The associations between dietary flavonoids intake and risk of depressive symptom in diabetic patients: Data from NHANES 2007-2008, 2009-2010, and 2017-2018.

BACKGROUND: The increasing incidence of depressive symptoms in diabetic patients contributes to the global burden of disease, but few epidemiological studies have evaluated the relationship between dietary flavonoids intake and depressive symptoms in diabetic patients in American adults. OBJECTIVE: This study intended to evaluate the associations of dietary flavonoids intake and depressive symptoms in diabetic patients in American adults. METHODS: We conducted a cross-sectional analysis of 1993 adults aged ≥20 years old who participated in the 2007-2008, 2009-2010, and 2017-2018 National Health and Nutrition Examination Surveys (NHANES). Chi-square test and independent-sample t-test were used to compare subjects' characteristics. Logistic regression model was further used to analyze the relationship between dietary flavonoid intake and depressive symptoms in diabetic patients. Restricted cubic spline (RCS) analysis was used to investigate the non-linear relationship between dietary flavonoid intake and the prevalence of depressive symptoms in diabetic patients. The weighted quartile sum (WQS) regression was used to analyze the effect of 29 flavonoids monomers. RESULTS: The results showed that the total flavonoid intake in the third quartile (OR, 0.635; 95 % CI,0.419-0.962; P, 0.032) was significantly associated with a reduced risk of depressive symptoms in diabetic patients compared with the lowest quartile. And there was a U-shaped association between dietary flavonoid intake and risk of depressive symptoms in diabetic patients. Top contributors of flavonoid monomers were eriodictyol, naringenin, and theaflavin-3'-gallate, accounting for a percentage of 30.83 %, 22.17 %, and 6.92 %, respectively. CONCLUSION: Moderate (56.07-207.12 mg/day) dietary flavonoid intake was associated with a reduced risk of depressive symptoms in diabetic patients. The important flavonoid monomers were eriodictyol, naringenin, and theaflavin-3'-gallate.

Quercetin prevented diabetic nephropathy by inhibiting renal tubular epithelial cell apoptosis via the PI3K/AKT pathway.

Diabetic nephropathy (DN) is the most common and serious complication of diabetes, posing a significant threat to human health. Currently, safe and effective preventive strategies for DN are lacking. The study aimed to explore the preventive effect and the underlying mechanism of quercetin against DN. In the in vivo experiments, we established a mouse model of type 2 diabetes mellitus (T2DM) induced by a combination of high-fat diet (HFD) and streptozotocin (STZ) to explore the preventive effect of quercetin on DN and its protective role against renal tubular epithelial cell apoptosis. Subsequently, in vitro experiments using human tubular epithelial cells (HK-2 cells) were conducted to further validate the protective effects of quercetin on renal tubular epithelial cell apoptosis. Additionally, we employed RNA sequencing analysis (RNA-seq) and network pharmacology analysis to comprehensively elucidate the molecular mechanisms involved. In vivo, we observed a significant increase in the ratio of urinary microalbumin to creatinine in diabetic mice compared to control mice, accompanied by the activation of renal tubular epithelial cell apoptosis. Remarkably, all of these changes were reversed after quercetin treatment. In vitro, high-glucose-induced apoptosis in HK-2 cells was significantly attenuated by quercetin. Subsequent RNA sequencing analysis and network pharmacology analysis revealed that quercetin was most likely to inhibit high-glucose-induced HK-2 cell apoptosis through the PI3K/AKT signaling pathway. Western Blotting results further demonstrated that quercetin could inhibit the activation of the PI3K/AKT signaling pathway in HK-2 cells induced by high glucose. Our results supported that quercetin could prevent DN by inhibiting tubular epithelial cell apoptosis via the PI3K/AKT pathway. Quercetin might be a promising candidate for the prevention of DN.

Functional testing is a complementary tool for the diagnosis of vaginitis.

