bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of artificial turf and concussion in competitive contact sports: a systematic review and meta-analysis
Authors: O' Leary Frank , Acampora Nic , Hand Fiona , O' Donovan James 
Published: May 2020

ObjectiveTo determine the incidence of head injuries and concussion in contact sports, comparing natural grass with artificial turf surfaces.DesignSystematic review and meta-analysis via the RevMan V.5.3 software.Eligibility criteria for selecting studiesAll studies describing competitive contact sports played on both natural grass and artificial turf. The primary outcome measured was occurrence of head injury and concussion.Data sourcesThe databases include PubMed, Embase, Cochrane, Medline and Sport Discus. The last search took place on 23 May 2019. The Newcastle-Ottawa Quality Assessment Scale evaluated the methodological quality of the selected studies with a funnel plot designed to determine publication bias. Study screening and data extraction were performed by two independent reviewers.ResultsInitial screening generated 42 publications, with 12 meeting criteria for inclusion. Eight studies described concussion only. The rate ratio (RR) of head injury and concussion was less on artificial turf compared with natural grass (RR=0.89, 95% CI 0.77 to 1.04) as was the rate ratio of concussion only (RR=0.72, 95% CI 0.58 to 0.89).ConclusionAnalysis of published data demonstrates a decreased incidence of head injury and concussion when contact sports are played on artificial turf. This difference was most marked for sports such as rugby and American football. However, artificial turf has no association with the incidence of head injury or concussion while playing soccer.
Granzyme B PET imaging of immune-mediated tumor killing as a tool for understanding immunotherapy response
Authors: LaSalle Thomas , Austin Emily E , Rigney Grant , Wehrenberg-Klee Eric , Nesti Sarah , Larimer Benjamin , Mahmood Umar 
Published: May 2020

BackgroundCancer immunotherapy research is expanding to include a more robust understanding of the mechanisms of treatment response and resistance. Identification of drivers of pro-tumor and anti-tumor immunity during treatment offers new strategies for effective alternative or combination immunotherapies. Currently, tissue or blood samples are collected and analyzed, then dichotomized based on clinical end points that may occur months or years after tissue is collected. While overall survival is ultimately the desired clinical outcome, this dichotomization fails to incorporate the nuances that may occur during an anti-tumor response. By failing to directly measure immune activation at the time of sampling, tumors may be misclassified and potentially obscure important biological information. Non-invasive techniques, such as positron emission tomography (PET), allow for global and quantitative measurements of cancer specific processes and are widely used clinically to help manage disease.MethodsWe have previously developed a novel PET agent that can non-invasively quantify granzyme B release in tumors and have demonstrated its ability to predict response to checkpoint inhibitor therapy in multiple murine models of cancer. Here, we used the quantitative measurement of granzyme B release as a direct and time-matched marker of immune cell activation in order to determine immune cell types and cytokines that correlate with effective checkpoint inhibitor therapy in both tumors and tumor-draining lymph nodes.ResultsThrough PET imaging, we were able to successfully distinguish distinct microenvironments, based on tumor type, which influenced immune cell subpopulations and cytokine release. Although each tumor was marked by functionally distinct pathways of immune cell activation and inflammation, they also shared commonalities that ultimately resulted in granzyme B release and tumor killing.ConclusionsThese results suggest that discrete tumor immune microenvironments can be identified in both responsive and non-responsive tumors and offers strategic targets for intervention to overcome checkpoint inhibitor resistance.
ATR inhibitor AZD6738 enhances the antitumor activity of radiotherapy and immune checkpoint inhibitors by potentiating the tumor immune microenvironment in hepatocellular carcinoma
Authors: Sheng Hailong , Huang Yan , Xiao Yazhi , Zhu Zhenru , Shen Mengying , Zhou Peitao , Guo Zeqin , Wang Jian , Wang Hui , Dai Wencong , Zhang Wanjun , Sun Jingyuan , Cao Chuanhui 
Published: May 2020

