVE: To determine the characteristics and spatiotemporal distribution of major gastrointestinal (GI) neoplasms in inpatients from 1995 to 2016 in Wuwei city, northwestern China. METHOD: Data from all paper and electronic medical records entered between 1995 and 2016 at 12 major public hospitals in Wuwei city were retrospectively collected. Patients with GI neoplasms were identified and classified according to the International Classification of Diseases (ICD)-10. Trends in the incidence of major GI neoplasms were expressed as an annual percentage change (APC), and the Z test was used to assess the time fluctuation trends. Age-standardized incidence rates (ASIRs) were also calculated and the corresponding APC was estimated by the Joinpoint software for long-term trend analysis. Thematic maps of annual incidence at the township level were produced. RESULTS: Among the 19,137 new inpatients identified with GI neoplasms in Wuwei, gastric cancer was the leading cause of morbidity, followed by cancers of the esophagus, colorectum, gastric cardia, liver, and pancreas with ASIRs of 21.8, 11.0, 5.8, 5.7, 4.4, and 1.7 per 100,000 person-years, respectively. Overall, there was a steady increase in the ASIR for all GI neoplasms, and male cases were 2.1 times more frequent than female cases. The ASIR significantly increased by 12.2% per year from 1995 to 2009 for all GI neoplasms, and the increase rates ranged 9.4%-16.7% per year for the individual GI neoplasm. Despite an increase by 1.4% per year from 2009 to 2016, the ASIR decreased for esophageal and gastric cardia cancers by 4.6% and 17.3% per year, respectively. The annual incidence of all GI neoplasms showed significantly differential geographic distributions among different townships of the city during the study period.

Nanoliposomal Delivery of MicroRNA-203 Suppresses Migration of Triple-Negative Breast Cancer through Distinct Target Suppression.

Triple-negative breast cancers affect thousands of women in the United States and disproportionately drive mortality from breast cancer. MicroRNAs are small, non-coding RNAs that negatively regulate gene expression post-transcriptionally by inhibiting target mRNA translation or by promoting mRNA degradation. We have identified that miRNA-203, silenced by epithelial-mesenchymal transition (EMT), is a tumor suppressor and can promote differentiation of breast cancer stem cells. In this study, we tested the ability of liposomal delivery of miR-203 to reverse aspects of breast cancer pathogenesis using breast cancer and EMT cell lines. We show that translationally relevant methods for increasing miR-203 abundance within a target tissue affects cellular properties associated with cancer progression. While stable miR-203 expression suppresses LASP1 and survivin, nanoliposomal delivery suppresses BMI1, indicating that suppression of distinct mRNA target profiles can lead to loss of cancer cell migration.

A Cluster Transmission of Coronavirus Disease 2019 and the Prevention and Control Measures in the Early Stage of the Epidemic in Xi'an, China, 2020.

BACKGROUND At the beginning of the COVID-19 pandemic, a cluster outbreak caused by an imported case from Hubei Province was reported in Xi'an City, Shaanxi Province, China. Ten patients from 2 families and 1 hospital were involved in the transmission. MATERIAL AND METHODS We conducted an epidemiological investigation to identify the cluster transmission of COVID-19. The demographic, epidemiological, clinical, laboratory, and cluster characteristics were described and analyzed. RESULTS From January 27 to February 13, 2020, a total of 10 individuals were confirmed to be infected with SARS-CoV-2 by the nucleic acid testing of nasopharyngeal swabs from 2 families and 1 hospital. Among the confirmed cases, 7 had atypical clinical symptoms and 3 were asymptomatic. The median times from onset to diagnosis and to discharge were 3.5 days (range, 1-5 days) and 19.5 days (range, 16-38 days), respectively. There were 4 patients whose exposure dates were 1, 3, 3, and 2 days earlier than the onset dates of their previous-generation cases, respectively. Four prevention and control measures were effectively used to interrupt the disease transmission. CONCLUSIONS SARS-CoV-2 can be easily transmitted within families and in hospitals, and asymptomatic patients could act as a source of disease transmission. The results of this outbreak at the early epidemic stage support the recommendation that individuals with confirmed COVID-19 and all their close contacts should be subjected to medical quarantined observation and nucleic acid screening as early as possible, even if they do not have any symptoms. Meanwhile, people in high-risk areas should improve their protective measures.

