Transfer Value Iteration Networks

Value iteration networks (VINs) have been demonstrated to have a good generalization ability for reinforcement learning tasks across similar domains. However, based on our experiments, a policy learned by VINs still fail to generalize well on the domain whose action space and feature space are not identical to those in the domain where it is trained. In this paper, we propose a transfer learning approach on top of VINs, termed Transfer VINs (TVINs), such that a learned policy from a source domain can be generalized to a target domain with only limited training data, even if the source domain and the target domain have domain-specific actions and features. We empirically verify that our proposed TVINs outperform VINs when the source and the target domains have similar but not identical action and feature spaces. Furthermore, we show that the performance improvement is consistent across different environments, maze sizes, dataset sizes as well as different values of hyperparameters such as number of iteration and kernel size

Decoder Choice Network for Metalearning

Metalearning has been widely applied for implementing few-shot learning and fast model adaptation. Particularly, existing metalearning methods have been exploited to learn the control mechanism for gradient descent processes, in an effort to facilitate gradient-based learning in gaining high speed and generalization ability. This article presents a novel method that controls the gradient descent process of the model parameters in a neural network, by limiting the model parameters within a low-dimensional latent space. The main challenge for implementing this idea is that a decoder with many parameters may be required. To tackle this problem, the article provides an alternative design of the decoder with a structure that shares certain weights, thereby reducing the number of required parameters. In addition, this work combines ensemble learning with the proposed approach to improve the overall learning performance. Systematic experimental studies demonstrate that the proposed approach offers results superior to the state of the art in performing the Omniglot classification and miniImageNet classification tasks

A retrospective study for prognostic significance of type II diabetes mellitus and hemoglobin A1c levels in non-small cell lung cancer patients treated with pembrolizumab

Background: Diabetes mellitus (DM) is common and recognized as a risk factor for developing non-small cell lung cancer (NSCLC) while the prognostic evaluation is still controversial. As immunotherapy is widely used in clinical practice, its efficacy and survival should be investigated in patients with DM. Methods: We retrospectively recruited 266 locally advanced and metastatic NSCLC patients who received pembrolizumab alone or in combination with chemotherapy. Patients\u27 clinicopathological data, including age, history of DM, hemoglobin A1c (HbA1c), genetic tumor profiling, and survival data were collected. Associations between clinical characteristics and survival were evaluated by univariate and multivariate analyses. Results: In this cohort, 15.04 % (40/266) of the patients had a history of DM. Fifty-nine (22.2 %) patients had a HbA1c level ≥ 6.5 %. A total of 169 (63.5 %) patients received 1st-line therapy, and 97 (36.5 %) received 2nd- or subsequent-line therapy. Patients with high ( ≥ 6.5 %) HbA1c and lower ( \u3c 35 g/L) albumin levels at baseline had worse survivals, and epidermal growth factor receptor (EGFR) mutants significantly associated with worse outcomes at normal HbA1c ( \u3c 6.5%) levels (all P \u3c 0.05). Among the 1st-line therapy patients, a higher HbA1c level ( ≥ 6.5 %) at baseline indicated a worse overall survival (OS) (2-year survival rate: 31.25 % vs. 27.03 %, P = 0.045), tumor protein p53 (TP53) alternations and high programmed death-ligand 1 (PD-L1) expression ( ≥ 50 %) were significantly associated with better outcomes (P \u3c 0.05). For 2nd- or subsequent-line patients, EGFR mutants and non-squamous carcinomas (non-SCs) indicated worse survivals, and the normal peripheral blood markers of the carcinoembryonic antigen (CEA), C-reactive protein (CRP), albumin levels were favorable prognostic factors for survivals. In non-SCs, Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations, high PD-L1 expression, and normal alkaline phosphatase (ALP) levels favored better progression-free survival (PFS), while EGFR mutants indicated poor PFS (P \u3c 0.05). Conclusions: Among patients treated with 1st-line immunotherapy, a higher HbA1c level ( ≥ 6.5 %) indicated dismal OS, while history of DM, baseline blood glucose levels, and glucose changes during the treatment process were not significantly associated with any of the outcomes

Identification of LncRNA Linc00513 Containing Lupus-Associated Genetic Variants as a Novel Regulator of Interferon Signaling Pathway

Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by augmented type I interferon signaling. High-throughput technologies have identified plenty of SLE susceptibility single-nucleotide polymorphisms (SNPs) yet the exact roles of most of them are still unknown. Functional studies are principally focused on SNPs in the coding regions, with limited attention paid to the SNPs in non-coding regions. Long non-coding RNAs (lncRNAs) are important players in shaping the immune response and show relationship to autoimmune diseases. In order to reveal the role of SNPs located near SLE related lncRNAs, we performed a transcriptome profiling of SLE patients and identified linc00513 as a significantly over expressed lncRNA containing functional SLE susceptibility loci in the promoter region. The risk-associated G allele of rs205764 and A allele of rs547311 enhanced linc00513 promoter activity and related to increased expression of linc00513 in SLE. We also identified linc00513 to be a novel positive regulator of type I interferon pathway by promoting the phosphorylation of STAT1 and STAT2. Elevated linc00513 expression positively correlated with IFN score in SLE patients. Linc00513 expression was higher in active disease patients than those inactive ones. In conclusion, our data identify two functional promoter variants of linc00513 that contribute to increased level of linc00513 and confer susceptibility on SLE. The study provides new insights into the genetics of SLE and extends the role of lncRNAs in the pathogenesis of SLE

SNP rs3803264 polymorphisms in THSD1 and abnormally expressed mRNA are associated with hemorrhagic stroke

