tbuckley/cabot-search huggingface dataset:
膣粘膜ワクチンアジュバント2重輸送システム(VADDS)としてマイクロニードルアレイを作る様々なタイプの重炭酸アンモニウム塩搭載多機能性リポソームの組合せ
Authors: Wang Ning, Zhen Yuanyuan, Jin Yiguang, Wang Xueting, Li Ning, Jiang Shaohong, Wang Ting
Journal: Journal of Controlled Release (2017)
Effect of Modified Vaccinia Ankara–5T4 and Low-Dose Cyclophosphamide on Antitumor Immunity in Metastatic Colorectal Cancer
Authors: Martin Scurr, Tom Pembroke, Anja Bloom, David Roberts, Amanda Thomson, Kathryn Smart, Hayley Bridgeman, Richard Adams, Alison Brewster, Robert Jones, Sarah Gwynne, Daniel Blount, Richard Harrop, Melissa Wright, Robert Hills, Awen Gallimore, Andrew Godkin
Journal: JAMA Oncology (2017)

The success of immunotherapy with checkpoint inhibitors is not replicated in most cases of colorectal cancer; therefore, different strategies are urgently required. The oncofetal antigen 5T4 is expressed in more than 90% of cases of metastatic colorectal cancer (mCRC). Preliminary data using modified vaccinia Ankara-5T4 (MVA-5T4) in mCRC demonstrated that it safely induced serologic and T-cell responses.
Functional Analysis of SRSF2 Mutations in Myelodysplastic Syndromes and Related Disorders
Authors: Ayana Kon, Masashi Sanada, Kenichi Yoshida, Yasunobu Nagata, Yuichi Shiraishi, Yusuke Sato, Aiko Sato-Otsubo, Ryo Yamamoto, Masao Nagasaki, Yutaka Suzuki, Tomoyuki Yamaguchi, Makoto Otsu, Sumio Sugano, Shigeru Chiba, H. Phillip Koeffler, Lee-Yung Shih, Hiromitsu Nakauchi, Satoru Miyano, Seishi Ogawa
Journal: Blood (2011)
A Radiomics Nomogram for the Preoperative Prediction of Lymph Node Metastasis in Bladder Cancer
Authors: Shaoxu Wu, Junjiong Zheng, Yong Li, Hao Yu, Siya Shi, Weibin Xie, Hao Liu, Yangfan Su, Jian Huang, Tianxin Lin
Journal: Clinical Cancer Research (2017)

Purpose: To develop and validate a radiomics nomogram for the preoperative prediction of lymph node (LN) metastasis in bladder cancer.Experimental Design: A total of 118 eligible bladder cancer patients were divided into a training set (n = 80) and a validation set (n = 38). Radiomics features were extracted from arterial-phase CT images of each patient. A radiomics signature was then constructed with the least absolute shrinkage and selection operator algorithm in the training set. Combined with independent risk factors, a radiomics nomogram was built with a multivariate logistic regression model. Nomogram performance was assessed in the training set and validated in the validation set. Finally, decision curve analysis was performed with the combined training and validation set to estimate the clinical usefulness of the nomogram.Results: The radiomics signature, consisting of nine LN status-related features, achieved favorable prediction efficacy. The radiomics nomogram, which incorporated the radiomics signature and CT-reported LN status, also showed good calibration and discrimination in the training set [AUC, 0.9262; 95% confidence interval (CI), 0.8657-0.9868] and the validation set (AUC, 0.8986; 95% CI, 0.7613-0.9901). The decision curve indicated the clinical usefulness of our nomogram. Encouragingly, the nomogram also showed favorable discriminatory ability in the CT-reported LN-negative (cN0) subgroup (AUC, 0.8810; 95% CI, 0.8021-0.9598).Conclusions: The presented radiomics nomogram, a noninvasive preoperative prediction tool that incorporates the radiomics signature and CT-reported LN status, shows favorable predictive accuracy for LN metastasis in patients with bladder cancer. Multicenter validation is needed to acquire high-level evidence for its clinical application. Clin Cancer Res; 23(22); 6904-11. ©2017 AACR.
ドラッグデリバリーの文脈における位置決め金属‐有機骨格ナノ粒子‐メソポーラスシリカナノ粒子とデンドリマとの比較【Powered by NICT】
Authors: Wuttke Stefan, Lismont Marjorie, Escudero Alberto, Rungtaweevoranit Bunyarat, J Parak Wolfgang
Journal: Biomaterials (2017)
Abstract 18554: Short-term Melatonin Treatment Protects the Hearts of Obese Rats Independent of Changes in Body Weight and Visceral Fat Mass
Authors: Amanda Lochner, Frederic Nduhirabandi
Journal: Circulation (2014)

