bluuebunny/crossref_metadata_2025 huggingface dataset:
Chinese Unknown Word Recognition for PCFG-LA Parsing
Authors: Huang Qiuping , He Liangye , Wong Derek F. , Chao Lidia S.
Published: April 2014

This paper investigates the recognition of unknown words in Chinese parsing. Two methods are proposed to handle this problem. One is the modification of a character-based model. We model the emission probability of an unknown word using the first and last characters in the word. It aims to reduce the POS tag ambiguities of unknown words to improve the parsing performance. In addition, a novel method, using graph-based semisupervised learning (SSL), is proposed to improve the syntax parsing of unknown words. Its goal is to discover additional lexical knowledge from a large amount of unlabeled data to help the syntax parsing. The method is mainly to propagate lexical emission probabilities to unknown words by building the similarity graphs over the words of labeled and unlabeled data. The derived distributions are incorporated into the parsing process. The proposed methods are effective in dealing with the unknown words to improve the parsing. Empirical results for Penn Chinese Treebank and TCT Treebank revealed its effectiveness.
A Two‐Dimensional Generalized Electromagnetothermoelastic Diffusion Problem for a Rotating Half‐Space
Authors: Zhang Jingrui , Li Yanyan
Published: April 2014

In the context of the theory of generalized thermoelastic diffusion, a two‐dimensional generalized electromagnetothermoelastic problem with diffusion for a rotating half‐space is investigated. The rotating half‐space is placed in an external magnetic field with constant intensity and its bounding surface is subjected to a thermal shock and a chemical potential shock. The problem is formulated based on finite element method and the derived finite element equations are solved directly in time domain. The nondimensional temperature, displacement, stress, chemical potential, concentration, and induced magnetic field are obtained and illustrated graphically. The results show that all the considered variables have a nonzero value only in a bounded region and vanish identically outside this region, which fully demonstrates the nature of the finite speeds of thermoelastic wave and diffusive wave.
Repeat FNA Significantly Lowers Number of False Negative Results in Patients with Benign Nodular Thyroid Disease and Features of Chronic Thyroiditis
Authors: Słowińska-Klencka Dorota , Woźniak-Oseła Ewa , Popowicz Bożena , Sporny Stanisław , Klencki Mariusz
Published: April 2014

Purpose. The aim of the study was to compare the risk of thyroid malignancy and efficacy of repeat FNA in patients with thyroid nodules diagnosed cytologically as benign lesion (BL) with features of chronic thyroiditis (BL-CT) and BL without CT features (BL-nCT).Methods. The analysis included 917 patients with BL-CT and 7046 with BL-nCT in the first FNA. Repeat biopsy was carried out in 787 patients of BL-CT and 5147 of BL-nCT; 218 patients of BL-CT and 2462 of BL-nCT were operated; in 88 cases of BL-CT and 563 of BL-nCT both ways of follow-up were available.Results. Outcome of repeat cytology implied surgery more frequently in patients with BL-CT than with BL-nCT—3.2% versus 1.9%,P< 0.05. Incidence of cancer (including incidentalomas) was higher in patients with BL-CT operated after one benign cytology than in patients with two benign FNA outcomes: 10.8% versus 1.6%,P< 0.05. In patients with BL-nCT that difference was not significant: 3.2% versus 2.6%.Conclusions. Patients with thyroid nodules diagnosed as BL with CT features have higher risk of malignancy than patients with BL without CT features. Repeat biopsy significantly lowers percentage of FN results in patients with BL-CT in the first FNA.
Evaluation of Novel Design Strategies for Developing Zinc Finger Nucleases Tools for Treating Human Diseases
Authors: Bach Christian , Sherman William , Pallis Jani , Patra Prabir , Bajwa Hassan
Published: April 2014

Zinc finger nucleases (ZFNs) are associated with cell death and apoptosis by binding at countless undesired locations. This cytotoxicity is associated with the binding ability of engineered zinc finger domains to bind dissimilar DNA sequences with high affinity. In general, binding preferences of transcription factors are associated with significant degenerated diversity and complexity which convolutes the design and engineering of precise DNA binding domains. Evolutionary success of natural zinc finger proteins, however, evinces that nature created specific evolutionary traits and strategies, such as modularity and rank-specific recognition to cope with binding complexity that are critical for creating clinical viable tools to precisely modify the human genome. Our findings indicate preservation of general modularity and significant alteration of the rank-specific binding preferences of the three-finger binding domain of transcription factor SP1 when exchanging amino acids in the 2nd finger.
Growth of Anodic Aluminum Oxide Templates and the Application in Fabrication of the BiSbTe-Based Thermoelectric Nanowires
Authors: Kuo Chin-Guo , Hsieh Yuan-Tai , Yang Cheng-Fu , Huang Ching-Ho , Yen Chia-Ying
Published: April 2014

A two-step electrochemical anodization was used to form the anodic aluminum oxide (AAO) thin films with nanotube arrays of self-organized honeycomb structure. Al foil was anodized in 10% sulfuric acid (H2SO4) and 3% oxalic acid (H2C2O4) at 25°C at constant voltage of 40 V for 60 min for two times. Ethylene glycol (C2H6O2) was used as a solution and 0.3 M potassium iodide (KI) was used to improve the solution’s conductivity. Different electrolyte concentrations of Bi(NO3)3-5H2O, SbCl3, and TeCl4were added into KI-C2H6O2solution and the cyclic voltammetry experiment was used to find the reduced voltages of Bi3+, Sb3+, and Te4+ions. The potentiostatic deposition and pulse electrodeposition (PED) processes were used to deposit the (Bi,Sb)2−xTe3+x-based materials. Field-emission scanning electron microscope and energy dispersive spectrometers were used to analyze the compositions of the deposited (Bi,Sb)2−xTe3+x-based materials. After finding the optimal deposition parameter of the PED process the AAO nanotube arrays were used as the templates to deposit the (Bi,Sb)2−xTe3+x-based thermoelectric nanowires.
Fatty Acid-Binding Protein E-FABP Restricts Tumor Growth by Promoting IFN-β Responses in Tumor-Associated Macrophages
Authors: Zhang Yuwen , Sun Yanwen , Rao Enyu , Yan Fei , Li Qiang , Zhang Ying , Silverstein Kevin A.T. , Liu Shujun , Sauter Edward , Cleary Margot P. , Li Bing
Published: April 2014

