Long-term effects of climate factors on dengue fever over a 40-year period.

BACKGROUND: Dengue fever stands as one of the most extensively disseminated mosquito-borne infectious diseases worldwide. While numerous studies have investigated its influencing factors, a gap remains in long-term analysis, impeding the identification of temporal patterns, periodicity in transmission, and the development of effective prevention and control strategies. Thus, we aim to analyze the periodicity of dengue fever incidence and explore the association between various climate factors and the disease over an extended time series. METHODS: By utilizing monthly dengue fever cases and climate data spanning four decades (1978-2018) in Guangdong province, China, we employed wavelet analysis to detect dengue fever periodicity and analyze the time-lag relationship with climate factors. Additionally, Geodetector q statistic was employed to quantify the explanatory power of each climate factor and assess interaction effects. RESULTS: Our findings revealed a prolonged transmission period of dengue fever over the 40-year period, transitioning from August to November in the 1970s to nearly year-round in the 2010s. Moreover, we observed lags of 1.5, 3.5, and 3 months between dengue fever and temperature, relative humidity, and precipitation, respectively. The explanatory power of precipitation, temperature, relative humidity, and the Oceanic Niño Index (ONI) on dengue fever was determined to be 18.19%, 12.04%, 11.37%, and 5.17%, respectively. Dengue fever exhibited susceptibility to various climate factors, with notable nonlinear enhancement arising from the interaction of any two variables. Notably, the interaction between precipitation and humidity yielded the most significant effect, accounting for an explanatory power of 75.32%. CONCLUSIONS: Consequently, future prevention and control strategies for dengue fever should take into account these climate changes and formulate corresponding measures accordingly. In regions experiencing the onset of high temperatures, humidity, and precipitation, it is imperative to initiate mosquito prevention and control measures within a specific window period of 1.5 months.

Geographical evolutionary pathway of global tuberculosis incidence trends.

BACKGROUNDS: Tuberculosis (TB) remains a serious public health and human development problem, especially in developing countries. Despite the effectiveness of directly observed therapy, short course programs in reducing transmission and progression of TB, poverty reduction and socioeconomic development remain crucial factors in decreasing TB incidence. However, the geographical pathway on the planet is not yet clear. OBJECTIVES: This study was to reconstruct the geographical evolutionary process of TB in 173 countries and territories from 2010 to 2019 to analyze the socioeconomic determinants that impact the global TB epidemic. In addition, the TB incidence in 2030 was predicted. METHODS: This study analyses TB incidence data from 173 countries and territories between 2010 and 2019. The Geotree model would be used to reconstruct the geographical evolutionary process of TB, which provides a simplified schema for geo-visualizing the trajectories of TB incidence and their socioeconomic drivers. Additionally, to estimate the future TB incidence in 2030, a multilevel model was utilized in conjunction with the hierarchical nature of the Geotree based on a stratified heterogeneity analysis. RESULTS: Global TB incidence was found to be associated with the country type and development stages. Between 2010 and 2019, the average TB incidence rate in 173 countries and territories was -27.48%, with marked spatially stratified heterogeneity by country type and development stage. Low-income and lower-middle-income countries were most vulnerable to TB. Upper-middle-income countries experienced a faster decline in TB incidence than high-income countries, and TB incidence generally decreased as the development stage increased, except for the lower-middle development stage in 2019.The highest average rate of decline in TB incidence was observed in the upper-middle development stage of high-income countries, with a reduction of 45.24%. Meanwhile, 37 high-income countries in the high development stage demonstrated an average rate of change of -13.93%. Socioeconomic determinants, including gross domestic product per capita, urbanization rate, and sociodemographic index, were found to inhibit TB incidence. Based on current trends, the predicted average global TB incidence in 2030 is 91.581 per 100,000 population. CONCLUSIONS: The trajectories of the global TB incidence have been reconstructed to formulate targeted public health responses. To eliminate TB, countries at similar development stage can draw on the experiences of countries at higher development stages that are tailored to their unique characteristics. By learning from successful TB control strategies, countries can take strategic steps toward eradicating TB and improving public health outcomes.

Spatial analysis of overweight prevalence in China: exploring the association with air pollution.

