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1.
Cell Host Microbe ; 2022 Nov 04.
Article in English | MEDLINE | ID: covidwho-2104545

ABSTRACT

Humanity has faced three recent outbreaks of novel betacoronaviruses, emphasizing the need to develop approaches that broadly target coronaviruses. Here, we identify 55 monoclonal antibodies from COVID-19 convalescent donors that bind diverse betacoronavirus spike proteins. Most antibodies targeted an S2 epitope that included the K814 residue and were non-neutralizing. However, 11 antibodies targeting the stem helix neutralized betacoronaviruses from different lineages. Eight antibodies in this group, including the six broadest and most potent neutralizers, were encoded by IGHV1-46 and IGKV3-20. Crystal structures of three antibodies of this class at 1.5-1.75-Å resolution revealed a conserved mode of binding. COV89-22 neutralized SARS-CoV-2 variants of concern including Omicron BA.4/5 and limited disease in Syrian hamsters. Collectively, these findings identify a class of IGHV1-46/IGKV3-20 antibodies that broadly neutralize betacoronaviruses by targeting the stem helix but indicate these antibodies constitute a small fraction of the broadly reactive antibody response to betacoronaviruses after SARS-CoV-2 infection.

2.
Mol Immunol ; 152: 215-223, 2022 Nov 03.
Article in English | MEDLINE | ID: covidwho-2095806

ABSTRACT

Identification of immunologic epitopes against SARS-CoV-2 is crucial for the discovery of diagnostic, therapeutic, and preventive targets. In this study, we used a pan-coronavirus peptide microarray to screen for potential B-cell epitopes and validated the results with peptide-based ELISA. Specifically, we identified three linear B-cell epitopes on the SARS-CoV-2 proteome, which were recognized by convalescent plasma from COVID-19 patients. Interestingly, two epitopes (S 809-823 and R1ab 909-923) strongly reacted to convalescent plasma collected at the early phase (< 90 days) of COVID-19 symptom onset, whereas one epitope (M 5-19) reacted to convalescent plasma collected > 90 days after COVID-19 symptom onset. Neutralization assays using antibody depletion with the identified spike (S) peptides revealed that three S epitopes (S 557-571, S 789-803, and S 809-823) elicited neutralizing antibodies in COVID-19 patients. However, the levels of virus-specific antibody targeting S 789-803 only positively correlated with the neutralizing rates at the early phase (<60 days) after disease onset, and the antibody titers diminished quickly with no correlation to the neutralizing activity beyond two months after recovery from COVID-19. Importantly, stimulation of peripheral blood mononuclear cells from COVID-19-recovered patients with these SARS-CoV-2 S peptides resulted in poor virus-specific B cell activation, proliferation, differentiation into memory B cells, and production of immunoglobulin G (IgG) antibodies, despite the B-cells being functionally competent as demonstrated by their response to non-specific stimulation. Taken together, these findings indicate that these newly identified SARS-CoV-2-specific B-cell epitopes can elicit neutralizing antibodies, with titers and/or neutralizing activities declining significantly within 2-3 months in the convalescent plasma of COVID-19 patients.

3.
Cell Discov ; 8(1): 114, 2022 Oct 21.
Article in English | MEDLINE | ID: covidwho-2087192

ABSTRACT

SARS-CoV-2 vaccine booster dose can induce a robust humoral immune response, however, its cellular mechanisms remain elusive. Here, we investigated the durability of antibody responses and single-cell immune profiles following booster dose immunization, longitudinally over 6 months, in recipients of a homologous BBIBP-CorV/BBIBP-CorV or a heterologous BBIBP-CorV/ZF2001 regimen. The production of neutralizing antibodies was dramatically enhanced by both booster regimens, and the antibodies could last at least six months. The heterologous booster induced a faster and more robust plasmablast response, characterized by activation of plasma cells than the homologous booster. The response was attributed to recall of memory B cells and the de novo activation of B cells. Expanded B cell clones upon booster dose vaccination could persist for months, and their B cell receptors displayed accumulated mutations. The production of antibody was positively correlated with antigen presentation by conventional dendritic cells (cDCs), which provides support for B cell maturation through activation and development of follicular helper T (Tfh) cells. The proper activation of cDC/Tfh/B cells was likely fueled by active energy metabolism, and glutaminolysis might also play a general role in promoting humoral immunity. Our study unveils the cellular mechanisms of booster-induced memory/adaptive humoral immunity and suggests potential strategies to optimize vaccine efficacy and durability in future iterations.