Fatty acid-binding proteins (FABP) are known central regulators of both metabolic and inflammatory pathways, but their role in tumor development remains largely unexplored. Here, we report that host expression of epidermal FABP (E-FABP) protects against mammary tumor growth. We find that E-FABP is highly expressed in macrophages, particularly in a specific subset, promoting their antitumor activity. In the tumor stroma, E-FABP–expressing tumor-associated macrophages (TAM) produce high levels of IFN-β through upregulation of lipid droplet formation in response to tumors. E-FABP–mediated IFN-β signaling can further enhance recruitment of tumoricidal effector cells, in particular natural killer cells, to the tumor stroma for antitumor activity. These findings identify E-FABP as a new protective factor to strengthen IFN-β responses against tumor growth. Cancer Res; 74(11); 2986–98. ©2014 AACR.
Global Transcriptome Analysis of Formalin-Fixed Prostate Cancer Specimens Identifies Biomarkers of Disease Recurrence
Authors: Long Qi , Xu Jianpeng , Osunkoya Adeboye O. , Sannigrahi Soma , Johnson Brent A. , Zhou Wei , Gillespie Theresa , Park Jong Y. , Nam Robert K. , Sugar Linda , Stanimirovic Aleksandra , Seth Arun K. , Petros John A. , Moreno Carlos S.
Published: April 2014

Prostate cancer remains the second leading cause of cancer death in American men and there is an unmet need for biomarkers to identify patients with aggressive disease. In an effort to identify biomarkers of recurrence, we performed global RNA sequencing on 106 formalin-fixed, paraffin-embedded prostatectomy samples from 100 patients at three independent sites, defining a 24-gene signature panel. The 24 genes in this panel function in cell-cycle progression, angiogenesis, hypoxia, apoptosis, PI3K signaling, steroid metabolism, translation, chromatin modification, and transcription. Sixteen genes have been associated with cancer, with five specifically associated with prostate cancer (BTG2, IGFBP3, SIRT1, MXI1, and FDPS). Validation was performed on an independent publicly available dataset of 140 patients, where the new signature panel outperformed markers published previously in terms of predicting biochemical recurrence. Our work also identified differences in gene expression between Gleason pattern 4 + 3 and 3 + 4 tumors, including several genes involved in the epithelial-to-mesenchymal transition and developmental pathways. Overall, this study defines a novel biomarker panel that has the potential to improve the clinical management of prostate cancer. Cancer Res; 74(12); 3228–37. ©2014 AACR.
Molecular Pathways: Can Activin-like Kinase Pathway Inhibition Enhance the Limited Efficacy of VEGF Inhibitors?
Authors: Bhatt Rupal S. , Atkins Michael B.
Published: April 2014

The vascular endothelial growth factor (VEGF) pathway is critical for tumor angiogenesis. However, VEGF pathway inhibition has been limited by intrinsic and acquired resistance. Simultaneously targeting multiple steps involved in tumor angiogenesis is a potential means of overcoming this resistance. Activin like kinase 1 (ALK1) and endoglin (ENG) have effects on angiogenesis that are distinct from those of VEGF. Whereas VEGF is important for vessel initiation, ALK1 and endoglin are involved in vessel network formation. Thus, ALK1 and endoglin pathway inhibitors are attractive partners for VEGF-based combination antiangiogenic therapy. Genetic evidence supports a role for this receptor family and its ligands, bone morphogenetic proteins (BMP) 9 and 10, in vascular development. Patients with genetic alterations in ALK1 or endoglin develop hereditary hemorrhagic telangiectasia, a disorder characterized by abnormal vessel development. There are several inhibitors of the ALK1 pathway advancing in clinical development for treatment of various tumor types, including renal cell and ovarian carcinomas. Targeting of alternate angiogenic pathways, particularly in combination with VEGF pathway blockade, holds the promise of optimally inhibiting angiogenically driven tumor progression. Clin Cancer Res; 20(11); 2838–45. ©2014 AACR.
Impact of Initial FDG-PET/CT and Serum-Free Light Chain on Transformation of Conventionally Defined Solitary Plasmacytoma to Multiple Myeloma
Authors: Fouquet Guillemette , Guidez Stéphanie , Herbaux Charles , Van de Wyngaert Zoé , Bonnet Sarah , Beauvais David , Demarquette Hélène , Adib Salim , Hivert Bénédicte , Wemeau Mathieu , Berthon Céline , Terriou Louis , Coiteux Valérie , Macro Margaret , Decaux Olivier , Facon Thierry , Huglo Damien , Leleu Xavier
Published: April 2014

Purpose: Solitary plasmacytoma (SP) is a localized proliferation of monoclonal plasma cells in either bone or soft tissue, without evidence of multiple myeloma (MM), and whose prognosis is marked by a high risk of transformation to MM.

Experimental Design: We studied the impact of FDG-PET/CT (2[18F]fluoro-2-deoxy-D-glucose positron emission tomography–computed tomography) on the risk of transformation of SP to overt MM among other markers in a series of 43 patients diagnosed with SP.

