bluuebunny/crossref_metadata_2025 huggingface dataset:
Histone H3.3K27M Mobilizes Multiple Cancer/Testis (CT) Antigens in Pediatric Glioma
Authors: Deng Houliang , Zeng Jianming , Zhang Ting , Gong Longcai , Zhang Hongjie , Cheung Edwin , Jones Chris , Li Gang
Published: February 2018

Lysine to methionine mutations at position 27 (K27M) in the histone H3 (H3.3 and H3.1) are highly prevalent in pediatric high-grade gliomas (HGG) that arise in the midline of the central nervous system. H3K27M perturbs the activity of polycomb repressor complex 2 and correlates with DNA hypomethylation; however, the pathways whereby H3K27M drives the development of pediatric HGG remain poorly understood. To understand the mechanism of pediatric HGG development driven by H3.3K27M and discover potential therapeutic targets or biomarkers, we established pediatric glioma cell model systems harboring H3.3K27M and performed microarray analysis. H3.3K27M caused the upregulation of multiple cancer/testis (CT) antigens, such as ADAMTS1, ADAM23, SPANXA1, SPANXB1/2, IL13RA2, VCY, and VCX3A, in pediatric glioma cells. Chromatin immunoprecipitation analysis from H3.3K27M cells revealed decreased H3K27me3 levels and increased H3K4me3 levels on the VCX3A promoter. Knockdown of VCX3A by siRNA significantly inhibited the growth of pediatric glioma cells harboring H3.3K27M. Overexpression of VCX3A/B genes stimulated the expression of several HLA genes, including HLA-A, HLA-B, HLA-E, HLA-F, and HLA-G. The expression of VCX3A in pediatric HGG was confirmed using a tissue microarray. Gene set enrichment analysis revealed that CT antigens are enriched in pediatric HGG clinical specimens with H3.3K27M, with the upregulation of IL13RA2 contributing to the enrichment significantly. These results indicate that the upregulation of CT antigens, such as VCX3A and IL13RA2, correlates with pediatric gliomagenesis. Mol Cancer Res; 16(4); 623–33. ©2018 AACR.
AR Expression in Breast Cancer CTCs Associates with Bone Metastases
Authors: Aceto Nicola , Bardia Aditya , Wittner Ben S. , Donaldson Maria C. , O'Keefe Ryan , Engstrom Amanda , Bersani Francesca , Zheng Yu , Comaills Valentine , Niederhoffer Kira , Zhu Huili , Mackenzie Olivia , Shioda Toshi , Sgroi Dennis , Kapur Ravi , Ting David T. , Moy Beverly , Ramaswamy Sridhar , Toner Mehmet , Haber Daniel A. , Maheswaran Shyamala
Published: February 2018

Molecular drivers underlying bone metastases in human cancer are not well understood, in part due to constraints in bone tissue sampling. Here, RNA sequencing was performed of circulating tumor cells (CTC) isolated from blood samples of women with metastatic estrogen receptor (ER)+ breast cancer, comparing cases with progression in bone versus visceral organs. Among the activated cellular pathways in CTCs from bone-predominant breast cancer is androgen receptor (AR) signaling. AR gene expression is evident, as is its constitutively active splice variant AR-v7. AR expression within CTCs is correlated with the duration of treatment with aromatase inhibitors, suggesting that it contributes to acquired resistance to endocrine therapy. In an established breast cancer xenograft model, a bone-tropic derivative displays increased AR expression, whose genetic or pharmacologic suppression reduces metastases to bone but not to lungs. Together, these observations identify AR signaling in CTCs from women with bone-predominant ER+ breast cancer, and provide a rationale for testing androgen inhibitors in this subset of patients.

Implications: This study highlights a role for the AR in breast cancer bone metastasis, and suggests that therapeutic targeting of the AR may benefit patients with metastatic breast cancer. Mol Cancer Res; 16(4); 720–7. ©2018 AACR.
Leptin Signaling Mediates Obesity-Associated CSC Enrichment and EMT in Preclinical TNBC Models
Authors: Bowers Laura W. , Rossi Emily L. , McDonell Shannon B. , Doerstling Steven S. , Khatib Subreen A. , Lineberger Claire G. , Albright Jody E. , Tang Xiaohu , deGraffenried Linda A. , Hursting Stephen D.
Published: February 2018

Obesity is associated with poor prognosis in triple-negative breast cancer (TNBC). Preclinical models of TNBC were used to test the hypothesis that increased leptin signaling drives obesity-associated TNBC development by promoting cancer stem cell (CSC) enrichment and/or epithelial-to-mesenchymal transition (EMT). MMTV-Wnt-1 transgenic mice, which develop spontaneous basal-like, triple-negative mammary tumors, received either a control diet (10% kcal from fat) or a diet-induced obesity regimen (DIO, 60% kcal from fat) for up to 42 weeks (n = 15/group). Mice were monitored for tumor development and euthanized when tumor diameter reached 1.5 cm. Tumoral gene expression was assessed via RNA sequencing (RNA-seq). DIO mice had greater body weight and percent body fat at termination than controls. DIO mice, versus controls, demonstrated reduced survival, increased systemic metabolic and inflammatory perturbations, upregulated tumoral CSC/EMT gene signature, elevated tumoral aldehyde dehydrogenase activity (a CSC marker), and greater leptin signaling. In cell culture experiments using TNBC cells (murine: E-Wnt and M-Wnt; human: MDA-MB-231), leptin enhanced mammosphere formation, and media supplemented with serum from DIO versus control mice increased cell viability, migration, invasion, and CSC- and EMT-related gene expression, including Foxc2, Twist2, Vim, Akt3, and Sox2. In E-Wnt cells, knockdown of leptin receptor ablated these procancer effects induced by DIO mouse serum. These findings indicate that increased leptin signaling is causally linked to obesity-associated TNBC development by promoting CSC enrichment and EMT.

