bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dysfunctional Antibodies in the Tumor Microenvironment Associate with Impaired Anticancer Immunity
Authors: Zhang Ningyan , Deng Hui , Fan Xuejun , Gonzalez Anneliese , Zhang Songlin , Brezski Randall J. , Choi Byung-Kwon , Rycyzyn Michael , Strohl William , Jordan Robert , An Zhiqiang 
Published: July 2015

Abstract
Purpose: Studies have demonstrated that cancer-associated matrix metalloproteinases (MMP) can generate single peptide bond cleavages in the hinge region of immunoglobulin G1 (IgG1). This study investigated the cleavage of endogenous IgGs by MMPs in the tumor microenvironment and the consequences of the IgG hinge cleavage for humoral immunity.
Experimental Design: We investigated the occurrence of single peptide bond cleaved IgGs (scIgG) in tumor tissues and plasma samples collected from a cohort of breast cancer patients (n = 60). Samples from healthy people (n = 20) were used as the control. Antibody hinge cleavage was detected by multiple assays, including IHC, ELISA, and flow cytometry. A correlation analysis was conducted between scIgG levels and patient clinical parameters.
Results: Levels of scIgGs in tumors were significantly higher than in normal tissues. In addition, scIgG levels in tumors were enriched compared with that in the plasma of the same patients. The appearance of scIgGs in tumor tissues was associated with altered host IgG content and decreased IgG1. Increased tumor scIgGs were found to be positively correlated with adverse clinical factors, such as elevated tumor-associated macrophages, increased expression of MMP9 and other MMPs, and local metastasis to axillary lymph nodes.
Conclusions: The study contributes to mounting evidence for the presence of hinge-cleaved antibodies with reduced Fc immune effector function in the tumor microenvironment. The results highlight a link between tumor scIgGs and poor patient outcomes, and reveal a component of compromised humoral immunity within tumors that could point to new immunotherapeutic strategies to rescue host immunity. Clin Cancer Res; 21(23); 5380–90. ©2015 AACR.
Mass Cytometry: A High-Throughput Platform to Visualize the Heterogeneity of Acute Myeloid Leukemia
Authors: Do Priscilla , Byrd John C. 
Published: July 2015

Abstract
Summary: Behbehani and colleagues use mass cytometry to profile the heterogeneity of acute myeloid leukemia (AML) as compared with normal hematopoiesis. By using this approach and characterizing leukemic stem cells, important differences in response to chemotherapy between AML subsets can potentially be explained and new targeted approaches considered. Cancer Discov; 5(9); 912–4. ©2015 AACR.
See related article by Behbehani et al., p. 988.
Polyphosphates form antigenic complexes with platelet factor 4 (PF4) and enhance PF4-binding to bacteria
Authors: Brandt Sven , Krauel Krystin , Jaax Miriam , Renné Thomas , Helm Christiane A. , Hammerschmidt Sven , Delcea Mihaela , Greinacher Andreas 
Published: July 2015

SummaryShort chain polyphosphates (polyP) are pro-coagulant and pro-inflammatory platelet released inorganic polymers. The platelet chemokine platelet factor 4 (PF4) binds to lipid A on bacteria, inducing an antibody mediated host defense mechanism, which can be misdirected against PF4/heparin complexes leading to the adverse drug reaction heparin-induced thrombocytopenia (HIT). Here, we demonstrate that PF4 complex formation with soluble short chain polyP contributes to host defense mechanisms. Circular dichroism spectroscopy and isothermal titration calorimetry revealed that PF4 changed its structure upon binding to polyP in a similar way as seen in PF4/heparin complexes. Consequently, PF4/polyP complexes exposed neoepitopes to which human anti-PF4/heparin antibodies bound. PolyP enhanced binding of PF4 to Escherichia coli, hereby facilitating bacterial opsonisation and, in the presence of human anti-PF4/polyanion antibodies, phagocytosis. Our study indicates a role of polyP in enhancing PF4-mediated defense mechanisms of innate immunity.
Physical and Psychological Consequences of Left Cardiac Sympathetic Denervation in Long-QT Syndrome and Catecholaminergic Polymorphic Ventricular Tachycardia
Authors: Waddell-Smith Kathryn E. , Ertresvaag Kjetil N. , Li Jian , Chaudhuri Krish , Crawford Jackie R. , Hamill James K. , Haydock David , Skinner Jonathan R. 
Published: July 2015

Background—
Left cardiac sympathetic denervation reduces risk in long-QT syndrome (LQTS) and catecholaminergic polymorphic ventricular tachycardia. Side effects and patient satisfaction have not been systematically analyzed in patients who underwent left cardiac sympathetic denervation. Aims of this study included documenting physical and psychological consequences and patient satisfaction after left cardiac sympathetic denervation in LQTS or catecholaminergic polymorphic ventricular tachycardia.