BackgroundRadioimmunotherapy has a promising antitumor effect in hepatocellular carcinoma (HCC), depending on the regulatory effect of radiotherapy on tumor immune microenvironment. Ionizing radiation (IR)-induced DNA damage repair (DDR) pathway activation leads to the inhibition of immune microenvironment, thus impairing the antitumor effect of radioimmunotherapy. However, it is unclear whether inhibition of the DDR pathway can enhance the effect of radioimmunotherapy. In this study, we aim to explore the role of DDR inhibitor AZD6738 on the combination of radiotherapy and immune checkpoint inhibitors (ICIs) in HCC.MethodsC57BL/6 mouse subcutaneous tumor model was used to evaluate the ability of different treatment regimens in tumor growth control and tumor recurrence inhibition. Effects of each treatment regimen on the alterations of immunophenotypes including the quantification, activation, proliferating ability, exhaustion marker expression, and memory status were assessed by flow cytometry.ResultsAZD6738 further increased radiotherapy-stimulated CD8+T cell infiltration and activation and reverted the immunosuppressive effect of radiation on the number of Tregs in mice xenografts. Moreover, compared with radioimmunotherapy (radiotherapy plus anti-PD-L1 (Programmed death ligand 1)), the addition of AZD6738 boosted the infiltration, increased cell proliferation, enhanced interferon (IFN)-γ production ability of TIL (tumor-infiltrating lymphocyte) CD8+T cells, and caused a decreasing trend in the number of TIL Tregs and exhausted T cells in mice xenografts. Thus, the tumor immune microenvironment was significantly improved. Meanwhile, triple therapy (AZD6738 plus radiotherapy plus anti-PD-L1) also induced a better immunophenotype than radioimmunotherapy in mice spleens. As a consequence, triple therapy displayed greater benefit in antitumor efficacy and mice survival than radioimmunotherapy. Mechanism study revealed that the synergistic antitumor effect of AZD6738 with radioimmunotherapy relied on the activation of cyclic GMP–AMP synthase /stimulator of interferon genes (cGAS/STING) signaling pathway. Furthermore, triple therapy led to stronger immunologic memory and lasting antitumor immunity than radioimmunotherapy, thus preventing tumor recurrence in mouse models.ConclusionsOur findings indicate that AZD6738 might be a potential synergistic treatment for radioimmunotherapy to control the proliferation of HCC cells, prolong survival, and prevent tumor recurrence in patients with HCC by improving the immune microenvironment.
Neoantigen load and HLA-class I expression identify a subgroup of tumors with a T-cell-inflamed phenotype and favorable prognosis in homologous recombination-proficient high-grade serous ovarian carcinoma
Authors: Matsushita Hirokazu , Hasegawa Kosei , Oda Katsutoshi , Yamamoto Shogo , Asada Kayo , Karasaki Takahiro , Yabuno Akira , Nishijima Akira , Nejo Takahide , Kobayashi Yukari , Sato Sho , Ikeda Yuji , Miyai Manami , Takahashi Yusuke , Yamaguchi Rui , Fujiwara Keiichi , Aburatani Hiroyuki , Kakimi Kazuhiro 
Published: May 2020

BackgroundThere is increasing evidence for the benefit of poly ADP ribose polymerase (PARP) inhibitors in a subset of high-grade serous ovarian carcinoma (HGSC) patients, especially those with homologous recombination (HR)-deficient tumors. However, new treatment strategies, such as immune checkpoint inhibition, are required for patients with HR-proficient tumors.MethodsA total of 80 cases of HGSC were analyzed in this study. Whole exome and RNA sequencing was performed for these tumors. Methylation arrays were also carried out to examineBRCA1andRAD51Cpromoter methylation status. Mutations, neoantigen load, antigen presentation machinery, and local immune profile were investigated, and the relationships of these factors with clinical outcome were also analyzed.ResultsAs expected, the numbers of predicted neoAgs were lower in HR-proficient (n=46) than HR-deficient tumors (n=34). However, 40% of the patients with HR-proficient tumors still had higher than median numbers of neoAgs and better survival than patients with lower numbers of neoAgs. Incorporation of human leukocyte antigen (HLA)-class I expression status into the survival analysis revealed that patients with both high neoAg numbers and high HLA-class I expression (neoAghiHLAhi) had the best progression-free survival (PFS) in HR-proficient HGSC (p=0.0087). Gene set enrichment analysis demonstrated that the genes for effector memory CD8 T cells, TH1 T cells, the interferon-γ response, and other immune-related genes, were enriched in these patients. Interestingly, this subset of patients also had better PFS (p=0.0015) and a more T-cell-inflamed tumor phenotype than patients with the same phenotype (neoAghiHLAhi) in HR-deficient HGSC.ConclusionsOur results suggest that immune checkpoint inhibitors might be an alternative to explore in HR-proficient cases which currently do not benefit from PARP inhibition.
Granzyme B is correlated with clinical outcome after PD-1 blockade in patients with stage IV non-small-cell lung cancer
Authors: Hurkmans Daan P. , Basak Edwin A. , Schepers Nina , Oomen-De Hoop Esther , Van der Leest Cor H. , El Bouazzaoui Samira , Bins Sander , Koolen Stijn L. W. , Sleijfer Stefan , Van der Veldt Astrid A. M. , Debets Reno , Van Schaik Ron H. N. , Aerts Joachim G. J. V. , Mathijssen Ron H. J. 
Published: May 2020