Implications: Leptin-associated signals impacting CSC and EMT may provide new targets and intervention strategies for decreasing TNBC burden in obese women. Mol Cancer Res; 16(5); 869–79. ©2018 AACR.
BRD1-Mediated Acetylation Promotes Integrin αV Gene Expression Via Interaction with Sulfatide
Authors: Cai Qian Qian , Dong Yi Wei , Qi Bing , Shao Xiao-Ting , Wang Rong , Chen Zhong Yi , He Bao Mei , Wu Xing Zhong
Published: February 2018

Integrin αV gene expression is often dysregulated in cancers especially in hepatocellular carcinoma (HCC); however, the mechanism of regulation is poorly understood. Here, it is demonstrated that sulfatide activated integrin αV gene transcription, through histone H3K9/14 acetylation at the promoter, and high integrin αV expression are closely associated with poor prognosis. To elucidate the mechanism of regulation of acetylation, sulfatide-bound proteins were screened by mass spectrometry (MS), and bromodomain containing protein 1 (BRD1) was identified as an interacting protein that also colocalized with sulfatide in HCC cells. BRD1 was also formed a complex with Sp1, which was recruited to the integrin αV gene promoter. Sulfatide was also found to induce BRD1, monocytic leukemia zinc finger (MOZ) and histone acetyltransferase binding to ORC1 (HBO1) acetyltransferase multiprotein complex recruitment to the integrin αV promoter, which is responsible for histone H3K9/14 acetylation. Finally, knockdown of BRD1 limited sulfatide-induced H3K9/14 acetylation and occupancy of MOZ or HBO1 on integrin αV gene promoter.

Implications: This study demonstrates that sulfatide interaction with BRD1 mediates acetylation and is important for regulation of integrin αV gene expression. Mol Cancer Res; 16(4); 610–22. ©2018 AACR.
Multigene Profiling of CTCs in mCRPC Identifies a Clinically Relevant Prognostic Signature
Authors: Singhal Udit , Wang Yugang , Henderson James , Niknafs Yashar S. , Qiao Yuanyuan , Gursky Amy , Zaslavsky Alexander , Chung Jae-Seung , Smith David C. , Karnes R. Jeffrey , Chang S. Laura , Feng Felix Y. , Palapattu Ganesh S. , Taichman Russell S. , Chinnaiyan Arul M. , Tomlins Scott A. , Morgan Todd M.
Published: February 2018

The trend toward precision-based therapeutic approaches dictated by molecular alterations offers substantial promise for men with metastatic castration-resistant prostate cancer (mCRPC). However, current approaches for molecular characterization are primarily tissue based, necessitating serial biopsies to understand changes over time and are limited by the challenges inherent to extracting genomic material from predominantly bone metastases. Therefore, a circulating tumor cell (CTC)-based assay was developed to determine gene expression across a panel of clinically relevant and potentially actionable prostate cancer–related genes. CTCs were isolated from the whole blood of mCRPC patients (n = 41) and multiplex qPCR was performed to evaluate expression of prostate cancer–related target genes (n = 78). A large fraction of patients (27/41, 66%) had detectable CTCs. Increased androgen receptor (AR) expression (70% of samples) and evidence of Wnt signaling (67% of samples) were observed. The TMPRSS2:ERG fusion was expressed in 41% of samples, and the aggressive prostate cancer–associated long noncoding RNA SChLAP1 was upregulated in 70%. WNT5a [HR 3.62, 95% confidence interval (CI), 1.63–8.05, P = 0.002], AURKA (HR 5.56, 95% CI, 1.79–17.20, P = 0.003), and BMP7 (HR 3.86, 95% CI, 1.60–9.32, P = 0.003) were independently predictive of overall survival (FDR < 10%) after adjusting for a panel of previously established prognostic variables in mCRPC (Halabi nomogram). A model including Halabi, WNT5a, and AURKA expression, termed the miCTC score, outperformed the Halabi nomogram alone (AUC = 0.89 vs. AUC = 0.70). Understanding the molecular landscape of CTCs has utility in predicting clinical outcomes in patients with aggressive prostate cancer and provides an additional tool in the arsenal of precision-based therapeutic approaches in oncology.

Implications: Analysis of CTC gene expression reveals a clinically prognostic “liquid biopsy” signature in patients with metastatic castrate-resistance prostate cancer. Mol Cancer Res; 16(4); 643–54. ©2018 AACR.
Inhibition of CD95/CD95L (FAS/FASLG) Signaling with APG101 Prevents Invasion and Enhances Radiation Therapy for Glioblastoma
Authors: Blaes Jonas , Thomé Carina M. , Pfenning Philipp-Niclas , Rübmann Petra , Sahm Felix , Wick Antje , Bunse Theresa , Schmenger Torsten , Sykora Jaromir , von Deimling Andreas , Wiestler Benedikt , Merz Christian , Jugold Manfred , Haberkorn Uwe , Abdollahi Amir , Debus Jürgen , Gieffers Christian , Kunz Claudia , Bendszus Martin , Kluge Michael , Platten Michael , Fricke Harald , Wick Wolfgang , Lemke Dieter
Published: February 2018

CD95 (Fas/APO-1), a death receptor family member, activity has been linked to tumorigenicity in multiple cancers, including glioblastoma multiforme (GBM). A phase II clinical trial on relapsed glioblastoma patients demonstrated that targeted inhibition of CD95 signaling via the CD95 ligand (CD95L) binding and neutralizing Fc-fusion protein APG101 (asunercept) prolonged patient survival. Although CD95 signaling may be relevant for multiple aspects of tumor growth, the mechanism of action of APG101 in glioblastoma is not clear. APG101 action was examined by in vitro proliferation, apoptosis, and invasion assays with human and murine glioma and human microglial cells, as well as in vivo therapy studies with orthotopic gliomas and clinical data. APG101 inhibits CD95L-mediated invasion of glioma cells. APG101 treatment was effective in glioma-bearing mice, independently of the presence or absence of CD4 and CD8 T lymphocytes, which should be sensitive to CD95L. Combined with radiotherapy, APG101 demonstrated a reduction of tumor growth, fewer tumor satellites, reduced activity of matrix metalloproteinases (MMP) as well as prolonged survival of tumor-bearing mice compared with radiotherapy alone. Inhibiting rather than inducing CD95 activity is a break-of-paradigm therapeutic approach for malignant gliomas. Evidence, both in vitro and in vivo, is provided that CD95L-binding fusion protein treatment enhanced the efficacy of radiotherapy and reduced unwanted proinfiltrative effects by reducing metalloproteinase activity by directly affecting the tumor cells.

