bluuebunny/crossref_metadata_2025_split huggingface dataset:
UV surface brightness of galaxies from the local universe to z ~ 5
Authors: Lerner Eric J. , Falomo Renato , Scarpa Riccardo 
Published: May 2014

The Tolman test for surface brightness (SB) dimming was originally proposed as a test for the expansion of the universe. The test, which is independent of the details of the assumed cosmology, is based on comparisons of the SB of identical objects at different cosmological distances. Claims have been made that the Tolman test provides compelling evidence against a static model for the universe. In this paper we reconsider this subject by adopting a static Euclidean universe (SEU) with a linear Hubble relation at all z (which is not the standard Einstein–de Sitter model), resulting in a relation between flux and luminosity that is virtually indistinguishable from the one used for ΛCDM models. Based on the analysis of the UV SB of luminous disk galaxies from HUDF and GALEX datasets, reaching from the local universe to z ~ 5, we show that the SB remains constant as expected in a static universe. A re-analysis of previously published data used for the Tolman test at lower redshift, when treated within the same framework, confirms the results of the present analysis by extending our claim to elliptical galaxies. We conclude that available observations of galactic SB are consistent with a SEU model. We do not claim that the consistency of the adopted model with SB data is sufficient by itself to confirm what would be a radical transformation in our understanding of the cosmos. However, we believe this result is more than sufficient reason to examine this combination of hypotheses further.
Complement C5a Receptor Facilitates Cancer Metastasis by Altering T-Cell Responses in the Metastatic Niche
Authors: Vadrevu Surya Kumari , Chintala Navin K. , Sharma Sharad K. , Sharma Priya , Cleveland Clayton , Riediger Linley , Manne Sasikanth , Fairlie David P. , Gorczyca Wojciech , Almanza Othon , Karbowniczek Magdalena , Markiewski Maciej M. 
Published: May 2014

Abstract
The impact of complement on cancer metastasis has not been well studied. In this report, we demonstrate in a preclinical mouse model of breast cancer that the complement anaphylatoxin C5a receptor (C5aR) facilitates metastasis by suppressing effector CD8+ and CD4+ T-cell responses in the lungs. Mechanisms of this suppression involve recruitment of immature myeloid cells to the lungs and regulation of TGFβ and IL10 production in these cells. TGFβ and IL10 favored generation of T regulatory cells (Treg) and Th2-oriented responses that rendered CD8+ T cells dysfunctional. Importantly, pharmacologic blockade of C5aR or its genetic ablation in C5aR-deficient mice were sufficient to reduce lung metastases. Depletion of CD8+ T cells abolished this beneficial effect, suggesting that CD8+ T cells were responsible for the effects of C5aR inhibition. In contrast to previous findings, we observed that C5aR signaling promoted Treg generation and suppressed T-cell responses in organs where metastases arose. Overall, our findings indicated that the immunomodulatory functions of C5aR are highly context dependent. Furthermore, they offered proof-of-concept for complement-based immunotherapies to prevent or reduce cancer metastasis. Cancer Res; 74(13); 3454–65. ©2014 AACR.
Paths of Resistance to EGFR Inhibitors: Is NF Enough?
Authors: Maertens Ophélia , Cichowski Karen 
Published: May 2014

Abstract
Summary: Although the majority of patients with EGFR-mutant lung cancer respond well to EGF receptor (EGFR) tyrosine kinase inhibitors (TKI), all patients eventually develop resistance. The mechanism of acquired resistance is still unknown for a considerable subset of cases. This study reveals the NF1 tumor suppressor gene as a new mediator of resistance to EGFR TKIs and provides a mechanistic rationale for developing combination therapies. Cancer Discov; 4(5); 519–21. ©2014 AACR.
See related article by de Bruin et al., p. 606
Affinity Enhancement of Antibodies: How Low-Affinity Antibodies Produced Early in Immune Responses Are Followed by High-Affinity Antibodies Later and in Memory B-Cell Responses
Authors: Eisen Herman N. 
Published: May 2014