BACKGROUND: Overweight is a known risk factor for various chronic diseases and poses a significant threat to middle-aged and elderly adults. Previous studies have reported a strong association between overweight and air pollution. However, the spatial relationship between the two remains unclear due to the confounding effects of spatial heterogeneity. METHODS: We gathered height and weight data from the 2015 China Health and Retirement Long-term Survey (CHARLS), comprising 16,171 middle-aged and elderly individuals. We also collected regional air pollution data. We then analyzed the spatial pattern of overweight prevalence using Moran's I and Getis-Ord Gi* statistics. To quantify the explanatory power of distinct air pollutants for spatial differences in overweight prevalence across Southern and Northern China, as well as across different age groups, we utilized Geodetector's q-statistic. RESULTS: The average prevalence of overweight among middle-aged and elderly individuals in each city was 67.27% and 57.39%, respectively. In general, the q-statistic in southern China was higher than that in northern China. In the north, the prevalence was significantly higher at 54.86% compared to the prevalence of 38.75% in the south. SO2 exhibited a relatively higher q-statistic in middle-aged individuals in both the north and south, while for the elderly in the south, NO2 was the most crucial factor (q = 0.24, p < 0.01). Moreover, fine particulate matter (PM2.5 and PM10) also demonstrated an important effect on overweight. Furthermore, we found that the pairwise interaction between various risk factors improved the explanatory power of the prevalence of overweight, with different effects for different age groups and regions. In northern China, the strongest interaction was found between NO2 and SO2 (q = 0.55) for middle-aged individuals and PM2.5 and SO2 (q = 0.27) for the elderly. Conversely, in southern China, middle-aged individuals demonstrated the strongest interaction between SO2 and PM10 (q = 0.60), while the elderly showed the highest interaction between NO2 and O3 (q = 0.42). CONCLUSION: Significant spatial heterogeneity was observed in the effects of air pollution on overweight. Specifically, air pollution in southern China was found to have a greater impact on overweight than that in northern China. And, the impact of air pollution on middle-aged individuals was more pronounced than on the elderly, with distinct pollutants demonstrating significant variation in their impact. Moreover, we found that SO2 had a greater impact on overweight prevalence among middle-aged individuals, while NO2 had a greater impact on the elderly. Additionally, we identified significant statistically interactions between O3 and other pollutants.

Spatiotemporal associations between hand, foot and mouth disease and meteorological factors over multiple climate zones.

Prior studies of hand, foot, and mouth disease (HFMD) have often observed inconsistent results regarding meteorological factors. We propose the hypothesis that these meteorological associations vary in regions because of the heterogeneity of their geographical characteristics. We have tested this hypothesis by applying a geographical detector and Bayesian space-time hierarchy model to measure stratified spatiotemporal heterogeneity and local associations between meteorological factors and HFMD risk in five climate zones in China from January 2016 to December 2017. We found a significant spatial stratified heterogeneity in HFMD risk and climate zone explained 15% of the spatial stratified heterogeneity. Meanwhile, there was a significant temporal stratified heterogeneity of 14% as determined by meteorological factors. Average temperatures and relative humidity had a significant positive effect on HFMD in all climate zones, they were the most obvious in the southern temperate zone. In northern temperate, southern temperate, northern subtropics, middle subtropics and southern subtropics climate zone, a 1 °C rise in temperature was related to an increase of 3.99%, 13.76%, 4.38%, 3.99%, and 7.74% in HFMD, and a 1% increment in relative humidity was associated with a 1.51%, 5.40%, 2.21%, 3.44%, and 4.78% increase, respectively. These findings provide strong support for our hypotheses that HFMD incidence has a significant spatiotemporal stratified heterogeneity and different climate zones have distinct influences on the disease. These findings provide strong support for our hypotheses: HFMD incidence had significant spatiotemporal stratified heterogeneity and different climate zones had distinct influences on it. The study suggested that HFMD prevention and policy should be made according to meteorological variation in each climate zone.

Risk of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Transmission Among Air Passengers in China.