Results: Median age was 57.5 years; 48% of patients had an abnormal involved serum-free light chain (sFLC) value, and 64% had an abnormal sFLC ratio at diagnosis. Thirty-three percent had two or more hypermetabolic lesions on initial PET/CT, and 20% had two or more focal lesions on initial MRI. With a median follow-up of 50 months, 14 patients transformed to MM with a median time (TTMM) of 71 months. The risk factors that significantly shortened TTMM at diagnosis were two or more hypermetabolic lesions on PET/CT, abnormal sFLC ratio and involved sFLC, and to a lesser extent at completion of treatment, absence of normalized involved sFLC and PET/CT or MRI. In a multivariate analysis, abnormal initial involved sFLC [OR = 10; 95% confidence interval (CI), 1–87; P = 0.008] and PET/CT (OR = 5; 95% CI, 0–9; P = 0.032) independently shortened TTMM.

Conclusions: An abnormal involved sFLC value and the presence of at least two hypermetabolic lesions on PET/CT at diagnosis of SP were the two predictors of early evolution to myeloma in our series. This data analysis will need confirmation in a larger study, and the study of these two risk factors may lead to a different management of patients with SP in the future. Clin Cancer Res; 20(12); 3254–60. ©2014 AACR.
Association of PD-1, PD-1 Ligands, and Other Features of the Tumor Immune Microenvironment with Response to Anti–PD-1 Therapy
Authors: Taube Janis M. , Klein Alison , Brahmer Julie R. , Xu Haiying , Pan Xiaoyu , Kim Jung H. , Chen Lieping , Pardoll Drew M. , Topalian Suzanne L. , Anders Robert A.
Published: April 2014

Purpose: Immunomodulatory drugs differ in mechanism-of-action from directly cytotoxic cancer therapies. Identifying factors predicting clinical response could guide patient selection and therapeutic optimization.

Experimental Design: Patients (N = 41) with melanoma, non–small cell lung carcinoma (NSCLC), renal cell carcinoma (RCC), colorectal carcinoma, or castration-resistant prostate cancer were treated on an early-phase trial of anti–PD-1 (nivolumab) at one institution and had evaluable pretreatment tumor specimens. Immunoarchitectural features, including PD-1, PD-L1, and PD-L2 expression, patterns of immune cell infiltration, and lymphocyte subpopulations, were assessed for interrelationships and potential correlations with clinical outcomes.

Results: Membranous (cell surface) PD-L1 expression by tumor cells and immune infiltrates varied significantly by tumor type and was most abundant in melanoma, NSCLC, and RCC. In the overall cohort, PD-L1 expression was geographically associated with infiltrating immune cells (P < 0.001), although lymphocyte-rich regions were not always associated with PD-L1 expression. Expression of PD-L1 by tumor cells and immune infiltrates was significantly associated with expression of PD-1 on lymphocytes. PD-L2, the second ligand for PD-1, was associated with PD-L1 expression. Tumor cell PD-L1 expression correlated with objective response to anti–PD-1 therapy, when analyzing either the specimen obtained closest to therapy or the highest scoring sample among multiple biopsies from individual patients. These correlations were stronger than borderline associations of PD-1 expression or the presence of intratumoral immune cell infiltrates with response.

Conclusions: Tumor PD-L1 expression reflects an immune-active microenvironment and, while associated other immunosuppressive molecules, including PD-1 and PD-L2, is the single factor most closely correlated with response to anti–PD-1 blockade. Clin Cancer Res; 20(19); 5064–74. ©2014 AACR.
Mitochondrial Topoisomerase I (Top1mt) Is a Novel Limiting Factor of Doxorubicin Cardiotoxicity
Authors: Khiati Salim , Dalla Rosa Ilaria , Sourbier Carole , Ma Xuefei , Rao V. Ashutosh , Neckers Leonard M. , Zhang Hongliang , Pommier Yves
Published: April 2014

Purpose: Doxorubicin is one of the most effective chemotherapeutic agents. However, up to 30% of the patients treated with doxorubicin suffer from congestive heart failure. The mechanism of doxorubicin cardiotoxicity is likely multifactorial and most importantly, the genetic factors predisposing to doxorubicin cardiotoxicity are unknown. On the basis of the fact that mtDNA lesions and mitochondrial dysfunctions have been found in human hearts exposed to doxorubicin and that mitochondrial topoisomerase 1 (Top1mt) specifically controls mtDNA homeostasis, we hypothesized that Top1mt knockout (KO) mice might exhibit hypersensitivity to doxorubicin.

Experimental Design: Wild-type (WT) and KO Top1mt mice were treated once a week with 4 mg/kg doxorubicin for 8 weeks. Heart tissues were analyzed one week after the last treatment.

Results: Genetic inactivation of Top1mt in mice accentuates mtDNA copy number loss and mtDNA damage in heart tissue following doxorubicin treatment. Top1mt KO mice also fail to maintain respiratory chain protein production and mitochondrial cristae ultrastructure organization. These mitochondrial defects result in decreased O2 consumption, increased reactive oxygen species production, and enhanced heart muscle damage in animals treated with doxorubicin. Accordingly, Top1mt KO mice die within 45 days after the last doxorubicin injection, whereas the WT mice survive.

