bluuebunny/crossref_metadata_2025 huggingface dataset:
Adherence to Cancer Prevention Guidelines and Cancer Risk in Low-Income and African American Populations
Authors: Warren Andersen Shaneda , Blot William J. , Shu Xiao-Ou , Sonderman Jennifer S. , Steinwandel Mark D. , Hargreaves Margaret K. , Zheng Wei
Published: March 2016

Background: The American Cancer Society (ACS) publishes behavioral guidelines for cancer prevention, including standards on body weight, physical activity, nutrition, alcohol, and tobacco use. The impact of these guidelines has been rarely studied in low-income and African American populations.

Methods: The study included 61,098 racially diverse, mainly low-income adults who participated in the Southern Community Cohort Study and were followed for a median of 6 years. Cox models were used to estimate HRs for cancer incidence associated with behaviors and with an ACS physical activity/nutrition 0-to-4 compliance score indicating the number of body weight, physical activity, healthy eating, and alcohol guidelines met.

Results: During the study period, 2,240 incident cancers were identified. Significantly lower cancer incidence was found among never smokers and non/moderate alcohol drinkers, but not among those meeting guidelines for obesity, physical activity, and diet. The ACS compliance score was inversely associated with cancer risk among the 25,509 participants without baseline chronic disease. HRs for cancer incidence among those without baseline chronic diseases and who met one, two, three, or four guidelines versus zero guidelines were 0.93 (95% confidence intervals, 0.71–1.21), 0.85 (0.65–1.12), 0.70 (0.51–0.97), and 0.55 (0.31–0.99), respectively. Associations were consistent in analyses stratified by sex, race, household income, and smoking status.

Conclusions: Meeting the ACS smoking and body weight/physical activity/dietary/alcohol guidelines for cancer prevention is associated with reductions in cancer incidence in low-income and African American populations.

Impact: This study provides strong evidence supporting lifestyle modification to lower cancer incidence in these underserved populations. Cancer Epidemiol Biomarkers Prev; 25(5); 846–53. ©2016 AACR.
HDAC Inhibitors Enhance T-Cell Chemokine Expression and Augment Response to PD-1 Immunotherapy in Lung Adenocarcinoma
Authors: Zheng Hong , Zhao Weipeng , Yan Cihui , Watson Crystina C. , Massengill Michael , Xie Mengyu , Massengill Chris , Noyes David R. , Martinez Gary V. , Afzal Roha , Chen Zhihua , Ren Xiubao , Antonia Scott J. , Haura Eric B. , Ruffell Brian , Beg Amer A.
Published: March 2016

Purpose: A significant limitation of checkpoint blockade immunotherapy is the relatively low response rate (e.g., ∼20% with PD-1 blockade in lung cancer). In this study, we tested whether strategies that increase T-cell infiltration to tumors can be efficacious in enhancing immunotherapy response.

Experimental Design: We performed an unbiased screen to identify FDA-approved oncology agents with an ability to enhance T-cell chemokine expression with the goal of identifying agents capable of augmenting immunotherapy response. Identified agents were tested in multiple lung tumor models as single agents and in combination with PD-1 blockade. Additional molecular and cellular analysis of tumors was used to define underlying mechanisms.

Results: We found that histone deacetylase (HDAC) inhibitors (HDACi) increased expression of multiple T-cell chemokines in cancer cells, macrophages, and T cells. Using the HDACi romidepsin in vivo, we observed increased chemokine expression, enhanced T-cell infiltration, and T-cell–dependent tumor regression. Importantly, romidepsin significantly enhanced the response to PD-1 blockade immunotherapy in multiple lung tumor models, including nearly complete rejection in two models. Combined romidepsin and PD-1 blockade also significantly enhanced activation of tumor-infiltrating T cells.

Conclusions: These results provide evidence for a novel role of HDACs in modulating T-cell chemokine expression in multiple cell types. In addition, our findings indicate that pharmacologic induction of T-cell chemokine expression represents a conceptually novel approach for enhancing immunotherapy response. Finally, these results suggest that combination of HDAC inhibitors with PD-1 blockade represents a promising strategy for lung cancer treatment. Clin Cancer Res; 22(16); 4119–32. ©2016 AACR.
Constitutive Activation of DNA Damage Checkpoint Signaling Contributes to Mutant p53 Accumulation via Modulation of p53 Ubiquitination
Authors: Frum Rebecca A. , Love Ian M. , Damle Priyadarshan K. , Mukhopadhyay Nitai D. , Palit Deb Swati , Deb Sumitra , Grossman Steven R.
Published: March 2016

Many mutant p53 proteins exhibit an abnormally long half-life and overall increased abundance compared with wild-type p53 in tumors, contributing to mutant p53's gain-of-function oncogenic properties. Here, a novel mechanism is revealed for the maintenance of mutant p53 abundance in cancer that is dependent on DNA damage checkpoint activation. High-level mutant p53 expression in lung cancer cells was associated with preferential p53 monoubiquitination versus polyubiquitination, suggesting a role for the ubiquitin/proteasome system in regulation of mutant p53 abundance in cancer cells. Interestingly, mutant p53 ubiquitination status was regulated by ataxia–telangectasia mutated (ATM) activation and downstream phosphorylation of mutant p53 (serine 15), both in resting and in genotoxin-treated lung cancer cells. Specifically, either inhibition of ATM with caffeine or mutation of p53 (serine 15 to alanine) restored MDM2-dependent polyubiquitination of otherwise monoubiquitinated mutant p53. Caffeine treatment rescued MDM2-dependent proteasome degradation of mutant p53 in cells exhibiting active DNA damage signaling, and ATM knockdown phenocopied the caffeine effect. Importantly, in cells analyzed individually by flow cytometry, p53 levels were highest in cells exhibiting the greatest levels of DNA damage response, and interference with DNA damage signaling preferentially decreased the relative percentage of cells in a population with the highest levels of mutant p53. These data demonstrate that active DNA damage signaling contributes to high levels of mutant p53 via modulation of ubiquitin/proteasome activity toward p53.

