bluuebunny/crossref_metadata_2025_split huggingface dataset:
Simulating Peace Negotiations
Authors: Kempin Reuter Tina 
Published: September 2016

Background. This article reflects on the use of a simulation of peace talks between Israeli and Palestinians in an upper-level undergraduate course at a liberal arts university in the United States. The university was commissioned to test an externally developed proposal and implementation plan for peace negotiations between Israeli and Palestinians (the “IMPLEMENTATION PLAN”). Aim. (1) To contribute to student’s academic learning and understanding of the conflict; (2) to find strengths and weaknesses of the model. Method. Analysis of data collected using a convergent parallel mixed method approach involving surveys, exit interviews, and guided reflection papers. Results. Student Learning Outcomes. The data supports a deeper understanding of the nature of the conflict as well as the complexity of peace negotiations. Students reported a higher level of engagement with the subject matter as a result of the simulation. The model encouraged innovative thinking and new solutions, which might be of interest in real life application. Challenges to student learning were mainly related to (1) student identification with their roles and (2) a need to compromise and finding quick answers. Model. The simulation demonstrated the strengths of the IMPLEMENTATION PLAN, namely to the focused, structured negotiation process with narrowly defined “tracks.” Challenges include the structure of the simulation, the question of applicability of the model to a real life situation, as well as the long-term implementation strategy of negotiation outcomes. Conclusion. The simulation of the IMPLEMENTATION PLAN greatly benefited student learning and led to thought-provoking outcomes concerning negotiations. However, the findings suggest the need for flexibility and modification of the model.
Advance Care Planning: Understanding Clinical Routines and Experiences of Interprofessional Team Members in Diverse Health Care Settings
Authors: Arnett Kelly , Sudore Rebecca L. , Nowels David , Feng Cindy X. , Levy Cari R. , Lum Hillary D. 
Published: September 2016

Background:Interprofessional health care team members consider advance care planning (ACP) to be important, yet gaps remain in systematic clinical routines to support ACP. A clearer understanding of the interprofessional team members’ perspectives on ACP clinical routines in diverse settings is needed.Methods:One hundred eighteen health care team members from community-based clinics, long-term care facilities, academic clinics, federally qualified health centers, and hospitals participated in a 35-question, cross-sectional online survey to assess clinical routines, workflow processes, and policies relating to ACP.Results:Respondents were 53% physicians, 18% advanced practice nurses, 11% nurses, and 18% other interprofessional team members including administrators, chaplains, social workers, and others. Regarding clinical routines, respondents reported that several interprofessional team members play a role in facilitating ACP (ie, physician, social worker, nurse, others). Most (62%) settings did not have, or did not know of, policies related to ACP documentation. Only 14% of settings had a patient education program. Two-thirds of the respondents said that addressing ACP is a high priority and 85% felt that nonphysicians could have ACP conversations with appropriate training. The clinical resources needed to improve clinical routines included training for providers and staff, dedicated staff to facilitate ACP, and availability of patient/family educational materials.Conclusion:Although interprofessional health care team members consider ACP a priority and several team members may be involved, clinical settings lack systematic clinical routines to support ACP. Patient educational materials, interprofessional team training, and policies to support ACP clinical workflows that do not rely solely on physicians could improve ACP across diverse clinical settings.
Material properties of Islamic paper
Authors: Mahgoub Hend , Bardon Tiphaine , Lichtblau Dirk , Fearn Tom , Strlič Matija 
Published: September 2016

