The P. falciparum CSP repeat region contains three distinct epitopes required for protection by antibodies in vivo.

Rare and potent monoclonal antibodies (mAbs) against the Plasmodium falciparum (Pf) circumsporozoite protein (CSP) on infective sporozoites (SPZ) preferentially bind the PfCSP junctional tetrapeptide NPDP or NVDP minor repeats while cross-reacting with NANP central repeats in vitro. The extent to which each of these epitopes is required for protection in vivo is unknown. Here, we assessed whether junction-, minor repeat- and central repeat-preferring human mAbs (CIS43, L9 and 317 respectively) bound and protected against in vivo challenge with transgenic P. berghei (Pb) SPZ expressing either PfCSP with the junction and minor repeats knocked out (KO), or PbCSP with the junction and minor repeats knocked in (KI). In vivo protection studies showed that the junction and minor repeats are necessary and sufficient for CIS43 and L9 to neutralize KO and KI SPZ, respectively. In contrast, 317 required major repeats for in vivo protection. These data establish that human mAbs can prevent malaria infection by targeting three different protective epitopes (NPDP, NVDP, NANP) in the PfCSP repeat region. This report will inform vaccine development and the use of mAbs to passively prevent malaria.

Uncertainty and Irreproducibility of Triboelectricity Based on Interface Mechanochemistry.

Triboelectrification mechanism is still not understood, despite centuries of investigations. Here, we propose a model showing that mechanochemistry is key to elucidate triboelectrification fundamental properties. Studying contact between gold and silicate glasses, we observe that the experimental triboelectric output is subject to large variations and polarity inversions. First principles analysis shows that electronic transfer is activated by mechanochemistry and the tribopolarity is determined by the termination exposed to contact, depending on the material composition, which can result in different charging at the macroscale. The electron transfer mechanism is driven by the interface barrier dynamics, regulated by mechanical forces. The model provides a unified framework to explain several experimental observations, including the systematic variations in the triboelectric output and the mixed positive-negative "mosaic" charging patterns, and paves the way to the theoretical prediction of the triboelectric properties.

Association between smoking status and subjective quality of sleep in the South Korean population: a cross-sectional study.

PURPOSE: This study aimed to investigate the relationship between smoking and subjective sleep quality in the Korean adult population. METHODS: We designed a cross-sectional survey using data from the 2018 Korean Community Health Service Conditions Survey and selected smoking status as our variable of interest. We divided the participants into people who currently, never, and formerly smoked, those who smoked < 20 cigarettes/day, and those who smoked > 20 cigarettes/day. Subjective sleep quality was analyzed using the Pittsburgh Sleep Quality Index. Multiple logistic regression analysis was performed for statistical analysis. RESULTS: A total of 174,665 participants were enrolled. People who formerly and currently smoked were found to have poorer subjective sleep quality than those who never smoked. The odds of poor subjective sleep quality in people who smoked > 20 cigarettes/day were 1.15 times (95% confidence interval: 1.09-1.21) for men and 1.51 times (95% confidence interval: 1.22-1.86) for women, compared with men and women who never smoked. CONCLUSIONS: Smoking was negatively associated with subjective sleep quality. Smoking cessation programs and lifestyle improvement education may be justifiable to improve the quality of sleep in Korean adults.

TAZ/Wnt-ß-catenin/c-MYC axis regulates cystogenesis in polycystic kidney disease.

Autosomal-dominant polycystic kidney disease (ADPKD) is the most common genetic renal disease, primarily caused by germline mutation of PKD1 or PKD2, leading to end-stage renal disease. The Hippo signaling pathway regulates organ growth and cell proliferation. Herein, we demonstrate the regulatory mechanism of cystogenesis in ADPKD by transcriptional coactivator with PDZ-binding motif (TAZ), a Hippo signaling effector. TAZ was highly expressed around the renal cyst-lining epithelial cells of Pkd1-deficient mice. Loss of Taz in Pkd1-deficient mice reduced cyst formation. In wild type, TAZ interacted with PKD1, which inactivated ß-catenin. In contrast, in PKD1-deficient cells, TAZ interacted with AXIN1, thus increasing ß-catenin activity. Interaction of TAZ with AXIN1 in PKD1-deficient cells resulted in nuclear accumulation of TAZ together with ß-catenin, which up-regulated c-MYC expression. Our findings suggest that the PKD1-TAZ-Wnt-ß-catenin-c-MYC signaling axis plays a critical role in cystogenesis and might be a potential therapeutic target against ADPKD.

