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    Head-to-head comparison of the test performance of self-administered qualitative vs. laboratory-based quantitative fecal immunochemical tests in detecting colorectal neoplasm. Chinese medical journal BACKGROUND:Fecal immunochemical tests (FITs) are the most widely used non-invasive tests in colorectal cancer (CRC) screening. However, evidence about the direct comparison of the test performance of the self-administered qualitative a laboratory-based quantitative FITs in a CRC screening setting is sparse. METHODS:Based on a CRC screening trial (TARGET-C), we included 3144 pre-colonoscopy fecal samples, including 24 CRCs, 230 advanced adenomas, 622 non-advanced adenomas, and 2268 participants without significant findings at colonoscopy. Three self-administered qualitative FITs (Pupu tube) with positivity thresholds of 8.0, 14.4, or 20.8 μg hemoglobin (Hb)/g preset by the manufacturer and one laboratory-based quantitative FIT (OC-Sensor) with a positivity threshold of 20 μg Hb/g recommended by the manufacturer were tested by trained staff in the central laboratory. The diagnostic performance of the FITs for detecting colorectal neoplasms was compared in the different scenarios using the preset and adjusted thresholds (for the quantitative FIT). RESULTS:At the thresholds preset by the manufacturers, apart from the qualitative FIT-3, significantly higher sensitivities for detecting advanced adenoma were observed for the qualitative FIT-1 (33.9% [95% CI: 28.7-39.4%]) and qualitative FIT-2 (22.2% [95% CI: 17.7-27.2%]) compared to the quantitative FIT (11.7% [95% CI: 8.4-15.8%]), while at a cost of significantly lower specificities. However, such difference was not observed for detecting CRC. For scenarios of adjusting the positivity thresholds of the quantitative FIT to yield comparable specificity or comparable positivity rate to the three qualitative FITs accordingly, there were no significant differences in terms of sensitivity, specificity, positive/negative predictive values and positive/negative likelihood ratios for detecting CRC or advanced adenoma between the two types of FITs, which was further evidenced in ROC analysis. CONCLUSIONS:Although the self-administered qualitative and the laboratory-based quantitative FITs had varied test performance at the positivity thresholds preset by the manufacturer, such heterogeneity could be overcome by adjusting thresholds to yield comparable specificities or positivity rates. Future CRC screening programs should select appropriate types of FITs and define the thresholds based on the targeted specificities and manageable positivity rates. 10.1097/CM9.0000000000001524
    Association between pre-diagnostic serum albumin and cancer risk: Results from a prospective population-based study. Yang Zhuoyu,Zheng Yadi,Wu Zheng,Wen Yan,Wang Gang,Chen Shuohua,Tan Fengwei,Li Jiang,Wu Shouling,Dai Min,Li Ni,He Jie Cancer medicine BACKGROUND:Albumin is supposed to be associated with cancer risk. However, evidence on serum albumin and cancer risk among the Chinese population is sparse. This study was conducted to evaluate the association between pre-diagnostic serum albumin and cancer risk among Chinese. METHODS:A total of 82,061 participants with baseline information on serum albumin concentration in the Kailuan cohort were recruited. Cox proportional hazards models and restricted cubic spline (RCS) analyses were used to evaluate the association between pre-diagnostic serum albumin and cancer risk. RESULTS:Albumin levels were inversely associated with overall cancer risk (HR [95% CI]: Q2, Q3, Q4 vs. Q1: 0.91 [0.78-1.07], 0.80 [0.70-0.92], 0.73 [0.63-0.85]), and the risk of lung, colorectal, and liver cancer (HR [95% CI]: Q4 vs. Q1: lung: 0.70 [0.52-0.95], colorectal: 0.43 [0.26-0.72], liver: 0.59 [0.36-0.95]). After excluding new cancer cases within 2 years since enrollment, a more significant association was observed for liver cancer (HR [95% CI]: Q4 vs. Q1: 0.41 [0.21-0.78]), while associations converted to nonsignificant for lung and colorectal cancer. The RCS model suggested an inverse linear association between albumin and the risk of overall cancer (p-overall < 0.0001, p-nonlinear = 0.3716) and liver cancer (p-overall = 0.0002, p-nonlinear = 0.1807). CONCLUSIONS:Our findings suggest that pre-diagnostic serum albumin is inversely and linearly associated with cancer risk among the Chinese population. This study provides evidence that albumin may be valuable to the prediction and stratification of cancer risk in the general population. However, the biological mechanism and clinical significance remain to be elucidated. Population studies with longer follow-up time as well as experimental studies are further required. 10.1002/cam4.3937