Implication: The ability of DNA damage checkpoint signaling to mediate accumulation of mutant p53 suggests that targeting this signaling pathway may provide therapeutic gain. Mol Cancer Res; 14(5); 423–36. ©2016 AACR.
Hyperuricemia, Cardiovascular Disease, and Hypertension
Authors: Kuwabara Masanari
Published: March 2016

In recent years, there has been an increase in the prevalence of hyperuricemia, and the latter has attracted attention as an adult lifestyle-associated disease, together with hypertension, diabetes, and dyslipidemia. Although hyperuricemia is known to be an independent risk factor for hypertension, whether it is an independent risk factor for cardiovascular disease remains controversial. Recently, some small-scale interventional studies on antihyperuricemic medications showed that the latter improved angina symptoms and prevented cardiovascular disease. Here, we will mainly explain the cause of hyperuricemia and the associations between hyperuricemia, hypertension, and cardiovascular disease based on the latest published evidence.
Serial 1- and 2-Dimensional Cerebral MRI Measurements in Full-Term Infants after Perinatal Asphyxia
Authors: Spring in ''t Veld Laura G. , de Vries Linda S. , Alderliesten Thomas , Benders Manon J.N.L. , Groenendaal Floris
Published: March 2016

Objective: Cranial magnetic resonance imaging (MRI) is associated with neurodevelopmental outcome in full-term infants with neonatal encephalopathy (NE) following presumed perinatal asphyxia. The aim of this study is to relate 2-dimensional measurements of the basal ganglia and thalami (BGT) and cerebellum in the first week after birth and after 3 months with neurodevelopmental outcome at 18 months. Methods: Retrospectively, 29 full-term infants with NE following presumed perinatal asphyxia who had a cranial MRI in the first week after birth were studied serially. One- and 2-dimensional measurements were obtained and related to different patterns of brain injury, and neurodevelopmental outcome at 18 months. A Griffiths developmental quotient <85 or cerebral palsy was considered adverse. Results: On the first MRI, the adverse outcome group showed increased basal ganglia width (42.1 ± 0.1 vs. 40.3 ± 0.3 mm, p < 0.001), thalamic width (40.3 ± 0.1 vs. 39.3 ± 1.0 mm, p < 0.001), and basal ganglia surface (1,230 ± 21 vs. 1,199 ± 36 mm2, p = 0.007) compared to the favorable outcome group. In the BGT lesions group, basal ganglia width and thalamic width were increased compared to the watershed infarction group (42.1 ± 0.1 vs. 40.9 ± 0.8 mm, p < 0.001, and 40.3 ± 0.1 vs. 39.9 ± 0.5 mm, p = 0.01, respectively). On the second MRI, cerebellar width was larger in the favorable outcome group (p = 0.025). There was a greater increase in dimensions between both MRI time points for basal ganglia width (p = 0.014), basal ganglia surface (p = 0.028) and thalamic width (p = 0.012) in the favorable outcome group. Conclusions: One- and 2-dimensional measurements for basal ganglia surface, BGT width and cerebellar width are associated with neurodevelopmental outcome at 18 months.
Association between Urinary Sodium Excretion and Bone Health in Male and Female Adults
Authors: Park Yongsoon , Kwon Soo Jung , Ha Yong Chan
Published: March 2016

Background: High salt intake is a well-known risk factor for osteoporosis, but the association between bone mass and urinary sodium excretion has not been studied as yet. This study investigates the hypothesis that urinary sodium excretion is negatively associated with bone mass and the risk of osteoporosis. Methods: This cross-sectional study was performed using data from the Korea National Health and Nutrition Examination Survey, 2008-2011. Participants (n = 16,279) were divided into age groups; men were categorized as younger than 50 years of age or 50 years or greater, women were categorized as pre- or post-menopausal. Results: Multivariate linear regression analysis showed that urinary sodium excretion was negatively associated with bone mineral content (BMC) and bone mineral density (BMD) in premenopausal and postmenopausal women. Sodium excretion was negatively associated with BMC and BMD of the lumbar spine in women with normal bone health, osteopenia and osteoporosis, but there was no association in men. Increased sodium excretion was significantly associated with risk for osteoporosis/osteopenia in premenopausal women. Conclusions: This study demonstrates that urinary sodium excretion is negatively associated with bone health, suggesting that high salt intake could be a possible risk factor for osteoporosis in Korean women, but not in men.
Hepatoid Adenocarcinoma of the Duodenum: An Unusual Location
Authors: Ogbonna Onyekachi Henry , Sakruti Susmita , Sulieman Maha , Ali Ahmed , Shokrani Babak , Oneal Patricia
Published: March 2016