Melatonin treatment has been shown to prevent the harmful effects of diet-induced obesity and reduce myocardial susceptibility to ischaemia-reperfusion injury (IRI) when administered from the onset of obesity. However, the exact mechanism whereby it exerts its beneficial actions on the heart in obesity and insulin resistance is unknown. In this study we investigated the effects of relatively short-term melatonin treatment on the heart in a rat model of diet-induced obesity. Control (C) and diet-induced obese (D) Wistar rats (fed for 20 weeks (wks)) were divided into 3 groups receiving drinking water with or without melatonin (4mg/kg/day) for the last 6 or 3 wks of experimentation. Isolated hearts were perfused in the working mode, subjected to regional (35min) or global ischaemia (15min) and reperfusion (2h); others were non-perfused (baseline). Myocardial infarct sizes as well as baseline and post-ischaemic activation of PKB/Akt, ERK42/44, GSK-3β and STAT-3 were determined. Blood was collected for study of metabolic parameters. Diet-induced obesity caused significant increases in body weight gain (14.5%), visceral adiposity (70.3%), fasting blood glucose (20%), serum insulin (55.6%) and triglyceride (84.2%) levels with a concomitant increase in post-ischaemic myocardial infarct size (41%) and a reduced cardiac output (12.7%). Melatonin treatment (both 3 and 6 wks) decreased serum insulin levels and the HOMA-index in the D group only (3 wks % reduction: 39%; 47.2%, p&lt;0.05 vs untreated D respectively) with no effect on body weight gain, visceral adiposity, serum triglycerides and glucose levels. It also increased serum adiponectin levels in the D group (113% p&lt;0.05 vs untreated D), reduced myocardial infarct sizes in both groups (3 wks %reduction: C 42.4%; D 61.6%) and activated baseline myocardial STAT-3, PKB/Akt, ERK42/44 and GSK-3β after 10 min reperfusion. Short-term melatonin administration to obese and insulin resistant rats reduced insulin resistance and protected the heart against ex vivo myocardial IRI independently of body weight gain and visceral adiposity. Melatonin-induced cardioprotection was associated with concomitant activation of the RISK and SAFE pathways.
Characterization of the T-cell receptor repertoire and immune microenvironment in patients with locoregionally advanced squamous cell carcinoma of the head and neck.
Authors: Vassiliki Saloura, Aiman Fatima, Makda Zewde, Kazuma Kiyotani, Ryan J. Brisson, Jae Hyun Park, Yuji Ikeda, Theodore Vougiouklakis, Riyue Bao, Tanguy Y. Seiwert, Nicole Cipriani, Mark W. Lingen, Everett E. Vokes, Yusuke Nakamura
Journal: Journal of Clinical Oncology (2017)

3080 Background: Immunotherapy with checkpoint blockade was recently approved for patients with recurrent/metastatic SCCHN, however it has not been investigated in the curative-intent setting yet. In this study, we investigated the T-cell receptor repertoire and the immune microenvironment in tumor tissues of SCCHN patients with locoregionally advanced disease. Methods: T-cell receptor sequencing and polymerase chain reaction for immune-related genes of tumor tissues from 44 patients with locoregionally advanced SCCHN prior to treatment with definitive chemoradiotherapy were conducted. T-cell receptor clonality and the mRNA expression levels of immune-related genes were correlated with various clinicopathological parameters. Results: In patients with locoregionally advanced SCCHN, tumor infiltrating T-cells clonally expand and GRZB mRNA levels were associated significantly with longer progression-free survival (PFS) (p = 0.003) independent of HPV status, tumor and nodal stage. The TCR-β DI was significantly lower in HPV-negative compared to HPV-positive tumors (p = 0.002), signifying more clonal T-cell expansion in HPV-negative tumors. A higher percentage of HPV-negative tumors expressed HLA-A protein compared to HPV-positive tumors (p = 0.049), suggesting that the greater T-cell clonal expansion might be due to more robust antigen presentation by HPV-negative tumors. Conclusions: This study suggests the pre-existence of clonally expanded T-cells in patients with locoregionally advanced SCCHN prior to treatment, and provides rationale to introduce immunotherapy in the curative-intent setting. The association of high GRZB mRNA levels with favorable PFS independent of HPV-status, tumor and nodal stage supports that the pre-existence of an intrinsically inflamed microenvironment enhances chemoradiotherapy effects. Finally, in HPV-positive tumors, the T-cell infiltrate seemed to be more diverse which could be secondary to virally-induced defective expression of HLA class I molecules.
CD155T/TIGIT Signaling Regulates CD8+ T-cell Metabolism and Promotes Tumor Progression in Human Gastric Cancer
Authors: Weiling He, Hui Zhang, Fei Han, Xinlin Chen, Run Lin, Wei Wang, Haibo Qiu, Zhenhong Zhuang, Qi Liao, Weijing Zhang, Qinbo Cai, Yongmei Cui, Wenting Jiang, Han Wang, Zunfu Ke
Journal: Cancer Research (2017)

