The prognostic role of circulating CD8+ T cell proliferation in patients with untreated extensive stage small cell lung cancer.

peer reviewed[en] BACKGROUND: Immunosuppression caused by tumorigenesis may promote tumor progress and invasion. Here, we investigated whether the characteristics of circulating T lymphocyte subtypes in patients with extensive small cell lung cancer (ED-SCLC) can be used as an alternative marker of tumor progression. METHODS: This study included 36 newly diagnosed ED-SCLC patients before treatment and the patients were followed up. 22 age and sex-matched healthy volunteers were selected as control. The percentages and proliferation potential of T lymphocyte subpopulations from peripheral blood were measured. RESULTS: CD4+ CD25+ Foxp3+ regulatory T cells (Tregs) were elevated in ED-SCLC patients compared with healthy controls (p = 0.0083). In contrast, the percentages of CD3+ and CD3+CD4+ T cells were significantly lower in SCLC patients (p < 0.001; p = 0.0014). The proliferation (%divided) of CD8+ T cells of SCLC patients was suppressed compared with healthy controls (p = 0.0058), but not of CD4+ T cells (p = 0.1611). Multivariate analyses showed that the %divided of CD8+ T cells is an independent predictor for PFS (HR: 4.342, 95% CI 1.324-14.245; p = 0.015). The percentages of peripheral Tregs and the degree of chemotherapy or radiotherapy induced lymphopenia negatively correlated with the proliferation of CD8+ T cells (p = 0.0225, r = - 0.379; p = 0.0003, r = - 0.464). CONCLUSION: The present study indicates that SCLC patients have impaired immunity in peripheral blood, and the proliferation potential of circulating CD8+ T cells is a significant predicator for PFS

Span-Based Semantic Role Labeling with Argument Pruning and Second-Order Inference

We study graph-based approaches to span-based semantic role labeling. This task is difficult due to the need to enumerate all possible predicate-argument pairs and the high degree of imbalance between positive and negative samples. Based on these difficulties, high-order inference that considers interactions between multiple arguments and predicates is often deemed beneficial but has rarely been used in span-based semantic role labeling. Because even for second-order inference, there are already O(n^5) parts for a sentence of length n, and exact high-order inference is intractable. In this paper, we propose a framework consisting of two networks: a predicate-agnostic argument pruning network that reduces the number of candidate arguments to O(n), and a semantic role labeling network with an optional second-order decoder that is unfolded from an approximate inference algorithm. Our experiments show that our framework achieves significant and consistent improvement over previous approaches

Learning from Training Dynamics: Identifying Mislabeled Data beyond Manually Designed Features

While mislabeled or ambiguously-labeled samples in the training set could negatively affect the performance of deep models, diagnosing the dataset and identifying mislabeled samples helps to improve the generalization power. Training dynamics, i.e., the traces left by iterations of optimization algorithms, have recently been proved to be effective to localize mislabeled samples with hand-crafted features. In this paper, beyond manually designed features, we introduce a novel learning-based solution, leveraging a noise detector, instanced by an LSTM network, which learns to predict whether a sample was mislabeled using the raw training dynamics as input. Specifically, the proposed method trains the noise detector in a supervised manner using the dataset with synthesized label noises and can adapt to various datasets (either naturally or synthesized label-noised) without retraining. We conduct extensive experiments to evaluate the proposed method. We train the noise detector based on the synthesized label-noised CIFAR dataset and test such noise detector on Tiny ImageNet, CUB-200, Caltech-256, WebVision and Clothing1M. Results show that the proposed method precisely detects mislabeled samples on various datasets without further adaptation, and outperforms state-of-the-art methods. Besides, more experiments demonstrate that the mislabel identification can guide a label correction, namely data debugging, providing orthogonal improvements of algorithm-centric state-of-the-art techniques from the data aspect

Theacrine: A purine alkaloid from Camellia assamica var. kucha with a hypnotic property via the adenosine system

Theacrine (1,3,7,9-tetramethyluric acid), a purine alkaloid from Camellia assamica var. kucha, has diverse pharmacological properties, including sedative and hypnotic activities, anti-inflammatory and analgesic activities, antidepressant effects, and a protective effect against stress-provoked liver damage. The present study aims to investigate the possible mechanism of the hypnotic activity of theacrine. The results revealed that theacrine significantly enhanced pentobarbital-induced sleep at a dose of 3.0 mg/kg (i.g.) in mice. Sleep parameter analysis by EEG and EMG showed that theacrine obviously shortened wake time and increased NREM sleep time and that theacrine almost had no effect on REM sleep. Meanwhile, theacrine markedly attenuated caffeine (a nonselective antagonist of adenosine receptor)-induced insomnia. In pretreatment with the adenosine A(1) receptor antagonist DPCPX and the A(2A) receptor antagonist SCH 58261, theacrine significantly reversed the decrease in sleeping time in pentobarbital-treated mice. In addition, theacrine also markedly increased the adenosine content in the hippocampus of rats. These results suggested that theacrine might mediate the adenosine system to augment pentobarbital-induced sleep.</p

Amorphous nickel-cobalt complexes hybridized with 1T-phase molybdenum disulfide via hydrazine-induced phase transformation for water splitting.

