TYPE I INTERFERON SCORE IS ASSOCIATED WITH THE SEVERITY AND POOR PROGNOSIS IN ANTI-MDA5 ANTIBODY-POSITIVE DERMATOMYOSITIS PATIENTS

BackgroundAnti-MDA5 antibody-positive dermatomyositis (anti-MDA5+DM) is a rare autoimmune disease associated with a high mortality rate due to rapid-progressive interstitial lung disease (RP-ILD), particularly in East Asia[1]. MDA5, acts as a cytoplasmic sensor of viral RNA, thus activating antiviral responses including the type I interferon (IFN) signaling pathway[2]. The involvement of type 1 IFN in the pathogenesis of MDA5+DM has been proposed based on the significantly elevated expression of its downstream stimulated genes(ISG) in muscle, skin, lung, and peripheral blood[3;4]. Janus kinase inhibitor, which targets the IFN pathway, combined with glucocorticoid could improve the survival of early-stage MDA5+DM-ILD patients[5]. In clinical practice, there is still an urgent demand for sensitive biomarkers to facilitate clinical risk assessment and precise treatment.ObjectivesThis study aimed to investigate the clinical significance of interferon score, especially IFN-I score, in patients with anti-MDA5+DM.MethodsDifferent subtypes of idiopathic inflammatory myopathy, including anti-MDA5+DM(n=61), anti-MDA5-DM(n=20), antisynthetase syndrome(ASS,n=22),polymyositis(PM,n=6) and immune-mediated necrotizing myopathy(IMNM,n=9), and 58 healthy controls were enrolled.. A multiplex quantitative real-time PCR(RT-qPCR) assay using four TaqMan probes was utilized to evaluate two type I ISGs (IFI44, MX1, which are used for IFN-I score), one type II ISG (IRF1), and one housekeeping gene (HRPT1). Clinical features and disease activity index were compared between high and low IFN-I score groups in 61 anti-MDA5+DM patients. The association between laboratory findings and the predictive value of baseline IFN-I score level for mortality was analyzed.ResultsThe IFN scores were significantly higher in patients with anti-MDA5+DM than in HC (Figure 1A). The IFN-I score correlated positively with serum IFN α(r = 0.335, P =0.008), ferritin (r = 0.302, P = 0.018), and Myositis Disease Activity Assessment Visual Analogue Scale (MYOACT) score(r=0.426, P=0.001). Compared with patients with low IFN-I scores, patients with high IFN-I scores showed increased MYOACT score, CRP, AST, ferritin, and the percentages of plasma cells (PC%) but decreased lymphocyte count, natural killer cell count, and monocyte count. The 3-month survival rate was significantly lower in patients with IFN-I score > 4.9 than in those with IFN-I score ≤ 4.9(72.9% vs. 100%, P=0.044)(Figure 1B).ConclusionIFN score, especially IFN-I score, detected by multiplex RT-qPCR, can be a valuable biomarker for monitoring disease activity and predicting mortality in anti-MDA5+DM patients.References[1]I.E. Lundberg, M. Fujimoto, J. Vencovsky, R. Aggarwal, M. Holmqvist, L. Christopher-Stine, A.L. Mammen, and F.W. Miller, Idiopathic inflammatory myopathies. Nat Rev Dis Primers 7 (2021) 86.[2]G. Liu, J.H. Lee, Z.M. Parker, D. Acharya, J.J. Chiang, M. van Gent, W. Riedl, M.E. Davis-Gardner, E. Wies, C. Chiang, and M.U. Gack, ISG15-dependent activation of the sensor MDA5 is antagonized by the SARS-CoV-2 papain-like protease to evade host innate immunity. Nat Microbiol 6 (2021) 467-478.[3]G.M. Moneta, D. Pires Marafon, E. Marasco, S. Rosina, M. Verardo, C. Fiorillo, C. Minetti, L. Bracci-Laudiero, A. Ravelli, F. De Benedetti, and R. Nicolai, Muscle Expression of Type I and Type II Interferons Is Increased in Juvenile Dermatomyositis and Related to Clinical and Histologic Features. Arthritis Rheumatol 71 (2019) 1011-1021.[4]Y. Ye, Z. Chen, S. Jiang, F. Jia, T. Li, X. Lu, J. Xue, X. Lian, J. Ma, P. Hao, L. Lu, S. Ye, N. Shen, C. Bao, Q. Fu, and X. Zhang, Single-cell profiling reveals distinct adaptive immune hallmarks in MDA5+ dermatomyositis with therapeutic implications. Nat Commun 13 (2022) 6458.[5]Z. Chen, X. Wang, and S. Ye, Tofacitinib in Amyopathic Dermatomyositis–Associated Interstitial Lung Disease. New England Journal of Medicine 381 (2019) 291-293.AcknowledgementsThis work was supported by the National Natural Science Foundation of China [81974251], and Shanghai Hospital Develop ent Center, Joint Research of New Advanced Technology Project [SHDC12018106]Disclosure of InterestsNone Declared.

