Pandemic fatigue impedes mitigation of COVID-19 in Hong Kong.

Hong Kong has implemented stringent public health and social measures (PHSMs) to curb each of the four COVID-19 epidemic waves since January 2020. The third wave between July and September 2020 was brought under control within 2 m, while the fourth wave starting from the end of October 2020 has taken longer to bring under control and lasted at least 5 mo. Here, we report the pandemic fatigue as one of the potential reasons for the reduced impact of PHSMs on transmission in the fourth wave. We contacted either 500 or 1,000 local residents through weekly random-digit dialing of landlines and mobile telephones from May 2020 to February 2021. We analyze the epidemiological impact of pandemic fatigue by using the large and detailed cross-sectional telephone surveys to quantify risk perception and self-reported protective behaviors and mathematical models to incorporate population protective behaviors. Our retrospective prediction suggests that an increase of 100 daily new reported cases would lead to 6.60% (95% CI: 4.03, 9.17) more people worrying about being infected, increase 3.77% (95% CI: 2.46, 5.09) more people to avoid social gatherings, and reduce the weekly mean reproduction number by 0.32 (95% CI: 0.20, 0.44). Accordingly, the fourth wave would have been 14% (95% CI%: -53%, 81%) smaller if not for pandemic fatigue. This indicates the important role of mitigating pandemic fatigue in maintaining population protective behaviors for controlling COVID-19.

Insights into COVID-19 epidemiology and control from temporal changes in serial interval distributions in Hong Kong.

The serial interval distribution is used to approximate the generation time distribution, an essential parameter to infer the transmissibility (${R}_t$) of an epidemic. However, serial interval distributions may change as an epidemic progresses. We examined detailed contact tracing data on laboratory-confirmed cases of COVID-19 in Hong Kong during the five waves from January 2020 to July 2022. We reconstructed the transmission pairs and estimated time-varying effective serial interval distributions and factors associated with longer or shorter intervals. Finally, we assessed the biases in estimating transmissibility using constant serial interval distributions. We found clear temporal changes in mean serial interval estimates within each epidemic wave studied and across waves, with mean serial intervals ranged from 5.5 days (95% CrI: 4.4, 6.6) to 2.7 (95% CrI: 2.2, 3.2) days. The mean serial intervals shortened or lengthened over time, which were found to be closely associated with the temporal variation in COVID-19 case profiles and public health and social measures and could lead to the biases in predicting ${R}_t$. Accounting for the impact of these factors, the time-varying quantification of serial interval distributions could lead to improved estimation of ${R}_t$, and provide additional insights into the impact of public health measures on transmission.

Colorimetric immunoassay of furazolidone metabolites based on iron-copper bimetallic organic framework nanoenzyme.

Based on the peroxidase activity of Cu-hemin metal-organic framework (Cu-hemin MOF) nanozyme, a colorimetric enzyme-linked immunosensor was developed for the detection of furazolidone (FZD). Cu-hemin MOF is a bimetallic nanozyme that exhibited a stronger catalytic effect compared with single-metal organic framework nanoenzymes. Cu-hemin-MOF catalyzes hydrogen peroxide (H2O2) to produce hydroxyl radicals (•OH), which oxidizes the chromogenic substrate 3,3',5,5'-tetramethylbenzidine (TMB) to blue oxidized TMB (oxTMB). The absorbance change is at 650 nm. The content of AOZ in animal food can be quickly and accurately determined by changes in absorbance. The linear range of the colorimetric biosensor for detecting FZD was 0.01 ~ 62.52 ng/mL, and the limit of detection was as low as 0.01 ng/mL. The recovery of spikes samples was in the range 94.2-108.0 % and reproducibility was less than 4.8%. In addition, the cross-reaction rate was less than 0.1% when detecting other metabolites except AOZ, indicating that the sensor has good applicability and specificity. This study not only provides a better understanding of the relationship between the dispersion of nanoenzymes and enzyme-like activity but also offers a general method for detecting antibiotics using the nanoenzyme colorimetric method.

