bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B096: Oncolytic vaccination for HPV induced cancer
Authors: Atherton Matthew J. , Stephenson Kyle B. , Wan Yonghong , Stojdl David F. , Lichty Brian D. 
Published: May 2016

Abstract
Oncogenic human papilloma virus (HPV) is directly responsible for 5% of the world's cancer burden. HPV has been etiologically implicated in virtually all cases of cervical carcinoma and is increasingly responsible for head and neck cancers in the developed world with strains 16 and 18 considered high risk. Recently it was estimated that there were over half a million new cases of cervical cancer worldwide and in the same year this disease was projected to claim over 250,00 lives, making it the third most prevalent and fourth most lethal non- skin tumor in women. Current standard of care for advanced cervical carcinoma and head and neck cancers involve chemo-radiation with or without prior surgical resection resulting in significant morbidity without guaranteed cure. Screening programs and prophylactic vaccination are reducing the incidence of some HPV induced tumors, however lack of compliance and unvaccinated populations mean that significant illness and mortality still exists. We therefore sought to develop a novel pre-clinical immunotherapeutic for HPV induced cancers. An oncolytic vaccination strategy utilizing an attenuated Maraba MG1 rhabdovirus expressing inactive HPV antigens based on the E6 and E7 transforming proteins of strains 16 and 18 has been designed (MG1 E6E7). The TC1 cell line, which is a C57BL/6 syngeneic murine HPV cancer model, was acquired. Specific anti-E7 CD8+ T cell responses have been induced after oncolytic vaccination of mice generating sterilizing immunity against future engraftment with TC1 cells. Oncolytic vaccination of tumor free mice has generated between 24 and 50 million, combined blood and splenic CD8+ T cells per mouse, determined by interferon gamma production in response to a single E7 peptide quantified using intracellular staining and flow cytometry. Primed mice, boosted with MG1 E6E7 develop long lasting, marked and specific immunity against E7 and to a lesser extent E6. The prime: boost regimen has therapeutic efficacy against established subcutaneous TC1 tumors (mean volumes of 250 mm3) resulting in durable cures in this model. Depletion of CD8+ T cells impairs the activity of the vaccination protocol supporting the key role of cytotoxic lymphocytes in our treatment regimen. The data generated here support the pre-clinical activity of this oncolytic vaccination and pave the way for future clinical trials for the treatment of advanced metastatic HPV induced carcinomas.
Citation Format: Matthew J. Atherton, Kyle B. Stephenson, Yonghong Wan, David F. Stojdl, Brian D. Lichty. Oncolytic vaccination for HPV induced cancer. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr B096.
Abstract B124: Immunotherapy of acute myeloid leukemia using Vg9Vd2 T-cells
Authors: Parente-Pereira Ana C. , Whilding Lynsey M. , Krishnamurthy Pramila , Beatson Richard , Zabinski Tomasz , Barber Linda , Farzaneh Farzin , Mufti Ghulam , Maher John 
Published: May 2016