OBJECTIVE: Vaginal microbiota evaluation is a methodology widely used in China to diagnose various vaginal inflammatory diseases. Although vaginal microbiota evaluation has many advantages, it is time-consuming and requires highly skilled and experienced operators. Here, we investigated a six-index functional test that analyzed pH, hydrogen peroxide (H2O2), leukocyte esterase (LEU), sialidase (SNA), ß-glucuronidase (GUS), and acetylglucossidase (NAG), and determined its diagnostic value by comparing it with morphological tests of vaginal microbiota. MATERIALS AND METHODS: The research was conducted using data extracted from the Laboratory Information System of Women and Children's Hospital. A total of 4902 subjects, ranging in age from 35.4 ± 9.7 years, were analyzed. During the consultation, a minimum of two vaginal swab specimens per patient were collected for both functional and morphological testing. Fisher's exact was used to analyze data using SPSS. RESULTS: Of the 4,902 patients, 2,454 were considered to have normal Lactobacillus morphotypes and 3,334 were considered to have normal dominant microbiota. The sensitivity and specificity of H2O2-indicating Lactobacillus morphotypes were 91.3% and 25.28%, respectively, while those of pH-indicating Lactobacillus morphotypes were 88.09% and 59.52%, respectively. The sensitivity and specificity of H2O2-indicating dominant microbiota were 91.3% and 25.3%, respectively, while those of pH-indicating dominant microbiota were 86.27% and 64.45%, respectively. The sensitivity and specificity of NAG for vulvovaginal candidiasis were 40.64% and 84.8%, respectively. For aerobic vaginitis, GUS sensitivity was low at 0.52%, while its specificity was high at 99.93%; the LEU sensitivity and specificity values were 94.73% and 27.49%, respectively. Finally, SNA sensitivity and specificity for bacterial vaginosis were 80.72% and 96.78%, respectively. CONCLUSION: Functional tests (pH, SNA, H2O2, LEU) showed satisfactory sensitivity for the detection of vaginal inflammatory diseases. However, these tests lacked specificity, making it difficult to accurately identify specific pathologies. By contrast, NAG and GUS showed excellent specificity in identifying vaginal inflammatory diseases, but their sensitivity was limited. Therefore, functional tests alone are not sufficient to diagnose various vaginal inflammatory diseases. When functional and morphological tests are inconsistent, morphological tests are currently considered the preferred reference method.

Association between Gut Microbiota and Muscle Strength in Japanese General Population of the Iwaki Health Promotion Project.

The association between the gut microbiota and muscle strength has garnered attention in the context of mitigating muscle decline. However, many study subjects have been individuals with existing illnesses or the elderly only. This study aims to elucidate the association between the gut microbiota and muscle strength indicators using grip strength/BMI in a large-scale study of community residents. The mean age of men (n = 442) and women (n = 588) was 50.5 (15.3) and 51.2 (15.9) years, respectively. The muscle strength indicator used was grip/BMI. The association between total read count and genus-level gut microbiota and muscle strength was analyzed. The mean grip/BMI was 1.8 (0.3) for men and 1.2 (0.2) for women. The genus of the gut microbiota that showed an association in both sexes was Eggerthella (men: ß = 0.18, CI: 0.04-0.31, p = 0.009; women: ß = 0.07, CI: 0.00-0.12, p = 0.028). Blautia, Eggerthella and Faecalibacterium were found to be significantly associated with grip/BMI in both the multiple regression analysis and Spearman's correlation analysis after the multiple comparison adjustment. These results suggest that an increase in Blautia and Eggerthella, coupled with a decrease in Faecalibacterium, may contribute to muscle strengthening or the suppression of muscle weakness.

Enhanced "Electronic Tongue" for Dental Bacterial Discrimination and Elimination Based on a DNA-Encoded Nanozyme Sensor Array.

