Differences in syncytia formation by SARS-CoV-2 variants modify host chromatin accessibility and cellular senescence via TP53 (preprint)

COVID-19 remains a significant public health threat due to the ability of SARS-CoV-2 variants to evade the immune system and cause breakthrough infections. Although pathogenic coronaviruses such as SARS-CoV-2 and MERS-CoV lead to severe respiratory infections, how these viruses affect the chromatin proteomic composition upon infection remains largely uncharacterized. Here we used our recently developed integrative DNA And Protein Tagging (iDAPT) methodology to identify changes in host chromatin accessibility states and chromatin proteomic composition upon infection with pathogenic coronaviruses. SARS-CoV-2 infection induces TP53 stabilization on chromatin, which contributes to its host cytopathic effect. We mapped this TP53 stabilization to the SARS-CoV-2 spike and its propensity to form syncytia, a consequence of cell-cell fusion. Differences in SARS-CoV-2 spike variant-induced syncytia formation modify chromatin accessibility, cellular senescence, and inflammatory cytokine release via TP53. Our findings suggest that differences in syncytia formation alter senescence-associated inflammation, which varies among SARS-CoV-2 variants.

Price guidance and discovery of the Chinese stock index Futures: Based on the rising, falling and fluctuating states.

Stock index futures have been around for more than 12 years in the Chinese market, but there are conflicting viewpoints on the role of Chinese stock index futures in the market. Many crises, including COVID-19, have heightened the financial system's vulnerability and instability. Do China's stock index futures play a role in stabilizing the market and discovering prices in turbulent times? This study employs a combination of VEC, PT, and IS methodologies to investigate the lead-lag relation and price discovery ability of stock index futures markets. By evaluating price interactions in three different scenarios, we reveal that stock index futures play a prominent role in price discovery, particularly in markets with excessive volatility. However, their impact on price discovery is weaker during stable market conditions. To the best of our knowledge, this study is the first to categorize the Chinese stock market into different states, providing valuable insights into the price discovery function of stock index futures. Our findings have important implications for policymakers and investors, as they highlight the need for increased attention to market manipulation and excessive speculation during volatile market conditions to protect the interests of investors.

Evaluation of a biotin-based surrogate virus neutralization test for detecting postvaccination antibodies against SARS-CoV-2 variants in sera.

A severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) surrogate virus neutralization test (sVNT) was used to determine the degree of inhibition of binding between human angiotensin converting enzyme 2 (hACE2) and the receptor binding domain (RBD) of spike protein by neutralizing antibodies in a biosafety level 2 facility. Here, to improve the sensitivity and specificity of the commercial sVNT, we developed a new biotin based sVNT using biotinylated RBD and HRP conjugated streptavidin instead of HRP conjugated RBD for direct detection in an ELISA assay that strongly correlated to the FDA approved cPass sVNT commercial kit (R2 = 0.8521) and pseudo virus neutralization test (R2 = 0.9006) (pVNT). The biotin based sVNT was evaluated in 535 postvaccination serum samples corresponding to second and third boosts of AZD1222 and BNT162b2 vaccines of the wild type strain. We confirmed that the neutralizing antibodies against SARS-CoV-2 variants in second vaccination sera decreased after a median of 141.5 days. Furthermore, vaccination sera from BNT162b2-BNT162b2 vaccines maintained neutralizing antibodies for longer than those of AZD1222 only vaccination. In addition, both vaccines maintained high neutralizing antibodies in third vaccination sera against Omicron BA.2 after a median of 27 days, but neutralizing antibodies significantly decreased after a median of 141.5 days. Along with the cPass sVNT commercial kit, biotin based sVNTs may also be suitable for specifically detecting neutralizing antibodies against multiple SARS-CoV-2 variants; however, to initially monitor the neutralizing antibodies in vaccinated sera using high throughput screening, conventional PRNT could be replaced by sVNT to circumvent the inconvenience of a long test time.

Data analysis guidelines for single-cell RNA-seq in biomedical studies and clinical applications.

The application of single-cell RNA sequencing (scRNA-seq) in biomedical research has advanced our understanding of the pathogenesis of disease and provided valuable insights into new diagnostic and therapeutic strategies. With the expansion of capacity for high-throughput scRNA-seq, including clinical samples, the analysis of these huge volumes of data has become a daunting prospect for researchers entering this field. Here, we review the workflow for typical scRNA-seq data analysis, covering raw data processing and quality control, basic data analysis applicable for almost all scRNA-seq data sets, and advanced data analysis that should be tailored to specific scientific questions. While summarizing the current methods for each analysis step, we also provide an online repository of software and wrapped-up scripts to support the implementation. Recommendations and caveats are pointed out for some specific analysis tasks and approaches. We hope this resource will be helpful to researchers engaging with scRNA-seq, in particular for emerging clinical applications.

