A novel prediction model based on decomposition-integration and error correction for COVID-19 daily confirmed and death cases.

Coronavirus disease (COVID-19) has infected billion people around the world and affected the economy, but most countries are considering reopening, so the COVID-19 daily confirmed and death cases have increased greatly. It is very necessary to predict the COVID-19 daily confirmed and death cases in order to help every country formulate prevention policies. To enhance the prediction performance, this paper proposes a prediction model based on improved variational mode decomposition by sparrow search algorithm (SVMD), improved kernel extreme learning machine by Aquila optimizer algorithm (AO-KELM) and error correction idea, named SVMD-AO-KELM-error for short-term prediction of COVID-19 cases. Firstly, to solve mode number and penalty factor selection of variational mode decomposition (VMD), an improved VMD based on sparrow search algorithm (SSA), named SVMD, is proposed. SVMD decomposes the COVID-19 case data into some intrinsic mode function (IMF) components and residual is considered. Secondly, to properly selected regularization coefficients and kernel parameters of kernel extreme learning machine (KELM) and improve the prediction performance of KELM, an improved KELM by Aquila optimizer (AO) algorithm, named AO-KELM, is proposed. Each component is predicted by AO-KELM. Then, the prediction error of IMF and residual are predicted by AO-KELM to correct prediction results, which is error correction idea. Finally, prediction results of each component and error prediction results are reconstructed to get final prediction results. Through the simulation experiment of the COVID-19 daily confirmed and death cases in Brazil, Mexico, and Russia and comparison with twelve comparative models, simulation experiment gives that SVMD-AO-KELM-error has best prediction accuracy. It also proves that the proposed model can be used to predict the pandemic COVID-19 cases and offers a novel approach for COVID-19 cases prediction.

Analyzing the Impact of COVID-19 Lockdowns on Violent Crime.

Existing research suggests that COVID-19 lockdowns tend to contribute to a decrease in overall urban crime rates. Most studies have compared pre-lockdown and post-lockdown periods to lockdown periods in Western cities. Few have touched on the fine variations during lockdowns. Equally rare are intracity studies conducted in China. This study tested the relationship between violent crime and COVID-19 lockdown policies in ZG City in southern China. The distance from the isolation location to the nearest violent crime site, called "the nearest crime distance", is a key variable in this study. Kernel density mapping and the Wilcoxon signed-rank test are used to compare the pre-lockdown and post-lockdown periods to the lockdown period. Panel logistic regression is used to test the fine variations among different stages during the lockdown. The result found an overall decline in violent crime during the lockdown and a bounce-back post-lockdown. Violent crime moved away from the isolation location during the lockdown. This outward spread continued for the first two months after the lifting of the lockdown, suggesting a lasting effect of the lockdown policy. During the lockdown, weekly changes in COVID-19 risk ratings at the district level in ZG City also affected changes in the nearest crime distance. In particular, an increase in the risk rating increased that distance, and a drop in the risk rating decreased that distance. These findings add new results to the literature and could have policy implications for joint crime and pandemic prevention and control.

Has the COVID-19 pandemic affected nursing students' career self-efficacy and professional calling? The mediating impact of professional identity.

BACKGROUND: Professional calling (PC) is crucial for ascertaining their professional goals and fulfilling career choices in nursing students. Thus, understanding its antecedents and helping schools improve PC among nursing students is critical. This study aims to explore whether professional identity (PI), as a crucial antecedent of PC, acts as an intermediary between career self-efficacy (CSE) and professional calling during the COVID-19 pandemic. METHODS: A sample of 565 nursing students were selected by a web-based survey through convenience sampling. The study was conducted from October to November 2020. Measures of CSE, PI, and PC were assessed during the COVID-19 pandemic. We analyzed demographic data and the correlation of the research variables. The significance of the mediation effect was assessed using a bootstrap method with SPSS. RESULTS: CSE during the COVID-19 pandemic outbreak (r = 0. 359, p < 0. 01) and PI (r = 0. 670, p < 0. 01) were both relevant to PC among nursing students. In addition, CSE had a positive indirect effect on PC through PI (ß = 0. 288, p < 0. 05). CONCLUSIONS: Higher scores in CSE and a better PI were associated with PC in nursing students. Furthermore, a better CSE had an indirect effect on the PC of students through PI. The favorable evidence in our study confirms that nursing educators can adopt PI interventions to improve the sense of PC among nursing students.