BackgroundThrombospondin Type 1 Domain Containing Protein 1 (THSD1) has been suggested to be a new regulator of endothelial barrier function in the angiogenesis process, preserving vascular integrity. We sought to characterize the association of THSD1 genetic variants and mRNA expression with the risk of hemorrhagic stroke (HS) with population-based evidence.MethodsA case–control study was conducted with 843 HS cases and 1,400 healthy controls. A cohort study enrolled 4,080 participants free of stroke at baseline in 2009 and followed up to 2022. A synonymous variant, the main tag SNP rs3803264 of the THSD1 gene, was genotyped in all subjects, and peripheral leukocyte THSD1 mRNA expression was detected using RT-qPCR in 57 HS cases and 119 controls.ResultsIn the case–control study, rs3803264 AG/GG variations are associated with a decreased risk of HS with odd ratio (OR) and 95% confidence interval (CI) of the dominant model of 0.788 (0.648–0.958), p = 0.017. In addition, rs3803264 and dyslipidemia had a multiplicative interaction [OR (95% CI) = 1.389 (1.032, 1.869), p = 0.030]. In the cohort study, a similar association strength of rs3803264 dominant model and the risk of HS was observed with the incidence rate ratio (IRR) of 0.734 and p-value of 0.383. Furthermore, the risk of HS showed a non-linear as THSD1 mRNA expression increased (p for non-linearity <0.001). For the subjects without hypertension, we observed THSD1 mRNA expression had a negative correlation with systolic blood pressure (SBP; ρ = −0.334, p = 0.022).ConclusionSNP rs3803264 polymorphisms in THSD1 are associated with the decreased risk of HS and interacted with dyslipidemia, and a non-linear association was observed between THSD1 mRNA expression and the risk of HS

Microwave Synthesis and High‐Mobility Charge Transport of Carbon‐Nanotube‐in‐Perovskite Single Crystals

Organolead trihalide perovskites have emerged as a new class of competitive solution-processed semiconductors due to their unique optoelectronic properties. However, poor ambient stability and charge transport are the Achilles’ heel of hybrid perovskites, thus limiting their applications. In this work, microwave-assisted synthesis is applied for the first time to rapidly grow perovskite single crystals embedded with single-wall carbon nanotubes. These nanotube-in-perovskite single crystals are endowed with a carrier mobility one order of magnitude higher than the pure counterpart and the related photodetectors show an ultrafast photo-response speed (5 and 80 ns for rise and decay time, respectively). The fast and uniform heating of microwave irradiation facilitates the synthesis of ambient-stable crystals with nanoscale additives, paving the way to creating a wide range of mixed-dimensional perovskite-based nanocomposites with optimal properties and device performance

Maintenance Chemotherapy With Chinese Herb Medicine Formulas vs. With Placebo in Patients With Advanced Non-small Cell Lung Cancer After First-Line Chemotherapy: A Multicenter, Randomized, Double-Blind Trial

Background: Chinese Herb Medicine Formulas (CHMF) was reported to improve the quality of life (QoL) in advanced NSCLC patients. The present study was designed to investigate whether maintenance chemotherapy plus CHMF in patients would improve QoL and progression-free survival (PFS).Methods: Seventy-one patients were enrolled from 8 medical centers in China, and were randomly assigned to a maintenance chemotherapy plus CHMF group (n = 35) or a maintenance chemotherapy plus placebo group (n = 36). The outcome measures included PFS, Karnofsky performance status (KPS) scores, QoL (assessed with the lung cancer symptom scale (LCSS) questionnaire), and adverse events (AEs).Results: Patients in the CHMF group showed significant improvements in median PFS (HR = 0.55, 95% CI 0.28–0.88, P = 0.019), KPS scores (P = 0.047), fatigue (cycle [C] 3: P = 0.03), interference with daily activities (C3: P = 0.04) and dyspnea (C2: P = 0.03) compared with patients in the placebo group. Compared with the placebo group, the incidence of AEs decreased in the CHMF group, including loss of appetite (C2: P = 0.011, C4: P = 0.004) and dry mouth (C4: P = 0.011).Conclusion: The essential finding of our study is that maintenance chemotherapy combined with CHMF may prolong PFS, relieve symptoms, improve QoL and alleviate the side effects

MiR-34a Represses Numbl in Murine Neural Progenitor Cells and Antagonizes Neuronal Differentiation

MicroRNA (miRNA) function is required for normal animal development, in particular in differentiation pathways from stem cell and precursor populations. In neurogenesis, it is becoming increasingly appreciated that miRNAs act at many stages to ensure proper progression. In this study we examined the role of miR-34a in neural progenitor cells (NPC) derived from murine embryonic cortex. We found that over-expression of miR-34a in NPC significantly reduced the neuron yield upon in vitro induction of differentiation. MiR-34a has several predicted targets in the Notch pathway, which operates to balance progenitor self-renewal and differentiation during cortical neurogenesis. We tested several Notch pathway players for regulation by miR-34a in undifferentiated NPC, and found that mRNA and protein levels of Numbl, a negative regulator of Notch signaling, as well as two downstream pro-neural genes usually blocked by Notch signaling, NeuroD1 and Mash1, were diminished, while Notch1 and Cbf1 transcripts were enhanced by miR-34a over-expression. Using a luciferase reporter assay, we verified the Numbl 3′-UTR as a direct miR-34a target. Correspondingly, knock-down of endogenous miR-34a resulted in increased Numbl, NeuroD1 and Mash1, and reduced Notch1 transcript levels. Together these results implicate Numbl as a physiologically relevant target of miR-34a in NPC, allowing for enhanced Notch signaling and inhibition of neuronal differentiation. This work extends our understanding of miR-34a-mediated control of cell differentiation from cancer to mammalian nervous system development