BACKGROUND: Modern transportation plays a key role in the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and new variants. However, little is known about the exact transmission risk of the virus on airplanes. METHODS: Using the itinerary and epidemiological data of coronavirus disease 2019 (COVID-19) cases and close contacts on domestic airplanes departing from Wuhan city in China before the lockdown on 23 January 2020, we estimated the upper and lower bounds of overall transmission risk of COVID-19 among travelers. RESULTS: In total, 175 index cases were identified among 5797 passengers on 177 airplanes. The upper and lower attack rates (ARs) of a seat were 0.60% (34/5622, 95% confidence interval [CI] .43-.84%) and 0.33% (18/5400, 95% CI .21-.53%), respectively. In the upper- and lower-bound risk estimates, each index case infected 0.19 (SD 0.45) and 0.10 (SD 0.32) cases, respectively. The seats immediately adjacent to the index cases had an AR of 9.2% (95% CI 5.7-14.4%), with a relative risk 27.8 (95% CI 14.4-53.7) compared to other seats in the upper limit estimation. The middle seat had the highest AR (0.7%, 95% CI .4%-1.2%). The upper-bound AR increased from 0.7% (95% CI 0.5%-1.0%) to 1.2% (95% CI .4-3.3%) when the co-travel time increased from 2.0 hours to 3.3 hours. CONCLUSIONS: The ARs among travelers varied by seat distance from the index case and joint travel time, but the variation was not significant between the types of aircraft. The overall risk of SARS-CoV-2 transmission during domestic travel on planes was relatively low. These findings can improve our understanding of COVID-19 spread during travel and inform response efforts in the pandemic.

Spatiotemporal trends and ecological determinants of cardiovascular mortality among 2844 counties in mainland China, 2006-2020: a Bayesian modeling study of national mortality registries.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death in China. No previous study has reported CVD mortality at county-level, and little was known about the nonmedical ecological factors of CVD mortality at such small scale in mainland China. Understanding the spatiotemporal variations of CVD mortality and examining its nonmedical ecological factors would be of great importance to tailor local public health policies. METHODS: By using national mortality registration data in China, this study used hierarchical spatiotemporal Bayesian model to demonstrate spatiotemporal distribution of CVD mortality in 2844 counties during 2006 to 2020 and investigate how nonmedical ecological determinants have affected CVD mortality inequities from the spatial perspectives. RESULTS: During 2006-2020, the age-standardized mortality rate (ASMR) of CVD decreased from 284.77 per 100,000 in 2006 to 241.34 per 100,000 in 2020. Among 2844 counties, 1144 (40.22%) were hot spots counties with a higher CVD mortality risk compared to the national average and located mostly in northeast, north central, and westernmost regions; on the contrary, 1551 (54.53%) were cold spots counties and located mostly in south and southeast coastal counties. CVD mortality risk decreased from 2006 to 2020 was larger in counties where CVD mortality rate had been higher in 2006 in most of the counties, vice versa. Nationwide, nighttime light intensity (NTL) was the major influencing factor of CVD mortality, a higher NTL appeared to be negatively associated with a lower CVD mortality, with one unit increase in NTL, and the CVD mortality risk will decrease 11% (relative risk of NTL was estimated as 0.89 with 95% confidence interval of 0.83-0.94). CONCLUSIONS: Substantial between-county discrepancies of CVD mortality distribution were observed during past 15 years in mainland China. Nonmedical ecological determinants were estimated to significantly explain the overall and local spatiotemporal patterns of this CVD mortality risk. Targeted considerations are needed to integrate primary care with clinical care through intensifying further strategies to narrow unequally distribution of CVD mortality at local scale. The approach to county-level analysis with small area models has the potential to provide novel insights into Chinese disease-specific mortality burden.

Development, validation, and implementation of a robust and quality control-friendly focused peptide mapping method for monitoring oxidation of co-formulated monoclonal antibodies.