Density Functional Theory Study of Bilayer Borophene-Based Anode Material for Rechargeable Lithium Ion Batteries.

The bilayer borophene has been successfully fabricated in experiments recently and possesses superior antioxidation and robust metallic properties, which holds great promise for the future anode materials of Li-ion batteries. Herein, using first-principles calculations, two bilayer borophenes including P6/mmm or P6̅m2 symmetry groups with or without vacancy defects are comprehensively explored and acted as electrode materials with high performance in Li-ion batteries. The charge density difference, adsorption energies, and Bader charge analysis are calculated and discussed for single lithium adsorbed on bilayer borophene. The results shown that with the increase of lithium concentration, the adsorption energies are rapidly decreased due to the repulsion of boron atoms except for the P6̅m2 systems with double side adsorption and corresponding energies remain the narrow range. Meanwhile, the partial density of states shows metallic character after lithium adsorption and indicates good conductivity for the charge-discharge process. Furthermore, small diffusion barriers, low average open-circuit voltage, can be achieved, and large storage capacity is up to 930.2 mA h/g at the lower lithium content of 0.375. These results propose that bilayer borophene might be a good choice for anode material applications in future Li-ion batteries with fast ion diffusion and high power density.

Structural Characterization of Boron Sheets beyond the Monolayer and Implication for Experimental Synthesis and Identification.

The successful synthesis of quasi-freestanding bilayer borophene has aroused much attention for its superior physical properties and holds great promise for future electronic devices. Herein, we comprehensively explore six boron sheets beyond the monolayer and structurally characterize them via various methods using first-principles calculations for experimental references. On the basis of atomic models of borophenes, simulated scanning tunneling microscope (STM) images show different morphologies at different bias voltages and are explained by the partial densities of states and the height differences in the vertical direction. Simulated transmission electron microscope images further probe the internal atomic arrangement of boron sheets and compensate for the shortcomings of STM images to better distinguish different phases of boron sheets. The interlayer coupling strength is stronger in bilayer borophenes than in the three-layer system via the electron localization function and Mulliken bond population. In addition, simulated X-ray diffraction and infrared spectra show different characteristic peaks and corresponding vibrational modes to further characterize these boron sheets. These theoretical results can decrease the prime cost and provide vital guidance for the experimental synthesis and identification of boron sheets beyond the monolayer.

Drinking water disinfection byproduct iodoacetic acid affects thyroid hormone synthesis in Nthy-ori 3-1 cells.

Iodoacetic acid (IAA) is an emerging and the most genotoxic iodinated disinfection byproduct to date. IAA can disrupt the thyroid endocrine function in vivo and in vitro, but the underlying mechanisms remain unclear. In this work, transcriptome sequencing was used to investigate the effect of IAA on the cellular pathways of human thyroid follicular epithelial cell line Nthy-ori 3-1 and determine the mechanism of IAA on the synthesis and secretion of thyroid hormone (TH) in Nthy-ori 3-1 cells. Results of transcriptome sequencing indicated that IAA affected the TH synthesis pathway in Nthy-ori 3-1 cells. IAA reduced the mRNA expression of thyroid stimulating hormone receptor, sodium iodide symporter, thyroid peroxidase, thyroglobulin, paired box 8 and thyroid transcription factor-2, inhibited the cAMP/PKA pathway and Na+-K+-ATPase, and decreased the iodine intake. The results were confirmed by our previous findings in vivo. Additionally, IAA downregulated glutathione and the mRNA expression of glutathione peroxidase 1, leading to increased reactive oxygen species production. This study is the first to elucidate the mechanisms of IAA on TH synthesis in vitro. The mechanisms are associated with down-regulating the expression of genes related to TH synthesis, inhibiting iodine uptake, and inducing oxidative stress. These findings may improve future health risk assessment of IAA on thyroid in human.

