Barriers to and facilitators of advance care planning implementation for medical staff after the coronavirus disease 2019 pandemic: An overview of reviews (preprint)

Background: The coronavirus disease 2019 (COVID-19) pandemic has impacted the capacity for advance care planning between patients, families, and healthcare teams. The barriers to and facilitators of advance care planning vary with settings. This study sought to identify and review the barriers to and facilitators of advance care planning implementation for medical staff in different settings (e.g., hospitals, outpatients, care and nursing homes) during the COVID-19 pandemic. Methods: This study followed an overview of review design and was registered in the International Prospective Register of Systematic Reviews (CRD42022351362). A search of MEDLINE, CENTRAL, Web of Science, and Embase databases was performed through November 14, 2022. AMSTAR 2 was used to assess the risk of bias. Results: The final analyses included seven studies. Common barriers to advance care planning implementation included visitation restrictions, limited resources and personnel, and lack of coordination among health professionals. In care and nursing homes, the lack of palliative care physicians and the psychological burden on staff were identified as barriers. Using telemedicine for information-sharing was a common facilitator. In hospitals, facilitators were short-term training in palliative care and palliative care physicians joining the acute care team; in care homes and nursing homes, they were advance care planning education and emotional support for staff. Conclusions: Although inadequate staff education regarding advance care planning in hospitals and facilities and the lack of community-level information-sharing have long been noted, the pandemic highlighted these issues. Short-term training programs for staff and immediate information-sharing could facilitate advance care planning.

Enhancing Food Supply Chain in Green Logistics with Multi-Level Processing Strategy under Disruptions

Food supply chains (FSCs) have long been exposed to environmental variability and shock events caused by various economic, political, and infrastructural factors. The outbreak of the COVID-19 pandemic has further exposed and identified the vulnerability of FSCs, and promoted integrated optimization approaches for building resilience. However, existing works focusing on general supply chains (SCs) and FSCs have not been fully aware of the distinct characteristics of FSCs in green logistics, i.e., the expiration of fresh products. In reality, perishable food materials can be processed into products of different processing levels (i.e., multi-level processing) for longer shelf lives, which can serve as a timely and economic strategy to increase safety stocks for mitigating disruption risks. Motivated by this fact, we study the problem of enhancing FSC with a multi-level processing strategy. An integrated location, inventory, and distribution planning model for a multi-echelon FSC under COVID-19-related disruptions is formulated to maximize the total profit over a finite planning horizon. Specifically, a two-stage stochastic programming model is presented to hedge against disruption risks, where scenarios are generated to characterize geographical impact induced by source-region disruptions. For small-scale problems, the model can be solved with commercial solvers. To exactly and efficiently solve the large-scale instances, we design an integer L-shaped method. Numerical experiments are conducted on a case study and randomly generated instances to show the efficiency of our model and solution method. Based on the case study, managerial insights are drawn.

Genome-wide CRISPR screens identify noncanonical translation factor eIF2A as an enhancer of SARS-CoV-2 programmed -1 ribosomal frameshifting (preprint)

Many positive-strand RNA viruses, including all known coronaviruses, employ programmed -1 ribosomal frameshifting (-1 PRF) to regulate the translation of polycistronic viral RNAs. However, only a few host factors have been shown to regulate -1 PRF. Through a reporter-based genome-wide CRISPR/Cas9 knockout screen, we identified several host factors that either suppressed or enhanced -1 PRF of SARS-CoV-2. One of these factors is eukaryotic translation initiation factor 2A (eIF2A), which specifically and directly enhanced -1 PRF in vitro and in cells. Consistent with the crucial role of efficient -1 PRF in transcriptase/replicase expression, loss of eIF2A reduced SARS-CoV-2 replication in cells. Transcriptome-wide analysis of eIF2A-interacting RNAs showed that eIF2A primarily interacted with 18S ribosomal RNA near the contacts between the SARS-CoV-2 frameshift-stimulatory element (FSE) and the ribosome. Thus, our results revealed an unexpected role for eIF2A in modulating the translation of specific RNAs independent of its previously described role during initiation.

