bluuebunny/crossref_metadata_2025_split huggingface dataset:
On left-symmetric conformal bialgebras
Authors: Hong Yanyong , Li Fang 
Published: April 2014

The notion of left-symmetric bialgebra was introduced in [C. M. Bai, Left-symmetric bialgebra and an analogue of the classical Yang–Baxter equation, Commun. Contemp. Math. 10(2) (2008) 221–260] which is equivalent to a parakähler Lie algebra which is the Lie algebra of a Lie group G with a G-invariant parakähler structure. In this paper, we study a conformal analog of left-symmetric bialgebras. The notions of left-symmetric conformal coalgebra and bialgebra are introduced. Moreover, the constructions of matched pairs of Lie conformal algebras and left-symmetric conformal algebras are presented. We show that a finite left-symmetric conformal bialgebra which is free as a ℂ[∂]-module is equivalent to a parakähler Lie conformal algebra. We also obtain a conformal analog of the S-equation (see [C. M. Bai, Left-symmetric bialgebras and an analogue of the classical Yang–Baxter equation, Commun. Contemp. Math. 10(2) (2008) 221–260]), and give a construction of the conformal symplectic double.
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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 &lt; 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

Abstract
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.
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.