A dual-labeled fluorescence quenching lateral flow assay based on one-pot enzyme-free isothermal cascade amplification for the rapid and sensitive detection of pathogens.

Rapid detection of nucleic acids is integral for clinical diagnostics, especially if a major public-health emergency occurs. However, such detection cannot be carried out efficiently in remote areas limited by medical resources. Herein, a dual-labeled fluorescence resonance energy transfer (FRET) lateral flow assay (LFA) based on one-pot enzyme-free cascade amplification was developed for rapid, convenient, and sensitive detection of open reading frame (ORF)1ab of severe acute respiratory syndrome-coronavirus-2. The catalyzed hairpin assembly (CHA) reaction of two well-designed hairpin probes was initiated by a target sequence and generated a hybridization chain reaction (HCR) initiator. Then, HCR probes modified with biotin were initiated to produce long DNA nanowires. After two-level amplification, the cascade-amplified product was detected by dual-labeled lateral flow strips. Gold nanoparticles (AuNPs)-streptavidin combined with the product and then ran along a nitrocellulose membrane under the action of capillary force. After binding with fluorescent microsphere-labeled-specific probes on the T line, a positive signal (red color) could be observed. Meanwhile, AuNPs could quench the fluorescence of the T line, and an inverse relationship between fluorescence intensity and the concentration of the CHA-HCR-amplified product was formed. The proposed strategy achieved a satisfactory limit of detection of 2.46 pM for colorimetric detection and 174 fM for fluorescent detection, respectively. Benefitting from the features of being one-pot, enzyme-free, low background, high sensitivity, and selectivity, this strategy shows great potential in bioanalysis and clinical diagnostics upon further development.

A cascade amplification strategy based on rolling circle amplification and hybridization chain reaction for ultrasensitive detection of pathogens.

Rapid and accurate detection of a variety of pathogens is very important for the prevention, control, and diagnosis of infectious diseases. Herein, an ultrasensitive nucleic acid isothermal cascade amplification technique based on rolling circle amplification (RCA) coupled with hybridization chain reaction (HCR) was developed for ORF1ab (opening reading frame 1a/b) for SARS-CoV-2 detection. In this scheme, the ORF1ab sequence hybridized with a padlock probe to trigger RCA reaction. Specifically, the recognition site for a unique nicking enzyme was incorporated into the padlock probe to cut the RCA products into short intermediate amplicons, which contain dual HCR initiation sites and can be directly used as primers for HCR. HCR probes, H1 and H2, labeled with FAM (FAM-H1 and FAM-H2) spontaneously participated in the HCR and formed a long nicked dsDNA. Additional probes were quenched by graphene oxide (GO) via π-stacking to decrease the background signal. Meanwhile, the fluorescence signal can be strongly amplified by the synergistic effect of FAM and SYBR green I. The proposed RCA-HCR method can be used to detect ORF1ab at concentrations as low as 7.65 fM. Moreover, the reliability of the RCA-HCR method in serum samples has also been validated. Satisfactory recoveries ranging from 85% to 113% for ORF1ab can be obtained. Therefore, this facile and ultrasensitive RCA-HCR assay provides a new promising tool for ORF1ab analysis and can be extended to the detection of various kinds of pathogens and genetic biomarkers.

Comparison between discarded facemask and common plastic waste on microbial colonization and physiochemical properties during aging in seawater.

Facemasks are indispensable for preventing the spread of COVID-19. However, improper disposal of discarded facemasks has led to their contamination in the marine environment. To understand the environmental risk of this emerging plastic pollution, it's important to clarify the features that distinguish discarded facemasks from common plastic waste during aging. This study compared the microbial colonization, degradation-related enzymes, and physicochemical properties among surgical masks, polystyrene cups, polycarbonate bottles, and polyethylene terephthalate bottles in their aging processes in natural seawater. Compared to the other plastic wastes, surgical masks were colonized by the most diverse microorganisms, reaching 1521 unique prokaryotic OTUs after 21-day exposure in seawater. Moreover, the activity of eukaryotic enzymes associated with plastic degradation was 80-fold higher than that in seawater, indicating that the colonized eukaryotes would be the major microorganisms degrading the surgical masks. Meanwhile, the nano-sized defects (depth between 8 and 61 nm) would evolve into cracks of bigger sizes and result in the breakage of the microfibers and releasing microplastics into the ocean. Overall, our study demonstrated a distinctive plastisphere occurred in surgical masks from both microbial and physiochemical aspects. This work provides new insights for assessing the potential risk of plastic pollution caused by the COVID-19 pandemic.