4.
Int J Environ Res Public Health ; 19(19)2022 Sep 28.
Article in English | MEDLINE | ID: covidwho-2065946

ABSTRACT

Physical activity (PA) and sleep are both important to mental health. However, their joint effects on mental distress have not been well explored. The aim of this study was to investigate the joint effects of PA and sleep on mental health, as well as the dose-response relationships between PA and mental health under different sleep health statuses. A longitudinal panel study was adopted to evaluate the relationship between PA, sleep, and mental health among 66 healthy Chinese college students with four online questionnaire surveys. A mixed-effect model with individual-level random effect was used to analyze the interactive regulation effect of PA and sleep on mental health, and a generalized additive model with splines was further fitted to analyze dose-response relationships between variables. When sleep was at a healthy level, no significant difference in mental health was observed between different levels of PA (p > 0.05). However, poor sleepers with moderate and high PA levels indicated significantly fewer negative emotions than those with low PA levels (p = 0.001, p = 0.004). Likewise, poor sleepers who engaged in more moderate intensity PA could significantly reduce negative emotions (ß = -0.470, p = 0.011) in a near-linear trend. In summary, both sleep and PA benefit mental health, and they probably regulate mental health through an interactive compensation mode. For good and poor sleepers, PA plays a different role in maintaining and improving mental health. Increasing moderate intensity PA up to moderate-and-high levels is recommended for those who simultaneously suffer from sleep and psychological health problems.


Subject(s)
COVID-19 , Mental Health , COVID-19/epidemiology , China/epidemiology , Exercise , Humans , Pandemics , Sleep/physiology , Students/psychology
5.
British Journal of Educational Technology ; 53(6):2012-2028, 2022.
Article in English | Academic Search Complete | ID: covidwho-2063594

ABSTRACT

Generating written explanations is a popular learning strategy in an online learning environment. Students can explain to themselves (ie, self‐explanations) or a peer‐student (ie, instructional explanations). However, for improving learning from video lectures, it is unclear whether writing self‐explanations is more beneficial than writing instructional explanations, and whether writing both types of explanation is more beneficial than writing only one type. We compared the learning‐related outcomes of students who wrote explanations under one of four conditions: self‐explanation (n = 30), instructional explanation (n = 30), self‐explanation then instructional explanation (n = 30) and instructional explanation then self‐explanation (n = 30). We assessed the participants' external and internal attention, explanation quality, and immediate and delayed learning performance. Students in the conditions that included self‐explanations showed higher internal attention, as well as better immediate and delayed performance than those in the instructional explanations condition. In addition, students in the two combined conditions showed a higher level of organization and elaboration than those in the instructional explanations condition. These results suggest that students should write explanations to themselves while learning from video lectures. Practitioner notesWhat is already known about this topic Generating explanations is a beneficial learning strategy.It is unclear whether explaining to oneself (self‐explanations) is more beneficial than explaining to a peer (instructional explanations).The benefits of writing instructional explanations on learning performance were not consistently found across diverse areas.What this paper adds Self‐explanations, both in oral and written form, were more effective for learning performance than instructional explanations.Students in the conditions that included both self‐explanations and instructional explanations demonstrated a higher level of organization and elaboration than those in the instructional explanation condition.When compared to the self‐explanations condition, additional instructional explanations had no effect on learning performance or internal attention.Implications for practice and/or policy Self‐explanations was an excellent approach for learning from video lectures.Students should write explanations to themselves while learning from video lectures. [ FROM AUTHOR] Copyright of British Journal of Educational Technology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