Methods and Results—

Patients with LQTS (N=40) and catecholaminergic polymorphic ventricular tachycardia (N=7) underwent video-assisted thoracoscopic left cardiac sympathetic denervation, with a median follow-up of 29 months (range, 1–67 months). Clinical records were reviewed; 44 patients completed a telephone survey. Of 47 patients (53%), 25 were preoperatively symptomatic (15 syncope, 7 near-drowning, and 3 resuscitated sudden death). Indications for left cardiac sympathetic denervation included β-blocker intolerance (15; 32%) or nonadherence (10; 21%) and disease factors (18; 38%; catecholaminergic polymorphic ventricular tachycardia [6], near-drowning [2], exertional syncope [1], symptoms on therapy [2], LQT3 [1], QTc>520 ms [6]). Other indications were competitive sports participation (2), family history of sudden death (1), and other (1). Median QTc did not change among patients with LQTS (461±60 to 476±54 ms;
P
=0.49). Side effects were reported by 42 of 44 (95%). Twenty-nine patients (66%) reported dryness on left side, 26 (59%) a Harlequin-type (unilateral) facial flush, 24 (55%) contralateral hyperhidrosis, 17 (39%) differential hand temperatures, 5 (11%) permanent and 4 (9%) transient ptosis, 5 (11%) thermoregulation difficulties, 4 (9%) a sensation of left arm paresthesia, and 3 (7%) sympathetic flight/fright response loss. Majority of the patients were satisfied postoperatively: 38 (86%) were happy with the procedure, 33 (75%) felt safer, 40 (91%) recommended the procedure to others, and 40 (91%) felt happy with their scar appearance.

Conclusions—
Despite significant morbidity resulting from left cardiac sympathetic denervation, patients with LQTS and CPVT have high levels of postoperative satisfaction.
Clinical Risk Stratification for Primary Prevention Implantable Cardioverter Defibrillators
Authors: Lee Douglas S. , Hardy Judy , Yee Raymond , Healey Jeffrey S. , Birnie David , Simpson Christopher S. , Crystal Eugene , Mangat Iqwal , Nanthakumar Kumaraswamy , Wang Xuesong , Krahn Andrew D. , Dorian Paul , Austin Peter C. , Tu Jack V. 
Published: July 2015

Background—
A conceptualized model may be useful for understanding risk stratification of primary prevention implantable cardioverter defibrillators considering the competing risks of appropriate implantable cardioverter defibrillator shock versus mortality.

Methods and Results—

In a prospective, multicenter, population-based cohort with left ventricular ejection fraction ≤35% referred for primary prevention implantable cardioverter defibrillator, we developed dual risk stratification models to determine the competing risks of appropriate defibrillator shock versus mortality using a Fine-Gray subdistribution hazard model. Among 7020 patients referred, 3445 underwent defibrillator implant (79.7% men, median, 66 years [25th, 75th: 58–73]). During 5918 person-years of follow-up, appropriate shock occurred in 204 patients (3.6 shocks/100 person-years) and 292 died (4.9 deaths/100 person-years). Competing risk predictors of appropriate shock included nonsustained ventricular tachycardia, atrial fibrillation, serum creatinine concentration, digoxin or amiodarone use, and QRS duration near 130-ms peak. One-year cumulative incidence of appropriate shock was 0.9% in the lowest risk category, and 1.7%, 2.5%, 4.9%, and 9.3% in low, intermediate, high, and highest risk groups, respectively. Hazard ratios for appropriate shock ranged from 4.04 to 7.79 in the highest 3 deciles (all
P
≤0.001 versus lowest risk). Cumulative incidence of 1-year death was 0.6%, 1.9%, 3.3%, 6.2%, and 17.7% in lowest, low, intermediate, high, and highest risk groups, respectively. Mortality hazard ratios ranged from 11.48 to 36.22 in the highest 3 deciles (all
P
<0.001 versus lowest risk).