Ginsenoside Rg5 allosterically interacts with P2RY12 and ameliorates deep venous thrombosis by counteracting neutrophil NETosis and inflammatory response.

Background: Deep venous thrombosis (DVT) highly occurs in patients with severe COVID-19 and probably accounted for their high mortality. DVT formation is a time-dependent inflammatory process in which NETosis plays an important role. However, whether ginsenoside Rg5 from species of Panax genus could alleviate DVT and its underlying mechanism has not been elucidated. Methods: The interaction between Rg5 and P2RY12 was studied by molecular docking, molecular dynamics, surface plasmon resonance (SPR), and molecular biology assays. The preventive effect of Rg5 on DVT was evaluated in inferior vena cava stasis-induced mice, and immunocytochemistry, Western blot, and calcium flux assay were performed in neutrophils from bone marrow to explore the mechanism of Rg5 in NETosis via P2RY12. Results: Rg5 allosterically interacted with P2RY12, formed stable complex, and antagonized its activity via residue E188 and R265. Rg5 ameliorated the formation of thrombus in DVT mice; accompanied by decreased release of Interleukin (IL)-6, IL-1ß, and tumor necrosis factor-α in plasma; and suppressed neutrophil infiltration and neutrophil extracellular trap (NET) release. In lipopolysaccharide- and platelet-activating factor-induced neutrophils, Rg5 reduced inflammatory responses via inhibiting the activation of ERK/NF-κB signaling pathway while decreasing cellular Ca2+ concentration, thus reducing the activity and expression of peptidyl arginine deiminase 4 to prevent NETosis. The inhibitory effect on neutrophil activity was dependent on P2RY12. Conclusions: Rg5 could attenuate experimental DVT by counteracting NETosis and inflammatory response in neutrophils via P2RY12, which may pave the road for its clinical application in the prevention of DVT-related disorders.

Structural and biochemical mechanism for increased infectivity and immune evasion of Omicron BA.2 variant compared to BA.1 and their possible mouse origins.

The Omicron BA.2 variant has become a dominant infective strain worldwide. Receptor binding studies show that the Omicron BA.2 spike trimer exhibits 11-fold and 2-fold higher potency in binding to human ACE2 than the spike trimer from the wildtype (WT) and Omicron BA.1 strains. The structure of the BA.2 spike trimer complexed with human ACE2 reveals that all three receptor-binding domains (RBDs) in the spike trimer are in open conformation, ready for ACE2 binding, thus providing a basis for the increased infectivity of the BA.2 strain. JMB2002, a therapeutic antibody that was shown to efficiently inhibit Omicron BA.1, also shows potent neutralization activities against Omicron BA.2. In addition, both BA.1 and BA.2 spike trimers are able to bind to mouse ACE2 with high potency. In contrast, the WT spike trimer binds well to cat ACE2 but not to mouse ACE2. The structures of both BA.1 and BA.2 spike trimer bound to mouse ACE2 reveal the basis for their high affinity interactions. Together, these results suggest a possible evolution pathway for Omicron BA.1 and BA.2 variants via a human-cat-mouse-human circle, which could have important implications in establishing an effective strategy for combating SARS-CoV-2 viral infections.

A general controllable release amplification strategy of liposomes for single-particle collision electrochemical biosensing.

As an important component of the COVID-19 mRNA vaccines, liposomes play a key role in the efficient protection and delivery of mRNA to cells. Herein, due to the controllable release amplification strategy of liposomes, a reliable and robust single-particle collision electrochemical (SPCE) biosensor was constructed for H9N2 avian influenza virus (H9N2 AIV) detection by combining liposome encapsulation-release strategy with immunomagnetic separation. The liposomes modified with biotin and loaded with platinum nanoparticles (Pt NPs) were used as signal probes for the first time. Biotin facilitated the coupling of biomolecules (DNA or antibodies) through the specific reaction of biotin-streptavidin. Each liposome can encapsulate multiple Pt NPs, which were ruptured under the presence of 1 × PBST (phosphate buffer saline with 0.05% Tween-20) within 2 min, and the encapsulated Pt NPs were released for SPCE experiment. The combination of immunomagnetic separation not only improved the anti-interference capabilities but also avoided the agglomeration of Pt NPs, enabling the SPCE biosensor to realize ultrasensitive detection of 18.1 fg/mL H9N2 AIV. Furthermore, the reliable SPCE biosensor was successfully applied in specific detection of H9N2 AIV in complex samples (chicken serum, chicken liver and chicken lung), which promoted the universality of SPCE biosensor and its application prospect in early diagnosis of diseases.