Abstract
In contrast to scientific research focussing on European paper, there is a significant gap in our knowledge of Islamic papermaking. This research surveys the evidence of techniques and materials typically used in Islamic papermaking, to deduce what might be considered as the most significant characteristics. A substantial collection of 228 Islamic papers (~18th–20th century) was characterized using chemical analytical methods: surface profilometry, gloss measurements, specular vs. diffuse reflectance ratio at 457 nm, scanning electron microscopy and infrared spectroscopy for identification of polishing, iodine test for identification of starch, Raspail test for identification of rosin, and fibre furnish analysis. Morphological analysis was performed to examine the presence of watermarks and sieve patterns. In addition, acidity and degree of polymerization of cellulose in paper were determined to explore the average material state of paper in the collection. Near infrared spectroscopic data of the collection were correlated to chemical properties with the aid of multivariate data analysis methods. Four different models were developed focusing on two main characteristics of Islamic paper: two for identification of polishing and starch, and two quantitative models to determine the acidity and degree of polymerization of cellulose in paper. While no single defining characteristic of Islamic paper was identified, 88 % of all papers in the studied collection either contain starch or are polished, or both. ~2 % of papers contain rosin. The majority of papers are neutral to mildly acidic, which is in contrast to their extensive degradation: ~69 % have DP < 1000. Polishing and starch appear to be associated with current values of pH and DP. The developed non-destructive characterization methodology could be applied to Islamic collections in libraries and archives to expand the database with the material properties of papers of known age and provenance and thus better understand geographic and temporal distributions of papermaking practices in Islamic countries.
Complete genome sequence of Halomonas sp. R5-57
Authors: Williamson Adele , De Santi Concetta , Altermark Bjørn , Karlsen Christian , Hjerde Erik 
Published: September 2016

AbstractThe marine Arctic isolate Halomonas sp. R5-57 was sequenced as part of a bioprospecting project which aims to discover novel enzymes and organisms from low-temperature environments, with potential uses in biotechnological applications. Phenotypically, Halomonas sp. R5-57 exhibits high salt tolerance over a wide range of temperatures and has extra-cellular hydrolytic activities with several substrates, indicating it secretes enzymes which may function in high salinity conditions. Genome sequencing identified the genes involved in the biosynthesis of the osmoprotectant ectoine, which has applications in food processing and pharmacy, as well as those involved in production of polyhydroxyalkanoates, which can serve as precursors to bioplastics. The percentage identity of these biosynthetic genes from Halomonas sp. R5-57 and current production strains varies between 99 % for some to 69 % for others, thus it is plausible that R5-57 may have a different production capacity to currently used strains, or that in the case of PHAs, the properties of the final product may vary. Here we present the finished genome sequence (LN813019) of Halomonas sp. R5-57 which will facilitate exploitation of this bacterium; either as a whole-cell production host, or by recombinant expression of its individual enzymes.
Interferon regulatory factor 4 (IRF4) controls myeloid-derived suppressor cell (MDSC) differentiation and function
Authors: Nam Sorim , Kang Kyeongah , Cha Jae Seon , Kim Jung Woo , Lee Hee Gu , Kim Yonghwan , Yang Young , Lee Myeong-Sok , Lim Jong-Seok 
Published: September 2016

Abstract
Myeloid-derived suppressor cells (MDSCs) are immature cells that do not differentiate into mature myeloid cells. Two major populations of PMN-MDSCs (Ly6GhighLy6ClowGr1highCD11b+) and MO-MDSCs (Ly6G−Ly6ChighGr-1intCD11b+) have an immune suppressive function. Interferon regulatory factor 4 (IRF4) has a role in the negative regulation of TLR signaling and is associated with lymphoid cell development. However, the roles of IRF4 in myeloid cell differentiation are unclear. In this study, we found that IRF4 expression was remarkably suppressed during the development of MDSCs in the tumor microenvironment. Both the mRNA and protein levels of IRF4 in MDSCs were gradually reduced, depending on the development of tumors in the 4T1 model. siRNA-mediated knockdown of IRF4 in bone marrow cells promoted the differentiation of PMN-MDSCs. Similarly, IRF4 inhibition in bone marrow cells using simvastatin, which has been known to inhibit IRF4 expression, increased PMN-MDSC numbers. In contrast, IRF4 overexpression in bone marrow cells inhibited the total numbers of MDSCs, especially PMN-MDSCs. Notably, treatment with IL-4, an upstream regulator of IRF4, induced IRF4 expression in the bone marrow cells, and consequently, IL-4–induced IRF4 expression resulted in a decrease in PMN-MDSC numbers. Finally, we confirmed that IRF4 expression in MDSCs can modulate their activity to inhibit T cell proliferation through IL-10 production and ROS generation, and myeloid-specific deletion of IRF4 leads to the increase of MDSC differentiation. Our present findings indicate that IRF4 reduction induced by tumor formation can increase the number of MDSCs, and increases in the IRF4 expression in MDSCs may infringe on the immune-suppressive function of MDSCs.
Selenoprotein K regulation of palmitoylation and calpain cleavage of ASAP2 is required for efficient FcγR-mediated phagocytosis
Authors: Norton Robert L , Fredericks Gregory J , Huang Zhi , Fay Jeffrey D , Hoffmann FuKun W , Hoffmann Peter R 
Published: September 2016