Bacterial infections are the second leading cause of death around the world, especially those caused by delayed treatment and misdiagnosis. Therefore, rapid discrimination and effective elimination of multiple bacteria are of great importance for improving the survival rate in clinic. Herein, a novel colorimetric sensor array for bacterial discrimination and elimination is constructed using programmable DNA-encoded iron oxide nanoparticles (IONPs) as sensing elements. Utilizing differential interactions of bacteria on DNA-encoded IONPs, 11 kinds of dental bacteria and 6 kinds of proteins have been successfully identified by linear discriminant analysis (LDA). Moreover, the developed sensing system also performs well in the quantitative determination of individual bacteria and identification of bacterial mixtures. More importantly, the practicability of this sensing strategy is further verified by precise differentiation of blind and artificial saliva samples. Furthermore, the sensor array is used for efficiently killing multiple bacteria, demonstrating great potential in clinical prophylaxis and therapy.

Global, regional, and national burden and quality of care of multiple myeloma, 1990-2019.

Background: Multiple myeloma (MM) is the second most common haematologic malignancy, presenting a great disease burden on the general population; however, the quality of care of MM is overlooked. We therefore assessed gains and disparity in quality of care worldwide from 1990 to 2019 based on a novel summary indicator - the quality of care index (QCI) - and examined its potential for improvement. Methods: Using the Global Burden of Disease 2019 data set, we calculated the QCI of MM for 195 countries and territories. We used the principal component analysis to extract the first principal component of ratios with the combinations of mortality to incidence, prevalence to incidence, disability-adjusted life years to prevalence, and years of life lost to years lived with disability as QCI. We also conducted a series of descriptive and comparative analyses of QCI disparities with age, gender, period, geographies, and sociodemographic development, and compared the QCI among countries with similar socio-demographic index (SDI) through frontier analysis. Results: The age-standardised rates of MM were 1.92 (95% uncertainty interval (UI) = 1.68, 2.12) in incidence and 1.42 (95% UI = 1.24, 1.52) in deaths per 100 000 population in 2019, and were predicted to increase in the future. The global age-standardised QCI increased from 51.31 in 1990 to 64.28 in 2019. In 2019, New Zealand had the highest QCI at 99.29 and the Central African Republic had the lowest QCI at 10.74. The gender disparity of QCI was reduced over the years, with the largest being observed in the sub-Saharan region. Regarding age, QCI maintained a decreasing trend in patients aged >60 in SDI quintiles. Generally, QCI improved with the SDI increase. Results of frontier analysis suggested that there is a potential to improve the quality of care across all levels of development spectrum. Conclusions: Quality of care of MM improved during the past three decades, yet disparities in MM care remain across different countries, age groups, and genders. It is crucial to establish local objectives aimed at enhancing MM care and closing the gap in health care inequality.

Reconstruction and analysis of the transmission network of African swine fever in People's Republic of China, August 2018-September 2019.

Introduction of African swine fever (ASF) to China in mid-2018 and the subsequent transboundary spread across Asia devastated regional swine production, affecting live pig and pork product-related markets worldwide. To explore the spatiotemporal spread of ASF in China, we reconstructed possible ASF transmission networks using nearest neighbour, exponential function, equal probability, and spatiotemporal case-distribution algorithms. From these networks, we estimated the reproduction numbers, serial intervals, and transmission distances of the outbreak. The mean serial interval between paired units was around 29 days for all algorithms, while the mean transmission distance ranged 332 -456 km. The reproduction numbers for each algorithm peaked during the first two weeks and steadily declined through the end of 2018 before hovering around the epidemic threshold value of 1 with sporadic increases during 2019. These results suggest that 1) swine husbandry practices and production systems that lend themselves to long-range transmission drove ASF spread; 2) outbreaks went undetected by the surveillance system. Efforts by China and other affected countries to control ASF within their jurisdictions may be aided by the reconstructed spatiotemporal model. Continued support for strict implementation of biosecurity standards and improvements to ASF surveillance is essential for halting transmission in China and spread across Asia.

Extracellular vesicle-mediated ferroptosis, pyroptosis, and necroptosis: potential clinical applications in cancer therapy.

