Impact analysis of environmental and social factors on early-stage COVID-19 transmission in China by machine learning.

As a highly contagious disease, COVID-19 caused a worldwide pandemic and it is still ongoing. However, the infection in China has been successfully controlled although its initial transmission was also nationwide and has caused a serious public health crisis. The analysis on the early-stage COVID-19 transmission in China is worth investigating for its guiding significance on prevention to other countries and regions. In this study, we conducted the experiments from the perspectives of COVID-19 occurrence and intensity. We eliminated unimportant factors from 113 variables and applied four machine learning-based classification and regression models to predict COVID-19 occurrence and intensity, respectively. The influence of each important factor was analysed when applicable. Our optimal model on COVID-19 occurrence prediction presented an accuracy of 91.91% and the best R2 of intensity prediction reached 0.778. Linear regression-based model was identified as unable to fit and predict the intensity, and thus only the variable influence on COVID-19 occurrence can be explained. We found that (1) CO VID-19 was more likely to occur in prosperous cities closer to the epicentre and located on higher altitudes, (2) and the occurrence was higher under extreme weather and high minimum relative humidity. (3) Most air pollutants increased the risk of COVID-19 occurrence except NO2 and O3, and there existed a lag effect of 6-7 days. (4) NPIs (non-pharmaceutical interventions) did not show apparent effect until two weeks after.

A Selective P2Y Purinergic Receptor Agonist 2-MesADP Enhances Locomotor Recovery after Acute Spinal Cord Injury.

INTRODUCTION: Spinal cord injury (SCI) causes most severe motor and sensory dysfunctions. In Chinese traditional medicine, the agonist of a purinergic receptor is believed to have a positive effect on SCIs, and 2-Methylthio-adenosine-5'-diphosphate (2-MesADP) is a selective agonist of the P2Y purinergic receptor. METHODS: To investigate its therapeutic function and molecular mechanism in SCI, transcriptome analysis associated with weighted gene co-expression network analysis (WGCNA) was carried out at various time points after T9 crush injury. RESULTS: 2-MesADP demonstrated recovery of limb motor function at the 6 weeks after injury, accompanied by neuronal regeneration and axon remyelination at 2 and 6 weeks. Furthermore, gene profiling revealed alternated gene expression with the treatment of 2-MesADP. These genes were assigned to a total of 38 modules, followed by gene ontology analysis; of these, 18 represented neuronal apoptosis and regeneration, immune response, synaptic transmission, cell cycle, and angiogenesis. In the neuronal apoptosis and regeneration module, Nefh, NeuroD6, and Dcx in the 2-MesADP group were noticed due to their interesting expression pattern. The gene expression patterns of Mag, Mog, and Cnp, which played key roles in myelination, were significantly changed with the treatment of 2-MesADP. Wnt signal pathway was the most important pathway in 2-MesADP treatment for acute SCI. CONCLUSION: 2-MesADP enhanced locomotor recovery in mouse SCI by altering the expression of neuronal apoptosis and remyelination-related genes and Wnt signaling pathways.

Governmental policies drive the LUCC trajectories in the Jianghan Plain.

The prosperity of farmers is closely tied to governmental policies. The Jianghan Plain is an important region for commodity grains, cotton and edible oil for China. The trajectories of land use and land cover change (LUCC) of the study area from 1995 to 2010 were studied based on the LUCC database of the Chinese Academy of Sciences. The LUCC was characterised by a continuous decrease of arable land and continuous increase of waters and construction land. The LUCC was obviously concurrent with the implementation of related national policies. The transition to construction land was ever well controlled by 'Notice regarding the further strengthening of land management and arable land protection' promulgated in 1997. However, it flourished again with the 'Rise of Central China Strategy' taking effect since 2006. The transition of construction land to others reflects an uncommon trend, which must be strengthened with the strict implementation of the overall plan, which imposes a limited acreage quota of construction land to each district. The policies were quite contradictory to the transition of waters. LUCC related to waters is most active, which was driven by both natural forces and national policies. Just after the devastating flood of 1998, the state council of China put forward the Green Policy to govern the major rivers. As to the study area, it is mainly to 'push over dykes to let flood through and return farmland to lakes'. In 2004, the Grain Direct Subsidy Policy was implemented, which, along with the surge in the price of rice, resulted in a strengthening trend of conversion of ponds to paddy fields.

Temporal and Spatial Evolution of the African Swine Fever Epidemic in Vietnam.