BackgroundA minority of patients with advanced non-small-cell lung cancer (NSCLC) benefit from treatment with immune checkpoint inhibitors (ICIs). Ineffective effector function of activated T and NK cells may lead to reduced tumor cell death, even when these activated effector cells are released from their immune checkpoint brake. Hence, in this study we aimed to assess the association of baseline serum granzyme B, as well as germline variation of theGZMBgene, with clinical outcome to programmed cell death protein 1 (PD-1) blockade.MethodsA total of 347 patients with stage IV NSCLC who started nivolumab treatment between June 2013 and June 2017 were prospectively included. Baseline serum and whole blood was available, allowing for protein quantification and targeted DNA sequencing. Clinical outcome was based on best overall response (BOR) according to Response Evaluation Criteria in Solid Tumors, V.1.1, progression-free survival (PFS), and overall survival (OS).ResultsPatients with low serum levels of granzyme B had worse PFS (HR: 1.96; 95% CI: 1.12 to 3.43; p=0.018) and worse OS (HR: 2.08; 95% CI: 1.12 to 3.87; p=0.021) than patients with high baseline serum levels. To validate the findings, germline variation ofGZMBrs8192917 was assessed. Patients with homozygous and heterozygous variants ofGZMBrs8192917 had worse BOR (OR: 1.60; 95% CI: 1.01 to 2.52; p=0.044) and worse PFS (HR: 1.38; 95% CI:1.02 to 1.87; p=0.036) than wild types.ConclusionsA low baseline serum level of granzyme B and germline variation ofGZMBwas associated with worse clinical outcome in NSCLC, emphasizing the relevance and additional value of monitoring germline genetic variations which mirror cytotoxic functions of T cells in ICI therapy.Trail registration numberDutch Trial Registry (NL6828).
Heterodimeric IL-15 delays tumor growth and promotes intratumoral CTL and dendritic cell accumulation by a cytokine network involving XCL1, IFN-γ, CXCL9 and CXCL10
Authors: Bergamaschi Cristina , Pandit Hrishikesh , Nagy Bethany A , Stellas Dimitris , Jensen Shawn M , Bear Jenifer , Cam Maggie , Valentin Antonio , Fox Bernard A , Felber Barbara K , Pavlakis George N 
Published: May 2020