Extracellular vesicles (EVs) have gained increasing recognition as significant regulators of intercellular communication in various physiological and pathological processes. These vesicles play a pivotal role in cancer progression by facilitating the transfer of diverse cargoes, including lipids, proteins, and nucleic acids. Regulated cell death (RCD), the orderly and autonomous death of cells, is controlled by a variety of biomacromolecules and, in turn, influences various biological processes and cancer progression. Recent studies have demonstrated that EV cargoes regulate diverse oncogenes and tumor suppressors to mediate different nonapoptotic forms of RCD, notably ferroptosis, pyroptosis, and necroptosis. Nevertheless, comprehensive exploration of EV-mediated nonapoptotic RCD forms in the context of cancer has not been performed. This review summarizes the progress regarding the biological functions and underlying mechanisms of EVs in mediating nonapoptotic RCD by delivery of cargoes to regulate tumor progression. Additionally, the review delves into the potential clinical applications of EV-mediated cell death and its significance in the areas of cancer diagnosis and therapy.

Applicable predictive factors extracted from peak flow trajectory for the prediction of asthma exacerbation.

BACKGROUND: Real-time asthma exacerbation prediction and acute asthma attack detection are essential for patients with severe asthma. Peak expiratory flow (PEF) exhibits a potential for use in long-term asthma self-monitoring. However, the method for processing PEF calculations remains to be clarified. OBJECTIVE: To develop clinically applicable novel exacerbation predictors calculated using PEF records. METHODS: Previously proposed exacerbation predictors, including the slope of PEF, percentage predicted PEF, percentage best PEF, the highest PEF over the lowest PEF within specific periods, and PEF coefficient of variation, in addition to a novel indicator delta PEF moving average (ΔMA), defined as the difference between 14-day and 3-day average PEF values, along with moving average (MA) adjusted for PEF reference (%ΔMA), were verified using the Hokkaido-based Investigative Cohort Analysis for Refractory Asthma data of 127 patients with severe asthma from whom 73,503 PEF observations were obtained. Receiver operating characteristic curves for all predictors were drawn, and the corresponding areas under the curve (AUCs) were computed. Regression analysis for MA and percentage MA were conducted. RESULTS: The most outstanding performance was shown by ΔMA and %ΔMA, with AUC values of 0.659 and 0.665 in the univariate model, respectively. When multivariate models were incorporated with random intercepts for individual participants, the AUC for ΔMA and %ΔMA increased to 0.907 and 0.919, respectively. CONCLUSION: The MA and percentage MA are valuable indicators that should be considered when deriving predictors from the PEF trajectory for monitoring exacerbations in patients with severe asthma. TRIAL REGISTRATION: The Hokkaido-based Investigative Cohort Analysis for Refractory Asthma was registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN ID: 000003254). https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000003917.

Does the Protective Effect of Zinc on Telomere Length Depend on the Presence of Hypertension or Type 2 Diabetes? Results from the Iwaki Health Promotion Project, Japan.

Telomeres, repeated TTAGGG sequences at chromosomal ends, shorten with age and indicate cellular lifespan. Zinc can protect against telomere damage through its anti-oxidative effect. Meanwhile, telomere shortening was correlated with metabolic diseases of hypertension and type 2 diabetes. The objective of this study was to investigate whether the association between zinc and telomere length differs by the presence or absence of hypertension/type 2 diabetes. This is a cross-sectional study with 1064 participants of the Iwaki area, Japan. Multiple linear regression models were performed to test the hypothesis. A higher serum zinc concentration was significantly associated with a longer G-tail length (ß = 48.11, 95% confidence intervals [CI]: 25.69, 70.54, p < 0.001). By multivariate linear regression analysis, there was a significant positive association between zinc and G-tail length in both hypertensive (ß = 46.84, 95%CI: 9.69, 84.0, p = 0.014) and non-hypertensive groups (ß = 49.47, 95%CI: 20.75, 78.18, p = 0.001), while the association was significant only in the non-diabetes group (ß = 50.82, 95%CI: 27.54, 74.11, p < 0.001). In conclusion, higher zinc concentration was significantly associated with longer G-tail length. The protective effect of zinc on G-tail did not differ by hypertension status; however, it disappeared in individuals with type 2 diabetes.

The Association between Gut Microbiota and Depression in the Japanese Population.