Hepatoid adenocarcinoma (HAC) is a rare extrahepatic tumor distinguished by having both hepatoid and adenomatous features, which can make the diagnosis challenging. Although it mostly originates in the stomach, several other sites of origin have been reported. We report a case of HAC originating in the duodenum, a very unusual location. We also discuss an approach to the diagnosis of HAC using morphological and immunohistochemical features, and explore possible therapeutic options.
Mast Cell-Targeted Strategies in Cancer Therapy
Authors: Ammendola Michele , Sacco Rosario , Sammarco Giuseppe , Luposella Maria , Patruno Rosa , Gadaleta Cosmo Damiano , De Sarro Giovambattista , Ranieri Girolamo
Published: March 2016

Mast cells (MCs) are cells that originate in the bone marrow from pluripotent CD34+ hematopoietic stem cells. Precursors of MCs migrate through the circulation to their target tissues, completing their maturation process into granulated cells under the influence of several microenvironment growth factors. The most important of these factors is the ligand for the c-Kit receptor (c-Kit-R) namely stem cell factor (SCF), secreted mainly by fibroblasts and endothelial cells (ECs). SCF also regulates development, survival and de novo proliferation of MCs. It has already been demonstrated that gain-of-function mutations of gene c-Kit encoding c-Kit-R result in the development of some tumors. Furthermore, MCs are able also to modulate both innate and adaptive immune response and to express the high-affinity IgE receptor following IgE activation. Among the other IgE-independent MC activation mechanisms, a wide variety of other surface receptors for cytokines, chemokines, immunoglobulins, and complement are also described. Interestingly, MCs can stimulate angiogenesis by releasing of several pro-angiogenic cytokines stored in their cytoplasm. Studies published in the last year suggest that angiogenesis stimulated by MCs may play an important role in tumor growth and progression. Here, we aim to focus several biological features of MCs and to summarize new anti-cancer MC-targeted strategies with potential translation in human clinical trials.
Network-Based Identification and Prioritization of Key Regulators of Coronary Artery Disease Loci
Authors: Zhao Yuqi , Chen Jing , Freudenberg Johannes M. , Meng Qingying ,   CARDIoGRAM Consortium, Rajpal Deepak K. , Yang Xia
Published: March 2016

Objective—

Recent genome-wide association studies of coronary artery disease (CAD) have revealed 58 genome-wide significant and 148 suggestive genetic loci. However, the molecular mechanisms through which they contribute to CAD and the clinical implications of these findings remain largely unknown. We aim to retrieve gene subnetworks of the 206 CAD loci and identify and prioritize candidate regulators to better understand the biological mechanisms underlying the genetic associations.

Approach and Results—

We devised a new integrative genomics approach that incorporated (1) candidate genes from the top CAD loci, (2) the complete genetic association results from the 1000 genomes-based CAD genome-wide association studies from the Coronary Artery Disease Genome Wide Replication and Meta-Analysis Plus the Coronary Artery Disease consortium, (3) tissue-specific gene regulatory networks that depict the potential relationship and interactions between genes, and (4) tissue-specific gene expression patterns between CAD patients and controls. The networks and top-ranked regulators according to these data-driven criteria were further queried against literature, experimental evidence, and drug information to evaluate their disease relevance and potential as drug targets. Our analysis uncovered several potential novel regulators of CAD such as
LUM
and
STAT3
, which possess properties suitable as drug targets. We also revealed molecular relations and potential mechanisms through which the top CAD loci operate. Furthermore, we found that multiple CAD-relevant biological processes such as extracellular matrix, inflammatory and immune pathways, complement and coagulation cascades, and lipid metabolism interact in the CAD networks.

Conclusions—

Our data-driven integrative genomics framework unraveled tissue-specific relations among the candidate genes of the CAD genome-wide association studies loci and prioritized novel network regulatory genes orchestrating biological processes relevant to CAD.
Modulation of Kinin B2 Receptor Signaling Controls Aortic Dilatation and Rupture in the Angiotensin II–Infused Apolipoprotein E–Deficient Mouse
Authors: Moran Corey S. , Rush Catherine M. , Dougan Tammy , Jose Roby J. , Biros Erik , Norman Paul E. , Gera Lajos , Golledge Jonathan
Published: March 2016

Objective—

Abdominal aortic aneurysm (AAA) is an important cause of mortality in older adults. Activity of the local kallikrein–kinin system may be important in cardiovascular disease. The effect of kinin B2 receptor (B2R) agonist and antagonist peptides on experimental AAA was investigated.

Approach and Results—

AAA was induced in apolipoprotein E–deficient mice via infusion of angiotensin II (1.0 μg/kg per minute SC). B2R agonists or antagonists were given via injection (2 mg/kg IP) every other day. The B2R agonist (B9772) promoted aortic rupture in response to angiotensin II associated with an increase in neutrophil infiltration of the aorta in comparison to controls. Mice receiving a B2R/kinin B1 receptor antagonist (B9430) were relatively protected from aortic rupture. Neutrophil depletion abrogated the ability of the B2R agonist to promote aortic rupture. Progression of angiotensin II–induced aortic dilatation was inhibited in mice receiving a B2R antagonist (B9330). Secretion of metalloproteinase-2 and -9, osteoprotegerin, and osteopontin by human AAA explant was reduced in the presence of the B2R antagonist (B9330). B2R agonist and antagonist peptides enhanced and inhibited, respectively, angiotensin II–induced neutrophil activation and aortic smooth muscle cell inflammatory phenotype. The B2R antagonist (B9330; 5 μg) delivered directly to the aortic wall 1 week post-AAA induction with calcium phosphate in a rat model reduced aneurysm growth associated with downregulation of aortic metalloproteinase-9.

