The role of categorical EPU indices in predicting stock-market returns

This study investigates the predictive ability of categorical economic-policy uncertainty (EPU) indices for stock-market returns. The results indicate that some categorical EPU indices have superior predictive ability for stock returns and even achieve higher realized utility than the original EPU index and popular predictors. Furthermore, the diffusion indices based on EPU categories, especially those that use partial least squares (PLS) to extract the principal components, more effectively use the forecast information contained in categorical EPU indices, resulting in improved forecast performance, including reduced forecast errors and increased economic value for investors. In addition, the categorical EPU indices show superior forecasting performance during economic-expansion, the China-US trade-war, and COVID-19 pandemic periods.

Predicting volatility in natural gas under a cloud of uncertainties.

The COVID-19 pandemic has triggered an economic crisis and the ensuing global uncertainty. The current Russian-Ukrainian conflict has escalated tensions in various regions and increased various uncertainties in the financial and economic system. These uncertainties have had a significant impact on the development of the natural gas market during the current critical period of carbon neutrality and energy transition. This paper explores the impact of various uncertainties on price volatility in the U.S. natural gas futures market using the GARCH-MIDAS model. We considered eleven types of uncertainties, including four US economic policy uncertainties, four global uncertainty indicators, and oil supply-demand uncertainty closely related to the natural gas market. The in-sample empirical results find that various uncertainties can impact the natural gas market. However, through out-of-sample testing, we find that economic policy uncertainty has more predictive power than other indicators in predicting natural gas price fluctuations. Interestingly, oil supply-demand uncertainty surpasses global indicators and can provide forecasting information for natural gas markets. Therefore, in the current context of high uncertainty, our research may offer better decision-making opinions for market participants.

Effect of inactivated COVID-19 vaccines on seizure frequency in patients with epilepsy: A multicenter, prospective study.

Objectives: Several COVID-19 vaccines list "uncontrolled epilepsy" as a contraindication for vaccination. This consequently restricts vaccination against COVID-19 in patients with epilepsy (PWE). However, there is no strong evidence that COVID-19 vaccination can exacerbate conditions in PWE. This study aims to determine the impact of COVID-19 vaccination on PWE. Methods: PWE were prospectively recruited from 25 epilepsy centers. We recorded the seizure frequency at three time periods (one month before the first vaccination and one month after the first and second vaccinations). A generalized linear mixed-effects model (GLMM) was used for analysis, and the adjusted incidence rate ratio (AIRR) with 95% CI was presented and interpreted accordingly. Results: Overall, 859 PWE were included in the analysis. Thirty-one (3.6%) and 35 (4.1%) patients were found to have increased seizure frequency after the two doses, respectively. Age had an interaction with time. The seizure frequency in adults decreased by 81% after the first dose (AIRR=0.19, 95% CI:0.11-0.34) and 85% after the second dose (AIRR=0.16, 95% CI:0.08-0.30). In juveniles (<18), it was 25% (AIRR=0.75, 95% CI:0.42-1.34) and 51% (AIRR=0.49, 95% CI:0.25-0.95), respectively. Interval between the last seizure before vaccination and the first dose of vaccination (ILSFV) had a significant effect on seizure frequency after vaccination. Seizure frequency in PWE with hereditary epilepsy after vaccination was significantly higher than that in PWE with unknown etiology (AIRR=1.95, 95% CI: 1.17-3.24). Two hundred and seventeen (25.3%) patients experienced non-epileptic but not serious adverse reactions. Discussion: The inactivated COVID-19 vaccine does not significantly increase seizure frequency in PWE. The limitations of vaccination in PWE should focus on aspects other than control status. Juvenile PWE should be of greater concern after vaccination because they have lower safety. Finally, PWE should not reduce the dosage of anti-seizure medication during the peri-vaccination period.

[Clinical features of children and their family members with family clusters of SARS-CoV-2 Omicron variant infection in Shanghai, China: an analysis of 380 cases]. / 上海380例家庭聚集性感染Omicronå˜å¼‚æ ªçš„å„¿ç«¥åŠå ¶å®¶å±žä¸´åºŠç‰¹å¾åˆ†æž.