    Advances in the epidemiology of pancreatic cancer: Trends, risk factors, screening, and prognosis. Cai Jie,Chen Hongda,Lu Ming,Zhang Yuhan,Lu Bin,You Lei,Zhang Taiping,Dai Min,Zhao Yupei Cancer letters Pancreatic cancer is a malignancy with poor prognosis and high mortality. The recent increase in pancreatic cancer incidence and mortality has resulted in an increased number of studies on its epidemiology. This comprehensive and systematic literature review summarizes the advances in the epidemiology of pancreatic cancer, including its epidemiological trends, risk factors, risk prediction models, screening modalities, and prognosis. The risk factors for pancreatic cancers can be categorized as those related to individual characteristics, lifestyle and environment, and disease status. Several prediction models for pancreatic cancer have been developed in populations with new-onset diabetes or a family history of pancreatic cancer; however, these models require further validation. Despite recent progress in pancreatic cancer screening, the quantity and quality of related studies are also unsatisfactory, especially with respect to the identification of high-risk populations and development of effective screening modality. Apart from the populations with familial genetic risk and those at a high risk of sporadic pancreatic cancer, risk factors such as new-onset diabetes may be a new direction for timely intervention. We hope this work will provide new ideas for further prevention and treatment of pancreatic cancer. 10.1016/j.canlet.2021.06.027
    Colorectal cancer incidence and mortality: the current status, temporal trends and their attributable risk factors in 60 countries in 2000-2019. Lu Bin,Li Na,Luo Chen-Yu,Cai Jie,Lu Ming,Zhang Yu-Han,Chen Hong-Da,Dai Min Chinese medical journal BACKGROUND:Globally, colorectal cancer (CRC) imposes a substantial burden on healthcare systems and confers considerable medical expenditures. We aimed to evaluate the global and regional burden in epidemiological trends and factors associated with the incidence and mortality of CRC. METHODS:We used data from the GLOBOCAN database to estimate CRC incidence and mortality worldwide in 2020 and their association with the human development index (HDI). Trends of age-standardized rates of incidence and mortality in 60 countries (2000-2019) were evaluated by Joinpoint regression analysis using data of Global Burden of Disease 2019. The association between exposure to country-level lifestyle, metabolic and socioeconomic factors obtained from the World Health Organization Global Health Observatory and World Bank DataBank data and CRC incidence and mortality was determined by multivariable linear regression. RESULTS:CRC incidence and mortality varied greatly in the 60 selected countries, and much higher incidence and mortality were observed in countries with higher HDIs, and vice versa. From 2000 to 2019, significant increases of incidence and mortality were observed for 33 countries (average annual percent changes [AAPCs], 0.24-3.82) and 18 countries (AAPCs, 0.41-2.22), respectively. A stronger increase in incidence was observed among males (AAPCs, 0.36-4.54) and individuals <50 years (AAPCs, 0.56-3.86). Notably, 15 countries showed significant decreases in both incidence (AAPCs, -0.24 to -2.19) and mortality (AAPCs, -0.84 to -2.74). A significant increase of incidence among individuals <50 years was observed in 30 countries (AAPCs, 0.28-3.62). Countries with higher incidence were more likely to have a higher prevalence of alcohol drinking, higher level of cholesterol level, higher level of unemployment, and a poorer healthcare system. CONCLUSIONS:Some high-HDI countries showed decreasing trends in CRC incidence and mortality, whereas developing countries that previously had low disease burden showed significantly increased incidence and mortality trends, especially in males and populations ≥50 years, which require targeted preventive health programs. 10.1097/CM9.0000000000001619
