Impact of the COVID-19 pandemic on cancer healthcare utilization in southwestern China on March 2021.

BACKGROUND: Oncological care has been disrupted worldwide during the COVID-19 pandemic. We aimed to quantify the long-term impact of the pandemic on cancer care utilization and to examine how this impact varied by sociodemographic and clinical factors in southwestern China, where the Dynamic Zero-COVID Strategy was implemented. This strategy mainly included lockdowns, stringent testing, and travel restrictions to prevent the spread of COVID-19. METHOD: We identified 859,497 episodes of the utilization of cancer care from electronic medical records between January 1, 2019, and March 31, 2021, from the cancer center of a tertiary hospital serving an estimated population of 8.4 million in southwestern China. Changes in weekly utilization were evaluated via segmented Poisson regression across service categories, stratified by cancer type and sociodemographic factors. RESULTS: A sharp reduction in utilization of in-person cancer services occurred during the first week of the pandemic outbreak in January 2020, followed by a quick rebound in February 2020. Although there were few COVID-19 cases from March 2020 until this analysis, the recovery of most in-person services was slow and remained incomplete as of March 31, 2021. The exceptions were outpatient radiation and surgery, which increased and exceeded pre-pandemic levels, particularly among lung cancer patients; meanwhile, telemedicine utilization increased substantially after the onset of the pandemic. Care disruptions were most prominent for women, rural residents, uninsured, and breast cancer patients. CONCLUSIONS: As of March 2021, despite few COVID-19 cases, the COVID-19 pandemic has had a strong and continuing impact on in-person oncology care utilization in southwestern China under the Dynamic Zero-COVID Strategy. Equitable and timely access to cancer care requires adjustment in strict policies for COVID-19 prevention and control, as well as targeted remedies for the most vulnerable populations during and beyond the pandemic. Future studies should monitor the long-term effects of the COVID-19 pandemic and response strategies on cancer care and outcomes.

Evaluating Community Capability to Prevent and Control COVID-19 Pandemic in Shenyang, China: An Empirical Study Based on a Modified Framework of Community Readiness Model

Community plays a crucial role in the successful prevention and control of the COVID-19 pandemic in China. However, evaluation of community capability to fight against COVID-19 is rarely reported. The present study provides a first attempt to assess community capability to combat COVID-19 in Shenyang, the capital city of Liaoning province in Northeast China, based on a modified framework of a community readiness model. We conducted semi-structured interviews with ninety key informants from fifteen randomly selected urban communities to collect the data. The empirical results indicate that the overall level of community capability for epidemic prevention and control in Shenyang was at the stage of preparation. The specific levels of the fifteen communities ranged from the stages of preplanning to preparation to initiation. Concerning the level of each dimension, community knowledge about the issue, leadership, and community attachment exhibited significant disparities between communities, while there were slight differences among communities on community efforts, community knowledge of efforts, and community resources. In addition, leadership demonstrated the highest overall level among all the six dimensions, followed by community attachment and community knowledge of efforts. Community resources displayed the lowest level, followed by community efforts. This study not only extends the application of the modified community readiness model to evaluate community capability of epidemic prevention in the Chinese community context, but also offers practical implications for enhancing Chinese communities' capabilities to deal with various future public health emergencies.

Evaluating Community Capability to Prevent and Control COVID-19 Pandemic in Shenyang, China: An Empirical Study Based on a Modified Framework of Community Readiness Model.

Community plays a crucial role in the successful prevention and control of the COVID-19 pandemic in China. However, evaluation of community capability to fight against COVID-19 is rarely reported. The present study provides a first attempt to assess community capability to combat COVID-19 in Shenyang, the capital city of Liaoning province in Northeast China, based on a modified framework of a community readiness model. We conducted semi-structured interviews with ninety key informants from fifteen randomly selected urban communities to collect the data. The empirical results indicate that the overall level of community capability for epidemic prevention and control in Shenyang was at the stage of preparation. The specific levels of the fifteen communities ranged from the stages of preplanning to preparation to initiation. Concerning the level of each dimension, community knowledge about the issue, leadership, and community attachment exhibited significant disparities between communities, while there were slight differences among communities on community efforts, community knowledge of efforts, and community resources. In addition, leadership demonstrated the highest overall level among all the six dimensions, followed by community attachment and community knowledge of efforts. Community resources displayed the lowest level, followed by community efforts. This study not only extends the application of the modified community readiness model to evaluate community capability of epidemic prevention in the Chinese community context, but also offers practical implications for enhancing Chinese communities' capabilities to deal with various future public health emergencies.