OBJECTIVES: To study the clinical features and prognosis of children and their family members with family clusters of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant infection under the admission mode of parent-child ward. METHODS: A retrospective analysis was performed on the medical data of 190 children and 190 family members with SARS-CoV-2 Omicron variant infection who were admitted to Shanghai Sixth People's Hospital, the designated hospital for coronavirus disease 2019 (COVID-19), April 8 to May 10, 2022. RESULTS: Both the child and adult groups were mainly mild COVID-19, and the proportion of mild cases in the child group was higher than that in the adult group (P<0.05). Respiratory symptoms were the main clinical manifestations in both groups. Compared with the adult group, the child group had higher incidence rates of fever, abdominal pain, diarrhea, and wheezing (P<0.05) and lower incidence rates of nasal obstruction, runny nose, cough, dry throat, throat itching, and throat pain (P<0.05). Compared with the child group, the adult group had higher rates of use of Chinese patent drugs, traditional Chinese medicine decoction, recombinant interferon spray, cough-relieving and phlegm-eliminating drugs, and nirmatrelvir/ritonavir tablets (P<0.05). Compared with the adult group, the child group had a lower vaccination rate of SARS-CoV-2 vaccine (30.5% vs 71.1%, P<0.001) and a shorter duration of positive SARS-CoV-2 nucleic acid (P<0.05). The patients with mild COVID-19 had a shorter duration of positive SARS-CoV-2 nucleic acid than those with common COVID-19 in both groups (P<0.05). The patients with underlying diseases had a longer duration of positive SARS-CoV-2 nucleic acid than those without such diseases in both groups (P<0.05). CONCLUSIONS: Both children and adults with family clusters of SARS-CoV-2 Omicron variant infection manifest mainly mild COVID-19. Despite lower vaccination rate of SARS-CoV-2 vaccine in children, they have rapid disease recovery, with a shorter duration of positive SARS-CoV-2 nucleic acid than adults, under the admission mode of parent-child ward.

Emerging trends of research on mRNA vaccines: A co-citation analysis.

This study was designed to evaluate the emerging trends of research on mRNA vaccines. Altogether 3056 research articles related to mRNA vaccines published since 2010 were retrieved from the Web of Science database, based on which a co-citation analysis was conducted using CiteSpace. A total of 12 clusters were derived, all of which were classified into three periods according to the content and publication time of articles: (1) The preliminary exploratory period before early 2010s, when the potential of mRNA to induce immune response was evaluated; (2) the growing up period from early 2010s to 2019, when the stability and immunogenicity of mRNA vaccines were improved and the clinical development of products were pushed forward; (3) the rapid maturity period after the outbreak of COVID-19, when two products for COVID-19 were authorized for the first time. The approval of COVID-19 vaccines is an encouraging start, while the enormous potential of mRNA vaccines remains to be explored. Future research on mRNA-based infectious disease vaccines will focus on further optimizing mRNA modification and delivery, solving problems of the approved vaccines in real world, investigating mRNA vaccines for other infectious indications, and developing self-amplifying or thermostable vaccines. Future research on mRNA-based therapeutic cancer vaccines will focus on screening proper neoantigens, enhancing the delivery of mRNA into antigen-presenting cells and overcoming suppressive tumor microenvironment.

Potential of ATP5MG to Treat Metabolic Syndrome-Associated Cardiovascular Diseases.