6.
Emerg Microbes Infect ; 11(1): 2636-2644, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-2062779

ABSTRACT

ABSTRACTA wave of Omicron infections rapidly emerged in China in 2022, but large-scale data concerning the safety profile of vaccines and Coronavirus disease 2019 (COVID-19) infection features in liver transplant (LT) recipients have not been collected. Therefore, the aim of this study was to assess the protectiveness and safety profile of the inactivated vaccines in LT patients against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant infections. A multi-centre retrospective study was conducted in a cohort with a history of liver transplantation. A total of 1881 participants (487 vaccinated and 1394 unvaccinated patients) were enrolled from seven centres in China. Fourteen of the participants were infected by Omicron, and 50% patients had over 14 days of viral shedding duration. The protection rate of COVID-19 vaccinations to Omicron was 2.59%. The three breakthrough infections occurred more than 6 months after fully vaccinated. A total of 96 (19.7%) vaccinated patients had adverse events, including fatigue, myalgia, liver dysfunction, swelling, and scleroma. There were more Grade 3 adverse events in the preoperative vaccination group than those in the postoperative vaccination group. Inactivated whole-virion SARS-CoV-2 vaccines are safe in patients with post-liver transplantation. The efficacy of inactivated vaccines decreases after 6 months of vaccination, it is recommended that liver transplant patients get boosted vaccinations as early as possible even when they are fully vaccinated. Although clinical manifestations of Omicron infections were mild in LT patients, unvaccinated patients might have a higher risk of liver dysfunction during infections.


Subject(s)
COVID-19 Vaccines , COVID-19 , Liver Transplantation , Humans , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Retrospective Studies , SARS-CoV-2 , Vaccination , Vaccines, Inactivated/adverse effects
7.
Talanta ; 253: 123978, 2022 Oct 04.
Article in English | MEDLINE | ID: covidwho-2061902

ABSTRACT

Recently, sensitive, fast and low cost nucleic acid isothermal amplification technologies (such as loop-mediated isothermal amplification, LAMP) have attracted great attention in the urgent needs of point-of-care testing (POCT) and regular epidemic prevention and control. However, unlike PCR which usually employs TaqMan probe to report specific signals, specific-signal-output strategies in isothermal amplification are immature and visual detection even rare, which limits their popularity in POCT. We hypothesize to address this issue by designing a visual-signal-report system to both filtrate and magnify the target information in isothermal amplification. In this work, we developed a specific signal filtration and magnification colorimetric isothermal sensing platform (SFMC for short) for ultrasensitive detection of DNA and RNA. SFMC consists of two processes: an isothermal amplification with specific signal filtration and a self-replication catalyzed hairpin assembly (SRCHA) for rapid target-specific signal magnification and outputting. With these unique properties, this biosensing platform could detect target DNA as low as 5 copies per reaction and target RNA as low as 10 copies per reaction by naked eyes. Benefited from the excellent colorimetric detection performance, this biosensing platform has been successfully used for African swine fever virus (ASFV) and SARS-CoV-2 detection.

8.
Frontiers in psychiatry ; 13, 2022.
Article in English | EuropePMC | ID: covidwho-2045528

ABSTRACT

Background Quarantine as one of the most effective epidemic prevention measures, significantly increased people's stress levels. Ongoing monitoring of the stress status of people under quarantine during the pandemic is an important part of assessing the long-term impact of COVID-19 on mental health. This study aimed to gain a more comprehensive understanding of the stress status of people under quarantine, including perceived stress and stress responses, during the third year of the COVID-19 pandemic in China. Methods An anonymous online survey was conducted among 464 participants from 39 cities in China from March 31 to April 12, 2022. The survey included three questionnaires: a self-designed questionnaire collecting demographic information and quarantine characteristics, the Perceived Stress Scale (PSS-10) and the Stress Response Questionnaire (SRQ). The t-test or one-way ANOVA or the Welch F-test were used to examine the differences among demographic and quarantine variables of perceived stress and stress responses, then multiple linear regressions were performed to identify the predictors of perceived stress and stress responses. Results 428 valid respondents were finally included. The average scores of perceived stress, total stress response, emotional response, physical response, and behavioral response were 14.70 ± 7.02, 50.24 ± 22.48, 20.35 ± 9.99, 15.23 ± 7.25, and 11.39 ± 5.27, respectively. The regression analysis showed that the degree of financial worries and days of continuous quarantine were the predictors of perceived stress. The degree of financial worries was a vital factor in predicting total stress response, emotional response, physical response and behavioral response, and in predicting emotional response, age was also a significant predictor. Conclusion The stress status of individuals under quarantine was generally stable but still needs further attention during the third year of the COVID-19 pandemic. People who are young, have a high degree of financial worries and have been quarantined for a long time may be at a higher risk of perceived stress and stress responses. Relevant authorities should pay closer attention to the risk groups, and additional support and assistance might be required for those mostly worried about their financial situations under quarantine.