Effectiveness of CoronaVac and BNT162b2 Vaccines Against Severe Acute Respiratory Syndrome Coronavirus 2 Omicron BA.2 Infections in Hong Kong.

There is limited evidence on vaccine effectiveness against asymptomatic or mild Omicron infections. We estimated that recent third doses of messenger RNA or inactivated vaccines reduced the risk of self-reported infection by 52% (95% confidence interval, 17%-73%) among randomly sampled adults during the Omicron BA.2-dominated surge in Hong Kong.

Universal Community Nucleic Acid Testing for Coronavirus Disease 2019 (COVID-19) in Hong Kong Reveals Insights Into Transmission Dynamics: A Cross-Sectional and Modeling Study.

BACKGROUND: Testing of an entire community has been used as an approach to control coronavirus disease 2019 (COVID-19). In Hong Kong, a universal community testing program (UCTP) was implemented at the fadeout phase of a community epidemic in July to September 2020. We described the utility of the UCTP in finding unrecognized infections and analyzed data from the UCTP and other sources to characterize transmission dynamics. METHODS: We described the characteristics of people participating in the UCTP and compared the clinical and epidemiological characteristics of COVID-19 cases detected by the UCTP versus those detected by clinical diagnosis and public health surveillance (CDPHS). We developed a Bayesian model to estimate the age-specific incidence of infection and the proportion of cases detected by CDPHS. RESULTS: In total, 1.77 million people, 24% of the Hong Kong population, participated in the UCTP from 1 to 14 September 2020. The UCTP identified 32 new infections (1.8 per 100000 samples tested), consisting of 29% of all local cases reported during the two-week UCTP period. Compared with the CDPHS, the UCTP detected a higher proportion of sporadic cases (62% vs 27%, P<.01) and identified 6 (out of 18) additional clusters during that period. We estimated that 27% (95% credible interval: 22%, 34%) of all infections were detected by the CDPHS in the third wave. CONCLUSIONS: We reported empirical evidence of the utility of population-wide COVID-19 testing in detecting unrecognized infections and clusters. Around three quarters of infections have not been identified through existing surveillance approaches including contact tracing.

Restaurant-Based Measures to Control Community Transmission of COVID-19, Hong Kong.

Controlling transmission in restaurants is an important component of public health and social measures for coronavirus disease. We examined the effects of restaurant measures in Hong Kong. Our findings indicate that shortening operating hours did not have an effect on time-varying effective reproduction number when capacity was already reduced.

Viral RNA and Infectious Influenza Virus on Mobile Phones of Patients With Influenza in Hong Kong and the United States.

Mobile phones are among the most highly touched personal objects. As part of a broader study on the contribution of fomites to influenza transmission, between 2017 and 2019, we swabbed mobile phones from 138 patients with influenza in 2 locations. Influenza viral RNA detection rates were 23% (23 of 99 phones) and 36% (14 of 39) in Hong Kong and Maryland, respectively. In Hong Kong, infectious influenza virus was recovered from 3 of 23 mobile phones which had influenza viral RNA detected. Mobile phone influenza contamination was positively associated with upper respiratory tract viral load and negatively associated with age. Cleaning personal objects of patients with influenza should be recommended, and individuals should avoid sharing objects with these patients.

Changing Disparities in Coronavirus Disease 2019 (COVID-19) Burden in the Ethnically Homogeneous Population of Hong Kong Through Pandemic Waves: An Observational Study.