Abstract
Effective activation of macrophages through phagocytic Fcγ receptors (FcγR) has been shown to require selenoprotein K (Selk). We set out to determine whether the FcγR-mediated uptake process itself also requires Selk and potential underlying mechanisms. Macrophages from Selk knockout (KO) mice were less efficient compared with wild-type (WT) controls in engulfing IgG-coated fluorescent beads. Using LC-MS/MS to screen for Selk-binding partners involved in FcγR-mediated phagocytosis, we identified Arf-GAP with SH3 domain, ANK repeat, and PH domain-containing protein 2 (ASAP2). Coimmunoprecipitation assays confirmed interactions between Selk and ASAP2. Selk was required for ASAP2 to be cleaved by calpain-2 within the Bin/Amphiphysin/Rvs (BAR) domain of ASAP2. BAR domains promote membrane association, which was consistent with our data showing that Selk deficiency led to retention of ASAP2 within the phagocytic cup. Because Selk was recently identified as a cofactor for the palmitoylation of certain proteins, we investigated whether ASAP2 was palmitoylated and whether this was related to its cleavage by calpain-2. Acyl/biotin exchange assays and MALDI-TOF analysis showed that cysteine-86 in ASAP2 was palmitoylated in WT, but to a much lesser extent in KO, mouse macrophages. Inhibitors of either palmitoylation or calpain-2 cleavage and rescue experiments with different versions of Selk demonstrated that Selk-dependent palmitoylation of ASAP2 leads to cleavage by calpain-2 within the BAR domain, which releases this protein from the maturing phagocytic cup. Overall, these findings identify ASAP2 as a new target of Selk-dependent palmitoylation and reveal a new mechanism regulating the efficiency of FcγR-mediated phagocytosis.
NK cells regulate CXCR2+ neutrophil recruitment during acute lung injury
Authors: Hoegl Sandra , Ehrentraut Heidi , Brodsky Kelley S , Victorino Francisco , Golden-Mason Lucy , Eltzschig Holger K , McNamee Eóin N 
Published: September 2016

Abstract
A critical step in the pathogenesis of acute lung injury (ALI) is excessive recruitment of polymorphonuclear neutrophils (PMNs) into the lungs, causing significant collateral tissue damage. Defining the molecular and cellular steps that control neutrophil infiltration and activation during ALI is therefore of important therapeutic relevance. Based on previous findings implicating the transcription factor Tbet in mucosal Th1-inflammation, we hypothesized a detrimental role for Tbet during ALI. In line with our hypothesis, initial studies of endotoxin-induced lung injury revealed a marked protection of Tbet−/− mice, including attenuated neutrophilia compared to WT counterparts. Surprisingly, subsequent studies identified natural killer (NK) cells as the major source of pulmonary Tbet during ALI. In addition, a chemokine screen suggested that mature Tbet+ NK-cells are critical for the production of pulmonary CXCL1 and -2, thereby contributing to pulmonary PMN recruitment. Indeed, both NK-cell Ab depletion and adoptive transfer studies provide evidence for NK cells in the orchestration of neutrophil recruitment during endotoxin-induced ALI. Taken together, these findings identify a novel role for Tbet+ NK-cells in initiating the early events of noninfectious pulmonary inflammation.
Health-Related Quality-of-Life Results From the Open-Label, Randomized, Phase III ASPIRE Trial Evaluating Carfilzomib, Lenalidomide, and Dexamethasone Versus Lenalidomide and Dexamethasone in Patients With Relapsed Multiple Myeloma
Authors: Stewart A. Keith , Dimopoulos Meletios A. , Masszi Tamás , Špička Ivan , Oriol Albert , Hájek Roman , Rosiñol Laura , Siegel David S. , Niesvizky Ruben , Jakubowiak Andrzej J. , San-Miguel Jesus F. , Ludwig Heinz , Buchanan Jacqui , Cocks Kim , Yang Xinqun , Xing Biao , Zojwalla Naseem , Tonda Margaret , Moreau Philippe , Palumbo Antonio 
Published: September 2016