Recent advances in cascade isothermal amplification techniques for ultra-sensitive nucleic acid detection.

Nucleic acid amplification techniques have always been one of the hot spots of research, especially in the outbreak of COVID-19. From the initial polymerase chain reaction (PCR) to the current popular isothermal amplification, each new amplification techniques provides new ideas and methods for nucleic acid detection. However, limited by thermostable DNA polymerase and expensive thermal cycler, PCR is difficult to achieve point of care testing (POCT). Although isothermal amplification techniques overcome the defects of temperature control, single isothermal amplification is also limited by false positives, nucleic acid sequence compatibility, and signal amplification capability to some extent. Fortunately, efforts to integrating different enzymes or amplification techniques that enable to achieve intercatalyst communication and cascaded biotransformations may overcome the corner of single isothermal amplification. In this review, we systematically summarized the design fundamentals, signal generation, evolution, and application of cascade amplification. More importantly, the challenges and trends of cascade amplification were discussed in depth.

COVID-19 infection in patients with haematological malignancies: A single-centre survey in the latest Omicron wave in China.

As the COVID-19 variant Omicron surge in Beijing, China, a better understanding of risk factors for adverse outcomes may improve clinical management in patients with haematological malignancies (HM) diagnosed with COVID-19. The study sample includes 412 cases, mainly represented by acute leukaemia, chronic myeloid leukaemia (CML), plasma cell disorders and lymphoma and chronic lymphocytic leukaemia. COVID-19 pneumonia was observed in 10.4% (43/412) of patients, and severe/critical illness was observed in 5.3% (22/412). Among the 86 cases with advanced malignancies, 17.6% (12/86) of patients developed severe/critical COVID-19, which was significantly higher than reported in patients with stable malignancies (9/326, 2.70%, p < 0.001). Similarly, the advanced malignancy cohort had a higher mortality rate (9/86, 10.5% vs. 0/326, 0%, p < 0.001) and a poor 30-day overall survival (OS) compared with the stable malignancy cohort (74.2% vs. 100.0%, p < 0.0001). Overall, nine patients (2.2%) died. The primary cause of death was progressive HM in four patients and a combination of both COVID-19 and HM in five patients. In the multivariable analysis, over 65 years of age, comorbidities and advanced malignancy were correlated with severe/critical COVID-19 in HM patients. This study sheds light on the poor outcomes among COVID-19 HM patients with the leading cause of advanced malignancy.

How information processing and risk/benefit perception affect COVID-19 vaccination intention of users in online health communities.

Objective: To investigate the relationship among information processing, risk/benefit perception and the COVID-19 vaccination intention of OHCs users with the heuristic-systematic model (HSM). Methods: This study conducted a cross-sectional questionnaire via an online survey among Chinese adults. A structural equation model (SEM) was used to examine the research hypotheses. Results: Systematic information processing positively influenced benefit perception, and heuristic information processing positively influenced risk perception. Benefit perception had a significant positive effect on users' vaccination intention. Risk perception had a negative impact on vaccination intention. Findings revealed that differences in information processing methods affect users' perceptions of risk and benefit, which decide their vaccination intention. Conclusion: Online health communities can provide more systematic cues and users should process information systematically to increase their perceived benefits, consequently increase their willingness to receive COVID-19 vaccine.

Self-neglect among older adults admitted to a Chinese comprehensive hospital in the COVID-19 pandemic era: a cross-sectional study.

This study aims to explore the prevalence of self-neglect and associated factors among older adults admitted to the hospital in the COVID-19 pandemic context. The cross-sectional study conducted at a Chinese comprehensive hospital between January and April 2021, 452 older adults were recruited to complete the Abrams Geriatric Self-Neglect Scale, Social Support Rate Scale, FRAIL scale, Barthel index, Patient Health Questionnaire-9, and 10-item Connor-Davidson Resilience Scale. Multivariate logistic regression was used to explore the factors associated with elder self-neglect. The results showed that the prevalence of self-neglect among our sample was 30.3%. Factors that were associated with the risk of elder self-neglect included male, having multiple children (≥4), receiving infrequent visits from children, frailty, and depression. There is a need to screen for self-neglect among older adults admitted to the hospital in the COVID-19 pandemic context. Tailored interventions are warranted to improve the quality of life of older adults.