Implications: APG101 (asunercept) successfully used in a controlled phase II glioblastoma trial (NCT01071837) acts anti-invasively by inhibiting matrix metalloproteinase signaling, resulting in additive effects together with radiotherapy and helping to further develop a treatment for this devastating disease. Mol Cancer Res; 16(5); 767–76. ©2018 AACR.
Distinct Chemopreventive Effects of Aspirin in Diffuse and Intestinal-Type Gastric Cancer
Authors: Niikura Ryota , Hayakawa Yoku , Hirata Yoshihiro , Konishi Mitsuru , Suzuki Nobumi , Ihara Sozaburo , Yamada Atsuo , Ushiku Tetsuo , Fujishiro Mitsuhiro , Fukayama Masashi , Koike Kazuhiko
Published: February 2018

Introduction: Although aspirin/NSAIDs may have potential preventive effects on several cancers, it remains unclear on gastric cancer. The purpose of this study is to compare the risk of developing gastric cancer and the histologic changes of intestinal metaplasia and neutrophil infiltration, between aspirin/NSAID users and nonusers.

Methods: Using an electronic endoscopy database in two hospitals from 1996 to 2017, we analyzed the data from patients with chronic gastritis who received aspirin or NSAIDs prior to upper gastrointestinal endoscopy. One-to-one propensity score matching was performed to compare the proportion of gastric cancer, intestinal metaplasia, and neutrophil infiltration between these drug users and nonusers.

Results: We analyzed 2,082 aspirin users and 2,082 nonusers as well as 898 NSAID users and 898 nonusers. Six diffuse-type and 19 intestinal-type gastric cancer, 1,243 intestinal metaplasia, and 1,503 neutrophil infiltration patients were identified. The proportion of diffuse-type gastric cancer (0.05%) was 80% lower in aspirin users compared with the nonusers (0.24%), and there was no case of diffuse-type cancer in patients who took aspirin for more than 2 years. In contrast, intestinal-type gastric cancer incidence was significantly higher in aspirin users (0.72%) compared with nonusers (0.14%). No significant differences in the incidence of gastric cancer were found between NSAID use and nonusers. NSAID use was significantly associated with decreased proportion of neutrophil infiltration compared with nonusers.

Conclusion: Aspirin may have distinct effects between intestinal-type and diffuse-type gastric cancer development. Cancer Prev Res; 11(5); 279–86. ©2018 AACR.
A Randomized Multicenter Phase II Study of Docosahexaenoic Acid in Patients with a History of Breast Cancer, Premalignant Lesions, or Benign Breast Disease
Authors: Gucalp Ayca , Zhou Xi K. , Cook Elise D. , Garber Judy E. , Crew Katherine D. , Nangia Julie R. , Bhardwaj Priya , Giri Dilip D. , Elemento Olivier , Verma Akanksha , Wang Hanhan , Lee J. Jack , Vornik Lana A. , Mays Carrie , Weber Diane , Sepeda Valerie , O'Kane Holly , Krasne Margaret , Williams Samantha , Morris Patrick G. , Heckman-Stoddard Brandy M. , Dunn Barbara K. , Hudis Clifford A. , Brown Powel H. , Dannenberg Andrew J.
Published: February 2018

Obesity, a cause of subclinical inflammation, is a risk factor for the development of postmenopausal breast cancer and is associated with poorer cancer outcomes. Docosahexaenoic acid (DHA), an omega-3 fatty acid, possesses anti-inflammatory properties. We hypothesized that treatment with DHA would reduce the expression of proinflammatory genes and aromatase, the rate-limiting enzyme for estrogen biosynthesis, in benign breast tissue of overweight/obese women. A randomized, placebo-controlled, double-blind phase II study of DHA given for 12 weeks to overweight/obese women with a history of stage I–III breast cancer, DCIS/LCIS, Paget's disease, or proliferative benign breast disease was carried out. In this placebo controlled trial, the primary objective was to determine whether DHA (1,000 mg by mouth twice daily) reduced breast tissue levels of TNFα. Secondary objectives included evaluation of the effect of DHA on breast tissue levels of COX-2, IL1β, aromatase, white adipose tissue inflammation, and gene expression by RNA-seq. Red blood cell fatty acid levels were measured to assess compliance. From July 2013 to November 2015, 64 participants were randomized and treated on trial (32 women per arm). Increased levels of omega-3 fatty acids in red blood cells were detected following treatment with DHA (P < 0.001) but not placebo. Treatment with DHA did not alter levels of TNFα (P = 0.71), or other biomarkers including the transcriptome in breast samples. Treatment with DHA was overall well-tolerated. Although compliance was confirmed, we did not observe changes in the levels of prespecified biomarkers in the breast after treatment with DHA when compared with placebo. Cancer Prev Res; 11(4); 203–14. ©2018 AACR.

