Mesenchymal Stem/Stromal Cells: HUMAN MESENCHYMAL STEM CELL THERAPY IN SEVERE COVID-19 PATIENTS: 2-YEAR FOLLOW-UP RESULTS OF A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL

Background & Aim: The long-term effects of human mesenchymal stem cell (MSC) treatment on COVID-19 patients have not been fully characterized. The aim of this study was to evaluate the safety and efficacy of a MSC treatment administered to severe COVID-19 patients enrolled in a randomized, double-blind, placebo-controlled clinical trial (NCT 04288102). Methods, Results & Conclusion(s): A total of 100 patients experiencing severe COVID-19 received either MSC treatment (n = 65, 4x107 cells per infusion) or a placebo (n = 35) combined with standard of care on days 0, 3, and 6. Patients were subsequently evaluated 18 and 24 months after treatment to evaluate the long-term safety and efficacy of the MSC treatment. The outcomes measured included: 6-minute walking distance (6-MWD), lung imaging, quality of life according to the Short Form 36 questionnaire, COVID-19-related symptoms, titers of SARS-CoV-2 neutralizing antibodies, MSC-related adverse events (AEs), and tumor markers. Two years after treatment, a marginally smaller proportion of patients had a 6-MWD below the lower limit of the normal range in the MSC group than in the placebo group (OR = 0.19, 95% CI: 0.04-0.80, Fisher's exact test, p = 0.015). On the SF-36 questionnaire, a marginally higher general health score was received by the MSC group at month 18 compared with the placebo group (50.00 vs. 35.00;95% CI: 0.00-20.00, Wilcoxon rank sum test, p = 0.016). In contrast, there were no differences in the total severity score of lung imaging or the titer of neutralizing antibodies between the two groups. Meanwhile, there were no MSC-related AEs reported at the 18- or 24-month follow-ups. The serum levels of most of the tumor markers examined remained within normal ranges and were similar between the MSC and placebo groups. Long-term safety was observed for the COVID-19 patients who received MSC treatment. Yet few sustained efficacy of MSC treatment was observed at the end of the 2-year follow-up period. Funding(s): The National Key Research and Development Program of China (2022YFA1105604, 2020YFC0860900), the specific research fund of The Innovation Platform for Academicians of Hainan Province (YSPTZX202216) and the Fund of National Clinical Center for Infectious Diseases, PLA General Hospital (NCRCID202105,413FZT6). [Figure presented]Copyright © 2023 International Society for Cell & Gene Therapy

Integrated smart analytics of nucleic acid amplification tests via paper microfluidics and deep learning in cloud computing

Pandemics such as COVID-19 have exposed global inequalities in essential health care. Here, we proposed a novel analytics of nucleic acid amplification tests (NAATs) by combining paper microfluidics with deep learning and cloud computing. Real-time amplifications of synthesized SARS-CoV-2 RNA templates were performed in paper devices. Information pertained to on-chip reactions in time-series format were transmitted to cloud server on which deep learning (DL) models were preloaded for data analysis. DL models enable prediction of NAAT results using partly gathered real-time fluorescence data. Using information provided by the G-channel, accurate prediction can be made as early as 9 min, a 78% reduction from the conventional 40 min mark. Reaction dynamics hidden in amplification curves were effectively leveraged. Positive and negative samples can be unbiasedly and automatically distinguished. Practical utility of the approach was validated by cross-platform study using clinical datasets. Predicted clinical accuracy, sensitivity and specificity were 98.6%, 97.6% and 99.1%. Not only the approach reduced the need for the use of bulky apparatus, but also provided intelligent, distributable and robotic insights for NAAT analysis. It set a novel paradigm for analyzing NAATs, and can be combined with the most cutting-edge technologies in fields of biosensor, artificial intelligence and cloud computing to facilitate fundamental and clinical research.Copyright © 2023 Elsevier Ltd

