Handling of Tied Failures in Competing Risks Analysis

Master'sMASTER OF SCIENC

Time-varying effect in the competing risks based on restricted mean time lost

Patients with breast cancer tend to die from other diseases, so for studies that focus on breast cancer, a competing risks model is more appropriate. Considering subdistribution hazard ratio, which is used often, limited to model assumptions and clinical interpretation, we aimed to quantify the effects of prognostic factors by an absolute indicator, the difference in restricted mean time lost (RMTL), which is more intuitive. Additionally, prognostic factors may have dynamic effects (time-varying effects) in long-term follow-up. However, existing competing risks regression models only provide a static view of covariate effects, leading to a distorted assessment of the prognostic factor. To address this issue, we proposed a dynamic effect RMTL regression that can explore the between-group cumulative difference in mean life lost over a period of time and obtain the real-time effect by the speed of accumulation, as well as personalized predictions on a time scale. Through Monte Carlo simulation, we validated the dynamic effects estimated by the proposed regression having low bias and a coverage rate of around 95%. Applying this model to an elderly early-stage breast cancer cohort, we found that most factors had different patterns of dynamic effects, revealing meaningful physiological mechanisms underlying diseases. Moreover, from the perspective of prediction, the mean C-index in external validation reached 0.78. Dynamic effect RMTL regression can analyze both dynamic cumulative effects and real-time effects of covariates, providing a more comprehensive prognosis and better prediction when competing risks exist

Bioassessment of a Drinking Water Reservoir Using Plankton: High Throughput Sequencing vs. Traditional Morphological Method

Drinking water safety is increasingly perceived as one of the top global environmental issues. Plankton has been commonly used as a bioindicator for water quality in lakes and reservoirs. Recently, DNA sequencing technology has been applied to bioassessment. In this study, we compared the effectiveness of the 16S and 18S rRNA high throughput sequencing method (HTS) and the traditional optical microscopy method (TOM) in the bioassessment of drinking water quality. Five stations reflecting different habitats and hydrological conditions in Danjiangkou Reservoir, one of the largest drinking water reservoirs in Asia, were sampled May 2016. Non-metric multi-dimensional scaling (NMDS) analysis showed that plankton assemblages varied among the stations and the spatial patterns revealed by the two methods were consistent. The correlation between TOM and HTS in a symmetric Procrustes analysis was 0.61, revealing overall good concordance between the two methods. Procrustes analysis also showed that site-specific differences between the two methods varied among the stations. Station Heijizui (H), a site heavily influenced by two tributaries, had the largest difference while station Qushou (Q), a confluence site close to the outlet dam, had the smallest difference between the two methods. Our results show that DNA sequencing has the potential to provide consistent identification of taxa, and reliable bioassessment in a long-term biomonitoring and assessment program for drinking water reservoirs

Novel hypoxia-related gene signature for predicting prognoses that correlate with the tumor immune microenvironment in NSCLC

Background: Intratumoral hypoxia is widely associated with the development of malignancy, treatment resistance, and worse prognoses. The global influence of hypoxia-related genes (HRGs) on prognostic significance, tumor microenvironment characteristics, and therapeutic response is unclear in patients with non-small cell lung cancer (NSCLC).Method: RNA-seq and clinical data for NSCLC patients were derived from The Cancer Genome Atlas (TCGA) database, and a group of HRGs was obtained from the MSigDB. The differentially expressed HRGs were determined using the limma package; prognostic HRGs were identified via univariate Cox regression. Using the least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression, an optimized prognostic model consisting of nine HRGs was constructed. The prognostic model’s capacity was evaluated by Kaplan‒Meier survival curve analysis and receiver operating characteristic (ROC) curve analysis in the TCGA (training set) and GEO (validation set) cohorts. Moreover, a potential biological pathway and immune infiltration differences were explained.Results: A prognostic model containing nine HRGs (STC2, ALDOA, MIF, LDHA, EXT1, PGM2, ENO3, INHA, and RORA) was developed. NSCLC patients were separated into two risk categories according to the risk score generated by the hypoxia model. The model-based risk score had better predictive power than the clinicopathological method. Patients in the high-risk category had poor recurrence-free survival in the TCGA (HR: 1.426; 95% CI: 0.997–2.042; p = 0.046) and GEO (HR: 2.4; 95% CI: 1.7–3.2; p < 0.0001) cohorts. The overall survival of the high-risk category was also inferior to that of the low-risk category in the TCGA (HR: 1.8; 95% CI: 1.5–2.2; p < 0.0001) and GEO (HR: 1.8; 95% CI: 1.4–2.3; p < 0.0001) cohorts. Additionally, we discovered a notable distinction in the enrichment of immune-related pathways, immune cell abundance, and immune checkpoint gene expression between the two subcategories.Conclusion: The proposed 9-HRG signature is a promising indicator for predicting NSCLC patient prognosis and may be potentially applicable in checkpoint therapy efficiency prediction