A colorimetric lateral flow immunoassay based on oriented antibody immobilization for sensitive detection of SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19). The high human-to-human transmission and rapid evolution of SARS-CoV-2 have resulted in a worldwide pandemic. To contain SARS-CoV-2, it is essential to efficiently control the transmission of the virus through the early diagnosis of infected individuals, including asymptomatic people. Therefore, a rapid and accurate assay is vital for the early diagnosis of SARS-CoV-2 in suspected individuals. In this study, we developed a colorimetric lateral flow immunoassay (LFIA) in which a CBP31-BC linker was used to immobilize antibodies on a cellulose membrane in an oriented manner. The developed LFIA enabled sensitive detection of cultured SARS-CoV-2 in 15 min with a detection limit of 5 × 104 copies/mL. The clinical performance of the LFIA for detecting SARS-CoV-2 was evaluated using 19 clinical samples validated by reverse transcription-polymerase chain reaction (RT-PCR). The LFIA detected all the positive and negative samples accurately, corresponding to 100% accuracy. Importantly, patient samples with low viral loads were accurately identified. Thus, the proposed method can provide a useful platform for rapid and accurate point-of-care testing of SARS-CoV-2 in infected individuals to efficiently control the COVID-19 pandemic.

Perception of human papilloma virus (HPV) vaccination during the COVID-19 pandemic.

The COVID 19 pandemic is far from over, and vaccines remain important tool for fighting the disease. As the preventive effects of the COVID-19 vaccine emerges, it is likely that the perception of importance and safety of vaccines have a positive effect on the acceptance of other vaccines. However, it is still unclear how COVID-19 pandemic has affected the general vaccination perception and acceptance. Therefore, the objective of this study was to investigate the impact of the COVID-19 pandemic on the perception of HPV vaccination. This study involved an offline survey of 161 women aged between 20 and 49 years who visited the gynecologic clinic at Chung-nam National University Sejong Hospital from January 2021 to June 2021. The questionnaire consists of items related to experience and knowledge of COVID-19 and HPV viruses, as well as attitudes toward HPV vaccination. Knowledge about COVID-19 virus and HPV correlated positively with their experiences (P = .011 and P = .045, respectively). Positive attitude was increased, and negative attitude was reduced toward HPV vaccination in the COVID-19 pandemic era. Participants stated that accurate information and cost reduction about HPV vaccine was needed to increase the HPV vaccination rate. During the COVID-19 pandemic era, positive attitudes towards HPV vaccination have tended to increase. To increase the HPV vaccination rate, public efforts are needed for further information and cost reduction.

Dynamic change of COVID-19 lung infection evaluated using co-registration of serial chest CT images.

Purpose: To evaluate the volumetric change of COVID-19 lesions in the lung of patients receiving serial CT imaging for monitoring the evolution of the disease and the response to treatment. Materials and methods: A total of 48 patients, 28 males and 20 females, who were confirmed to have COVID-19 infection and received chest CT examination, were identified. The age range was 21-93 years old, with a mean of 54 ± 18 years. Of them, 33 patients received the first follow-up (F/U) scan, 29 patients received the second F/U scan, and 11 patients received the third F/U scan. The lesion region of interest (ROI) was manually outlined. A two-step registration method, first using the Affine alignment, followed by the non-rigid Demons algorithm, was developed to match the lung areas on the baseline and F/U images. The baseline lesion ROI was mapped to the F/U images using the obtained geometric transformation matrix, and the radiologist outlined the lesion ROI on F/U CT again. Results: The median (interquartile range) lesion volume (cm3) was 30.9 (83.1) at baseline CT exam, 18.3 (43.9) at first F/U, 7.6 (18.9) at second F/U, and 0.6 (19.1) at third F/U, which showed a significant trend of decrease with time. The two-step registration could significantly decrease the mean squared error (MSE) between baseline and F/U images with p < 0.001. The method could match the lung areas and the large vessels inside the lung. When using the mapped baseline ROIs as references, the second-look ROI drawing showed a significantly increased volume, p < 0.05, presumably due to the consideration of all the infected areas at baseline. Conclusion: The results suggest that the registration method can be applied to assist in the evaluation of longitudinal changes of COVID-19 lesions on chest CT.

Ideology and COVID-19 Vaccination Intention: Perceptual Mediators and Communication Moderators.