Conclusions: Our results provide evidence that Top1mt, which is conserved across vertebrates, is critical for cardiac tolerance to doxorubicin and adaptive response to doxorubicin cardiotoxicity. They also suggest the potential of Top1mt single-nucleotide polymorphisms testing to investigate patient susceptibility to doxorubicin-induced cardiotoxicity. Clin Cancer Res; 20(18); 4873–81. ©2014 AACR.
Modified S-Ileal Neobladder for Continent Urinary Diversion: Functional and Urodynamic Results after 20 Years of Follow-Up
Authors: Dellis Athanasios E. , Papatsoris Athanasios G. , Skolarikos Andreas A. , Varkarakis Ioannis M. , Deliveliotis Charalambos N.
Published: April 2014

Objective: To report continence and urodynamic findings after radical cystectomy and urinary diversion with modified S-ileal neobladder between January 1993 and January 2013. Patients and Methods: 181 patients were enrolled. Continence status, reservoir sensation, compliance, capacity and activity were assessed. Results: Daytime continence was reported by 88.0, 98.4 and 99.2%, while nighttime continence was reported by 70.2, 94.0 and 95.8% of our patients at 6 months, 5 years and 20 years, respectively. Enterocystometric capacity and maximum reservoir pressure were 366 vs. 405 ml and 502 ml, and 29 vs. 18 and 11 cm H2O, at 6 months, 5 years and 20 years, respectively. Median post-void residual urine volume was 32 ml at 6 months, 50 ml at 5 years and 120 ml at 20 years. Conclusions: The modified S-ileal neobladder technique has a very good long-lasting functional outcome, with high day- and nighttime continence levels as well as high acceptability rates from our patients.
The Potentially Protective Effect of Donepezil in Alzheimer's Disease
Authors: Ishiwata Akiko , Mizumura Sunao , Mishina Masahiro , Yamazaki Mineo , Katayama Yasuo
Published: April 2014

Background/Aims: Donepezil is an acetylcholinesterase inhibitor used to treat Alzheimer's disease (AD). In this study, we used a voxel-based specific regional analysis system for AD (VSRAD) to analyze the hippocampal volume and to assess the pharmacologic effects of donepezil as a disease modifier. Methods: A total of 185 AD patients underwent MRI, 120 (43 men and 77 women, 77.8 ± 7.1 years) without and 65 (29 men and 36 women, 78.4 ± 6.0 years) with donepezil treatment. VSRAD was compared in both groups and against a database of 80 normal subjects. The Z-score was used to assess the degree of hippocampal atrophy. Results: No significant difference between the groups was found for age, sex, or Z-scores, but a significant difference was found for mean Mini-Mental State Examination (MMSE) scores (p = 0.02, Student's t test). Single regression analysis showed no significant association between Z-scores and MMSE scores in the treated group (p = 0.494), but a significant association in the untreated group (p = 0.001) was observed. This implies that the MMSE score becomes lower when the Z-score is higher in the untreated group, whereas there is no significant trend in the treated group. Conclusion: Donepezil affects the relationship between hippocampal volume and cognitive function and may therefore have a pharmacologic effect as a disease modifier.
Serum Triglyceride Levels Correlated with the Rate of Change in Insulin Secretion Over Two Years in Prediabetic Subjects
Authors: Shimodaira Masanori , Niwa Tomohiro , Nakajima Koji , Kobayashi Mutsuhiro , Hanyu Norinao , Nakayama Tomohiro
Published: April 2014

Background/Aims: Increased triglyceride (TG) and decreased high-density lipoprotein cholesterol (HDL-C) levels are considered risk factors for diabetes among prediabetic subjects. In this study, we retrospectively investigated the relationship between lipid profiles and the rate of change in early-phase insulin secretion in prediabetic subjects. Methods: To evaluate insulin secretion, 50 prediabetic subjects underwent a 75-gram oral glucose tolerance test at the beginning of the study (baseline), and they were reexamined after a 2-year interval. The results were expressed as insulinogenic index (IGI) and disposition index (DI). Results: The lipid profiles and indices of insulin secretion had not significantly changed over 2 years. However, Pearson's correlation analyses indicated that the rate of change in IGI and DI was negatively correlated with log-transformed baseline TG level, but not with baseline HDL-C level. Multiple linear regression analysis confirmed that the rate of change in IGI and DI was negatively correlated with the log-transformed baseline TG level (β = -0.38, p = 0.006, and β = -0.39, p = 0.006, respectively). Conclusions: Baseline TG level of prediabetic subjects appeared to be associated with rate of change in IGI and DI over a 2-year period, indicating that TG levels among prediabetic subjects should be carefully monitored.
The Combination of Dysexecutive and Amnestic Deficits Strongly Predicts Conversion to Dementia in Young Mild Cognitive Impairment Patients: A Report from the Gothenburg-Oslo MCI Study
Authors: Hessen Erik , Reinvang Ivar , Eliassen Carl F. , Nordlund Arto , Gjerstad Leif , Fladby Tormod , Wallin Anders
Published: April 2014

Background/Aims: The present study aimed to add to the knowledge of mild cognitive impairment (MCI) by studying the prognosis in a relatively young cohort of patients characterized by neuropsychological criteria. Methods: Patients (mean age: 63 years) with cognitive complaints and MCI (n = 302) were recruited from two university clinics and followed for 2 years. Results: Pure dysexecutive MCI occurred in 11.7% of the neuropsychologically impaired patients, while 59.3 and 29.0% were characterized as having pure amnestic MCI or multidomain MCI. During the study period, the state of 2 (10.5%) of the patients with single-domain dysexecutive MCI converted to dementia, while 28 (29.2%) of the patients with pure amnestic MCI became demented. Of the patients with both executive and amnestic deficits, 28 (59.6%) became demented. Conclusion: The results suggest that dysexecutive symptoms in combination with amnestic symptoms constitute a strong risk factor for dementia in young MCI patients. A significant number of patients in all subgroups showed normal test results at follow-up, indicating that a neuropsychological diagnosis needs to be supported by imaging or biomarker data.
Combination of Echocardiography and Pulse Wave Velocity Provides Clues for the Differentiation between White Coat Hypertension and Hypertension in Postmenopausal Women
Authors: Suzuki Hiromichi , Kobayashi Kazuhiro , Okada Hirokazu
Published: April 2014

