Cognitive diagnostic assessment: A Q-matrix constraint-based neural network method.

Cognitive diagnosis is a crucial element of intelligent education that aims to assess the proficiency of specific skills or traits in students at a refined level and provide insights into their strengths and weaknesses for personalized learning. Researchers have developed numerous cognitive diagnostic models. However, previous studies indicate that diagnostic accuracy can be significantly influenced by the appropriateness of the model and the sample size. Thus, designing a general model that can adapt to different assumptions and sample sizes remains a considerable challenge. Artificial neural networks have been proposed as a promising approach in some studies. In this paper, we propose a cognitive diagnosis model of a neural network constrained by a Q-matrix and named QNN. Specifically, we employ the Q-matrix to determine the connections between neurons and the width and depth of the neural network. Moreover, to reduce the human effort in the training algorithm, we designed a self-organizing map-based cognitive diagnosis training framework called SOM-NN, which enables the QNN to be trained unsupervised. Extensive experimental results on simulated and real datasets demonstrate that our approaches are effective in both accuracy and interpretability. Notably, under unsupervised conditions, our approach has significant advantages on small sample datasets with high levels of guessing and slipping, especially on the pattern-wise agreement rates. This work bridges the gap between psychometrics and machine learning and provides a realistic and implementable reference solution for classroom instructional assessment and the cold start of personalized and adaptive assessment systems.

Effects of 1p/19q Codeletion on Immune Phenotype in Low Grade Glioma.

Background: Chromosome 1p/19q codeletion is one of the most important genetic alterations for low grade gliomas (LGGs), and patients with 1p/19q codeletion have significantly prolonged survival compared to those without the codeletion. And the tumor immune microenvironment also plays a vital role in the tumor progression and prognosis. However, the effect of 1p/19q codeletion on the tumor immune microenvironment in LGGs is unclear. Methods: Immune cell infiltration of 281 LGGs from The Cancer Genome Atlas (TCGA) and 543 LGGs from the Chinese Glioma Genome Atlas (CGGA) were analyzed for immune cell infiltration through three bioinformatics tools: ESTIMATE algorithm, TIMER, and xCell. The infiltrating level of immune cells and expression of immune checkpoint genes were compared between different groups classified by 1p/19q codeletion and IDH (isocitrate dehydrogenase) mutation status. The differential biological processes and signaling pathways were evaluated through Gene Set Enrichment Analysis (GSEA). Correlations were analyzed using Spearman correlation. Results: 1p/19q codeletion was associated with immune-related biological processes in LGGs. The infiltrating level of multiple kinds of immune cells and expression of immune checkpoint genes were significantly lower in 1p/19q codeletion LGGs compared to 1p/19q non-codeletion cohorts. There are 127 immune-related genes on chromosome 1p or 19q, such as TGFB1, JAK1, and CSF1. The mRNA expression of these genes was positively correlated with their DNA copy number. These genes are distributed in multiple immune categories, such as chemokines/cytokines, TGF-ß family members, and TNF family members, regulating immune cell infiltration and expression of the immune checkpoint genes in tumors. Conclusion: Our results indicated that 1p/19q codeletion status is closely associated with the immunosuppressive microenvironment in LGGs. LGGs with 1p/19q codeletion display less immune cell infiltration and lower expression of immune checkpoint genes than 1p/19q non-codeletion cases. Mechanistically, this may be, at least in part, due to the deletion of copy number of immune-related genes in LGGs with 1p/19q codeletion. Our findings may be relevant to investigate immune evasion in LGGs and contribute to the design of immunotherapeutic strategies for patients with LGGs.

RIPK1 contributes to cisplatin-induced apoptosis of esophageal squamous cell carcinoma cells via activation of JNK pathway.

AIMS: Previous studies have uncovered the function of receptor-interacting protein kinase 1 (RIPK1) to mediate both cell survival and death. Moreover, RIPK1 modulates apoptosis and necroptosis depending on its activity, phosphorylation or ubiquitylation status. Many studies have explained the role or mechanism of RIPK1 in necroptosis. However, the role of RIPK1 has not been elucidated fully in human esophageal squamous cell carcinoma (ESCC) cells. MATERIALS AND METHODS: The protein and mRNA expression levels of RIPK1 in a panel of ESCC cell lines by Western blot and real-time quantitative reverse transcription PCR (qRT-PCR) were analyzed. MTS assay was used to examine cellular proliferation, flow cytometric analysis to detect apoptosis, mitochondrial membrane potential and reactive oxygen species production. ESCC cells with either inhibitor or overexpressed RIPK1were analyzed to determine cell proliferation, colony formation and apoptosis. Flow cytometry and western blotting assays were used to explore the underlying mechanism. KEY FINDINGS: In our study, RIPK1 expression was found to contribute significantly to cisplatin-induced apoptosis in the human ESCC cells. The reduced RIPK1 expression promoted cells proliferation and overexpressed RIPK1 facilitated cell apoptosis. Mechanistic investigations have revealed that the inhibition of proliferation for RIPK1 in ESCC cells was regulated via activation of c-Jun NH2-terminal kinase signaling. Additionally, damages were observed in the mitochondrial membrane, depletion of ATP and increased generation in reactive oxygen species. SIGNIFICANCE: Our findings verified the evidence that RIPK1 can promote cell death in ESCC cells, with potential implications for activating c-Jun NH2-terminal kinase pathway as a novel approach to the disease.

