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In the wake of the ongoing nationwide antiracist movement, the academy at large has been reflecting on its role in society and the pursuit of social justice. Here, we examine the state of diversity...

The development of smartphones and social networks has brought great convenience to our lives. Due to the increasing requirements of user privacy, user data are protected by encryption protocol. Nevertheless, the encrypted traffic may still be identificated by a third party. In order to improve the privacy protection of users, it is necessary to study the existing encrypted user behavior system. The existing user behavior identification adopts the statistical features of encrypted traffic, which fluctuates greatly in different transmission environments. In this paper, we propose a Stable Features Identification Method(SFIM), which concentrate on filtering out the stable features from the encrypted traffic to identify user behavior. Based on the principle of maximum entropy, we put forward an approach to divide the distribution ranges of these stable features, and map the feature space into vector space. Our research focuses on multiple user behavior in the Instagram application. The best evaluation results achieve 99.8% accuracy, 99.3% precision, 99.3% recall, and 0.09% false positive rate(FPR) on average.

Background: The Hong Kong Brief Cognitive Test (HKBC), a brief instrument designed to screen for cognitive impairment in older adults, has been validated in Cantonese-speaking populations and has shown better performance than the Mini-Mental State Examination (MMSE) in detecting both mild and major neurocognitive disorder (NCD). Objective: This study aimed to validate the HKBC for detecting patients with amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD) in a Mandarin-speaking Chinese population. Methods: Two hundred forty-eight patients with aMCI, 67 patients with mild AD and 306 healthy controls (HCs) were recruited for this study and completed both the HKBC and the MMSE. The performance of the HKBC and MMSE in distinguishing patients with aMCI from HCs and distinguishing patients with AD from patients with aMCI was compared in the whole population and in age- and education-stratified subgroups. Results: The optimal HKBC cutoff score for distinguishing patients with aMCI from HCs was 23, and the optimal cutoff score for distinguishing patients with AD from patients with aMCI was 17. The HKBC significantly outperformed the MMSE at differentiating patients with aMCI from HCs in the whole population (z = 12.38, p

Serum interleukin-8 (IL-8) levels and tumor neutrophil infiltration are associated with worse prognosis in advanced cancers. Here, using a large-scale retrospective analysis, we show that elevated baseline serum IL-8 levels are associated with poor outcome in patients (n = 1,344) with advanced cancers treated with nivolumab and/or ipilimumab, everolimus or docetaxel in phase 3 clinical trials, revealing the importance of assessing serum IL-8 levels in identifying unfavorable tumor immunobiology and as an independent biomarker in patients receiving immune-checkpoint inhibitors. In a retrospective analysis of data from four phase 3 clinical trials, elevated baseline serum IL-8 levels were associated with worse clinical outcomes in patients with multiple tumor types treated with anti-PD-1 monotherapy or anti-PD-1 and anti-CTLA-4 combinatorial therapy.

RNA interference (RNAi) has potential advantages over other gene therapy approaches due to its high specificity and the ability to inhibit target gene expression. However, the stability and tissue-specific delivery of siRNA remain as the biggest obstacles for RNAi therapeutics. Here, we developed such a system by conjugating gelatin-based nanogels with the nucleolin-targeted AS1411 aptamer and deoxynucleotide-substituted siRNA together (Apt-GS/siRNA) via a disulfide linker to achieve transient docking of siRNA. These Apt-GS/siRNA nanogels demonstrated favorable release of siRNA under reducing conditions owing to disulfide cleavage. Furthermore, this smart system could electively release siRNA into the cytosol in nucleolin-positive cells (A549) by a glutathione-triggered disassembly and subsequently efficient RNAi for luciferase. Besides, disulfide-equipped Apt-GS nanogels showed good biocompatibility in vitro. Taken together, this redox-responsive, tumor-targeting smart nanogels display great potential in exploiting functionalized siRNA delivery and tumor therapy.