Fate of face masks after being discarded into seawater: Aging and microbial colonization.

Billions of discarded masks have entered the oceans since the outbreak of the COVID-19 pandemic. Current reports mostly discuss the potential of masks as plastic pollution, but there has been no study on the fate of this emerging plastic waste in the marine environment. Therefore, we exposed masks in natural seawater and evaluated their aging and effects on the microbial community using a combination of physicochemical and biological techniques. After 30-day exposure in natural seawater, the masks suffered from significant aging. Microbial colonizers such as Rhodobacteraceae Flavobacteriaceae, Vibrionaceae and fouling organisms like calcareous tubeworms Hydroides elegans were massively present on the masks. The roughness and modulus of the mask fiber increased 3 and 5 times, respectively, and the molecular weight decreased 7%. The growth of biofouling organisms caused the masks negatively buoyant after 14-30 days. Our study sheds some light on the fate of discarded masks in a coastal area and provides fundamental data to manage this important plastic waste during COVID-19 pandemic.

Effect of Information Framing on Wearing Masks During the COVID-19 Pandemic: Interaction With Social Norms and Information Credibility

Objective The main objectives of this study were to use the effect of information framing (different expressions of the same issue, e.g., positive messages and negative messages) to explore key factors that influence the attitude of and intention of the public toward wearing masks and to understand the internal and external factors of intervention on information framing perception. Methods This study performed an online questionnaire survey to explore the influence of demographic characteristics, information framing, social norms, and information credibility on the attitude of the public toward masks and their intention to wear them. Results (1) Information framing had a significant impact on the attitudes of people toward masks and their intention to wear them, and the persuasion effect of gain-framed messages was higher than that of loss-framed messages. (2) Gender, income, occupation, educational background, and residence have no significant difference in attitude and intention to wear masks. There was a significant correlation between age and wearing of masks (p = 0.041 < 0.05). (3) Social norms affected people's perception of information framing and their attitude toward wearing masks, but only the impact of loss-framed messages on intention was significant. (4) Information framing affected people's perception of information credibility, which had a positive impact on their intention to wear masks;however, information credibility only had a significant impact on attitude toward wearing masks under the gain-framed messages and played an intermediary role. Conclusion The impact of information framing on the attitude of people toward masks and their intention to wear them varies. Individuals involved in the publicity of health information related to this issue should pay attention to the influence of information framing and content on the public wearing masks as a means of enhancing public health awareness.

The Uptake and Vaccination Willingness of COVID-19 Vaccine among Chinese Residents: Web-Based Online Cross-Sectional Study.

OBJECTIVE: To investigate the uptake and vaccination willingness of the COVID-19 vaccine among Chinese residents and analyze the difference and factors that impact vaccination. METHODS: The snowball sampling method was used to distribute online questionnaires. Relevant sociodemographic data along with the circumstances of COVID-19 vaccination were collected from the respondents. The χ2 test, independent samples t test and binary logistic regression analysis were used to analyze the data. RESULTS: Among 786 respondents, 84.22% had been vaccinated. Over 80% of the vaccinated population have completed all the injections because of supporting the national vaccination policies of China, while the unvaccinated population (23.91%) is mainly due to personal health status. Meanwhile, statistical analysis revealed that the main predictors of not being vaccinated were younger age (3 to 18 years old), personal health status, and lower vaccinated proportion of family members and close friends (p < 0.05). CONCLUSIONS: There was a high level of uptake of the COVID-19 vaccine in China, and people who have not been vaccinated generally had a low willingness to vaccinate in the future. Based on our results, it suggested the next work to expand the coverage of the COVID-19 vaccination should be concentrated on targeted publicity and education for people who have not been vaccinated.

Recognition efficiency of atypical cardiovascular readings on ECG devices through fogged goggles.