Lymphocytes regulate expression of the SARS-CoV-2 cell entry factor ACE2 in the pancreas of T2DM patients.

AIMS: COVID-19 patients with type 2 diabetes mellitus (T2DM) show both poorer clinical outcomes and have an increased risk of death. SARS-CoV-2 virus infection requires simultaneous expression of the SARS-CoV-2 cell entry factors angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine type 2 (TMPRSS2) in the same cell. The aim of the study was to explore the underlying mechanisms of a COVID-19 infection in patients with T2DM. METHODS: The distribution and expression of AEC2 and TMPRSS2 in different pancreatic cell types in clinical samples of T2DM patients and diabetic mouse models were analysed by single-cell sequencing, bioinformatics analysis and basic experiments. RESULTS: The results showed that ACE2 and TMPRSS2 are expressed in the ducts of the human pancreas. These findings suggest that SARS-CoV-2 can infect ductal cells in vivo through ACE2 and TMPRSS2. T2DM can promote the co-expression of ACE2 and TMPRSS2 in exocrine ducts, including in the human pancreas. We hypothesize that ACE2 expression levels are associated with increased numbers of lymphocytes in vivo. CONCLUSIONS: Increased blood glucose levels are associated with increased ACE2 expression and an increased number of lymphocytes. At the same time, lymphocytes can promote ACE2 expression.

Phospholipid remodeling and its derivatives are associated with COVID-19 severity.

BACKGROUND: Timely medical intervention in severe cases of coronavirus disease 2019 (COVID-19) and better understanding of the disease's pathogenesis are essential for reducing mortality, but early classification of severe cases and its progression is challenging. OBJECTIVE: We investigated the levels of circulating phospholipid metabolites and their relationship with COVID-19 severity, as well as the potential role of phospholipids in disease progression. METHODS: We performed nontargeted lipidomic analysis of plasma samples (n = 150) collected from COVID-19 patients (n = 46) with 3 levels of disease severity, healthy individuals, and subjects with metabolic disease. RESULTS: Phospholipid metabolism was significantly altered in COVID-19 patients. Results of a panel of phosphatidylcholine (PC) and lysophosphatidylcholine (LPC) and of phosphatidylethanolamine and lysophosphatidylethanolamine (LPE) ratios were significantly correlated with COVID-19 severity, in which 16 phospholipid ratios were shown to distinguish between patients with severe disease, mild disease, and healthy controls, 9 of which were at variance with those in subjects with metabolic disease. In particular, relatively lower ratios of circulating (PC16:1/22:6)/LPC 16:1 and (PE18:1/22:6)/LPE 18:1 were the most indicative of severe COVID-19. The elevation of levels of LPC 16:1 and LPE 18:1 contributed to the changes of related lipid ratios. An exploratory functional study of LPC 16:1 and LPE 18:1 demonstrated their ability in causing membrane perturbation, increased intracellular calcium, cytokines, and apoptosis in cellular models. CONCLUSION: Significant Lands cycle remodeling is present in patients with severe COVID-19, suggesting a potential utility of selective phospholipids with functional consequences in evaluating COVID-19's severity and pathogenesis.

Phospholipid remodeling and its derivatives are associated with the severity of COVID-19

Graphical Background Timely medical interventions in severe cases of COVID-19 and better understanding of the pathogenesis are essential for reducing the mortality, but early classification of severe cases and its progression is challenging. Objective To investigate the levels of circulating phospholipid metabolites and their relationship with the severity of COVID-19 and the potential role of phospholipids in the progression of the disease. Methods In this study, we performed non-targeted lipidomic analysis of plasma samples (n=150) collected from COVID-19 patients (N=46) with three levels of severity, healthy individuals and subjects with metabolic diseases. Results Results showed that phospholipid metabolism was significantly altered in COVID-19 patients. A panel of phosphatidylcholine (PC) and lysophosphatidylcholine (LPC) and of phosphatidylethanolamine (PE) and lysophosphatidylethanolamine (LPE) ratios were significantly correlated with the severity of COVID-19, in which 16 phospholipid ratios were shown to distinguish severe patients from mild cases and healthy controls, and 9 of which were at variance with those in subjects with metabolic diseases. In particular, relatively lower ratios of circulating (PC16:1/22:6)/LPC16:1 and (PE18:1/22:6)/LPE18:1 were the most indicative of severe COVID-19. The elevation of levels of LPC16:1 and LPE18:1 contributed to the changes of related lipid ratios. An exploratory functional study of LPC16:1 and LPE18:1 demonstrated their ability in causing membrane perturbation, increased intracellular calcium, cytokines, and apoptosis in cellular models. Conclusion These results demonstrate significant Lands cycle remodeling in patients with severe COVID-19, and suggest the potential utility of selective phospholipids with functional consequences in evaluating COVID-19 severity and its pathogenesis. Phospholipid ratio correlated with the severity of COVID-19, and the biological functions of phospholipid derivatives may be associated with exacerbation of the disease