9.
Jpn J Infect Dis ; 75(5): 511-518, 2022 Sep 22.
Article in English | MEDLINE | ID: covidwho-2040398

ABSTRACT

To estimate the effect of the corona virus disease 2019 (COVID-19) control measures taken to mitigate community transmission in many regions, we analyzed data from the influenza surveillance system in Beijing from week 27 of 2014 to week 26 of 2020. We collected weekly numbers of influenza-like illness (ILI) cases, weekly positive proportion of ILI cases, weekly ILI case proportion in outpatients, and the dates of implementation of COVID-19 measures. We compared the influenza activity indicators of the 2019/2020 season with the preceding five seasons and built two ARIMAX models to estimate the effectiveness of COVID-19 measures declared since January 24, 2020 by the emergency response. Based on the observed data, compared to the preceding five influenza seasons, ILIs, positive proportion of ILIs, and duration of the influenza epidemic period in 2019/2020 had increased from 13% to 54%; in particular, the number of weeks from the peak to the end of the influenza epidemic period had decreased from 12 to 1. According to ARIMAX model forecasting, after considering natural decline, weekly ILIs had decreased by 48.6%, weekly positive proportion had dropped by 15% in the second week after the emergency response was declared, and COVID-19 measures had reduced by 83%. We conclude that the public health emergency response can significantly interrupt the transmission of influenza.


Subject(s)
COVID-19 , Influenza, Human , Virus Diseases , Beijing/epidemiology , COVID-19/epidemiology , Humans , Influenza, Human/epidemiology , Influenza, Human/prevention & control , Public Health , Seasons
10.
Transl Neurodegener ; 11(1): 39, 2022 08 23.
Article in English | MEDLINE | ID: covidwho-2038939

ABSTRACT

Furin is an important mammalian proprotein convertase that catalyzes the proteolytic maturation of a variety of prohormones and proproteins in the secretory pathway. In the brain, the substrates of furin include the proproteins of growth factors, receptors and enzymes. Emerging evidence, such as reduced FURIN mRNA expression in the brains of Alzheimer's disease patients or schizophrenia patients, has implicated a crucial role of furin in the pathophysiology of neurodegenerative and neuropsychiatric diseases. Currently, compared to cancer and infectious diseases, the aberrant expression of furin and its pharmaceutical potentials in neurological diseases remain poorly understood. In this article, we provide an overview on the physiological roles of furin and its substrates in the brain, summarize the deregulation of furin expression and its effects in neurodegenerative and neuropsychiatric disorders, and discuss the implications and current approaches that target furin for therapeutic interventions. This review may expedite future studies to clarify the molecular mechanisms of furin deregulation and involvement in the pathogenesis of neurodegenerative and neuropsychiatric diseases, and to develop new diagnosis and treatment strategies for these diseases.


Subject(s)
Furin , Neurodegenerative Diseases , Animals , Furin/genetics , Furin/physiology , Humans , Proprotein Convertases/genetics
11.
Nat Chem Biol ; 2022 Sep 22.
Article in English | MEDLINE | ID: covidwho-2036839

ABSTRACT

Clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 13 (Cas13) has been rapidly developed for nucleic-acid-based diagnostics by using its characteristic collateral activity. Despite the recent progress in optimizing the Cas13 system for the detection of nucleic acids, engineering Cas13 protein with enhanced collateral activity has been challenging, mostly because of its complex structural dynamics. Here we successfully employed a novel strategy to engineer the Leptotrichia wadei (Lwa)Cas13a by inserting different RNA-binding domains into a unique active-site-proximal loop within its higher eukaryotes and prokaryotes nucleotide-binding domain. Two LwaCas13a variants showed enhanced collateral activity and improved sensitivity over the wild type in various buffer conditions. By combining with an electrochemical method, our variants detected the SARS-CoV-2 genome at attomolar concentrations from both inactive viral and unextracted clinical samples, without target preamplification. Our engineered LwaCas13a enzymes with enhanced collateral activity are ready to be integrated into other Cas13a-based platforms for ultrasensitive detection of nucleic acids.