The T-cell surface molecule TIGIT is an immune checkpoint molecule that inhibits T-cell responses, but its roles in cancer are little understood. In this study, we evaluated the role TIGIT checkpoint plays in the development and progression of gastric cancer. We show that the percentage of CD8 T cells that are TIGIT+ was increased in gastric cancer patients compared with healthy individuals. These cells showed functional exhaustion with impaired activation, proliferation, cytokine production, and metabolism, all of which were rescued by glucose. In addition, gastric cancer tissue and cell lines expressed CD155, which bound TIGIT receptors and inactivated CD8 T cells. In a T cell-gastric cancer cell coculture system, gastric cancer cells deprived CD8 T cells of glucose and impaired CD8 T-cell effector functions; these effects were neutralized by the additional glucose or by TIGIT blockade. In gastric cancer tumor cells, CD155 silencing increased T-cell metabolism and IFNγ production, whereas CD155 overexpression inhibited T-cell metabolism and IFNγ production; this inhibition was neutralized by TIGIT blockade. Targeting CD155/TIGIT enhanced CD8 T-cell reaction and improved survival in tumor-bearing mice. Combined targeting of TIGIT and PD-1 further enhanced CD8 T-cell activation and improved survival in tumor-bearing mice. Our results suggest that gastric cancer cells inhibit CD8 T-cell metabolism through CD155/TIGIT signaling, which inhibits CD8 T-cell effector functions, resulting in hyporesponsive antitumor immunity. These findings support the candidacy of CD155/TIGIT as a potential therapeutic target in gastric cancer. Cancer Res; 77(22); 6375-88. ©2017 AACR.
Editorial: Anti–Citrullinated Protein Antibody, Anti–Carbamylated Protein Antibody, and Rheumatoid Arthritis: Azurophilic Granules Sing the Blues
Authors: William F. C. Rigby, Sladjana Skopelja‐Gardner, Jonathan D. Jones
Journal: Arthritis & Rheumatology (2017)

Arginine and lysine are distinguished by their identity as the most cationic (basic) amino acids. They are also the target of many post-translational modifications, e.g. acetylation, citrullination, hydroxylation, methylation, ubiquitination. These modifications are catalyzed by a series of enzymes, presumably to enable a tapestry of functionality by a single protein, including regulation of DNA transcription, repair and replication. Besides their functional roles in normal physiological conditions, some of these protein modifications have been recognized as inflammatory triggers and targets of autoimmune reactions.

This article is protected by copyright. All rights reserved.
Graphene quantum dots suppress proinflammatory T cell responses via autophagy-dependent induction of tolerogenic dendritic cells
Authors: Sergej Tomić, Kristina Janjetović, Dušan Mihajlović, Marina Milenković, Tamara Kravić-Stevović, Zoran Marković, Biljana Todorović-Marković, Zdenko Spitalsky, Matej Micusik, Dragana Vučević, Miodrag Čolić, Vladimir Trajković
Journal: Biomaterials (2017)
A multi-center prospective cohort study of patient transfers from the intensive care unit to the hospital ward
Authors: Henry T. Stelfox, Jeanna Parsons Leigh, Peter M. Dodek, Alexis F. Turgeon, Alan J. Forster, Francois Lamontagne, Rob A. Fowler, Andrea Soo, Sean M. Bagshaw
Journal: Intensive Care Medicine (2017)
Identification of high-confidence RNA regulatory elements by combinatorial classification of RNA–protein binding sites
Authors: Yang Eric Li, Mu Xiao, Binbin Shi, Yu-Cheng T. Yang, Dong Wang, Fei Wang, Marco Marcia, Zhi John Lu
Journal: Genome biology (2017)