In their continuing battle against the COVID-19 pandemic, medical workers in hospitals worldwide need to wear safety glasses and goggles to protect their eyes from the possible transmission of the virus. However, they work for long hours and need to wear a mask and other personal protective equipment, which causes their protective eye wear to fog up. This fogging up of eye wear, in turn, has a substantial impact in the speed and accuracy of reading information on the interface of electrocardiogram (ECG) machines. To gain a better understanding of the extent of the impact, this study experimentally simulates the fogging of protective goggles when viewing the interface with three variables: the degree of fogging of the goggles, brightness of the screen, and color of the font of the cardiovascular readings. This experimental study on the target recognition of digital font is carried out by simulating the interface of an ECG machine and readability of the ECG machine with fogged eye wear. The experimental results indicate that the fogging of the lenses has a significant impact on the recognition speed and the degree of fogging has a significant correlation with the font color and brightness of the screen. With a reduction in screen brightness, its influence on recognition speed shows a v-shaped trend, and the response time is the shortest when the screen brightness is 150 cd/m2. When eyewear is fogged, yellow and green font colors allow a quicker response with a higher accuracy. On the whole, the subjects show a better performance with the use of green font, but there are inconsistencies. In terms of the interaction among the three variables, the same results are also found and the same conclusion can be made accordingly. This research study can act as a reference for the interface design of medical equipment in events where medical staff wear protective eyewear for a long period of time.

Oral etoposide combined with oral arsenic plus retinoic acid for two cases with newly diagnosed high-risk acute promyelocytic leukemia during COVID19 pandemic.

Acute promyelocytic leukemia (APL) is a highly curable hematology malignancy. The major factor influence prognosis of APL is early deaths (ED) during the course of induction therapy, especially in high-risk APL. Therefore, effective reduction of white blood cells and correction of coagulation abnormalities are the key points of treatment for high-risk APL. Due to COVID19 pandemic in China since Jan 2020, some patients with hematologic malignancies suspected of COVID-19 infection had been isolated and traditional intravenous chemotherapy drugs is not available in isolated wards. We had explored a regimen of an oral etoposide to reduce the tumor burden for high-risk APL and dual induction with retinoic acid (ATRA) and oral arsenic realgar-Indigo nautralis formula (RIF), and finally two cases of high-risk APL patients received complete remission in one month. It is indicated that pure oral induction regimen: oral etoposide, ATRA and RIF provides a novel therapy in outpatient clinics.

Face masks as a source of nanoplastics and microplastics in the environment: Quantification, characterization, and potential for bioaccumulation.

Billions of disposable face masks are consumed daily due to the COVID-19 pandemic. The role of these masks as a source of nanoplastics (NPs) and microplastics (MPs) in the environment has not been studied in previous studies. We quantified and characterized face mask released particles and evaluated their potential for accumulation in humans and marine organisms. More than one billion of NPs and MPs were released from each surgical or N95 face mask. These irregularly-shaped particles sized from c. 5 nm to c. 600 µm. But most of them were nano scale sized <1 µm. The middle layers of the masks had released more particles than the outer and inner layers. That MPs were detected in the nasal mucus of mask wearers suggests they can be inhaled while wearing a mask. Mask released particles also adsorbed onto diatom surfaces and were ingested by marine organisms of different trophic levels. This data is useful for assessing the health and environmental risks of face masks.

Does Mutual Fund Illiquidity Introduce Fragility into Asset Prices? Evidence from the Corporate Bond Market

Open-end corporate bond mutual funds invest in illiquid assets while providing liquid claims to shareholders. Does such liquidity transformation introduce fragility to the corporate bond market? To address this question, we create a novel bond-level latent fragility measure based on asset illiquidity of mutual funds holding the bond. We find that corporate bonds bearing higher fragility subsequently experience higher return volatility and more outflows-induced mutual fund selling over the period of 2006–2019. Using the COVID-19 crisis as a natural experiment, we find that bonds with higher precrisis fragility experienced more negative returns and larger reversals around March 2020.

Comparison of Public Responses to Containment Measures During the Initial Outbreak and Resurgence of COVID-19 in China: Infodemiology Study.