Creating Knowledge Assets under Biocapitalism: Analyzing China’s Biomedical Industry and Its Patent Networks

Breakthroughs in biotechnology, globalizing intellectual property rights legislations, and growing venture capital in the past thirty years have given rise to new forms of capitalist accumulation that scholars called biocapitalism. Bioscientific knowledge under biocapitalism is increasingly parceled out from a global common to private enclosures for biotech and pharmaceutical companies, contributing to vast inequalities and fractures of global access to innovation evident in the COVID-19 pandemic. The assetization and financialization of knowledge have shifted the ground of innovation from competitive commodity production and exchanges to generating, managing, and commercializing patents and associated monopoly rights, thus raising the challenges of innovation for those developing countries specialized in production. Many Asian countries have invested heavily in biomedical sciences to enhance their knowledge assets but had limited success in translating the scientific development to a globally significant biomedical industry. This article discusses the evolution of China’s biomedical industry from a technological laggard to a recent innovation boom after a regulatory overhaul in 2015. Analyzing the patent collaborative networks of China’s biomedical industry since 2003, we found the central roles of domestic public research institutions, in contrast to multinational corporations, as cutting-edge knowledge providers. We argue that China’s path of the biomedical industry is distinct from its other technology industries that rely on multinational corporations for core knowledge. It represents a national articulation in response to global biocapitalism by situating the domestic research institutions and biomedical firms at the center of knowledge assets production and engaging globally in the science and drug regulatory systems. [ FROM AUTHOR] Copyright of Economic Geography is the property of Taylor & Francis Ltd 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.)

China’s Port Carbon Emission Reduction: A Study of Emission-Driven Factors

Ports offer an effective way to facilitate the global economy. However, massive carbon emission during port operating aggravates the atmospheric pollution in port cities. Capturing characteristics of port carbon emission is vital to reduce GHG (greenhouse gas) in the maritime realm as well as to achieve China’s carbon neutral objective. In this work, an integrated framework is proposed for exploring the driving factors of China ports’ emissions combined with stochastic effects on population, affluence and technology regression (STIRPAT), Global Malmquist-Luenberger (GML) and multiple linear regression (MLR). The port efficiency is estimated for each port and the potential driving factors of carbon emission are explored. The results indicate that port carbon emissions have a strong connection with port throughput, productivity, containerization and intermodal transshipment. It is worth noting that the containerization ratio and port physical facility with fossil-free energy improvement have positively correlated with carbon emissions. However, the specific value of waterborne transshipment shows a complex impact on carbon dioxide emission as the ratio increases. The findings reveal that China port authorities need to improve containerization ratio and develop intermodal transportation;meanwhile, it is responsible for port authorities to update energy use and improve energy efficiency in ways to minimize the proportion of non-green energy consumption in accordance with optimizing port operation management including peak shaving and intelligent management systems under a new horizon of clean energy and automatic equipment.

Evolution of the plandemic communication network among serial participants on Twitter

The coronavirus pandemic has been accompanied by the spread of misinformation on social media. The Plandemic conspiracy theory holds that the pandemic outbreak was planned to create a new social order. This study examines the evolution of this popular conspiracy theory from a dynamic network perspective. Guided by the analytical framework of network evolution, the current study explores drivers of tie changes in the Plandemic communication network among serial participants over a 4-month period. Results show that tie changes are explained by degree-based and closure-based structural features (i.e. tendencies toward transitive closure and shared popularity and tendencies against in-degree activity and transitive reciprocated triplet) and nodal attributes (i.e. bot probability and political preference). However, a participant’s level of anger expression does not predict the evolution of the observed network. [ABSTRACT FROM AUTHOR] Copyright of New Media & Society is the property of Sage Publications, Ltd. 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 abstract 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 abstract. (Copyright applies to all Abstracts.)