African swine fever (ASF) is a severe infectious disease affecting domestic and wild suids. Spatiotemporal dynamics analysis of the ASF is crucial to understanding its transmission. The ASF broke out in Vietnam in February 2019. The research on the spatiotemporal evolution characteristics of ASF in Vietnam is lacking. Spatiotemporal statistical methods, including direction analysis, spatial autocorrelation analysis, and spatiotemporal scan statistics were used to reveal the dynamics of the spatial diffusion direction and spatiotemporal aggregation characteristics of ASF in Vietnam. According to the cessation of the epidemic, it was divided into three phases: February to August 2019 (phase 1), April to December 2020 (phase 2), and January 2021 to March 2022 (phase 3). The ASF showed a significant spread trend from north to south in phase 1. The occurrence rate of the ASF aggregated spatially in phase 1 and became random in phases 2 and 3. The high-high ASF clusters (the province was a high cluster and both it and its neighbors had a high ASF occurrence rate) were concentrated in the north in phases 1 and 2. Four spatiotemporal high-risk ASF clusters were identified with a mean radius of 121.88 km. In general, there were significant concentrated outbreak areas and directional spread in the early stage and small-scale, high-frequency, and randomly scattered outbreaks in the later stage. The findings could contribute to a deeper understanding of the spatiotemporal spread of the ASF in Vietnam.

Stevens-Johnson Syndrome Following Non-steroidal Anti-inflammatory Drugs: A Real-World Analysis of Post-marketing Surveillance Data.

Background: The Stevens-Johnson syndrome (SJS) is a severe skin reaction to non-steroidal anti-inflammatory drugs (NSAIDs), and can even be life-threatening. However, there are still few real-world studies to compare the specific differences in the adverse effects of skin and mucosal invasion. Methods: Disproportionality analysis and Bayesian analysis were devoted to data-mining of the suspected SJS after using NSAIDs based on the FDA's Adverse Event Reporting System (FAERS) from January 2004 to March 2021. The times to onset, fatality, and hospitalization rates of antipyretic analgesic-associated SJS were also investigated. Results: A total of 1,868 reports of SJS adverse events were identified with NSAIDs. Among 5 NSAIDs monotherapies we studied (acetaminophen, ibuprofen, aspirin, diclofenac and celecoxib), ibuprofen had the highest association with SJS based on the highest reporting odds ratio (ROR = 7.06, 95% two-sided CI = 6.59-7.56), proportional reporting ratio (PRR = 6.98, χ2 = 4201.14) and empirical Bayes geometric mean (EBGM = 6.78, 95% one-sided CI = 6.40). However, ibuprofen-associated SJS had the lowest fatality rate (6.87%, p < 0.0001) and the highest hospitalization rate (79.27%, p < 0.0001). Celecoxib-associated SJS had the latest time to onset (317.56 days, p < 0.0001). Diclofenac-associated SJS cases appeared to be associated with the highest risk of death (25.00%, p < 0.0001). Conclusions: The analysis of FAERS data provides a more accurate profile of the incidence and prognosis of SJS after NSAIDs treatment, enabling continued surveillance and timely intervention in patients at risk of SJS following these NSAIDs.

Antifungal Drugs and Drug-Induced Liver Injury: A Real-World Study Leveraging the FDA Adverse Event Reporting System Database.

Aims: We aimed to estimate the risk of drug-induced liver injury (DILI) from various antifungal treatments with azoles and echinocandins causing in real-world practice. Methods: We performed disproportionality and Bayesian analyses based on data from the first quarter in 2004 to the third quarter in 2021 in the Food and Drug Administration Adverse Event Reporting System to characterize the signal differences of antifungal drugs-related DILI. We also compared the onset time and mortality differences of different antifungal agents. Results: A total of 2943 antifungal drugs-related DILI were identified. Affected patients tended to be aged >45 years (51.38%), with more males than females (49.03% vs. 38.09%). Antifungal drug-induced liver injury is most commonly reported with voriconazole (32.45%), fluconazole (19.37%), and itraconazole (14.51%). Almost all antifungal drugs were shown to be associated with DILI under disproportionality and Bayesian analyses. The intraclass analysis of correlation between different antifungal agents and DILI showed the following ranking: caspofungin (ROR = 6.12; 95%CI: 5.36-6.98) > anidulafungin (5.15; 3.69-7.18) > itraconazole (5.06; 4.58-5.60) > voriconazole (4.58; 4.29-4.90) > micafungin (4.53; 3.89-5.27) > posaconazole (3.99; 3.47-4.59) > fluconazole (3.19; 2.93-3.47) > ketoconazole (2.28; 1.96-2.64). The onset time of DILI was significantly different among different antifungal drugs (p < 0.0001), and anidulafungin result in the highest mortality rate (50.00%), while ketoconazole has the lowest mortality rate (9.60%). Conclusion: Based on the Food and Drug Administration Adverse Event Reporting System database, antifungal drugs are significantly associated with DILI, and itraconazole and voriconazole had the greatest risk of liver injury. Due to indication bias, more clinical studies are needed to confirm the safety of echinocandins.