BACKGROUND: Disparities were marked in previous pandemics, usually with higher attack rates reported for those in lower socioeconomic positions and for ethnic minorities. METHODS: We examined characteristics of laboratory-confirmed coronavirus disease 2019 (COVID-19) cases in Hong Kong, assessed associations between incidence and population-level characteristics at the level of small geographic areas, and evaluated relations between socioeconomics and work-from-home (WFH) arrangements. RESULTS: The largest source of COVID-19 importations switched from students studying overseas in the second wave to foreign domestic helpers in the third. The local cases were mostly individuals not in formal employment (retirees and homemakers) and production workers who were unable to WFH. For every 10% increase in the proportion of population employed as executives or professionals in a given geographic region, there was an 84% (95% confidence interval [CI], 1-97%) reduction in the incidence of COVID-19 during the third wave. In contrast, in the first 2 waves, the same was associated with 3.69 times (95% CI, 1.02-13.33) higher incidence. Executives and professionals were more likely to implement WFH and experienced frequent changes in WFH practice compared with production workers. CONCLUSIONS: Consistent findings on the reversed socioeconomic patterning of COVID-19 burden between infection waves in Hong Kong in both individual- and population-level analyses indicated that risks of infections may be related to occupations involving high exposure frequency and WFH flexibility. Contextual determinants should be taken into account in policy planning aiming at mitigating such disparities.

Predictive Model of Early Neurological Deterioration in Patients with Acute Ischemic Stroke: A Retrospective Cohort Study.

OBJECTIVE: This study aimed to develop a predictive model of early neurological deterioration (END) in patients with acute ischemic stroke (AIS). METHODS: The present retrospective cohort study considered patients with AIS who were admitted to a tertiary hospital in Shenzhen, China between January 2014 and December 2018. An increase of 2 points or more on the National Institute of Health Stroke Scale (NIHSS) within 7 days indicated END. We selected baseline clinical, laboratory, and neuroimaging variables to construct predictive models through multivariate logistic regression. The receiver operating characteristic curve and calibration plots were calculated. RESULTS: A total of 391 patients with AIS were enrolled in the study. END was observed in 64 (16.4%) cases. A prediction model developed from the initial NIHSS score, middle cerebral artery stenosis, and carotid stenosis of≥ 50% showed good discriminative ability: area under the receiver operating characteristic curve, 0.870 (95%CI, 0.813-0.911); threshold, -1.570; specificity, 84.40%; sensitivity, 75.00%; positive predictive value, 48.48%; and a negative predictive value, 94.52%. CONCLUSION: Our predictive model developed from the initial NIHSS score, middle cerebral artery stenosis, and carotid stenosis of ≥ 50% could identify patients with AIS who were at risk of developing END. The model requires validation by larger studies performed at other institutions.

Presence of Influenza Virus on Touch Surfaces in Kindergartens and Primary Schools.

BACKGROUNDS: Influenza virus can survive on some surfaces, facilitating indirect person-to-person transmission. METHODS: We collected swab samples weekly from commonly touched surfaces in 7 kindergartens and primary schools during the 2017/2018 winter influenza season in Hong Kong. RESULTS: We detected influenza virus ribonucleic acid (RNA) in 12 of 1352 samples (<1%) collected from 7 of 11 classrooms (5 to 2 × 106 RNA copies/mL). Viral RNA was more frequently recovered from communal items inside classrooms such as bookshelves and doorknobs. CONCLUSIONS: Surface contamination indicates the potential role of fomites in influenza virus transmission in schools. Communal items inside classrooms may cause greater potential risks of transmission during influenza epidemics.

Nonpharmaceutical Measures for Pandemic Influenza in Nonhealthcare Settings-Social Distancing Measures.

Influenza virus infections are believed to spread mostly by close contact in the community. Social distancing measures are essential components of the public health response to influenza pandemics. The objective of these mitigation measures is to reduce transmission, thereby delaying the epidemic peak, reducing the size of the epidemic peak, and spreading cases over a longer time to relieve pressure on the healthcare system. We conducted systematic reviews of the evidence base for effectiveness of multiple mitigation measures: isolating ill persons, contact tracing, quarantining exposed persons, school closures, workplace measures/closures, and avoiding crowding. Evidence supporting the effectiveness of these measures was obtained largely from observational studies and simulation studies. Voluntary isolation at home might be a more feasible social distancing measure, and pandemic plans should consider how to facilitate this measure. More drastic social distancing measures might be reserved for severe pandemics.