Impact of Coinsurance Reduction Policy on Healthcare Utilization Among Children Under 15.

BACKGROUND: On October 1, 2017, a new coinsurance reduction policy for children under 15 was introduced to minimize the lack of inpatient medical services for economic reasons and secure children's access to medical care. METHODS: This study analyzes the effect of this coinsurance reduction policy on healthcare utilization using data from the National Health Insurance Service-National Sample Cohort between 2015 and 2019. Groups were classified by 3 case groups and a control group according to age. The dependent variables were inpatient cost, admission, length of hospitalization, outpatient cost and visit, and total cost. The difference-in-differences method was used to examine changes in healthcare utilization among the case and control groups after policy implementation. RESULTS: Children of the age group 1-5 exhibited an increase in inpatient services and a decrease in outpatient services. There was a 16.17% increase in inpatient cost, 8.55% increase in inpatient admission, 10.67% increase in inpatient length of hospitalization, -9.14% decline in outpatient cost, and -6.79% decline in outpatient visits. Regarding children in the age groups of 6-10 and 11-15, the effect of the policy was inconclusive. CONCLUSION: The reduction in coinsurance rate policy in hospitalization among children has increased inpatient services and reduced outpatient services for 1-5-year-olds-a substitute effect was observed in this group. There is need for further research to examine the long-term effects of the coinsurance reduction policy.

Structural analysis of the pseudaminic acid synthase PseI from Campylobacter jejuni.

Campylobacter jejuni PseI is a pseudaminic acid synthase that condenses the 2,4-diacetamido-2,4,6-trideoxy-l-altrose sugar (6-deoxy AltdiNAc) and phosphoenolpyruvate to generate pseudaminic acid, a sialic acid-like 9-carbon backbone α-keto sugar. Pseudaminic acid is conjugated to cell surface proteins and lipids and plays a key role in the mobility and virulence of C. jejuni and other pathogenic bacteria. To provide insights into the catalytic mechanism of PseI, we performed a structural study on PseI. PseI forms a two-domain structure and assembles into a domain-swapped homodimer. The PseI dimer has two cavities, each of which accommodates a metal ion using conserved histidine residues. A comparative analysis of structures and sequences suggests that the cavity of PseI functions as an active site that binds the 6-deoxy AltdiNAc and phosphoenolpyruvate substrates and mediates their condensation. Furthermore, we propose the substrate binding-induced structural rearrangement of PseI and predict 6-deoxy AltdiNAc recognition residues that are specific to PseI.

Estimating direct and spill-over impacts of political elections on COVID-19 transmission using synthetic control methods.

Mass gathering events have been identified as high-risk environments for community transmission of coronavirus disease 2019 (COVID-19). Empirical estimates of their direct and spill-over effects however remain challenging to identify. In this study, we propose the use of a novel synthetic control framework to obtain causal estimates for direct and spill-over impacts of these events. The Sabah state elections in Malaysia were used as an example for our proposed methodology and we investigate the event's spatial and temporal impacts on COVID-19 transmission. Results indicate an estimated (i) 70.0% of COVID-19 case counts within Sabah post-state election were attributable to the election's direct effect; (ii) 64.4% of COVID-19 cases in the rest of Malaysia post-state election were attributable to the election's spill-over effects. Sensitivity analysis was further conducted by examining epidemiological pre-trends, surveillance efforts, varying synthetic control matching characteristics and spill-over specifications. We demonstrate that our estimates are not due to pre-existing epidemiological trends, surveillance efforts, and/or preventive policies. These estimates highlight the potential of mass gatherings in one region to spill-over into an outbreak of national scale. Relaxations of mass gathering restrictions must therefore be carefully considered, even in the context of low community transmission and enforcement of safe distancing guidelines.

Difference in medical service use among Korean gastric cancer survivors according to regional healthcare vulnerabilities: a cohort study.