Conclusions—

B2R signaling promotes aortic rupture within a mouse model associated with the ability to stimulate inflammatory phenotypes of neutrophils and vascular smooth muscle cells. B2R antagonism could be a potential therapy for AAA.
Mineralocorticoid Receptor Deficiency in Macrophages Inhibits Neointimal Hyperplasia and Suppresses Macrophage Inflammation Through SGK1-AP1/NF-κB Pathways
Authors: Sun Jian-Yong , Li Chao , Shen Zhu-Xia , Zhang Wu-Chang , Ai Tang-Jun , Du Lin-Juan , Zhang Yu-Yao , Yao Gao-Feng , Liu Yan , Sun Shuyang , Naray-Fejes-Toth Aniko , Fejes-Toth Geza , Peng Yong , Chen Mao , Liu Xiaojing , Tao Jun , Zhou Bin , Yu Ying , Guo Feifan , Du Jie , Duan Sheng-Zhong
Published: March 2016

Objective—

Restenosis after percutaneous coronary intervention remains to be a serious medical problem. Although mineralocorticoid receptor (MR) has been implicated as a potential target for treating restenosis, the cellular and molecular mechanisms are largely unknown. This study aims to explore the functions of macrophage MR in neointimal hyperplasia and to delineate the molecular mechanisms.

Approach and Results—

Myeloid MR knockout (MMRKO) mice and controls were subjected to femoral artery injury. MMRKO reduced intima area and intima/media ratio, Ki67- and BrdU-positive vascular smooth muscle cells, expression of proinflammatory molecules, and macrophage accumulation in injured arteries. MMRKO macrophages migrated less in culture. MMRKO decreased Ki67- and BrdU-positive macrophages in injured arteries. MMRKO macrophages were less Ki67-positive in culture. Conditioned media from MMRKO macrophages induced less migration, Ki67 positivity, and proinflammatory gene expression of vascular smooth muscle cells. After lipopolysaccharide treatment, MMRKO macrophages had decreased p-cFos and p-cJun compared with control macrophages, suggesting suppressed activation of activator protein-1 (AP1). Nuclear factor-κB (NF-κB) pathway was also inhibited by MMRKO, manifested by decreased p-IκB kinase-β and p-IκBα, increased IκBα expression, decreased nuclear translocation of p65 and p50, as welll as decreased phosphorylation and expression of p65. Finally, overexpression of serum-and-glucocorticoid-inducible-kinase-1 (SGK1) attenuated the effects of MR deficiency in macrophages.

Conclusions—

Selective deletion of MR in myeloid cells limits macrophage accumulation and vascular inflammation and, therefore, inhibits neointimal hyperplasia and vascular remodeling. Mechanistically, MR deficiency suppresses migration and proliferation of macrophages and leads to less vascular smooth muscle cell activation. At the molecular level, MR deficiency suppresses macrophage inflammatory response via SGK1-AP1/NF-κB pathways.
Diabetes Mellitus Is Associated With Reduced High-Density Lipoprotein Sphingosine-1-Phosphate Content and Impaired High-Density Lipoprotein Cardiac Cell Protection
Authors: Brinck Jonas W. , Thomas Aurélien , Lauer Estelle , Jornayvaz François R. , Brulhart-Meynet Marie-Claude , Prost Jean-Christophe , Pataky Zoltan , Löfgren Patrik , Hoffstedt Johan , Eriksson Mats , Pramfalk Camilla , Morel Sandrine , Kwak Brenda R. , van Eck Miranda , James Richard W. , Frias Miguel A.
Published: March 2016

Objective—

The dyslipidemia of type 2 diabetes mellitus has multiple etiologies and impairs lipoprotein functionality, thereby increasing risk for cardiovascular disease. High-density lipoproteins (HDLs) have several beneficial effects, notably protecting the heart from myocardial ischemia. We hypothesized that glycation of HDL could compromise this cardioprotective effect.

Approach and Results—

We used in vitro (cardiomyocytes) and ex vivo (whole heart) models subjected to oxidative stress together with HDL isolated from diabetic patients and nondiabetic HDL glycated in vitro (methylglyoxal). Diabetic and in vitro glycated HDL were less effective (
P
<0.05) than control HDL in protecting from oxidative stress. Protection was significantly, inversely correlated with the degree of in vitro glycation (
P
<0.001) and the levels of hemoglobin A1c in diabetic patients (
P
<0.007). The ability to activate protective, intracellular survival pathways involving Akt, Stat3, and Erk1/2 was significantly reduced (
P
<0.05) using glycated HDL. Glycation reduced the sphingosine-1-phosphate (S1P) content of HDL, whereas the S1P concentrations of diabetic HDL were inversely correlated with hemoglobin A1c (
P
<0.005). The S1P contents of in vitro glycated and diabetic HDL were significantly, positively correlated (both <0.01) with cardiomyocyte survival during oxidative stress. Adding S1P to diabetic HDL increased its S1P content and restored its cardioprotective function.

Conclusions—

Our data demonstrate that glycation can reduce the S1P content of HDL, leading to increased cardiomyocyte cell death because of less effective activation of intracellular survival pathways. It has important implications for the functionality of HDL in diabetes mellitus because HDL-S1P has several beneficial effects on the vasculature.
Protease-Activated Receptor 4 Variant p.Tyr157Cys Reduces Platelet Functional Responses and Alters Receptor Trafficking
Authors: Norman Jane E. , Cunningham Margaret R. , Jones Matthew L. , Walker Mary E. , Westbury Sarah K. , Sessions Richard B. , Mundell Stuart J. , Mumford Andrew D.
Published: March 2016

Objective—

Protease-activated receptor 4 (PAR4) is a key regulator of platelet reactivity and is encoded by
F2RL3
, which has abundant rare missense variants. We aimed to provide proof of principle that rare
F2LR3
variants potentially affect platelet reactivity and responsiveness to PAR1 antagonist drugs and to explore underlying molecular mechanisms.