Nonpharmaceutical Measures for Pandemic Influenza in Nonhealthcare Settings-Personal Protective and Environmental Measures.

There were 3 influenza pandemics in the 20th century, and there has been 1 so far in the 21st century. Local, national, and international health authorities regularly update their plans for mitigating the next influenza pandemic in light of the latest available evidence on the effectiveness of various control measures in reducing transmission. Here, we review the evidence base on the effectiveness of nonpharmaceutical personal protective measures and environmental hygiene measures in nonhealthcare settings and discuss their potential inclusion in pandemic plans. Although mechanistic studies support the potential effect of hand hygiene or face masks, evidence from 14 randomized controlled trials of these measures did not support a substantial effect on transmission of laboratory-confirmed influenza. We similarly found limited evidence on the effectiveness of improved hygiene and environmental cleaning. We identified several major knowledge gaps requiring further research, most fundamentally an improved characterization of the modes of person-to-person transmission.

Nonpharmaceutical Measures for Pandemic Influenza in Nonhealthcare Settings-International Travel-Related Measures.

International travel-related nonpharmaceutical interventions (NPIs), which can include traveler screening, travel restrictions, and border closures, often are included in national influenza pandemic preparedness plans. We performed systematic reviews to identify evidence for their effectiveness. We found 15 studies in total. Some studies reported that NPIs could delay the introduction of influenza virus. However, no available evidence indicated that screening of inbound travelers would have a substantial effect on preventing spread of pandemic influenza, and no studies examining exit screening were found. Some studies reported that travel restrictions could delay the start of local transmission and slow international spread, and 1 study indicated that small Pacific islands were able to prevent importation of pandemic influenza during 1918-19 through complete border closure. This limited evidence base indicates that international travel-related NPIs would have limited effectiveness in controlling pandemic influenza and that these measures require considerable resources to implement.

Portable real-time determination of Escherichia coli O157:H7 and Staphylococcus aureus based on smartphones and hydrogels.

The aptamers functionalized orange-emission carbon dots (OCDs) and green-emission carbon dots (GCDs) had dual-emission peaks with single excitation. Tungsten disulfide nanosheets (WS2 NSs)-triggered fluorescence quenching achieved the ratiometric fluorescence determination of Escherichia coli O157:H7 (E. coli O157:H7) and Staphylococcus aureus (S. aureus) with wide ranges of 18-1.8 × 106 and 37-3.7 × 107 CFU/mL and low detection limits of 8 and 20 CFU/mL, respectively. The results in real sample with recoveries of 90-101 % and RSD < 4.12 % were no significant difference from standard plate counting method. Meanwhile, the dual-color CDs were further adopted in the smartphone-assisted hydrogel platform and achieved speedy, sensitive, portable and real-time determination of E. coli O157:H7 and S. aureus in real samples. This work has not only developed ratiometric fluorescence detection and constructed a portable hydrogel platform, but also provided a unique strategy in developing a time-efficient and easy-to-use portable device in food safety monitoring.

Association Between the Hepatic Steatosis Index and Risk of Incident Type 2 Diabetes Mellitus in the Normoglycemic Population:A Longitudinal Prospective Study in Japan.