Highly active and robust eletcrocatalysts based on earth-abundant elements are desirable to generate hydrogen and oxygen as fuels from water sustainably to replace noble metal materials. Here we report an approach to synthesize porous hybrid nanostructures combining amorphous nickel-cobalt complexes with 1T phase molybdenum disulfide (MoS2) via hydrazine-induced phase transformation for water splitting. The hybrid nanostructures exhibit overpotentials of 70 mV for hydrogen evolution and 235 mV for oxygen evolution at 10 mA cm-2 with long-term stability, which have superior kinetics for hydrogen- and oxygen-evolution with Tafel slope values of 38.1 and 45.7 mV dec-1. Moreover, we achieve 10 mA cm-2 at a low voltage of 1.44 V for 48 h in basic media for overall water splitting. We propose that such performance is likely due to the complete transformation of MoS2 to metallic 1T phase, high porosity and stabilization effect of nickel-cobalt complexes on 1T phase MoS2

Therapeutic Effect Of First-Line EGFR-TKIs Combined With Concurrent Cranial Radiotherapy On NSCLC Patients With EGFR Activating Mutation And Brain Metastasis: A Retrospective Study.

peer reviewed[en] PURPOSE: Non-small cell lung cancer (NSCLC) patients with EGFR mutation are suffering from a high incidence of brain metastasis (BM). It is still controversial whether cranial radiotherapy could be delayed when the EGFR-tyrosine kinase inhibitors (TKIs) used as first-line therapy for EGFR-positive patients with BM. This study aims to investigate the therapeutic effect of TKIs combined with concurrent cranial radiotherapy on BM. PATIENTS AND METHODS: NSCLC patients with EGFR mutation and BM were retrospectively analyzed from January 2013 to December 2016 in Shandong Cancer Hospital. Identified cases were treated with first-line EGFR-TKIs with or without concurrent cranial radiation. RESULTS: A total of 64 eligible patients were enrolled in this study, while 35 patients received first-line EGFR-TKIs plus cranial radiotherapy (RT+TKI group) and 29 patients received first-line EGFR-TKIs only (TKI alone group). The intracranial progression-free survival (PFS) of the RT+TKI group was significantly longer than the TKI alone group (25 vs 16 months; p=0.019), but no significant differences were observed between the two groups on extracranial PFS (20 vs 17 months, p=0.660). The median overall survival was also longer in the RT+TKI group (31 vs 24 months, p=0.019). CONCLUSION: Our retrospective data suggest that first-line TKIs plus concurrent cranial radiotherapy is a promising therapeutic strategy that led to remarkable intracranial PFS improvement and survival benefits for EGFR-mutant NSCLC with BM. Hence, it should be considered as a crucial treatment method during clinical management

Prospects for Heavy WIMP Dark Matter Searches at Muon Colliders

Plots summarizing the constraints on Dark Matter models can help visualize synergies between different searches for the same kind of experiment, as well as between different experiments. In this whitepaper, we present an update to the European Strategy Briefing Book plots, from the perspective of collider searches within the Dark Matter at the Energy Frontier (EF10) Snowmass Topical Group, starting from inputs from future collider facilities. We take as a starting point the plots currently made for LHC searches using benchmark models recommended by the Dark Matter Working Group, also used for the BSM and Dark Matter chapters of the European Strategy Briefing Book. These plots can also serve as a starting point for cross-frontier discussions about dark matter complementarity, and could be updated as a consequence of these discussions. This is a whitepaper submitted to the APS Snowmass process for the EF10 topical group.Comment: contribution to Snowmass 202

Systematic design of superaerophobic nanotube-array electrode comprised of transition-metal sulfides for overall water splitting.

Great attention has been focused on the design of electrocatalysts to enable electrochemical water splitting-a technology that allows energy derived from renewable resources to be stored in readily accessible and non-polluting chemical fuels. Herein we report a bifunctional nanotube-array electrode for water splitting in alkaline electrolyte. The electrode requires the overpotentials of 58 mV and 184 mV for hydrogen and oxygen evolution reactions respectively, meanwhile maintaining remarkable long-term durability. The prominent performance is due to the systematic optimization of chemical composition and geometric structure principally-that is, abundant electrocatalytic active sites, excellent conductivity of metallic 1T' MoS2, synergistic effects among iron, cobalt, nickel ions, and the superaerophobicity of electrode surface for fast mass transfer. The electrode is also demonstrated to function as anode and cathode, simultaneously, delivering 10 mA cm-2 at a cell voltage of 1.429 V. Our results demonstrate substantial improvement in the design of high-efficiency electrodes for water electrolysis