Epithelial-mesenchymal transition sensitizes breast cancer cells to cell death via the fungus-derived sesterterpenoid ophiobolin A.

The epithelial-mesenchymal transition (EMT) imparts properties of cancer stem-like cells, including resistance to frequently used chemotherapies, necessitating the identification of molecules that induce cell death specifically in stem-like cells with EMT properties. Herein, we demonstrate that breast cancer cells enriched for EMT features are more sensitive to cytotoxicity induced by ophiobolin A (OpA), a sesterterpenoid natural product. Using a model of experimentally induced EMT in human mammary epithelial (HMLE) cells, we show that EMT is both necessary and sufficient for OpA sensitivity. Moreover prolonged, sub-cytotoxic exposure to OpA is sufficient to suppress EMT-imparted CSC features including sphere formation and resistance to doxorubicin. In vivo growth of CSC-rich mammary cell tumors, is suppressed by OpA treatment. These data identify a driver of EMT-driven cytotoxicity with significant potential for use either in combination with standard chemotherapy or for tumors enriched for EMT features.

Epidemiological Characteristics, Seasonal Dynamic Patterns, and Associations with Meteorological Factors of Rubella in Shaanxi Province, China, 2005-2018.

Rubella occurs worldwide, causing approximately 100,000 cases annually of congenital rubella syndrome, leading to severe birth defects. Better targeting of public health interventions is needed to achieve rubella elimination goals. To that end, we measured the epidemiological characteristics and seasonal dynamic patterns of rubella and determined its association with meteorological factors in Shaanxi Province, China. Data on rubella cases in Shaanxi Province from 2005 to 2018 were obtained from the Chinese National Notifiable Disease Reporting System. The Morlet wavelet analysis was used to estimate temporal periodicity of rubella incidence. Mixed generalized additive models were used to measure associations between meteorological variables (temperature and relative humidity) and rubella incidence. A total of 17,185 rubella cases were reported in Shaanxi during the study period, for an annual incidence of 3.27 cases per 100,000 population. Interannual oscillations in rubella incidence of 0.8-1.4 years, 3.8-4.8 years, and 0.5 years were detected. Both temperature and relative humidity exhibited nonlinear associations with the incidence of rubella. The accumulative relative risk of transmission for the overall pooled estimates was maximized at a temperature of 0.23°C and relative humidity of 41.6%. This study found that seasonality and meteorological factors have impact on the transmission of rubella; public health interventions to eliminate rubella must consider periodic and seasonal fluctuations as well as meteorological factors.

Spatiotemporal expansion of human brucellosis in Shaanxi Province, Northwestern China and model for risk prediction.

BACKGROUND: Human brucellosis imposes a heavy burden on the health and economy of endemic regions. Since 2011, China has reported at least 35,000 human brucellosis cases annually, with more than 90% of these cases reported in the northern. Given the alarmingly high incidence and variation in the geographical distribution of human brucellosis cases, there is an urgent need to decipher the causes of such variation in geographical distribution. METHOD: We conducted a retrospective epidemiological study in Shaanxi Province from January 1, 2005 to December 31, 2018 to investigate the association between meteorological factors and transmission of human brucellosis according to differences in geographical distribution and seasonal fluctuation in northwestern China for the first time. RESULTS: Human brucellosis cases were mainly distributed in the Shaanbei upland plateau before 2008 and then slowly extended towards the southern region with significant seasonal fluctuation. The results of quasi-Poisson generalized additive mixed model (GAMM) indicated that air temperature, sunshine duration, rainfall, relative humidity, and evaporation with maximum lag time within 7 months played crucial roles in the transmission of human brucellosis with seasonal fluctuation. Compared with the Shaanbei upland plateau, Guanzhong basin had more obvious fluctuations in the occurrence of human brucellosis due to changes in meteorological factors. Additionally, the established GAMM model showed high accuracy in predicting the occurrence of human brucellosis based on the meteorological factors. CONCLUSION: These findings may be used to predict the seasonal fluctuations of human brucellosis and to develop reliable and cost-effective prevention strategies in Shaanxi Province and other areas with similar environmental conditions.

