bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk Engagement and Protection Survey (REPS): developing and validating a survey tool on fathers’ attitudes towards child injury protection and risk engagement
Authors: Olsen Lise L , Ishikawa Takuro , Mâsse Louise C , Chan Grace , Brussoni Mariana 
Published: October 2017

IntroductionFathers play a unique role in keeping children safe from injury yet understanding of their views and attitudes towards protecting children from injury and allowing them to engage in risks is limited. The purpose of this study was to develop and validate an instrument to measure fathers’ attitudes towards these two constructs.Methods and findingsAn instrument was developed that used prior qualitative research to inform item generation. The questions were assessed for content validity with experts, then pilot-tested with fathers. The survey was completed by 302 fathers attending hospital with their child for an injury or non-injury reason. Results of confirmatory factor analysis identified eight items relating to the protection from injury factor and six items relating to the risk engagement factor. Correlation between the two factors was low, suggesting these are two independent constructs.ConclusionsThe Risk Engagement and Protection Survey offers a tool for measuring attitudes and assisting with intervention strategy development in ways that reflect fathers’ views and promotes a balanced view of children’s needs for safety with their needs for engaging in active, healthy risk-taking.
Does size matter concerning impact of position on oxygenation status in spontaneously breathing patients with unilateral effusion?
Authors: Michaelides Stylianos A , Michailidis Avgerinos-Romanos , Bablekos George D , Analitis Antonis , Michalatou Maria , Koulouris Nikolaos 
Published: October 2017

AbstractBackgroundInconsistent and contradictory findings have appeared in the literature concerning the impact of body position on oxygenation in pleural effusion.MethodsWe attempted to elucidate whether the size of the pleural effusion in patients with no parenchymal disease is the main determinant of posture-induced alterations in oxygenation parameters. We studied 62 spontaneously breathing patients aged 65.3±7.8 years (mean±SD), of whom 36 had large and massive-sized effusions (Group A) and 26 had small and moderate-sized effusions (Group B). Arterial blood gases were determined in four different body positions: sitting (SIT), supine (SUP), ipsilateral (IPS) and contralateral (CON) to the effusion side, after remaining relaxed for at least 20 min in each position. Separation into groups A and B was deliberately set from the position of the fluid meniscus line on a posteroanterior chest film just above the upper costal margin of the sixth anterior rib. A two-way ANOVA model with outcome variables PaO2, PaCO2 and [A–a] DO2 was used.ResultsIn both groups the best oxygenation was found in SIT. The worst oxygenation (highest [A–a] DO2 value) occurred in group A in CON compared with IPS (59.4±7.6 vs 49.0±7.5 mm Hg, p&lt;0.001) and in group B in IPS compared with CON (51.0±8.7 vs 39.5±9.2 mm Hg, p&lt;0.001). Also, PaCO2 showed significant differences in both groups in IPS compared with CON (p=0.002).ConclusionsPatients with large-sized effusions exhibit the worst oxygenation when lying on the side contralateral to the effusion, while those with small-sized effusions exhibit the worst oxygenation when lying on the side ipsilateral to the effusion.
“I kind of feel like sometimes I am shoving it under the carpet”: Documenting women’s experiences with post-abortion support in Ontario
Authors: LaRoche Kathryn J. , Foster Angel M. 
Published: October 2017

Background: Abortion has been available without criminal restriction in Canada since 1988, and approximately 33 000 terminations take place in Ontario each year. Objectives: This study aimed to explore women’s expressed desire for post-abortion support services, document the priorities expressed by women in seeking post-abortion support, and identify actionable strategies to improve post-abortion support services in Ontario. Methods: Between 2012 and 2014 we conducted in-depth, open-ended interviews with 60 Anglophone women from across Ontario who had recently had an abortion. We aimed to rigorously explore the compounding issues of age and geography on women’s abortion experiences. We analyzed our data for content and themes and reported on the findings related to post-abortion support. Results: One third of our participants expressed a desire for post-abortion support, yet few were able to access a timely, affordable, non-directive service. Women were uncertain about how to find services; most contacted a provider recommended by the clinic or searched online. Women were enthusiastic about a talkline format citing anonymity and convenience as the main advantages. Conclusion: Our results suggest that exploring ways to expand post-abortion support services in Ontario is warranted. A talkline format could provide an anonymous, convenient, non-judgmental, and non-directive way to address this unmet need.
Testing dark matter with the anomalous magnetic moment in a dark matter quantum electrodynamics model
Authors: Das Ashok K. , Gamboa Jorge , Méndez Fernando , Tapia Natalia 
Published: October 2017