Farmer Households' Livelihood Resilience in Ethnic Tourism Villages: A Case Study of the Wuling Mountain Area, China

Farmer households in tourist villages have been severely impacted by the COVID-19 pandemic, and the recovery of livelihood is proving difficult. In order to improve farmer households' ability to cope with external shocks, we have applied the theoretical framework of resilience to study farmer households' livelihood in ethnic tourism villages. Based on the survey data of 480 farmer households from 10 ethnic tourism villages in the Wuling Mountain area, this study constructs a livelihood resilience evaluation index system from three of the following dimensions: buffer capacity, adaptive capacity, and transformation capacity. These households are classified into three types: government-led, company-led, and community-led. In addition, the livelihood resilience and its influencing factors of each type is quantitatively assessed. The results show that the livelihood resilience of farmer households administered by the government, companies, and communities is 0.2984, 0.3250, and 0.2442, respectively. Government-led farmer households have the greatest transformation capacity, company-led farmer households have the largest buffer capacity and adaptive capacity, and community-led farmer households have the least capacity across the board. The results indicated that the company-led management of tourism development is currently the most appropriate mode of management for the local area. Four factors, namely, the number of family members engaged in tourism, the training opportunities for the development of professional skills, the education level of core family members, and the type of assistance subsidy available to a family, are the dominant obstacle factors with respect to the livelihood resilience of different types of farmer households. Finally, some recommendations are made to improve the farmer households' livelihood resilience in ethnic tourism villages based on two aspects of organization management and farmer households' behavior. The findings of this study can be used as a theoretical foundation for future research on farmer households' resilience to poverty in underdeveloped ethnic tourism villages. © 2022 by the authors.

Health Literacy Regarding Infection Disease Prevention and Treatment among Residents of Taizhou, Zhejiang: Temporal Trends and Associated Factors

Background: Due to repeated COVID-19 outbreaks worldwide, COVID-19 containment in China has become a routine social issue, entering a new phase of containment, and residents' health literacy about infection disease prevention and treatment has obtained increasing attentions. Objective: To explore the health literacy about infection disease prevention and treatment in residents of Taizhou, Zhejiang during 2017-2020, and to analyze the trend of changes as well as influencing factors, providing scientific evidence for the precise implementation of actions for achieving "Healthy Taizhou 2030". Methods: This study was implemented from 2017 to 2020 with Taizhou permanent residents aged between 15 and 69 selected using multistage random sampling, for investigating their demographics, socioeconomic features and health literacy about infection disease prevention and treatment using the National Residents' Health Literacy Monitoring Questionnaire developed by us. In January 2021, the data of health literacy about infection disease prevention and treatment of residents in Taizhou City in four years was analyzed. The health literacy data during 2017-2020 were comparatively analyzed after being processed with weight standardization, and the trend of changes during the period was analyzed using a Chi-squared test for linear trend. Binary logistic regression was used for identifying factors associated with relevant health literacy of these residents in 2020. Results: The number of respondents for the survey conducted in four consecutive years from 2017 to 2020, was 3 595, 5 389, 5 929, and 5 847, respectively. The samples in the four yearly surveys showed basically similar demographics, with those aged 45-54 (27.42%-30.46%), education level was junior high school(27.78%-29.93%), occupation was farmer(44.52%-58.03%)accounting for the largest proportion. The urban to rural population ratio for the sample of four consecutive yearly surveys was 0.50: 1, 0.55: 1, 0.54: 1 and 0.52: 1, respectively. And the male to female ratio was 1: 1, 0.95: 1, 0.99: 1 and 0.94: 1, respectively. The prevalence of having health literacy about infection disease prevention and treatment for 2017-2020 was 7.86% (642/3 595), 19.00%(1 024/5 389), 19.51%(1 157/5 929), and 27.14%(1 587/5 847), respectively. After the data were processed with weight standardization, the prevalence of health literacy regarding infectious disease prevention and treatment in 15-69-year-old residents in 2017-2020 was 22.25%, 24.72%, 25.34% and 33.14%, respectively. The health literary level regarding infectious disease prevention and treatment in the residents showed a successive linear increment during the study period regardless of living in rural or urban areas, sex, age(except for 65-69 year olds), and education level(except for illiteracy/lower illiteracy), and occupation(P< 0.05). Multivariate Logistic regression analysis showed that gender, age, education level, out-of-pocket health care costs in the past year, and annual household income were associated with health literacy regarding infectious disease prevention and treatment(P< 0.05). Conclusion: Our analysis indicates that some advances in prevention and control as well as health education regarding infectious diseases have been achieved in Taizhou, but there is still much room for improvement. In the "golden window" period for normalized prevention and control of COVID-19, it is suggested that Taizhou should strengthen health education regarding infectious disease prevention and treatment for key groups, such as those who are middle-aged and elderly, lower educated, or engage in a career as a farmer or worker, to further improve relevant heath literacy of Taizhou residents. Copyright © 2022 by the Chinese General Practice.