Peptides Derived From S and N Proteins of Severe Acute Respiratory Syndrome Coronavirus 2 Induce T Cell Responses: A Proof of Concept for T Cell Vaccines.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that escape vaccine-induced neutralizing antibodies has indicated the importance of T cell responses against this virus. In this study, we highlight the SARS-CoV-2 epitopes that induce potent T cell responses and discuss whether T cell responses alone are adequate to confer protection against SARS-CoV-2 and describe the administration of 20 peptides with an RNA adjuvant in mice. The peptides have been synthesized based on SARS-CoV-2 spike and nucleocapsid protein sequences. Our study demonstrates that immunization with these peptides significantly increases the proportion of effector memory T cell population and interferon-γ (IFN-γ)-, interleukin-4 (IL-4)-, tumor necrosis factor-α (TNF-α)-, and granzyme B-producing T cells. Of these 20 peptides, four induce the generation of IFN-γ-producing T cells, elicit CD8+ T cell (CTL) responses in a dose-dependent manner, and induce cytotoxic T lymphocytes that eliminate peptide-pulsed target cells in vivo. Although it is not statistically significant, these peptide vaccines reduce viral titers in infected hamsters and alleviate pulmonary pathology in SARS-CoV-2-infected human ACE2 transgenic mice. These findings may aid the design of effective SARS-CoV-2 peptide vaccines, while providing insights into the role of T cells in SARS-CoV-2 infection.

Study on the Impact of the COVID-19 Pandemic on the Spatial Behavior of Urban Tourists Based on Commentary Big Data: A Case Study of Nanjing, China

The global outbreak of the COVID-19 epidemic has caused a considerable impact on humans, which expresses the urgency and importance of studying its impacts. Previous studies either frequently use aggregated research methods of statistic data or stay during COVID-19. The afterward impacts of COVID-19 on human behaviors need to be explored further. This article carries out a non-aggregated study methodology in human geography based on big data from social media comments and takes Nanjing, China, as the research case to explore the afterward impact of the COVID-19 epidemic on the spatial behavior of urban tourists. Precisely, we propose the methodology covers two main aspects regarding travel contact trajectory and spatial trajectory. In contact trajectory, we explore three indicators—Connection Strength, Degree Centrality, and Betweenness Centrality—of the collected attractions. Then, in spatial trajectory, we input the results from contact trajectory into ArcGIS by using the Orientation–Destination Model and Standard Deviation Ellipse to explore the influences on the spatial pattern. By setting up comparative groups for the three periods of before, during, and after the COVID-19 in Nanjing, this study found that, in the post-epidemic era, (1) the spatial behavior of urban tourists showed a state of overall contraction;(2) the objects of contraction changed from urban architectural attractions to urban natural attractions;(3) the form of contraction presents concentric circles with the central city (Old City of Nanjing) as the core;(4) the direction of contraction heads to the large-scale natural landscape in the central city, which highlights the importance of green open spaces in the post-epidemic era.

Signatures of adaptive evolution during human to mink SARS CoV2 cross species transmission inform estimates of the COVID19 pandemic timing (preprint)

One of the unique features of SARS-CoV-2 is that it mainly evolved neutrally or under purifying selection during the early pandemic. This contrasts with the preceding epidemics of the closely related SARS-CoV and MERS-CoV, both of which evolved adaptively. It is possible that the SARS-CoV-2 exhibits a unique or adaptive feature which deviates from other coronaviruses. Alternatively, the virus may have been cryptically circulating in humans for a sufficient time to have acquired adaptive changes for efficient transmission before the onset of the current pandemic. In order to test the above scenarios, we analyzed the SARS-CoV-2 sequences from minks (Neovision vision) and parenteral human strains. In the early phase of the mink epidemic (April to May 2020), nonsynonymous to synonymous mutation ratios per site within the spike protein was 2.93, indicating a selection process favoring adaptive amino acid changes. In addition, mutations within this protein concentrated within its receptor binding domain and receptor binding motif. Positive selection also left a trace on linked neutral variation. An excess of high frequency derived variants produced by genetic hitchhiking was found during middle (June to July 2020) and early late (August to September 2020) phases of the mink epidemic, but quickly diminished in October and November 2020. Strong positive selection found in SARS-CoV-2 from minks implies that the virus may be not unique in super-adapting to a wide range of new hosts. The mink study suggests that SARS-CoV-2 already went through adaptive evolution in humans, and likely been circulating in humans at least six months before the first case found in Wuhan, China. We also discuss circumstances under which the virus can be well-adapted to its host but fail to induce an outbreak.