Crosslinking immunoprecipitation sequencing (CLIP-seq) technologies have enabled researchers to characterize transcriptome-wide binding sites of RNA-binding protein (RBP) with high resolution. We apply a soft-clustering method, RBPgroup, to various CLIP-seq datasets to group together RBPs that specifically bind the same RNA sites. Such combinatorial clustering of RBPs helps interpret CLIP-seq data and suggests functional RNA regulatory elements. Furthermore, we validate two RBP–RBP interactions in cell lines. Our approach links proteins and RNA motifs known to possess similar biochemical and cellular properties and can, when used in conjunction with additional experimental data, identify high-confidence RBP groups and their associated RNA regulatory elements.
Rare autosomal trisomies, revealed by maternal plasma DNA sequencing, suggest increased risk of feto-placental disease
Authors: Mark D. Pertile, Meredith Halks-Miller, Nicola Flowers, Catalin Barbacioru, Sarah L. Kinnings, Darcy Vavrek, William K. Seltzer, Diana W. Bianchi
Journal: Science Translational Medicine (2017)

Whole-genome sequencing (WGS) of maternal plasma cell-free DNA (cfDNA) can potentially evaluate all 24 chromosomes to identify abnormalities of the placenta, fetus, or pregnant woman. Current bioinformatics algorithms typically only report on chromosomes 21, 18, 13, X, and Y; sequencing results from other chromosomes may be masked. We hypothesized that by systematically analyzing WGS data from all chromosomes, we could identify rare autosomal trisomies (RATs) to improve understanding of feto-placental biology. We analyzed two independent cohorts from clinical laboratories, both of which used a similar quality control parameter, normalized chromosome denominator quality. The entire data set included 89,817 samples. Samples flagged for analysis and classified as abnormal were 328 of 72,932 (0.45%) and 71 of 16,885 (0.42%) in cohorts 1 and 2, respectively. Clinical outcome data were available for 57 of 71 (80%) of abnormal cases in cohort 2. Visual analysis of WGS data demonstrated RATs, copy number variants, and extensive genome-wide imbalances. Trisomies 7, 15, 16, and 22 were the most frequently observed RATs in both cohorts. Cytogenetic or pregnancy outcome data were available in 52 of 60 (87%) of cases with RATs in cohort 2. Cases with RATs detected were associated with miscarriage, true fetal mosaicism, and confirmed or suspected uniparental disomy. Comparing the trisomic fraction with the fetal fraction allowed estimation of possible mosaicism. Analysis and reporting of aneuploidies in all chromosomes can clarify cases in which cfDNA findings on selected "target" chromosomes (21, 18, and 13) are discordant with the fetal karyotype and may identify pregnancies at risk of miscarriage and other complications.
Differential eNOS-signalling by platelet subpopulations regulates adhesion and aggregation
Authors: Aneta Radziwon-Balicka, Gabriela Lesyk, Valentina Back, Teresa Fong, Erica L Loredo-Calderon, Bin Dong, Haitham El-Sikhry, Ahmed A El-Sherbeni, Ayman El-Kadi, Stephen Ogg, Arno Siraki, John M Seubert, Maria Jose Santos-Martinez, Marek W Radomski, Carlos A Velazquez-Martinez, Ian R Winship, Paul Jurasz
Journal: Cardiovascular Research (2017)

In addition to maintaining haemostasis, circulating blood platelets are the cellular culprits that form occlusive thrombi in arteries and veins. Compared to blood leucocytes, which exist as functionally distinct subtypes, platelets are considered to be relatively simple cell fragments that form vascular system plugs without a differentially regulated cellular response. Hence, investigation into platelet subpopulations with distinct functional roles in haemostasis/thrombosis has been limited. In our present study, we investigated whether functionally distinct platelet subpopulations exist based on their ability to generate and respond to nitric oxide (NO), an endogenous platelet inhibitor.Utilizing highly sensitive and selective flow cytometry protocols, we demonstrate that human platelet subpopulations exist based on the presence and absence of endothelial nitric oxide synthase (eNOS). Platelets lacking eNOS (approximately 20% of total platelets) fail to produce NO and have a down-regulated soluble guanylate cyclase-protein kinase G (sGC-PKG)-signalling pathway. In flow chamber and aggregation experiments eNOS-negative platelets primarily initiate adhesion to collagen, more readily activate integrin αIIbβ3 and secrete matrix metalloproteinase-2, and form larger aggregates than their eNOS-positive counterparts. Conversely, platelets having an intact eNOS-sGC-PKG-signalling pathway (approximately 80% of total platelets) form the bulk of an aggregate via increased thromboxane synthesis and ultimately limit its size via NO generation.These findings reveal previously unrecognized characteristics and complexity of platelets and their regulation of adhesion/aggregation. The identification of platelet subpopulations also has potentially important consequences to human health and disease as impaired platelet NO-signalling has been identified in patients with coronary artery disease.
Scissor-type needle-knife for colorectal endoscopic submucosal dissection
Authors: Saowanee Ngamruengphong, Anthony Kalloo
Journal: Endoscopy (2017)