Approach and Results—

We identified 6 rare
F2RL3
missense variants in 236 cardiac patients, of which the variant causing a tyrosine 157 to cysteine substitution (Y157C) was predicted computationally to have the greatest effect on PAR4 structure. Y157C platelets from 3 cases showed reduced responses to PAR4-activating peptide and to α-thrombin compared with controls, but no reduction in responses to PAR1-activating peptide. Pretreatment with the PAR1 antagonist vorapaxar caused lower residual α-thrombin responses in Y157C platelets than in controls, indicating greater platelet inhibition. HEK293 cells transfected with a PAR4 Y157C expression construct had reduced PAR4 functional responses, unchanged total PAR4 expression but reduced surface expression. PAR4 Y157C was partially retained in the endoplasmic reticulum and displayed an expression pattern consistent with defective
N
-glycosylation. Mutagenesis of Y322, which is the putative hydrogen bond partner of Y157, also reduced PAR4 surface expression in HEK293 cells.

Conclusions—

Reduced PAR4 responses associated with Y157C result from aberrant anterograde surface receptor trafficking, in part, because of disrupted intramolecular hydrogen bonding. Characterization of PAR4 Y157C establishes that rare
F2RL3
variants have the potential to markedly alter platelet PAR4 reactivity particularly after exposure to therapeutic PAR1 antagonists.
The High-Density Lipoprotein Puzzle
Authors: Rosenson Robert S.
Published: March 2016

Classical epidemiology has established the incremental contribution of the high-density lipoprotein (HDL) cholesterol measure in the assessment of atherosclerotic cardiovascular disease risk; yet, genetic epidemiology does not support a causal relationship between HDL cholesterol and the future risk of myocardial infarction. Therapeutic interventions directed toward cholesterol loading of the HDL particle have been based on epidemiological studies that have established HDL cholesterol as a biomarker of atherosclerotic cardiovascular risk. However, therapeutic interventions such as niacin, cholesteryl ester transfer protein inhibitors increase HDL cholesterol in patients treated with statins, but have repeatedly failed to reduce cardiovascular events. Statin therapy interferes with ATP-binding cassette transporter–mediated macrophage cholesterol efflux via miR33 and thus may diminish certain HDL functional properties. Unraveling the HDL puzzle will require continued technical advances in the characterization and quantification of multiple HDL subclasses and their functional properties. Key mechanistic criteria for clinical outcomes trials with HDL-based therapies include formation of HDL subclasses that improve the efficiency of macrophage cholesterol efflux and compositional changes in the proteome and lipidome of the HDL particle that are associated with improved antioxidant and anti-inflammatory properties. These measures require validation in genetic studies and clinical trials of HDL-based therapies on the background of statins.
Association Between Left Atrial Stiffness Index and Atrial Fibrillation Recurrence in Patients Undergoing Left Atrial Ablation
Authors: Khurram Irfan M. , Maqbool Farhan , Berger Ronald D. , Marine Joseph E. , Spragg David D. , Ashikaga Hiroshi , Zipunnikov Vadim , Kass David A. , Calkins Hugh , Nazarian Saman , Zimmerman Stefan L.
Published: March 2016

Background—

Atrial fibrillation (AF) is associated with significant abnormalities of left atrial (LA) systolic and diastolic function. This study describes a novel measure, LA stiffness index, that estimates LA diastolic function and its association with clinical outcomes of catheter ablation.

Methods and Results—

A total of 219 AF patients referred for ablation (59% paroxysmal, mean CHA
2
DS
2
VASc score 1.7±1.4) were enrolled. Atrial pressure and volume loops were prepared from invasive pressure measures and cardiac magnetic resonance imaging volumetric data during sinus rhythm for all patients. An LA stiffness index was created, defined by the ratio of change in LA pressure to volume during passive filling of LA (ΔP/ΔV). Patients were followed prospectively. Mean LA stiffness index for AF patients was 0.6±0.5 mm Hg/mL (paroxysmal AF 0.51±0.4 and persistent AF 0.73±0.6;
P
<0.001). Linear regression analysis showed a rise in the stiffness index with age, increasing at a rate of 0.02 mm Hg/mL per year (
P
<0.001). The LA stiffness index was higher in patients with previous LA ablation(s) for AF (0.51±0.35 versus 0.83±0.70;
P
<0.001). Forty of 160 patients had recurrence after AF ablation with a mean follow-up of 10.4±7.6 months. Patients with recurrence had higher stiffness index than those without recurrence (0.83±0.46 versus 0.40±0.22;
P
<0.001).