Pregnant Through the COVID-19 Chaos: Insights on How Women Use Information in the Perinatal Period During a Pandemic.

PURPOSE/AIMS: To gain insights in how women use technology to address health information needs during the prenatal and postpartum time frame. DESIGN: An exploratory qualitative study recruited pregnant and recent postpartum women to share their perspectives on information they needed and how they obtained it. METHODS: Women who were pregnant or <90 days postpartum (n = 26) were recruited via social media and invited to share their experiences. Design thinking methodology was used to develop questions to understand information needs in the perinatal period as well as in context of the COVID-19 pandemic. Verbatim transcripts were coded by the research team according to Braun and Clarke's reflexive thematic analysis. RESULTS: Five themes explain the experience of seeking information to support the perinatal period. Women explained the need for the following: (1) information and relationships are inseparable, (2) current practices leave needs unmet, (3) the pandemic exposes vulnerability in prenatal care, (4) left to figure it out alone, and (5) bridging the gap through technology. CONCLUSIONS: Aggregated findings suggest how usual care can be modified to improve support for women through personalized care, improved information support, and use of technology. The study findings inform innovative strategies using current technologies to improve health promotion in a dynamic health environment.

S Protein of SARS-CoV-2: research progress and challenges

SARS-CoV-2, which caused a pandemic, is a new coronavirus pathogen that can spread rapidly from person to person. The spike protein (S) on the surface of coronavirus plays an important role in determining the host specificity. pathogenicity and interspecies transmission of the virus. S protein is the most studied SARS - CoV-2 protein after the outbreak of SARS-CoV-2. S protein is also the most important antigenic protein for the development of SAES - CoV -2 vaccine and the important target of antiviral drugs. Here the latest research progress of SARS-CoV-2 S protein was reviewed, and the problems and challenges in current research were discussed. .

Radiation therapy practice changes in the COVID-19 pandemic era: A pilot study in California.

PURPOSE: This study aims to investigate practice changes among Southern and Northern California's radiation oncology centers during the COVID-19 pandemic. METHODS: On the online survey platform SurveyMonkey, we designed 10 survey questions to measure changes in various aspects of medical physics practice. The questions covered patient load and travel rules; scopes to work from home; new protocols to reduce corona virus disease-2019 (COVID-19) infection risk; availability of telemedicine; and changes in fractionation schedules and/or type of treatment plans. We emailed the survey to radiation oncology centers throughout Northern and Southern California, requesting one completed survey per center. All responses were anonymized, and data were analyzed using both qualitative and quantitative research methods. RESULTS: At the end of a 4-month collection period (July 2, 2021 to October 11, 2021), we received a total of 61 responses throughout Southern and Northern California. On average, 4111 patients were treated per day across the 61 centers. New COVID-19-related department and hospital policies, along with hybrid workflow changes, infectious control policies, and changes in patient load have been reported. Results also showed changes in treatment methods during the pandemic, such as increased use of telemedicine, hypofractionation for palliative, breast cancer, and prostate cancer cases; and simultaneous boosts, compared to sequential boosts. CONCLUSION: Our California radiation oncology center population study shows changes in various aspects of radiation oncology practices during the COVID-19 pandemic. This study serves as a pilot study to identify possible correlations and new strategies that allow radiation oncology centers to continue providing quality patient care while ensuring the safety of both staff and patients.

Improving antibody affinity through in vitro mutagenesis in complementarity determining regions.