See related editorial by Fabian and Kimler, p. 187
Long-Term Vitamin D Supplementation and the Effects on Recurrence and Metabolic Status of Cervical Intraepithelial Neoplasia Grade 2 or 3: A Randomized, Double-Blind, Placebo-Controlled Trial
Authors: Vahedpoor Zahra , Mahmoodi Samaneh , Samimi Mansooreh , Gilasi Hamid Reza , Bahmani Fereshteh , Soltani Ali , Sharifi Esfahani Mehran , Asemi Zatollah
Published: February 2018

Objective: This study was conducted to evaluate the effects of vitamin D supplementation on the recurrence and metabolic status of patients with cervical intraepithelial neoplasia grade 2 or 3 (CIN2/3). Methods: This randomized, double-blind, placebo-controlled trial was carried out among 58 women diagnosed with CIN2/3. Participants were randomly assigned into 2 groups to receive either 50,000 IU vitamin D3 (n = 29) or placebo (n = 29) every 2 weeks for 6 months. Results: The recurrence rate of CIN1/2/3 was 18.5 and 48.1% in the vitamin D and placebo groups respectively (p = 0.02). When we excluded CIN1, the recurrence rate of CIN2/3 became nonsignificant. Vitamin D supplementation significantly decreased fasting plasma glucose (–7.8 ± 9.2 vs. –1.1 ± 8.6 mg/dL, p = 0.006) and insulin levels (–3.2 ± 4.8 vs. –0.9 ± 3.4 µIU/mL, p = 0.03), and significantly increased quantitative insulin sensitivity check index (0.01 ± 0.02 vs. 0.002 ± 0.01, p = 0.02) compared with the placebo. Additionally, there was a significant decrease in high-sensitivity C-reactive protein (–815.3 ± 1,786.2 vs. 717.5 ± 1,827.3 ng/mL, p = 0.002) and a significant increase in total antioxidant capacity (113.4 ± 137.4 vs. –53.7 ± 186.7 mmol/L, p < 0.001) following the supplementation of vitamin D compared with the placebo. Conclusions: Vitamin D3 supplementation for 6 months among women with CIN2/3 had beneficial effects on CIN1/2/3 recurrence and metabolic status; however, it did not affect CIN2/3 recurrence.
The Importance of Excluding Cutaneous T-Cell Lymphomas in Patients with a Working Diagnosis of Papuloerythroderma of Ofuji: A Case Series
Authors: Maher Anthony M. , Ward Chloé E. , Glassman Steven , Litvinov Ivan V.
Published: February 2018

Papuloerythroderma of Ofuji (PEO) is an erythroderma-like eruption with flat-topped papules that spare the skin folds (a “deck-chair sign” finding). Many infections, medications, and systemic diseases have been associated with PEO, including cutaneous T-cell lymphomas (CTCL). The relationship between the clinical presentation of PEO and CTCL remains poorly elucidated. Clinical, laboratory, and histopathological data were obtained from the Lymphoma Clinic at the Ottawa Hospital, Canada. We report 5 patients with deck-chair-sign-positive CTCL, mycosis fungoides, and Sézary syndrome variants. We contend that PEO should be viewed as a diagnosis of exclusion and that these patients should be monitored carefully for possible emergence of CTCL. Skin biopsy alone is not sufficient to exclude CTCL in these patients. A skin eruption demonstrating a positive deck-chair sign may signify systemic/leukemic CTCL and, therefore, warrants a thorough investigation, including skin biopsy, flow cytometry, and T-cell receptor clonality studies.
Dialysate Creatinine Response Patterns During Peritoneal Equilibration Test and the Association Between Cardiovascular Mortality: Findings from a Prospective Cohort Study
Authors: Yu Dahai , Cai Yamei , Qin Rui , Tian Xing , Xiao Jing , Zhao Zhanzheng
Published: February 2018

Background/Aims: During peritoneal equilibrium test (PET), intermediate measures of Dt/P (dialysate/plasma creatinine ratio), D0/P, D2/P and D4/P ratios might provide additional information regarding a patient’s cardiovascular mortality. We aimed to characterise heterogeneity of dialysate creatinine response patterns based on three ratios and compare cardiovascular mortality risks by response patterns. Methods: 3,477 patients initialising peritoneal dialysis (PD) between 2007-2015 were measured D0/P, D2/P and D4/P at baseline and 2-year cardiovascular mortality was defined as the primary outcome. Latent class mixed-effect models were fitted to identify distinct patterns of dialysate creatinine response. Multivariable Logistic regression model with adjustment of cardiometabolic factors were used to compare cardiovascular mortality by latent classes. Results: The 1st latent class including 36% of participants was characterised by consistently increasing and high Dt/P ratios both at 2-hour and 4-hour. The 2nd class including 61% of participants characterised by sharply increased ratio at 2-hour and slightly increased ratio at 4-hour. The 3rd class included 3% of participants with decreased ratio at 2-hour and increased ratio at 4-hour. Comparing the 1st class, the lower cardiovascular mortality risk was identified in the 2nd and 3rd class with adjusted odds ratio 0.65 (95% confidence interval: 0.62-0.69) and 0.48 (0.41-0.57), respectively. Conclusion: Patients with decreased Dt/P ratio between 0-hour and 2-hour and low ratios at 2-hour and 4-hour tend to have low cardiovascular mortality. Latent class analysis seems to be a promising method to reveal unidentified subgroups that do not fit into the risk category defined by Dt/P ratio at 4-hour.
Down-Regulation of H3K4me3 by MM-102 Facilitates Epigenetic Reprogramming of Porcine Somatic Cell Nuclear Transfer Embryos
Authors: Zhang Zhiren , Zhai Yanhui , Ma Xiaoling , Zhang Sheng , An Xinglan , Yu Hao , Li Ziyi
Published: February 2018