AbstractThe antibodies produced initially in response to most antigens are high molecular weight (MW) immunoglobulins (IgM) with low affinity for the antigen, while the antibodies produced later are lower MW classes (e.g., IgG and IgA) with, on average, orders of magnitude higher affinity for that antigen. These changes, often termed affinity maturation, take place largely in small B-cell clusters (germinal center; GC) in lymphoid tissues in which proliferating antigen-stimulated B cells express the highly mutagenic cytidine deaminase that mediates immunoglobulin class-switching and sequence diversification of the immunoglobulin variable domains of antigen-binding receptors on B cells (BCR). Of the large library of BCR-mutated B cells thus rapidly generated, a small minority with affinity-enhancing mutations are selected to survive and differentiate into long-lived antibody-secreting plasma cells and memory B cells. BCRs are also endocytic receptors; they internalize and cleave BCR-bound antigen, yielding peptide–MHC complexes that are recognized by follicular helper T cells. Imperfect correlation between BCR affinity for antigen and cognate T-cell engagement may account for the increasing affinity heterogeneity that accompanies the increasing average affinity of antibodies. Conservation of mechanisms underlying mutation and selection of high-affinity antibodies over the ≈200 million years of evolution separating bird and mammal lineages points to the crucial role of antibody affinity enhancement in adaptive immunity. Cancer Immunol Res; 2(5); 381–92. ©2014 AACR.
Pharmacological Activation of the Melanocortin System Limits Plaque Inflammation and Ameliorates Vascular Dysfunction in Atherosclerotic Mice
Authors: Rinne Petteri , Silvola Johanna M.U. , Hellberg Sanna , Ståhle Mia , Liljenbäck Heidi , Salomäki Henriikka , Koskinen Emilia , Nuutinen Salla , Saukko Pekka , Knuuti Juhani , Saraste Antti , Roivainen Anne , Savontaus Eriika 
Published: May 2014

Objective—
Melanocortin peptides have been shown to elicit anti-inflammatory actions and to promote vascular endothelial function by activating type 1 and 3 melanocortin receptors. Here, we addressed whether these favorable properties of melanocortins could reduce atherosclerotic plaque inflammation and improve vasoreactivity in atherosclerotic mice.

Approach and Results—
Low-density lipoprotein receptor–deficient mice expressing only apolipoprotein B100 were fed a high-fat diet for 8 or 16 weeks and treated with either vehicle or a stable melanocortin analog, melanotan II (MT-II, 0.3 mg/kg per day, 4 weeks). We determined plaque uptake of fluorine-18–labeled fluorodeoxyglucose as a surrogate marker for atherosclerotic plaque inflammation and vascular function of the aorta by ex vivo analyses. MT-II had no effect on body weight or composition, or plasma cholesterol levels in atherosclerotic mice. Without attenuating atherosclerotic lesion size or lesional macrophage accumulation, MT-II treatment reduced fluorine-18–labeled fluorodeoxyglucose uptake in the atherosclerotic plaques. Resident macrophages in the lesions of MT-II–treated mice were polarized toward the anti-inflammatory M2 phenotype. Systemic inflammation was also attenuated by MT-II intervention as evidenced by decreased plasma levels of proinflammatory cytokines. In terms of aortic vasoreactivity, MT-II–treated mice showed enhanced endothelium-dependent relaxations, as well as promotion of vascular sensitivity to nitric oxide–mediated vasodilation, which were markedly impaired in control mice after prolonged duration of diet exposure.