12.
Frontiers in psychiatry ; 13, 2022.
Article in English | EuropePMC | ID: covidwho-2034050

ABSTRACT

Objective To investigate the incidence of post-traumatic stress disorder (PTSD), turnover intention and psychological resilience of medical staff during the Outbreak of the Omicron Variant in the COVID-19 pandemic in 2022 and to provide a basis for adopting relevant psychological interventions to reduce medical staff turnover. Methods Using the PTSD Checklist-Civilian Version (PCL-C) and a total score ranging from 17 to 85 points, a total score ≥ 38 indicates significant PTSD symptoms and a diagnosis of PTSD. The Chinese version of the Turnover Intention Scale (TIS) has a total score of 6 to 24 points;the higher the score, the stronger the turnover intention. The Chinese version of the Connor-Davidson Resilience Scale (CD-RISC) has a total score of 0 to 100 points, with higher scores indicating a better level of psychological resilience. A total of 443 front-line medical staff working in Chinese public hospitals and still treating all patients normally during COVID-19 were invited via the internet to complete a survey from 15 May to 30 May 2022 in China. Results The incidence of PTSD was 14.4%, the total turnover intention score was 13.38 ± 4.08, and the total psychological resilience score was 87.16 ± 18.42. The prevalence of PTSD was higher among medical staff who were married, had children, and were worried about being infected;in addition, the PTSD group had a higher level of education, higher turnover intention, and lower psychological resilience than the non-PTSD group. The total scores for turnover intention and fear of being infected were risk factors for PTSD, while a high total psychological resilience score and high education level were protective factors for PTSD;the differences were statistically significant (all P < 0.05). Conclusion Post-traumatic stress disorder among Chinese medical personnel was associated with the marital status, childbirth, education level, turnover intention, and psychological resilience. Among these factors, psychological resilience might be exploited as a protective factor.

13.
Emerg Microbes Infect ; 11(1): 2501-2509, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-2028962

ABSTRACT

To further describe the effect of the "fragile population" and their "higher-risk" comorbidities on prognosis among hospitalized Omicron patients, this observational cohort study enrolled hospitalized patients confirmed with SARS-CoV-2 during the 2022 Omicron wave in Shanghai, China. The primary outcome was progression to severe or critical cases. The secondary outcome was viral shedding time from the first positive SARS-CoV-2 detection. A total of 847 participants were enrolled, most of whom featured as advanced age (>70 years old: 30.34%), not fully vaccinated (55.84%), combined with at least 1 comorbidity (65.41%). Multivariate cox regression suggested age >70 years old (aHR[95%CI] 0.78[0.61-0.99]), chronic kidney disease (CKD) stage 4-5 (aHR[95%CI] 0.61[0.46-0.80]), heart conditions (aHR[95%CI] 0.76[0.60-0.97]) would elongate viral shedding time and fully/booster vaccination (aHR[95%CI] 1.4 [1.14-1.72]) would shorten this duration. Multivariate logistic regression suggested CKD stage 4-5 (aHR[95%CI] 3.21[1.45-7.27]), cancer (aHR[95%CI] 9.52[4.19-22.61]), and long-term bedridden status (aHR[95%CI] 4.94[2.36-10.44]) were the "higher" risk factor compared with the elderly, heart conditions, metabolic disorders, isolated hypertension, etc. for severity while female (aHR[95%CI] 0.34[0.16-0.68]) and fully/booster Vaccination (aHR[95%CI] 0.35[0.12-0.87]) could provide protection from illness progression. CKD stage 4-5, cancer and long-term bedridden history were "higher-risk" factors among hospitalized Omicron patients for severity progression while full vaccination could provide protection from illness progression.