Research Progress of Pharmacogenomics in Drug-Induced Liver Injury.

Background: Drug-induced liver injury (DILI) is a common and serious adverse drug reaction with insufficient clinical diagnostic strategies and treatment methods. The only clinically well-received method is the Roussel UCLAF Causality Assessment Method scale, which can be applied to both individuals and prospective or retrospective studies. However, in severe cases, patients with DILI still would develop acute liver failure or even death. Pharmacogenomics, a powerful tool to achieve precision medicine, has been used to study the polymorphism of DILI related genes. Summary: We summarized the pathogenesis of DILI and findings on associated genes and variations with DILI, including but not limited to HLA genes, drug metabolizing enzymes, and transporters genes, and pointed out further fields for DILI related pharmacogenomics study to provide references for DILI clinical diagnosis and treatment. Key Messages: At present, most of the studies are mainly limited to CGS and GWAS, and there is still a long way to achieve clinical transformation. DNA methylation could be a new consideration, and ethnic differences and special populations also deserve attention.

A multiplicity of environmental, economic and social factor analyses to understand COVID-19 diffusion.

Research on the impact of the environment on COVID-19 diffusion lacks a full-comprehensive perspective, and neglecting the multiplicity of the human-environment system can lead to misleading conclusions. We attempted to reveal all pre-existing environmental-to-human and human-to-human determinants that influence the transmission of COVID-19. As such, We estimated the daily case incidence ratios (CIR) of COVID-19 for prefectures across mainland China, and used a mixed-effects mixed-distribution model to study the association between the CIR and 114 factors related to climate, atmospheric environmental quality, terrain, population, economic, human mobility as well as non-pharmaceutical interventions (NPIs). Not only the changes in determinants over time as the pandemic progresses but also their lag and interaction effects were examined. CO, O3, PM10 and PM2.5 were found positively linked with CIR, but the effect of NO2 was negative. The temperature had no significant association with CIR, and the daily minimum humidity was a significant negatively predictor. NPIs' level was negatively associated with CIR until with a lag of 15 days. Higher accumulated destination migration scale flow from the epicenter and lower distance to the epicenter (DisWH) were associated with a higher CIR, however, the interaction between DisWH and the time was positive. The more economically developed and more densely populated cities have a higher probability of CIR occurrence, but they may not have a higher CIR intensity.The COVID-19 diffusion are caused by a multiplicity of environmental, economic, social factors as well as NPIs. First, multiple pollutants carried simultaneously on particulate matter affect COVID-19 transmission. Second, the temperature has a limited impact on the spread of the epidemic. Third, NPIs must last for at least 15 days or longer before the effect has been apparent. Fourth, the impact of population movement from the epicenter on COVID-19 gradually diminished over time and intraregional migration deserves more attention.

Kidney Injury Following Ibuprofen and Acetaminophen: A Real-World Analysis of Post-Marketing Surveillance Data.

Background: Although kidney injury has been reported as a serious adverse effect in patients treated with ibuprofen or acetaminophen (APAP), there are still few real-world studies to compare the specific differences in the adverse effects of nephrotoxicity. Methods: Disproportionality analysis and Bayesian analysis were devoted to data-mining of the suspected kidney injury after using ibuprofen and APAP based on the FDA's Adverse Event Reporting System (FAERS) from January 2004 to March 2021. The times to onset, fatality, and hospitalization rates of ibuprofen-associated kidney injury and APAP-associated kidney injury were also investigated. Results: 2,453 reports of ibuprofen-associated kidney injury and 1,288 reports of APAP-associated kidney injury were identified. Ibuprofen appeared to affected more middle-aged patients than elderly ones (27.76 vs 16.53%) while APAP appeared to affected more young patients than middle-aged patients (45.24 vs 29.10%) and elderly patients were fewer (13.99%). Compared to ibuprofen, APAP had the higher association with renal injury based on the higher reporting odds ratio (ROR = 2.45, 95% two-sided CI = 2.36-2.56), proportional reporting ratio (PRR = 2.39, χ 2 = 2002.94) and empirical Bayes geometric mean (EBGM = 2.38, 95% one-sided CI = 2.3). In addition, APAP-associated kidney injury had earlier onset (32.74 vs 115.82 days, p < 0.0001) and a higher fatality rate (44.43 vs 7.36%, p < 0.001) than those of ibuprofen-associated kidney injury. Conclusion: The analysis of FAERS data provides a more accurate profile on the incidence and prognosis of kidney injury after ibuprofen and acetaminophen treatment, enabling continued surveillance and timely intervention in patients at risk of kidney injury using these drugs.