BackgroundInterleukin-15 (IL-15) promotes growth and activation of cytotoxic CD8+T and natural killer (NK) cells. Bioactive IL-15 is produced in the body as a heterodimeric cytokine, comprising the IL-15 and IL-15 receptor alpha chains (hetIL-15). Several preclinical models support the antitumor activity of hetIL-15 promoting its application in clinical trials.MethodsThe antitumor activity of hetIL-15 produced from mammalian cells was tested in mouse tumor models (MC38 colon carcinoma and TC-1 epithelial carcinoma). The functional diversity of the immune infiltrate and the cytokine/chemokine network within the tumor was evaluated by flow cytometry, multicolor immunohistochemistry (IHC), gene expression profiling by Nanostring Technologies, and protein analysis by electrochemiluminescence and ELISA assays.ResultshetIL-15 treatment resulted in delayed primary tumor growth. Increased NK and CD8+T cell tumoral infiltration with an increased CD8+/Treg ratio were found by flow cytometry and IHC in hetIL-15 treated animals. Intratumoral NK and CD8+T cells showed activation features with enhanced interferon-γ (IFN-γ) production, proliferation (Ki67+), cytotoxic potential (Granzyme B+) and expression of the survival factor Bcl-2. Transcriptomics and proteomics analyses revealed complex effects on the tumor microenvironment triggered by hetIL-15 therapy, including increased levels of IFN-γ and XCL1 with intratumoral accumulation of XCR1+IRF8+CD103+conventional type 1 dendritic cells (cDC1). Concomitantly, the production of the chemokines CXCL9 and CXCL10 by tumor-localized myeloid cells, including cDC1, was boosted by hetIL-15 in an IFN-γ-dependent manner. An increased frequency of circulating CXCR3+NK and CD8+T cells was found, suggesting their ability to migrate toward the tumors following the CXCL9 and CXCL10 chemokine gradient.ConclusionsOur results show that hetIL-15 administration enhances T cell entry into tumors, increasing the success rate of immunotherapy interventions. Our study further supports the incorporation of hetIL-15 in tumor immunotherapy approaches to promote the development of antitumor responses by favoring effector over regulatory cells and by promoting lymphocyte and DC localization into tumors through the modification of the tumor chemokine and cytokine milieu.
Tumor ablation plus co-administration of CpG and saponin adjuvants affects IL-1 production and multifunctional T cell numbers in tumor draining lymph nodes
Authors: Raaijmakers Tonke K , van den Bijgaart Renske J E , den Brok Martijn H , Wassink Melissa , de Graaf Annemarie , Wagenaars Jori A , Nierkens Stefan , Ansems Marleen , Scheffer Gert Jan , Adema Gosse J 
Published: May 2020

BackgroundTumor ablation techniques, like cryoablation, are successfully used in the clinic to treat tumors. The tumor debris remaining in situ after ablation is a major antigen depot, including neoantigens, which are presented by dendritic cells (DCs) in the draining lymph nodes to induce tumor-specific CD8+T cells. We have previously shown that co-administration of adjuvants is essential to evoke strong in vivo antitumor immunity and the induction of long-term memory. However, which adjuvants most effectively combine with in situ tumor ablation remains unclear.Methods and resultsHere, we show that simultaneous administration of cytidyl guanosyl (CpG) with saponin-based adjuvants following cryoablation affects multifunctional T-cell numbers and interleukin (IL)-1 induced polymorphonuclear neutrophil recruitment in the tumor draining lymph nodes, relative to either adjuvant alone. The combination of CpG and saponin-based adjuvants induces potent DC maturation (mainly CpG-mediated), antigen cross-presentation (mainly saponin-based adjuvant mediated), while excretion of IL-1β by DCs in vitro depends on the presence of both adjuvants. Most strikingly, CpG/saponin-based adjuvant exposed DCs potentiate antigen-specific T-cell proliferation resulting in multipotent T cells with increased capacity to produce interferon (IFN)γ, IL-2 and tumor necrosis factor-α in vitro. Also in vivo the CpG/saponin-based adjuvant combination plus cryoablation increased the numbers of tumor-specific CD8+T cells showing enhanced IFNγ production as compared with single adjuvant treatments.ConclusionsCollectively, these data indicate that co-injection of CpG with saponin-based adjuvants after cryoablation induces an increased amount of tumor-specific multifunctional T cells. The combination of saponin-based adjuvants with toll-like receptor 9 adjuvant CpG in a cryoablative setting therefore represents a promising in situ vaccination strategy.
A broadband metamaterial absorber based on multilayer-stacked structure
Authors: Lu Xiaojie , Xiao Zhongyin , Chen Mingming 
Published: May 2020

In this paper, a broadband metamaterial absorber (MA) based on multilayer structure is proposed in the terahertz region. Different from the general multilayer structure, the structure we designed superimposes with different resonators in the “horizontal direction” of the bottom metal plate. The unit of the absorber is composed of several different size metal and dielectric layers which are placed vertically on a metal plate. The numerical results show that the MA has a broadband absorption from 5 THz to 7.75 THz, with the absorption rate larger than 80%. A calculation formula is first given to calculate the absorption frequency, and we compare the simulation results with the calculation results to verify the accuracy of the formula. What is more, the physical mechanism of the perfect absorption can be studied based on the distribution of E-field in the absorber, the standing wave theory, the distribution of energy density and the equivalent impedance theory.
From the Ptolemies to the Romans: Empire in Jewish Literature from Egypt
Authors: Glass R. Gillian , Keddie G. Anthony 
Published: May 2020