Background/Aims: Aberrantly high levels of H3K4me3, caused by incomplete epigenetic reprogramming, likely cause a low efficiency of somatic cell nuclear transfer (SCNT). Smal molecule inhibitors aimed at epigenetic modification can be used to improve porcine SCNT embryo development. In this study, we examined the effects of MM-102, an H3K4 histone methyltransferase inhibitor, on porcine SCNT preimplantation embryos to investigate the mechanism by which H3K4 methylation regulated global epigenetic reprograming during SCNT. Methods: MM-102 was added to the SCNT embryos culture system and the global levels of various epigenetic modifications were measured by immunofluorescence (IF) staining and were quantified by Image J software. Relative genes expression levels were detected by quantitative real-time PCR. Results: MM-102 (75 μM) treatment reduced global H3K4, H3K9 methylation and 5mC levels especially at the zygotic gene activation (ZGA) and blastocyst stages. MM-102 treatment mainly down-regulated a series of DNA and histone methyltransferases, and up-regulated a number of hitone acetyltransferases and transcriptional activators. Furthermore, MM-102 treatment positively regulated the mRNA expression of genes related to pluripotency (OCT4, NANOG, CDX2) and apoptosis (BCL2). Conclusion: Down-regulation of H3K4me3 with MM-102 rescued aberrant gene expression patterns of a series of epigenetic chromatin modification enzymes, pluripotent and apoptotic genes at the ZGA and blastocyst stages, thereby greatly improving porcine SCNT efficiency and blastocyst quality, making them more similar to in vivo embryos (IVV).
Performance of the 2015 International Task Force Consensus Statement Risk Stratification Algorithm for Implantable Cardioverter-Defibrillator Placement in Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy
Authors: Orgeron Gabriela M. , te Riele Anneline , Tichnell Crystal , Wang Weijia , Murray Brittney , Bhonsale Aditya , Judge Daniel P. , Kamel Ihab R. , Zimmerman Stefan L. , Tandri Harikrishna , Calkins Hugh , James Cynthia A.
Published: February 2018

Background:

Ventricular arrhythmias are a feared complication of arrhythmogenic right ventricular dysplasia/cardiomyopathy. In 2015, an International Task Force Consensus Statement proposed a risk stratification algorithm for implantable cardioverter-defibrillator placement in arrhythmogenic right ventricular dysplasia/cardiomyopathy.

Methods and Results:

To evaluate performance of the algorithm, 365 arrhythmogenic right ventricular dysplasia/cardiomyopathy patients were classified as having a Class I, IIa, IIb, or III indication per the algorithm at baseline. Survival free from sustained ventricular arrhythmia (VT/VF) in follow-up was the primary outcome. Incidence of ventricular fibrillation/flutter cycle length <240 ms was also assessed. Two hundred twenty-four (61%) patients had a Class I implantable cardioverter-defibrillator indication; 80 (22%), Class IIa; 54 (15%), Class IIb; and 7 (2%), Class III. During a median 4.2 (interquartile range, 1.7–8.4)-year follow-up, 190 (52%) patients had VT/VF and 60 (16%) had ventricular fibrillation/flutter. Although the algorithm appropriately differentiated risk of VT/VF, incidence of VT/VF was underestimated (observed versus expected: 29.6 [95% confidence interval, 25.2–34.0] versus >10%/year Class I; 15.5 [confidence interval 11.1–21.6] versus 1% to 10%/year Class IIa). In addition, the algorithm did not differentiate survival free from ventricular fibrillation/flutter between Class I and IIa patients (
P
=0.97) or for VT/VF in Class I and IIa primary prevention patients (
P
=0.22). Adding Holter results (<1000 premature ventricular contractions/24 hours) to International Task Force Consensus classification differentiated risks.

Conclusions:

While the algorithm differentiates arrhythmic risk well overall, it did not distinguish ventricular fibrillation/flutter risks of patients with Class I and IIa implantable cardioverter-defibrillator indications. Limited differentiation was seen for primary prevention cases. As these are vital uncertainties in clinical decision-making, refinements to the algorithm are suggested prior to implementation.
Frequency and Outcomes of Reduced Dose Non–Vitamin K Antagonist Anticoagulants: Results From ORBIT‐AF II (The Outcomes Registry for Better Informed Treatment of Atrial Fibrillation II)
Authors: Steinberg Benjamin A. , Shrader Peter , Pieper Karen , Thomas Laine , Allen Larry A. , Ansell Jack , Chan Paul S. , Ezekowitz Michael D. , Fonarow Gregg C. , Freeman James V. , Gersh Bernard J. , Kowey Peter R. , Mahaffey Kenneth W. , Naccarelli Gerald V. , Reiffel James A. , Singer Daniel E. , Peterson Eric D. , Piccini Jonathan P. ,   the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT‐AF) II Investigators
Published: February 2018

Background

Non–vitamin K antagonist oral anticoagulants (NOACs) are indicated for stroke prevention in atrial fibrillation (AF) but require lower doses in certain patients. We sought to describe the frequency, appropriateness (according to Food and Drug Administration labeling), and outcomes of patients prescribed reduced doses of NOACs in community practice.

Methods and Results

We analyzed data from the ORBIT‐AF II (The Outcomes Registry for Better Informed Treatment of Atrial Fibrillation II) registry, a prospective, national, observational registry of AF patients. Among 7925 AF patients receiving NOACs, we assessed patterns of use of reduced NOAC doses and associated cardiovascular and bleeding outcomes at median follow‐up of 1 year. Overall, 6636 patients (84%) received a NOAC at standard dose, which was consistent with US Food and Drug Administration labeling in 6376 (96%). Reduced NOAC dose was prescribed to 1289 (16% overall), which was consistent with Food and Drug Administration labeling in only 555 patients (43%). Compared with those whose NOAC dose was appropriately reduced, patients receiving inappropriate dose reductions were younger (median age 79 versus 84,
P
<0.0001) and had lower ORBIT bleeding risk scores (26% ≥4 versus 45%,
P
<0.0001). Compared with those appropriately receiving standard dosing, patients receiving inappropriately reduced‐dose NOACs had higher unadjusted rates of thromboembolic events (2.11 versus 1.35 events per 100 patient years, hazard ratio 1.56, 95% confidence interval 0.92‐2.67) and death (6.77 versus 2.60, hazard ratio 2.61, 95% confidence interval 1.86‐3.67). After adjustment, outcomes were not significantly different but tended to favor patients dosed appropriately.