Introduction: Metabolic syndrome-associated cardiovascular disease (MetS-CVD) is a cluster of metabolism-immunity highly integrated diseases. Emerging evidence hints that mitochondrial energy metabolism may be involved in MetS-CVD development. The physiopathological role of ATP5MG, a subunit of the F0 ATPase complex, has not been fully elucidated. Methods: In this study, we selected ATP5MG to identify the immunity-mediated pathway and mine drugs targeting this pathway for treating MetS-CVD. Using big data from public databases, we dissected co-expressed RNA (coRNA), competing endogenous RNA (ceRNA), and interacting RNA (interRNA) genes for ATP5MG. Results: It was identified that ATP5MG may form ceRNA with COX5A through hsa-miR-142-5p and interplay with NDUFB8, SOD1, and MDH2 through RNA-RNA interaction under the immune pathway. We dug out 251 chemicals that may target this network and identified some of them as clinical drugs. We proposed five medicines for treating MetS-CVD. Interestingly, six drugs are being tested to treat COVID-19, which unexpectedly offers a new potential host-targeting antiviral strategy. Conclusion: Collectively, we revealed the potential significance of the ATP5MG-centered network for developing drugs to treat MetS-CVD, which offers insights into the epigenetic regulation for metabolism-immunity highly integrated diseases.

Genome-wide association study of SARS-CoV-2 infection in Chinese population.

Coronavirus disease 2019 (COVID-19) is a global public health concern. The purpose of this study was to investigate the association between genetic variants and SARS-CoV-2 infection and the COVID-19 severity in Chinese population. A total of 256 individuals including 87 symptomatic patients (tested positive for SARS-CoV-2), 84 asymptomatic cases, and 85 close contacts of confirmed patients (tested negative for SARS-CoV-2) were recruited from February 2020 to May 2020. We carried out the whole exome genome sequencing between the individuals and conducted a genetic association study for SARS-CoV-2 infection and the COVID-19 severity. In total, we analyzed more than 100,000 single-nucleotide polymorphisms. The genome-wide association study suggested potential correlation between genetic variability in POLR2A, ANKRD27, MAN1A2, and ERAP1 genes and SARS-CoV-2 infection susceptibility. The most significant gene locus associated with SARS-CoV-2 infection was located in POLR2A (p = 5.71 × 10-6). Furthermore, genetic variants in PCNX2, CD200R1L, ZMAT3, PLCL2, NEIL3, and LINC00700 genes (p < 1 × 10-5) were closely associated with the COVID-19 severity in Chinese population. Our study confirmed that new genetic variant loci had significant association with SARS-CoV-2 infection and the COVID-19 severity in Chinese population, which provided new clues for the studies on the susceptibility of SARS-CoV-2 infection and the COVID-19 severity. These findings may give a better understanding on the molecular pathogenesis of COVID-19 and genetic basis of heterogeneous susceptibility, with potential impact on new therapeutic options.

Distinct immune responses in the early phase to natural SARS-CoV-2 infection or vaccination.

Immune responses elicited by viral infection or vaccination play key roles in the viral elimination and the prevention of reinfection, as well as the protection of healthy persons. As one of the most widely used Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines, there have been increasing concerns about the necessity of additional doses of inactivated vaccines, due to the waning immune response several months after vaccination. To further optimize inactivated SARS-CoV-2 vaccines, we compared immune responses to SARS-CoV-2 elicited by natural infection and immunization with inactivated vaccines in the early phase. We observed the lower antibody levels against SARS-CoV-2 spike (S) and nucleocapsid (N) proteins in the early phase of postvaccination with a slow increase, compared to the acute phase of SARS-CoV-2 natural infection. Specifically, IgA antibodies have the most significant differences. Moreover, we further analyzed cytokine expression between these two groups. A wide variety of cytokines presented high expression in the infected individuals, while a few cytokines were elicited by inactivated vaccines. The differences in antibody responses and cytokine levels between natural SARS-CoV-2 infection and vaccination with the inactivated vaccines may provide implications for the optimization of inactivated SARS-CoV-2 vaccines and the additional application of serological tests.

Protein sensors combining both on-and-off model for antibody homogeneous assay.