Effectiveness of the WHO-authorized Covid-19 Vaccines: a Rapid Review of Global Reports till June 30, 2021 (preprint)

ObjectiveLarge clinical trials have proved the efficacy of Covid-19 vaccine, and the number of literature about the effectiveness is rapidly growing in the first half of year after mass vaccination was administrated globally. This rapid review aims to provide evidence syntheses as a means to complement the current evidence on the vaccine effectiveness (VE) against various outcomes in real-world settings. MethodsThis review is conducted based on the updated guideline of PRISMA 2020. Databases (PubMed, EMBASE, and MedRxiv) were searched up to 30 June 2021, (PROSPERO ID: 266866). The studies that assessed the VE of the 6 WHO-authorized vaccines (BNT162b2, ChAdOx1, Ad26.COV2.S, mRNA-1273, BBIBP-CorV, and CoronaVac) were eligible to be included. Quality assessment was performed based on ROBINS-I by 2 independent reviewers. FindingsA total of 39 studies were included, covering over 15 million of participants from 11 nations. Among the general population after 2 doses of vaccination, the VE against symptomatic SARS-CoV-2 infection was estimated at 89%-97%, 92% (95% CI, 78%-97%) and 94% (95% CI, 86%-97%) for BNT162b2, ChAdOx1 and mRNA-1273, respectively. As for the protective effects against B.1.617.2 related symptomatic infection, the VE was 88% (95% CI, 85.3%-90.1%) by BNT162b2 and 67.0% (95% CI, 61.3%-71.8%) by ChAdOx1 after fully vaccination. ConclusionThis review revealed a consistently high effectiveness of vaccines among the general population in real-world settings. Further studies are needed to provide the information on different races/ethnicity, the effects against SARS-CoV-2 variants, and the duration of protection with longer study time.

Investigation on compliance with sepsis bundle and outcomes in patients with septic shock in Changshu area

Objective: To perform a statistical analysis of the ABO blood group distribution of COVID-19 convalescents, and further analyze the ABO blood group distribution in COVID-l9 convalescents with different plasma antibody titer against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-Z).

Immunization with RBD-P2 and N protects against SARS-CoV-2 in nonhuman primates.

Since the emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), various vaccines are being developed, with most vaccine candidates focusing on the viral spike protein. Here, we developed a previously unknown subunit vaccine comprising the receptor binding domain (RBD) of the spike protein fused with the tetanus toxoid epitope P2 (RBD-P2) and tested its efficacy in rodents and nonhuman primates (NHPs). We also investigated whether the SARS-CoV-2 nucleocapsid protein (N) could increase vaccine efficacy. Immunization with N and RBD-P2 (RBDP2/N) + alum increased T cell responses in mice and neutralizing antibody levels in rats compared with those obtained using RBD-P2 + alum. Furthermore, in NHPs, RBD-P2/N + alum induced slightly faster SARS-CoV-2 clearance than that induced by RBD-P2 + alum, albeit without statistical significance. Our study supports further development of RBD-P2 as a vaccine candidate against SARS-CoV-2. Also, it provides insights regarding the use of N in protein-based vaccines against SARS-CoV-2.