Subject(s)
COVID-19 , Neoplasms , Renal Insufficiency, Chronic , Humans , Female , Aged , SARS-CoV-2 , COVID-19/epidemiology , China , Cohort Studies , Comorbidity , Prognosis , Renal Insufficiency, Chronic/epidemiology , Neoplasms/epidemiology
14.
MedComm (2020) ; 3(3): e151, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-2013677

ABSTRACT

The main proteases (Mpro), also termed 3-chymotrypsin-like proteases (3CLpro), are a class of highly conserved cysteine hydrolases in ß-coronaviruses. Increasing evidence has demonstrated that 3CLpros play an indispensable role in viral replication and have been recognized as key targets for preventing and treating coronavirus-caused infectious diseases, including COVID-19. This review is focused on the structural features and biological function of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease Mpro (also known as 3CLpro), as well as recent advances in discovering and developing SARS-CoV-2 3CLpro inhibitors. To better understand the characteristics of SARS-CoV-2 3CLpro inhibitors, the inhibition activities, inhibitory mechanisms, and key structural features of various 3CLpro inhibitors (including marketed drugs, peptidomimetic, and non-peptidomimetic synthetic compounds, as well as natural compounds and their derivatives) are summarized comprehensively. Meanwhile, the challenges in this field are highlighted, while future directions for designing and developing efficacious 3CLpro inhibitors as novel anti-coronavirus therapies are also proposed. Collectively, all information and knowledge presented here are very helpful for understanding the structural features and inhibitory mechanisms of SARS-CoV-2 3CLpro inhibitors, which offers new insights or inspiration to medicinal chemists for designing and developing more efficacious 3CLpro inhibitors as novel anti-coronavirus agents.

15.
Scientometrics ; 127(9): 5227-5231, 2022.
Article in English | MEDLINE | ID: covidwho-2014327

ABSTRACT

Since the first Global Tech Mining (GTM) conference was held in Atlanta in 2011, the GTM conference has created a platform to connect tech mining researchers, exchange ideas and research progress, and promote collaborations. When it came to its 10th anniversary in 2020, COVID-19 forced the GTM conference into an online format. In tumultuous times for ST&I research activity, the GTM conference sought to focus on several issues: How to better collect and combine multiple "large data" sources? How to analyze these data effectively? And how to utilize these results more powerfully in ST&I management? In this collection, 15 papers are selected after evaluating by the science advisory committee, the guest editor team, and our peer review experts to address the following aspects regarding "tech mining": (1) DATA: Maximizing the potential of traditional and novel data; (2) METHODS: Advancing and integrating methods; (3) APPLICATIONS: Innovative analyses translating to usefulintelligence.

16.
Chin Med J (Engl) ; 135(14): 1756-1758, 2022 07 20.
Article in English | MEDLINE | ID: covidwho-2001465

Subject(s)
COVID-19 , Humans , Vaccination
17.
Nat Chem Biol ; 18(11): 1214-1223, 2022 11.
Article in English | MEDLINE | ID: covidwho-1991635

ABSTRACT

The E3 ligase TRIM7 has emerged as a critical player in viral infection and pathogenesis. However, the mechanism governing the TRIM7-substrate association remains to be defined. Here we report the crystal structures of TRIM7 in complex with 2C peptides of human enterovirus. Structure-guided studies reveal the C-terminal glutamine residue of 2C as the primary determinant for TRIM7 binding. Leveraged by this finding, we identify norovirus and SARS-CoV-2 proteins, and physiological proteins, as new TRIM7 substrates. Crystal structures of TRIM7 in complex with multiple peptides derived from SARS-CoV-2 proteins display the same glutamine-end recognition mode. Furthermore, TRIM7 could trigger the ubiquitination and degradation of these substrates, possibly representing a new Gln/C-degron pathway. Together, these findings unveil a common recognition mode by TRIM7, providing the foundation for further mechanistic characterization of antiviral and cellular functions of TRIM7.