Prevalence of psychological symptoms and associated risk factors among nurses in 30 provinces during the COVID-19 pandemic in China

Background With the outbreak of the coronavirus disease 2019 (COVID-19), nurses have won well-deserved recog-nition for their indispensable roles in providing humane and professional healthcare for patients. However, by the nature of their role working at the forefront of patient care, nurses are prone to experiencing mental health conse-quences. Therefore, we pay attention to measuring the magnitude of psychological symptoms and identifying associ-ated factors among nurses in China.Methods We launched a nationwide, cross-sectional survey of nurses who worked in secondary or tertiary hospitals and public or private hospitals from 30 provinces in China. The prevalence and severity of symptoms of burnout, depression, and anxiety were investigated, respectively. Multivariable logistic regression analyses were performed to identify factors associated with each psychological symptom.Findings A total of 138 279 respondents who worked in 243 hospitals completed this survey. A substantial propor-tion of nurses reported symptoms of burnout (34%), depression (55.5%), and anxiety (41.8%). In line with the dispro-portionality of economic development, we noted that the middle or western region was an independent risk factor for depression and anxiety. Compared with those working in the secondary hospital, nurses who worked in tertiary hospitals were associated with a higher likelihood of burnout and depression.Interpretation Nurses are experiencing emotional, physical, and mental exhaustion during the COVID-19 epidemic. Governments and health policymakers need to draw attention to reinforcing prevention and ameliorating counter-measures to safeguard nurses' health.Funding The strategic consulting project of the Chinese Academy of Engineering [2021-32-5]. Advanced Institute of Infomation Technology, Peking University, Zhejiang Province [2020-Z-17]Copyright (c) 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Towards Exploring Large Molecular Space: An Efficient Chemical Genetic Algorithm.

Generating molecules with desired properties is an important task in chemistry and pharmacy. An efficient method may have a positive impact on finding drugs to treat diseases like COVID-19. Data mining and artificial intelligence may be good ways to find an efficient method. Recently, both the generative models based on deep learning and the work based on genetic algorithms have made some progress in generating molecules and optimizing the molecule's properties. However, existing methods need to be improved in efficiency and performance. To solve these problems, we propose a method named the Chemical Genetic Algorithm for Large Molecular Space (CALM). Specifically, CALM employs a scalable and efficient molecular representation called molecular matrix. Then, we design corresponding crossover, mutation, and mask operators inspired by domain knowledge and previous studies. We apply our genetic algorithm to several tasks related to molecular property optimization and constraint molecular optimization. The results of these tasks show that our approach outperforms the other state-of-the-art deep learning and genetic algorithm methods, where the z tests performed on the results of several experiments show that our method is more than 99% likely to be significant. At the same time, based on the experimental results, we point out the insufficiency in the experimental evaluation standard which affects the fair evaluation of previous work. Supplementary Information: The online version contains supplementary material available at 10.1007/s11390-021-0970-3.

FXR inhibition may protect from SARS-CoV-2 infection by reducing ACE2.

Prevention of SARS-CoV-2 infection through the modulation of viral host receptors, such as ACE21, could represent a new chemoprophylactic approach for COVID-19 complementing vaccination2,3. However, the mechanisms controlling ACE2 expression remain elusive. Here, we identify the farnesoid X receptor (FXR) as a direct regulator of ACE2 transcription in multiple COVID19-affected tissues, including the gastrointestinal and respiratory systems. We then use the over-the-counter compound z-guggulsterone (ZGG) and the off-patent drug ursodeoxycholic acid (UDCA) to reduce FXR signalling and downregulate ACE2 in human lung, cholangiocyte and intestinal organoids and in the corresponding tissues in mice and hamsters. We demonstrate that UDCA-mediated ACE2 downregulation reduces susceptibility to SARS-CoV-2 infection in vitro, in vivo and in human lungs and livers perfused ex situ. Furthermore, we illustrate that UDCA reduces ACE2 expression in the nasal epithelium in humans. Finally, we identify a correlation between UDCA treatment and positive clinical outcomes following SARS-CoV-2 infection using retrospective registry data, and confirm these findings in an independent validation cohort of liver transplant recipients. In conclusion, we identify a novel function of FXR in controlling ACE2 expression and provide evidence that modulation of this pathway could be beneficial for reducing SARS-CoV-2 infection, paving the road for future clinical trials.

A community-based cross-sectional study of anxiety and metabolic syndrome.

BACKGROUND: The prevalence of anxiety and other psychological disorders has increased during the COVID-19 pandemic, especially among the elderly. Anxiety and metabolic syndrome (MetS) may aggravate each other. This study further clarified the correlation between the two. METHODS: Adopting a convenience sampling method, this study investigated 162 elderly people over 65 years of age in Fangzhuang Community, Beijing. All participants provided baseline data on sex, age, lifestyle, and health status. The Hamilton Anxiety Scale (HAMA) was used to assess anxiety. Blood samples, abdominal circumference, and blood pressure were used to diagnose MetS. The elderly were divided into MetS and control groups according to the diagnosis of MetS. Differences in anxiety between the two groups were analysed and further stratified by age and gender. Multivariate logistic regression analysis was used to analyse the possible risk factors for MetS. RESULTS: Compared with the control group, anxiety scores of the MetS group were statistically higher (Z = 4.78, P < 0.001). There was a significant correlation between anxiety levels and MetS (r = 0.353, P < 0.001). Multivariate logistic regression revealed that anxiety (possible anxiety vs no anxiety: odds ratio [OR] = 2.982, 95% confidence interval [CI] 1.295-6.969; definite anxiety vs no anxiety: OR = 14.573, 95%CI 3.675-57.788; P < 0.001) and BMI (OR = 1.504, 95% CI 1.275-1.774; P < 0.001) were possible risk factors for MetS. CONCLUSION: The elderly with MetS had higher anxiety scores. Anxiety may be a potential risk factor for MetS, which provides a new perspective on anxiety and MetS.