Ginkgolide B inhibits lung cancer cells promotion via beclin-1-dependent autophagy.

BACKGROUND: Ginkgolide B (GKB) is a major active component of the extracts of Ginkgo biloba leaves, and it has been used as an anti-cancer agent. However, it is unknown whether GKB has the therapeutic effects on lung cancer. Here, we studied the effects of GKB on lung cancer cells. METHODS: The effects of GKB on lung cancer cell proliferation and invasion were analyzed by cell counting kit (CCK-8) and cell invasion assays, respectively. Apoptosis was detected by flow cytometry. Western blot analysis was used to confirm the expression of autophagy-associated proteins in GKB-treated cells. Immunofluorescence analysis was used to analyze the level of light chain 3B (LC3B). RESULTS: Treatment with GKB time-dependently inhibited the proliferation and decreased the invasive capacity of A549 and H1975 cells. GKB induced apoptosis of these cells, but there was no significant effect on apoptosis compared to the control treatment. GKB-induced inhibition of cell proliferation and GKB-induced cell death were due to autophagy rather than apoptosis. GKB-induced autophagy of lung cancer cells was dependent on beclin-1, and autophagy-induced inhibition of the NLRP3 inflammasome contributed to the anti-tumor effect of GKB. CONCLUSIONS: GKB-mediated autophagy of lung cancer cells is beclin-1-dependent and results in inhibition of the NLRP3 inflammasome. Therefore, GKB might be a potential therapeutic candidate for the treatment of lung cancer.

Identifying and Predicting the Geographical Distribution Patterns of Oncomelania hupensis.

Schistosomiasis is a snail-borne parasitic disease endemic to the tropics and subtropics, whose distribution depends on snail prevalence as determined by climatic and environmental factors. Here, dynamic spatial and temporal patterns of Oncomelania hupensis distributions were quantified using general statistics, global Moran's I, and standard deviation ellipses, with Maxent modeling used to predict the distribution of habitat areas suitable for this snail in Gong'an County, a severely affected region of Jianghan Plain, China, based on annual average temperature, humidity of the climate, soil type, normalized difference vegetation index, land use, ditch density, land surface temperature, and digital elevation model variables; each variable's contribution was tested using the jackknife method. Several key results emerged. First, coverage area of O. hupensis had changed little from 2007 to 2012, with some cities, counties, and districts alternately increasing and decreasing, with ditch and bottomland being the main habitat types. Second, although it showed a weak spatial autocorrelation, changing negligibly, there was a significant east-west gradient in the O. hupensis habitat area. Third, 21.9% of Gong'an County's area was at high risk of snail presence; and ditch density, temperature, elevation, and wetting index contributed most to their occurrence. Our findings and methods provide valuable and timely insight for the control, monitoring, and management of schistosomiasis in China.

Spatiotemporal Heterogeneity in Human Schistosoma japonicum Infection at Village Level in Hubei Province, China.

The spatiotemporal dynamics of Schistosoma japonicum, combined with temporal heterogeneity among regions of different epidemic areal-types from a microscale viewpoint might capture the local change dynamics and thus aid in optimizing the combinations of precise schistosomiasis control measures. The prevalence data on schistosomiasis infection from 2007 to 2012 in the 30 most endemic counties of Hubei Province, Central China, were appended to the village-level administrative division polygon layer. Anselin local Moran's I, a retrospective space-time scan statistic and a multilevel-growth model analysis framework, was used to investigate the spatiotemporal pattern of schistosomiasis resident infection rate (RIR) at the village level and how natural geographical environment influence the schistosomiasis RIR over time. Two spatiotemporal high-risk clusters and continuous high-rate clusters were identified mainly in the embankment region across flooding areas of lakes connected with the Yangze and Hanjiang Rivers. Moreover, 12 other clusters and outlier evolution modes were detected to be scattered across the continuous high-rate clusters. Villages located in embankment region had the highest initial values and most rapidly reduced RIRs over time, followed by villages located in marshland-and-lake regions and finally by villages located in hilly region. Moreover, initial RIR values and rates of change did significantly vary (p < 0.001 and p < 0.001, respectively) irrespective of their epidemic areal-type. These local spatiotemporal heterogeneities could contribute to the formulation of distinct control strategies based on local transmission dynamics and be applied in other endemic areas of schistosomiasis.