Poly(ethylene glycol) shell-sheddable TAT-modified core cross-linked nano-micelles: TAT-enhanced cellular uptake and lysosomal pH-triggered doxorubicin release.

This study aimed to develop sheddable polyethylene glycol (PEG) shells with TAT-modified core cross-linked nanomicelles as drug-delivery carriers of doxorubicin (DOX) to establish a programmed response against the tumor microenvironment, enhanced endocytosis, and lysosomal pH-triggered DOX release. First, poly(L-succinimide) (PSI) underwent a ring-opening reaction with ethylenediamine to generate poly(N-(2-aminoethyl)-l-aspartamide) (P(ae-Asp)). Next, the thiolytic cleavable PEG, 3,4-dihydroxyphenylacetic acid, and TAT were grafted onto P(ae-Asp) to synthesize the amphiphilic graft copolymer of mPEG-SS-g-P(ae-Asp)-MCA-DA-TAT. In aqueous solution, the amphiphilic polymer self-assembled into nanomicelles, encapsulating DOX into the hydrophobic core of micelles. TAT was shielded by the PEG corona during circulation to avoid non-specific transmembrane interaction with normal cells, while the tumor redox environment-responsive shedding of PEG could expose TAT to promote internalization of tumor cells. In order to improve the stability of nanomicelles and achieve pH-triggered drug release, a core cross-linking strategy based on the coordination of catechol and Fe3+ was adopted. In vitro studies demonstrated that core cross-linked nanomicelles maintained the nanostructure in 100 times dilution in pH 7.4 phosphate-buffered saline (PBS). Moreover, DOX release from DOX-loaded core cross-linked nanomicelles (DOX-TAT-CCLMs) was favored at simulated lysosomal conditions over simulated plasma conditions, indicating that these nanomicelles demonstrate characteristics of pH-triggered DOX release. The TAT modification considerably enhanced the mean fluorescence intensity of the nanomicelles endocytosed by MCF-7/ADR cells by 8 times, compared with DOX·HCl after 8 h of incubation. Notably, the IC50 value of nanomicelles (11.61 ±â€¯0.95 µg/mL) was nearly 4 times lower than that of DOX·HCl against MCF-7/ADR cells, implying that the nanomicelles could overcome drug resistance observed in MCF-7/ADR cells. Furthermore, the DOX-TAT-CCLMs reported superior tumor growth suppression in a 4T1 tumor-bearing mouse model. Thus, the redox- and pH- stimuli stepwise-responsive novel nanomicelles fabricated from the mPEG-SS-g-P(ae-Asp)-MCA-DA-TAT graft copolymer exhibited multifunctionality and displayed great potential for drug delivery.

A retrospective study of paclitaxel combining nedaplatin chemotherapy for esophageal cancer.

The aim of this study was to evaluate the efficacy and tolerability of the combination of paclitaxel and nedaplatin in patients with advanced esophageal cancer. Patients (n = 310) with recurrent or metastatic esophageal squamous cell carcinoma, who had a maximum of one previous chemotherapy regimen, were enrolled in this study. All patients had bidimensionally measurable disease. Patients received 175 mg/m of paclitaxel over a 3 h infusion, followed by nedaplatin 80 mg/m in a 1 h infusion on day 1 every 3 weeks for up to 6 treatment cycles. The overall response rate was 47.7%, with complete and partial response rates of 6.1 and 41.7%, respectively. The median time to progression for all patients was 6.8 months (95% confidence interval, 6.2-7.4 months) and the 3-year disease-free survival probability was 3 (15.8%). The major toxicity observed was cumulative neutropenia, with 29% patients developing grade 4 toxicity. There was no treatment-related death. The most common nonhematologic toxicity encountered with this regimen was pain and cumulative peripheral neuropathy, with 26% patients experiencing grade 2 or 3 toxicity. The combination of paclitaxel and nedaplatin shows significant antitumor activity and a favorable toxicity profile in patients with metastatic carcinoma of esophageal cancer.