Effect of Methylprednisolone on Mortality and Clinical Courses in Patients with Severe COVID-19: A Propensity Score Matching Analysis

Background Whether methylprednisolone therapy can reduce the mortality rate of patients with severe coronavirus disease 2019 (COVID-19) remains controversial, and its effects on the length of hospital stay and virus shedding time are also unknown. This retrospective study investigates the previous issues to provide more evidence for methylprednisolone treatment in severe COVID-19. Methods This retrospective study included 563 of 4827 patients with confirmed COVID-19 admitted to Wuhan Huoshenshan Hospital or Wuhan Guanggu Hospital between February 3, 2020 and March 30, 2020 who met the screening criteria. The participants' epidemiological and demographic data, comorbidities, laboratory test results, treatments, outcomes, and vital clinical time points were extracted from electronic medical records. The primary outcome was in-hospital death, and the secondary outcomes were 2 clinical courses: length from admission to viral clearance and discharge. Univariate and multivariate logistic or linear regression analyses were used to assess the role of methylprednisolone in different outcomes. Propensity score matching was performed to control for confounding factors. Results Of the 563 patients who met the screening criteria and were included in the subsequent analysis, 138 were included in the methylprednisolone group and 425 in the nonmethylprednisolone group. The in-hospital death rate between the methylprednisolone and nonmethylprednisolone groups showed a significant difference (23.91% vs. 1.65%, P < 0.001), which was maintained after propensity score matching (13.98% vs. 5.38%, P = 0.048). However, univariate logistic analysis in the matched groups showed that methylprednisolone treatment (odds ratio [OR], 5.242;95% confidence interval [CI], 0.802 to 34.246;P = 0.084) was not a risk factor for in-hospital death in severe patients. Further multivariate logistic regression analysis found comorbidities (OR, 3.327;95% CI, 1.702 to 6.501;P < 0.001), lower lymphocyte count (OR, 0.076;95% CI, 0.012 to 0.461;P = 0.005), higher lactate dehydrogenase (LDH) levels (OR, 1.008;95% CI, 1.003 to 1.013;P = 0.002), and anticoagulation therapy (OR, 11.187;95% CI, 2.459 to 50.900;P = 0.002) were associated with in-hospital mortality. Multivariate linear regression analysis in the matched groups showed that methylprednisolone treatment was not a risk factor for a prolonged duration from admission to viral clearance (β Value 0.081;95% CI, −1.012 to 3.657;P = 0.265) or discharge (β Value 0.114;95% CI, −0.723 to 6.408;P = 0.117). d-dimer (β Value, 0.144;95% CI, 0.012 to 0.817;P = 0.044), LDH (β Value 0.260;95% CI, 0.010 to 0.034;P < 0.001), and antiviral therapy (β Value 0.220;95% CI, 1.373 to 6.263;P = 0.002) were associated with a longer length from admission to viral clearance. The lymphocyte count (β Value −0.206;95% CI, −6.248 to −1.197;P = 0.004), LDH (β Value 0.231;95% CI, 0.012 to 0.048;P = 0.001), antiviral therapy (β Value 0.143;95% CI, 0.058 to 7.497;P = 0.047), and antibacterial therapy (β Value 0.152;95% CI, 0.133 to 8.154;P = 0.043) were associated with a longer hospitalization duration from admission to discharge. Further stratified analysis revealed that the low daily dose group (≤60 mg/d) and the low total dose group (≤200 mg) had shorter duration from admission to viral clearance (Z=−2.362, P = 0.018;Z=−2.010, P = 0.044) and a shorter hospital stay (Z=−2.735, P = 0.006;Z=−3.858, P < 0.001). Conclusions In patients with severe COVID-19, methylprednisolone is safe and does not prolong the duration from admission to viral clearance or discharge. Low-dose, short-term methylprednisolone treatment may be more beneficial in shortening the disease course.

Effect of Methylprednisolone on Mortality and Clinical Courses in Patients with Severe COVID-19: A Propensity Score Matching Analysis.