    Colorectal cancer risk variant rs7017386 modulates two oncogenic lncRNAs expression via ATF1-mediated long-range chromatin loop. Wang Haoxue,Zhu Ying,Chen Hongda,Yang Nan,Wang Xiaoyang,Li Bin,Ying Pingting,He Heng,Cai Yimin,Zhang Ming,Niu Siyuan,Li Yue,Lu Zequn,Peng Xiating,Zou Danyi,Zhong Rong,Chang Jiang,Dai Min,Tian Jianbo,Miao Xiaoping Cancer letters The activating transcription factor 1 (ATF1) has been identified as a vital pathogenic factor in the progression of colorectal cancer (CRC), whiles, the precise regulatory mechanisms remain elusive. Here, we comprehensively characterized the ATF1 cistrome by RNA-seq and ChIP-seq assays in CRC cell lines. As the results, we identified 358 genes differentially regulated and 15,029 ATF1 binding sites and demonstrated that ATF1 was widely involved in major signaling pathways in CRC, such as Wnt, TNF, Jak-STAT. Subsequently, by the expression quantitative trait loci (eQTL) analyses, we found that rs7017386 was associated with the expression of CCAT1 and PVT1 in the Wnt pathway. By a two-stage population study with 6,131 CRC cases and 10,022 healthy controls, we identified the variant was associated with CRC risk. Mechanistically, we found rs7017386 allele-specifically enhanced the binding affinity of ATF1 and promoted the expressions of PVT1 and CCAT1, via forming a long-range chromatin loop. Moreover, those two lncRNAs could synergistically facilitate c-Myc expression to activate the Wnt pathway in CRC progression. Our findings not only demonstrated the transcriptomic profiling of ATF1 in CRC, but also provided important clues for the etiology of CRC. 10.1016/j.canlet.2021.07.021
    Implications of Lifestyle Factors and Polygenic Risk Score for Absolute Risk Prediction of Colorectal Neoplasm and Risk-Adapted Screening. Chen Hongda,Liu Li,Lu Ming,Zhang Yuhan,Lu Bin,Zhu Ying,Tian Jianbo,Li Xinying,Nie Shaofa,Miao Xiaoping,Dai Min Frontiers in molecular biosciences Estimation of absolute risk of developing colorectal neoplasm is essential for personalized colorectal cancer (CRC) screening. We developed models to determine relative and absolute risks of colorectal neoplasm based on lifestyle and genetic variants and to validate their application in risk-adapted screening. We prospectively collected data from 203 advanced neoplasms, 464 non-advanced adenomas, and 1,213 healthy controls from a CRC screening trial in China in 2018-2019. The risk prediction model based on four lifestyle factors and a polygenic risk score (PRS) consisted of 19 CRC-associated single-nucleotide polymorphisms. We assessed the relative and 10-year absolute risks of developing colorectal neoplasm and the yield of a risk-adapted screening approach incorporating risk models, fecal immunochemical test, and colonoscopy. Compared to the participants with favorable lifestyle and lower PRS, those with unfavorable lifestyle and higher PRS had 2.87- and 3.79-fold higher risk of colorectal neoplasm in males and females, respectively. For a 50-year-old man or a 50-year-old woman with the highest risk profile, the estimated 10-year absolute risk of developing colorectal neoplasm was 6.59% (95% CI: 6.53-6.65%) and 4.19% (95% CI: 4.11-4.28%), respectively, compared to 2.80% (95% CI: 2.78-2.81%) for men and 2.24% (95% CI: 2.21-2.27%) for women with the lowest risk profile. The positive predictive value for advanced neoplasm was 31.7%, and the number of colonoscopies needed to detect one advanced neoplasm was 3.2. The risk models, absolute risk estimates, and risk-adapted screening presented in our study would contribute to developing effective personalized CRC prevention and screening strategies. 10.3389/fmolb.2021.685410
    Optimizing Positivity Thresholds for a Risk-Adapted Screening Strategy in Colorectal Cancer Screening. Lu Ming,Wang Le,Zhang Yuhan,Liu Chengcheng,Lu Bin,Du Lingbin,Liao Xianzhen,Dong Dong,Wei Donghua,Gao Yi,Shi Jufang,Ren Jiansong,Chen Hongda,Dai Min Clinical and translational gastroenterology INTRODUCTION:Risk-adapted screening combining the Asia-Pacific Colorectal Screening score, fecal immunochemical test (FIT), and colonoscopy improved the yield of colorectal cancer screening than FIT. However, the optimal positivity thresholds of risk scoring and FIT of such a strategy warrant further investigation. METHODS:We included 3,407 participants aged 50-74 years undergoing colonoscopy from a colorectal cancer screening trial. For the risk-adapted screening strategy, subjects were referred for subsequent colonoscopy or FIT according to their risk scores. Diagnostic performance was evaluated for FIT and the risk-adapted screening method with various positivity thresholds. Furthermore, a modeled screening cohort was established to compare the yield and cost using colonoscopy, FIT, and the risk-adapted screening