High-affinity antibodies are widely used in diagnostics and for the treatment of human diseases. However, most antibodies are isolated from semi-synthetic libraries by phage display and do not possess in vivo affinity maturation, which is triggered by antigen immunization. It is therefore necessary to engineer the affinity of these antibodies by way of in vitro assaying. In this study, we optimized the affinity of two human monoclonal antibodies which were isolated by phage display in a previous related study. For the 42A1 antibody, which targets the liver cancer antigen glypican-3, the variant T57H in the second complementarity-determining region of the heavy chain (CDR-H2) exhibited a 2.6-fold improvement in affinity, as well as enhanced cell-binding activity. For the I4A3 antibody to severe acute respiratory syndrome coronavirus 2, beneficial single mutations in CDR-H2 and CDR-H3 were randomly combined to select the best synergistic mutations. Among these, the mutation S53P-S98T improved binding affinity (about 3.7 fold) and the neutralizing activity (about 12 fold) compared to the parent antibody. Taken together, single mutations of key residues in antibody CDRs were enough to increase binding affinity with improved antibody functions. The mutagenic combination of key residues in different CDRs creates additive enhancements. Therefore, this study provides a safe and effective in vitro strategy for optimizing antibody affinity.

Temporal variation of gaseous elemental mercury in a northern coastal city in China: Monsoon and COVID-19 lockdown effects

Continuous measurements of gaseous elemental mercury (GEM) were conducted in Qingdao from March 2020 to March 2021. The average concentration of GEM was (2.39 ± 1.07 ng/m3) with a variation range of 0.27–10.78 ng/m3. GEM exhibited a clear pattern of daily variation, with daily peaks occurring between 11:00–13:00. GEM concentrations were higher in winter (2.80 ± 1.28 ng/m3) than that in summer (2.18 ± 1.05 ng/m3). The high winter concentrations were related to coal-fired heating and the increased frequency of polluted weather in northern China. Principal component analysis showed that the main factors affecting GEM concentration were fossil fuel combustion, natural source release and atmospheric diffusion conditions. The anthropogenic emission sources were the main source of GEM in spring and winter, and natural sources of GEM was large in summer. The potential source contribution function suggested that North and Central China were the main potential sources of GEM, and there were large differences in the potential sources of GEM in different seasons. Comparing the GEM in the same time periods in 2018, 2020, and 2021, government policies, temporary lockdown measures for the COVID-19 epidemic, and urban village renovation led to a decreasing trend of GEM concentrations. This study contributes to a better understanding of the effects of long-range transport of air masses and anthropogenic emissions on atmospheric mercury in eastern coastal cities and offshore areas.

Clarifying real receptor binding site between coronavirus HCoV-HKU1 and 9-O-Ac-Sia based on molecular docking.

HCoV-HKU1 is a [Formula: see text]-coronavirus with low pathogenicity, which usually leads to respiratory diseases. At present, a controversial issue is that whether the receptor binding site (RBS) of HCoV-HKU1 is located in the N-terminal domain (NTD) or the C-terminal domain (CTD) in the HCoV-HKU1 S protein. To address this issue, we used molecular docking technology to dock the NTD and CTD with 9-oxoacetylated sialic acid (9-O-Ac-Sia), respectively, with the results showing that the RBS of HCoV-HKU1 is located in the NTD (amino acid residues 80-95, 25-32). Our findings clarified the structural basis and molecular mechanism of the HCoV-HKU1 infection, providing important information for the development of therapeutic antibody drugs and the design of vaccines.

Non-viral vectors for RNA delivery.

RNA-based therapy is a promising and potential strategy for disease treatment by introducing exogenous nucleic acids such as messenger RNA (mRNA), small interfering RNA (siRNA), microRNA (miRNA) or antisense oligonucleotides (ASO) to modulate gene expression in specific cells. It is exciting that mRNA encoding the spike protein of COVID-19 (coronavirus disease 2019) delivered by lipid nanoparticles (LNPs) exhibits the efficient protection of lungs infection against the virus. In this review, we introduce the biological barriers to RNA delivery in vivo and discuss recent advances in non-viral delivery systems, such as lipid-based nanoparticles, polymeric nanoparticles, N-acetylgalactosamine (GalNAc)-siRNA conjugate, and biomimetic nanovectors, which can protect RNAs against degradation by ribonucleases, accumulate in specific tissue, facilitate cell internalization, and allow for the controlled release of the encapsulated therapeutics.