Background: Whether methylprednisolone therapy can reduce the mortality rate of patients with severe coronavirus disease 2019 (COVID-19) remains controversial, and its effects on the length of hospital stay and virus shedding time are also unknown. This retrospective study investigates the previous issues to provide more evidence for methylprednisolone treatment in severe COVID-19. Methods: This retrospective study included 563 of 4827 patients with confirmed COVID-19 admitted to Wuhan Huoshenshan Hospital or Wuhan Guanggu Hospital between February 3, 2020 and March 30, 2020 who met the screening criteria. The participants' epidemiological and demographic data, comorbidities, laboratory test results, treatments, outcomes, and vital clinical time points were extracted from electronic medical records. The primary outcome was in-hospital death, and the secondary outcomes were 2 clinical courses: length from admission to viral clearance and discharge. Univariate and multivariate logistic or linear regression analyses were used to assess the role of methylprednisolone in different outcomes. Propensity score matching was performed to control for confounding factors. Results: Of the 563 patients who met the screening criteria and were included in the subsequent analysis, 138 were included in the methylprednisolone group and 425 in the nonmethylprednisolone group. The in-hospital death rate between the methylprednisolone and nonmethylprednisolone groups showed a significant difference (23.91% vs. 1.65%, P < 0.001), which was maintained after propensity score matching (13.98% vs. 5.38%, P = 0.048). However, univariate logistic analysis in the matched groups showed that methylprednisolone treatment (odds ratio [OR], 5.242; 95% confidence interval [CI], 0.802 to 34.246; P = 0.084) was not a risk factor for in-hospital death in severe patients. Further multivariate logistic regression analysis found comorbidities (OR, 3.327; 95% CI, 1.702 to 6.501; P < 0.001), lower lymphocyte count (OR, 0.076; 95% CI, 0.012 to 0.461; P = 0.005), higher lactate dehydrogenase (LDH) levels (OR, 1.008; 95% CI, 1.003 to 1.013; P = 0.002), and anticoagulation therapy (OR, 11.187; 95% CI, 2.459 to 50.900; P = 0.002) were associated with in-hospital mortality. Multivariate linear regression analysis in the matched groups showed that methylprednisolone treatment was not a risk factor for a prolonged duration from admission to viral clearance (ß Value 0.081; 95% CI, -1.012 to 3.657; P = 0.265) or discharge (ß Value 0.114; 95% CI, -0.723 to 6.408; P = 0.117). d-dimer (ß Value, 0.144; 95% CI, 0.012 to 0.817; P = 0.044), LDH (ß Value 0.260; 95% CI, 0.010 to 0.034; P < 0.001), and antiviral therapy (ß Value 0.220; 95% CI, 1.373 to 6.263; P = 0.002) were associated with a longer length from admission to viral clearance. The lymphocyte count (ß Value -0.206; 95% CI, -6.248 to -1.197; P = 0.004), LDH (ß Value 0.231; 95% CI, 0.012 to 0.048; P = 0.001), antiviral therapy (ß Value 0.143; 95% CI, 0.058 to 7.497; P = 0.047), and antibacterial therapy (ß Value 0.152; 95% CI, 0.133 to 8.154; P = 0.043) were associated with a longer hospitalization duration from admission to discharge. Further stratified analysis revealed that the low daily dose group (≤60 mg/d) and the low total dose group (≤200 mg) had shorter duration from admission to viral clearance (Z=-2.362, P = 0.018; Z=-2.010, P = 0.044) and a shorter hospital stay (Z=-2.735, P = 0.006; Z=-3.858, P < 0.001). Conclusions: In patients with severe COVID-19, methylprednisolone is safe and does not prolong the duration from admission to viral clearance or discharge. Low-dose, short-term methylprednisolone treatment may be more beneficial in shortening the disease course.

Towards Exploring Large Molecular Space: An Efficient Chemical Genetic Algorithm

Generating molecules with desired properties is an important task in chemistry and pharmacy. An efficient method may have a positive impact on finding drugs to treat diseases like COVID-19. Data mining and artificial intelligence may be good ways to find an efficient method. Recently, both the generative models based on deep learning and the work based on genetic algorithms have made some progress in generating molecules and optimizing the molecule's properties. However, existing methods need to be improved in efficiency and performance. To solve these problems, we propose a method named the Chemical Genetic Algorithm for Large Molecular Space (CALM). Specifically, CALM employs a scalable and efficient molecular representation called molecular matrix. Then, we design corresponding crossover, mutation, and mask operators inspired by domain knowledge and previous studies. We apply our genetic algorithm to several tasks related to molecular property optimization and constraint molecular optimization. The results of these tasks show that our approach outperforms the other state-of-the-art deep learning and genetic algorithm methods, where the z tests performed on the results of several experiments show that our method is more than 99% likely to be significant. At the same time, based on the experimental results, we point out the insufficiency in the experimental evaluation standard which affects the fair evaluation of previous work. Supplementary Information The online version contains supplementary material available at 10.1007/s11390-021-0970-3.

SARS-CoV-2 Z-RNA activates the ZBP1-RIPK3 pathway to promote virus-induced inflammatory responses.

SARS-CoV-2 infection can trigger strong inflammatory responses and cause severe lung damage in COVID-19 patients with critical illness. However, the molecular mechanisms by which the infection induces excessive inflammatory responses are not fully understood. Here, we report that SARS-CoV-2 infection results in the formation of viral Z-RNA in the cytoplasm of infected cells and thereby activates the ZBP1-RIPK3 pathway. Pharmacological inhibition of RIPK3 by GSK872 or genetic deletion of MLKL reduced SARS-CoV-2-induced IL-1ß release. ZBP1 or RIPK3 deficiency leads to reduced production of both inflammatory cytokines and chemokines during SARS-CoV-2 infection both in vitro and in vivo. Furthermore, deletion of ZBP1 or RIPK3 alleviated SARS-CoV-2 infection-induced immune cell infiltration and lung damage in infected mouse models. These results suggest that the ZBP1-RIPK3 pathway plays a critical role in SARS-CoV-2-induced inflammatory responses and lung damage. Our study provides novel insights into how SARS-CoV-2 infection triggers inflammatory responses and lung pathology, and implicates the therapeutic potential of targeting ZBP1-RIPK3 axis in treating COVID-19.

[Effects of vaccines on the viral negative conversion of children with COVID-19].

