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Background: Person-centred services are inherently related to patients/caregivers' needs. However, the extent to which dysphagia services within Singapore meet consumer needs is largely unknown. Involving patients/caregivers in service evaluation/redesign deepens the understanding of consumer needs. This process also increases the success of implementing service enhancements through relevant and meaningful change. Aim: This study aimed to identify aspects of dysphagia services, within acute and subacute settings in Singapore, perceived as highly important and easy to change by patients/caregivers. Methods & Procedures: Using concept mapping methodology, 5 patients and 11 caregivers reflected on their experiences of receiving dysphagia care and proposed 59 unique suggestions to improve dysphagia services within Singapore. Then, each individual sorted the suggestions into groups based on similarity and rated each statement for its perceived importance and changeability for service enhancement. Data were analysed using multidimensional scaling, hierarchical cluster analysis, and bivariate analysis to generate clusters of conceptually similar suggestions and a prioritised list of suggestions for service enhancement. Results: Twelve clusters were identified, with most rated as more important than changeable for service improvement. Participants prioritised 23 (39%) of the suggestions as highly important and easy to change, and these focused on ensuring effective communication among consumers and healthcare team, enhancing patients and carers' access to support at home, increasing patients and carers' access to educational resources, and improving service quality and access through technology. Conclusion: These findings provide future directions on how to develop and implement dysphagia services in Singapore to better meet the needs of patients/caregivers.

Setting up a global SARS-CoV-2 surveillance system requires an understanding of how virus isolation and propagation practices, use of animal or human sera, and different neutralisation assay platforms influence assessment of SARS-CoV-2 antigenicity. In this study, with the contribution of 15 independent laboratories across all WHO regions, we carried out a controlled analysis of neutralisation assay platforms using the first WHO International Standard for antibodies to SARS-CoV-2 variants of concern (source: NIBSC). Live virus isolates (source: WHO BioHub or individual labs) or spike plasmids (individual labs) for pseudovirus production were used to perform neutralisation assays using the same serum panels. When comparing fold drops, excellent data consistency was observed across the labs using common reagents, including between pseudovirus and live virus neutralisation assays (RMSD of data from mean fold drop was 0.59). Utilising a Bayesian model, geometric mean titres and assay titre magnitudes (offsets) can describe the data efficiently. Titre magnitudes were seen to vary largely even for labs within the same assay group. We have observed that overall, live Microneutralisation assays tend to have the lowest titres, whereas Pseudovirus Neutralisation have the highest (with a mean difference of 3.2 log2 units between the two). These findings are relevant for laboratory networks, such as the WHO Coronavirus Laboratory Network (CoViNet), that seek to support a global surveillance system for evolution and antigenic characterisation of variants to support monitoring of population immunity and vaccine composition policy.

Middle East respiratory syndrome coronavirus (MERS-CoV) is enzootic in dromedary camels and causes zoonotic infection and disease in humans. Although over 80% of the global population of infected dromedary camels are found in Africa, zoonotic disease had only been reported in the Arabia Peninsula and travel-associated disease has been reported elsewhere. In this study, genetic diversity and molecular epidemiology of MERS-CoV in dromedary camels in Ethiopia were investigated during 2017–2020. Of 1766 nasal swab samples collected, 61 (3.5%) were detected positive for MERS-CoV RNA. Of 484 turbinate swab samples collected, 10 (2.1%) were detected positive for MERS-CoV RNA. Twenty-five whole genome sequences were obtained from these MERS-CoV positive samples. Phylogenetically, these Ethiopian camel-originated MERS-CoV belonged to clade C2, clustering with other East African camel strains. Virus sequences from camel herds clustered geographically while in an abattoir, two distinct phylogenetic clusters of MERS-CoVs were observed in two sequential sampling collections, which indicates the greater genetic diversity of MERS-CoV in abattoirs. In contrast to clade A and B viruses from the Arabian Peninsula, clade C camel-originated MERS-CoV from Ethiopia had various nucleotide insertions and deletions in non-structural gene nsp3, accessory genes ORF3 and ORF5 and structural gene N. This study demonstrates the genetic instability of MERS-CoV in dromedaries in East Africa, which indicates that the virus is still actively adapting to its camel host. The impact of the observed nucleotide insertions and deletions on virus evolution, viral fitness, and zoonotic potential deserves further study.