PURPOSE: This study investigated the relationship between medical service use and healthcare vulnerability, pre- and post-gastric cancer diagnosis. Differences between healthcare-vulnerable and healthcare-nonvulnerable regions identified inequities that require intervention. METHODS: This cohort study was done using the National Health Insurance claims data of patients diagnosed with gastric cancer between 2004 and 2013. The Position Value for Relative Comparison Index was used to determine whether the patients lived in a healthcare-vulnerable region. Medical service use was classified into annual outpatient treatment, hospitalization days, and emergency treatment. We used a generalized linear model to which the Poisson distribution was applied and compared regional differences in medical service use. RESULTS: A total of 1797 gastric cancer patients who had survived 5 years post-diagnosis were included in the study, of which 14.2% lived in healthcare-vulnerable regions. The patients in vulnerable regions surviving 5-7 years post-diagnosis had a higher number of outpatient visits than those in nonvulnerable regions. Furthermore, hospitalization days were lesser for patients in vulnerable regions who survived 6 years post-diagnosis than those in nonvulnerable regions; however, this number increased in the seventh year. CONCLUSIONS: Our results suggest that gastric cancer survivors living in healthcare-vulnerable regions have a higher probability of increased medical service use 5 years post-diagnosis compared with patients in nonvulnerable regions, which may significantly increase healthcare disparities over time. Therefore, in the future, additional research is needed to elucidate the causes of the disparities in healthcare use and the results of the differences in health outcomes.

Revealing regional disparities in the transmission potential of SARS-CoV-2 from interventions in Southeast Asia.

SARS-CoV-2 is a new pathogen responsible for the coronavirus disease 2019 (COVID-19) outbreak. Southeast Asia was the first region to be affected outside China, and although COVID-19 cases have been reported in all countries of Southeast Asia, both the policies and epidemic trajectories differ substantially, potentially due to marked differences in social distancing measures that have been implemented by governments in the region. This paper studies the across-country relationships between social distancing and each population's response to policy, the subsequent effects of these responses to the transmissibility and epidemic trajectories of SARS-CoV-2. The analysis couples COVID-19 case counts with real-time mobility data across Southeast Asia to estimate the effects of host population response to social distancing policy and the subsequent effects on the transmissibility and epidemic trajectories of SARS-CoV-2. A novel inference strategy for the time-varying reproduction number is developed to allow explicit inference of the effects of social distancing on the transmissibility of SARS-CoV-2 through a regression structure. This framework replicates the observed epidemic trajectories across most Southeast Asian countries, provides estimates of the effects of social distancing on the transmissibility of disease and can simulate epidemic histories conditional on changes in the degree of intervention scenarios and compliance within Southeast Asia.

Estimates of global seasonal influenza-associated respiratory mortality: a modelling study.

BACKGROUND: Estimates of influenza-associated mortality are important for national and international decision making on public health priorities. Previous estimates of 250 000-500 000 annual influenza deaths are outdated. We updated the estimated number of global annual influenza-associated respiratory deaths using country-specific influenza-associated excess respiratory mortality estimates from 1999-2015. METHODS: We estimated country-specific influenza-associated respiratory excess mortality rates (EMR) for 33 countries using time series log-linear regression models with vital death records and influenza surveillance data. To extrapolate estimates to countries without data, we divided countries into three analytic divisions for three age groups (<65 years, 65-74 years, and ≥75 years) using WHO Global Health Estimate (GHE) respiratory infection mortality rates. We calculated mortality rate ratios (MRR) to account for differences in risk of influenza death across countries by comparing GHE respiratory infection mortality rates from countries without EMR estimates with those with estimates. To calculate death estimates for individual countries within each age-specific analytic division, we multiplied randomly selected mean annual EMRs by the country's MRR and population. Global 95% credible interval (CrI) estimates were obtained from the posterior distribution of the sum of country-specific estimates to represent the range of possible influenza-associated deaths in a season or year. We calculated influenza-associated deaths for children younger than 5 years for 92 countries with high rates of mortality due to respiratory infection using the same methods. FINDINGS: EMR-contributing countries represented 57% of the global population. The estimated mean annual influenza-associated respiratory EMR ranged from 0·1 to 6·4 per 100 000 individuals for people younger than 65 years, 2·9 to 44·0 per 100 000 individuals for people aged between 65 and 74 years, and 17·9 to 223·5 per 100 000 for people older than 75 years. We estimated that 291 243-645 832 seasonal influenza-associated respiratory deaths (4·0-8·8 per 100 000 individuals) occur annually. The highest mortality rates were estimated in sub-Saharan Africa (2·8-16·5 per 100 000 individuals), southeast Asia (3·5-9·2 per 100 000 individuals), and among people aged 75 years or older (51·3-99·4 per 100 000 individuals). For 92 countries, we estimated that among children younger than 5 years, 9243-105 690 influenza-associated respiratory deaths occur annually. INTERPRETATION: These global influenza-associated respiratory mortality estimates are higher than previously reported, suggesting that previous estimates might have underestimated disease burden. The contribution of non-respiratory causes of death to global influenza-associated mortality should be investigated. FUNDING: None.