BACKGROUND: COVID-19 cases resurged worldwide in the second half of 2020. Not much is known about the changes in public responses to containment measures from the initial outbreak to resurgence. Monitoring public responses is crucial to inform policy measures to prepare for COVID-19 resurgence. OBJECTIVE: This study aimed to assess and compare public responses to containment measures during the initial outbreak and resurgence of COVID-19 in China. METHODS: We curated all COVID-19-related posts from Sina Weibo (China's version of Twitter) during the initial outbreak and resurgence of COVID-19 in Beijing, China. With a Python script, we constructed subsets of Weibo posts focusing on 3 containment measures: lockdown, the test-trace-isolate strategy, and suspension of gatherings. The Baidu open-source sentiment analysis model and latent Dirichlet allocation topic modeling, a widely used machine learning algorithm, were used to assess public engagement, sentiments, and frequently discussed topics on each containment measure. RESULTS: A total of 8,985,221 Weibo posts were curated. In China, the containment measures evolved from a complete lockdown for the general population during the initial outbreak to a more targeted response strategy for high-risk populations during COVID-19 resurgence. Between the initial outbreak and resurgence, the average daily proportion of Weibo posts with negative sentiments decreased from 57% to 47% for the lockdown, 56% to 51% for the test-trace-isolate strategy, and 55% to 48% for the suspension of gatherings. Among the top 3 frequently discussed topics on lockdown measures, discussions on containment measures accounted for approximately 32% in both periods, but those on the second-most frequently discussed topic shifted from the expression of negative emotions (11%) to its impacts on daily life or work (26%). The public expressed a high level of panic (21%) during the initial outbreak but almost no panic (1%) during resurgence. The more targeted test-trace-isolate measure received the most support (60%) among all 3 containment measures in the initial outbreak, and its support rate approached 90% during resurgence. CONCLUSIONS: Compared to the initial outbreak, the public expressed less engagement and less negative sentiments on containment measures and were more supportive toward containment measures during resurgence. Targeted test-trace-isolate strategies were more acceptable to the public. Our results indicate that when COVID-19 resurges, more targeted test-trace-isolate strategies for high-risk populations should be promoted to balance pandemic control and its impact on daily life and the economy.

Deep learning for COVID-19 chest CT (computed tomography) image analysis: A lesson from lung cancer.

As a recent global health emergency, the quick and reliable diagnosis of COVID-19 is urgently needed. Thus, many artificial intelligence (AI)-base methods are proposed for COVID-19 chest CT (computed tomography) image analysis. However, there are very limited COVID-19 chest CT images publicly available to evaluate those deep neural networks. On the other hand, a huge amount of CT images from lung cancer are publicly available. To build a reliable deep learning model trained and tested with a larger scale dataset, the proposed model builds a public COVID-19 CT dataset, containing 1186 CT images synthesized from lung cancer CT images using CycleGAN. Additionally, various deep learning models are tested with synthesized or real chest CT images for COVID-19 and Non-COVID-19 classification. In comparison, all models achieve excellent results in accuracy, precision, recall and F1 score for both synthesized and real COVID-19 CT images, demonstrating the reliable of the synthesized dataset. The public dataset and deep learning models can facilitate the development of accurate and efficient diagnostic testing for COVID-19.

Cross-Country Comparison of Public Awareness, Rumors, and Behavioral Responses to the COVID-19 Epidemic: Infodemiology Study.

BACKGROUND: Understanding public behavioral responses to the coronavirus disease (COVID-19) epidemic and the accompanying infodemic is crucial to controlling the epidemic. OBJECTIVE: The aim of this study was to assess real-time public awareness and behavioral responses to the COVID-19 epidemic across 12 selected countries. METHODS: Internet surveillance was used to collect real-time data from the general public to assess public awareness and rumors (China: Baidu; worldwide: Google Trends) and behavior responses (China: Ali Index; worldwide: Google Shopping). These indices measured the daily number of searches or purchases and were compared with the numbers of daily COVID-19 cases. The trend comparisons across selected countries were observed from December 1, 2019 (prepandemic baseline) to April 11, 2020 (at least one month after the governments of selected countries took actions for the pandemic). RESULTS: We identified missed windows of opportunity for early epidemic control in 12 countries, when public awareness was very low despite the emerging epidemic. China's epidemic and the declaration of a public health emergency of international concern did not prompt a worldwide public reaction to adopt health-protective measures; instead, most countries and regions only responded to the epidemic after their own case counts increased. Rumors and misinformation led to a surge of sales in herbal remedies in China and antimalarial drugs worldwide, and timely clarification of rumors mitigated the rush to purchase unproven remedies. CONCLUSIONS: Our comparative study highlights the urgent need for international coordination to promote mutual learning about epidemic characteristics and effective control measures as well as to trigger early and timely responses in individual countries. Early release of official guidelines and timely clarification of rumors led by governments are necessary to guide the public to take rational action.