We consider a model of dark quantum electrodynamics (QEDs) which is coupled to a visible photon through a kinetic mixing term. We compute the [Formula: see text] for the dark fermion, where [Formula: see text] is its gyromagnetic factor. We show that the [Formula: see text] of the dark fermion is related to the [Formula: see text] of (visible) QEDs through a constant which depends on the kinetic mixing factor. We determine [Formula: see text] as a function of the mass ratio [Formula: see text], where [Formula: see text] and [Formula: see text] denote the masses of the dark photon and the dark fermion, respectively, and we show how [Formula: see text] becomes very different for light and heavy fermions around [Formula: see text] eV.
Earth surface processes and landscape evolution in the Himalaya: a framework for sustainable development and geohazard mitigation
Authors: Owen Lewis A. 
Published: October 2017

Abstract
Successful sustainable development and geohazard mitigation in the Himalaya requires an understanding of the nature and dynamics of Earth surface processes and landscape evolution. In recent years, geoscience studies of Himalayan environments have been increasing due to better accessibility, modern technologies and the understanding that there is a necessity to determine the nature and predict likely environmental changes that are occurring due to natural and human influences. The Himalaya is one of the most dynamically active tectonic and geomorphic regions on our planet, and it is the most glaciated mountain area outside of the polar realms. The high mountains and deep valleys are a consequence of the continued collision of the Indian and Eurasian continental plates, rapid uplift and intense denudation by glacial, fluvial, landsliding, aeolian and weathering processes. These processes change over time, influenced by topographic development, climate change and humans. Defining the rates and magnitudes of these processes and their interactions is fundamental in developing a framework to quantify, model and predict future changes for geohazard mitigation and sustainable development.
S-allyl-glutathione improves experimental liver fibrosis by regulating Kupffer cell activation in rats
Authors: Takemura Shigekazu , Azuma Hideki , Osada-Oka Mayuko , Kubo Shoji , Shibata Toshihiko , Minamiyama Yukiko 
Published: October 2017

S-allyl-glutathione (SAG) is one of the metabolites of diallyl sulfide (DAS), a component of garlic. DAS has shown preventative effects on carcinogenesis in animal models. However, whether synthetic SAG can improve liver fibrosis has not been investigated. We examined the potential preventive effects of SAG on acute and chronic models of liver fibrosis by chronic carbon tetrachloride (CCl4) administration. SAG inhibited liver fibrogenesis induced by CCl4in a dose-dependent manner and reduced heat shock protein-47 (HSP47), a collagen-specific chaperone, and other fibrosis markers. In fibrosis regression models, after administration of either CCl4for 9 wk or dimethyl nitrosamine (DMN) for 6 wk, SAG markedly accelerated fibrolysis in both models. In the regression stage of DMN-treated liver, SAG normalized the ratio of M2 phenotype (expression of mannose receptor) in Kupffer cells (KCs). Consistent with these results, the culture supernatants of SAG-treated M2-phenotype KCs inhibited collagen-α1(I) chain (COL1A1) mRNA expression in primary culture-activated rat hepatic stellate cells (HSCs). However, SAG did not directly inhibit HSC activation. In an acute model of CCl4single injection, SAG inhibited hepatic injury dose dependently consistent with the inhibited the elevation of the bilirubin and ALT levels. These findings suggest that SAG could improve the fibrogenic and fibrolysis cascade via the regulation of excess activated and polarized KCs. SAG may also serve as a preventive and therapeutic agent in fibrosis of other organs for which current clinical therapy is unavailable.NEW & NOTEWORTHY S-allyl-glutathione (SAG) is a metabolite of diallyl sulfide, a component of garlic. SAG increased hepatic glutathione levels and GSH-to-GSSG ratio in normal rats. SAG treatment before or after liver fibrosis from chronic CCl4administration improved liver fibrosis and regression. SAG decreased heat shock protein-47 (HSP47), a collagen-specific chaperone, and other fibrosis markers in CCl4-treated livers. SAG-treated Kupffer cell conditioned medium also inhibited collagen-α1(I) chain (COL1A1) mRNA expression and other markers in primary culture hepatic stellate cells.
JAM-C Identifies Src Family Kinase-Activated Leukemia-Initiating Cells and Predicts Poor Prognosis in Acute Myeloid Leukemia
Authors: De Grandis Maria , Bardin Florence , Fauriat Cyril , Zemmour Christophe , El-Kaoutari Abdessamad , Sergé Arnauld , Granjeaud Samuel , Pouyet Laurent , Montersino Camille , Chretien Anne-Sophie , Mozziconacci Marie-Joelle , Castellano Remy , Bidaut Ghislain , Boher Jean-Marie , Collette Yves , Mancini Stéphane J.C. , Vey Norbert , Aurrand-Lions Michel 
Published: October 2017