Cost-benefit analysis of vaccination: a comparative analysis of eight approaches for valuing changes to mortality and morbidity risks.

BACKGROUND: There is increasing interest in estimating the broader benefits of public health interventions beyond those captured in traditional cost-utility analyses. Cost-benefit analysis (CBA) in principle offers a way to capture such benefits, but a wide variety of methods have been used to monetise benefits in CBAs. METHODS: To understand the implications of different CBA approaches for capturing and monetising benefits and their potential impact on public health decision-making, we conducted a CBA of human papillomavirus (HPV) vaccination in the United Kingdom using eight methods for monetising health and economic benefits, valuing productivity loss using either (1) the human capital or (2) the friction cost method, including the value of unpaid work in (3) human capital or (4) friction cost approaches, (5) adjusting for hard-to-fill vacancies in the labour market, (6) using the value of a statistical life, (7) monetising quality-adjusted life years and (8) including both productivity losses and monetised quality-adjusted life years. A previously described transmission dynamic model was used to project the impact of vaccination on cervical cancer outcomes. Probabilistic sensitivity analysis was conducted to capture uncertainty in epidemiologic and economic parameters. RESULTS: Total benefits of vaccination varied by more than 20-fold (£0.6-12.4 billion) across the approaches. The threshold vaccine cost (maximum vaccine cost at which HPV vaccination has a benefit-to-cost ratio above one) ranged from £69 (95% CI £56-£84) to £1417 (£1291-£1541). CONCLUSIONS: Applying different approaches to monetise benefits in CBA can lead to widely varying outcomes on public health interventions such as vaccination. Use of CBA to inform priority setting in public health will require greater convergence around appropriate methodology to achieve consistency and comparability across different studies.

Association between Severity of MERS-CoV Infection and Incubation Period.

We analyzed data for 170 patients in South Korea who had laboratory-confirmed infection with Middle East respiratory syndrome coronavirus. A longer incubation period was associated with a reduction in the risk for death (adjusted odds ratio/1-day increase in incubation period 0.83, 95% credibility interval 0.68-1.03).

Effects of 4-nonylphenol and bisphenol A on stimulation of cell growth via disruption of the transforming growth factor-ß signaling pathway in ovarian cancer models.

Transforming growth factor ß (TGF-ß) signaling pathway is a major pathway in cellular processes such as cell growth, apoptosis, and cellular homeostasis. The signaling pathway activated by 17ß-estadiol (E2) appeared to inhibit the TGF-ß signaling pathway by cross-talk with the TGF-ß components in estrogen receptor (ER) positive cells. In this study, we examined the inhibitory effects of endocrine disrupting chemicals (EDCs), including 4-nonylphenol (NP), 4-otylphenol (OP), bisphenol A (BPA), and benzophenon-1 (BP-1), in the TGF-ß signaling pathway in BG-1 ovarian cancer cells expressing estrogen receptors (ERs). The transcriptional and translational levels of TGF-ß related genes were examined by reverse transcription-PCR (RT-PCR), Western blot analysis, and xenograft mouse models of ovarian cancer cells. As a result, treatment with NP, OP, and BPA induced the expressions of SnoN, a TGF-ß pathway inhibitor, and c-Fos, a TGF-ß target transcription factor. Treatment with NP, BPA, and BP-1 resulted in decreased phosphorylation of Smad3, a downstream target of TGF-ß. These results indicate that NP and BPA may stimulate the proliferation of BG-1 cells via inhibition of the TGF-ß signaling pathway. In a xenograft mouse model, transplanted BG-1 ovarian cancer cells showed significantly decreased phosphorylation of Smad3 and increased expression of SnoN in the ovarian tumor masses following treatment with E2, NP, or BPA. In parallel with an in vitro model, the expressions of these TGF-ß signaling pathway were similarly regulated by NP or BPA in a xenograft mouse model. These results support the fact that the existence of an unproven relationship between EDCs/ER-α and TGF-ß signaling pathway and a further study are required in order to verify more profound and distinct mechanism(s) for the disturbance of the TGF-ß signaling pathway by diverse EDCs.