Purpose: Piwi-interacting RNAs (piRNAs) are a novel class of small non-coding RNAs, which are not easily degraded but detectable in human body fluids. Recent studies have shown that aberrant piRNA expression is a signature feature across multiple tumor types. However, the expressions of piRNAs in serum of tumor patients and their potential clinical values remain largely unclear. Patients and methods: High-throughput sequencing was performed to investigate the serum piRNA profiles, followed by evaluations in serum samples of 220 colorectal cancer (CRC) patients and 220 healthy controls using reverse transcription quantitative real-time PCR (RT-qPCR). Biomarker panels including piRNA-based Panel I and carcinoembryonic antigen (CEA)-based Panel II, were developed by logistic regression model, and their diagnostic potentials were compared. Fagan's nomogram was plotted to promote clinical application. Results: We identified five differentially expressed serum piRNAs (piR-001311, piR-004153, piR-017723, piR-017724 and piR-020365), which, when combined in the piRNA-based Panel I, outperformed the CEA-based Panel II (P

Two new 2D → 2D zinc(II) coordination polymers, [Zn(btre)0.5(nbdc)(H2O)]n (1) and {[Zn(btre)0.5(MeOip)(H2O)2]·H2O}n (2) (btre = 1,2-bis(1,2,4-triazol-4-yl)ethane, nbdc=3-nitro-1, 2-benzenedicarboxylate, MeOip=4-methoxybenzene-1, 3-dicarboxylate) were synthesized at room temperature condition and characterized by IR spectra, elemental analyses, single-crystal and powder X-ray diffractions. Three sets of equivalent 2D (6, 3) networks parallel polycatenated with each other to give a 2D → 2D network in 1 and 2. There are strong π-π interactions and hydrogen bonding interactions between adjacent parallel polycatenated 2D (6, 3) network in 1. Only hydrogen bonding interactions exist in 2. Thermal stabilities and luminescence of 1 and 2 were investigated.

Aim Nivolumab, a fully human immunoglobulin G4 programmed death-1 (PD-1) immune checkpoint inhibitor antibody, has activity in melanoma, non–small-cell lung cancer (NSCLC), renal cell carcinoma (RCC), and Hodgkin lymphoma. Nivolumab is approved in the USA and EU for advanced melanoma, NSCLC, and RCC, and relapsed Hodgkin lymphoma in the USA. Programmed death-ligand 1 (PD-L1), a PD-1 ligand, is expressed on mononuclear leukocytes, myeloid cells, and tumor cells. PD-L1 is being investigated as a potential biomarker to predict the association of tumor PD-L1 expression with nivolumab efficacy. Methods Bristol-Myers Squibb and Dako previously reported on an automated PD-L1 immunohistochemical (IHC) assay that detects cell surface PD-L1 in formalin-fixed, paraffin-embedded, human tumor tissue specimens using Dako’s Autostainer Link 48. The primary antibody for this assay is a rabbit monoclonal antihuman PD-L1 antibody, clone 28-8. Another rabbit monoclonal antihuman PD-L1 antibody, clone E1L3N, was compared with 28-8 for specificity and sensitivity using an identical detection method followed by vendor-recommended detection methods. Results Using PD-L1 null clones of L2987 and ES-2 tumor cell lines, both antibodies were specific for detection of PD-L1 on the plasma membrane, although E1L3N also stained cytoplasm in ES-2 knockout cells. Using the identical method, E1L3N was slightly more sensitive than 28-8 based on staining intensities. Using manufacturer-recommended detection methods and predefined scoring criteria for plasma membrane staining of tumor and immune cells, 28-8 demonstrated significantly improved detection compared with E1L3N. Conclusions Epitope retrieval and highly sensitive detection reagents are key determinants in IHC detection of PD-L1. Electronic supplementary material The online version of this article (doi:10.1007/s40291-016-0237-9) contains supplementary material, which is available to authorized users.

To determine the relationships among retinal/choroidal thickness, retinal microvascular network and visual field in high myopia.This cross-sectional study included a total of 62 subjects, comprising 31 eyes with high myopia and 31 eyes with emmetropia or low myopia. Optical coherence tomography was used to quantify the thickness of ganglion cell complex (GCC), inner nuclear layer and outer plexiform layer (INOPL), outer retinal layer (ORL) and choroid layer (ChL). Optical coherence tomography angiography was used to quantify the superficial vessel density (SVD) and deep vessel density (DVD). Retinal light sensitivity (RLS) was measured by microperimetry-1 (MP1). The inner ring (1-1.75 mm), the outer ring (1.75-2.5 mm) and the whole ring (1-2.5 mm) around the macula were analysed and compared between the two groups. Pearson correlation analysis was performed to analyse the relationship among them.In the highly myopic group, the thinning of retinal/choroidal thickness and the decrease in retinal vessel density and RLS were found when compared to the emmetropia or low myopia (p 0.05). Decreased RLS was correlated with decreased ORL thickness (r = -0.469, p = 0.008) and choroid thickness (r = 0.398, p = 0.030). There was no correlation between retinal microvascular network parameters and RLS (p 0.05), but DVD showed a negative correlation with ORL (r = -0.474, p = 0.007).Early visual field defects in highly myopic eyes may be influenced by the ORL loss and defect of choroidal circulation. The deep retinal microvascular network may have a compensatory action in the hypoxic setting of high myopia.