Widespread COVID-19 vaccination is critical to slow the spread of the illness. This study investigates how political ideology is associated with COVID-19 vaccine intention via perceived effectiveness of the vaccine, perceived side effects, and perceived severity of the illness, three key aspects of the Health Belief Model (HBM). This study also examines how partisan information flow moderates the effects of ideology on these three HBM components. Using survey data collected from two battleground states in the 2020 election (N = 1849), regression, mediation and moderation analyses revealed that conservatives were less likely to intend to get vaccinated against COVID-19, and this association was significantly mediated by perceived effectiveness and perceived side effects of vaccination, as well as perceived severity of COVID-19. In addition, partisanship of news sources and discussion partners were significant moderators of ideology's association with perceived vaccine effectiveness, with conservatives viewing COVID-19 vaccination as less effective if they were frequently exposed to liberal news, and if they had frequent conversations with fellow conservatives. This suggests boomerang effects for cross-cutting mass media exposure, and reinforcement effect for interpersonal communication. Implications for efforts to promote COVID-19 vaccine uptake are discussed, including tailored and targeted campaign strategies.

Vaccine discourse during the onset of the COVID-19 pandemic: Topical structure and source patterns informing efforts to combat vaccine hesitancy.

BACKGROUND: Understanding public discourse about a COVID-19 vaccine in the early phase of the COVID-19 pandemic may provide key insights concerning vaccine hesitancy. However, few studies have investigated the communicative patterns in which Twitter users participate discursively in vaccine discussions. OBJECTIVES: This study aims to investigate 1) the major topics that emerged from public conversation on Twitter concerning vaccines for COVID-19, 2) the topics that were emphasized in tweets with either positive or negative sentiment toward a COVID-19 vaccine, and 3) the type of online accounts in which tweets with either positive or negative sentiment were more likely to circulate. METHODS: We randomly extracted a total of 349,979 COVID-19 vaccine-related tweets from the initial period of the pandemic. Out of 64,216 unique tweets, a total of 23,133 (36.03%) tweets were classified as positive and 14,051 (21.88%) as negative toward a COVID-19 vaccine. We conducted Structural Topic Modeling and Network Analysis to reveal the distinct topical structure and connection patterns that characterize positive and negative discourse toward a COVID-19 vaccine. RESULTS: Our STM analysis revealed the most prominent topic emerged on Twitter of a COVID-19 vaccine was "other infectious diseases", followed by "vaccine safety concerns", and "conspiracy theory." While the positive discourse demonstrated a broad range of topics such as "vaccine development", "vaccine effectiveness", and "safety test", negative discourse was more narrowly focused on topics such as "conspiracy theory" and "safety concerns." Beyond topical differences, positive discourse was more likely to interact with verified sources such as scientists/medical sources and the media/journalists, whereas negative discourse tended to interact with politicians and online influencers. CONCLUSIONS: Positive and negative discourse was not only structured around distinct topics but also circulated within different networks. Public health communicators need to address specific topics of public concern in varying information hubs based on audience segmentation, potentially increasing COVID-19 vaccine uptake.

Relationship between the Chinese Main Air Transport Network and COVID-19 Pandemic Transmission

The COVID-19 pandemic had an unprecedented impact on the civil aviation passenger transport industry. This study analyzes the scale change and spatial distribution of the Chinese main air transport network (CMATN) and its role in the early spread of the pandemic using a complex network analysis method and econometric model. The result shows that CMATN is mainly located in the economically developed and densely populated central and eastern regions of China. The normalized degree, closeness, and betweenness centralities of CMATN node cities show an overall increasing trend, indicating that the air transport network is constantly improving. There was a significant positive relationship between the centrality of node cities, the duration of the COVID-19 pandemic, and the number of confirmed cases, indicating that air transport networks were crucial in the pandemic's early spread. Furthermore, social and economic variables such as GDP and population had a significant positive impact on the duration of the pandemic, indicating that higher levels of social and economic development increased the seriousness of the pandemic. Our findings are expected to supplement existing research and serve as a point of reference for pandemic prevention and control.

