Informer: Beyond Efficient Transformer for Long Sequence Time-Series Forecasting

Many real-world applications require the prediction of long sequence time-series, such as electricity consumption planning. Long sequence time-series forecasting (LSTF) demands a high prediction capacity of the model, which is the ability to capture precise long-range dependency coupling between output and input efficiently. Recent studies have shown the potential of Transformer to increase the prediction capacity. However, there are several severe issues with Transformer that prevent it from being directly applicable to LSTF, including quadratic time complexity, high memory usage, and inherent limitation of the encoder-decoder architecture. To address these issues, we design an efficient transformer-based model for LSTF, named Informer, with three distinctive characteristics: (i) a $ProbSparse$ self-attention mechanism, which achieves $O(L \log L)$ in time complexity and memory usage, and has comparable performance on sequences' dependency alignment. (ii) the self-attention distilling highlights dominating attention by halving cascading layer input, and efficiently handles extreme long input sequences. (iii) the generative style decoder, while conceptually simple, predicts the long time-series sequences at one forward operation rather than a step-by-step way, which drastically improves the inference speed of long-sequence predictions. Extensive experiments on four large-scale datasets demonstrate that Informer significantly outperforms existing methods and provides a new solution to the LSTF problem.Comment: 8 pages (main), 5 pages (appendix) and to be appeared in AAAI202

The Involvement of p53-miR-34a-CDK4 Signaling During the Development of Cervical Cancer

Aim: The aim was to explore the epigenetic mechanisms underlying cervical oncogenesis, we compared the level of microRNA-34a (miR-34a), p53, and cell cycle-related protein CDK4 within normal cervical tissue, cervical intraepithelial neoplasia III (CINIII) tissue, and cervical cancer tissue. Methods: Fresh normal cervical tissue, CINIII tissue, and cervical cancer tissue specimens were collected from patients not receiving chemotherapy, radiotherapy or immunotherapy prior to surgery. Stem-loop real-time polymerase chain reaction was employed to analyze the level of miR-34a. p53 was detected by immunohistochemistry, and cell cycle-related protein CDK4 was detected by Western blot. Results: The positive rates of p53 in CINIII and cervical cancer tissues were 35% and 68%, respectively (P < 0.01) while no p53 was detected in normal cervical tissue. miR-34a levels in CINIII and cervical cancer tissues were significantly down-regulated (0.53 ± 0.13-fold and 0.11 ± 0.07-fold, compared with normal cervical tissue, P < 0.01). CDK4 level in CINIII (0.31 ± 0.02) and cervical cancer (0.64 ± 0.04) tissue were significantly higher than that of normal cervical tissue (0.18 ± 0.01, P < 0.01). Meanwhile, the differences between the levels of these molecules in cervical cancer tissue and in CINIII tissue were notable (P < 0.05). Conclusion: With the progression of cervical cancer lesions, the positive rate of p53 was greatly increased which may indicate its mutation, while miR-34a was down-regulated and CDK4 was up-regulated, which suggested that all these factors might be involved in the process of cervical oncogenesis

Neoadjuvant chemotherapy followed by concurrent chemoradiotherapy with or without nimotuzumab in the treatment of locally advanced nasopharyngeal carcinoma: a retrospective study

Abstract Purpose We aimed to investigate the efficacy and side effects of concurrent chemoradiotherapy, with or without nimotuzumab, for the treatment of locally advanced nasopharyngeal carcinoma after neoadjuvant chemotherapy. Methods This study retrospectively enrolled 109 patients with NPC from our hospital from July 2019 to May 2021.All patients were treated with docetaxel, cisplatin, and fluorouracil(TPF) neoadjuvant chemotherapy for 2 cycles, and concurrent chemoradiotherapy was performed 2 weeks after chemotherapy. According to whether nimotuzumab was added in concurrent chemoradiotherapy, they were divided into the nimotuzumab group and the control group, with 52 cases in the nimotuzumab group and 57 cases in the control group.The efficacy and adverse reactions of the two groups were retrospectively analyzed. Results The objective remission and complete remission rates in the nimotuzumab and control groups were 100% vs 98.2% (p = 1.000), and 92.3% vs 78.9% (p = 0.049), respectively. The 3-year distant metastasis-free survival of the nimotuzumab and control groups was 91.6% and 77.3% (p = 0.047), respectively.The 3-year progression-free survival, locoregional relapse-free survival, and overall survival of the nimotuzumab and control groups were 87.6% vs 75.5% (p = 0.110), 90.5% vs 86.9% (p = 0.566), and 94.5% vs 87.1% (p = 0.295), respectively. In the nimotuzumab group, subgroup analysis showed that patients aged  0.05). Conclusion The concurrent chemoradiotherapy plus nimotuzumab after neoadjuvant chemotherapy for locally advanced nasopharyngeal carcinoma achieved a higher complete remission rate and significantly improved distant metastasis-free survival compared with concurrent chemoradiotherapy alone. Additionally, an increasing trend was observed in progression-free survival, and the incidence of side effects was similar in both groups

