Graphical abstract

Recent studies have indicated that the epithelial-mesenchymal transition (EMT) is a key molecular mechanism involved in the development of colorectal cancer (CRC). N-cadherin is a mesenchymal marker of the EMT and has been closely linked to several human malignancies. However, its role in CRC has remained elusive. In the present study, qRT-PCR and western blot analysis indicated that N-cadherin expression was higher in tumor tissues than in that in their adjacent normal tissues. Immunohistochemical evaluation of N-cadherin and E-cadherin (an epithelial marker of the EMT), indicated that N-cadherin expression was significantly associated with tumor differentiation, tumor size as well as tumor, nodes and metastasis stage. Correlation analysis suggested the expression of N-cadherin was negatively correlated with that of E-cadherin in CRC tissues. Kaplan-Meier analysis indicated that patients with high N-cadherin expression had a significantly lower overall survival and disease-free survival rate than those with low N-cadherin expression, while the opposite was found for E-cadherin. Of note, the present study found that high N-cadherin expression was an independent prognostic factor for CRC. In vitro assays showed that N-cadherin was widely expressed in CRC cell lines and silencing of N-cadherin suppressed the proliferation and migration of the CRC cell line HT-29 by upregulating E-cadherin, suggesting a potential role of N-cadherin in inducing EMT. In conclusion, the present study suggested that N-cadherin has the potential of serving as a novel prognostic predictor and a promising therapeutic target for CRC.

Detecting out-of-domain (OOD) input intents is critical in the task-oriented dialog system. Different from most existing methods that rely heavily on manually labeled OOD samples, we focus on the unsupervised OOD detection scenario where there are no labeled OOD samples except for labeled in-domain data. In this paper, we propose a simple but strong generative distancebased classifier to detect OOD samples. We estimate the class-conditional distribution on feature spaces of DNNs via Gaussian discriminant analysis (GDA) to avoid over-confidence problems. And we use two distance functions, Euclidean and Mahalanobis distances, to measure the confidence score of whether a test sample belongs to OOD. Experiments on four benchmark datasets show that our method can consistently outperform the baselines.

Child maltreatment is a robust risk factor for suicidal ideation and behaviors during adolescence. Elevations in internalizing and externalizing symptomology have been identified as two distinct developmental pathways linking child maltreatment and adolescent risk for suicide. However, recent research suggests that the co-occurrence of internalizing and externalizing symptomology may form a distinct etiological pathway for adolescent risk behaviors. Using the Longitudinal Studies on Child Abuse and Neglect (LONGSCAN) sample (N= 1,314), the present study employed a person-centered approach to identify patterns of concurrent change in internalizing and externalizing psychopathology over five time points from early childhood to adolescence in relation to previous experiences of child maltreatment and subsequent suicidal ideation and behaviors. Results indicated four distinct bivariate externalizing and internalizing growth trajectories. Group membership in a heightened comorbid internalizing and externalizing symptom trajectory mediated the association between childhood abuse and adolescent suicidal ideation and suicidal behaviors. These findings suggest that the concurrent development of externalizing and internalizing symptoms in childhood and adolescence may constitute a unique developmental trajectory that confers risk for suicide-related outcomes.

During adolescence, a positive outlook toward the future (i.e., future orientation) can protect youth from the risks conferred by childhood adversity. Research to date, however, has largely considered future orientation as a static attribute. Developmental systems perspectives suggest that future orientation, when considered across time, will exhibit dynamic trajectories with levels changing in response to the varying balance of risks and resources in youths' environments. Investigating the developmental course and consequences of future orientation is particularly germane to maltreated youth who may benefit from programs that target this protective mechanism. The present study tested hypotheses regarding the developmental course of future orientation, including the association of distinct future orientation trajectories with time-varying risk factors and resources, and the association of continuity and change in future orientation trajectories with young adult psychosocial functioning. Hypotheses were investigated with longitudinal (T1 = 12.22, T2 = 13.52, T3 = 14.79, T4 = 18.54), multireporter data from a nationally representative sample of maltreated youth ( = 1,461). Growth mixture modeling (GMM) identified three classes of growth trajectories in future orientation: and. Time-variant and -invariant risk factors and resources differentiated youths' future orientation trajectories. Youth in the high-persistent and low start/increasing trajectories were more likely to attain young adulthood developmental milestones-including independent living skills, social capital, employment, and higher weekly income. This study documents how an important component of resilient adaptation emerges and promotes positive outcomes among highly vulnerable youth. (PsycINFO Database Record

Prolonged exposure to socioeconomic hardship (SH) is associated with greater delayed reward discounting (DRD), a form of impulsive decision-making that reflects a reduced capacity to delay gratification and a significant correlate of diverse risk behaviors, but the neurobehavioral mechanisms linking SH and DRD are unknown. An emerging hypothesis suggests that cognitive and affective stress associated with poverty may tax neurocognitive functions, such as working memory (WM), and lead to impulsive DRD. Furthermore, research suggests that emotional reactivity (ER) is an important dispositional factor to consider in the link between executive functions and DRD. Thus, we longitudinally examined the indirect effect of SH on impulsive DRD via a network of brain regions associated with WM function in a sample of young adults, and whether that link was moderated by ER. Participants were 119 rural African Americans (aged 19-24 years) assessed behaviorally on four occasions, with fMRI at the last time point. Results showed that, among emerging adults with higher ER, SH severity was predictive of increased DRD via reduced response in brain regions activated during an n-back WM task. These findings reveal both the cognitive and affective mechanisms that underlie the relationship between SH and DRD.

a b s t r a c tThe notion of using a meta-heuristic approach to solve nonlinear resource-leveling problems has been intensively studied in recent years. Premature convergence and poor exploitation are the main obstacles for the heuristic algorithms. Analyzing the characteristics of the project topology network, this paper introduces a directional ant colony optimization (DACO) algorithm for solving nonlinear resource-leveling problems. The DACO algorithm introduced can efficiently improve the convergence rate and the quality of solution for real-project scheduling.

The aim of the present study was two-fold: 1) to utilize improved amygdala segmentation and exploratory factor analysis to characterize the latent volumetric structure among amygdala nuclei, and 2) to assess the effect of adverse childhood experiences (ACEs) on amygdalar morphometry and current psychiatric symptoms. To investigate these aims, structural (T1) MRI and self-report data were obtained from119 emerging adults. Regression analysis showed that higher ACE scores were related to reduced volume of the right, but not the left, amygdalar segments. Further, exploratory factor analysis yielded a two-factor structure, basolateral and central-medial nuclei of the right amygdala. Path analyses revealed that higher ACE scores were significantly related to a reduced volume of the right basolateral and central-medial segments. Furthermore, reduction in the right basolateral amygdala was associated with increased anxiety, depressive symptoms, and alcohol use. This association supports an indirect effect between early adversity and psychiatric problems via reduced right basolateral amygdalar volume. The high-resolution segmentation results reveal a latent structure among amygdalar nuclei that is consistent with prior work conducted in non-human mammals. These findings extend previous reports linking early adversity, right amygdala volume, and psychopathology.