Conclusions—

LA stiffness index, a novel measure to assess LA diastolic function, increases with age and is higher in persistent AF and in the setting of repeat AF ablation. Greater LA stiffness index was independently associated with recurrence of AF after LA ablation.
Top–Down Activation of Spatiotopic Sensory Codes in Perceptual and Working Memory Search
Authors: Kuo Bo-Cheng , Nobre Anna Christina , Scerif Gaia , Astle Duncan E.
Published: March 2016

A critical requirement of an efficient cognitive system is the selection and prioritization of relevant information. This occurs when selecting specific items from our sensory inputs, which then receive preferential status at subsequent levels of processing. Many everyday tasks also require us to select internal representations, such as a relevant item from memory. We show that both of these types of search are underpinned by the spatiotopic activation of sensory codes, using both fMRI and MEG data. When individuals searched for perceived and remembered targets, the MEG data highlighted a sensor level electrophysiological effect that reflects the contralateral organization of the visual system—namely, the N2pc. The fMRI data were used to identify a network of frontoparietal areas common to both types of search, as well as the early visual areas activated by the search display. We then combined fMRI and MEG data to explore the temporal dynamics of functional connections between the frontoparietal network and the early visual areas. Searching for a target item resulted in significantly enhanced phase–phase coupling between the frontoparietal network and the visual areas contralateral to the perceived or remembered location of that target. This enhancement of spatially specific phase–phase coupling occurred before the N2pc effect and was significantly associated with it on a trial-by-trial basis. The combination of these two imaging modalities suggests that perceptual and working memory search are underpinned by the synchronization of a frontoparietal network and the relevant sensory cortices.
Eight new species of Cycloneuroterus Melika & Tang gallwasps from Taiwan and mainland China (Hymenoptera: Cynipidae: Cynipini)
Authors: TANG CHANG-TI , SINCLAIR FRAZER , HEARN JACK , YANG MAN-MIAO , STONE GRAHAM N. , NICHOLLS JAMES A. , SCHWÉGER SZABINA , MELIKA GEORGE
Published: March 2016

Eight new species of cynipid gallwasps, Cycloneuroterus abei Melika & Tang, C. ergei Tang & Melika, C. gilvus Melika & Tang, C. globosus Melika & Tang, C. jianwui Tang & Melika, C. lohsei Melika & Tang, C. tumiclavus Tang & Melika, C. uraianus Tang & Melika, from Taiwan and mainland China are described. Descriptions, diagnoses, biology, and host associations for the new species and a key to all Cycloneuroterus species are given. All taxa are supported by morphological and molecular data. Seven newly described species induce galls on Quercus subgenus Cyclobalanopsis, while one, C. uraianus, induces galls on Castanopsis. This is the first Cycloneuroterus species known to associate with Castanopsis.
New species of Claustropyga Hippa, Vilkamaa & Mohrig (Diptera, Sciaridae) from the Holarctic region
Authors: HIPPA HEIKKI , VILKAMAA PEKKA
Published: March 2016

The following four new species are described: Claustropyga clavulata sp. n. (Canada), C. lobigera sp. n. (Finland), C. modica sp. n. (Finland) and C. stupenda sp. n. (Canada, Russia). A fifth, probably new species is briefly discussed. Claustropyga stupenda has spectacular morphological characters in its hypopygium. There are now 23 species in Claustropyga.
Carcinoecium-forming Epizoanthus [Hexacorallia: Zoantharia] and the biology of E. papillosus in the eastern Atlantic, with special reference to the cnidom
Authors: RYLAND JOHN S. , WARD HELEN
Published: March 2016

Epizoanthus is a poorly known zoantharian genus in need of further study. Benthic surveys have shown that E. papillosus (until recently considered rare) is quite abundant in the Celtic Sea, Minches and northern North Sea, occurring as carcin-oecia formed in association with Anapagurus laevis (Anomura, Paguridae) and as smaller free-living colonies. It is also extensively distributed in the western Atlantic. A study of the cnidom in tentacles and mesenteric filaments has shown that carcinoecia contained fewer types and smaller numbers of nematocysts (basitrichs, p-mastigophores, and two different holotrich types) and spirocysts than free-living colonies, probably a consequence of being able to scavenge food from the pagurid. A method for obtaining quantitative estimates of spirocyst abundance is described. The mesenteric filaments of two of the three carcinoecia analysed contained numerous unexploded nematocysts (kleptocnidae) sequestered from the scyphomedusan Cyanea (probably C. capillata), presumably derived from the long tentacles trailing over the sea bed. This occurrence has never previously been recorded. The taxonomic study of larger, deep-sea, carcinoecium-forming species of Epizoanthus is complicated by the same paucity of nematocysts noted for E. papillosus.
Using Gordiid cysts to discover the hidden diversity, potential distribution,
and new species of Gordiids (Phylum Nematomorpha)
Authors: HARKINS CLEO , SHANNON RYAN , PAPEŞ MONICA , SCHMIDT-RHAESA ANDREAS , HANELT BEN , BOLEK MATTHEW G.
Published: March 2016

In this study, we sampled aquatic snails for the presence of hairworm cysts from 46 streams in Payne County, Oklahoma. Gordiid cysts were found at 70 % (32/46) of sites examined. Based on cyst morphology, we were able to identify three morphological types of gordiid cysts, including Paragordius, Gordius, and Chordodes/Neochordodes. Using our gordiid cyst presence data in conjunction with environmental variables, we developed an ecological niche model using Maxent to identify areas suitable for snail infections with gordiids. The model successfully predicted all presence localities of gordiid cysts in snails over a geographic area of 1,810 km2. We used this information, along with arthropod host infections and crowdsourcing, citizen scientists sampling for adult free-living worms during peak emergent times in areas predicted suitable by the model, to document Paragordius varius, Chordodes morgani, and a new species of gordiid (Gordius n. sp.). To our knowledge, this is the first ecological niche model attempted on such a narrow geographic scale (county level) that recovered known locations successfully. We provide new scanning electron micrographs and molecular data for these species. Our field data and ecological niche model clearly indicate that gordiid cysts are easy to detect in the environment and together these sampling techniques can be useful in discovering new species of gordiids, even in relatively well sampled areas for these cryptic parasites.
A new species of Amaralia Fowler (Siluriformes: Aspredinidae) from the Paraná-Paraguay River Basin
Authors: FRIEL JOHN P. , CARVALHO TIAGO P.
Published: March 2016