Abstract
Disease remission is successfully induced in the majority of patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS), but is generally not sustained without stem cell transplantation. Adoptive immunotherapy offers an attractive option to consolidate AML remission. Here, we hypothesized that ex-vivo expanded Vg9Vd2 T-cells will mediate a therapeutically beneficial graft versus leukemia (GvL) effect in this disease.
Peripheral blood mononuclear cells from healthy donors and from patients with AML were activated in-vitro using zoledronic acid and a cytokine cocktail, containing IL-2. As a result, we observed an average 200-fold expansion of Vg9Vd2 T-cells from AML patients, over 15 days. Such expansion was only observed in patients without circulating AML blasts. Expanded patient-derived Vg9Vd2 T-cells exhibited a less differentiated phenotype than cells from healthy donors, indicated by higher expression of CD62L, CCR7 and CD27. A four hour Annexin V cytotoxicity assay using KG-1 and U937 leukemic cells showed that these Vg9Vd2 T-cells were cytotoxic and produced nanogram amounts of interferon-g; (IFN-g).
In a parallel approach, we investigated feasibility of developing a universal allogeneic Vg9Vd2 T-cell therapy. Feasibility of this approach has been demonstrated in a small trial in which haploidentical donor-derived Vg9Vd2 T-cells were safely infused and achieved an efficacy signal in patients with advanced haematological diseases. We have recently developed a novel method to expand Vg9Vd2 T-cells from healthy donors ex-vivo (“Method 2 (M2)” cells – patent protected), which improves their expansion over 2 weeks to 1700 fold. Cytotoxicity data shows that M2 cells destroy luciferase-expressing U937 and KG-1 target cells at 2-3 fold enhanced efficiency, accompanied by 2-3.5-fold increased IFN-g; release when compared to cells expanded using conventional approaches. Furthermore, M2 cells can achieve serial killing of AML cell lines through up to 4 cycles of re-stimulation. Treatment of SCID-Beige mice with an established U937 leukemic burden is also more effective using M2 expanded Vg9Vd2 T-cells, particularly when combined with zoledronic acid. Together these data highlight the promise of Vg9Vd2 T-cell immunotherapy of AML.
Citation Format: Ana C. Parente-Pereira, Lynsey M. Whilding, Pramila Krishnamurthy, Richard Beatson, Tomasz Zabinski, Linda Barber, Farzin Farzaneh, Ghulam Mufti, John Maher. Immunotherapy of acute myeloid leukemia using Vg9Vd2 T-cells. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr B124.
Abstract IA10: Combination checkpoint blockade
Authors: Wolchok Jedd D. 
Published: May 2016

Abstract
Given the activity noted with both CTLA-4 or PD-1 blockade, clinical trials are now investigating combination checkpoint blockade. The most mature data with a combination of ipilimumab + nivolumab in melanoma showed a response rate of 40% across dose cohorts with &gt;50% in some cohorts in the context of manageable toxicity. Such responses are generally durable, even when treatment was stopped early for toxicity. Unlike in studies of PD-1 blockade monotherapy, there was no significant difference in clinical activity based on tumor expression of PD-L1. Phase 2 and 3 trials of this combination have similarly shown high rates of activity in melanoma with phase 1 programs in numerous other tumor types. Attention is being paid to the reasons underlying the efficacy of checkpoint blockade in certain malignancies. One hypothesis has been that cancers having a high mutational load may be more amenable to immune modulation by virtue of the larger number of potential neo-epitopes present, fostering baseline immune recognition that can then be potentiated by checkpoint blockade. We have found that melanoma patients having long term clinical activity with ipilimumab have a significantly greater median number of non-synonymous passenger mutations, compared with patients who do not respond or those who have only short-term regression. Strategies to enhance baseline immune reactivity are therefore necessary to investigate as means to improve the impact of checkpoint blockade on a broad spectrum of cancers.
Citation Format: Jedd D. Wolchok. Combination checkpoint blockade. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr IA10.
Abstract IA29: Towards synthetic immune cells for cancer immunotherapy
Authors: Figdor Carl G. , Mandal Subhra , Hammink Roel , Eggermont Loek , Weiden Jorieke , Voerman Dion , Tel Jurjen , Eksteen-Akeroyd Zaskia H. , Blank Kerstin , Rowan Alan E. 
Published: May 2016