Objective: To explore the effect of vaccination on viral negative conversion of children with COVID-19. Methods: A retrospective cohort study was conducted. A cohort of 189 children aged 3-14 years with COVID-19 admitted to Renji Hospital (South branch) of Shanghai Jiao Tong University School of Medicine from April 7th to May 19th 2022 was enrolled in the study. According to the vaccination status, the infected children were divided into an unvaccinated group and a vaccinated group. Age, gender, severity, clinical manifestations, and laboratory tests, etc. were compared between groups, by rank sum test or chi-square test. The effects of vaccination on viral negative conversion were analyzed by a Cox mixed-effects regression model. Additionally, a questionnaire survey was conducted among the parents of unvaccinated children to analyze the reasons for not being vaccinated. Results: A total of 189 children aged 3-14 years were enrolled, including 95 males (50.3%) and 94 females (49.7%), aged 5.7 (4.1,8.6) years. There were 117 cases (61.9%) in the unvaccinated group and 72 cases (38.1%) in the vaccinated group. The age of the vaccinated group was higher than that of the unvaccinated group (8.8 (6.8, 10.6) vs. 4.5 (3.6, 5.9) years, Z=9.45, P<0.001). No significant differences were found in clinical manifestations, disease severity, and laboratory results between groups (all P>0.05), except for the occurrence rate of cough symptoms, which was significantly higher in the vaccinated group than in the non-vaccinated group (68.1% (49/72) vs. 50.4% (59/117),χ2=5.67, P=0.017). The Kaplan-Meier survival curve and Cox mixed-effects regression model showed that the time to the viral negative conversion was significantly shorter in the vaccinated group compared with the unvaccinated group (8 (7, 10) vs. 11 (9, 12) d, Z=5.20, P<0.001; adjusted HR=2.19 (95%CI 1.62-2.97)). For questionnaire survey on the reasons for not receiving a vaccination, 115 questionnaires were distributed and 112 valid questionnaires (97.4%) were collected. The main reasons for not being vaccinated were that parents thought that their children were not in the range of appropriate age for vaccination (51 cases, 45.5%) and children were in special physical conditions (47 cases, 42.0%). Conclusion: Vaccination can effectively shorten the negative conversion time of children with COVID-19 and targeted programs should be developed to increase eligible children's vaccination rate for SARS-CoV-2 vaccination.

Prevalence of psychological symptoms and associated risk factors among nurses in 30 provinces during the COVID-19 pandemic in China: Prevalence of psychological symptoms among Chinese nurses

Background: With the outbreak of the coronavirus disease 2019 (COVID-19), nurses have won well-deserved recognition for their indispensable roles in providing humane and professional healthcare for patients. However, by the nature of their role working at the forefront of patient care, nurses are prone to experiencing mental health consequences. Therefore, we pay attention to measuring the magnitude of psychological symptoms and identifying associated factors among nurses in China. Methods: We launched a nationwide, cross-sectional survey of nurses who worked in secondary or tertiary hospitals and public or private hospitals from 30 provinces in China. The prevalence and severity of symptoms of burnout, depression, and anxiety were investigated, respectively. Multivariable logistic regression analyses were performed to identify factors associated with each psychological symptom. Findings: A total of 138 279 respondents who worked in 243 hospitals completed this survey. A substantial proportion of nurses reported symptoms of burnout (34%), depression (55·5%), and anxiety (41·8%). In line with the disproportionality of economic development, we noted that the middle or western region was an independent risk factor for depression and anxiety. Compared with those working in the secondary hospital, nurses who worked in tertiary hospitals were associated with a higher likelihood of burnout and depression. Interpretation: Nurses are experiencing emotional, physical, and mental exhaustion during the COVID-19 epidemic. Governments and health policymakers need to draw attention to reinforcing prevention and ameliorating countermeasures to safeguard nurses' health. Funding: The strategic consulting project of the Chinese Academy of Engineering [2021-32-5]. Advanced Institute of Infomation Technology, Peking University, Zhejiang Province [2020-Z-17] © 2022 The Author(s)

Changes in primary and secondary aerosols during a controlled Chinese New Year.

Large reductions in anthropogenic emissions during the Chinese New Year (CNY) holiday in Beijing have been well reported. However, the changes during the CNY of 2021 are different because most people stayed in Beijing to control the spread of coronavirus disease (COVID-19). Here a high-resolution aerosol mass spectrometer (HR-AMS) was deployed for characterization of the changes in size-resolved aerosol composition and sources during the CNY. We found that the reductions in traffic-related NOx and fossil fuel-related organic aerosol (OA), and cooking OA (1.3-12.7%) during the CNY of 2021 were much smaller than those in previous CNY holidays of 2013, 2015, and 2020. In contrast, the mass concentrations of secondary aerosol species except nitrate showed ubiquitous increases (17.6-30.4%) during the CNY of 2021 mainly due to a 4-day severe haze episode. OA composition also changed substantially during the CNY of 2021. In particular, we observed a large increase by nearly a factor of 2 in oxidized primary OA likely from biomass burning, and a decrease of 50.1% in aqueous-phase secondary OA. A further analysis of the severe haze episode during the CNY illustrated a rapid transition of secondary formation from photochemical to aqueous-phase processing followed by a scavenging process, leading to significant changes in aerosol composition, size distributions, and oxidation degree of OA. A parameterization relationship between oxygen-to-carbon (O/C) and f44 (fraction of m/z 44 in OA) from a collocated capture vaporizer aerosol chemical speciation monitor (CV-ACSM) was developed, which has a significant implication for characterization of OA evolution and the impacts on hygroscopicity due to the rapidly increased deployments of CV-ACSM worldwide.