Depression is a leading cause of disease worldwide. The association between gut microbiota and depression has barely been investigated in the Japanese population. We analyzed Iwaki health check-up data collected from 2017 to 2019 and constructed generalized linear mixed models. The independent variable was the relative abundance of each of the 37 gut microbiota genera that were reported to be associated with depression. The dependent variable was the presence of depression assessed by the Center for Epidemiologic Studies Depression Scale. Potential confounders, including grip strength, gender, height, weight, smoking, and drinking habits, were adjusted in the regression models. Nine genera's regression coefficients (Alistipes, Blautia, Coprococcus, Dorea, Faecalibacterium, Holdemania, Lactobacillus, Mitsuokella, and Oscillibacter) showed statistical significance after multiple comparisons adjustment. Among these nine gut bacteria genera, Alistipes, Blautia, Coprococcus, Dorea, Faecalibacterium, and Oscillibacter were reported to be associated with butyrate production in the intestine. Our results indicate that gut microbiotas may influence the depression condition of the host via the butyrate-producing process.

Dietary flavonoid intake is associated with a lower risk of diabetic nephropathy in US adults: data from NHANES 2007-2008, 2009-2010, and 2017-2018.

Few epidemiological studies have investigated the relationship between flavonoids and diabetic nephropathy (DN). Therefore, we explored the association between dietary flavonoid intake and DN among 1949 US adults from the National Health and Nutrition Examination Survey (NHANES) 2007-2008, 2009-2010, and 2017-2018. Weighted logistic regression models demonstrated that the total flavonoid intake in the second (OR: 0.642; 95% CI: 0.456-0.906), third (OR: 0.665; 95% CI: 0.447-0.988), and the highest (OR: 0.551; 95% CI: 0.382-0.796) quantiles (versus the lowest) were associated with the decreased risk of DN. Restricted cubic spline (RCS) analyses showed that the total flavonoid intake had a negative linear association with DN (p-value for non-linearity was 0.003). Weighted quantile sum (WQS) regression analyses revealed that flavan-3-ols, flavones, and anthocyanidins were the main contributors for the combined effects of six flavonoid subclasses. Our findings suggested that higher dietary flavonoid intake was associated with a decreased risk of DN, with the greatest influence coming from flavan-3-ols, flavones, and anthocyanidins.

Relationship between dietary selenium intake and serum thyroid function measures in U.S. adults: Data from NHANES 2007-2012.

Although numerous studies have explored the relationship between selenium intake and thyroid diseases, few epidemiological studies have investigated the association between selenium intake and thyroid hormones. Therefore, we conducted this analysis to investigate the association between dietary selenium intake and thyroid hormones. Our sample included 5,575 adults (age ≥ 20) years from the National Health and Nutrition Examination Survey (NHANES) 2007-2012. Thyroid hormones, including total triiodothyronine (T3), total thyroxine (T4), free T3 (FT3), free T4 (FT4), and thyroid-stimulating hormone (TSH), were detected. Multivariable linear regression models showed that log10-transformed selenium intake (LogSe) was negatively correlated with TT4 (ß = -0.383, 95% CI: -0.695, -0.070) and TT4/TT3 (ß = -0.003, 95% CI: -0.006, -0.0004) in U.S. adults. Besides, additional stratified analyses by sex demonstrated that LogSe was negatively associated with TT4 (ß = -0.007, 95% CI: -0.013, -0.001) and TT4/TT3 (ß = -0.664, 95% CI: -1.182, -0.146) and positively associated with FT4/TT4 (ß = 0.031, 95% CI: 0.004, 0.059) in male adults. Meanwhile, subgroup analysis by iodine status showed that LogSe was negatively associated with TT4 (ß = -0.006, 95% CI: -0.011, -0.002), FT4/FT3 (ß = -0.011, 95% CI: -0.023, -0.00002) and TT4/TT3 (ß = -0.456, 95% CI: -0.886, -0.026) in iodine sufficiency but not in iodine deficiency adults. Our results demonstrated that the increased dietary selenium intake was negatively correlated with TT4 and TT4/TT3 in U.S. adults. Furthermore, the association between dietary selenium intake and thyroid hormones was more pronounced in males and iodine sufficiency adults.