Protein sensors based on allosteric enzymes responding to target binding with rapid changes in enzymatic activity are potential tools for homogeneous assays. However, a high signal-to-noise ratio (S/N) is difficult to achieve in their construction. A high S/N is critical to discriminate signals from the background, a phenomenon that might largely vary among serum samples from different individuals. Herein, based on the modularized luciferase NanoLuc, we designed a novel biosensor called NanoSwitch. This sensor allows direct detection of antibodies in 1 µl serum in 45 min without washing steps. In the detection of Flag and HA antibodies, NanoSwitches respond to antibodies with S/N ratios of 33-fold and 42-fold, respectively. Further, we constructed a NanoSwitch for detecting SARS-CoV-2-specific antibodies, which showed over 200-fold S/N in serum samples. High S/N was achieved by a new working model, combining the turn-off of the sensor with human serum albumin and turn-on with a specific antibody. Also, we constructed NanoSwitches for detecting antibodies against the core protein of hepatitis C virus (HCV) and gp41 of the human immunodeficiency virus (HIV). Interestingly, these sensors demonstrated a high S/N and good performance in the assays of clinical samples; this was partly attributed to the combination of off-and-on models. In summary, we provide a novel type of protein sensor and a working model that potentially guides new sensor design with better performance.

Restriction-Assembly: A Solution to Construct Novel Adenovirus Vector.

Gene therapy and vaccine development need more novel adenovirus vectors. Here, we attempt to provide strategies to construct adenovirus vectors based on restriction-assembly for researchers with little experience in this field. Restriction-assembly is a combined method of restriction digestion and Gibson assembly, by which the major part of the obtained plasmid comes from digested DNA fragments instead of PCR products. We demonstrated the capability of restriction-assembly in manipulating the genome of simian adenovirus 1 (SAdV-1) in this study. A PCR product of the plasmid backbone was combined with SAdV-1 genomic DNA to construct an infectious clone, plasmid pKSAV1, by Gibson assembly. Restriction-assembly was performed repeatedly in the steps of intermediate plasmid isolation, modification, and restoration. The generated adenoviral plasmid was linearized by restriction enzyme digestion and transfected into packaging 293 cells to rescue E3-deleted replication-competent SAdV1XE3-CGA virus. Interestingly, SAdV1XE3-CGA could propagate in human chronic myelogenous leukemia K562 cells. The E1 region was similarly modified to generate E1/E3-deleted replication-defective virus SAdV1-EG. SAdV1-EG had a moderate gene transfer ability to adherent mammalian cells, and it could efficiently transduce suspension cells when compared with the human adenovirus 5 control vector. Restriction-assembly is easy to use and can be performed without special experimental materials and instruments. It is highly effective with verifiable outcomes at each step. More importantly, restriction-assembly makes the established vector system modifiable, upgradable and under sustainable development, and it can serve as the instructive method or strategy for the synthetic biology of adenoviruses.

Antibody responses to SARS-CoV-2 in patients with COVID-19.

We report acute antibody responses to SARS-CoV-2 in 285 patients with COVID-19. Within 19 days after symptom onset, 100% of patients tested positive for antiviral immunoglobulin-G (IgG). Seroconversion for IgG and IgM occurred simultaneously or sequentially. Both IgG and IgM titers plateaued within 6 days after seroconversion. Serological testing may be helpful for the diagnosis of suspected patients with negative RT-PCR results and for the identification of asymptomatic infections.

Transportation connectivity strategies and regional tourism economy - empirical analysis of 153 cities in China

PurposeA transportation connectivity strategy is a crucial part of an adaptive, congruent and sustainable tourism transportation system and is of concern to countries focusing on growing their tourism economy. This study aims to gain a better understanding of the relationship between transportation connectivity and the tourism economy through a configuration analysis.Design/methodology/approachThis study uses fuzzy-set qualitative comparative analysis on a sample of 153 cities in China to provide an understanding of the impacts of transportation connectivity strategies, with the co-effecting factors of socio-economic status, tourism resource endowment and hospitality capacity, on the development of regional tourism economies.FindingsThere are multiple paths that lead to regional tourism economic development (a high level of tourist arrivals or a high level of tourism revenue). High-speed rail can play a supportive role, while air travel or traditional rail remains central to the tourism economy. Socio-economic status (i.e. city size and city gross domestic product) and hospitality capacity are identified as crucial influencers for the development of the tourism economy.Research limitations/implicationsThis study confirms the validity of deploying configuration analysis (based on the equifinality theory) to establish the relationship between transportation and the tourism economy. The finding of more than one configuration led to a new consensus on how multiple factors influence the tourism economy.Practical implicationsSuggestions on transportation connectivity strategies for different regions are provided.Originality/valueThis study demonstrates the need to place greater emphasis on configurations that lead to tourism economy development instead of the effect of a single transportation mode.

m6A Regulator-Mediated Methylation Modification Patterns and Characteristics of Immunity in Blood Leukocytes of COVID-19 Patients.