Review on Source Emission and Source Identification of Bioaerosols in the Atmosphere

Recent pandemic outbreak of the corona-virus disease 2019 (COVID-19) has raised widespread concerns about the importance of the bioaerosols. Bioaerosols are an important part of atmospheric aerosols. Due to its physico-chemical properties and inherent biological characteristics, bioaerosols play a key role in global ecosystem, climate change, air quality and public health. A large number of studies have been focused on the sampling and detection techniques of bioaerosols, disinfection protection, effects on health and environment. However, little is known about the source characteristics of bioaerosols. Therefore, the research status of airborne microbes source was focused, and the progress on the emission characteristics of natural and anthropogenic source of bioaerosols in the past 20 years was comprehensively summarized. Combined with our study, the main factors affecting the source emission and transport process were also highlighted, such as biogeographic regions, land-use types, and environmental factors. Subsequently, the various source analysis methods of current bioaerosols were discussed. Finally, the future work prospects of bioaerosols source characteristics were prospected. It is expected to provide reference for in-depth understanding of the source and transmission change mechanism of bioaerosols, and to better evaluate the level of atmospheric microbial pollution and monitor the aerosol transmission of pathogens. © 2021, Editorial Department of Journal of Earth Sciences and Environment. All right reserved.

How Did Depositors Respond to COVID-19?

Why did banks experience massive deposit inflows during the pandemic? We discover that deposit interest rates at bank branches in counties with higher COVID-19 infection rates fell by more than rates at branches-even branches of the same bank-in counties with lower infection rates. Credit drawdowns, national policies, such as the Payment Protection Program, and a flight-to-safety do not account for these cross-branch changes in deposit rates. Evidence suggests that higher local COVID-19 infection rates are associated with households' greater anxiety about future job and income losses, anxiety that induces households to reduce spending and increase deposits.

Epidemiological characteristics of COVID-19 patients in convalescence period.

This study aimed to investigate the clinical characteristics and to analyse the epidemiological features of coronavirus disease 2019 (COVID-19) patients during convalescence. In this study, we enrolled 71 confirmed cases of COVID-19 who were discharged from hospital and transferred to isolation wards from 6 February to 26 March 2020. They were all employees of Zhongnan Hospital of Wuhan University or their family members of which three cases were <18 years of age. Clinical data were collected and analysed statistically. Forty-one cases (41/71, 57.7%) comprised medical faculty, young and middle-aged patients (aged ⩽60 years) accounted for 81.7% (58/71). The average isolation time period for all adult patients was 13.8 ± 6.1 days. During convalescence, RNA detection results of 35.2% patients (25/71) turned from negative to positive. The longest RNA reversed phase time was 7 days. In all, 52.9% of adult patients (36/68) had no obvious clinical symptoms, and the remaining ones had mild and non-specific clinical symptoms (e.g. cough, sputum, sore throat, disorders of the gastrointestinal tract etc.). Chest CT signs in 89.7% of adult patients (61/68) gradually improved, and in the others, the lesions were eventually absorbed and improved after short-term repeated progression. The main chest CT manifestations of adult patients were normal, GGO or fibre streak shadow, and six patients (8.8%) had extrapulmonary manifestations, but there was no significant correlation with RNA detection results (r = -0.008, P > 0.05). The drug treatment was mainly symptomatic support therapy, and antibiotics and antiviral drugs were ineffective. It is necessary to re-evaluate the isolation time and standard to terminate isolation for discharged COVID-19 patients.