Higher HEI-2015 scores are associated with lower risk of gout and hyperuricemia: Results from the national health and nutrition examination survey 2007-2016.

Gout, the most prevalent inflammatory arthritis, is becoming increasingly prevalent in the United States and across the world, and it adversely impacts people's quality of life and their health. Few studies have focused on the relationship between daily dietary quality and gout, so the topic requires further exploration. Data were derived from the National Health and Nutrition Examination Survey 2007-2016, and the inclusion criteria of the analytic sample were (1) adults, age ≥20 years, with complete information about HEI-2015, gout, and uric acid; (2) complete information of demographics, lifestyle (BMI, smoking, drinking), and disease history [hypertension, chronic kidney disease (CKD), diabetes]. The quality of the daily diet was reflected using the Healthy Eating Index 2015 (HEI-2015). The baseline features of different groups were examined using the Scott-Rao chi-square tests, and the association between the HEI-2015 score and the risk of gout/hyperuricemia (HUA) was investigated using weighted logistic regression models. The effects of different dietary components in the HEI-2015 on reducing the risk of gout/HUA were evaluated by weighted quantile sum (WQS) regression models. After adjusting for demographic characteristics, behavioral covariates, and disease history, higher HEI-2015 scores were associated with a significantly lower risk of gout (OR: 0.878, 95% CI: 0.876-0.880) and HUA (OR: 0.978, 95% CI: 0.976-0.979) in weighted logistic regression. Dairy, whole grains, plant proteins, and added sugar contributed greatly in HEI-2015 to reducing gout risk (weights of WQS index: 42, 17.18, 16.13, and 7.93%, respectively). Dairy, total fruits, greens and beans, and plant proteins contributed greatly in HEI-2015 to reducing HUA risk (weights of WQS index: 28.9, 17.13, 16.84, and 11.39%, respectively). As the result, adherence to the American Dietary Guidelines may assist to decrease the risk of gout/HUA in American adults, and greater emphasis should be placed on dairy products, whole grains, fruits, legumes, and added sugars.

Phenomenological and mechanistic models for predicting early transmission data of COVID-19.

Forecasting future epidemics helps inform policy decisions regarding interventions. During the early coronavirus disease 2019 epidemic period in January-February 2020, limited information was available, and it was too challenging to build detailed mechanistic models reflecting population behavior. This study compared the performance of phenomenological and mechanistic models for forecasting epidemics. For the former, we employed the Richards model and the approximate solution of the susceptible-infected-recovered (SIR) model. For the latter, we examined the exponential growth (with lockdown) model and SIR model with lockdown. The phenomenological models yielded higher root mean square error (RMSE) values than the mechanistic models. When using the numbers from reported data for February 1 and 5, the Richards model had the highest RMSE, whereas when using the February 9 data, the SIR approximation model was the highest. The exponential model with a lockdown effect had the lowest RMSE, except when using the February 9 data. Once interventions or other factors that influence transmission patterns are identified, they should be additionally taken into account to improve forecasting.

Assessing the geographic range of classical swine fever vaccinations by spatiotemporal modelling in Japan.

A classical swine fever (CSF) epidemic has been ongoing in Japan since September 2018. The outbreak started in Gifu Prefecture and involved 21 prefectures by the end of October 2020, posing a serious threat to pork industries. The present study was conducted to capture the spatiotemporal dynamics of CSF in Japan and assess the geographic range of the CSF vaccination on pig farms. First infection dates were collected for wild boars and on swine farms by prefecture. A simple statistical model was used to describe the spatiotemporal dynamics of CSF, describing the infection risk in wild boars and the subsequent transmission hazards to swine farms for 47 prefectures. Because the spatial transmission mechanisms and wild boar population dynamics involved substantial uncertainties, 16 models were applied to the empirical data. Estimated hazard parameters were used to predict the risk of infection on swine farms by 15 December 2020 to explicitly evaluate the governmental recommendation for vaccinations on pig farms by prefecture in light of the predicted infection risk in domestic pigs. The best-fit model for the wild boars indicated that transmission occurred via neighbouring prefectures and involved seasonality. The estimated conditional hazard was 0.008 (95% confidence interval [CI]: 0.001-0.014) per day for infections transmitted from wild boars to swine farms, and the median time from wild boar infection to swine farm infection was 129.4 days (95% CI: 69.5-935.0). Our prediction indicated that prefectures connected by land to those with wild boar infections had a higher risk of infection on swine farms. CSF transmission in Japan likely progressed diffusively via wild boar movement, and tracking wild boar infections may help determine the risk of infection on swine farms. Our risk map highlights the importance of deciding vaccination policies according to predicted risk.