Abstract
This article studies the use of τὰ πράγματα in Jewish literature written in Ptolemaic and early Imperial Egypt. While there was no Greek term for “empire” that aligns with the modern sense of an empire as a territorial polity, τὰ πράγματα most closely resembles our modern notion of empire. First, we analyze the range of meanings of πράγματα in Ptolemaic documents and literature. Next, we examine the uses of this concept in Jewish sources from Ptolemaic Egypt. Then, we investigate the shifting understandings of πράγματα in the Jewish sources from Roman Egypt. We conclude that Jewish texts have much more complex views of empire than the descriptors pro- or anti-empire allow. This approach redirects our attention from empire as a static and tangible entity to a dynamic suite of practices through which power is exercised and derived.
The Welfare Church in Nigerian Prisons
Authors: Njeukam Lionel 
Published: May 2020

Abstract
In Nigeria, religious groups have played an important role to help prisoners. Although it is not unusual for religious organizations to operate within penitentiaries, this article gives attention to the scope and importance of the involvement of such organizations in the lives of inmates in Nigeria. In fact, faith-based organizations have been providing so much assistance in the form of clothing, food, medicine, and counselling that they have become an unofficial “welfare church” within the state. Indeed, churches have also considerably assisted in the rehabilitation of prisoners. In effect, religious organizations can be seen as a substitute to the quasi-absent welfare state in Nigeria.
Policy Integration for Sustainable Development through Multilateral Environmental Agreements
Authors: Azizi Dona , Biermann Frank , Kim Rakhyun E. 
Published: May 2020

Abstract
Over the past three decades, policy integration has become a key objective for guiding and harmonizing policies for sustainable development. Most recently, the 2015 Sustainable Development Goals have added new impetus to efforts of integrating competing objectives of environmental sustainability, social development, and economic growth, as well as of integrating issue-specific environmental policies on climate change and terrestrial and marine biodiversity. While multilateral environmental agreements are important international instruments for achieving sustainable development, there has been little focus so far on their contribution to policy integration. Covering the years from 2007 to 2016, this article presents an empirical analysis of sustainability policy integration (i.e., how multilateral environmental agreements integrate environmental, social, and economic issues in their decisions) and environmental policy integration (i.e., the outreach of multilateral environmental agreements to different environmental issue areas beyond their mandate). The analysis finds that multilateral environmental agreements have not moved toward further policy integration over the studied period. If policy and institutional coherence is a key global governance target in the post-2015 era, a concerted effort will be required to improve the extent of policy integration by multilateral environmental agreements.
The Hashtag Game: Disrupting Dissent during the Bersih 4 Protest
Authors: Azlan Nurul Azreen 
Published: May 2020

Abstract
This paper demonstrates how protest tactics, such as the use of hashtags, can be co-opted by counter-protesters, as evidenced by how the cybertroopers operated against the Bersih 4 protest in 2015. This is achieved via focusing the analysis on how geographic places were communicated on Twitter around the time of the protest. The Bersih movement in Malaysia is an example of how a digital-savvy social movement organisation (SMO) operates in a hybrid regime. In this paper, I explore a form of reaction that, on the surface, appeared to be a bottom-up initiative against the Bersih movement. Based on the fieldwork conducted around the Bersih 4 protest in 2015, I focus on place mentions on Twitter to detect the cybertroopers who attempted to disrupt the discussion and narrative through the use of hashtags.
<p><strong>A new combination and an updated identification key for <em>Rhabdocaulon</em> and the differences from <em>Hoehnea </em>(Lamiaceae, Nepetoideae, Mentheae, Menthinae)</strong></p>
Authors: BRÄUCHLER CHRISTIAN 
Published: May 2020

A new combination for the recently described Hoehnea grandiflora Funez & Hassemer (2018: 160) is porposed in Rhabdocaulon (Bentham, 1834: 411) Epling (1936: 134). Characters distinguishing Rhabdocaulon and Hoehnea Epling in Epling & Stewart (1939: 8) are outlined and an updated identification key is provided for Rhabdocaulon.