A new species of the banjo catfish genus Amaralia is described from the Paraná-Paraguay River Basin in central-western Brazil, Paraguay and northern Argentina. Amaralia oviraptor is distinguished from its single and allopatric congener, Amaralia hypsiura, by the greater number of dorsal-fin rays (3 vs. 2); by the absence of lateral contact between middle and posterior nuchal plates (vs. middle and posterior nuchal plates contacting each other laterally); and by a longer cleithral process (17.4–19.5 % of SL, mean 18.2 % vs. 14.0–17.2 % of SL, mean=15.5 %). Comments on the peculiar oophagic diet of Amaralia and an extended diagnosis of the genus are provided.
New species of Rhagoletotrypeta (Diptera: Tephritidae) from the Dominican Republic and southern Brazil and Paraguay
Authors: NORRBOM ALLEN L. , SAVARIS MARCOANDRE , MARINONI LUCIANE
Published: March 2016

Rhagoletotrypeta chapecensis Norrbom & Savaris, new species, and R. gelabertae Norrbom & Savaris, new species, are described and illustrated from specimens from southern Brazil (Paraná, Santa Catarina) and Paraguay, and from the Dominican Republic, respectively. The larvae of R. chapecensis develop in fruits of Celtis iguanaea (Jacq.) Sarg. (Ulmaceae). A key to the species of the xanthogastra species group is provided.
Review of the Polistes (Polistella) "Stenopolistes" species-group (Hymenoptera: Vespidae: Polistinae) from Vietnam, with description of a new species and key to species
Authors: NGUYEN LIEN T.P. , CARPENTER JAMES M.
Published: March 2016

The "Stenopolistes" species-group of the subgenus Polistella Ashmead, 1904 comprising in Vietnam by six species. Polistes adsimilis Nguyen & Carpenter sp. nov. is described and figured. Polistes khasianus Cameron, 1900 is confirmed to occur in Vietnam, P. pallidus Gusenleitner, 2011 is newly recorded from Vietnam. A key to Vietnamese species is provided. The nest of P. khasianus is described.
Effect of Shear Applied During a Pharmaceutical Process on Near Infrared Spectra
Authors: Hernández Eduardo , Pawar Pallavi , Rodriguez Sandra , Lysenko Sergiy , Muzzio Fernando J. , Romañach Rodolfo J.
Published: March 2016

This study describes changes observed in the near-infrared (NIR) diffuse reflectance (DR) spectra of pharmaceutical tablets after these tablets were subjected to different levels of strain (exposure to shear) during the mixing process. Powder shearing is important in the mixing of powders that are cohesive. Shear stress is created in a system by moving one surface over another causing displacements in the direction of the moving surface and is part of the mixing dynamics of particulates in many industries including the pharmaceutical industry. In continuous mixing, shear strain is developed within the process when powder particles are in constant movement and can affect the quality attributes of the final product such as dissolution. These changes in the NIR spectra could affect results obtained from NIR calibration models. The aim of the study was to understand changes in the NIR diffuse reflectance spectra that can be associated with different levels of strain developed during blend shearing of laboratory samples. Shear was applied using a Couette cell and tablets were produced using a tablet press emulator. Tablets with different shear levels were measured using NIR spectroscopy in the diffuse reflectance mode. The NIR spectra were baseline corrected to maintain the scattering effect associated with the physical properties of the tablet surface. Principal component analysis was used to establish the principal sources of variation within the samples. The angular dependence of elastic light scattering shows that the shear treatment reduces the size of particles and produces their uniform and highly isotropic distribution. Tablet compaction further reduces the diffuse component of scattering due to realignment of particles.
Application of In-Line Mid-Infrared (MIR) Spectroscopy Coupled with Calorimetry for the Determination of the Molar Enthalpy of Reaction between Ammonium Chloride and Sodium Nitrite
Authors: Kartnaller Vinicius , Mariano Danielly C.O. , Cajaiba João
Published: March 2016

The reaction between ammonium chloride and sodium nitrite has been known for its application as a source of heat because of its large enthalpy of reaction, for which it has been used by the oil industry. There have been no known calorimetric studies for the experimental determination of its molar enthalpy of reaction, which is necessary in order to predict the limits achieved for up-scale applications. Attenuated total reflection Fourier transform infrared spectroscopy (ATR FT-IR) and reaction calorimetry were used to determine this value by using a simple methodology. Both techniques were used concomitantly as a source of information regarding the time-dependent moles converted (Δ n) and the amount of exchanged heat (Δ H). The molar enthalpy of reaction was calculated to be −74 ± 4 kcal mol−1. The percentage between the confidence interval and the calculated value was 5.4%, which shows that the methodology was precise. After the determination of the molar enthalpy of reaction, it was proved that the ATR FT-IR alone was able to be used as a substitute for the reaction calorimetry technique, in which the IR signal is converted to the heat information, presenting as an easier technique for the monitoring of the heat released by this system for future applications.
FDI in Central and Eastern Europe’s (CEE) Agribusiness
Authors: István Takács , Bharti Nalin
Published: March 2016