Conclusions

The majority of dose reductions of NOACs in AF are inconsistent with US Food and Drug Administration recommendations. There appear to be opportunities to improve current NOAC dosing in community practice.

Clinical Trial Registration

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01701817.
Explication Work for Science and Philosophy
Authors: Schickore Jutta
Published: February 2018

This article disentangles the various assumptions and expectations tied to case studies, to testing philosophy through cases, and to historical adequacy. Several notions of historical adequacy are distinguished: 1) adequacy to the standards of professional history of science, 2) historical accuracy, i.e. capturing the historical record, 3) relevance of historical episodes to the epistemic interests of philosophers of science, and 4) withstanding tests by historical cases. I argue that philosophers’ preoccupation with historical adequacy is misplaced if we understand “historical adequacy” as adequacy to professional history of science, capturing the historical record, a path to philosophical discovery, or as a test. In the last part of the article, I identify two important roles for philosophically informed studies of science: case studies of current issues can do explication work for the sciences. Tracing the history of philosophical reflections in past science can do explication work in the service of philosophy. Both kinds of endeavors are worthwhile but have very different goals and should not be conflated.
Evaluation of Franz Marc’s Color Theory using Implicit Testing Procedures
Authors: Grotjohann Annika , Oberfeld Daniel
Published: February 2018

In the early 20th century, the German expressionist painter Franz Marc formulated assumptions concerning the meanings of color, based on his individual sensations. He characterized the ‘cool’ blue as the ‘masculine principle’. Yellow represented the ‘feminine principle’ which he declared as ‘gentle, cheerful, and sensual’. This leaves red, the color he perceived as ‘brutal and heavy’. Here, we tested some of the color–meaning associations assumed by Franz Marc via implicit measures based on response times, using Single Category Implicit Association Tests. The participants had to classify words as belonging to one of two semantic categories (e.g., masculine or feminine) by pressing one of two response buttons. One of the semantic categories shared a response button with a hue (e.g., masculine–blue), and this button needed to be pressed whenever a color patch was presented on the screen. The results showed that response times were faster when related hues and meaning categories (according to Marc’s assumptions) shared the same response button, compared to when unrelated hues and meaning categories were assigned to the same button. The pattern of response times was compatible with the associations of blue–masculine, yellow–feminine, blue–cool and yellow–gentle as proposed by Marc. In addition, our data indicate associations of yellow–warm and red–warm, which were not explicitly formulated by Franz Marc. However, the proposed red–brutal association was not confirmed.
A review of the deepwater cardinalfish genus Epigonus (Perciformes: Epigonidae) of the Western Indian Ocean, with description of two new species
Authors: OKAMOTO MAKOTO , GON OFER
Published: February 2018

The fishes of the genus Epigonus Rafinesque, 1810 in the Western Indian Ocean (including the Red Sea and the Gulf of Aden) are reviewed. Twelve species of the genus are recognized: Epigonus angustifrons Abramov & Manilo, 1987; E. denticulatus Dieuzeide, 1950; E. elongatus Parin & Abramov, 1986; E. exodon Okamoto & Motomura, 2012; E. lenimen (Whitley, 1935); E. macrops (Brauer, 1906); E. marimonticolus Parin & Abramov, 1986; E. marisrubri Krupp, Zajonz & Khalaf, 2009; E. pectinifer Mayer, 1974; E. robustus (Barnard, 1927); E. telescopus (Risso, 1810); E. waltersensis Parin & Abramov, 1986, and two new species, E. bispinosus n. sp. and E. idai n. sp. Epigonus bispinosus and E. idai belong to the E. constanciae group, defined as having a pungent opercular spine, more than 45 pored lateral-line scales, and lacking an isolated dorsal fin spine between the first- and second dorsal fins. Epigonus bispinosus differs from other members of the group in having two small spines on the symphysis of lower jaw, a pair of ribs on the last abdominal vertebra, 10 + 15 vertebrae, 31–33 gill rakers and lacking a maxillary mustache-like process. Epigonus idai differs from other members of the group in having a pair of ribs on the last abdominal vertebra, 4–5 tiny projections present on symphysis of lower jaw, 10 + 15 vertebrae, strongly ctenoid scales, and 28–29 gill rakers, and in lacking a maxillary mustache-like process. A key to the species, photographs, diagnoses, and distributions in the Western Indian Ocean are given.
New species of Pseudosinella Schäffer, 1897 (Collembola, Entomobryidae) from Hungary
Authors: WINKLER DANIEL , MATEOS EDUARDO
Published: February 2018

Two new species of the genus Pseudosinella Schäffer, 1897 from Hungary are described and illustrated. Characters shared by both species are the number of eyes (0+0), the labial chaetotaxy (M1M2rEL1L2) and the chaetotaxy of abdominal segment II (pABq1q2). P. csafordi sp. nov., characterized by dorsal macrochaetae formula R0R1R2R3TP/32/0201+2s, inhabits alluvial forests, while P. dungeri sp. nov., characterized by dorsal macrochaetae formula R0R1sR1R2TP/10/0201+2, was collected from a mid-montain steppic grassland.
Zabójcza sympatia: O książce Jodi Melamed "Represent and destroy: Rationalizing violence in a new racial capitalism" [Killing symphathy: About Jodi Melamed’s "Represent and destroy: Rationalizing violence in a new racial capitalism"]
Authors: Zawadzka Anna
Published: February 2018