Monoclonal antibody (mAb) coformulation containing two therapeutic proteins provides benefits of improved therapeutic efficacy and better patient compliance. Monitoring of the individual mAb stability in the coformulation is critical to ensure its quality and safety. Among post-translational modifications (PTMs), oxidation is often considered as one of the critical quality attributes (CQAs) as it potentially affects the structure and potency. Although hydrophobic interaction chromatography (HIC) and reversed phase liquid chromatography (RPLC) have been used to monitor overall protein oxidation, mass spectrometry of peptide digests resolved by LC methods can afford superior selectivity and sensitivity for specific PTMs. With the advent of the Quadrupole Dalton (QDa) mass spectrometer as an affordable add-on detector, implementation of targeted oxidation assays in development and quality control (QC) laboratories is now feasible. In this study, as the first effort to implement MS-based methods for antibody coformulation in QC laboratories, we developed and validated a high-throughput and robust focused peptide mapping method using QDa for simultaneous site-specific monitoring of oxidation of methionine and tryptophan residues in heavy-chain (HC) complementary determining regions (CDRs) of two co-formulated mAbs. The method was validated in terms of accuracy, precision, linearity, range, quantitation limit (QL), specificity, and solution stability per recommendations in ICH Q2. The method robustness was systematically assessed involving multiple sample preparation and instrument method parameters. The method met the validation criteria in GMP laboratories with excellent robustness and was implemented in both GMP and development environments.

Risk of Coronavirus Disease 2019 Transmission in Train Passengers: an Epidemiological and Modeling Study.

BACKGROUND: Train travel is a common mode of public transport across the globe; however, the risk of coronavirus disease 2019 (COVID-19) transmission among individual train passengers remains unclear. METHODS: We quantified the transmission risk of COVID-19 on high-speed train passengers using data from 2334 index patients and 72 093 close contacts who had co-travel times of 0-8 hours from 19 December 2019 through 6 March 2020 in China. We analyzed the spatial and temporal distribution of COVID-19 transmission among train passengers to elucidate the associations between infection, spatial distance, and co-travel time. RESULTS: The attack rate in train passengers on seats within a distance of 3 rows and 5 columns of the index patient varied from 0 to 10.3% (95% confidence interval [CI], 5.3%-19.0%), with a mean of 0.32% (95% CI, .29%-.37%). Passengers in seats on the same row (including the adjacent passengers to the index patient) as the index patient had an average attack rate of 1.5% (95% CI, 1.3%-1.8%), higher than that in other rows (0.14% [95% CI, .11%-.17%]), with a relative risk (RR) of 11.2 (95% CI, 8.6-14.6). Travelers adjacent to the index patient had the highest attack rate (3.5% [95% CI, 2.9%-4.3%]) of COVID-19 infection (RR, 18.0 [95% CI, 13.9-23.4]) among all seats. The attack rate decreased with increasing distance, but increased with increasing co-travel time. The attack rate increased on average by 0.15% (P = .005) per hour of co-travel; for passengers in adjacent seats, this increase was 1.3% (P = .008), the highest among all seats considered. CONCLUSIONS: COVID-19 has a high transmission risk among train passengers, but this risk shows significant differences with co-travel time and seat location. During disease outbreaks, when traveling on public transportation in confined spaces such as trains, measures should be taken to reduce the risk of transmission, including increasing seat distance, reducing passenger density, and use of personal hygiene protection.

Anonymous Linkage Between College Students and Human Immunodeficiency Virus (HIV) Facilities: Systematic Evaluation of Urine Self-Collection for HIV Testing Initiative in China.

BACKGROUND: Identifying young individuals living with human immunodeficiency virus (HIV) who are unaware of their status is a major challenge for HIV control in China. To address this, an innovative, anonymous vending machine-based urine self-collection for HIV testing (USCT) program was implemented in 2016 in colleges across China. METHODS: From June 2016 to December 2019, 146 vending machines stocked with urine self-collection kits were distributed on 73 college campuses across 11 provinces of China. Urine samples were collected, delivered, and tested in an anonymous manner. We analyzed the returned rate, reactive rate (likelihood of HIV screening positive), testing effectiveness (the annual number of college students living with HIV screened by USCT or other testing methods), and the spatiotemporal relationship between USCT usage and student activity per college generated from the usage of a social networking application. RESULTS: Among the 5178 kits sold, 3109 (60%) samples were returned; of these, 2933 (94%) were eligible for testing. The HIV reactive rate was 2.3% (66 of 2933). The average effectiveness ratio among the 34 participating Beijing colleges was 0.39 (12:31) between USCT and conventional testing methods. A strong spatiotemporal correlation between USCT numbers and online student activity was observed during school semesters in Beijing. CONCLUSIONS: USCT is a powerful complement to current interventions that target at-risk students and promote HIV testing. The social networking-based evaluation framework can be a guide in prioritizing at-risk target populations.