Purpose: The Hepatic Steatosis Index (HSI) is a reliable predictor of non-alcoholic fatty liver disease (NAFLD), which can increase the risk of type 2 diabetes mellitus (T2DM). However, limited research has directly predicted HSI's association with T2DM occurrence at normal blood glucose levels. Hence, this study aimed to assess the link between baseline HSI and T2DM development under euglycemic conditions while also exploring potential sex differences. Methods: Using data from the NAGALA cohort study, a Cox regression model analyzed the relationship between HSI and T2DM risk, calculating hazard ratios (HR) and 95% confidence intervals (CI). Subgroup analyses were conducted to investigate factors influencing HSI's prediction of incident T2DM. Results: During a mean 6.1-year follow-up, 238 individuals (1.65% of participants) developed T2DM. After adjusting for age, ethanol consumption, smoking status, SBP, DBP, TG, and TC, HSI showed a significant association with incident T2DM in individuals with normal glucose levels, consistent across sexes. Compared to the lowest quartile group (Q1), the HR and 95% CI for Q2, Q3, and Q4 were 1.09 (0.61, 1.93), 1.16 (0.68, 1.98), and 3.30 (2.04, 5.33), respectively (P for trend < 0.001). Subgroup analysis indicated that elevated HSI significantly increased the risk of incident T2DM in individuals with normal TG levels (P for interaction = 0.0170). Conclusion: This study highlights the significant association between elevated HSI levels and the likelihood of developing incident T2DM in individuals with normal glucose levels. Furthermore, it offers a simple and valuable screening tool for predicting T2DM.

Halobenzoquinone-induced potential carcinogenicity associated with p53-mediated cell cycle pathway.

2,6-Dibromo-1,4-benzoquinone (2,6-DBBQ) and 2,6-dichloro-1,4-benzoquinone (2,6-DCBQ), two emerging halobenzoquinones (HBQs), have the highest detection frequencies and levels in drinking water among all HBQs. They are more toxic than the regulated disinfection byproducts. Quantitative structure toxicity relationship analysis predicted that HBQs are a class of potential bladder carcinogens. However, direct experimental evidence for the carcinogenicity of 2,6-DBBQ and 2,6-DCBQ is lacking and the associated toxicity mechanisms remain unclear. In this study, we confirmed the potential carcinogenicity of 2,6-DBBQ and 2,6-DCBQ using an in vitro malignant transformation assay, evaluated their cytotoxicity and genotoxicity, and investigated their toxicity mechanisms. The results showed that 2,6-DBBQ and 2,6-DCBQ significantly decreased the viability of human uroepithelial SV-HUC-1 cells and induced DNA damage in SV-HUC-1 cells, and chromosomal damage in HepG2 cells, and malignant transformation of SV-HUC-1 cells. Moreover, transcriptome sequencing revealed that 2,6-DBBQ and 2,6-DCBQ activated the p53-mediated cell cycle pathway in bladder cancer. In the p53-mediated cell cycle pathway, 2,6-DBBQ and 2,6-DCBQ induced cell cycle arrest at the S phase by downregulating p53 and upregulating p21. Additionally, 2,6-DBBQ and 2,6-DCBQ may have produced excessive reactive oxygen species, damaging DNA and chromosomes. These results not only first confirm the potential carcinogenicity of 2,6-DBBQ and 2,6-DCBQ but also provide an important reference for exploring the cytotoxicity and genotoxicity mechanisms of these HBQs.

The Role of the PI3K/Akt/mTOR Axis in Head and Neck Squamous Cell Carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignancies globally, representing a significant public health problem with a poor prognosis. The development of efficient therapeutic strategies for HNSCC prevention and treatment is urgently needed. The PI3K/AKT/mTOR (PAM) signaling pathway is a highly conserved transduction network in eukaryotic cells that promotes cell survival, growth, and cycle progression. Dysfunction in components of this pathway, such as hyperactivity of PI3K, loss of PTEN function, and gain-of-function mutations in AKT, are well-known drivers of treatment resistance and disease progression in cancer. In this review, we discuss the major mutations and dysregulations in the PAM signaling pathway in HNSCC. We highlight the results of clinical trials involving inhibitors targeting the PAM signaling pathway as a strategy for treating HNSCC. Additionally, we examine the primary mechanisms of resistance to drugs targeting the PAM pathway and potential therapeutic strategies.