Increased Risk of New-Onset Parkinson's Disease Following a Diagnosis of Retinal Vascular Occlusion: A 14-Year Cohort Study.

BACKGROUND: Although the role of the vascular component in the pathophysiology of Parkinson's disease is widely accepted and retinal vascular abnormalities are commonly observed in Parkinson's disease patients, evidence connecting retinal vascular disorders with the risk of developing Parkinson's disease is limited. We aimed to investigate the association between retinal vascular occlusion (RVO) and the risk of developing Parkinson's disease in people over 60 years using a nationwide cohort. METHODS: From the 14-year South Korean National Health Insurance Service-Senior cohort, 11 210 incident RVO patients and 11 210 propensity scores, risk-matched controls were included. The incidence of Parkinson's disease was estimated with a Poisson regression. A Cox proportional hazards regression model was used to investigate the associations between RVO and the risk of Parkinson's disease. RESULTS: The incidence of Parkinson's disease was 664.4 cases per 100 000 person-years (95% confidence interval [CI], 599.7-736.0) in the RVO cohort. Individuals with RVO had an increased incidence of Parkinson's disease (hazard ratio [HR], 1.28; 95% CI: 1.10-1.49). Increased PD risk was predominantly observed in retinal artery occlusion patients (HR, 1.53; 95% CI: 1.11-2.12), male patients (HR, 1.67; 95% CI: 1.29-2.17), and 5 years after diagnosis (HR, 1.46; 95% CI: 1.10-1.93). CONCLUSIONS: Our findings suggest that a common pathophysiological pathway, such as vasculature changes, may exist between RVO and Parkinson's disease. RVO may be one of the risk factors associated with future development of Parkinson's disease. The nature of this association warrants further investigation.

Association between Sudden Sensorineural Hearing Loss and the Risk of Cardio Cerebrovascular Disease.

OBJECTIVES: This study investigated the association between sudden sensorineural hearing loss (SSNHL) and the risk of cardio-cerebrovascular disease (CCVD) among older adults in South Korea. METHODS: Data from 38,426 patients in the Korean National Health Insurance Service-Senior Cohort from 2002 to 2019 were collected. The risk of CCVD includes both stroke and acute myocardial infarction. Propensity score matching (1:1) was used to identify pairs of individuals with and without SSNHL (n = 19,213 for cases and controls). Cox proportional hazards regression models were used to analyze the associations between variables. RESULTS: Patients with SSNHL had a higher risk of CCVD (hazard ratio [HR] = 1.17, 95% confidence interval [CI] = 1.11-1.24) compared to those without. The risk of CCVD was higher among those who experienced a stroke than those who did not (HR = 1.17 95% CI = 1.10-1.25). Compared to their matched controls, patients with SSNHL were 1.69 times (HR = 1.69 CI = 1.46-1.94) more likely to have CCVD during the first 12 months of the follow-up period. CONCLUSION: Older patients with SSNHL are at an increased risk of CCVD. Hence, a more attentive approach featuring aggressive monitoring of patients with SSNHL is required to lessen their risk of CCVD. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:2372-2376, 2024.

Increased Risk of Dementia Following a Diagnosis of Hearing Impairment: A South Korean Nationwide Cohort Study.