Prevalence of psychological symptoms and associated risk factors among nurses in 30 provinces during the COVID-19 pandemic in China

Summary Background With the outbreak of the coronavirus disease 2019 (COVID-19), nurses have won well-deserved recognition for their indispensable roles in providing humane and professional healthcare for patients. However, by the nature of their role working at the forefront of patient care, nurses are prone to experiencing mental health consequences. Therefore, we pay attention to measuring the magnitude of psychological symptoms and identifying associated factors among nurses in China. Methods We launched a nationwide, cross-sectional survey of nurses who worked in secondary or tertiary hospitals and public or private hospitals from 30 provinces in China. The prevalence and severity of symptoms of burnout, depression, and anxiety were investigated, respectively. Multivariable logistic regression analyses were performed to identify factors associated with each psychological symptom. Findings A total of 138 279 respondents who worked in 243 hospitals completed this survey. A substantial proportion of nurses reported symptoms of burnout (34%), depression (55·5%), and anxiety (41·8%). In line with the disproportionality of economic development, we noted that the middle or western region was an independent risk factor for depression and anxiety. Compared with those working in the secondary hospital, nurses who worked in tertiary hospitals were associated with a higher likelihood of burnout and depression. Interpretation Nurses are experiencing emotional, physical, and mental exhaustion during the COVID-19 epidemic. Governments and health policymakers need to draw attention to reinforcing prevention and ameliorating countermeasures to safeguard nurses' health. Funding The strategic consulting project of the Chinese Academy of Engineering [2021-32-5]. Advanced Institute of Infomation Technology, Peking University, Zhejiang Province [2020-Z-17]

[Epidemiological characteristics of imported malaria in Zhengzhou City from 2016 to 2020].

OBJECTIVE: To analyze the epidemiological characteristics of reported imported malaria cases in Zhengzhou City from 2016 to 2020, so as to provide insights into the management of imported malaria in the city. METHODS: All data pertaining to cases with definitive diagnosis of malaria in Zhengzhou City from 2016 to 2020 were captured from the National Notifiable Disease Report System and the Information Management System for Parasitic Disease Control in China, including individual demographic data, and malaria onset, initial diagnosis and definitive diagnosis data. All data were descriptively analyzed. The duration from malaria onset to initial diagnosis, from initial diagnosis to definitive diagnosis and from onset to definitive diagnosis was compared among cases. In addition, the diagnoses of imported malaria cases in which definitive diagnosis was made were compared with the reexaminations by Zhengzhou Municipal Malaria Diagnosis Reference Laboratory. RESULTS: A total of 302 cases with definitive diagnosis of malaria were reported in Zhengzhou City from 2016 to 2020, and all were imported cases, with Plasmodium falciparum malaria as the predominant type (230 cases, 76.2%). There were 293 malaria cases imported from Africa (293 cases, 97.0%), which mainly included Nigeria (48 cases, 15.9%), Angola (40 cases, 13.2%), and the Democratic Republic of the Congo (29 cases, 9.6%). There was no obvious seasonality found in the date of malaria onset and time of reporting malaria. The ratio of male to female malaria cases was 49.3:1, and there were 103 cases (34.1%) with the current residency address in Zhengzhou City, 193 cases (63.9%) with the current residency address in other cities of Henan Province and 6 cases (2.0%) in other provinces of China. There were 271 cases (89.7%) seeking initial diagnosis in medical institutions, and the diagnostic accuracy of malaria was 56.6% (171/302) at initial diagnosis institutions. A total of 122 cases (40.4%) sought medical care on the day of malaria onset, and 252 cases (86.4%) within 3 days; however, only 22 cases (7.3%) were definitively diagnosed on the day of onset, and 162 cases (53.6%) diagnosed within 3 days. There were no significant differences between malaria cases seeking initial diagnosis at medical institutions and disease control and prevention institutions in terms of the duration from malaria onset to initial diagnosis (Z = -1.663, P > 0.05), from initial diagnosis to definitive diagnosis (Z = -0.413, P > 0.05) or from malaria onset to definitive diagnosis (Z = -0.838, P > 0.05). The median duration (interquartile range) from initial diagnosis to definitive diagnosis of malaria was 3.00 (2.00), 3.00 (6.00), 2.00 (4.00) d and 1.00 (1.00) d among cases seeking medical care at township-level and lower, county-, city- and province-level medical institutions, and the median duration from initial diagnosis to definitive diagnosis of malaria was significantly longer among cases seeking medical care at township-level and lower medical institutions than at city (Z = -3.286, P < 0.008 33) and province-level medical institutions (Z = -9.119, P < 0.008 33), while the median duration from initial diagnosis to definitive diagnosis [1.00 (3.00) d vs. 2.00 (4.00) d; Z = -4.099, P < 0.016] and from malaria onset to definitive diagnosis [3.00 (4.00) d vs. 4.00 (5.00) d; Z = -2.868, P < 0.016] among malaria cases with the current residency address in Zhengzhou City was both shorter than in other cities of Henan Province. The diagnostic accuracy was 89.1% (269/302) among malaria cases in which definitive diagnosis was made, and the accuracy of malaria reexaminations was 94.0% (284/302) in Zhengzhou Municipal Malaria Diagnosis Reference Laboratory. CONCLUSIONS: P. falciparum malaria was predominant among reported imported malaria cases in Zhengzhou City from 2016 to 2020, and these imported malaria cases were predominantly diagnosed at medical institutions; however, the diagnostic capability of malaria is poor in township-level and lower medical institutions. Strengthening the collaboration between medical institutions and disease control and prevention institutions and improving the diagnostic capability building at medical institutions are recommended to consolidate malaria elimination achivements.