method in a single round of screening. RESULTS:Risk-adapted screening method had higher sensitivity for advanced neoplasm (AN) (27.6%-76.3% vs 13.8%-17.3%) but lower specificity (46.6%-90.8% vs 97.4%-98.8%) than FIT did. In a modeled screening cohort, FIT-based screening would be slightly affected because the threshold varied with a reduction of 76.0%-80.9% in AN detection and 82.0%-84.4% in cost when compared with colonoscopy. By contrast, adjusting the threshold of Asia-Pacific Colorectal Screening score from 3 to 5 points for risk-adapted screening varied from an increase of 12.6%-14.1% to a decrease of 55.6%-60.1% in AN detection, with the reduction of cost from 4.2%-5.3% rising to 66.4%-68.5%. DISCUSSION:With an appropriate positivity threshold tailored to clinical practice, the risk-adapted screening could save colonoscopy resources and cost compared with the colonoscopy-only and FIT-only strategies. 10.14309/ctg.0000000000000398
    Leveraging Fecal Microbial Markers to Improve the Diagnostic Accuracy of the Fecal Immunochemical Test for Advanced Colorectal Adenoma. Zhang Yuhan,Lu Ming,Lu Bin,Liu Chengcheng,Ma Yiming,Liu Li,Miao Xiaoping,Qin Junjie,Chen Hongda,Dai Min Clinical and translational gastroenterology INTRODUCTION:Fecal immunochemical tests (FITs) detect colorectal adenoma inefficiently. The gut microbiota participates in colorectal cancer development. We aimed to explore fecal microbial signatures for advanced adenomas and evaluate their diagnostic value and complementary capacity to FIT. METHODS:Using 16S rRNA sequencing, we studied gut microbiota in feces from 1,546 subjects in a screening setting, including 268 patients with advanced adenomas, 490 patients with nonadvanced adenomas, and 788 healthy subjects. Feature selections were performed using linear discriminant analysis effect size, multivariate association with linear models, and least absolute shrinkage and selection operator. The diagnostic performance of microbial signatures and their auxiliary role to FITs and the added value of the Asia-Pacific Colorectal Screening score were evaluated. We applied 0.632+ bootstrapping to adjust the potential overfitting. RESULTS:We identified 13 microbial signatures to show the joint diagnostic value for advanced adenoma, with genus Tyzzerella 4 demonstrating the highest adjusted area under the curve (AUC) of 0.545 (95% confidence interval [CI], 0.520-0.610). The 13-bacteria increased the adjusted AUC to 0.607 (95% CI, 0.548-0.660). Compared with individual FIT (adjusted AUC = 0.527; 95% CI, 0.519-0.571), 13-bacteria and FITs collectively reached an adjusted AUC of 0.641 (95% CI, 0.579-0.691). At cutoff values yielding specificities of 90% and 80%, the adjusted sensitivities were 28.4% (95% CI, 19.3-36.8) and 41.1% (95% CI, 29.9-49.4), respectively. The Asia-Pacific Colorectal Screening score further boosted the adjusted AUC to 0.706 (95% CI, 0.648-0.750). DISCUSSION:In this study using fecal samples from a screening setting, the identified microbial signatures could complement FITs for detecting advanced adenomas. Gut microbiota can act as a promising tool to optimize the current colorectal cancer screening modalities. 10.14309/ctg.0000000000000389
    Incidence, mortality, survival, risk factor and screening of colorectal cancer: A comparison among China, Europe, and northern America. Li Na,Lu Bin,Luo Chenyu,Cai Jie,Lu Ming,Zhang Yuhan,Chen Hongda,Dai Min Cancer letters Colorectal cancer (CRC) is one of the most common malignancies worldwide. China, Europe and northern America account for more than half of the new CRC cases and associated deaths globally. This review summarizes the current status and temporal trends of CRC in China, Europe, and northern America. The potential primary preventive strategies and latest advances in CRC screening techniques and programs are discussed. Recently, the incidence and mortality of CRC in some European and northern American countries have decreased; conversely, CRC incidence and mortality continue to increase in China. The overall 5-year relative survival rate for CRC is similar between these regions, but there is considerable heterogeneity among European countries. Implementing population-based CRC screening programs can effectively address the growing disease burden. The effectiveness of nationwide CRC screening programs in these regions has been limited by relatively low coverage and participation rate. The deployment of state-of-the-art techniques and precise risk-adapted screening strategies incorporating effective risk prediction models and screening techniques may boost screening effectiveness. Our review provides novel foundations for the development and optimization of CRC preventive strategies. 10.1016/j.canlet.2021.09.034