The influence of coronavirus disease 2019 on emergency department visits in Nanjing, China: A multicentre cross-sectional study.

INTRODUCTION: Influenza has been linked to the crowding in emergency departments (ED) across the world. The impact of the Coronavirus Disease 2019 (COVID-19) pandemic on China EDs has been quite different from those during past influenza outbreaks. Our objective was to determine if COVID-19 changed ED visit disease severity during the pandemic. METHODS: This was a retrospective cross sectional study conducted in Nanjing, China. We captured ED visit data from 28 hospitals. We then compared visit numbers from October 2019 to February 2020 for a month-to-month analysis and every February from 2017 to 2020 for a year-to-year analysis. Inter-group chi-square test and time series trend tests were performed to compare visit numbers. The primary outcome was the proportion of severe disease visits in the EDs. RESULTS: Through February 29 th 2020, there were 93 laboratory-confirmed COVID-19 patients in Nanjing, of which 40 cases (43.01%) were first seen in the ED. The total number of ED visits in Nanjing in February 2020, were dramatically decreased (n = 99,949) in compared to January 2020 (n = 313,125) and February 2019 (n = 262,503). Except for poisoning, the severe diseases in EDs all decreased in absolute number, but increased in proportion both in year-to-year and month-to-month analyses. This increase in proportional ED disease severity was greater in higher-level referral hospitals when compared year by year. CONCLUSION: The COVID-19 outbreak has been associated with decreases in ED visits in Nanjing, China, but increases in the proportion of severe ED visits.

Clinical imaging characteristics of inpatients with coronavirus disease-2019 in Heilongjiang Province, China: a retrospective study.

OBJECTIVE: To investigate the clinical, laboratory, and radiological characteristics of patients with coronavirus disease-2019 (COVID-19) in Heilongjiang Province. RESULTS: Patients in the ICU group were older and their incidence of cardiovascular disease was higher than those in the non-ICU group. Lymphocyte levels were lower and neutrophil and D-dimer levels were higher in the ICU than that in the non-ICU group. Compared to the non-ICU group, the incidence of pulmonary consolidation and ground-glass opacity with consolidation was significantly higher in the ICU group, all lung lobes were more likely to be involved, with higher number of lung lobes and areas surrounding the bronchi. Of the 59 patients with COVID-19 in this group, 15 received mechanical ventilation. All intubated patients involved lung lobes, and a large number of lesions were observed in the area around the bronchial vessels. CONCLUSION: Significant differences were observed in clinical symptoms, laboratory tests, and computed tomography features between the ICU and non-ICU groups. METHODS: A total of 59 patients with COVID-19, comprising 44 patients in the intensive care unit (ICU) and 15 in the non-ICU, were retrospectively analyzed. Characteristics of the two groups of patients were compared.

CT findings of severe novel coronavirus disease (COVID-19): A case report of Heilongjiang Province, China.

2019 novel coronavirus disease (COVID-19, previously known as novel coronavirus pneumonia) was first discovered in December 2019 and spread widely in China and all over the world in 2020. The initial symptoms of most patients include fever, cough, and fatigue. Dyspnea may occur with the progress of the disease, and acute respiratory distress syndrome may occur in severe cases. The CT manifestations of this disease are mainly ground-glass opacity (GGO) in the lung, which may be accompanied by patchy consolidation, and fibrous changes may appear in the lung at the later stage of the disease. Combined with typical clinical and imaging findings and positive nucleic acid test results, the disease can be diagnosed. We report the first case of novel coronavirus disease (COVID-19) in Heilongjiang Province, China. The patient was seriously ill, who felt that he suffered from fever, fatigue, cough, and expectoration and sought medical treatment, with a history of contact with Wuhan. The leukocyte count was normal, and the lymphocyte count was decreased. CT imaging showed large GGO and partial patchy consolidation in both lungs. The patient recovered and was discharged after 26 days of treatment. This study is helpful for early diagnosis and timely clinical management by mastering the typical imaging of novel coronavirus disease (COVID-19).