Purpose To determine the effects of carfilzomib, lenalidomide, and dexamethasone (KRd) versus lenalidomide and dexamethasone (Rd) on health-related quality of life (HR-QoL) in the Carfilzomib, Lenalidomide, and Dexamethasone Versus Lenalidomide and Dexamethasone for the Treatment of Patients With Relapsed Multiple Myeloma (ASPIRE) trial. Methods Patients with relapsed multiple myeloma were randomly assigned to receive KRd or Rd. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 and myeloma-specific module were administered at baseline; day 1 of cycles 3, 6, 12, and 18; and after treatment. The Global Health Status/Quality of Life (GHS/QoL) scale and seven subscales (fatigue, nausea and vomiting, pain, physical functioning, role functioning, disease symptoms, and adverse effects of treatment) were compared between groups using a mixed model for repeated measures. The percentages of responders with ≥ 5- or 15-point GHS/QoL improvement at each cycle were compared between groups. Results Baseline questionnaire compliance was excellent (94.1% of randomly assigned patients). KRd patients had higher GHS/QoL scores versus Rd patients over 18 treatment cycles (two-sided P < .001). The minimal important difference was met at cycle 12 (5.6 points) and approached at cycle 18 (4.8 points). There was no difference between groups for the other prespecified subscales from ASPIRE. A higher proportion of KRd patients met the GHS/QoL responder definition (≥ 5-point improvement) with statistical differences at cycle 12 (KRd v Rd patients, 25.5% v 17.4%, respectively) and 18 (KRd v Rd patients, 24.2% v 12.9%, respectively). Conclusion KRd improves GHS/QoL without negatively affecting patient-reported symptoms when compared with Rd. These data further support the benefit of KRd in patients with relapsed multiple myeloma.
Clinical Effects of Driver Somatic Mutations on the Outcomes of Patients With Myelodysplastic Syndromes Treated With Allogeneic Hematopoietic Stem-Cell Transplantation
Authors: Della Porta Matteo G. , Gallì Anna , Bacigalupo Andrea , Zibellini Silvia , Bernardi Massimo , Rizzo Ettore , Allione Bernardino , van Lint Maria Teresa , Pioltelli Pietro , Marenco Paola , Bosi Alberto , Voso Maria Teresa , Sica Simona , Cuzzola Mariella , Angelucci Emanuele , Rossi Marianna , Ubezio Marta , Malovini Alberto , Limongelli Ivan , Ferretti Virginia V. , Spinelli Orietta , Tresoldi Cristina , Pozzi Sarah , Luchetti Silvia , Pezzetti Laura , Catricalà Silvia , Milanesi Chiara , Riva Alberto , Bruno Benedetto , Ciceri Fabio , Bonifazi Francesca , Bellazzi Riccardo , Papaemmanuil Elli , Santoro Armando , Alessandrino Emilio P. , Rambaldi Alessandro , Cazzola Mario 
Published: September 2016