Study of the Inactivated COVID-19 Vaccine Contamination in Vaccination Sites — Zigong City, Sichuan Province, China, January, 2021

Vaccines are a crucial weapon in combating the global coronavirus disease 2019 (COVID-19) pandemic. At present, China is in a critical period of COVID-19 vaccination, and most of the approved vaccines are developed by inactivated vaccine technology, which contains the complete nucleic acid sequence of the virus (1-2). The inactivated COVID-19 vaccine may contaminate people and environments during the vaccination process, thus triggering a false alarm of the COVID-19 surveillance system. In this study, we selected some vaccination sites to assess the intensity and distribution of vaccine contamination.;;Before field study, we used Reverse Transcription-Polymerase Chain Reaction (RT-PCR) method with kits that produced by Da An Gene and ZJ Bio-Tech to estimate the signal strength of inactivated COVID-19 vaccine (SinovacBiotech). The average Cycle threshold (Ct) value of ORF1Ab /N gene of the vaccine solution was 15.30±0.77, while the Ct value of the kit’s positive control was 28.01±2.38.

An Easy-to-Understand Method to Construct Desired Distance-Like Measures

Metrics and their weaker forms are used to measure the difference between two data (or other things). There are many metrics that are available but not desired by a practitioner. This paper recommends in a plausible reasoning manner an easy-to-understand method to construct desired distance-like measures: to fuse easy-to-obtain (or easy to be coined by practitioners) pseudo-semi-metrics, pseudo-metrics, or metrics by making full use of well-known t-norms, t-conorms, aggregation operators, and similar operators (easy to be coined by practitioners). The simple reason to do this is that data for a real world problem are sometimes from multiagents. A distance-like notion, called weak interval-valued pseudo-metrics (briefly, WIVP-metrics), is defined by using known notions of pseudo-semi-metrics, pseudo-metrics, and metrics;this notion is topologically good and shows precision, flexibility, and compatibility than single pseudo-semi-metrics, pseudo-metrics, or metrics. Propositions and detailed examples are given to illustrate how to fabricate (including using what “material”) an expected or demanded WIVP-metric (even interval-valued metric) in practical problems, and WIVP-metric and its special cases are characterized by using axioms. Moreover, some WIVP-metrics pertinent to quantitative logic theory or interval-valued fuzzy graphs are constructed, and fixed point theorems and common fixed point theorems in weak interval-valued metric spaces are also presented. Topics and strategies for further study are also put forward concretely and clearly.

Malnutrition is associated with hyperinflammation and immunosuppression in COVID-19 patients: A prospective observational study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is spreading globally and has caused many deaths. This study investigated, for the first time, COVID-19 patients' nutrition status and its effects on their inflammatory and immune responses. METHODS: Forty-seven COVID-19 patients were recruited for this prospective study. According to the subjective global assessment at admission, patients were divided into the normal nutrition (NN), risk of malnutrition (RMN), or MN group. Serum cytokines and whole blood T-cell subpopulations were measured to assess the inflammatory and immune responses in COVID-19 patients. Analysis of covariance and χ2 tests were used. RESULTS: On admission, the incidences of MN and the RMN in COVID-19 patients were 17.0% and 38.3%, respectively. The MN group had a higher proportion with severe/critical COVID-19 and a longer hospitalization duration than the NN group. Serum interleukin (IL) 6 concentrations were elevated in 97.9% of the patients and were the highest in malnourished patients. The IL-4 and IL-10 levels were elevated in 46.8% and 48.9% of the patients, respectively. The proportion of CD8+ T cells was significantly lower in the MN group than in the NN group. CONCLUSION: A high proportion of COVID-19 patients are malnourished or at risk of malnuourishment, especially those with severe disease. MN is associated with hyperinflammation and immunosuppression in COVID-19 patients, and it may contribute to disease progression.

Positive reverse transcription-polymerase chain reaction assay results in patients recovered from COVID-19: Report of two cases.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has spread around the globe. On February 28, 2020, the World Health Organization adjusted the risk of spread and impact of COVID-19 to "very high" at the global level. Studies have mainly focused on the etiology, epidemiology, and treatment of COVID-19 to limit further spread and the negative impact of the disease, while less attention has been devoted to the follow-up and reexamination of patients who recovered from COVID-19 or were released from quarantine. CASE SUMMARY: This study reports two cases where patients who had negative reverse transcription-polymerase chain reaction (RT-PCR) test results and met the criteria for discharge subsequently had positive RT-PCR test results. The clinical manifestations and computed tomography (CT) findings of these patients were examined. The conversion of RT-PCR test results in these two patients may be related to false-negative and false-positive outcomes of the test. CT images helped track improvement of pulmonary lesions. CONCLUSION: The timing of discharge of COVID-19 patients should be determined by comprehensive analysis of CT images and RT-PCR test results.