Spatiotemporal heterogeneity and its determinants of COVID-19 transmission in typical labor export provinces of China.

BACKGROUND: Previous studies have indicated that the risk of infectious disease spread is greatest in locations where a population has massive and convenient access to the epicenter of an outbreak. However, the spatiotemporal variations and risk determinants of COVID-19 in typical labor export regions of China remain unclear. Understanding the geographical distribution of the disease and the socio-economic factors affecting its transmission is critical for disease prevention and control. METHODS: A total of 2152 COVID-19 cases were reported from January 21 to February 24, 2020 across the 34 cities in Henan and Anhui. A Bayesian spatiotemporal hierarchy model was used to detect the spatiotemporal variations of the risk posed by COVID-19, and the GeoDetector q statistic was used to evaluate the determinant power of the potential influence factors. RESULTS: The risk posed by COVID-19 showed geographical spatiotemporal heterogeneity. Temporally, there was an outbreak period and control period. Spatially, there were high-risk regions and low-risk regions. The high-risk regions were mainly in the southwest areas adjacent to Hubei and cities that served as economic and traffic hubs, while the low-risk regions were mainly in western Henan and eastern Anhui, far away from the epicenter. The accessibility, local economic conditions, and medical infrastructure of Wuhan in Hubei province all played an important role in the spatiotemporal heterogeneity of COVID-19 transmission. The results indicated that the q statistics of the per capita GDP and the proportion of primary industry GDP were 0.47 and 0.47, respectively. The q statistic of the population flow from Wuhan was 0.33. In particular, the results showed that the q statistics for the interaction effects between population density and urbanization, population flow from Wuhan, per capita GDP, and the number of doctors were all greater than 0.8. CONCLUSIONS: COVID-19 showed significant spatiotemporal heterogeneity in the labor export regions of China. The high-risk regions were mainly located in areas adjacent to the epicenter as well as in big cities that served as traffic hubs. Population access to the epicenter, as well as local economic and medical conditions, played an important role in the interactive effects of the disease transmission.

Spatial pattern of the population casualty rate caused by super typhoon Lekima and quantification of the interactive effects of potential impact factors.

BACKGROUND: Typhoons greatly threaten human life and property, especially in China. Therefore, it is important to make effective policy decisions to minimize losses associated with typhoons. METHODS: In this study, the GeoDetector method was used to quantify the determinant powers of natural and socioeconomic factors, and their interactions, on the population casualty rate of super typhoon Lekima. The local indicator of spatial association (LISA) method was followed to explore the spatial pattern of the population casualty rate under the influence of the identified dominant factors. RESULTS: Both natural and socioeconomic factors were found to have significantly impacted the population casualty rate due to super typhoon Lekima. Among the selected factors, maximum precipitation was dominant factor (q = 0.56), followed by maximum wind speed (q = 0.45). In addition, number of health technicians (q = 0.35) and number of health beds (q = 0.27) have a strong influence on the population casualty rate. Among the interactive effects of 12 influencing factors, the combined effects of maximum precipitation and ratio of brick-wood houses, the maximum precipitation and ratio of steel-concrete houses, maximum precipitation and number of health technicians were highest (q = 0.72). Furthermore, high-risk areas with very high casualty rates were concentrated in the southeastern part of Zhejiang and northern Shandong Provinces, while lower-risk areas were mainly distributed in northern Liaoning and eastern Jiangsu provinces. CONCLUSIONS: These results contribute to the development of more specific policies aimed at safety and successful property protection according to the regional differences during typhoons.

Spatio-temporal variation in tuberculosis incidence and risk factors for the disease in a region of unbalanced socio-economic development.