Willow (Salix spp.), a woody plant in forms of tree, sub-tree, or shrub, has long been cultivated as an important fiber resource and for environmental protection. To manage commercial willow plantations, there is an increasing demand for the genetic discrimination of willow cultivars based on molecular markers. In this study, based on the genomic sequences of Salix suchowensis, a core set of 16 highly polymorphic simple sequence repeat (SSR) primer pairs were selected for the molecular discrimination of different willow cultivars. Using these primer pairs, DNA fingerprints of a collection of 25 elite willow cultivars were generated and their genetic identities were analyzed based on the SSR genotyping profiles and the UPGMA clustering. Subsequently, we examined the ploidy levels of these cultivars by combining SSR marker genotyping with flow cytometry measurements. It was found that, in this collection, the shrub cultivars were mainly presented as diploids, while cultivars in tree form mainly existed as polyploids. This study established a reference DNA fingerprinting database for managing the commercial willow cultivars, and the determination of their ploidy levels provided critical information for aiding the polyploid breeding programs in willows.

Purpose To identify macular intraretinal layer changes of patients in remission from Behcet's disease (BD) of short and long duration and evaluate the associations with visual acuity (VA). Methods Thirty-two eyes from 26 BD patients were enrolled, including 16 eyes with a duration less than 3 years (0.5-2.5 years; BD1) and 16 eyes of longer duration (3-12 years; BD2). Their intraretinal layer thicknesses and integrity of ellipsoid zone (EZ) and interdigitation zone (IZ) were evaluated by spectral-domain optical coherence tomography (SD-OCT). Associations between VA and retinal structural changes were analyzed. Results Compared to controls, the inner retina was significantly thicker in BD groups, especially the nerve fiber layer (NFL). The outer retinal layer (ORL) was thicker in BD1 in the central and temporal regions and thinner in BD2 compared to controls in all regions. In BD2, there were more eyes with disruption of the EZ and IZ. Worsening VA was correlated with thickening of the NFL and inner nuclear layer (INL), thinning of the ORL, and greater disruption of the EZ and IZ. Multiple linear regression analysis revealed EZ disruption, nasal ORL, inferior NFL, and temporal and nasal INLs were independent predictors of best-corrected (BCVA). Conclusions Behcet's disease patients in remission had significant changes in the inner and outer retinal structures, associated with worse VA. Thickness and integrity of the intraretinal layers by SD-OCT and segmentation might be useful predictors for the degree of VA damage in BD remission.

To compare the difference in clinical efficacy on bronchial asthma at chronic persistent stage between acupuncture for warming yang and benefiting qi and seretide.One hundred and eighty patients of bronchial asthma at chronic persistent stage were randomized into an acupuncture group and a western medication group, 90 cases in each one. In the acupuncture group, acupuncture for warming yang and benefiting qi was applied at Dazhui (GV 14), Feishu (BL 13), Danzhong (CV 17), Dingchuan (EX-B 1), Jianshi (PC 5), Zhigou (TE 6), Taixi (KI 3) and Zusanli (ST 36), once every two days. In the western medication group, inhalation therapy with seretide was applied, 1 to 2 inhalations each time, twice a day. The treatment for 20 days was as one session in the two groups, at the intervals of 2 days after each session. Four sessions of treatment were required. The immune function indices were observed before and after treatment in the patients of two groups, named immunoglobulin IgG, IgM and IgE; peripheral T lymphocytes (CD3+), helper T lymphocytes (CD4+), inhibitory T lymphocytes (CD8+) and the ratio of CD4+ and CD8+; as well as the pulmonary ventilation function indices, named maximum pulmonary expiratory flow (PEF), forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). The clinical efficacy was compared between the two groups.The total effective rate was 93.3% (84/90) in the acupuncture group, better than 88.9% (80/90) in the western medication group (P0.05). After treatment, the immune function indices and pulmonary ventilation function indices were apparently improved as compared with those before treatment in the two groups (all P0.05). The improvements in the acupuncture group were much more significant (all P0.05).Acupuncture for warming yang and benefiting qi effectively controls the symptoms of bronchial asthma at chronic persistent stage and improves immune and pulmonary functions. The efficacy is better than that of seretide.