Specific urban units identified in tuberculosis epidemic using a geographical detector in Guangzhou, China.

BACKGROUND: A remarkable drop in tuberculosis (TB) incidence has been achieved in China, although in 2019 it was still considered the second most communicable disease. However, TB's spatial features and risk factors in urban areas remain poorly understood. This study aims to identify the spatial differentiations and potential influencing factors of TB in highly urbanized regions on a fine scale. METHODS: This study included 18 socioeconomic and environmental variables in the four central districts of Guangzhou, China. TB case data obtained from the Guangzhou Institute of Tuberculosis Control and Prevention. Before using Pearson correlation and a geographical detector (GD) to identify potential influencing factors, we conducted a global spatial autocorrelation analysis to select an appropriate spatial scales. RESULTS: Owing to its strong spatial autocorrelation (Moran's I = 0.33, Z = 4.71), the 2 km × 2 km grid was selected as the spatial scale. At this level, TB incidence was closely associated with most socioeconomic variables (0.31 < r < 0.76, P < 0.01). Of five environmental factors, only the concentration of fine particulate matter displayed significant correlation (r = 0.21, P < 0.05). Similarly, in terms of q values derived from the GD, socioeconomic variables had stronger explanatory abilities (0.08 < q < 0.57) for the spatial differentiation of the 2017 incidence of TB than environmental variables (0.06 < q < 0.27). Moreover, a much larger proportion (0.16 < q < 0.89) of the spatial differentiation was interpreted by pairwise interactions, especially those (0.60 < q < 0.89) related to the 2016 incidence of TB, officially appointed medical institutions, bus stops, and road density. CONCLUSIONS: The spatial heterogeneity of the 2017 incidence of TB in the study area was considerably influenced by several socioeconomic and environmental factors and their pairwise interactions on a fine scale. We suggest that more attention should be paid to the units with pairwise interacting factors in Guangzhou. Our study provides helpful clues for local authorities implementing more effective intervention measures to reduce TB incidence in China's municipal areas, which are featured by both a high degree of urbanization and a high incidence of TB.

Differentiating COVID-19 Cases from Others by an Anatomy Similarity-Inspired Sensitive Merit from CT Images

Computed tomography (CT) of COVID-19 manifests a relatively global effect through the whole lungs, like peripheral ground glass, consolidation, reticular pattern, nodules etc. This characteristic effect renders the difficulties in differentiating COVID-19 from the normal body or other lung diseases by CT. This work presents a novel method to relieve the difficulties by reducing the global effect through the 3D whole lung volume into 2D-like domain. The hypothesis is that the lung tissue shares the similar anatomic structure within a small lung sub-volume for normal subjects. Therefore, the anatomic land-markers along the z-axis, denoted as Lung Marks are used to eliminate axial variable. Our experiments indicated that 30 Lung Marks are sufficient to eliminate the axial variable. The method computes texture measures from each 2D-like volumetric data and maps the measures on to the corresponding Lung Mark, resulting in a profile along the z-axis. The difference of the profiles between two different abnormalities is the proposed sensitive merit to differentiate COVID-19 cases from others in CT images. 48 COVID-19 cases and 48 normal screening cases were used to test the effectiveness of the proposed sensitive merit. Intensity and gradient based texture descriptors were computed from each axial cross image at the corresponding Lung Mark along the z-axis. Euclidean, Jaccard and Dice distances are calculated to generate the profiles of the proposed sensitive merit. Consistent results are observed across texture descriptor types and distance types in the texture measure between the normal and COVID-19 subjects. Uneven Profiles demonstrate the variation along the z-axis. With Lung Mark, the variation of texture descriptor has been reduced prominently. The Gradient based descriptor is more sensitive. Individual Haralick features analysis shows the 2nd and 10th dimensions are most distinguishable. © 2020 IEEE

MagicChem: a MR system based on needs theory for chemical experiments.

Real chemical experiments may be dangerous or pollute the environment; meanwhile, the preparation of drugs and reagents is time-consuming. Due to the above-mentioned reasons, few experiments can be actually operated by students, which is not conducive to the chemistry learning and the phenomena principle understanding. Recently, due to the impact of Covid-19, many schools adopt online teaching, which is even more detrimental to students' learning of chemistry. Fortunately, MR(mixed reality) technology provides us with the possibility of solving the safety issues and breaking the space-time constraints, while the theory of human needs (Maslow's hierarchical needs) provides us with a way to design a comfortable and stimulant MR system with realistic visual presentation and interaction. The paper combines with the theory of human needs to propose a new needs model for virtual experiment. Based on this needs model, we design and develop a comprehensive MR system called MagicChem, which offers a robust 6-DoF interactive and illumination consistent experimental space with virtual-real occlusion, supporting realistic visual interaction, tangible interaction, gesture interaction with touching, voice interaction, temperature interaction, olfactory interaction and virtual human interaction. User study shows that MagicChem satisfies the needs model better than other MR experimental environments that partially meet the needs model. In addition, we explore the application of the needs model in VR environment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10055-021-00560-z.