Abstract
Most cellular therapies targeting cancer require culture of autologous cells. The dedicated facilities and personnel needed, the variability in quality of the product depending on the condition of the patient and state of disease, hamper widespread use. In an attempt to generate an of the shelf product to target cancer we exploited the ever expanding possibilities to build supramolecular structures offered by chemistry to mimic nature including the construction of artificial immune cells or functions thereof. Effective immunotherapy critically depends on efficient production of antigen-specific cytotoxic T-cells. Herein lies an opportunity for both chemists and immunologists to design and synthesize so-called artificial antigen presenting cells (aAPCs) that can generate in vivo T-cell expansion. We have designed a novel synthetic dendritic cell (sDC) that possesses essential features of natural DCs. Our sDC is based on a semi-flexible poly(isocyano peptide) polymer and, as proof of principle, carries both anti-CD3 antibodies for triggering the T cell receptor/CD3 complex as well as anti-CD28 antibodies as a co-stimulatory signal. Multiple copies of both antibodies facilitate multivalent binding similar to natural DCs. The high mobility of these polymer-bound antibodies, reminiscent of protein motility in a natural plasma membrane, enables receptor rearrangements to occur during T cell activation. We observed effective T cell activation at significantly lower antibody concentrations than freely soluble antibodies. We also demonstrate antigen specific T cell activation when MHC/peptide complexes were bound. These findings demonstrate the potential of multifunctional polymers for mimicking functions of natural DCs or other immune cells, paving the way for their exploitation in immunotherapeutic strategies.
Citation Format: Carl G. Figdor, Subhra Mandal, Roel Hammink, Loek Eggermont, Jorieke Weiden, Dion Voerman, Jurjen Tel, Zaskia H. Eksteen-Akeroyd, Kerstin Blank, Alan E. Rowan. Towards synthetic immune cells for cancer immunotherapy. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr IA29.
Initial depression severity and response to antidepressants v. placebo: patient-level data analysis from 34 randomised controlled trials
Authors: Rabinowitz Jonathan , Werbeloff Nomi , Mandel Francine S. , Menard François , Marangell Lauren , Kapur Shitij 
Published: May 2016

SummarySeveral often-cited meta-analyses have reported that the efficacy of antidepressant medications depends on the severity of depression. They found that drug–placebo differences increased as a function of initial severity, which was attributed to decreased responsiveness to placebo among patients with severe depression rather than to increased responsiveness to medication. We retested this using patient-level data and also undertaking a meta-analysis of trial-level data from 34 randomised placebo controlled trials (n = 10 737) from the NEWMEDS registry. Although our trial-level data support prevous findings, patient-level data did not show any significant effect of initial depression severity on drug v. placebo difference.
(Un)Reliability in Narrative Discourse: A Comprehensive Overview
Authors: Sternberg Meir , Yacobi Tamar 
Published: May 2016

1 The State of the Art: A Field in Trouble.2 (Un)Reliable Discourse off to a Stimulating Equivocal Start: Why Wayne Booth's The Rhetoric of Fiction Falls Short and Where to Go from There: 2.1 Stammering between Narrator and Implied Author, or, Why the Author Needs to Keep Silent; 2.1.1 The Best Version, Considering; 2.1.2 Two-Mindedness; 2.1.3 Confusing the Communicators: Forms, Penalties, Lessons; 2.1.4 The Implied Author Vulnerable to Reliability Judgments?; 2.2 “Person” Overworked or Underworked? The Line between Mediators Erased and Redrawn; 2.2.1 Narrator, Reflector, Informant; 2.2.2 Author vs. Narrator, Narrator vs. Nonnarrator: Distinctions Compared and Correlated; 2.3 Do Narrators Act, Reliably or Otherwise? Narrating-I vs. Experiencing-I; 2.3.1 “Speaks or Acts”?; 2.3.2 Other Variations on the Enacted Narrator: A Brief Comparison of Oddities; 2.3.3 An Example from Proust; 2.3.4 Impossible Ontology: The Mediator Accompanied or Abandoned by the Author; 2.4 Making Bricks without Straw: How to Do Things with an Unworkable Formula?3 The Constructivist Turn: (Un)Reliability as a Mechanism of Integration: 3.1 The Perspectival Mechanism among Other Lines of Sense-Making; 3.2 The Perspectival Mechanism vis-à-vis Its Rivals and Partners; 3.3 The Theory Reviewed from a Different Perspective: Correcting Some Misunderstandings and Misapplications; 3.3.1 The Figurative Mechanism; 3.3.2 Reasoning in Face of Unreason: (Un) Reliability as Explained Problem and Explanatory Principle; 3.3.3 Paradigms and/or Participants Misnamed, Misgrouped, Monopolized: Is the Implied Author Necessary for Reliability Judgments?; 3.3.4 (Re)Construction; 3.3.5 (Re)Constructive Modulations: Defining (Un)Reliability and Making Reliability Judgments; 3.3.6 Dangerous Liaisons.4 Approaches to (Un)Reliability and the Wavering among Them: 4.1 (Un)Reliability in the Beholder's Eye: The Pedophile among Reliability Judges of Humbert; 4.2 The Reader Mixed-up with Other Reference Points; 4.3 Tissues of Incompatibility: A Brief Comparison; 4.4 The Interactive, Text/Reader Orientation; 4.5 Objectivism: Miniature and Large-Scale Reflexes (Expressions, Giveaways); 4.6 How the Implied Author and Author-Centeredness (Re)Enter by the Backstairs.
Impact of Mobile Dose-Tracking Technology on Medication Distribution at an Academic Medical Center
Authors: Kelm Matthew , Campbell Udobi 
Published: May 2016