Baveno-VII criteria to predict decompensation and initiate non-selective beta-blocker in compensated advanced chronic liver disease patients

Background/Aims The utility of Baveno-VII criteria of clinically significant portal hypertension (CSPH) to predict decompensation in compensated advanced chronic liver disease (cACLD) patient needs validation. We aim to validate the performance of CSPH criteria to predict the risk of decompensation in an international real-world cohort of cACLD patients. Methods cACLD patients were stratified into three categories (CSPH excluded, grey zone, and CSPH). The risks of decompensation across different CSPH categories were estimated using competing risk regression for clustered data, with death and hepatocellular carcinoma as competing events. The performance of “treating definite CSPH” strategy to prevent decompensation using non-selective beta-blocker (NSBB) was compared against other strategies in decision curve analysis. Results One thousand one hundred fifty-nine cACLD patients (36.8% had CSPH) were included; 7.2% experienced decompensation over a median follow-up of 40 months. Non-invasive assessment of CSPH predicts a 5-fold higher risk of liver decompensation in cACLD patients (subdistribution hazard ratio, 5.5; 95% confidence interval, 4.0–7.4). “Probable CSPH” is suboptimal to predict decompensation risk in cACLD patients. CSPH exclusion criteria reliably exclude cACLD patients at risk of decompensation, regardless of etiology. Among the grey zone, the decompensation risk was negligible among viral-related cACLD, but was substantially higher among the non-viral cACLD group. Decision curve analysis showed that “treating definite CSPH” strategy is superior to “treating all varices” or “treating probable CSPH” strategy to prevent decompensation using NSBB. Conclusions Non-invasive assessment of CSPH may stratify decompensation risk and the need for NSBB in cACLD patients

Detection of magnetospheric ion drift patterns at Mars

Mars lacks a global magnetic field, and instead possesses small-scale crustal magnetic fields, making its magnetic environment fundamentally different from intrinsic magnetospheres like those of Earth or Saturn. Here we report the discovery of magnetospheric ion drift patterns, typical of intrinsic magnetospheres, at Mars usingmeasurements fromMarsAtmosphere and Volatile EvolutioNmission. Specifically, we observewedge-like dispersion structures of hydrogen ions exhibiting butterfly-shaped distributions within the Martian crustal fields, a feature previously observed only in planetary-scale intrinsic magnetospheres. These dispersed structures are the results of driftmotions that fundamentally resemble those observed in intrinsic magnetospheres. Our findings indicate that the Martian magnetosphere embodies an intermediate case where both the unmagnetized and magnetized ion behaviors could be observed because of the wide range of strengths and spatial scales of the crustal magnetic fields around Mars.Comment: 10 pages, 6 figure

Allergic sensitization trajectories to age 8 years in the Singapore GUSTO cohort

Background: Allergic sensitization is linked to allergy development, with early sensitization often associated with worse outcomes. We aimed to identify if distinct allergic sensitization trajectories existed within a diverse and multi-ethnic Asian cohort.Methods: We administered modified ISAAC questionnaires in the first 8 years and conducted skin prick testing at ages 18 months, 3, 5 and 8 years in the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort. We used latent class analysis to derive allergic sensitization trajectories, and adjusted odds ratios (AOR) to evaluate predictive risk factors and associations with allergic comorbidities.Results: Among 997 children, three trajectories were identified: early food and mite sensitization (16.2%), late mite sensitization (24.2%) and no/low sensitization (59.6%). Early food and mite sensitization was associated with early eczema by 6 months [AOR (95%CI) 4.67 (1.78-12.28)], increased risk of wheeze by 3-8 years (ARR 1.72-1.99) and eczema in the first 8 years of life (ARR 1.87-2.41). Late mite sensitization was associated with female sex [AOR 0.58 (0.35-0.96)], cesar-ean section [AOR 0.54 (0.30-0.98)], early eczema by 6 months [AOR 3.40 (1.38-8.42)], and increased risk of eczema by 18 months [ARR 1.47 (1.03-2.08)] and 8 years [ARR 1.35 (1.05-1.73)].Conclusion: Early onset of eczema and early allergic sensitization were strongly associated. Early sensitization, especially to house dust mites, was associated with increased risks of developing wheeze and eczema, pointing to the importance of developing preventive perinatal interventions and effective therapeutics for sensitized toddlers.Peer reviewe