Abstract Hong Kong experienced a surge of Omicron BA.2 infections in early 2022, resulting in one of the highest per-capita death rates of COVID-19. The outbreak occurred in a dense population with low immunity towards natural SARS-CoV-2 infection, high vaccine hesitancy in vulnerable populations, comprehensive disease surveillance and the capacity for stringent public health and social measures (PHSMs). By analyzing genome sequences and epidemiological data, we reconstructed the epidemic trajectory of BA.2 wave and found that the initial BA.2 community transmission emerged from cross-infection within hotel quarantine. The rapid implementation of PHSMs suppressed early epidemic growth but the effective reproduction number (R e ) increased again during the Spring festival in early February and remained around 1 until early April. Independent estimates of point prevalence and incidence using phylodynamics also showed extensive superspreading at this time, which likely contributed to the rapid expansion of the epidemic. Discordant inferences based on genomic and epidemiological data underscore the need for research to improve near real-time epidemic growth estimates by combining multiple disparate data sources to better inform outbreak response policy.

Vaccination and infection history determine the breadth of neutralizing antibody response to SARS-CoV-2 variants and other sarbecoviruses with breakthrough or natural infection combined with vaccination or booster vaccination with mRNA vaccine providing highest neutralization.

The antibody response of children to SARS-CoV-2 is less well studied than in adults. Here Hachim et al. show that children have reduced antibody levels to structural proteins and suggest that the predominance of antibody responses to non-structural proteins can be used to discriminate infection and vaccination.

Hong Kong has used an elimination strategy to control SARS-CoV-2 with stringent measures including traveller quarantine. Here, the authors show that the majority of community-acquired cases until January 2021 resulted from three importations, and that increased transmission followed prolonged periods of restrictions, likely due to adherence fatigue.

Abstract Transfer of SARS-CoV-2 from solids to fingers is one step in infection via contaminated solids, and the possibility of infection from this route has driven calls for increased frequency of handwashing during the COVID-19 pandemic. To analyze this route of infection, we measured the percentage of SARS-CoV-2 that was transferred from a solid to an artificial finger. A droplet of SARS-CoV-2 suspension (1 µL) was placed on a solid, and then artificial skin was briefly pressed against the solid with a light force (3 N). Transfer from a variety of solids was detected, and transfer from the non-porous solids, glass, stainless steel, and Teflon, was substantial when the droplet was still wet. The viral titer for the finger was 13–16% or 0.8–0.9 log less than for the input droplet. Transfer still occurred after the droplet evaporated, but was smaller, 3–9%. We found a lower level of transfer from porous solids but did not find a significant effect of solid wettability for non-porous solids.

BackgroundLow health literacy (HL) is negatively associated with mammography screening uptake. However, evidence of the links between poor HL and low mammography screening participation is scarce.MethodsWe conducted a cross-sectional questionnaire survey among participants of a cancer screening program. We measured HL using a validated Chinese instrument. We assessed breast cancer screening-related beliefs using the Health Belief Model and the accuracy of risk perception. We used multivariable regression models to estimate the relationship between HL and the outcomes.ResultsA total of 821 females were included. 264 (32.2%) had excellent or sufficient, 353 (43.0%) had problematic, and 204 (24.8%) had inadequate health literacy (IHL). Women with IHL were more likely to agree that high price (β = -0.211, 95% CI -0.354 to -0.069), lack of time (β = -0.219, 95% CI -0.351 to -0.088), inconvenient service time (β = -0.291, 95% CI -0.421 to -0.160), long waiting time (β = -0.305, 95% CI -0.447 to -0.164), fear of positive results (β = -0.200, 95% CI -0.342 to -0.058), embarrassment (β = -0.225, 95% CI -0.364 to -0.086), fear of pain (β = -0.154, 95% CI -0.298 to -0.010), fear of radiation (β = -0.177, 95% CI -0.298 to -0.056), lack of knowledge on service location (β = -0.475, 95% CI -0.615 to -0.335), and lack of knowledge on mammography (β = -0.360, 95% CI -0.492 to -0.228) were barriers. They were also less likely to have an accurate breast cancer risk perception (aOR 0.572, 95% CI 0.341 to 0.956).ConclusionWomen with lower HL could have stronger perceived barriers to BC screening and an over-estimation of their breast cancer risk. Tackling emotional and knowledge barriers, financial and logistical assistance, and guidance on risk perception are needed to increase their breast cancer screening uptake.

Why children are generally less susceptible than adults to COVID-19 is unclear and has not extensively been examined longitudinally. Here the authors compare antibodies, cytokines and immune cell responses in adults and children over 6 months post-infection showing, among other things, a reduced CD4+ and CD8+ T cell response in children.