Background Medication dose-tracking technologies have the potential to improve efficiency and reduce costs associated with re-dispensing doses reported as missing. Data describing this technology and its impact on the medication use process are limited. Objective The purpose of this study is to assess the impact of dose-tracking technology on pharmacy workload and drug expense at an academic, acute care medical center. Methods Dose-tracking technology was implemented in June 2014. Pre-implementation data were collected from February to April 2014. Post-implementation data were collected from July to September 2014. The primary endpoint was the percent of re-dispensed oral syringe and compounded sterile product (CSP) doses within the pre- and post-implementation periods per 1,000 discharges. Secondary endpoints included pharmaceutical expense generated from re-dispensing doses, labor costs, and staff satisfaction with the medication distribution process. Results We observed an average 6% decrease in re-dispensing of oral syringe and CSP doses from pre- to post-implementation (15,440 vs 14,547 doses; p = .047). However, when values were adjusted per 1,000 discharges, this trend did not reach statistical significance ( p = .074). Pharmaceutical expense generated from re-dispensing doses was significantly reduced from pre- to postimplementation ($834,830 vs $746,466 [savings of $88,364]; p = .047). We estimated that $2,563 worth of technician labor was avoided in re-dispensing missing doses. We also saw significant improvement in staff perception of technology assisting in reducing missing doses ( p = .0003), as well as improvement in effectiveness of resolving or minimizing missing doses ( p = .01). Conclusion The use of mobile dose-tracking technology demonstrated meaningful reductions in both the number of doses re-dispensed and cost of pharmaceuticals dispensed.
Direct Comparison of Metastasis-Related miRNAs Expression Levels in Circulating Tumor Cells, Corresponding Plasma, and Primary Tumors of Breast Cancer Patients
Authors: Markou Athina , Zavridou Martha , Sourvinou Ioanna , Yousef George , Kounelis Sofia , Malamos Nikos , Georgoulias Vasilis , Lianidou Evi 
Published: May 2016

Abstract

BACKGROUND
Circulating tumor cells (CTCs) and microRNAs (miRNAs) are important in liquid biopsies in which peripheral blood is used to characterize the evolution of solid tumors. We evaluated the expression levels of miR-21, miR-146a, miR-200c, and miR-210 in CTCs of breast cancer patients with verified metastasis and compared their expression levels in corresponding plasma and primary tumors.

METHODS
Expression levels of the miRNAs were quantified by quantitative reverse transcription PCR (RT-qPCR) in (a) 89 primary breast tumors and 30 noncancerous breast tissues and (b) CTCs and corresponding plasma of 55 patients with metastatic breast cancer and 20 healthy donors. For 30 of these patients, CTCs, corresponding plasma, and primary tumor tissues were available.

RESULTS
In formalin-fixed, paraffin-embedded tissues, these miRNAs were differentially expressed between primary breast tumors and noncancerous breast tissues. miR-21 (P &lt; 0.001) and miR-146a (P = 0.001) were overexpressed, whereas miR-200c (P = 0.004) and miR-210 (P = 0.002) were underexpressed. In multivariate analysis, miR-146a overexpression was significantly [hazard ratio 2.969 (1.231–7.157), P = 0.015] associated with progression-free survival. In peripheral blood, all miRNAs studied were overexpressed in both CTC and corresponding plasma. There was a significant association between miR-21 expression levels in CTCs and plasma for 36 of 55 samples (P = 0.008). In plasma, ROC curve analysis revealed that miR-21, miR-146a, and miR-210 could discriminate patients from healthy individuals.