Epidemic Changes and Spatio-Temporal Analysis of Japanese Encephalitis in Shaanxi Province, China, 2005-2018.

Japanese encephalitis (JE) is a mosquito-borne viral disease, which is the most serious viral encephalitis in China and other countries of the Asia-Pacific region. Since 2005, the epidemic patterns of JE have changed dramatically in China because of the vaccination of children younger than 15 years old, and JE is expanding geographically along with global warming. This retrospective epidemiological study analyzed dynamic environmental factors and the spatio-temporal distribution of human cases of JE in Shaanxi Province-one of the most severely affected areas of China-from 2005 to 2018. The results demonstrated that the high-risk population changed rapidly as the annual rate of JE cases increased by more than 40% in the age group >60 years during the study period, and endemic areas expanded northward in Shaanxi. Hotspot analysis detected four hotspots accounting for 52.38% the total cases, and the panel negative binomial regression model revealed that the spatio-temporal distribution of JE was significantly affected by temperature, relative humidity, wind velocity, El Niño-Southern Oscillation, coniferous forest coverage, and urban areas. These findings can provide useful information for improving current strategies and measures to reduce disease incidence.

Population Movement, City Closure in Wuhan, and Geographical Expansion of the COVID-19 Infection in China in January 2020.

BACKGROUND: The unprecedented outbreak of corona virus disease 2019 (COVID-19) infection in Wuhan City has caused global concern; the outflow of the population from Wuhan was believed to be a main reason for the rapid and large-scale spread of the disease, so the government implemented a city-closure measure to prevent its transmission considering the large amount of travel before the Chinese New Year. METHODS: Based on the daily reported new cases and the population-movement data between 1 and 31 January, we examined the effects of population outflow from Wuhan on the geographical expansion of the infection in other provinces and cities of China, as well as the impacts of the city closure in Wuhan using different closing-date scenarios. RESULTS: We observed a significantly positive association between population movement and the number of the COVID-19 cases. The spatial distribution of cases per unit of outflow population indicated that the infection in some areas with a large outflow of population might have been underestimated, such as Henan and Hunan provinces. Further analysis revealed that if the city-closure policy had been implemented 2 days earlier, 1420 (95% confidence interval, 1059-1833) cases could have been prevented, and if 2 days later, 1462 (1090-1886) more cases would have been possible. CONCLUSIONS: Our findings suggest that population movement might be one important trigger for the transmission of COVID-19 infection in China, and the policy of city closure is effective in controlling the epidemic.

Seasonal Distribution and Meteorological Factors Associated with Hand, Foot, and Mouth Disease among Children in Xi'an, Northwestern China.

Hand, foot, and mouth disease (HFMD) is a common infectious disease in the Asia-Pacific region that primarily affects children younger than 5 years. Previous studies have confirmed that the seasonal transmission of this disease is strongly related to meteorological factors, but the results are not consistent. In addition, the associations between weather conditions and HFMD in northwestern China have not been investigated. Therefore, we aimed to examine this issue in Xi'an, the largest city of northwestern China that has been suffering from serious HFMD epidemics. In the current study, data for HFMD and six meteorological factors were collected from 2009 to 2018. Using cross-correlation analysis, the Granger causality test, and the distributed lag nonlinear model, we estimated the quantitative relationships and exposure-lag-response effects between weekly meteorological factors and HFMD incidence among children. We found that the seasonal distribution of HFMD in Xi'an has two peaks each year and is significantly impacted by the weekly temperature, precipitation, and evaporation over an 8-week period. Higher values of temperature and evaporation had positive associations with disease transmission, whereas the association between precipitation and HFMD showed an inverted-U shape. The maximum relative risks (RRs) of HFMD for the weekly mean temperature (approximately 31.1°C), weekly cumulative evaporation (57.9 mm), and weekly cumulative precipitation (30.0 mm) were 1.56 (95% CI: 1.35-1.81), 1.40 (95% CI: 1.05-1.88), and 1.16 (95% CI: 1.11-1.70), respectively. The identified risk determinants and lag effects could provide important information for early interventions to reduce the local disease burden.