Effect of SARS-CoV-2 infection on fetal umbilical vein flow and cardiac function: a prospective study.

OBJECTIVES: To explore whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can affect umbilical vein blood flow (UVBF) and fetal cardiac function. METHODS: Prospective case-control study of consecutive pregnancies complicated by SARS-CoV-2 infection during the second half of pregnancy matched with unaffected women. Measurements of UVBF normalized for fetal abdominal circumference (UVBF/AC), atrial area (AA) and ventricular sphericity indices (SI) were compared between the two study groups. Chi-square and Mann-Whitney U tests were sued to analyze the data. RESULTS: Fifty-four consecutive pregnancies complicated and 108 not complicated by SARS-CoV-2 infection were included. The median gestational age at infection was 30.2 (interquartile range [IQR] 26.2 34.1). General baseline and pregnancy characteristics were similar between pregnant women with compared to those without SARS-CoV-2 infection. There was no difference in UVBF/AC (study groups z value -0.11 vs. 0.14 control p 0.751) values between pregnancies complicated compared to those not complicated by SARS-CoV-2 infection. Likewise, there was no difference in the left and right AA (left 1.30 vs. 1.28 p=0.221 and right 1.33 vs. 1.31 p=0.324) and SI (left 1.75 vs. 1.77 p=0.208 and right 1.51 vs. 1.54 p=0.121) between the two groups. CONCLUSIONS: SARS-CoV-2 infection does not affect UVBF and fetal cardiac function in uncomplicated pregnancies.

Dynamic changes of IgM and IgG antibodies in asymptomatic patients as an effective way to detect SARS-CoV-2 infection.

BACKGROUND: COVID-19 has become a global pandemic, and close contacts and asymptomatic patients are worthy of attention. METHODS: A total of 1844 people in close contacts with 76 COVID-19 patients were investigated, and nasopharyngeal swabs and venous blood were collected for centralized medical quarantine observation. Real-time fluorescence was used to detect SARS-CoV-2 nucleic acid in nasopharyngeal swabs of all close contacts, and the colloidal gold method was used to detect serum-specific antibodies. Levels of IgM- and IgG-specific antibodies were detected quantitatively through chemiluminescence from the first nucleic acid turned negative date (0 week) and on weekly intervals of ≤1 week, 1-2 weeks, 2-3 weeks, 3-4 weeks, 4-5 weeks, 5-6 weeks, and 6-7 weeks. RESULTS: The total positive rate of the colloidal gold method (88.5%, 23/26) was significantly higher (χ2  = 59.182, p < 0.001) than that of the healthy control group (2.0%, 1/50). There was significant difference in IgG concentration at different time points (0-7 weeks) after negative nucleic acid conversion (χ2  = 14.034, p = 0.029). Serum IgG levels were significantly higher at weekly time points of 4-5 weeks (Z = -2.399, p = 0.016), 5-6 weeks (Z = -2.049, p = 0.040), and 6-7 weeks (Z = -2.197, p = 0.028) compared with 1-2 weeks after negative nucleic acid conversion. However, there was no significant difference (χ2  = 4.936, p = 0.552) in IgM concentration between time points tested (0-7 weeks) after negative nucleic acid conversion. The positive rates of IgM and IgG in asymptomatic patients (χ2  = 84.660, p < 0.001) were significantly higher than those in the healthy control group (χ2  = 9.201, p = 0.002) within 7 weeks of negative nucleic acid conversion. CONCLUSIONS: The IgG concentration in asymptomatic cases remained at a high level after nucleic acid turned negative. Nucleic acid detection combined with IgM and IgG antibody detection is an effective way to screen asymptomatic infections.

Expression of plasma IFN signaling-related miRNAs during acute SARS-CoV-2 infection and its association with RBD-IgG antibody response.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a huge challenge worldwide. Although previous studies have suggested that type I interferon (IFN-I) could inhibit the virus replication, the expression characteristics of IFN-I signaling-related miRNAs (ISR-miRNAs) during acute severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and its relationship with receptor-binding domain (RBD) IgG antibody response at the recovery phase remain unclear. METHODS: Expression profiles of 12 plasma ISR-miRNAs in COVID-19 patients and healthy controls were analyzed using RT-qPCR. The level of RBD-IgG antibody was determined using the competitive ELISA. Spearman correlation was done to measure the associations of plasma ISR-miRNAs with clinical characteristics during acute SARS-CoV-2 infection and RBD-IgG antibody response at the recovery phase. RESULTS: Compared with the healthy controls, COVID-19 patients exhibited higher levels of miR-29b-3p (Z = 3.15, P = 0.002) and miR-1246 (Z = 4.98, P < 0.001). However, the expression of miR-186-5p and miR-15a-5p were significantly decreased. As the results shown, miR-30b-5p was negatively correlated with CD4 + T cell counts (r = - 0.41, P = 0.027) and marginally positively correlated with fasting plasma glucose in COVID-19 patients (r = 0.37, P = 0.052). The competitive ELISA analysis showed the plasma level of miR-497-5p at the acute phase was positively correlated with RBD-IgG antibody response (r = 0.48, P = 0.038). CONCLUSIONS: Our present results suggested that the expression level of ISR-miRNAs was not only associated with acute SARS-CoV-2 infection but also with RBD-IgG antibody response at the recovery phase of COVID-19. Future studies should be performed to explore the biological significance of ISR-miRNAs in SARS-CoV-2 infection.