BACKGROUND: Previous research pointed to a close relationship between the incidence of tuberculosis (TB) in aging populations and socio-economic conditions, however there has been lack of studies focused on a region of unbalanced socio-economic development. The aim of this paper is to explore the spatio-temporal variation in TB incidence and examine risk determinants of the disease among aging populations in a typical region. METHODS: Data on TB-registered cases between 2009 and 2014, in addition to social-economic factors, were collected for each district/county in Beijing, Tianjin and Hebei, a region characterized by an aging population and disparities in social-economic development. A Bayesian space-time hierarchy model (BSTHM) was used to reveal spatio-temporal variation in the incidence of TB among the elderly in this region between 2009 to 2014. GeoDetector was applied to measure the determinant power (q statistic) of risk factors for TB among the elderly. RESULTS: The incidence of TB among the elderly exhibited geographical spatial heterogeneity, with a higher incidence in underdeveloped rural areas compared with that in urban areas. Hotspots of TB incidence risk among the elderly were mostly located in north-eastern and southern areas in the study region, far from metropolitan areas. Areas with low risk were distributed mainly in the Beijing-Tianjin metropolitan areas. Social-economic factors had a non-linear influence on elderly TB incidence, with the dominant factors among rural populations being income (q = 0.20) and medical conditions (q = 0.17). These factors had a non-linear interactive effect on the incidence of TB among the elderly, with medical conditions and the level of economic development having the strongest effect (q = 0.54). CONCLUSIONS: The findings explain spatio-temporal variation in TB incidence and risk determinants of elderly TB in the presence of disparities in social-economic development. High-risk zones were located mainly in rural areas, far from metropolitan centres. Medical conditions and the economic development level were significantly associated with elderly TB incidence, and these factors had a non-linear interactive effect on elderly TB incidence. The findings can help to optimize the allocation of health resources and to control TB transmission in the aging population in this region.

Spatial heterogeneity of bacillary dysentery and the impact of temperature in the Beijing-Tianjin-Hebei region of China.

Previous studies indicate that the incidence of bacillary dysentery is closely related to meteorological factors. However, the impact of temperature and the spatial heterogeneity of the disease in regions of unbalanced socioeconomic development remains unclear. Therefore, this research collected data for 29,639 daily bacillary dysentery cases in children under 5 years of age, as well as the meteorological variables from China's Beijing-Tianjin-Hebei region, to analyze the spatial pattern of bacillary dysentery and reveal its nonlinear association with temperature. The SatScan method was employed first, to detect the spatial heterogeneity of the disease risk, and then the distributed lag nonlinear model (DLNM) was used to analyze the relationships between the daily minimum, mean, and maximum temperatures and bacillary dysentery in the stratified heterogeneous regions. The results indicated that bacillary dysentery incidence presented statistically significant spatial heterogeneity. The area of highest risk was found to be Beijing and its neighboring regions, which have high population densities. There was also a positive association between bacillary dysentery and temperature. Hotter temperatures were accompanied by higher relative risks. In the most likely spatial cluster region, the excess risk (ER) values for a 1°C rise in minimum, mean, and maximum temperatures above the median were 4.65%, 11.30%, and 19.21%, respectively. The effect of temperature on bacillary dysentery peaked at a lag of 3 to 4 days. The findings of this study will aid risk assessments and early warning systems for bacillary dysentery.

Integration of a Kalman filter in the geographically weighted regression for modeling the transmission of hand, foot and mouth disease.