Clinical characteristics and prognosis of COVID-19 patients with tracheal intubation

This study aimed to describe the clinical characteristics and prognosis of COVID-19 patients who received tracheal intubation and mechanical ventilation. A total of 52 critical COVID-19 patients who received tracheal intubation were retrospectively included. The primary data including clinical features, laboratory results, and the outcomes were collected and analyzed. Among the 52 patients who received tracheal intubation, 14 were successfully extubated within two weeks and 38 failed extubation. The patients in the extubation failure group were significantly older than the patients in the successful extubation group (median age, 67.50 years vs 55.50 years). The median values of SpO2 and the PaO2/FiO2 (P/F) before tracheal intubation were significantly lower in extubation failure group than the those in successful extubation group (SpO2: 78.50% vs 85%, P/F: 71.50 mmHg vs 84.50 mmHg). Compared with the successful extubation group, the extubation failure group was found to have a significantly lower 28-day survival rate (21.05% vs 100%). Patients with extubation failure had more severe multi-organ injuries. Besides, a more severe hypoxia level was found to be associated with the failure of extubation and subsequent poor prognosis. Therefore, tracheal intubation and timely invasive mechanical ventilation should be administered in COVID-19 patients with refractory hypoxemia.

The teaching design and application of online - Offline hybrid curriculum under the influence of the novel coronavirus pneumonia epidemic

This paper analyzes the differences between online and offline courses in teaching organization, course content and practice, as well as the differences between hybrid teaching and hybrid courses in concept and emphasis. This paper puts forward the basic principles and requirements of hybrid courses teaching design, and discusses the key points and application scenarios of hybrid courses teaching design from three aspects: teaching objectives, teaching elements and teaching activities. And the key issues that need to be figured out are explained. © The Authors, published by EDP Sciences, 2021.

View Identification Assisted Fully Convolutional Network for Lung Field Segmentation of Frontal and Lateral Chest Radiographs

Locating lung field is a critical and fundamental processing stage in the automated analysis of chest radiographs (CXRs) for pulmonary disorders. During the routine examination of CXRs, using both frontal and lateral CXRs can benefit clinical diagnosis of cardiothoracic and lung diseases. However, the accurate segmentation of lung fields on both frontal and lateral CXRs is still challenging due to the blurry boundary of the lung field on lateral CXRs and the poor generalization ability of the models. Existing deep learning-based methods focused on lung field segmentation on frontal CXRs, and the generalization ability of these methods on the different type of CXRs (e.g., pediatric CXRs) and new lung diseases (e.g., COVID-19) has not been tested. In this paper, a view identification assisted fully convolutional network (VI-FCN) is proposed for the segmentation of lung fields on frontal and lateral CXRs simultaneously. The VI-FCN consists of an FCN branch for lung field segmentation and a view identification branch for identification of the frontal and lateral CXRs and for enhancing the lung field segmentation. To improve the generalization ability of VI-FCN, six public datasets and our frontal and lateral CXRs (over 2000 CXRs) were collected for training. The segmentation of lung fields on the Japanese Society of Radiological Technology (JSRT) dataset yields mean dice similarity coefficient (DSC) of 0.979 ±0.008, mean Jaccard index (Ω) of 0.959 ±0.016, and mean boundary distance (MBD) of 1.023 ±0.487mm. Besides, the VI-FCN achieves mean DSC of 0.973 ±0.010, mean Ωof 0.947 ±0.018, and mean MBD of 1.923 ±0.755mm for the segmentation of lung fields on our lateral CXRs. The experiments demonstrate the superior performance of the proposed VI-FCN over most of existing state-of-the-art methods. Moreover, the proposed VI-FCN achieves promising results on untrained pediatric CXRs and COVID-19 datasets. CCBYNCND