Central and Eastern Europe (CEE) had adopted restricted industrialization policy until 1990. The economic and social transition started after 1990, providing free atmosphere for foreign investments in CEE. Due to such interference, the early eminent countries were replaced by new eminent ones. This article examines the affirmative as well as unimpressed role of foreign direct investment (FDI) in agribusiness in CEE during 1990s–2000s. Like CEE, India was also a restricted economy until 1991. As a part of continuing reforms, India has recently allowed a bulk of FDI in agribusiness sectors which have prompted farmers and local industrialists to raise their voice against such decision. Agriculture, being a livelihood of major population, needs a better farm–firm link through investment. Evidence from the CEE has proved many positive outcome of FDI. However, India cannot ignore some eccentric lessons from CEE.
A study on mechanical properties of Al5052/CFRP/Al5052 composite through three-point bending tests and shear lap tests according to surface roughness
Authors: Lee MS , Kim SJ , Lim OD , Kang CG
Published: March 2016

In this study, aluminum samples with various microsurface roughness values were produced by sandblasting to investigate the effect of the Ra (Surface roughness) value on the samples’ mechanical properties. Toward this end, a carbon fiber reinforced plastic/Al5052 hybrid sample was produced, and its mechanical properties were investigated through a tensile test, three-point bending test, and shear lap test. The theoretical and experimental tensile strength values of the hybrid composite were compared. During the bending test, CFRP and AI5052 separated in untreated specimens. A side-view examination revealed that the adhesion was best when the surface roughness was greatest ( Ra = 1.2 µm). Furthermore, shear load increased with the surface roughness. Therefore, the surface treatment was a crucial factor in making the specimen surface even and in increasing the roughness and therefore improving adhesion.
Analytical model of the stress–strain state of multilayer composite plates under the influence of different load types with asymmetrical boundary conditions
Authors: Bitkina Olga , Lee Jang-Ho , Kang Ki-Weon , Darlington Elena
Published: March 2016

Composite structure design experience has demonstrated that use of the finite element method during the first stage of the design process is unfounded and that analytical methods to determine the stress–strain state are needed for more accurate calculations. Therefore, an analytical model of the stress–strain state of multilayer composite plates under the influence of temperature, technological, and power loads with different boundary conditions around four boundaries of a rectangular plate was developed. This model enables the solution of more than 240 different boundary value problems with a combination of the following boundary conditions: fixed, moving, hinged, and free edge. In the derivation of this mathematical analytic model, the Kirchhoff hypothesis was applied to the entire body of the anisotropic medium for the interconnected deflection and bending in the plate plane. The resulting equation is an octic linear partial differential equation to express the generalized function of movements.
The Emotional Brain as a Predictor and Amplifier of Chronic Pain
Authors: Vachon-Presseau E. , Centeno M.V. , Ren W. , Berger S.E. , Tétreault P. , Ghantous M. , Baria A. , Farmer M. , Baliki M.N. , Schnitzer T.J. , Apkarian A.V.
Published: March 2016

Human neuroimaging studies and complementary animal experiments now identify the gross elements of the brain involved in the chronification of pain. We briefly review these advances in relation to somatic and orofacial persistent pain conditions. First, we emphasize the importance of reverse translational research for understanding chronic pain—that is, the power of deriving hypotheses directly from human brain imaging of clinical conditions that can be invasively and mechanistically studied in animal models. We then review recent findings demonstrating the importance of the emotional brain (i.e., the corticolimbic system) in the modulation of acute pain and in the prediction and amplification of chronic pain, contrasting this evidence with recent findings regarding the role of central sensitization in pain chronification, especially for orofacial pain. We next elaborate on the corticolimbic circuitry and underlying mechanisms that determine the transition to chronic pain. Given this knowledge, we advance a new mechanistic definition of chronic pain and discuss the clinical implications of this new definition as well as novel therapeutic potentials suggested by these advances.
The state and employment relations in the Philippines
Authors: Hutchison Jane
Published: March 2016

Employment relations in the Philippines feature significant formal rights and protections for workers on the one hand, and feeble enforcement of these by the state on the other. This is not explained by weak state capacities, separate from political logics. Hence, with some modifications to accommodate the character of the Philippine state, this article applies Hyman’s conceptualisation of ‘three broad and often contradictory’ logics to state power across the areas of labour standards, labour relations and labour policy participation. Across these, legitimation concerns – both domestic and international – have shaped much of the formal architecture of employment relations in the Philippines, whilst pacification and accumulation priorities tend to underlie lax state enforcement of labour standards, employer impunity with respect to unfair labour practices, extrajudicial violence against leftists, as well as the legal restrictions on strikes. International actors – the United States and the International Labour Organisation – have also determined the formal architecture, but in ways that stress associational freedoms over associational strength. This has left the mainstream of the labour movement with significant organisational interests in the status quo, despite its attendant weaknesses.
Error Patterns in Ordering Fractions Among At-Risk Fourth-Grade Students
Authors: Malone Amelia S. , Fuchs Lynn S.
Published: March 2016

The three purposes of this study were to (a) describe fraction ordering errors among at-risk fourth grade students, (b) assess the effect of part-whole understanding and accuracy of fraction magnitude estimation on the probability of committing errors, and (c) examine the effect of students’ ability to explain comparing problems on the probability of committing errors. Students ( N = 227) completed a nine-item ordering test. A high proportion (81%) of problems were completed incorrectly. Most (65%) errors were due to students misapplying whole number logic to fractions. Fraction-magnitude estimation skill, but not part-whole understanding, significantly predicted the probability of committing this type of error. Implications for practice are discussed.