BACKGROUND: Among the older adults, hearing impairment is a common problem and may contribute to dementia. OBJECTIVE: Therefore, we aimed to examine the association between hearing impairment and the risk of dementia among older adults in South Korea. METHODS: Using the Korean National Health Insurance Service-Senior Cohort from 2005 to 2019, we collected data of 44,728 patients. Hearing impairment was determined using the national disability registry. Propensity score matching (1:1) was performed to match patients with and without hearing impairment (case: 22,364, control: 22,364). A Cox proportional hazards regression model was built to analyze the association between hearing impairment and dementia. RESULTS: Patients with hearing impairment had a higher risk of dementia than those without hearing impairment (hazard ratio [HR] = 1.28, 95% confidence interval [CI] = 1.23-1.34). Assessing the degree of disability, both severe (HR = 1.25, 95% CI = 1.16-1.35) and mild conditions (HR = 1.29, 95% CI = 1.23-1.35) had an increased risk of dementia, respectively. CONCLUSIONS: Older patients with hearing impairment exhibit an increased risk of dementia, thereby warranting a new approach to dementia care among these patients regardless of the degree of hearing impairment.

Estimating the Epidemic Size of Superspreading Coronavirus Outbreaks in Real Time: Quantitative Study.

BACKGROUND: Novel coronaviruses have emerged and caused major epidemics and pandemics in the past 2 decades, including SARS-CoV-1, MERS-CoV, and SARS-CoV-2, which led to the current COVID-19 pandemic. These coronaviruses are marked by their potential to produce disproportionally large transmission clusters from superspreading events (SSEs). As prompt action is crucial to contain and mitigate SSEs, real-time epidemic size estimation could characterize the transmission heterogeneity and inform timely implementation of control measures. OBJECTIVE: This study aimed to estimate the epidemic size of SSEs to inform effective surveillance and rapid mitigation responses. METHODS: We developed a statistical framework based on back-calculation to estimate the epidemic size of ongoing coronavirus SSEs. We first validated the framework in simulated scenarios with the epidemiological characteristics of SARS, MERS, and COVID-19 SSEs. As case studies, we retrospectively applied the framework to the Amoy Gardens SARS outbreak in Hong Kong in 2003, a series of nosocomial MERS outbreaks in South Korea in 2015, and 2 COVID-19 outbreaks originating from restaurants in Hong Kong in 2020. RESULTS: The accuracy and precision of the estimation of epidemic size of SSEs improved with longer observation time; larger SSE size; and more accurate prior information about the epidemiological characteristics, such as the distribution of the incubation period and the distribution of the onset-to-confirmation delay. By retrospectively applying the framework, we found that the 95% credible interval of the estimates contained the true epidemic size after 37% of cases were reported in the Amoy Garden SARS SSE in Hong Kong, 41% to 62% of cases were observed in the 3 nosocomial MERS SSEs in South Korea, and 76% to 86% of cases were confirmed in the 2 COVID-19 SSEs in Hong Kong. CONCLUSIONS: Our framework can be readily integrated into coronavirus surveillance systems to enhance situation awareness of ongoing SSEs.

Effectiveness of COVID-19 vaccines against severe outcomes in cancer patients: Real-world evidence from self-controlled risk interval and retrospective cohort studies.

BACKGROUND: The effectiveness of COVID-19 vaccines is generally reduced in cancer patients compared to the general population. However, there are only a few studies that compare the relative risk of breakthrough infections and severe COVID-19 outcomes in fully vaccinated cancer patients versus their unvaccinated counterparts. METHODS: To assess the effectiveness of COVID-19 vaccines in cancer patients, we employed (1) a self-controlled risk interval (SCRI) design, and (2) a retrospective matched cohort design. A SCRI design was used to compare the risk of breakthrough infection in vaccinated cancer patients during the period immediately following vaccination ("control window") and the period in which immunity is achieved ("exposure windows"). The retrospective matched cohort design was used to compare the risk of severe COVID-19 outcomes between vaccinated and unvaccinated cancer patients. For both studies, data were extracted from the Korea Disease Control and Prevention Agency-COVID-19-National Health Insurance Service cohort, including demographics, medical history, and vaccination records of all individuals confirmed with COVID-19. We used conditional Poisson regression to calculate the incidence rate ratio (IRR) for breakthrough infection and Cox regression to estimate the hazard ratio (HR) for severe outcomes. RESULTS: Of 14,448 cancer patients diagnosed with COVID-19 between October 2020 and December 2021, a total of 217 and 3996 cancer patients were included in the SCRI and cohort study respectively. While the risk of breakthrough infections, measured by the incidence rate in the control and exposure windows, did not show statistically significant difference in vaccinated cancer patients (IRR=0.88, 95% CI: 0.64-1.22), the risk of severe COVID-19 outcomes was significantly lower in vaccinated cancer patients compared to those unvaccinated (HR=0.27, 95% CI: 0.22-0.34). CONCLUSION: COVID-19 vaccines significantly reduce the risk of severe outcomes in cancer patients, though their efficacy against breakthrough infections is less evident.