See also: Endoscopic submucosal dissection of early colorectal neoplasms with a monopolar scissor-type knife: short- to long-term outcomes Endoscopy 2017; 49(09): 913-918DOI: 10.1055/s-0043-113631
An Essential Role of Maspin in Embryogenesis and Tumor Suppression—Letter
Authors: James C. Whisstock, Phillip I. Bird
Journal: Cancer Research (2017)

The title of a new article on maspin by Dzinic and colleagues ([1][1]) is inconsistent with the data contained within it. Maspin (SERPINB5) was first identified in screens for potential tumor suppressors absent in human breast cancer cells ([2][2]). Reexpression of maspin in cloned breast tumor cell
Prevalence and determinants of seborrhoeic dermatitis in a middle‐aged and elderly population: the Rotterdam Study
Authors: M.G.H. Sanders, L.M. Pardo, O.H. Franco, R.S. Ginger, T. Nijsten
Journal: British Journal of Dermatology (2017)

Seborrhoeic dermatitis is a chronic relapsing inflammatory skin disease with unclear pathophysiological mechanisms.To establish which lifestyle and physiological determinants are associated with seborrhoeic dermatitis.Seborrhoeic dermatitis was diagnosed by a trained physician during a full-body skin examination within the Rotterdam Study, a prospective population-based cohort study in middle-aged and elderly people. The current design is a comparative cross-sectional study embedded in the Rotterdam Study. Potential factors were identified from the literature and analysed in a multivariable logistic regression, including: age, sex, obesity, skin colour, stress, depression, education level, hypertension, climate, xerosis cutis, alcohol and tobacco use.Of the 5498 participants, 788 participants were diagnosed with seborrhoeic dermatitis (14·3%). We found associations between seborrhoeic dermatitis and male sex [adjusted odds ratio (OR) 2·09, 95% confidence interval (CI) 1·77-2·47], darker skin (adjusted OR 0·39, 95% CI 0·22-0·69), season (summer vs. winter: adjusted OR 0·63, 95% CI 0·48-0·82) and generalized xerosis cutis (adjusted OR 1·41, 95% CI 1·11-1·80).Seborrhoeic dermatitis is one of the most common inflammatory dermatoses in middle-aged and elderly individuals, especially during winter. Men, and people with a light and dry skin were most likely to have seborrhoeic dermatitis.
in vivoイメージングと治療のためのランタニド(Gd~3+及びYb~3+)官能化金ナノ粒子【Powered by NICT】
Authors: Ge Xiaoqian, Song Zheng-Mei, Sun Lining, Yang Yi-Fan, Shi Liyi, Si Rui, Ren Wei, Qiu Xueer, Wang Haifang
Journal: Biomaterials (2016)
Stable Positioning of Unc13 Restricts Synaptic Vesicle Fusion to Defined Release Sites to Promote Synchronous Neurotransmission
Authors: Suneel Reddy-Alla, Mathias A. Böhme, Eric Reynolds, Christina Beis, Andreas T. Grasskamp, Malou M. Mampell, Marta Maglione, Meida Jusyte, Ulises Rey, Husam Babikir, Anthony W. McCarthy, Christine Quentin, Tanja Matkovic, Dominique Dufour Bergeron, Zeeshan Mushtaq, Fabian Göttfert, David Owald, Thorsten Mielke, Stefan W. Hell, Stephan J. Sigrist, Alexander M. Walter
Journal: Neuron (2017)
Association Between Low Barometric Pressure and Completed Suicides
Authors: Rif S. El-Mallakh, Kanwar Brar, Claire Watkins, Sharon Nuss, Stephen S. O’Connor, Yonglin Gao, Jesse H. Wright
Journal: American Journal of Psychiatry (2017)

might trigger the understanding of facial expressions and increase facial expressivity in individuals with ASD.An important future study would be one with a single-case experimental design with regular information gathered regarding the key outcome variables and other relevant variables.
高分子,リポソームおよびマイクロバブルを用いたin vivoでの異なる骨髄細胞集団を標的とする【Powered by NICT】
Authors: Ergen Can, Heymann Felix, Al Rawashdeh Wa’el, Gremse Felix, Bartneck Matthias, Panzer Ulf, Pola Robert, Pechar Michal, Storm Gert, Mohr Nicole, Barz Matthias, Zentel Rudolf, Kiessling Fabian, Trautwein Christian, Lammers Twan, Tacke Frank
Journal: Biomaterials (2017)