Objective: To determine whether or not noninvasive assessment of the cardiovascular system can discriminate white coat hypertension and hypertension in postmenopausal women. The major reason is the high prevalence of white coat hypertension in these subjects and the uncertain associations of white coat hypertension with cardiovascular risk. Patients and Methods: Selected women were required to be naturally or surgically menopausal for at least 1 year but not more than 5 years past their menstrual period. White coat hypertension patients were defined as subjects who had office blood pressures >150/90 mm Hg but who had both systolic and diastolic ambulatory pressures <120/80 mm Hg. In total, 44 subjects with a mean age of 52 years were recruited from the outpatient clinic and examined. Office and home blood pressures were measured using the HEM 401C (Omron Life Science Co. Ltd., Tokyo, Japan), a semi-automatic device that operates on the cuff-oscillometric principle and generates a digital display of the systolic (SBP) and diastolic blood pressure as well as the pulse rate. The pulse wave velocity (PWV) was recorded, and the left ventricular (LV) diameter, septal wall thickness, and left posterior wall thickness were assessed by M-mode echocardiography after selecting the measurement section by B-mode echocardiography. Results: Twenty patients were diagnosed as having white coat hypertension based on the criteria in the trial. Pulse wave patterns were different between subjects with white coat hypertension and those with hypertension. PWV of subjects with white coat hypertension was 1.32 ± 0.33 m/s and that of patients with hypertension was 1.46 ± 0.37 m/s (p < 0.01). In addition to these findings, there was a significant association between the values of home SBP and PWV and the LV mass index. However, this association was not seen for office SBP. When the data of the LV mass index and PWV were combined, white coat hypertension could be easily differentiated from hypertension. Conclusions: The combination of blood pressure self-monitoring, echocardiographic data, and PWV can be a powerful indicator for the treatment of hypertension in postmenopausal women.
Strong and Sustained Response to Treatment with Carboplatin plus Nab-Paclitaxel in a Patient with Metastatic, Triple-Negative, BRCA1-Positive Breast Cancer
Authors: Shakir Abdur R.
Published: April 2014

Our case describes a 51-year-old female, diagnosed in April 2008 with a triple-negative, BRCA1-positive, infiltrating ductal carcinoma of the left breast. Initial platinum-based therapy resulted in a complete regression until November 2009, when a recurrence of the disease was detected. As no evidence of metastasis was found, a dose-dense regimen of doxorubicin plus cyclophosphamide was administered, followed by paclitaxel. The patient was actively monitored until March 2012, when brain metastases were discovered and successfully treated with whole-brain radiation therapy. Three months later, the patient experienced severe abdominal pain, and CT scans revealed extensive metastatic disease, including a large mass in the abdomen and more than 20 bilateral pulmonary metastases. Treatment commenced with carboplatin plus nab-paclitaxel. However, carboplatin was stopped after 4 cycles due to persistent neutropenia, and nab-paclitaxel was continued as monotherapy. Whole-body CT scans performed in October 2012 and March 2013 revealed a significant response to therapy, and the patient reported feeling well and being fully mobile. No treatment-related adverse events were observed. A routine brain MRI scan carried out on April 18, 2013, revealed a recurrence of brain metastases; however, CT scans confirmed that disease progression was not systemic, but confined to the central nervous system. Despite the initiation of treatment with irinotecan plus temozolomide on April 24, the patient died on July 2, 2013. The author believes that this case is the first report of a robust response to nab-paclitaxel monotherapy in triple-negative BRCA1-positive breast cancer, and that it supports further studies of nab-paclitaxel in this aggressive indication.
A Metastatic Ovarian Angiosarcoma Mimicking Hematologic Neoplasia at Diagnosis
Authors: Gaiolla Rafael Dezen , Duarte Ívison Xavier , Bacchi Carlos Eduardo , Paiva Carlos Eduardo
Published: April 2014

Angiosarcomas are rare aggressive neoplasms of vascular endothelial origin with a high metastatic rate and poor prognosis. Involvement of the bone marrow by the angiosarcoma is exceedingly uncommon, and there have only been a few cases reported in the literature to date. Clinical manifestations and common laboratory findings of bone marrow involvement can mimic other more common bone marrow-replacing neoplasias such as lymphomas and acute leukemia. A definitive diagnosis is difficult to make from cytologic material, probably due to an associated bone marrow fibrosis, and requires bone marrow trephine biopsy with an immunohistochemical profile. Here we had the opportunity to study a case of metastatic angiosarcoma with positive cytologic findings and an unusual presentation that challenged its primary diagnosis.
Abnormal Cardiac Formation in Hypertrophic Cardiomyopathy
Authors: Captur Gabriella , Lopes Luis R. , Patel Vimal , Li Chunming , Bassett Paul , Syrris Petros , Sado Daniel M. , Maestrini Viviana , Mohun Timothy J. , McKenna William J. , Muthurangu Vivek , Elliott Perry M. , Moon James C.
Published: April 2014

Background—

Mutations in genes coding for sarcomeric proteins cause hypertrophic cardiomyopathy. Subtle abnormalities of the myocardium may be present in mutation carriers without left ventricular hypertrophy (G+LVH−) but are difficult to quantify. Fractal analysis has been used to define trabeculae in left ventricular noncompaction and to identify normal racial variations. We hypothesized that trabeculae measured by fractal analysis of cardiovascular magnetic resonance images are abnormal in G+LVH− patients, providing a preclinical marker of disease in hypertrophic cardiomyopathy.