Here, the authors perform plaque reduction neutralization (PRNT) assays quantitating SARS-CoV-2 specific neutralizing antibodies from 195 patients in different disease states and find that patients with severe disease exhibit higher peaks of neutralizing antibody titres than patients with mild or asymptomatic infections and that serum neutralizing antibody persists for over 6 months in most people.

Since its first introduction into China in 2009, influenza A/H1N1pdm virus has undergone a rapid expansion and replaced the classical seasonal A(H1N1) virus. To characterize the ongoing evolution and national transmission dynamics of this virus, we analyzed 335 complete genome, 1259 HA, and 1043 NA sequences of the A/H1N1pdm strains detected in China. We found that the dN/dS value and relative genetic diversity of the A/H1N1pdm virus experienced a decrease from 2009 to 2017, and then a rapid increase during 2018–2019. Importantly, elevated relative genetic diversity was observed in the A/H1N1pdm and the A/H3N2 viruses, as well as two lineages (Victoria and Yamagata) of influenza B virus during 2018–2019, suggesting the simultaneous changes of these viruses in terms of genetic diversity might be associated with the recent large outbreak of seasonal influenza epidemic in China during 2018–2019. Fifteen amino acid mutations were found to be fixed along the main trunks of both HA and NA phylogenetic trees, and some of them are located in the antigen binding site or the receptor binding site. A sequential accumulation of mutations relative to the 2009-vaccine strain was observed in the circulating A/H1N1pdm strains during 2009–2016, while a rapid accumulation of mutations relative to the 2015-vaccine strain appeared in the emerging variants in 2017 shortly after the release of the vaccine. Multiple introductions of the A/H1N1pdm lineages into China were observed during 2009–2019, and East China and South China were found to serve as two major epicenters responsible for the national migration of the virus. In summary, these data provide important insights into the understanding of the evolution, epidemiology and transmission of the A/H1N1pdm virus, and highlight the importance of strengthening influenza surveillance in East China and South China.

ABSTRACT Anti-galactose-α-1,3-galactose (anti-α-Gal) antibody is naturally expressed at a high level in humans. It constitutes about 1% of immunoglobulins found in human blood. Here, we designed a live attenuated influenza virus vaccine that can generate α-Gal epitopes in infected cells in order to facilitate opsonization of infected cells, thereby enhancing vaccine-induced immune responses. In the presence of normal human sera, cells infected with this mutant can enhance phagocytosis of human macrophages and cytotoxicity of NK cells in vitro. Using a knockout mouse strain that allows expression of anti-α-Gal antibody in vivo, we showed that this strategy can increase vaccine immunogenicity and the breadth of protection. This vaccine can induce 100% protection against a lethal heterosubtypic group 1 (H5) or group 2 (mouse-adapted H3) influenza virus challenge in the mouse model. In contrast, its heterosubtypic protective effect in wild-type or knockout mice that do not have anti-α-Gal antibody expression is only partial, demonstrating that the enhanced vaccine-induced protection requires anti-α-Gal antibody upon vaccination. Anti-α-Gal-expressing knockout mice immunized with this vaccine produce robust humoral and cell-mediated responses upon a lethal virus challenge. This vaccine can stimulate CD11blo/− pulmonary dendritic cells, which are known to be crucial for clearance of influenza virus. Our approach provides a novel strategy for developing next-generation influenza virus vaccines. IMPORTANCE Influenza A viruses have multiple HA subtypes that are antigenically diverse. Classical influenza virus vaccines are subtype specific, and they cannot induce satisfactory heterosubtypic immunity against multiple influenza virus subtypes. Here, we developed a live attenuated H1N1 influenza virus vaccine that allows the expression of α-Gal epitopes by infected cells. Anti-α-Gal antibody is naturally produced by humans. In the presence of this antibody, human cells infected with this experimental vaccine virus can enhance several antibody-mediated immune responses in vitro. Importantly, mice expressing anti-α-Gal antibody in vivo can be fully protected by this H1N1 vaccine against a lethal H5 or H3 virus challenge. Our work demonstrates a new strategy for using a single influenza virus strain to induce broadly cross-reactive immune responses against different influenza virus subtypes.