Purpose The genetic basis of myelodysplastic syndromes (MDS) is heterogeneous, and various combinations of somatic mutations are associated with different clinical phenotypes and outcomes. Whether the genetic basis of MDS influences the outcome of allogeneic hematopoietic stem-cell transplantation (HSCT) is unclear. Patients and Methods We studied 401 patients with MDS or acute myeloid leukemia (AML) evolving from MDS (MDS/AML). We used massively parallel sequencing to examine tumor samples collected before HSCT for somatic mutations in 34 recurrently mutated genes in myeloid neoplasms. We then analyzed the impact of mutations on the outcome of HSCT. Results Overall, 87% of patients carried one or more oncogenic mutations. Somatic mutations of ASXL1, RUNX1, and TP53 were independent predictors of relapse and overall survival after HSCT in both patients with MDS and patients with MDS/AML (P values ranging from .003 to .035). In patients with MDS/AML, gene ontology (ie, secondary-type AML carrying mutations in genes of RNA splicing machinery, TP53-mutated AML, or de novo AML) was an independent predictor of posttransplantation outcome (P = .013). The impact of ASXL1, RUNX1, and TP53 mutations on posttransplantation survival was independent of the revised International Prognostic Scoring System (IPSS-R). Combining somatic mutations and IPSS-R risk improved the ability to stratify patients by capturing more prognostic information at an individual level. Accounting for various combinations of IPSS-R risk and somatic mutations, the 5-year probability of survival after HSCT ranged from 0% to 73%. Conclusion Somatic mutation in ASXL1, RUNX1, or TP53 is independently associated with unfavorable outcomes and shorter survival after allogeneic HSCT for patients with MDS and MDS/AML. Accounting for these genetic lesions may improve the prognostication precision in clinical practice and in designing clinical trials.
Cautionary Note on Using Cross-Validation for Molecular Classification
Authors: Qin Li-Xuan , Huang Huei-Chung , Begg Colin B. 
Published: September 2016

PurposeReproducibility of scientific experimentation has become a major concern because of the perception that many published biomedical studies cannot be replicated. In this article, we draw attention to the connection between inflated overoptimistic findings and the use of cross-validation for error estimation in molecular classification studies. We show that, in the absence of careful design to prevent artifacts caused by systematic differences in the processing of specimens, established tools such as cross-validation can lead to a spurious estimate of the error rate in the overoptimistic direction, regardless of the use of data normalization as an effort to remove these artifacts.MethodsWe demonstrated this important yet overlooked complication of cross-validation using a unique pair of data sets on the same set of tumor samples. One data set was collected with uniform handling to prevent handling effects; the other was collected without uniform handling and exhibited handling effects. The paired data sets were used to estimate the biologic effects of the samples and the handling effects of the arrays in the latter data set, which were then used to simulate data using virtual rehybridization following various array-to-sample assignment schemes.ResultsOur study showed that (1) cross-validation tended to underestimate the error rate when the data possessed confounding handling effects; (2) depending on the relative amount of handling effects, normalization may further worsen the underestimation of the error rate; and (3) balanced assignment of arrays to comparison groups allowed cross-validation to provide an unbiased error estimate.ConclusionOur study demonstrates the benefits of balanced array assignment for reproducible molecular classification and calls for caution on the routine use of data normalization and cross-validation in such analysis.
Timing Is Everything: What Is the Optimal Duration After Chemoradiation for Surgery for Rectal Cancer?
Authors: Goodman Karyn A. 
Published: September 2016

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors’ suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology , to patients seen in their own clinical practice. A 47-year-old woman was referred for management of a newly diagnosed rectal cancer. She presented with a 2-month history of rectal bleeding and change in bowel habits. She underwent a colonoscopy that demonstrated a 5-cm fungating, friable, and partially obstructing mass in the distal rectum, approximately 5 cm from the anal verge. The tumor was palpable on digital rectal examination on the anterior wall of rectum. The biopsy demonstrated a moderately differentiated invasive adenocarcinoma, microsatellite stable. A staging work-up, including a computed tomography scan of the chest, abdomen, and pelvis, demonstrated rectal wall thickening in the midrectum and small lymph nodes in the left perirectal fat. There was a nonspecific 3-mm right lower lobe pulmonary nodule. Rectal magnetic resonance imaging demonstrated a 3-cm mass arising from mid-distal rectum with minimal extension beyond muscularis propria into the mesorectal fat, but without invasion of mesorectal fascia ( Fig 1 ). There were at least three small mesorectal lymph nodes present; the largest rounded node measured up to 5 mm, and no additional pelvic lymphadenopathy was identified. Her carcinoembryonic antigen was 1.1, and all other laboratory studies were within normal limits. She was seen in the Colorectal Multidisciplinary Conference for a discussion of her treatment options.