Chronic lymphocytic leukemia presence impairs antigen-specific CD8+ T-cell responses through epigenetic reprogramming towards short-lived effectors (preprint)

T-cell dysregulation in chronic lymphocytic leukemia (CLL) associates with low response rates to autologous T cell-based therapies. How CLL affects antigen-specific T-cell responses remains largely unknown. We investigated (epi)genetic and functional consequences of antigen-specific T-cell responses in presence of CLL in vitro and in an adoptive-transfer murine model. Already at steady-state, antigen-experienced patient-derived T cells were skewed towards short-lived effector cells (SLEC) at the expense of memory-precursor effector cells (MPEC). Stimulation of these T cells in vitro showed rapid induction of effector genes and suppression of key memory transcription factors only in presence of CLL cells, indicating epigenetic regulation. This was investigated in vivo by following antigen-specific responses of naïve OT-I CD8 + cells to mCMV-OVA in presence/absence of TCL1 B-cell leukemia. Presence of leukemia resulted in increased SLEC formation, with disturbed inflammatory cytokine production. Chromatin and transcriptome profiling revealed strong epigenetic modifications, leading to activation of an effector and silencing of a memory profile through presence of CLL cells. Secondary challenge in vivo confirmed dysfunctional memory responses by antigen-experienced OT-I cells generated in presence of CLL. Altogether, we show that presence of CLL induces a short-lived effector phenotype and impaired memory responses by epigenetic reprogramming during primary responses.

Body Map of Droplet Distributions During Oropharyngeal Suction to Protect Health Care Workers From Airborne Diseases.

PURPOSE: Health care workers (HCWs), and in particular anesthesia providers, often must perform aerosol-generating medical procedures (AGMPs). However, no studies have analyzed droplet distributions on the bodies of HCWs during AGMPs. Therefore, the purpose of this study was to assess and analyze droplet distributions on the bodies of HCWs during suction of oral cavities with and without oral airways and during extubations. DESIGN: Using a quasi-experiemental design, we assumed the HCWs perform suction and extubation on intubated patients, and we prepared an intubated mannequin mimicking a patient. This study performed the oral suction and extubation on the intubated mannequin (with or without oral airways in place) and analyzed the droplet distributions. METHODS: We prepared a mannequin intubated with an 8.0 mm endotracheal tube, assuming the situation of general anesthesia. We designed the body mapping gown, and divided it into 10 areas including the head, neck, chest, abdomen, upper arms, forearms, and hands. We classified experiments into group O when suctions were performed on the mannequin with an oral airway, and into group X when the suctions were performed on the mannequin without an oral airway. An experienced board-certified anesthesiologist performed 10 oral suctions on each mannequin, and 10 extubations. We counted the droplets on the anesthesiologist's gown according to the divided areas after each procedure. FINDINGS: The mean droplet count after suction was 6.20 ± 2.201 in group O and 13.6 ± 4.300 in group X, with a significant difference between the two groups (P < .001). The right and left hands were the most contaminated areas in group O (2.8 ± 1.033 droplets and 2.0 ± 0.943 droplets, respectively). The abdomen, right hand, left forearm, and left hand showed many droplets in group X. (1.3 ± 1.337 droplets, 3.1 ± 1.792 droplets, 3.2 ± 3.910 droplets, and 4.3 ± 2.214 droplets, respectively). The chest, abdomen, and left hand presented significantly more droplets in group X than in group O. The trunk area (chest and abdomen) was exposed to more droplets during extubations than during suctions. CONCLUSIONS: During suctions, more droplets are splattered from mannequins without oral airways than from those with oral airways. The right and left hands were the most contaminated areas in group O. Moreover, the abdomen, right hand, left forearm, and left hand presented a lot of droplets in group X. In addition, extubations contaminate wider areas (the head, neck, chest and abdomen) of an HCW than suctions.

US Evaluation of Axillary Lymphadenopathy Following COVID-19 Vaccination: A Prospective Longitudinal Study.

Background Both temporal changes in imaging characteristics of lymphadenopathy on US scans after COVID-19 vaccination and expected duration of radiologically evident lymphadenopathy remain uncertain. Purpose To longitudinally evaluate COVID-19 vaccine-associated lymphadenopathy on axillary US scans at various time intervals in both messenger (mRNA) and vector vaccine recipients. Materials and Methods This prospective cohort study was conducted between March 2021 and January 2022. The participants were asymptomatic women without breast cancer who had received COVID-19 vaccination. Serial follow-up US was performed in women with lymphadenopathy. The following variables were assessed: cortical thickness, number of lymph nodes, morphologic characteristics, and Doppler signal. Temporal changes in cortical thickness and number of lymph nodes during follow-up were assessed using a linear mixed model. Results Ninety-one women with lymphadenopathy in the vaccinated arm had undergone a total of 215 serial US examinations (mean age, 44 years ± 13 [SD]). Fifty-one participants had received a vector vaccine (ChAdOx1 nCoV-19 vaccine) and 40 had received an mRNA vaccine (BNT162b2 vaccine [n = 37] and mRNA-1273 vaccine [n = 3]). Three of the 91 women were lost to follow-up; thus, 88 women underwent serial US. Complete resolution of axillary lymphadenopathy was observed at a median of 6 weeks after vaccination (range, 4-7 weeks) in 26% of women (23 of 88). Among 49 women with follow-up US at a median of 12 weeks after vaccination (range, 8-14 weeks), persistent lymphadenopathy was observed in 25 (51%). During the follow-up period, the cortical thickness gradually decreased (P < .001) over time regardless of vaccine type; however, values were higher in recipients of the mRNA vaccine than in recipients of the vector vaccine (P = .02). Conclusion COVID-19 vaccine-associated axillary lymphadenopathy frequently persisted for more than 6 weeks on US scans. Lymphadenopathy should be interpreted considering vaccine type and time elapsed since vaccination. Follow-up US examination at least 12 weeks after vaccination may be reasonable, particularly for recipients of the messenger RNA vaccine. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Moy and Kim in this issue.