Conclusions—
Simultaneous estimation of risks of appropriate shock and mortality can be performed using clinical variables, providing a potential framework for identification of patients who are unlikely to benefit from prophylactic implantable cardioverter defibrillator.
Autotaxin Derived From Lipoprotein(a) and Valve Interstitial Cells Promotes Inflammation and Mineralization of the Aortic Valve
Authors: Bouchareb Rihab , Mahmut Ablajan , Nsaibia Mohamed Jalloul , Boulanger Marie-Chloé , Dahou Abdellaziz , Lépine Jamie-Lee , Laflamme Marie-Hélène , Hadji Fayez , Couture Christian , Trahan Sylvain , Pagé Sylvain , Bossé Yohan , Pibarot Philippe , Scipione Corey A. , Romagnuolo Rocco , Koschinsky Marlys L. , Arsenault Benoît J. , Marette André , Mathieu Patrick 
Published: July 2015

Background—
Mendelian randomization studies have highlighted that lipoprotein(a) [Lp(a)] was associated with calcific aortic valve disease (CAVD). Lp(a) transports oxidized phospholipids with a high content in lysophosphatidylcholine. Autotaxin (ATX) transforms lysophosphatidylcholine into lysophosphatidic acid. We hypothesized that ATX-lysophosphatidic acid could promote inflammation/mineralization of the aortic valve.

Methods and Results—

We have documented the expression of ATX in control and mineralized aortic valves. By using different approaches, we have also investigated the role of ATX-lysophosphatidic acid in the mineralization of isolated valve interstitial cells and in a mouse model of CAVD. Enzyme-specific ATX activity was elevated by 60% in mineralized aortic valves in comparison with control valves. Immunohistochemistry studies showed a high level of ATX in mineralized aortic valves, which colocalized with oxidized phospholipids and apolipoprotein(a). We detected a high level of ATX activity in the Lp(a) fraction in circulation. Interaction between ATX and Lp(a) was confirmed by in situ proximity ligation assay. Moreover, we documented that valve interstitial cells also expressed ATX in CAVD. We showed that ATX-lysophosphatidic acid promotes the mineralization of the aortic valve through a nuclear factor κB/interleukin 6/bone morphogenetic protein pathway. In LDLR
–/–
/ApoB
100/100
/IGFII mice, ATX is overexpressed and lysophosphatidic acid promotes a strong deposition of hydroxyapatite of calcium in aortic valve leaflets and accelerates the development of CAVD.

Conclusions—
ATX is transported in the aortic valve by Lp(a) and is also secreted by valve interstitial cells. ATX-lysophosphatidic acid promotes inflammation and mineralization of the aortic valve and thus could represent a novel therapeutic target in CAVD.
SMA Selectively Codes the Active Accumulation of Temporal, Not Spatial, Magnitude
Authors: Coull Jennifer T. , Charras Pom , Donadieu Maxime , Droit-Volet Sylvie , Vidal Franck 
Published: July 2015

Abstract
Estimating duration depends on the sequential integration (accumulation) of temporal information in working memory. Using fMRI, we directly compared the accumulation of information in temporal versus spatial domains. Participants estimated either the duration or distance of the dynamic trajectory of a moving dot or, in a control condition, a static line stimulus. Comparing the duration versus distance of static lines activated an extensive cortico-striatal network. By contrast, comparing the duration versus distance of dynamic trajectories, both of which required sequential integration of information, activated SMA alone. Indeed, activity in SMA, as well as right inferior occipital cortex, increased parametrically as a function of stimulus duration and also correlated with individual differences in the propensity to overestimate stimulus duration. By contrast, activity in primary visual cortex increased parametrically as a function of stimulus distance. Crucially, a direct comparison of the parametric responses to duration versus distance revealed that activity in SMA increased incrementally as a function of stimulus duration but not as a function of stimulus distance. Collectively, our results indicate that SMA responds to the active accumulation of information selectively in the temporal domain.
Numerical Modeling of Multiscale Dynamics at a High Reynolds Number: Instabilities, Turbulence, and an Assessment of Ozmidov and Thorpe Scales
Authors: Fritts David C. , Wang Ling , Geller Marvin A. , Lawrence Dale A. , Werne Joe , Balsley Ben B. 
Published: July 2015