Conclusions—
The present study demonstrates that pharmacological activation of the melanocortin system has therapeutic benefits in pre-established atherosclerosis by limiting plaque inflammation and promoting vascular endothelial function, which may provide a novel therapeutic approach for atherosclerosis.
von Willebrand Factor Directly Interacts With DNA From Neutrophil Extracellular Traps
Authors: Grässle Sandra , Huck Volker , Pappelbaum Karin I. , Gorzelanny Christian , Aponte-Santamaría Camilo , Baldauf Carsten , Gräter Frauke , Schneppenheim Reinhard , Obser Tobias , Schneider Stefan W. 
Published: May 2014

Objective—
Inflammatory conditions provoke essential processes in the human vascular system. It leads to the formation of ultralarge von Willebrand factor (VWF) fibers, which are immobilized on the endothelial cell surface and transform to highly adhesive strings under shear conditions. Furthermore, leukocytes release a meshwork of DNA (neutrophil extracellular traps) during the process of the recently discovered cell death program NETosis. In the present study, we characterized the interaction between VWF and DNA and possible binding sites to underline the role of VWF in thrombosis and inflammation besides its function in platelet adhesion.

Approach and Results—
Both functionalized surfaces and intact cell layers of human umbilical vein endothelial cells were perfused with isolated, protein-free DNA or leukocytes from whole blood at distinct shear rates. DNA–VWF interaction was monitored using fluorescence microscopy, ELISA-based assays, molecular dynamics simulations, and electrostatic potential calculations. Isolated DNA, as well as DNA released by stimulated leukocytes, was able to bind to shear-activated, but not inactivated, VWF. However, DNA–VWF binding does not alter VWF degradation by a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13. Moreover, DNA–VWF interaction can be blocked using unfractionated and low-molecular-weight heparin, and DNA–VWF complexes attenuate platelet binding to VWF. These findings were supported using molecular dynamics simulations and electrostatic calculations of the A1- and A2-domains.

Conclusions—
Our findings suggest that VWF directly binds and immobilizes extracellular DNA released from leukocytes. Therefore, we hypothesize that VWF might act as a linker for leukocyte adhesion to endothelial cells, supporting leukocyte extravasation and inflammation.
Oxidative Modification of Fibrinogen Is Associated With Altered Function and Structure in the Subacute Phase of Myocardial Infarction
Authors: Becatti Matteo , Marcucci Rossella , Bruschi Giulia , Taddei Niccolò , Bani Daniele , Gori Anna Maria , Giusti Betti , Gensini Gian Franco , Abbate Rosanna , Fiorillo Claudia 
Published: May 2014

Objective—
Among plasma proteins, fibrinogen represents a major target of oxidative modifications. In patients with post–acute myocardial infarction (6 months after the acute event), fibrinogen oxidation-induced carbonyls and fibrinogen function were estimated using in vitro and ex vivo approaches. Fibrinogen structural features and clot architecture were also explored.

Approach and Results—

In 39 patients with post–acute myocardial infarction and 28 age-, sex-, and risk factor-matched controls, oxidative stress markers (in plasma and in purified fibrinogen fractions), thrombin-catalyzed fibrin polymerization, and plasmin-induced fibrin lysis were estimated. Circular dichroism spectra of purified fibrinogen extracts, electron microscopy, and differential interference contrast microscopy analyses of fibrin clots were also performed. Marked signs of oxidative stress in plasma (
P
<0.01 versus controls) and, correspondingly, an increased extent of fibrinogen carbonylation (3.5-fold over control values;
P
<0.01 versus controls) were observed in patients. Furthermore, fibrinogen fractions purified from patients exhibited significantly reduced clotting ability and decreased susceptibility to plasmin-induced lysis (
P
<0.01 versus controls). Alterations in fibrinogen secondary structure, as suggested by circular dichroism spectroscopy, and in fibrin clot architecture, as analyzed by electron and differential interference contrast microscopy, were also identified.