In silico analysis and experimental validation to exhibit anti-nasopharyngeal carcinoma effects of plumbagin, an anti-cancer compound.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is publicly known as a malignant tumor. Our previous study reported that plumbagin exhibits potent anti-cancer actions. Nevertheless, more mechanical details of plumbagin against NPC remain unknown. The present study aimed to unmask the core targets/genes and anti-NPC mechanisms involved in the signaling pathways of plumbagin prior to biochemical validation. METHODS: A network pharmacology approach was employed to respective identification of mutual and core targets/genes in plumbagin and/treating NPC. Molecular docking determination was used to identify core target proteins for biochemical validation using human and cell line samples. RESULTS: In total, 60 anti-NPC genes of plumbagin were screened out, and then nine core target genes of plumbagin against NPC were identified accordingly. The enrichment findings revealed detailed biological functions and pharmacological pathways of plumbagin against NPC. Moreover, in silico analysis using molecular docking had determined the core targets for further experimental validation, comprising protein kinase B (AKT1) and sarcoma gene (SRC). In human sample validation, clinical NPC sections showed increased positive expression of AKT1 and SRC. Additionally, plumbagin-treated NPC cells resulted in inactivated protein expression of AKT1 and SRC. CONCLUSION: The re-identified core targets/genes in the molecular docking report may function as plumbagin-related pharmacological targets for treating NPC via experimental validation. Furthermore, additional anti-NPC molecular mechanisms of plumbagin action were disclosed on the basis of enrichment findings. © 2022 Society of Chemical Industry.

Ipsilateral Lymphadenopathy After COVID-19 Vaccination in Patients With Newly Diagnosed Breast Cancer.

This study aimed to evaluate the imaging and pathological findings in axillary lymph nodes in patients with breast cancer who received concurrent ipsilateral coronavirus disease 2019 (COVID-19) vaccination. Of the 19 women with breast cancer who received concurrent COVID-19 vaccination shot in the arm ipsilateral to breast cancer, axillary lymphadenopathy was observed in 84.2% (16 of 19) of patients on ultrasound (US) and 71.4% (10 of 14) of patients on magnetic resonance imaging (MRI), and 21.0% (4 of 19) of patients were diagnosed with metastasis. Abnormal US and MRI findings of cortical thickening, effacement of the fatty hilum, round shape, and asymmetry in the number or size relative to the contralateral side were noted in more than half of the non-metastatic and metastatic lymph nodes; however, statistical significance was not noted. Axillary lymphadenopathy is commonly observed in patients with breast cancer who receive concurrent ipsilateral COVID-19 vaccination without specific differential imaging features. Thus, understanding the limitations of axillary imaging and cautious interpretation is necessary to avoid overestimation or underestimation of the axillary disease burden.

SARS-CoV-2-Specific Vaccine Candidates; the Contribution of Structural Vaccinology.

SARS-CoV-2 vaccine production has taken us by storm. We aim to fill in the history of concepts and the work of pioneers and provide a framework of strategies employing structural vaccinology. Cryo-electron microscopy became crucial in providing three-dimensional (3D) structures and creating candidates eliciting T and B cell-mediated immunity. It also determined structural changes in the emerging mutants in order to design new constructs that can be easily, quickly and safely added to the vaccines. The full-length spike (S) protein, the S1 subunit and its receptor binding domain (RBD) of the virus are the best candidates. The vaccine development to cease this COVID-19 pandemic sets a milestone for the pan-coronavirus vaccine's designing and manufacturing. By employing structural vaccinology, we propose that the mRNA and the protein sequences of the currently approved vaccines should be modified rapidly to keep up with the more infectious new variants.