Clinicopathological Significance and Prognostic Value of DNA Methyltransferase 1, 3a, and 3b Expressions in Sporadic Epithelial Ovarian Cancer

Altered DNA methylation of tumor suppressor gene promoters plays a role in human carcinogenesis and DNA methyltransferases (DNMTs) are responsible for it. This study aimed to determine aberrant expression of DNMT1, DNMT3a, and DNMT3b in benign and malignant ovarian tumor tissues for their association with clinicopathological significance and prognostic value. A total of 142 ovarian cancers and 44 benign ovarian tumors were recruited for immunohistochemical analysis of their expression. The data showed that expression of DNMT1, DNMT3a, and DNMT3b was observed in 76 (53.5%), 92 (64.8%) and 79 (55.6%) of 142 cases of ovarian cancer tissues, respectively. Of the serious tumors, DNMT3a protein expression was significantly higher than that in benign tumor samples (P = 0.001); DNMT3b was marginally significant down regulated in ovarian cancers compared to that of the benign tumors (P = 0.054); DNMT1 expression has no statistical difference between ovarian cancers and benign tumor tissues (P = 0.837). Of the mucious tumors, the expression of DNMT3a, DNMT3b, and DNMT1 was not different between malignant and benign tumors. Moreover, DNMT1 expression was associated with DNMT3b expression (P = 0.020, r = 0.195). DNMT1 expression was associated with age of the patients, menopause status, and tumor localization, while DNMT3a expression was associated with histological types and serum CA125 levels and DNMT3b expression was associated with lymph node metastasis. In addition, patients with DNMT1 or DNMT3b expression had a trend of better survival than those with negative expression. Co-expression of DNMT1 and DNMT3b was significantly associated with better overall survival (P = 0.014). The data from this study provided the first evidence for differential expression of DNMTs proteins in ovarian cancer tissues and their associations with clinicopathological and survival data in sporadic ovarian cancer patients

Urban Shrinkage and Urban Vitality Correlation Research in the Three Northeastern Provinces of China

In the global trend of urban shrinkage, urban vitality, as one of the important representations of high-quality urban development, has become a breakthrough. More and more scholars advocate to awaken urban vitality, so as to realize the high-quality development of shrinking cities. This paper takes the municipal districts of 34 cities in the three northeastern provinces of China as study areas, based on the broad concept of urban shrinkage, selects the indicators of population, economy and society, and uses the “two-step diagnostic method” which is consistent with Chinese conditions to identify the urban shrinkage from 2010 to 2018. In this research, the indexes of economic, social, cultural, environmental and spatial dimensions are selected, and the urban vitality and the vitality of each dimension from 2010 to 2018 are calculated and analyzed by using the entropy weight method (EWM). Then, this paper analyzes the correlation between urban shrinkage and urban vitality by Pearson correlation coefficient. The results show that: (1) urban shrinkage in the three northeastern provinces of China has become a regional remarkable phenomenon, which is also an inevitable process in some regions of China and even the world; (2) overall, the urban vitality of cities in the three northeastern provinces of China is steady and rising a little, and there is an obvious spatial agglomeration pattern like “central city polarization”; (3) there is a significant correlation between urban shrinkage and urban vitality, that is, the lower the degree of urban shrinkage, the higher the urban vitality, showing the opposite trend in the process of urban development; (4) the influence of urban shrinkage on each dimension of urban vitality is different, and the correlation results are different, too. In the planning process of shrinking cities in the future, paying attention to the relationship between urban vitality and urban shrinkage, conducting benign guidance on this basis, and adjusting urban vitality elements of different dimensions to stimulate urban development power can enhance urban competitiveness and achieve better development

Ultrasound-guided thyroid nodule biopsy: Outcomes and correlation with imaging features

Clinical Imaging392200-20