UNDERESTIMATION OF NOVEL RISKS AND ANTI-PANDEMIC PERFORMANCE: THE MODERATING EFFECTS OF POLITICS AND ADAPTIVE INNOVATION

Based on prior research and observations of global responses to the COVID-19 pandemic, we study the relationship between underestimation of novel risks and the performance of fighting adversities (PFA). While prior research suggests that underestimation of risks may have some positive effects on PFA, we propose that, for novel adversities such as the COVID-19 pandemic, underestimation of its risk can be very harmful and damaging. We also propose that the relationship between the underestimation and PFA can be moderated by intensiveness of politics (IPS) and adaptive innovation. The contingent model in this paper provides insightful practical implications to risk and disaster management in human collectives.

Insights into the secondary structural ensembles of the full SARS-CoV-2 RNA genome in infected cells (preprint)

SARS-CoV-2 is a betacoronavirus with a single-stranded, positive-sense, 30-kilobase RNA genome responsible for the ongoing COVID-19 pandemic. Currently, there are no antiviral drugs with proven efficacy, and development of these treatments are hampered by our limited understanding of the molecular and structural biology of the virus. Like many other RNA viruses, RNA structures in coronaviruses regulate gene expression and are crucial for viral replication. Although genome and transcriptome data were recently reported, there is to date little experimental data on native RNA structures in SARS-CoV-2 and most putative regulatory sequences are functionally uncharacterized. Here we report secondary structure ensembles of the entire SARS-CoV-2 genome in infected cells at single nucleotide resolution using dimethyl sulfate mutational profiling with sequencing (DMS-MaPseq) and the algorithm ‘detection of RNA folding ensembles using expectation–maximization’ clustering (DREEM). Our results reveal previously undescribed alternative RNA conformations across the genome, including structures of the frameshift stimulating element (FSE), a major drug target, that are drastically different from prevailing in vitro population average models. Importantly, we find that this structural ensemble promotes frameshifting rates (~40%) similar to in vivo ribosome profiling studies and much higher than the canonical minimal FSE (~20%). Overall, our result highlight the value of studying RNA folding in its native, dynamic and cellular context. The genomic structures detailed here lays the groundwork for coronavirus RNA biology and will guide the design of SARS-CoV-2 RNA-based therapeutics.

A framework for predicting potential host ranges of pathogenic viruses based on receptor ortholog analysis (preprint)

Viral zoonoses are a serious threat to public health and global security, as reflected by the current scenario of the growing number of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cases. However, as pathogenic viruses are highly diverse, identification of their host ranges remains a major challenge. Here, we present a combined computational and experimental framework, called REceptor ortholog-based POtential virus hoST prediction (REPOST), for the prediction of potential virus hosts. REPOST first selects orthologs from a diverse species by identity and phylogenetic analyses. Secondly, these orthologs is classified preliminarily as permissive or non-permissive type by infection experiments. Then, key residues are identified by comparing permissive and non-permissive orthologs. Finally, potential virus hosts are predicted by a key residue-specific weighted module. We performed REPOST on SARS-CoV-2 by studying angiotensin-converting enzyme 2 orthologs from 287 vertebrate animals. REPOST efficiently narrowed the range of potential virus host species (with 95.74% accuracy).

The accessible promoter–mediated supplementary effect of ACE2 provides new insight into the tissue tropism of SARS-CoV-2 (preprint)

Background：Angiotensin-converting enzyme 2 (ACE2) has been confirmed to be a receptor for the newly discovered severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, cell surface ACE2 expression is reported to be inconsistent with clinical tissue tropism of SARS-CoV-2, which complicates understanding of the pathogenesis of 2019 novel coronavirus disease (COVID-19). The consumption of ACE2 by internalization and shedding processes may explain this discordance. Results：To understand the discordance between ACE2 expression and the tissue tropism of SARS-CoV-2, we examined the chromatin accessibility of ACE2 promoter in hundreds of tissues and cell lines using public DNase-seq and assay for transposase-accessible chromatin with high throughput sequencing (ATAC-seq) data. We find that ACE2 promoter is only accessible in three tissues including lung, large intestine and placenta. Also, we examined tumors tissues and ACE2 promoter is observed accessible in five tumors with reported SARS-CoV-2 susceptibility. We confirmed the susceptibility by performing SARS-CoV-2 pseudovirus infection in several cell lines. Conclusions：We propose that open chromatin at the promoter mediates the ACE2 supplementary effect and ensures the entry of SARS-CoV-2. This hypothesis provides a new view and potential clues for further investigation of COVID-19 pathogenesis.