Versatile and multivalent nanobodies efficiently neutralize SARS-CoV-2.

Cost-effective, efficacious therapeutics are urgently needed to combat the COVID-19 pandemic. In this study, we used camelid immunization and proteomics to identify a large repertoire of highly potent neutralizing nanobodies (Nbs) to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein receptor binding domain (RBD). We discovered Nbs with picomolar to femtomolar affinities that inhibit viral infection at concentrations below the nanograms-per-milliliter level, and we determined a structure of one of the most potent Nbs in complex with the RBD. Structural proteomics and integrative modeling revealed multiple distinct and nonoverlapping epitopes and indicated an array of potential neutralization mechanisms. We bioengineered multivalent Nb constructs that achieved ultrahigh neutralization potency (half-maximal inhibitory concentration as low as 0.058 ng/ml) and may prevent mutational escape. These thermostable Nbs can be rapidly produced in bulk from microbes and resist lyophilization and aerosolization.

Structure of human steroid 5α-reductase 2 with anti-androgen drug finasteride.

Human steroid 5α-reductase 2 (SRD5α2) as a critical integral membrane enzyme in steroid metabolism catalyzes testosterone to dihydrotestosterone. Mutations on its gene have been linked to 5α-reductase deficiency and prostate cancer. Finasteride and dutasteride as SRD5α2 inhibitors are widely used anti-androgen drugs for benign prostate hyperplasia, which have recently been indicated in the treatment of COVID-19. The molecular mechanisms underlying enzyme catalysis and inhibition remained elusive for SRD5α2 and other eukaryotic integral membrane steroid reductases due to a lack of structural information. Here, we report a crystal structure of human SRD5α2 at 2.8 Å revealing a unique 7-TM structural topology and an intermediate adduct of finasteride and NADPH as NADP-dihydrofinasteride in a largely enclosed binding cavity inside the membrane. Structural analysis together with computational and mutagenesis studies reveals molecular mechanisms for the 5α-reduction of testosterone and the finasteride inhibition involving residues E57 and Y91. Molecular dynamics simulation results indicate high conformational dynamics of the cytosolic region regulating the NADPH/NADP + exchange. Mapping disease-causing mutations of SRD5α2 to our structure suggests molecular mechanisms for their pathological effects. Our results offer critical structural insights into the function of integral membrane steroid reductases and will facilitate drug development.

A retrospective analysis of the epidemiology, clinical manifestations, and imaging characteristics of familial cluster-onset COVID-19.

BACKGROUND: The coronavirus disease 2019 (COVID-19) virus has a high incidence rate and strong infectivity. The diagnosis and evaluation of familial outbreaks requires a collective consideration of epidemiological history, molecular detection methods, chest computed tomography (CT), and clinical symptoms. METHODS: A group of family patients with COVID-19 diagnosed in Guizhou, China, in February 2020, was retrospectively analyzed. As of March 1, all patients in the group have been discharged from hospital. This study tracked all patients in the group. We report the epidemiology, radiological characteristics, treatment, and clinical outcomes of these patients. RESULTS: We collected a group of 8 clustered cases (3 men and 5 women) from a family with confirmed COVID-19 infection. In the first admission diagnosis, according to the degree of clinical symptoms, the 8 patients were defined as mild type (4/8) or moderate type (4/8). They were also divided according to the CT findings into early period (1/8), progressive period (3/8), and negative on CT scan (4/8); for the first 4 patients, the corresponding CT image scores were 1, 4, 5, and 5 respectively. In this group of COVID-19 patients, half of the patients showed occult clinical manifestations and negative CT performance. We defined these patients as COVID-19-infected patients, or asymptomatic carriers. CONCLUSIONS: The family cluster analysis indicated that COVID-19-infected patients (asymptomatic carriers) and symptomatic COVID-19 patients are distinct but coexistent. This may indicate that the infectivity and virulence of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) has decreased. In order to block the transmission pathway of this virus before it spreads, we need to identify the presence of asymptomatic carriers as early as possible.