AbstractAcute myeloid leukemia (AML) originates from hematopoietic stem and progenitor cells that acquire somatic mutations, leading to disease and clonogenic evolution. AML is characterized by accumulation of immature myeloid cells in the bone marrow and phenotypic cellular heterogeneity reflective of normal hematopoietic differentiation. Here, we show that JAM-C expression defines a subset of leukemic cells endowed with leukemia-initiating cell activity (LIC). Stratification of de novo AML patients at diagnosis based on JAM-C–expressing cells frequencies in the blood served as an independent prognostic marker for disease outcome. Using publicly available leukemic stem cell (LSC) gene expression profiles and gene expression data generated from JAM-C–expressing leukemic cells, we defined a single cell core gene expression signature correlated to JAM-C expression that reveals LSC heterogeneity. Finally, we demonstrated that JAM-C controls Src family kinase (SFK) activation in LSC and that LIC with exacerbated SFK activation was uniquely found within the JAM-C–expressing LSC compartment. Cancer Res; 77(23); 6627–40. ©2017 AACR.
Transmembrane and Coiled-Coil Domain 1 Impairs the AKT Signaling Pathway in Urinary Bladder Urothelial Carcinoma: A Characterization of a Tumor Suppressor
Authors: Li Chien-Feng , Wu Wen-Ren , Chan Ti-Chun , Wang Yu-Hui , Chen Lih-Ren , Wu Wen-Jeng , Yeh Bi-Wen , Liang Shih-Shin , Shiue Yow-Ling 
Published: October 2017

Abstract
Purpose: Urinary bladder urothelial carcinoma (UBUC) is a common malignant disease in developed countries. Cell-cycle dysregulation resulting in uncontrolled cell proliferation has been associated with UBUC development. This study aimed to explore the roles of TMCO1 in UBUCs.
Experimental Design: Data mining, branched DNA assay, immunohistochemistry, xenograft, cell culture, quantitative RT-PCR, immunoblotting, stable and transient transfection, lentivirus production and stable knockdown, cell-cycle, cell viability and proliferation, soft-agar, wound-healing, transwell migration and invasion, coimmunoprecipitation, immunocytochemistry, and AKT serine/threonine kinase (AKT) activity assays and site-directed mutagenesis were used to study TMCO1 involvement in vivo and in vitro.
Results: Data mining identified that the TMCO1 transcript was downregulated during the progression of UBUCs. In distinct UBUC-derived cell lines, changes in TMCO1 levels altered the cell-cycle distribution, cell viability, cell proliferation, and colony formation and modulated the AKT pathway. TMCO1 recruited the PH domain and leucine-rich repeat protein phosphatase 2 (PHLPP2) to dephosphorylate pAKT1(serine 473) (S473). Mutagenesis at S60 of the TMCO1 protein released TMCO1-induced cell-cycle arrest and restored the AKT pathway in BFTC905 cells. Stable TMCO1 (wild-type) overexpression suppressed, whereas T33A and S60A mutants recovered, tumor size in xenograft mice.
Conclusions: Clinical associations, xenograft mice, and in vitro indications provide solid evidence that the TMCO1 gene is a novel tumor suppressor in UBUCs. TMCO1 dysregulates cell-cycle progression via suppression of the AKT pathway, and S60 of the TMCO1 protein is crucial for its tumor-suppressor roles. Clin Cancer Res; 23(24); 7650–63. ©2017 AACR.
A Complex Network of Tumor Microenvironment in Human High-Grade Serous Ovarian Cancer
Authors: Kreuzinger Caroline , Geroldinger Angelika , Smeets Dominiek , Braicu Elena Ioana , Sehouli Jalid , Koller Julia , Wolf Andrea , Darb-Esfahani Silvia , Joehrens Korinna , Vergote Ignace , Vanderstichele Adriaan , Boeckx Bram , Lambrechts Diether , Gabra Hani , Wisman G. Bea A. , Trillsch Fabian , Heinze Georg , Horvat Reinhard , Polterauer Stephan , Berns Els , Theillet Charles , Cacsire Castillo-Tong Dan 
Published: October 2017