Author Correction: The dual role of anti-viral therapy in the treatment of Coronavirus disease 2019.

Correction to: European Review for Medical and Pharmacological Sciences 2020; 24 (22): 11939-11944-DOI: 10.26355/eurrev_202011_23854-PMID: 33275267, published online 30 November, 2020. The authors state that "Figures 3 and 4 were used twice due to a careless mistake during the preparation of Figures". There are amendments to this paper.  The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/23854.

The dual role of anti-viral therapy in the treatment of Coronavirus disease 2019.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) has become a worldwide public health emergency; unfortunately, there is currently no treatment for improving outcomes or reducing viral-clearance times in infected patients. The aim of the present study was to evaluate the efficacy of interferon (IFN) with or without lopinavir and ritonavir as antiviral therapeutic option for treating COVID-19 infection. PATIENTS AND METHODS: The present study enrolled 148 patients that received either standard care, treatment with IFN alfa-2b, or IFN alfa-2b combined with lopinavir plus ritonavir. Viral testing was performed using Reverse-Transcription Polymerase Chain Reaction (RT-PCR). RESULTS: There was no significant difference in the viral-clearance time at 28 days after treatment between patients receiving standard care and those receiving anti-viral treatments. However, the average viral-clearance time of patients receiving standard care (14 days) was shorter than that for patients receiving IFN alfa-2b or IFN alfa-2b combined with lopinavir plus ritonavir (15.5 or 17.5 days) (p<0.05). Patients treated with IFN alfa-2b within five days or IFN alfa-2b combined with lopinavir plus ritonavir after three days of symptoms exhibited shorter viral-clearance times than the other groups (p<0.05). Moreover, viral-clearance times were significantly longer in patients receiving standard care or anti-viral treatment 5 days after symptoms appeared than those of patients who received these treatments within five days of symptom onset (p<0.05). CONCLUSIONS: Early symptomatic treatment is most critical for maximizing amelioration of COVID-19 infection. Anti-viral treatment might have complicated effect on viral-clearance.

Comparison between chemiluminescence and colloidal gold method in the detection of 2019 novel coronavirus specific antibodies and the value in COVID-19 diagnosis and treatment

Objective: To compare the chemiluminescence and colloidal gold method in the detection of 2019 novel Coronavirus (2019-nCoV, or SARS-CoV-2) specific antibody and to evaluate the importance in the diagnosis and treatment of COVID-19. Methods: A total of 191 cases of diagnosed and suspected COVID-19 patients admitted in Febrary 2020 in Wuhan Leishenshan Hospital were included. The patients were divided into 2019-nCoV continuous positive group, 2019-nCoV positive to negative group, and 2019-nCoV suspect group according to the results of pharyngeal swab 2019-nCoV nucleic acid detection. In addition, 27 patients without COVID-19 were set as control group to test the specificity. The serum samples were collected, and colloidal gold and chemiluminescence method were used to detect total antibodies (IgM+IgG) and IgM. SPSS 24.0 was used to compare the difference in antibody detection rates between the two methods. Results: The specificity of total antibodies (IgM+IgG) and IgM detection was 100%. Two methods of total antibody detection had no significant difference in continuous positive group (P=1.00). In positive to negative group and suspect group, the positive detection rate of chemiluminescence method was significantly higher than colloidal gold method (95.2% vs 76.2% and 94.9% vs 70.5%, respectively, both P0.05). The chemiluminescence method showed no significant difference between the three groups in IgM detection (P0.05). Conclusion: The detection of 2019-nCoV specific antibody can be an important supplemental method to pharyngeal swab 2019-nCoV nucleic acid detection during the diagnosis and treatment of COVID-19. The chemiluminescence method is better than colloidal gold method in the detection of total antibody. The IgM detection using chemiluminescence method is suitable for all stages of the disease. © 2020, Editorial Board of Medical Journal of Wuhan University. All right reserved.