The cytotoxicity of epitope-specific CD8+ T cells is usually measured indirectly through IFNγ production. Existing assays that directly measure this activity are limited mainly to measurements of up to two specificities in a single reaction. Here, we develop a multiplex cytotoxicity assay that allows direct, simultaneous measurement of up to 23 different specificities of CD8+ T cells in a single reaction. This can greatly reduce the amount of starting clinical materials for a systematic screening of CD8+ T cell epitopes. In addition, this greatly enhanced capacity enables the incorporation of irrelevant epitopes for determining the non-specific killing activity of CD8+ T cells, thereby allowing to measure the actual epitope-specific cytotoxicity activities. This technique is shown to be useful to study both human and mouse CD8+ T cells. Besides, our results from human PBMCs and three independent infectious animal models (MERS, influenza and malaria) further reveal that IFNγ expression by epitope-specific CD8+ T cells does not always correlate with their cell-killing potential, highlighting the need for using cytotoxicity assays in specific contexts (e.g., evaluating vaccine candidates). Overall, our approach opens up new possibilities for comprehensive analyses of CD8+ T cell cytotoxicity in a practical manner.

This work is an extension to a formerly reported work on development of integrated chemical kinetic mechanism reduction scheme to produce compact mechanisms for computational fluid dynamics (CFD) simulations. Upon successful application on large-scale mechanisms in the previous work, the reduction scheme is employed here to investigate its applicability on small-scale mechanism using a 111-species detailed ethylene model. The final reduced model consists of 27 species with 147 elementary reactions, and it is 75.7% smaller than the detailed model in terms of total number of species. The reduced model is then applied in one-dimensional laminar flame-speed simulations for model validations. The flame temperature profile computed by the detailed model is successfully replicated by the reduced model, with a maximum deviation of 2.8%. Subsequently, the fidelity of the reduced model is further assessed in erodimensional chemical kinetic simulations under a wide range of shock tube and jet stirred reactor (JSR) conditions. The simulation results show that the reduce model is able to reproduce the species concentration profiles and kinetics of the fuel oxidation adequately in view of its simplified fuel chemistry. The maximum relative error between the computations of the detailed and reduced models is recorded at 20%. In addition, the reduced model is also validated against the experimental results of ethylene oxidation in a JSR. Overall, agreement between the predictions and measurements is obtained, with a maximum deviation of 30%. In this present work, the integrated reduction scheme is demonstrated to be applicable to small-scale mechanism reduction while maintaining the corresponding accuracy for a given application. The compact model proposed here is ready to be used in ethylene flame simulations.

Natural language processing (NLP) is an effective tool for generating structured information from unstructured data, the one that is commonly found in clinical trial texts. Such interdisciplinary research has gradually grown into a flourishing research field with accumulated scientific outputs available. In this study, bibliographical data collected from Web of Science, PubMed, and Scopus databases from 2001 to 2018 had been investigated with the use of three prominent methods, including performance analysis, science mapping, and, particularly, an automatic text analysis approach named structural topic modeling. Topical trend visualization and test analysis were further employed to quantify the effects of the year of publication on topic proportions. Topical diverse distributions across prolific countries/regions and institutions were also visualized and compared. In addition, scientific collaborations between countries/regions, institutions, and authors were also explored using social network analysis. The findings obtained were essential for facilitating the development of the NLP-enhanced clinical trial texts processing, boosting scientific and technological NLP-enhanced clinical trial research, and facilitating inter-country/region and inter-institution collaborations.

Influenza viruses circulate worldwide causing annual epidemics that have a substantial impact on public health. This is despite vaccines being in use for over 70 years and currently being administered to around 500 million people each year. Improvements in vaccine design are needed to increase the strength, breadth, and duration of immunity against diverse strains that circulate during regular epidemics, occasional pandemics, and from animal reservoirs. Universal vaccine strategies that target more conserved regions of the virus, such as the hemagglutinin (HA)-stalk, or recruit other cellular responses, such as T cells and NK cells, have the potential to provide broader immunity. Many pre-pandemic vaccines in clinical development do not utilize new vaccine platforms but use “tried and true” recombinant HA protein or inactivated virus strategies despite substantial leaps in fundamental research on universal vaccines. Significant hurdles exist for universal vaccine development from bench to bedside, so that promising preclinical data is not yet translating to human clinical trials. Few studies have assessed immune correlates derived from asymptomatic influenza virus infections, due to the scale of a study required to identity these cases. The realization and implementation of a universal influenza vaccine requires identification and standardization of set points of protective immune correlates, and consideration of dosage schedule to maximize vaccine uptake.