Abstract
A high–Reynolds number direct numerical simulation (DNS) is employed to explore the instability and turbulence dynamics accompanying an idealized multiscale flow that approximates such environments observed throughout the atmosphere. The DNS describes the superposition of a stable gravity wave (GW) and a stable, oscillatory, finescale shear flow that together yield significant wave–wave interactions, GW breaking, Kelvin–Helmholtz instabilities (KHI), fluid intrusions, and turbulence. Larger-scale GW breaking and KHI events account for the strongest turbulence intensities, with intrusions competing with KHI and GW breaking at smaller spatial scales and later times. These dynamics drive a series of sheet-and-layer structures in the velocity, stability, and dissipation fields that persist for many buoyancy periods. Measures of local turbulence intensities include energy dissipation rates, Ozmidov and Thorpe scales (LO and LT, respectively), and a buoyancy Reynolds number sufficient to ensure sustained, strong turbulence events. These exhibit significant variability between and within instability events of different types. The Ozmidov and Thorpe scales for individual events are employed to assess variations of their ratio, C = LO/LT, with time. The value of C is highly variable with event type and time but typically increases with time because significant fluid overturning most often precedes turbulence. The value of C determined for the entire domain varies from 0 prior to instability to approximately 2 or larger at late times, with minima (maxima) prior to (following) significant instability and turbulence events. This appears to preclude an assumption that C is constant in stratified flows, except perhaps as an event average that may depend on event type.
Probabilistic Forecasts of Snow Water Equivalent and Runoff in Mountainous Areas*
Authors: Jörg-Hess Stefanie , Griessinger Nena , Zappa Massimiliano 
Published: July 2015

Abstract
Good initial states can improve the skill of hydrological ensemble predictions. In mountainous regions such as Switzerland, snow is an important component of the hydrological system. Including estimates of snow cover in hydrological models is of great significance for the prediction of both flood and streamflow drought events. In this study, gridded snow water equivalent (SWE) maps, derived from daily snow depth measurements, are used within the gridded version of the conceptual hydrological model Precipitation Runoff Evapotranspiration Hydrotope (PREVAH) to replace the model SWE at initialization. The ECMWF Ensemble Prediction System (ENS) reforecast is used as meteorological input for 32-day forecasts of streamflow and SWE. Experiments were performed in several parts of the Alpine Rhine and the Thur River. Predictions where modeled SWE estimates were replaced with SWE maps could successfully enhance the predictability of SWE up to a lead time of 25 days, especially at the beginning and the end of the snow season. Additionally, the prediction of the runoff volume was improved, particularly in catchments where the snow accumulation, and thus the runoff volume, had been greatly overestimated. These improvements in predictions have been made without affecting the ability of the forecast system to discriminate between the different runoff volumes observed. A spatial similarity score was first used in the context of SWE forecast verification. This confirmed the findings of the time series analysis and yielded additional insight on regional patterns of extended range SWE predictability.
Evaluation of blood neutrophil to lymphocyte and platelet to lymphocyte ratios according to plasma glucose status and serum insulin-like growth factor 1 levels in patients with acromegaly
Authors: Üçler R , Aslan M , Atmaca M , Alay M , Ademoğlu EN , Gülşen İ 
Published: July 2015