Methods and Results—

Cardiovascular magnetic resonance was performed on 40 G+LVH− patients (33±15 years, 38% men), 67 patients with a clinical diagnosis of hypertrophic cardiomyopathy (53±15 years, 76% men; 31 with a pathogenic mutation [G+LVH+]), and 69 matched healthy volunteers (44±15 years, 57% men). Trabeculae were quantified by fractal analysis of cine slices to calculate the fractal dimension, a unitless index of endocardial complexity calculated from endocardial contours after segmentation. In G+LVH− patients, apical left ventricular trabeculation was increased compared with controls (maximal apical fractal dimension, 1.249±0.07 versus 1.199±0.05;
P
=0.001). In G+LVH+ and G−LVH+ cohorts, maximal apical fractal dimension was greater than in controls (
P
<0.0001) irrespective of gene status (G+LVH+: 1.370±0.08; G−LVH+: 1.380±0.09). Compared with controls, G+LVH− patients also had a higher frequency of clefts (28% versus 8%;
P
=0.02), longer anterior mitral valve leaflets (23.5±3.0 versus 19.7±3.1 mm;
P
<0.0001), greater septal systolic wall thickness (12.6±3.2 versus 11.2±2.1 mm;
P
=0.03), higher ejection fraction (71±4% versus 69±4%;
P
=0.03), and smaller end-systolic volumes (38±9 versus 43±12 mL;
P
=0.03).

Conclusions—

Increased myocardial trabecular complexity is one of several preclinical abnormalities in hypertrophic cardiomyopathy sarcomere gene mutation carriers without LVH.
Lipoprotein(a) Levels, Genotype, and Incident Aortic Valve Stenosis
Authors: Arsenault Benoit J. , Boekholdt S. Matthijs , Dubé Marie-Pierre , Rhéaume Éric , Wareham Nicholas J. , Khaw Kay-Tee , Sandhu Manjinder S. , Tardif Jean-Claude
Published: April 2014

Background—

Although a previous study has suggested that a genetic variant in the
LPA
region was associated with the presence of aortic valve stenosis (AVS), no prospective study has suggested a role for lipoprotein(a) levels in the pathophysiology of AVS. Our objective was to determine whether lipoprotein(a) levels and a common genetic variant that is strongly associated with lipoprotein(a) levels are associated with an increased risk of developing AVS.

Methods and Results—

Serum lipoprotein(a) levels were measured in 17 553 participants of the European Prospective Investigation into Cancer (EPIC)-Norfolk study. Among these study participants, 118 developed AVS during a mean follow-up of 11.7 years. The rs10455872 genetic variant in
LPA
was genotyped in 14 735 study participants, who simultaneously had lipoprotein(a) level measurements, and in a replication study of 379 patients with echocardiography-confirmed AVS and 404 controls. In EPIC-Norfolk, compared with participants in the bottom lipoprotein(a) tertile, those in the top lipoprotein(a) tertile had a higher risk of AVS (hazard ratio, 1.57; 95% confidence interval, 1.02–2.42) after adjusting for age, sex, and smoking. Compared with rs10455872 AA homozygotes, carriers of 1 or 2 G alleles were at increased risk of AVS (hazard ratio, 1.78; 95% confidence interval, 1.11–2.87, versus hazard ratio, 4.83; 95% confidence interval, 1.77–13.20, respectively). In the replication study, the genetic variant rs10455872 also showed a positive association with AVS (odds ratio, 1.57; 95% confidence interval, 1.10–2.26).

Conclusions—

Patients with high lipoprotein(a) levels are at increased risk for AVS. The rs10455872 variant, which is associated with higher lipoprotein(a) levels, is also associated with increased risk of AVS, suggesting that this association may be causal.
Optical Coherence Tomographic Evaluation of Transplant Coronary Artery Vasculopathy With Correlation to Cellular Rejection
Authors: Dong Liang , Maehara Akiko , Nazif Tamim M. , Pollack Ari T. , Saito Shigeo , Rabbani LeRoy E. , Apfelbaum Mark A. , Dalton Kate , Moses Jeffrey W. , Jorde Ulrich P. , Xu Ke , Mintz Gary S. , Mancini Donna M. , Weisz Giora
Published: April 2014

Background—

Cardiac allograft vasculopathy is an accelerated fibroproliferative process that affects the coronary arteries of transplanted hearts. Intracoronary imaging with optical coherence tomography enables detection of subangiographic cardiac allograft vasculopathy.

Methods and Results—

At the time of routine surveillance coronary angiography, 48 consecutive heart transplant recipients underwent optical coherence tomographic imaging of 1 coronary artery. Imaging findings were compared per rejection history that was graded according to the International Society of Heart and Lung Transplantation classification as none/mild (International Society of Heart and Lung Transplantation 0, 1A/1B, or 2) or high-grade rejection (≥3A). Compared with the none/mild rejection group (37 patients) using Mann–Whitney
U
test, patients in the high-grade rejection group (11 patients) had a thicker intima in all coronary segments (distal: 0.22 mm [0.09–0.41] versus 0.09 mm [0.06–0.17],
P
=0.02; middle: 0.35 mm [0.00–0.45] versus 0.14 mm [0.08–0.24],
P
=0.002; and proximal: 0.34 mm [0.21–0.44] versus 0.15 mm [0.11–0.21],
P
=0.005) and a higher prevalence of foamy macrophages (distal: 55% versus 9%,
P
=0.003; middle: 55% versus 22%,
P
=0.004; and proximal: 44% versus 13%,
P
=0.05) using χ
2
statistics. Side branches in the high-grade rejection group had smaller lumen diameters and a higher prevalence of intimal thickening (54% versus 36%;
P
=0.01). Intimal microvessels were also more prevalent in the high-grade rejection group versus the none/mild rejection group (46% versus 11%;
P
=0.02).