CONCLUSIONS
Metastasis-related miRNAs are overexpressed in CTCs and corresponding plasma; miR-21 expression levels highly correlate in CTCs and plasma; and miR-21, miR-146a, and miR-210 are valuable plasma biomarkers for discriminating patients from healthy individuals.
Consolidation in the UK commercial radio sector: The impact on newsroom practice of recent changes in regulation, ownership and local content requirement
Authors: McDonald Katy , Starkey Guy 
Published: May 2016

Abstract
This article aims to explore the implications for local radio news in the UK commercial radio industry of a series of changes to the regulation of the sector since it was first established in the 1970s. A recent regulatory focus on product rather than process has enabled groups of stations to move not only programming production but also much news journalism out of the editorial areas it is intended to serve and into news ‘hubs’ intended to rationalize the process of news gathering and bulletin presentation and enable the groups to become increasingly profitable. The article considers a number of issues around the management of commercial radio groups in the United Kingdom, the development and, most recently, exploitation of the group ownership system of what mainly began as locally owned and locally operated radio stations, and the appropriateness of the current regulatory regime in the much altered media landscape of today. It uses original data derived from the ownership groups themselves to show the extent to which ‘hubs’ are routinely being used to increase profitability by making economies of scale, while also taking news journalism out of the editorial areas it is intended to cover.
No more ‘voices from down south’: Parallel voices in remote Queensland Indigenous communities
Authors: Watson Ian 
Published: May 2016

Abstract
This study examines the interaction between audience and producer in the production of local content by Indigenous radio stations in remote areas of far north Queensland, Australia. In the past three years, these stations have changed from being primarily carriers of content from Indigenous and non-Indigenous radio networks in other parts of Australia (from media organizations located ‘down south’ in major cities) to a network of stations broadcasting their own locally relevant and culturally specific programming 24 hours a day. Qualitative research, including participant observation of community broadcasters, reveals high levels of active audience engagement with local broadcasting, with content that is ‘hyper-local’ valued more than content produced outside of the community. Underpinning the engagement with radio in these communities is the accessibility of local producers and the ability of community members to have input into local content.
Hepatitis C Screening of the “Birth Cohort” (Born 1945–1965) and Younger Inmates of New York City Jails
Authors: Akiyama Matthew J. , Kaba Fatos , Rosner Zachary , Alper Howard , Holzman Robert S. , MacDonald Ross 
Published: May 2016

Objectives. To examine uptake of screening for all individuals born between 1945 and 1965 (referred to by the Centers for Disease Control and Prevention as the “birth cohort”) and outline preliminary HCV prevalence data in the New York City jail system. Methods. Data were extracted from electronic health records for all individuals screened for HCV between June 13, 2013, and June 13, 2014, in New York City jails. We used the Abbott EIA 2.0 HCV antibody assay for testing. Results. In the year of study, 56 590 individuals were incarcerated; 15.1% were born between 1945 and 1965, and 84.6% were born after 1965. HCV screening was completed for 64.1% of the birth cohort and for 11.1% born after 1965, with 55.1% and 43.8% of cases found in these groups, respectively. The overall seropositivity rate was 20.6%. Conclusions. Birth cohort screening in a large jail system identified many HCV cases, but HCV infection was common among younger age groups. Public Health Implications. Universal screening may be warranted pending further study including cost-effectiveness analyses.
Challenges in Identifying Refugees in National Health Data Sets
Authors: Semere Wagahta , Yun Katherine , Ahalt Cyrus , Williams Brie , Wang Emily A. 
Published: May 2016

Objectives. To evaluate publicly available data sets to determine their utility for studying refugee health. Methods. We searched for keywords describing refugees in data sets within the Society of General Internal Medicine Dataset Compendium and the Inter-University Consortium for Political and Social Research database. We included in our analysis US-based data sets with publicly available documentation and a self-defined, health-related focus that allowed for an examination of patient-level factors. Results. Of the 68 data sets that met the study criteria, 37 (54%) registered keyword matches related to refugees, but only 2 uniquely identified refugees. Conclusions. Few health data sets identify refugee status among participants, presenting barriers to understanding refugees’ health and health care needs. Public Health Implications. Information about refugee status in national health surveys should include expanded demographic questions and focus on mental health and chronic disease.