Haloarene-guided cascade arylation of cyclic vinylogous esters under palladium catalysis.

A method is presented for the synthesis of diaryl cyclic vinylogous esters. The sequence of C(sp3)-H arylation events is programed under the differentiated reactivity of the aryl halides, and the optimized reaction system is effectively diverted from producing dihomo-arylated products. The site selectivity of the second arylation is notably modulated by the substitution pattern of the substrates.

A novel strategy for SARS-CoV-2 mass screening with quantitative antigen testing of saliva: a diagnostic accuracy study.

BACKGROUND: Quantitative RT-PCR (RT-qPCR) of nasopharyngeal swab (NPS) samples for SARS-CoV-2 detection requires medical personnel and is time consuming, and thus is poorly suited to mass screening. In June, 2020, a chemiluminescent enzyme immunoassay (CLEIA; Lumipulse G SARS-CoV-2 Ag kit, Fujirebio, Tokyo, Japan) was developed that can detect SARS-CoV-2 nucleoproteins in NPS or saliva samples within 35 min. In this study, we assessed the utility of CLEIA in mass SARS-CoV-2 screening. METHODS: We did a diagnostic accuracy study to develop a mass-screening strategy for salivary detection of SARS-CoV-2 by CLEIA, enrolling hospitalised patients with clinically confirmed COVID-19, close contacts identified at community health centres, and asymptomatic international arrivals at two airports, all based in Japan. All test participants were enrolled consecutively. We assessed the diagnostic accuracy of CLEIA compared with RT-qPCR, estimated according to concordance (Kendall's coefficient of concordance, W), and sensitivity (probability of CLEIA positivity given RT-qPCR positivity) and specificity (probability of CLEIA negativity given RT-qPCR negativity) for different antigen concentration cutoffs (0·19 pg/mL, 0·67 pg/mL, and 4·00 pg/mL; with samples considered positive if the antigen concentration was equal to or more than the cutoff and negative if it was less than the cutoff). We also assessed a two-step testing strategy post hoc with CLEIA as an initial test, using separate antigen cutoff values for test negativity and positivity from the predefined cutoff values. The proportion of intermediate results requiring secondary RT-qPCR was then quantified assuming prevalence values of RT-qPCR positivity in the overall tested population of 10%, 30%, and 50%. FINDINGS: Self-collected saliva was obtained from 2056 participants between June 12 and Aug 6, 2020. Results of CLEIA and RT-qPCR were concordant in 2020 (98·2%) samples (Kendall's W=0·99). Test sensitivity was 85·4% (76 of 89 positive samples; 90% credible interval [CrI] 78·0-90·3) at the cutoff of 0·19 pg/mL; 76·4% (68 of 89; 68·2-82·8) at the cutoff of 0·67 pg/mL; and 52·8% (47 of 89; 44·1-61·3) at the cutoff of 4·0 pg/mL. Test specificity was 91·3% (1796 of 1967 negative samples; 90% CrI 90·2-92·3) at the cutoff of 0·19 pg/mL, 99·2% (1952 of 1967; 98·8-99·5) at the cutoff of 0·67 pg/mL, and 100·0% (1967 of 1967; 99·8-100·0) at the cutoff of 4·00 pg/mL. Using a two-step testing strategy with a CLEIA negativity cutoff of 0·19 pg/mL (to maximise sensitivity) and a CLEIA positivity cutoff of 4·00 pg/mL (to maximise specificity), the proportions of indeterminate results (ie, samples requiring secondary RT-qPCR) would be approximately 11% assuming a prevalence of RT-qPCR positivity of 10%, 16% assuming a prevalence of RT-qPCR positivity of 30%, and 21% assuming a prevalence of RT-qPCR positivity of 50%. INTERPRETATION: CLEIA testing of self-collected saliva is simple and provides results quickly, and is thus suitable for mass testing. To improve accuracy, we propose a two-step screening strategy with an initial CLEIA test followed by confirmatory RT-qPCR for intermediate concentrations, varying positive and negative thresholds depending on local prevalence. Implementation of this strategy has expedited sample processing at Japanese airports since July, 2020, and might apply to other large-scale mass screening initiatives. FUNDING: Ministry of Health, Labour and Welfare, Japan.