Abstract
Purpose: Most high-grade serous ovarian cancer (HGSOC) patients develop recurrent disease after first-line treatment, frequently with fatal outcome. This work aims at studying the molecular biology of both primary and recurrent HGSOC.
Experimental Design: Gene expression profiles of matched primary and recurrent fresh-frozen tumor tissues from 66 HGSOC patients were obtained by RNA sequencing. Clustering analyses and pairwise comparison of the profiles between matched samples and subsequent functional alignment were used for the identification of molecular characteristics of HGSOC.
Results: Both primary and recurrent HGSOC samples presented predominant gene expression differences in their microenvironment, determined by a panel of genes covering all major pathways of immune activation together with a number of genes involved in the remodeling of extracellular matrix and adipose tissues. Stratifying tumor tissues into immune active and silent groups, we further discovered that although some recurrent tumors shared the same immune status as their primary counterparts, others switched the immune status, either from silent to active or active to silent. Interestingly, genes belonging to the B7-CD28 immune checkpoint family, known for their major role as negative regulators of the immune response, were overexpressed in the immune active tumors. Searching for potential tumor antigens, CEACAM21, a member of the carcinoembryonic antigen family, was found to be significantly overexpressed in immune active tissues in comparison with the silent ones.
Conclusions: The results illustrate the complexity of the tumor microenvironment in HGSOC and reveal the molecular relationship between primary and recurrent tumors, which have multiple therapeutic implications. Clin Cancer Res; 23(24); 7621–32. ©2017 AACR.
Downregulation of DNMT3A by miR-708-5p Inhibits Lung Cancer Stem Cell–like Phenotypes through Repressing Wnt/β-catenin Signaling
Authors: Liu Tianchi , Wu Xiaoping , Chen Tong , Luo Zewei , Hu Xiaohua 
Published: October 2017

Abstract
Purpose: Lung cancer is the leading cause of cancer-related death in the world, and emerging evidences suggest that lung cancer stem cells (CSC) are associated with its poor prognosis, tumor recurrence, and therapy resistance. Here we reveal a novel role for miR-708-5p in inhibiting lung CSC–like features.
Experimental Design: Phenotypic effects of miR-708-5p on the lung CSC–like properties were examined by in vitro sphere formation assay and in xenografted animal models. Immunoblotting, dual luciferase reporter, and immunocytochemistry were performed to determine the target of miR-708-5p. DNA methylation of CDH1 promoter region was tested using bisulfate sequencing. Genome-wide miRNA sequencing data of 990 patients from The Cancer Genome Atlas (TCGA) dataset and 148 patients from China cohort were analyzed to excavate the pathogenic implications of miR-708-5p.
Results: Expression of miR-708-5p inhibits the CSC traits of NSCLC cells in vitro while antagonizing miR-708-5p promotes tumorigenesis in vivo. miR-708-5p directly suppresses the translation of DNMT3A, which results in a substantial reduction of global DNA methylation and the upregulated expression of tumor suppressor CDH1. The upregulation of CDH1 decreased the activity of Wnt/β-catenin signaling and then impaired the stemness characteristics of NSCLC cells. Clinically, patients with high miR-708-5p expression show significantly better survival and lower recurrence. Furthermore, miR-708-5p has a promising potential to apply to differentiating histologic subtypes in NSCLC.
Conclusions: Our findings support that miR-708-5p suppresses NSCLC initiation, development, and stemness through interfering DNMT3A-dependent DNA methylation. miR-708-5p may function as a novel diagnostic and prognostic biomarker in NSCLC. Clin Cancer Res; 24(7); 1748–60. ©2017 AACR.
Gene Expression Signatures and Immunohistochemical Subtypes Add Prognostic Value to Each Other in Breast Cancer Cohorts
Authors: Lundberg Arian , Lindström Linda S. , Harrell J. Chuck , Falato Claudette , Carlson Joseph W. , Wright Paul K. , Foukakis Theodoros , Perou Charles M. , Czene Kamila , Bergh Jonas , Tobin Nicholas P. 
Published: October 2017