Anticancer effect of genistein on BG-1 ovarian cancer growth induced by 17 ß-estradiol or bisphenol A via the suppression of the crosstalk between estrogen receptor α and insulin-like growth factor-1 receptor signaling pathways.

The interaction between estrogen receptor (ER) and insulin-like growth factor-1 receptor (IGF-1R) signaling pathway plays an important role in proliferation of and resistance to endocrine therapy to estrogen dependent cancers. Estrogen (E2) upregulates the expression of components of IGF-1 system and induces the downstream of mitogenic signaling cascades via phosphorylation of insulin receptor substrate-1 (IRS-1). In the present study, we evaluated the xenoestrogenic effect of bisphenol A (BPA) and antiproliferative activity of genistein (GEN) in accordance with the influence on this crosstalk. BPA was determined to affect this crosstalk by upregulating mRNA expressions of ERα and IGF-1R and inducing phosphorylation of IRS-1 and Akt in protein level in BG-1 ovarian cancer cells as E2 did. In the mouse model xenografted with BG-1 cells, BPA significantly increased a tumor burden of mice and expressions of ERα, pIRS-1, and cyclin D1 in tumor mass compared to vehicle, indicating that BPA induces ovarian cancer growth by promoting the crosstalk between ER and IGF-1R signals. On the other hand, GEN effectively reversed estrogenicity of BPA by reversing mRNA and protein expressions of ERα, IGF-1R, pIRS-1, and pAkt induced by BPA in cellular model and also significantly decreased tumor growth and in vivo expressions of ERα, pIRS-1, and pAkt in xenografted mouse model. Also, GEN was confirmed to have an antiproliferative effect by inducing apoptotic signaling cascades. Taken together, these results suggest that GEN effectively reversed the increased proliferation of BG-1 ovarian cancer by suppressing the crosstalk between ERα and IGF-1R signaling pathways upregulated by BPA or E2.

Use of Bluetooth contact tracing technology to model COVID-19 quarantine policies in high-risk closed populations.

Containment measures in high-risk closed settings, like migrant worker (MW) dormitories, are critical for mitigating emerging infectious disease outbreaks and protecting potentially vulnerable populations in outbreaks such as coronavirus disease 2019 (COVID-19). The direct impact of social distancing measures can be assessed through wearable contact tracing devices. Here, we developed an individual-based model using data collected through a Bluetooth wearable device that collected 33.6M and 52.8M contact events in two dormitories in Singapore, one apartment style and the other a barrack style, to assess the impact of measures to reduce the social contact of cases and their contacts. The simulation of highly detailed contact networks accounts for different infrastructural levels, including room, floor, block, and dormitory, and intensity in terms of being regular or transient. Via a branching process model, we then simulated outbreaks that matched the prevalence during the COVID-19 outbreak in the two dormitories and explored alternative scenarios for control. We found that strict isolation of all cases and quarantine of all contacts would lead to very low prevalence but that quarantining only regular contacts would lead to only marginally higher prevalence but substantially fewer total man-hours lost in quarantine. Reducing the density of contacts by 30% through the construction of additional dormitories was modelled to reduce the prevalence by 14 and 9% under smaller and larger outbreaks, respectively. Wearable contact tracing devices may be used not just for contact tracing efforts but also to inform alternative containment measures in high-risk closed settings.