Conclusions—

Coronary optical coherence tomographic evaluation revealed that patients with a history of high-grade cellular rejection, compared with those with none/mild rejection, had more coronary artery intimal thickening with macrophage infiltration, involving all coronary segments and side branches.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01403142.
De Novo Ivy Sign Indicates Postoperative Hyperperfusion in Moyamoya Disease
Authors: Horie Nobutaka , Morikawa Minoru , Morofuji Youichi , Hiu Takeshi , Izumo Tsuyoshi , Hayashi Kentaro , Nagata Izumi
Published: April 2014

Background and Purpose—

The ivy sign on fluid-attenuated inversion recovery MRI is a specific finding in moyamoya disease (MMD). This sign indicates decreased cerebral perfusion, dilated pial vasculature, and slow leptomeningeal collateral flow. This study aimed to clarify the characteristics of perioperative changes in the ivy sign in relation to cerebral hyperperfusion, which frequently occurs in MMD of unknown pathogenesis.

Methods—

This prospective study included patients with MMD who underwent superior temporal artery–middle cerebral artery single bypass. Fluid-attenuated inversion recovery MRI was performed to evaluate the appearance of the ivy sign in the ipsilateral hemisphere preoperatively and on postoperative days 2 and 30. The ivy sign was assessed in combination with perioperative symptoms and cerebral hemodynamics using single-photon emission computed tomography.

Results—

Of 42 consecutive patients (55 sides) who underwent bypass surgery, 32 (58.2%) showed an increase in the ivy sign (de novo ivy sign) on postoperative day 2; this had disappeared by day 30. Interestingly, these 32 patients had a significantly higher incidence of hyperperfusion on single-photon emission computed tomography and hyperperfusion syndrome, and there was no correlation between the de novo ivy sign and a preoperative ivy sign or the preoperative cerebral hemodynamics. In multivariate analysis, a de novo ivy sign was significantly correlated with postoperative hyperperfusion.

Conclusions—

In MMD, a de novo ivy sign could indicate postoperative hyperperfusion after bypass, which is not always correlated with preoperative hemodynamic impairment. Additional factors other than preoperative cerebral hemodynamics might be involved in postoperative hyperperfusion in MMD.
Dichotomous Effects of Chronic Intermittent Hypoxia on Focal Cerebral Ischemic Injury
Authors: Jackman Katherine A. , Zhou Ping , Faraco Giuseppe , Peixoto Pablo M. , Coleman Christal , Voss Henning U. , Pickel Virginia , Manfredi Giovanni , Iadecola Costantino
Published: April 2014

Background and Purpose—

Obstructive sleep apnea, a condition associated with chronic intermittent hypoxia (CIH), carries an increased risk of stroke. However, CIH has been reported to either increase or decrease brain injury in models of focal cerebral ischemia. The factors determining the differential effects of CIH on ischemic injury and their mechanisms remain unclear. Here, we tested the hypothesis that the intensity of the hypoxic challenge determines the protective or destructive nature of CIH by modulating mitochondrial resistance to injury.

Methods—

Male C57Bl/6J mice were exposed to CIH with 10% or 6% O
2
for ≤35 days and subjected to transient middle cerebral artery occlusion. Motor deficits and infarct volume were assessed 3 days later. Intraischemic cerebral blood flow was measured by laser-Doppler flowmetry and resting cerebral blood flow by arterial spin labeling MRI. Ca
2+
-induced mitochondrial depolarization and reactive oxygen species production were evaluated in isolated brain mitochondria.

Results—

We found that 10% CIH is neuroprotective, whereas 6% CIH exacerbates tissue damage. No differences in resting or intraischemic cerebral blood flow were observed between 6% and 10% CIH. However, 10% CIH reduced, whereas 6% CIH increased, mitochondrial reactive oxygen species production and susceptibility to Ca
2+
-induced depolarizations.

Conclusions—

The influence of CIH on the ischemic brain is dichotomous and can be attributed, in part, to changes in the mitochondrial susceptibility to injury. The findings highlight a previously unappreciated complexity in the effect of CIH on the brain, which needs to be considered in evaluating the neurological effect of conditions associated with cyclic hypoxia.
On the Design of an International Governance Framework for Geoengineering
Authors: Lloyd Ian D. , Oppenheimer Michael
Published: April 2014

This paper explores the governance options surrounding geoengineering—the deliberate, large-scale manipulation of the Earth's climate system to counteract climate change. The authors focus solely on methods that affect the incoming solar radiation to the atmosphere, referred to as solar radiation management (SRM). They examine whether an international governance framework for SRM is needed, how it should be designed, and whether it is feasible. The authors propose a governance regime that initially has small membership and weak legalization, and is flexible in that future institutional reforms allow for broader membership and deeper commitments. The article provides supporting evidence for key aspects of the regime through past international treaties in arms control and environmental protection, including the Antarctica, Outer Space, and Montreal Protocol treaty regimes. For these cases, acting early and treating the respective problems as part of the “regulation of unexplored territory” produced more effective outcomes than the “national appropriation” approach that characterizes arms control.
Rescuing EU Emissions Trading: Mission Impossible?
Authors: Wettestad Jørgen
Published: April 2014