By taking advantage of the semantic-syntactic characteristics of Chinese verbs, the current study examined the brain activity of automatic activation of syntactic features at the single word level. Both syntactic (transitivity) and semantic (integrity) features of the verb were manipulated. Event-related potentials were measured while subjects performed lexical decision tasks on visually presented verbs at the single word level. The results showed that there was a significant transitivity effect in both lateral and midline areas for the 150-200ms time window (N200 effect), indicating the retrieval of the syntactic feature. There was also a significant syntactic-semantic interaction at the late stage of verb processing (N400 effect) in the midline central-parietal region, reflecting syntactic influences on semantic processing. These findings suggest that transitivity is an integral part of the mental representation of Chinese verbs and such information can be retrieved at the early stage of single verb processing and can influence subsequent semantic integration. These results also reveal the special features of Chinese language processing.

Background: Immunotherapy with PD-1 inhibitors is associated with increased survival in NSCLC. While PD-L1 expression enriches for clinical benefit, additional predictive biomarkers are critically needed to further define patient subsets associated with specific response/resistance profiles and to develop optimal combination strategies. We hypothesized that integration of pathology features derived from H&E and PD-L1 immunohistochemistry with genetic/genomic data from NSCLC could identify phenotypic/genotypic associations that highlight specific immunosuppressive mechanisms. Towards that end, we present data from an initial pilot analysis. Methods: Twenty-nine NSCLC (23 adenocarcinoma; 6 squamous cell carcinoma) were included. H&E-stained sections were scored for tumor grade (1-3), relative proportion of tumor stroma (stroma score 1-3), percent necrosis and intensity of chronic inflammatory infiltrate (1-3+). PD-L1 immunohistochemistry was performed using the DAKO 28-8 antibody. PD-L1 expression was scored in tumor cells by modified H-score and by the predominant pattern observed - diffuse, heterogeneous, tumor-stroma interface or negative, and in immune cells using a semi-quantitative intensity scale (1-3+). DNA and RNA extracts from FFPE tissue were subjected to whole exome sequencing and RNAseq from which mutation load, oncogene/tumor suppressor genotypes and inflammation signatures were derived. Results: The highest PD-L1 H-scores were associated with diffuse expression patterns and were observed in high grade tumors (Grade 3). Deleterious mutations in TP53, STK11, KEAP1, KRAS, EGFR and MET occurred at expected frequencies. These mutations occurred across multiple PD-L1 expression patterns except for STK11 which was restricted to PD-L1 negative tumors (p=0.077, Fisher exact test). STK11-mutant tumors also displayed a lower PD-L1+ inflammation score (p=0.046, Fisher exact test). Trends toward an increase in mutation load with increasing levels of chronic inflammation on H&E stain as well as with PD-L1+ chronic immune infiltrates were noted. Inflammation signatures derived from RNAseq showed an association between diffuse PD-L1 expression by IHC and the highest levels of inflammation mRNA signatures comprising T-cells (CD8, Tregs), B-cells, macrophages and MDSCs. Conclusions: The potential association between tumor grade, PD-L1 expression, intensity of the immune infiltrate and mutation load raise the possibility that tumor morphology predicts mutation load and associated immune response. The finding that STK11 mutation is restricted to PD-L1 negative tumors suggests an immunosuppressive mechanism is invoked in this setting. This dataset is currently being expanded to establish the significance of these findings. Citation Format: Robin Edwards, Patrik Vitazka, Peter Szabo, Han Chang, John Cogswell, Hao Tang, Kaushal Desai, Darren Locke, Qiuyan Wu, Joseph Szustakowski, Steven Bernstein, Michele Cleary. Cross-platform integrative analysis of NSCLC reveals association between PD-L1 expression patterns and tumor genetic profile [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 593. doi:10.1158/1538-7445.AM2017-593