Killing symphathy: About Jodi Melamed’s Represent and destroy: Rationalizing violence in a new racial capitalismThis article discusses the book Represent and destroy: Rationalizing violence in a new racial capitalism by Jodi Melamed. The author of the book identifies and describes three different theories of race, all officially antiracist, which over the last seventy years successively enjoyed dominant status in the United States, meaning that they have been produced and reproduced by state institutions and initiatives. The three theories are racial liberalism, liberal multiculturalism and neoliberal multiculturalism. Jodi Melamed argues that their purpose was, first and foremost, to legitimize the capitalist exploitation of colored people, both locally and globally. As Melamed examines the critical attitudes to the dominant approach to race in the USA, and how their polemical potential has been contained, she demonstrates how post-war antiracist ideologies have limited the understanding of racism and provided the foundations for and normalized new forms of racialized violence. Zabójcza sympatia: O książce Jodi Melamed Represent and destroy: Rationalizing violence in a new racial capitalismArtykuł stanowi omówienie książki Jodi Melamed Represent and destroy: Rationalizing violence in a new racial capitalism. W książce tej autorka wyodrębnia i opisuje trzy kolejne ideologie związane z rasą – wszystkie oficjalnie antyrasistowskie – które na przestrzeni ostatnich 70 lat miały w Stanach Zjednoczonych status dominujących, to znaczy były wytwarzane i reprodukowane przez instytucje i inicjatywy państwowe: rasowy liberalizm, liberalny multikulturalizm i neoliberalny multikulturalizm. Jodi Melamed dowodzi, że ideologie te służyły przede wszystkim legitymizacji kapitalistycznego wyzysku osób kolorowych, zarówno w skali lokalnej, jak i globalnej. Śledząc dzieje narracji krytycznych wobec dominującego rozumienia rasy w USA oraz sposoby wygaszania ich polemicznego potencjału, Melamed pokazuje, jak powojenne ideologie antyrasistowskie nie tylko ograniczyły rozumienie rasizmu, ale ufundowały i znormalizowały nowe formy urasowionej przemocy.
Komentarz do artykułu „Dla kogo i o czym? Muzeum Polin, historiografia Żydów a Żydzi jako «sprawa polska»” Kamila Kijka [Commentary on the article “For whom and about what? The Polin Museum, Jewish historiography and Jews as a 'Polish cause'” by Kamil Kijek]
Authors: Stoll Katrin
Published: February 2018

Commentary on the article For whom and about what? The Polin Museum, Jewish historiography and Jews as a “Polish cause” by Kamil KijekThe text is a short commentary on the article For whom and about what? The Polin Museum, Jewish historiography and Jews as a “Polish cause” by Kamil Kijek, reconstructing and deconstructing the author’s argument. Komentarz do artykułu Dla kogo i o czym? Muzeum Polin, historiografia Żydów a Żydzi jako "sprawa polska” Kamila KijkaTekst jest krótkim komentarzem do artykułu Dla kogo i o czym? Muzeum Polin, historiografia Żydów a Żydzi jako „sprawa polska” Kamila Kijka, rekonstruującym i dekonstruującym argumenty autora.
Klasa, etniczność i państwo w procesie tworzenia marginalności: Ponowne spojrzenie na obszary miejskiej relegacji
Authors: Wacquant Loïc
Published: February 2018

Class, ethnicity, and state in the making of marginality: Revisiting territories of urban relegationIn the postindustrial city, relegation takes the form of real or imaginary consignment to distinctive sociospatial formations variously and vaguely referred to as “inner cities,” “ghettos,” “enclaves,” “no-go areas,” “problem districts,” or simply “rough neighborhoods.” How are we characterize and differentiate these spaces, what determines their trajectory (birth, growth, decay and death), whence comes the intense stigma attached to them, and what constellations of class, ethnicity and state do they both materialize and signify? These are the questions I pursued in my book “Urban outcasts” (2008) through a methodical comparison of the trajectories of the black American ghetto and the European working-class peripheries in the era of neoliberal ascendancy. In this article, I revisit this cross-continental sociology of “advanced marginality” to tease out its broader lessons for our understanding of the tangled nexus of symbolic, social and physical space in the polarizing metropolis at century’s threshold in particular, and for bringing the core principles of Bourdieu’s sociology to bear on comparative urban studies in general. Klasa, etniczność i państwo w procesie tworzenia marginalności: Ponowne spojrzenie na obszary miejskiej relegacjiW mieście epoki postprzemysłowej relegacja przybiera formę realnego lub wyobrażonego przypisania do odrębnych formacji społeczno-przestrzennych, na różne sposoby i niezbyt precyzyjnie określanych jako „śródmieścia” (inner cities), „getta”, „enklawy”, „rejony niebezpieczne” (no-go areas), „dzielnice stwarzające problemy” (problem districts) czy po prostu „nieprzyjemne dzielnice” (rough neighborhoods). W jaki sposób opisujemy i odróżniamy owe przestrzenie, co określa ich trajektorię (powstanie, rozwój, upadek i zanik), skąd wzięło się silne symboliczne piętno nadane im na przełomie stuleci, a także jakiego rodzaju powiązania między klasowością, etnicznością i państwem znajdują w nich materialny oraz znaczeniowy wyraz? Kwestie te podejmuję w książce "Urban outcasts" [Miejscy wyrzutkowie] (2008), w której metodycznie porównuję trajektorie amerykańskiego czarnego getta i europejskich peryferii robotniczych w czasach panowania neoliberalizmu. W niniejszym artykule powracam do tej międzykontynentalnej socjologii „zaawansowanej marginalności”, mając na celu odsłonięcie płynących z niej wniosków dla lepszego zrozumienia skomplikowanych powiązań przestrzeni symbolicznej, społecznej i fizycznej w obrębie polaryzującej metropolii na przełomie stuleci oraz, ogólniej, zastosowanie podstawowych zasad socjologii Pierre’a Bourdieu do badań porównawczych nad obszarami miejskimi.
Kim, czym, kiedy, gdzie i dlaczego są polscy Żydzi? Wyobrażanie, konstruowanie i zawłaszczanie Żydów polskich
Authors: Ury Scott
Published: February 2018