    BMI changes and the risk of lung cancer in male never-smokers: A prospective cohort study. Cancer medicine BACKGROUND:To investigate the association between the risk of lung cancer and short-term body mass index (BMI) changes in male never-smokers of a large population-based prospective study. METHODS:A total of 37,085 male never-smokers from Kailuan cohort with at least ≥2 BMI measurements were recruited in the present study. The BMI change in the follow-up was calculated as the annual percent change between BMI at last examination and that at baseline, and categorized into five groups: stable (-0.1 to <0.1 kg/m /year), minor loss (-1.0 to <0.1 kg/m /year) or gain (0.1 to <1.0 kg/m /year), and major loss (<-1.0 kg/m /year) or gain (≥1.0 kg/m /year). The hazards ratios (HRs) and its 95% confidence intervals (CI) were estimated using Cox regression models. RESULTS:During a median follow-up of 5.16 years, 224 lung cancer cases were identified. We found a U-shaped association between BMI changes and lung cancer risk. Compared to men with stable BMI, those with major loss had a nearly twofold higher risk of lung cancer (HR = 1.97, 95% CI: 1.12-3.45), as well as those with major gain had more than twofold higher risk of lung cancer (HR = 2.15, 95% CI: 1.15-4.02). The associations existed when the analysis was stratified by BMI, waist circumference and blood lipids, and lipoproteins concentration at baseline examination. CONCLUSIONS:The dramatic changes in BMI, both gain and loss, might increase lung cancer risk. The control of body weight would be a potential way for lung cancer prevention especially for the nonsmokers. 10.1002/cam4.4546
    Head-to-head comparison of a risk-adapted screening strategy using various risk prediction models in detecting colorectal neoplasm. Journal of gastroenterology and hepatology BACKGROUND AND AIM:The risk-adapted screening strategy showed satisfying colorectal cancer (CRC) screening yield and efficiency. We therefore further explored the diagnostic performance variation of this strategy using different risk prediction models. METHODS:A literature search was conducted to identify studies evaluating risk models for advanced colorectal neoplasm (ACN). The included models were retrospectively validated in a subset sample (N = 3219) from a population-based CRC screening trial in China. Diagnosis-related indictors were compared between the risk-adapted screening strategy using different models and the fecal immunochemical test (FIT)-only strategy. For simulated populations with ACN prevalence of 3% to 12%, the trade-off of additional false positives for each additional true positive were calculated. RESULTS:We included 14 eligible risk models with the area under the curves ranging 0.570 to 0.652 in the validation set. The overall sensitivities of the risk-adapted screening strategy using different risk models for ACN varied from 46.0% to 69.8%, higher than FIT (21.9%), but at the expense of specificities (51.6% to 78.3% vs 97.1%). For population having ACN prevalence of 3%, risk-adapted screening strategies needed 20.5 to 31.1 additional false positives for each additional true positive compared with FIT, and respective number would substantially reduce (4.7 to 7.1) as the ACN prevalence increased to 12%. CONCLUSIONS:Risk-adapted screening strategy using the current risk models showed improved sensitivity for ACN compared with FIT, at the cost of increased colonoscopy workload. The optimal strategy for screening practice should be tailored considering the disease burden and availability of healthcare resources. 10.1111/jgh.15825
    One-off low-dose CT for lung cancer screening in China: a multicentre, population-based, prospective cohort study. The Lancet. Respiratory medicine BACKGROUND:Lung cancer is the leading cause of cancer death worldwide. Data on the effectiveness of one-off low-dose CT (LDCT) in reducing lung cancer mortality and all-cause mortality are needed to inform screening programmes in countries with limited medical resources. We aimed to evaluate the effectiveness of one-off LDCT screening in the early detection of lung cancer in China. METHODS:A multicentre, population-based, prospective cohort study was done in 12 cities of eight provinces across China, recruiting individuals aged 40-74 years who were