BACKGROUND: Hand, foot and mouth disease (HFMD) is a common infectious disease whose mechanism of transmission continues to remain a puzzle for researchers. The measurement and prediction of the HFMD incidence can be combined to improve the estimation accuracy, and provide a novel perspective to explore the spatiotemporal patterns and determinant factors of an HFMD epidemic. METHODS: In this study, we collected weekly HFMD incidence reports for a total of 138 districts in Shandong province, China, from May 2008 to March 2009. A Kalman filter was integrated with geographically weighted regression (GWR) to estimate the HFMD incidence. Spatiotemporal variation characteristics were explored and potential risk regions were identified, along with quantitatively evaluating the influence of meteorological and socioeconomic factors on the HFMD incidence. RESULTS: The results showed that the average error covariance of the estimated HFMD incidence by district was reduced from 0.3841 to 0.1846 compared to the measured incidence, indicating an overall improvement of over 50% in error reduction. Furthermore, three specific categories of potential risk regions of HFMD epidemics in Shandong were identified by the filter processing, with manifest filtering oscillations in the initial, local and long-term periods, respectively. Amongst meteorological and socioeconomic factors, the temperature and number of hospital beds per capita, respectively, were recognized as the dominant determinants that influence HFMD incidence variation. CONCLUSIONS: The estimation accuracy of the HFMD incidence can be significantly improved by integrating a Kalman filter with GWR and the integration is effective for exploring spatiotemporal patterns and determinants of an HFMD epidemic. Our findings could help establish more accurate HFMD prevention and control strategies in Shandong. The present study demonstrates a novel approach to exploring spatiotemporal patterns and determinant factors of HFMD epidemics, and it can be easily extended to other regions and other infectious diseases similar to HFMD.

Elucidation of roles for vitamin B12 in regulation of folate, ubiquinone, and methionine metabolism.

Only a small fraction of vitamin B12-requiring organisms are able to synthesize B12 de novo, making it a common commodity in microbial communities. Initially recognized as an enzyme cofactor of a few enzymes, recent studies have revealed additional B12-binding enzymes and regulatory roles for B12 Here we report the development and use of a B12-based chemical probe to identify B12-binding proteins in a nonphototrophic B12-producing bacterium. Two unexpected discoveries resulted from this study. First, we identified a light-sensing B12-binding transcriptional regulator and demonstrated that it controls folate and ubiquinone biosynthesis. Second, our probe captured proteins involved in folate, methionine, and ubiquinone metabolism, suggesting that it may play a role as an allosteric effector of these processes. These metabolic processes produce precursors for synthesis of DNA, RNA, and protein. Thereby, B12 likely modulates growth, and by limiting its availability to auxotrophs, B12-producing organisms may facilitate coordination of community metabolism.

Sensitive detection of topiramate degradation products by high-performance liquid chromatography/electrospray ionization mass spectrometry using ion-pairing reagents and polarity switching.

RATIONALE: The chromatographic analysis of topiramate and its degradation products is challenging due to the absence of chromophoric moieties in their structures, the wide polarity range of the compounds and their ionization differences. This work proposes two new mass spectrometry approaches for evaluating these analytes. METHODS: Based on the calculated experimental limit of detection (LOD), a highly sensitive high-performance liquid chromatography (HPLC) paired-ion electrospray ionization mass spectrometry (PIESI-MS) method was developed for the determination of topiramate inorganic degradation products. The influence of different solvent systems on the LODs for topiramate and its main degradation products was determined in both positive/negative ionization modes. In addition, a HPLC method to analyze both organic and inorganic degradation products was proposed by mass spectrometry with positive/negative ion switching electrospray ionization. RESULTS: A sensitive HPLC/PIESI-MS method was achieved for the efficient separation of topiramate inorganic degradation products. Both sulfate and sulfamate were detected in the positive selected ion monitoring (SIM) mode with an increased sensitivity compared with the negative SIM mode. The HPLC/ESI-MS analysis with positive/negative ion switching allowed the simultaneous separation and detection of the major degradation products of topiramate in a 10-min run using a single column and a single detector. CONCLUSIONS: Two new alternative MS approaches for analyzing the main degradation products of topiramate were developed. The proposed methods are considered advantageous over the existing methods and can be applied to quality control studies of topiramate.

Pyrimidine Nucleosides from Streptomyces sp. SSA28.

Eleven new pyrimidine nucleosides (1-11) and 12 known analogues (12-23) were isolated from the marine-derived Streptomyces sp. SSA28. All of the new structures were elucidated by extensive NMR spectroscopic analysis and HRESIMS data. The absolute configurations of compound 1 were determined by X-ray diffraction. The configurations of 2-16 were investigated by ECD calculations. Compounds 11-16 showed cytotoxicity against HCT-116 human colon cancer cell lines with IC50 values from 0.39 ± 0.03 to 6.63 ± 0.47 µM.