Introduction: Cardiovascular, respiratory, and cerebrovascular diseases and malignancies are responsible for morbidity and mortality in acromegaly. Also these diseases are associated with chronic inflammation. The neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) are currently gaining interest as new markers of inflammation. Moreover, increased morbidity and mortality are positively correlated with the presence of diabetes and levels of insulin-like growth factor 1 (IGF-1) in acromegaly. The objective of the present study was to investigate the relationship between these markers and acromegaly according to plasma glucose status and serum IGF-1 levels. Materials and Methods: We retrospectively analyzed data from 61 acromegaly patients who were in a newly diagnosed period (35 male, 26 female; mean age 38.13 ± 13.98). Patients with normal plasma glucose ( n = 27), impaired fasting glucose ( n = 18), and diabetes mellitus ( n = 16) were categorized into three different groups. NLR and PLR were compared between the study groups and were evaluated according to IGF-1 levels. Results: There were no statistically significant differences in NLR and PLR measurements among the study groups ( p > 0.05). However, there were significant positive correlations between NLR and IGF-1 levels and between PLR and IGF-1 levels when all patients were evaluated ( r = 0.334, p = 0.011 and r = 0.277, p = 0.035, respectively). Conclusions: This is the first report studying the relationship of NLR and PLR with glucose status and IGF-1 levels in acromegaly patients. Our study results suggest that subclinical inflammation may play a role in increased incidence of mortality and morbidity, which depends on uncontrolled IGF-1 levels in patients with acromegaly.
Why undocumented immigrant workers should have workplace rights
Authors: Clibborn Stephen 
Published: July 2015

AbstractThere exists a gap at the intersection of Australia’s immigration and employment laws that has serious implications for employees, employers and policy. Australia is host to a large and growing population of immigrants working without authorisation, described as the most significant problem facing Australian immigration authorities. These undocumented workers are often exploited by employers through wage theft, sexual harassment and unsafe working conditions. Yet, they are not entitled to protection under Australia’s employment laws. In addition to the implications for workers, there are broader policy concerns arising from the current system of regulation that effectively rewards employers who are equally in breach of immigration law. Left uncorrected, current regulation may in fact be encouraging a ‘race to the bottom’ for employment standards and increasing undocumented immigrant work. As well as highlighting the inadequacy of the existing regulatory framework, potential avenues for addressing this are explored.
Delays in accessing electroconvulsive therapy: a comparison between two urban and two rural populations in Australia
Authors: Johnston Natalie E 
Published: July 2015

Objective: A comparison of the timing, rates and characteristics of electroconvulsive therapy use between urban and rural populations. Method: The medical records of patients who received an acute course of electroconvulsive therapy at two rural and two urban psychiatric hospitals in New South Wales (NSW), Australia, in 2010 were reviewed retrospectively. Main outcome measures were the time from symptom onset, diagnosis and admission to commencing electroconvulsive therapy. Rates of use of electroconvulsive therapy were also compared between rural and urban hospitals using NSW statewide data. Results: There was a significant delay in the time it took for rural patients to receive electroconvulsive therapy compared with urban patients when measured both from the time of symptom onset and from when they received a diagnosis. There were corresponding delays in the time taken for rural patients to be admitted to hospital compared with urban patients. There was no difference in the time it took to commence electroconvulsive therapy once a patient was admitted to hospital. NSW statewide urban–rural comparisons showed rates of electroconvulsive therapy treatment were significantly higher in urban hospitals. Conclusions: Patients in rural areas receive electroconvulsive therapy later in their acute illness due to delays in being admitted to hospital. The rate of use of electroconvulsive therapy also differs geographically.
Developmental staging models in bipolar disorder
Authors: Passos Ives C , Jansen Karen , Kapczinski Flavio 
Published: July 2015

AbstractThe previous contribution of Duffy and colleagues suggests that a chain of behavioral events starting during childhood precedes the development of full-blown bipolar disorder. In this vein, the recent contribution of Keown-Stoneman and colleagues brings a new perspective to the study of prodromal symptoms of bipolar disorder.
The “Barbarous Game”: Entrudo and Its Critics in Rio de Janeiro, 1810s–1850s
Authors: Kraay Hendrik 
Published: July 2015

Abstract
This article examines the pre-Lenten festivities labeled entrudo in early nineteenth-century Rio de Janeiro and traces the efforts to repress them, which enjoyed a measure of success by the mid-1850s. During this period, the predominant form of pre-Lenten revelry involved various forms of water play that transgressed the boundaries between the sexes but tended to respect other social hierarchies. After independence, authorities and members of a self-proclaimed “civilized” elite sought to repress what they condemned as a “barbarous” game. These efforts obtained some success in the 1840s and 1850s as masked balls and parading by elite carnival societies came to dominate middle- and upper-class forms of celebration, although entrudo persisted longer among the lower classes. Based on travelers' accounts and the extensive newspaper debates about entrudo and its repression, this article analyzes a major cultural change among the Brazilian capital's elite.