Selenium Dioxide Induced Apoptosis in Cervical Cancer Cells via Regulating Apoptosis-related Let-7a MicroRNA and Proteins

Aim: To investigate the effects of selenium dioxide (SeO2) on the apoptosis and the involved epigenetic mechanisms in two cervical cancer cell lines. Methods: Human cervical carcinoma cell lines HeLa and CaSki were treated with 1.875–30 µmol/L SeO2 for 24 h. Morphological changes were observed by optical microscope; anti-proliferative effects were examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay; flow cytometry (FCM) was employed to detect the cell apoptosis; real-time polymerase chain reaction was used to detect the expression of let-7a; and the levels of caspase-3 and p53 proteins in HeLa cells were determined by Western blot analysis. Differences between the mean values of multiple groups were analyzed by one-way analysis of variance or Student's t test. P < 0.05 was considered statistically significant. Results: Compared to control group, obvious morphological changes were observed in the SeO2 group. SeO2 significantly (P < 0.05) inhibited cell proliferation and viability in a dose-dependent manner (7.5 μmol/L, 15 μmol/L, and 30 μmol/L of SeO2), as demonstrated by MTT assay. FCM analysis revealed that SeO2, dose dependently, increased the apoptotic rate of the treated cells. SeO2 up-regulated the caspase-3 and p53 levels which peaked at the concentration of 7.5 μmol/L in HeLa cells. It also significantly (P < 0.05) induced the expression of apoptosis-related microRNA let-7a in both cell lines, which reached its peak at the concentration of 7.5 μmol/L. Conclusion: SeO2 showed anti-tumor properties via apoptotic pathway by up-regulating the expressions of let-7a, as well as caspase-3 and p53 in cervical cancer cells

Targeting histone demethylases JMJD3 and UTX: selenium as a potential therapeutic agent for cervical cancer

Abstract Background The intriguing connection between selenium and cancer resembles a captivating puzzle that keeps researchers engaged and curious. While selenium has shown promise in reducing cancer risks through supplementation, its interaction with epigenetics in cervical cancer remains a fascinating yet largely unexplored realm. Unraveling the intricacies of selenium's role and its interaction with epigenetic factors could unlock valuable insights in the battle against this complex disease. Result Selenium has shown remarkable inhibitory effects on cervical cancer cells in various ways. In in vitro studies, it effectively inhibits the proliferation, migration, and invasion of cervical cancer cells, while promoting apoptosis. Selenium also demonstrates significant inhibitory effects on human cervical cancer-derived organoids. Furthermore, in an in vivo study, the administration of selenium dioxide solution effectively suppresses the growth of cervical cancer tumors in mice. One of the mechanisms behind selenium's inhibitory effects is its ability to inhibit histone demethylases, specifically JMJD3 and UTX. This inhibition is observed both in vitro and in vivo. Notably, when JMJD3 and UTX are inhibited with GSK-J4, similar biological effects are observed in both in vitro and in vivo models, effectively inhibiting organoid models derived from cervical cancer patients. Inhibiting JMJD3 and UTX also induces G2/M phase arrest, promotes cellular apoptosis, and reverses epithelial-mesenchymal transition (EMT). ChIP-qPCR analysis confirms that JMJD3 and UTX inhibition increases the recruitment of a specific histone modification, H3K27me3, to the transcription start sites (TSS) of target genes in cervical cancer cells (HeLa and SiHa cells). Furthermore, the expressions of JMJD3 and UTX are found to be significantly higher in cervical cancer tissues compared to adjacent normal cervical tissues, suggesting their potential as therapeutic targets. Conclusions Our study highlights the significant inhibitory effects of selenium on the growth, migration, and invasion of cervical cancer cells, promoting apoptosis and displaying promising potential as a therapeutic agent. We identified the histone demethylases JMJD3 and UTX as specific targets of selenium, and their inhibition replicates the observed effects on cancer cell behavior. These findings suggest that JMJD3 and UTX could be valuable targets for selenium-based treatments of cervical cancer

Additional file 1 of Targeting histone demethylases JMJD3 and UTX: selenium as a potential therapeutic agent for cervical cancer

Additional file 1: Table S1. Primers used for the qPCR assay; Table S2. Primers used for the ChIP-qPCR assay