Spatial-temporal heterogeneity of hand, foot and mouth disease and impact of meteorological factors in arid/ semi-arid regions: a case study in Ningxia, China.

BACKGROUND: The incidence of hand, foot and mouth disease (HFMD) varies over space and time and this variability is related to climate and social-economic factors. Majority of studies on HFMD were carried out in humid regions while few have focused on the disease in arid/semi-arid regions, more research in such climates would potentially make the mechanism of HFMD transmission clearer under different climate conditions. METHODS: In this paper, we explore spatial-temporal distribution of HFMD in Ningxia province, which has an arid/semi-arid climate in northwest China. We first employed a Bayesian space-time hierarchy model (BSTHM) to assess the spatial-temporal heterogeneity of the HFMD cases and its relationship with meteorological factors in Ningxia from 2009 to 2013, then used a novel spatial statistical software package GeoDetector to test the spatial-temporal heterogeneity of HFMD risk. RESULTS: The results showed that the spatial relative risks in northern part of Ningxia were higher than those in the south. The highest temporal risk of HFMD incidence was in fall season, with a secondary peak in spring. Meteorological factors, such as average temperature, relative humidity, and wind speed played significant roles in the spatial-temporal distribution of HFMD risk. CONCLUSIONS: The study provide valuable information on HFMD distribution in arid/semi-arid areas in northwest China and facilitate understanding of the concentration of HFMD.

Space-time heterogeneity of hand, foot and mouth disease in children and its potential driving factors in Henan, China.

BACKGROUND: Hand, foot and mouth disease (HFMD) has become a substantial threat recently. However few studies have quantified spatiotemporal heterogeneity of HFMD and detected spatiotemporal interactive effect of potential driving factors on this disease. METHODS: Using GeoDetector and Bayesian space-time hierarchy model, we characterized the epidemiology of HFMD in Henan, one of the largest population provinces in China, from 2012 to 2013, and quantified the impacts of potential driving factors. RESULTS: Notably, 21.43 and 24.60% counties were identified as hot and cold spots, respectively. Spatially, the hotspots were mainly clustered in regions where the economic level was high. Temporally, the highest incidence period of HFMD was discovered to be in late spring and early summer. The impact of meteorological and socio-economic factors on the disease are significant, and this study found that a 1 °C rise in temperature was related to an increase of 4.09% in the HFMD incidence, a 1% increment in relative humidity was associated with a 1.77% increase of the disease, and a 1% increment in ratio of urban to rural population was associated with a 0.16% increase of the disease. CONCLUSION: Meteorological and socio-economic factors presented significantly association with HFMD incidence, high-risk mainly appeared in large cities and their adjacent regions in hot and humid season. These findings will be helpful for HFMD risk control and disease-prevention policies implementation.

Risk factors spatial-temporal detection for dengue fever in Guangzhou.

Dengue fever (DF) has been a growing public-health concern in China since its emergence in Guangdong Province in 1978. Of all the regions that have experienced dengue outbreaks in mainland China, the city of Guangzhou is the most affected. This study aims to investigate the potential risk factors for dengue virus (DENV) transmission in Guangzhou, China, from 2006 to 2014. The impact of risk factors on DENV transmission was qualified by the q-values calculated using a novel spatial-temporal method, the GeoDetector model. Both climatic and socioeconomic factors were considered. The impacts on DF incidence of each single factor and the interaction of two factors were analysed. The results show that the number of days with rainfall of the month before last has the highest determinant power, with a q-value of 0.898 (P < 0.01); the q-values of the other factors related to temperature and precipitation were around 0.38-0.50. Integrating a Pearson correlation analysis, nonlinear associations were found between the DF incidence in Guangzhou and the climatic factors considered. The coupled impact of the different variables considered was enhanced compared with their individual effects. In addition, an increased number of tourists in the city were associated with a high incidence of DF. This study demonstrates that the number of rain days in a month has great influence on the DF incidence of the month after next; the temperature and precipitation have nonlinear impacts on the DF incidence in Guangzhou; both the domestic and overseas tourists coming to the city increase the risk of DENV transmission. These findings are useful in the risk assessment of DENV transmission, to predict DF outbreaks and to implement preventive DF reduction strategies.