Rapid SARS-CoV-2 Detection by Carbon Nanotube-Based Near-Infrared Nanosensors (preprint)

To effectively track and eliminate COVID-19, it is critical to develop tools for rapid and accessible diagnosis of actively infected individuals. Here, we introduce a single-walled carbon nanotube (SWCNT)-based optical sensing approach towards these ends. We construct a nanosensor based on SWCNTs noncovalently functionalized with ACE2, a host protein with high binding affinity for the SARS-CoV-2 spike protein. Presence of the SARS-CoV-2 spike protein elicits a robust, two-fold nanosensor fluorescence increase within 90 min of spike protein exposure. We characterize the nanosensor stability and sensing mechanism, and passivate the nanosensor to preserve sensing response in saliva and viral transport medium. We further demonstrate that these ACE2-SWCNT nanosensors retain sensing capacity in a surface-immobilized format, exhibiting a 73% fluorescence turn-on response within 5 s of exposure to 35 mg/L SARS-CoV-2 virus-like particles. Our data demonstrate that ACE2-SWCNT nanosensors can be developed into an optical tool for rapid SARS-CoV-2 detection. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=86 SRC="FIGDIR/small/20223404v1_ufig1.gif" ALT="Figure 1"> View larger version (21K): org.highwire.dtl.DTLVardef@b78f2dorg.highwire.dtl.DTLVardef@118fdc8org.highwire.dtl.DTLVardef@1bd5e3corg.highwire.dtl.DTLVardef@175f6a8_HPS_FORMAT_FIGEXP M_FIG C_FIG

Restriction of SARS-CoV-2 Replication by Targeting Programmed -1 Ribosomal Frameshifting In Vitro (preprint)

Translation of open reading frame 1b (ORF1b) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires programmed -1 ribosomal frameshifting (-1 PRF) promoted by an RNA pseudoknot. The extent to which SARS-CoV-2 replication may be sensitive to changes in -1 PRF efficiency is currently unknown. Through an unbiased, reporter-based high-throughput compound screen, we identified merafloxacin, a fluoroquinolone antibacterial, as a -1 PRF inhibitor of SARS-CoV-2. Frameshift inhibition by merafloxacin is robust to mutations within the pseudoknot region and is similarly effective on -1 PRF of other beta coronaviruses. Importantly, frameshift inhibition by merafloxacin substantially impedes SARS-CoV-2 replication in Vero E6 cells, thereby providing the proof of principle of targeting -1 PRF as an effective antiviral strategy for SARS-CoV-2.

Neutrophil surged for mortality of COVID-19: a correlational study (preprint)

Background: Multiorgan damage by SARS-CoV-2 results in alterations of many clinical measures associated with mortality of COVID-19. This research discussed the pioneering pathogenicity factors that lead to the extensive damage elusive. Objectives: A cohort of COVID-19 patients. Methods: : We conducted a correlational analysis of hospital outcomes with an independent cohort of COVID-19 patients and we also presented a death case to illustrate for time course of immune cell density. Results: : The results showed that dysregulated immune cell densities were correlated with hospitalization duration before death, not before discharge. High neutrophil densities allowed sorting out one third of total death cases while a density of less than 70% of the white blood cells allowed sorting out 70% of surviving cases. Conclusion: Collectively surged neutrophil was a top trigger for mortality in patients with COVID-19.