Both RNA N6-methyladenosine (m6A) modification of SARS-CoV-2 and immune characteristics of the human body have been reported to play an important role in COVID-19, but how the m6A methylation modification of leukocytes responds to the virus infection remains unknown. Based on the RNA-seq of 126 samples from the GEO database, we disclosed that there is a remarkably higher m6A modification level of blood leukocytes in patients with COVID-19 compared to patients without COVID-19, and this difference was related to CD4+ T cells. Two clusters were identified by unsupervised clustering, m6A cluster A characterized by T cell activation had a higher prognosis than m6A cluster B. Elevated metabolism level, blockage of the immune checkpoint, and lower level of m6A score were observed in m6A cluster B. A protective model was constructed based on nine selected genes and it exhibited an excellent predictive value in COVID-19. Further analysis revealed that the protective score was positively correlated to HFD45 and ventilator-free days, while negatively correlated to SOFA score, APACHE-II score, and crp. Our works systematically depicted a complicated correlation between m6A methylation modification and host lymphocytes in patients infected with SARS-CoV-2 and provided a well-performing model to predict the patients' outcomes.

Exploring the Pattern of Early COVID-19 Transmission Caused by Population Migration Based on 14 Cities in Hubei Province, China.

BACKGROUND AND AIM: Relevant studies show that population migration has a great impact on the early spread of infectious diseases. Therefore, it is important to explore whether there is an explicit relationship between population migration and the number of confirmed cases for the control of the COVID-19 epidemic. This paper mainly explores the impact of population migration on early COVID-19 transmission, and establishes a predictive nonlinear mathematical model to predict the number of early cases. METHODS: Data of confirmed cases were sourced from the official website of the Municipal Health Committee, and the proportions of migration from Wuhan to other cities were sourced from the Baidu data platform. The data of confirmed cases and the migration proportions of 14 cities in Hubei Province were collected, the COVID-19 cases study period was determined as 10 days based on the third quartile of the interval of the incubation period, and a non-linear mathematical model was constructed to clarify the relationship between the migration proportion and the number of confirmed COVID-19 cases. Finally, eight typical regions were selected to verify the accuracy of the model. RESULTS: The daily population migration rates and the growth curves of the number of confirmed cases in the 14 cities were basically consistent, and Pearson's correlation coefficient was 0.91. The specific mathematical expression of 14 regions is . In each of the fourteen cities, The nonlinear exponential model structure is as follows:. It was found that the R 2 values of the fitted mathematical model were greater than 0.8 in all studied regions, excluding Suizhou (p < 0.05). The established mathematical model was used to fit eight regions in China, and the correlations between the predicted and actual numbers of confirmed cases were greater than 0.9, excluding that of Hebei Province (0.82). CONCLUSION: The study found that population migration has a positive and significant impact on the spread of COVID-19. Modeling COVID-19 risk may be a useful strategy for directing public health surveillance and interventions. Restricting the migration of the population is of great significance to the joint prevention and control of the pandemic worldwide.

Distinct immune signatures discriminate between asymptomatic and presymptomatic SARS-CoV-2pos subjects.