Is rescuing the EU's emissions trading system impossible? Despite the substantial reform in 2008, subsequent problems of allowance surplus and a low carbon price have spurred new efforts to reform the system for the 2013–2020 phase. But these efforts have met resistance both among member states and in the European parliament, and the EU is struggling in its efforts to improve the ETS. This article draws on four central EU and political science theory approaches to more systematically explore why. The financial crisis and slow international policy progress have narrowed the window of opportunity that was open in 2008. Factors that could open that window again include an economic upswing, a new European commission and parliament, and new global negotiations in 2015. But even without short-term reform, the linear reduction factor will gradually tighten the system and lead to a higher carbon price.
The Reception of Athanasius within Contemporary Roman Catholic Theology
Authors: van Wilgenburg Arwin
Published: April 2014

This article gives a brief overview of the reception of Athanasius in nineteenth- and twentieth-century Roman Catholic theology. Besides papal documents, mainly German theologians are discussed. First, Johann Adam Möhler’s Athanasius der Grosse (1827) is analyzed. Möhler was convinced that Athanasius was of great importance for modern society. However, Möhler’s attempt to give Athanasius a prominent position in contemporary theology seemed to fail. Although Athanasius is not absent in nineteenth-century dogmatic compendia, nor in papal documents of the last two centuries and many dogmatics of the twentieth century, his quantitative reception is rather poor, especially in comparison to Augustine. The dogmatic compendia and Neo-Thomistic theology did not have an interest in a historical interpretation of Athanasius and Thomas, himself, hardly referred to Athanasius. Moreover, the Trinitarian and Christological dogmas were not really contested. This changed in twentieth-century theology, because of a new understanding of historical development and the rise of phenomenology and existentialism. The doctrines of the Trinity and Christology were reinterpreted from the perspective of salvation history (Heilsgeschichte). Many theologians wanted to correct the anti-Arian tendency, stressing that Christ was truly God and truly man. Athanasius overlooked Christ’s humanity and the Alexandrian Logos-Sarx-Christology needed the complementation of the Antiochene Logos-Antropos-Christology. Nevertheless, Athanasius’s has received great formal authority within Roman Catholicism. He is a Saint and honored as doctor ecclesiae, because of his impact on Christian doctrine and the development of monasticism.
A new species of Coleusia Galil, 2006 (Decapoda: Brachyura: Leucosiidae) from southern Asia
Authors: PROMDAM RUEANGRIT , NABHITABHATA JARUWAT , GALIL BELLA S.
Published: April 2014

A new species of leucosiid crab of the genus Coleusia Galil, 2006, is described from South and Southeast Asia. Coleusia huilianae n. sp. is distinguished from the superficially similar C. urania (Herbst, 1801) in the shape of the apical process of the first male gonopod which is digitate and curved laterally in the former (beak-like and curved interiorly in the latter); possessing smaller and sparser granulation on the posterior and lower margin of the cheliped and ambulatory meri; and the granulation is entirely missing from the lower external surface of the palm.
New species of Hybos Meigen from Northwest China (Diptera: Empidoidea, Hybotinae)
Authors: LI ZHU , WANG NING , YANG DING
Published: April 2014

The species of the genus Hybos Meigen from Northwest China are reviewed. The following five species are described as new to science: Hybos elongatus sp. nov., H. flavitibialis sp. nov., H. projectus sp. nov., H. qinlingensis sp. nov., and H. xii sp. nov. A key to the 17 species of the genus Hybos from Northwest China is provided.
A new species of arboreal forest-dwelling gecko (Hemidactylus: Squamata: Gekkonidae) from coastal Kenya, East Africa
Authors: MALONZA PATRICK K. , BAUER AARON M.
Published: April 2014

A new species of Hemidactylus, H. mrimaensis sp. nov., is described from coastal kaya forests of Kenya. This small-sized, arboreal gecko may be distinguished from its probable close relative, the sympatric H. mabouia, by its more slender habitus, golden color, small adult body length (maximum SVL 50 mm in females) and features of scalation including keeled dorsal tubercles in 11–14 longitudinal rows, pointed tubercles on tail larger than those on the dorsum, and 32–34 precloacal pores in males. This gecko may be endemic to the coastal forests and given the ongoing threats to this habitat, the species is of high conservation concern.
Causes of Increasing Aridification of the Mediterranean Region in Response to Rising Greenhouse Gases*
Authors: Seager Richard , Liu Haibo , Henderson Naomi , Simpson Isla , Kelley Colin , Shaw Tiffany , Kushnir Yochanan , Ting Mingfang
Published: April 2014

The hydrological cycle in the Mediterranean region, as well as its change over the coming decades, is investigated using the Interim European Centre for Medium-Range Weather Forecasts Re-Analysis (ERA-Interim) and phase 5 of the Coupled Model Intercomparison Project (CMIP5) historical simulations and projections of the coming decades. The Mediterranean land regions have positive precipitation minus evaporation, P − E, in winter and negative P − E in summer. According to ERA-Interim, positive P − E over land in winter is sustained by transient eddy moisture convergence and opposed by mean flow moisture divergence. Dry mean flow advection is important for opposing the transient eddy moisture flux convergence in the winter half year and the mass divergent mean flow is a prime cause of negative P − E in the summer half year. These features are well reproduced in the CMIP5 ensemble. The models predict reduced P − E over the Mediterranean region in the future year-round. For both land and sea, a common cause of drying is increased mean flow moisture divergence. Changes in transient eddy moisture fluxes largely act diffusively and cause drying over the sea and moistening over many land areas to the north in winter and drying over western land areas and moistening over the eastern sea in summer. Increased mean flow moisture divergence is caused by both the increase in atmospheric humidity in a region of mean flow divergence and strengthening of the mass divergence. Increased mass divergence is related to increased high pressure over the central Mediterranean in winter and over the Atlantic and northern Europe in summer, which favors subsidence and low-level divergence over the Mediterranean region.