Molecular evolutionary characteristics of SARS-CoV-2 emerging in the United States.

SARS-CoV-2 is a newly discovered beta coronavirus at the end of 2019, which is highly pathogenic and poses a serious threat to human health. In this paper, 1875 SARS-CoV-2 whole genome sequences and the sequence coding spike protein (S gene) sampled from the United States were used for bioinformatics analysis to study the molecular evolutionary characteristics of its genome and spike protein. The MCMC method was used to calculate the evolution rate of the whole genome sequence and the nucleotide mutation rate of the S gene. The results showed that the nucleotide mutation rate of the whole genome was 6.677 × 10-4 substitution per site per year, and the nucleotide mutation rate of the S gene was 8.066 × 10-4 substitution per site per year, which was at a medium level compared with other RNA viruses. Our findings confirmed the scientific hypothesis that the rate of evolution of the virus gradually decreases over time. We also found 13 statistically significant positive selection sites in the SARS-CoV-2 genome. In addition, the results showed that there were 101 nonsynonymous mutation sites in the amino acid sequence of S protein, including seven putative harmful mutation sites. This paper has preliminarily clarified the evolutionary characteristics of SARS-CoV-2 in the United States, providing a scientific basis for future surveillance and prevention of virus variants.

Transformation of antiviral ribavirin during ozone/PMS intensified disinfection amid COVID-19 pandemic.

Due to the spread of coronavirus disease 2019 (COVID-19), large amounts of antivirals were consumed and released into wastewater, posing risks to the ecosystem and human health. Ozonation is commonly utilized as pre-oxidation process to enhance the disinfection of hospital wastewater during COVID-19 spread. In this study, the transformation of ribavirin, antiviral for COVID-19, during ozone/PMS­chlorine intensified disinfection process was investigated. •OH followed by O3 accounted for the dominant ribavirin degradation in most conditions due to higher reaction rate constant between ribavirin and •OH vs. SO4•- (1.9 × 109 vs. 7.9 × 107 M-1 s-1, respectively). During the O3/PMS process, ribavirin was dehydrogenated at the hydroxyl groups first, then lost the amide or the methanol group. Chloride at low concentrations (e.g., 0.5- 2 mg/L) slightly accelerated ribavirin degradation, while bromide, iodide, bicarbonate, and dissolved organic matter all reduced the degradation efficiency. In the presence of bromide, O3/PMS process resulted in the formation of organic brominated oxidation by-products (OBPs), the concentration of which increased with increasing bromide dosage. However, the formation of halogenated OBPs was negligible when chloride or iodide existed. Compared to the O3/H2O2 process, the concentration of brominated OBPs was significantly higher after ozonation or the O3/PMS process. This study suggests that the potential risks of the organic brominated OBPs should be taken into consideration when ozonation and ozone-based processes are used to enhance disinfection in the presence of bromide amid COVID-19 pandemic.

Ecotoxicological effects of disinfected wastewater effluents: a short review of in vivo toxicity bioassays on aquatic organisms. (Themed issue on drinking water oxidation and disinfection processes.)

Wastewater disinfection has attracted attention with regard to fecal-oral transmission during the current coronavirus disease 2019 (COVID-19) outbreak in China. Disinfection reduces the risk posed by waterborne pathogens;however, it threatens ecological safety. Comprising residual disinfectants, disinfection byproducts (DBPs), and other contaminants, disinfected wastewater effluents have a negative impact on aquatic organisms as well as on the balance of the aquatic ecosystem of the recipient water body. Here, we reviewed the in vivo toxicity bioassays of disinfected wastewater effluents on the aquatic organisms at different trophic levels, including freshwater organisms and marine organisms. Associated variables, i.e., total suspended solids (TSSs), ammonia nitrogen (NH3-N), residual disinfectants, and features of the effluent (water temperature and sampling season), can significantly influence the results of these in vivo toxicity bioassays. Each typical test organism has its own pros and cons, where the species type, life stages, and test endpoints have crucial influences on the bioassays;therefore, they should be taken into account before and during the studies on ecotoxicological effects. More efforts should be expended toward conducting more practical bioassays involving the scenarios of the recipient water body in order to better simulate real ecotoxicological effects of disinfected wastewater effluents;extended exposure time should be considered to gain additional insights into the long-term or pass-generation ecotoxicological effects, approaching true levels in the recipient water body.