asymptomatic for lung cancer with no lung cancer history. Participants were classified as at high risk or low risk of lung cancer using a sex-specific risk score that incorporated cigarette smoking, level of physical activity, occupational exposures, history of chronic respiratory diseases, family history of lung cancer, diet, and passive smoking (women only). Participants at high risk were invited for a one-off LDCT scan and were classified into screened and non-screened groups on the basis of whether or not they had the scan. Lung cancer incidence density, lung cancer mortality, and all-cause mortality were calculated for the screened and non-screened groups. The effectiveness of a one-off LDCT scan was evaluated by a comparison of the screened and non-screened groups in terms of lung cancer mortality and all-cause mortality in the period from cohort entry until administrative censoring (June 20, 2020). Inverse probability weighting was adopted to account for potential imbalanced factors between the two groups and Cox proportional hazards model was used to estimate the weighted associations between mortality and one-off LDCT scans. FINDINGS:Between Feb 19, 2013, and Oct 31, 2018, 1 032 639 individuals were assessed for eligibility. 1 016 740 participants were enrolled in the study, of whom 3581 had a lung cancer diagnosis after a median follow-up of 3·6 years (IQR 2·8-5·1). Among the 223 302 participants at high risk, 79 581 (35·6%) had an LDCT scan (screened group) and 143 721 (64·4%) did not (non-screened group). After inverse probability weighting, lung cancer incidence density was 47·0% higher (hazard ratio 1·47 [95% CI 1·27-1·70]; p<0·0001), lung cancer mortality was 31·0% lower (0·69 [95% CI 0·53-0·92]; p=0·010) and all-cause mortality was 32·0% lower (0·68 [0·57-0·82]; p<0·0001) for participants in the screened group compared with those in the non-screened group. INTERPRETATION:One-off LDCT screening was associated with significantly lower lung cancer mortality and all-cause mortality in a large population in China. Our results point to the promise of one-off LDCT screening in countries with limited medical resources. Further studies are needed to explore interactions by subgroup-including sex, age, smoking status, and economic status-to develop population-specific screening strategies. FUNDING:Ministry of Finance and National Health Commission of the People's Republic of China. TRANSLATION:For the Chinese translation of the abstract see Supplementary Materials section. 10.1016/S2213-2600(21)00560-9
    Microsimulation Model for Prevention and Intervention of Coloretal Cancer in China (MIMIC-CRC): Development, Calibration, Validation, and Application. Frontiers in oncology Introduction:A microsimulation model provides important references for decision-making regarding colorectal cancer (CRC) prevention strategies, yet such a well-validated model is scarce in China. Methods:We comprehensively introduce the development of MIcrosimulation Model for the prevention and Intervention of Colorectal Cancer in China (MIMIC-CRC). The MIMIC-CRC was first constructed to simulate the natural history of CRC based on the adenoma-carcinoma pathway. The parameters were calibrated and validated using data from population-based cancer registry data and CRC screening programs. Furthermore, to assess the model's external validity, we compared the model-derived results to outcome patterns of a sigmoidoscopy screening trial in the UK [UK Flexible Sigmoidoscopy Screening (UKFSS) trial]. Finally, we evaluated the application potential of the MIMIC-CRC model in CRC screening by comparing the 8 different strategies. Results:We found that most of the model-predicted colorectal lesion prevalence was within the 95% CIs of observed prevalence in a large population-based CRC screening program in China. In addition, model-predicted sex- and age-specific CRC incidence and mortality were equivalent to the registry-based data. The hazard ratios of model-estimated CRC-related incidence and mortality for sigmoidoscopy screening compared to no screening were 0.60 and 0.51, respectively, which were comparable to the reported results of the UKFSS trial. Moreover, we found that all 8 strategies could reduce CRC incidence and mortality compared to no screening. Conclusions:The well-calibrated and validated MIMIC-CRC model may represent a valid tool to assess the comparative effectiveness of CRC screening strategies and will be useful for further decision-making to CRC prevention. 10.3389/fonc.2022.883401