A method for estimating the transmissibility of influenza using serial cross-sectional seroepidemiological data.

BACKGROUND: Seroepidemiological surveillance data has been demonstrated to be useful for estimating the cumulative incidence of influenza, and measures the difference between pre- and post-epidemic seropositive fractions. Despite this, such studies relied on a chosen cut-off value for seropositivity. The aim of the present study is to develop a method to analyze distributions of serial cross-sectional seroepidemiological surveillance datasets using an epidemiological model so that the transmission potential can be estimated without imposing a cut-off value. METHODS: A mathematical model of influenza transmission with a discrete antibody titer level was constructed. The final size equation for pre- and post-epidemic titer levels was derived. Subsequently, using the estimated distribution of the dilution increase caused by infection and the measurement error distribution, the model parameters were optimized using the maximum likelihood method. A bootstrap-based confidence interval calculation and sensitivity analysis were also performed. RESULTS: Without imposing a cut-off value, the cumulative incidence was quantified, thereby yielding an estimate of the basic reproduction number. For the purpose of exposition, the proposed method was applied to influenza A/Victoria/3/75(H3N2) data, and serological data between 1975 and 1976 were compared. The estimated reproduction number was greater than that using the cut-off value of the hemagglutination inhibition level with titer level 20 (dilution 1:20) or above to define positives. CONCLUSION: The proposed method without a cut-off value offers an unbiased approach to estimating the cumulative incidence along with the reproduction number. If a cut-off value is required, the results imply that titer level 20 or above may better represent a reasonable cut-off value for calculating the incidence, but it could underestimate the basic reproduction number.

Mass Screening of Asymptomatic Persons for Severe Acute Respiratory Syndrome Coronavirus 2 Using Saliva.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has rapidly evolved to become a global pandemic, largely owing to the transmission of its causative virus through asymptomatic carriers. Detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in asymptomatic people is an urgent priority for the prevention and containment of disease outbreaks in communities. However, few data are available in asymptomatic persons regarding the accuracy of polymerase chain reaction testing. In addition, although self-collected saliva samples have significant logistical advantages in mass screening, their utility as an alternative specimen in asymptomatic persons is yet to be determined. METHODS: We conducted a mass screening study to compare the utility of nucleic acid amplification, such as reverse-transcription polymerase chain reaction testing, using nasopharyngeal swab (NPS) and saliva samples from each individual in 2 cohorts of asymptomatic persons: the contact-tracing cohort and the airport quarantine cohort. RESULTS: In this mass screening study including 1924 individuals, the sensitivities of nucleic acid amplification testing with NPS and saliva specimens were 86% (90% credible interval, 77%-93%) and 92% (83%-97%), respectively, with specificities >99.9%. The true concordance probability between the NPS and saliva tests was estimated at 0.998 (90% credible interval, .996-.999) given the recent airport prevalence of 0.3%. In individuals testing positive, viral load was highly correlated between NPS and saliva specimens. CONCLUSION: Both NPS and saliva specimens had high sensitivity and specificity. Self-collected saliva specimens are valuable for detecting SARS-CoV-2 in mass screening of asymptomatic persons.