Abstract
Purpose: Gene signatures and Ki67 stratify the same breast tumor into opposing good/poor prognosis groups in approximately 20% of patients. Given this discrepancy, we hypothesized that the combination of a clinically relevant signature and IHC markers may provide more prognostic information than either classifier alone.
Experimental Design: We assessed Ki67 alone or combined with ER, PR and HER2 (forming IHC subtypes), and the research versions of the Genomic Grade Index, 70-gene, cell-cycle score, recurrence score (RS), and PAM50 signatures on matching TMA/whole tumor sections and microarray data in two Swedish breast cancer cohorts of 379 and 209 patients, with median follow-up of 12.4 and 12.5 years, respectively. First, we fit Cox proportional hazards models and used the change in likelihood ratio (Δ LR) to determine the additional prognostic information provided by signatures beyond that of (i) Ki67 and (ii) IHC subtypes. Second and uniquely, we then assessed whether signatures could compete well with pathology-based IHC classifiers by calculating the additional prognostic information of Ki67/IHC subtypes beyond signatures.
Results: In cohort 1, only RS and PAM50 provided additional prognostic information beyond Ki67 and IHC subtypes (Δ LR-χ2 Ki67: RS = 12.8, PAM50 = 20.7, IHC subtypes: RS = 12.9, PAM50 = 11.7). Conversely, IHC subtypes added prognostic information beyond all signatures except PAM50. Similar results were observed in cohort 2.
Conclusions: RS and PAM50 provided more prognostic information than the IHC subtypes in all breast cancer patients; however, the IHC subtypes did not add any prognostic information to PAM50. Clin Cancer Res; 23(24); 7512–20. ©2017 AACR.
Neuroblastoma Patients' KIR and KIR-Ligand Genotypes Influence Clinical Outcome for Dinutuximab-based Immunotherapy: A Report from the Children's Oncology Group
Authors: Erbe Amy K. , Wang Wei , Carmichael Lakeesha , Kim KyungMann , Mendonça Eneida A. , Song Yiqiang , Hess Dustin , Reville Patrick K. , London Wendy B. , Naranjo Arlene , Hank Jacquelyn A. , Diccianni Mitchell B. , Reisfeld Ralph A. , Gillies Stephen D. , Matthay Katherine K. , Cohn Susan L. , Hogarty Michael D. , Maris John M. , Park Julie R. , Ozkaynak M. Fevzi , Gilman Andrew L. , Yu Alice L. , Sondel Paul M. 
Published: October 2017

Abstract
Purpose: In 2010, a Children's Oncology Group (COG) phase III randomized trial for patients with high-risk neuroblastoma (ANBL0032) demonstrated improved event-free survival (EFS) and overall survival (OS) following treatment with an immunotherapy regimen of dinutuximab, GM-CSF, IL2, and isotretinoin compared with treatment with isotretinoin alone. Dinutuximab, a chimeric anti-GD2 monoclonal antibody, acts in part via natural killer (NK) cells. Killer immunoglobulin-like receptors (KIR) on NK cells and their interactions with KIR-ligands can influence NK cell function. We investigated whether KIR/KIR-ligand genotypes were associated with EFS or OS in this trial.
Experimental Design: We genotyped patients from COG study ANBL0032 and evaluated the effect of KIR/KIR-ligand genotypes on clinical outcomes. Cox regression models and log-rank tests were used to evaluate associations of EFS and OS with KIR/KIR-ligand genotypes.
Results: In this trial, patients with the “all KIR-ligands present” genotype as well as patients with inhibitory KIR2DL2 with its ligand (HLA-C1) together with inhibitory KIR3DL1 with its ligand (HLA-Bw4) were associated with improved outcome if they received immunotherapy. In contrast, for patients with the complementary KIR/KIR-ligand genotypes, clinical outcome was not significantly different for patients who received immunotherapy versus those receiving isotretinoin alone.
Conclusions: These data show that administration of immunotherapy is associated with improved outcome for neuroblastoma patients with certain KIR/KIR-ligand genotypes, although this was not seen for patients with other KIR/KIR-ligand genotypes. Further investigation of KIR/KIR-ligand genotypes may clarify their role in cancer immunotherapy and may enable KIR/KIR-ligand genotyping to be used prospectively for identifying patients likely to benefit from certain cancer immunotherapy regimens. Clin Cancer Res; 24(1); 189–96. ©2017 AACR.
See related commentary by Cheung and Hsu, p. 3