Increasing numbers of SARS-CoV-2-positive (SARS-CoV-2pos) subjects are detected at silent SARS-CoV-2 infection stage (SSIS). Yet, SSIS represents a poorly examined time-window wherein unknown immunity patterns may contribute to the fate determination towards persistently asymptomatic or overt disease. Here, we retrieved blood samples from 19 asymptomatic and 12 presymptomatic SARS-CoV-2pos subjects, 47 age/gender-matched patients with mild or moderate COVID-19 and 27 normal subjects, and interrogated them with combined assays of 44-plex CyTOF, RNA-seq and Olink. Notably, both asymptomatic and presymptomatic subjects exhibited numerous readily detectable immunological alterations, while certain parameters including more severely decreased frequencies of CD107alow classical monocytes, intermediate monocytes, non-classical monocytes and CD62Lhi CD8+ Tnaïve cells, reduced plasma STC1 level but an increased frequency of CD4+ NKT cells combined to distinguish the latter. Intercorrelation analyses revealed a particular presymptomatic immunotype mainly manifesting as monocytic overactivation and differentiation blockage, a likely lymphocyte exhaustion and immunosuppression, yielding mechanistic insights into SSIS fate determination, which could potentially improve SARS-CoV-2 management.

Clinical features of Chinese children with COVID-19 and other viral respiratory infections.

OBJECTIVE: Few studies have explored the clinical features in children infected with SARS-CoV-2 and other common respiratory viruses, including respiratory syncytial virus (RSV), Influenza virus (IV), and adenovirus (ADV). Herein, we reported the clinical characteristics and cytokine profiling in children with COVID-19 or other acute respiratory tract infections (ARTI). METHODS: We enrolled 20 hospitalized children confirmed as COVID-19 positive, 58 patients with ARTI, and 20 age and sex-matched healthy children. The clinical information and blood test results were collected. A total of 27 cytokines and chemokines were measured and analyzed. RESULTS: The median age in the COVID-19 positive group was 14.5 years, which was higher than that of the ARTI groups. Around one-third of patients in the COVID-19 group experienced moderate fever, with a peak temperature of 38.27°C. None of the patients displayed wheezing or dyspnea. In addition, patients in the COVID-19 group had lower white blood cells, platelet counts as well as a neutrophil-lymphocyte ratio. Lower serum concentrations of 14 out of 27 cytokines were observed in the COVID-19 group than in healthy individuals. Seven cytokines (IL-1Ra, IL-1ß, IL-9, IL-10, TNF-α, MIP-1α, and VEGF) changed serum concentration in COVID-19 compared with other ARTI groups. CONCLUSION: Patients with COVID-19 were older and showed milder symptoms and a favorable prognosis than ARTI caused by RSV, IV, and ADV. There was a low grade or constrained innate immune reaction in children with mild COVID-19.

A case describing patients with COVID-19 that secondarily transmitted.

BACKGROUND: The recent emergence of coronavirus disease 2019 (COVID-19) is a major global health threat. Monitoring viral transmission and disease characteristics as the disease spreads globally is vital. This study aimed to describe the clinical characteristics and source of infection in patients with secondary transmission of COVID-19 outside the outbreak area. METHODS: The epidemiological, demographic, clinical, laboratory, radiological, and treatment data of five patients with laboratory-confirmed COVID-19 who were treated in the General Hospital of Ningxia Medical University (Ningxia, China) from 1 January 2020 to 1 March 2020 were presented. The final follow-up evaluation was performed on 12 March 2020. RESULTS: The five participants included two couples and a young woman, none of whom had visited Hubei. It was likely that four of the participants had been infected by exposure to asymptomatic visitors from Wuhan. The other participant lived in a densely-populated community with potential COVID-19 cases. A variety of symptoms were presented by four participants, including cough, fevers, sputum, breathlessness, chest pain, fatigue, sore limbs, sore throats, headaches, and rhinorrhea. A severe infection, with dyspnea and decreased oxygen saturation, was experienced by one participant who had a history of chronic bronchitis. A single participant was asymptomatic, but had ground-glass opacities (GGOs) on chest imaging. Another two participants also displayed GGOs. Lymphopenia was noted in three participants. During the follow-up period, all participants were cured and discharged to their homes. CONCLUSIONS: This study included patients who had acquired infections of COVID-19 through local transmission. These findings will provide a better understanding of secondary transmission of COVID-19.