[Experience in the treatment of burn patients combined with inhalation injury during the epidemic of coronavirus disease 2019].

Objective: To introduce the experience in treating burn patients with inhalation injury during the epidemic of coronavirus disease 2019 (COVID-19). Methods: Six burn patients combined with inhalation injury were hospitalized in Department of Burns of Tongren Hospital of Wuhan University & Wuhan Third Hospital from February 1 to March 1 in 2020 during the high-incidence period of COVID-19, including 4 males and 2 females, aged 21-63 years, admitted at 2-4 hours after burns, with total burn areas of 1%-20% total body surface area (TBSA) and full-thickness burn areas of 1%-12% TBSA. Among them, 1 case had severe inhalation injury, 2 cases had mild inhalation injury, and 3 cases had moderate inhalation injury. The body temperatures of the patients were normal at the time of admission, with no fever or cough in the past 2 weeks. At admission, chest CT of one patient showed double lower lobes and left upper lobes had multiple slices and slightly high-density shadow of nodules. Chest CT of two patients showed thickening of bilateral lung texture, and the chest CT of remaining patients were normal. After admission, 6 patients were given routine treatment, the medical staffs paid attention to the protection and screened for COVID-19 according to the diagnosis and treatment plan of COVID-19. On post injury day (PID) 1, 3, 6, and 9, vein blood of patients were collected for determination of white blood cell (WBC) count, neutrophil, lymphocyte absolute value, and level of procalcitonin (PCT). Nucleic acid of novel coronavirus was detected by real-time fluorescence quantitative reverse transcription polymerase chain reaction on PID 3 and 6. The temperatures of patients were recorded after admission. The results of chest CT within one week after injury and the prognosis of the patients were recorded. Measurement data distributed normally were expressed as x±s, and measurement data distributed abnormally were expressed as M(P(25), P(75)). Results: (1) On PID 1, 3, 6, and 9, WBC counts of patients were respectively (19.8±3.8)×10(9)/L, (17.2±3.4)×10(9)/L, (13.3±3.1)×10(9)/L, and (11.1±1.6)×10(9)/L, neutrophils of patients were respectively 0.919±0.019, 0.899±0.011, 0.855±0.034, and 0.811±0.035, absolute values of lymphocytes of patients were respectively (0.65±0.18)×10(9)/L, (0.65±0.24)×10(9)/L, (0.91±0.34)×10(9)/L, and (1.23±0.42)×10(9)/L, and PCT values of patients were respectively 0.49 (0.36, 1.64), 0.39 (0.26, 0.73), 0.28 (0.18, 0.33), and 0.12 (0.11, 0.20) ng/mL. The values of WBC and neutrophils of patients were higher than the normal value, showing a downward trend. The absolute values of lymphocyte of patients returned to the normal value from PID 6. The PCT values of patients were higher than the normal value. (2) Nucleic acid test results of novel coronavirus of 6 patients were negative on PID 3 and 6. The temperatures of 6 patients ranged from 36.5 to 38.6 ℃. The typical imaging features of COVID-19 were not found in 6 patients within 1 week after injury by chest CT. After treatment for 14-32 days, 6 patients were cured and discharged. Conclusions: During COVID-19 pandemic, burn patients combined with inhalation injury should be treated under condition of good protection for doctors and nurses. Meanwhile, virus should be actively screened to reduce the risk of COVID-19 infection among doctors and patients.