Who, what, when, where, and why is Polish Jewry? Envisioning, constructing, and possessing Polish JewryThis article examines the different ways that various communities of scholars imagine, research and teach about “Polish Jewry.” Focusing on scholarship written in Israel, Poland and the United States over the past generation or two, the article argues that each particular community of scholars constructs a particular version of Polish Jewry and that each of these versions is deeply influenced by contemporary social, political and communal needs and demands. As a result, scholars very often end up constructing radically different versions of Polish Jewish history and society. These scholarly differences reflect many of the challenges and difficulties related to researching and writing about the history and culture of Polish Jews since 1989. Kim, czym, kiedy, gdzie i dlaczego są polscy Żydzi? Wyobrażanie, konstruowanie i zawłaszczanie Żydów polskichArtykuł stanowi omówienie odmiennych sposobów, jakimi różne społeczności badaczy wyobrażają grupę polskich Żydów, badają ją i nauczają o niej. Na podstawie analizy działalności naukowej badaczy z Izraela, Polski i Stanów Zjednoczonych ostatnich dwóch pokoleń autor pokazuje, że każda społeczność badaczy konstruuje własny, specyficzny obraz grupy zwanej „polskimi Żydami” i że obrazy te pozostają pod przemożnym wpływem współczesnych potrzeb i wymogów o naturze społecznej, politycznej i wspólnotowej. Na skutek tych różnic uczeni tworzą często radykalnie odmienne obrazy historii i społeczeństwa polskich Żydów. Różnice stanowią odzwierciedlenie przeszkód i utrudnień, jakie po 1989 roku wiążą się z badaniem i opisywaniem historii i kultury polskich Żydów.
When Consent Does Not Help
Authors: Stohl Hindi E.
Published: February 2018

Pregnant women with a prior cesarean delivery face challenges in accessing a vaginal birth due to both hospital and provider preferences and practices. Although the doctrine of informed consent secures women's reproductive rights, it is not a viable legal remedy. Instead, women should champion increased maternity-related education and transparency as well as medical malpractice reform to increase the desired access.
A review on effect of thinning, wrinkling and spring-back on deep drawing process
Authors: Atul S Takalkar , Babu M C Lenin
Published: February 2018

There are various processes practiced in a market for manufacturing axisymmetrical cup with significant forming depth among which deep drawing process is most prompt. The deep drawing process is a forming process with ongoing interest which will have a major impact on industries in coming years. This article focuses on the current status and potential of future development of technology in the deep drawing process. First, it describes various types of approaches and techniques used in the deep drawing of different materials. This is followed by brief reviews of advantages and limitations of these technologies with its application in industries. The details of these technologies are just referred rather than explaining in detail. The further part of this article focuses on advanced methods for predicting defects like thinning, wrinkling and spring-back in deep drawing process which are mostly responsible for rejection of the components. The opportunity in the development of flexibility in deep drawing process is covered with an observed barrier in the prediction of defects such as thinning, wrinkling and spring-back. The obtained evidence indicates that deep drawing process may not be applicable for all materials, but represents an excellent opportunity in the drawing of multilayer metal and composite material sheets to complex shapes.
Collaborative control of a dual electro-hydraulic regenerative brake system for a rear-wheel-drive electric vehicle
Authors: Nadeau Jonathan , Micheau Philippe , Boisvert Maxime
Published: February 2018

Within the field of electric vehicles, the cooperative control of a dual electro-hydraulic regenerative brake system using the foot brake pedal as the sole input of driver brake requests is a challenging control problem, especially when the electro-hydraulic brake system features on/off solenoid valves which are widely used in the automotive industry. This type of hydraulic actuator is hard to use to perform a fine brake pressure regulation. Thus, this paper focuses on the implementation of a novel controller design for a dual electro-hydraulic regenerative brake system featuring on/off solenoid valves which track an “ideal” brake force distribution. As an improvement to a standard brake force distribution, it can provide the reach of the maximum braking adherence and can improve the energy recovery of a rear-wheel-drive electric vehicle. This improvement in energy recovery is possible with the complete substitution of the rear hydraulic brake force with a regenerative brake force until the reach of the electric powertrain constraints. It is done by performing a proper brake pressure fine regulation through the proposed variable structure control of the on/off solenoid valves provided by the hydraulic platform of the vehicle stability system. Through road tests, the tracking feasibility of the proposed brake force distribution with the mechatronic system developed is validated.
Normalized amplitude of channel state information: The robust parameter for indoor localization in wireless sensor networks
Authors: Wang Yan , Li Min , Bai Lin , Fu Tielian , Gao Fengyue
Published: February 2018

Location information plays a remarkable role in wireless sensor networks in collecting information to support distributed spectrum sensing and directional wireless charging. To decide the optimal operating frequency band of wireless sensor network, the location information of the wireless sensor network nodes should be known to fulfill the geographical map of the spectrum using the technique of distributed spectrum sensing. In addition, wireless charging also needs the location information of the wireless sensor network node for the directional wireless charging is much more efficient than the omnidirectional wireless charging. The location of the wireless sensor network node is estimated by Wi-Fi signal because the Wi-Fi infrastructures are widely deployed not only for Internet wireless access but also for the communication between wireless sensor network nodes. The most of our daily life is spent in the indoor environment, and the channel state information is one of the most important parameters of fingerprint in indoor localization. The channel state information is not a constant parameter for various timing synchronization and frequency offset even in the same location; therefore, a new parameter—normalized amplitude of channel state information—is proposed to be a robust parameter, which is insensitive to timing synchronization and frequency offset. In this article, we first formulate the received signal in a multipath channel by taking timing synchronization and frequency offset into consideration, then we derive the closed-form expression of channel state information, and propose the new parameter—normalized amplitude of channel state information. Finally, the robustness of the new parameter is verified by numerical simulations.