Subject(s)
COVID-19 , Ubiquitin-Protein Ligases , Humans , Ubiquitin-Protein Ligases/metabolism , Glutamine/metabolism , SARS-CoV-2 , Ubiquitination , Antiviral Agents , Tripartite Motif Proteins/metabolism
18.
Angewandte Chemie ; 134(32), 2022.
Article in English | ProQuest Central | ID: covidwho-1981566

ABSTRACT

The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR‐associated (Cas) systems have recently received notable attention for their applications in nucleic acid detection. Despite many attempts, the majority of current CRISPR‐based biosensors in infectious respiratory disease diagnostic applications still require target preamplifications. This study reports a new biosensor for amplification‐free nucleic acid detection via harnessing the trans‐cleavage mechanism of Cas13a and ultrasensitive graphene field‐effect transistors (gFETs). CRISPR Cas13a‐gFET achieves the detection of SARS‐CoV‐2 and respiratory syncytial virus (RSV) genome down to 1 attomolar without target preamplifications. Additionally, we validate the detection performance using clinical SARS‐CoV‐2 samples, including those with low viral loads (Ct value >30). Overall, these findings establish our CRISPR Cas13a‐gFET among the most sensitive amplification‐free nucleic acid diagnostic platforms to date.

19.
Angewandte Chemie (International ed. in English) ; 61(32), 2022.
Article in English | EuropePMC | ID: covidwho-1980079

ABSTRACT

Nucleic acid detection plays a critical role in medical diagnostics, environmental monitoring, and food safety. In their Research Article (e202203826), Xue Gao, Yi Zhang and co‐workers developed a new biosensor for amplification‐free nucleic acid detection via harnessing the trans‐cleavage mechanism of Cas13a and ultrasensitive graphene field‐effect transistors (gFETs). The illustration shows the Cas13a‐mediated RNA trans‐cleavage on a gFET surface for sensor signal transduction.

20.
BMC Pulm Med ; 22(1): 304, 2022 Aug 08.
Article in English | MEDLINE | ID: covidwho-1976497

ABSTRACT

BACKGROUND: Noninvasive ventilation (NIV) has been widely used in critically ill patients after extubation. However, NIV failure is associated with poor outcomes. This study aimed to determine early predictors of NIV failure and to construct an accurate machine-learning model to identify patients at risks of NIV failure after extubation in intensive care units (ICUs). METHODS: Patients who underwent NIV after extubation in the eICU Collaborative Research Database (eICU-CRD) were included. NIV failure was defined as need for invasive ventilatory support (reintubation or tracheotomy) or death after NIV initiation. A total of 93 clinical and laboratory variables were assessed, and the recursive feature elimination algorithm was used to select key features. Hyperparameter optimization was conducted with an automated machine-learning toolkit called Neural Network Intelligence. A machine-learning model called Categorical Boosting (CatBoost) was developed and compared with nine other models. The model was then prospectively validated among patients enrolled in the Cardiac Surgical ICU of Zhongshan Hospital, Fudan University. RESULTS: Of 929 patients included in the eICU-CRD cohort, 248 (26.7%) had NIV failure. The time from extubation to NIV, age, Glasgow Coma Scale (GCS) score, heart rate, respiratory rate, mean blood pressure (MBP), saturation of pulse oxygen (SpO2), temperature, glucose, pH, pressure of oxygen in blood (PaO2), urine output, input volume, ventilation duration, and mean airway pressure were selected. After hyperparameter optimization, our model showed the greatest accuracy in predicting NIV failure (AUROC: 0.872 [95% CI 0.82-0.92]) among all predictive methods in an internal validation. In the prospective validation cohort, our model was also superior (AUROC: 0.846 [95% CI 0.80-0.89]). The sensitivity and specificity in the prediction group is 89% and 75%, while in the validation group they are 90% and 70%. MV duration and respiratory rate were the most important features. Additionally, we developed a web-based tool to help clinicians use our model. CONCLUSIONS: This study developed and prospectively validated the CatBoost model, which can be used to identify patients who are at risk of NIV failure. Thus, those patients might benefit from early triage and more intensive monitoring. TRIAL REGISTRATION: NCT03704324. Registered 1 September 2018, https://register. CLINICALTRIALS: gov .


Subject(s)
Machine Learning , Noninvasive Ventilation , Respiratory Insufficiency , Airway Extubation , Humans , Intensive Care Units , Noninvasive Ventilation/methods , Oxygen , Reproducibility of Results , Respiration, Artificial , Respiratory Insufficiency/etiology , Respiratory Insufficiency/therapy
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