Conclusions—
Here, we report for the first time that patients with post–acute myocardial infarction present with an overall imbalance in redox status and marked fibrinogen carbonylation associated with altered fibrinogen function, thus suggesting a role for carbonylation as a direct mechanism of fibrinogen function. The observed features occur along with modifications in protein structure and in clot architecture.
Catheter Ablation of Ventricular Arrhythmia in Nonischemic Cardiomyopathy
Authors: Oloriz Teresa , Silberbauer John , Maccabelli Giuseppe , Mizuno Hiroya , Baratto Francesca , Kirubakaran Senthil , Vergara Pasquale , Bisceglia Caterina , Santagostino Giulia , Marzi Alessandra , Sora Nicoleta , Roque Carla , Guarracini Fabrizio , Tsiachris Dimitris , Radinovic Andrea , Cireddu Manuela , Sala Simone , Gulletta Simone , Paglino Gabriele , Mazzone Patrizio , Trevisi Nicola , Bella Paolo Della 
Published: May 2014

Background—
The aim was to relate distinct scar distributions found in nonischemic cardiomyopathy with ventricular tachycardia (VT) morphology, late potential distribution, ablation strategy, and outcome.

Methods and Results—

Eighty-seven patients underwent catheter ablation for drug-refractory VT. Based on endocardial unipolar voltage, 44 were classified as predominantly anteroseptal and 43 as inferolateral. Anteroseptal patients more frequently fulfilled diagnostic criteria for dilated cardiomyopathy (64% versus 36%), associated with more extensive endocardial unipolar scar (41 [22–83] versus 9 [1–29] cm
2
;
P
<0.001). Left inferior VT axis was predictive of anteroseptal scar (positive predictive value, 100%) and right superior axis for inferolateral (positive predictive value, 89%). Late potentials were infrequent in the anteroseptal group (11% versus 74%;
P
<0.001). Epicardial late potentials were common in the inferolateral group (81% versus 4%;
P
<0.001) and correlated with VT termination sites (κ=0.667;
P
=0.014), whereas no anteroseptal patient had an epicardial VT termination (
P
<0.001). VT recurred in 44 patients (51%) during a median follow-up of 1.5 years. Anteroseptal scar was associated with higher VT recurrence (74% versus 25%; log-rank
P
<0.001) and redo procedure rates (59% versus 7%; log-rank
P
<0.001). After multivariable analysis, clinical predictors of VT recurrence were electrical storm (hazard ratio, 3.211;
P
=0.001) and New York Heart Association class (hazard ratio, 1.608;
P
=0.018); the only procedural predictor of VT recurrence was anteroseptal scar pattern (hazard ratio, 5.547;
P
<0.001).

Conclusions—
Unipolar low-voltage distribution in nonischemic cardiomyopathy allows categorization of scar pattern as inferolateral, often requiring epicardial ablation mainly based on late potentials, and anteroseptal, which frequently involves an intramural septal substrate, leading to a higher VT recurrence.
Remote or Extraischemic Intracerebral Hemorrhage—An Uncommon Complication of Stroke Thrombolysis
Authors: Mazya Michael V. , Ahmed Niaz , Ford Gary A. , Hobohm Carsten , Mikulik Robert , Nunes A. Paiva , Wahlgren Nils ,   Scientific Committee of SITS International, Wahlgren Nils , Dávalos Antoni , Ford Gary A. , Grond Martin , Hacke Werner , Hennerici Michael , Kaste Markku , Lees Kennedy R. , Roine Risto , Tatlisumak Turgut , Toni Danilo , Wang K.S. ,   Scientific Committee of Fighting Stroke (Uppdrag Besegra Stroke), Wahlgren Nils , Ahmed Niaz , Castrén Maaret , Eriksson Ulf , Frisén Jonas , Hedin Ulf , Holmin Staffan , Sjöholm Åke , Svensson Mikael , von Euler Mia 
Published: May 2014

Background and Purpose—
Intracerebral hemorrhage after treatment with intravenous recombinant tissue-type plasminogen activator for ischemic stroke can occur in local relation to the infarct, as well as in brain areas remote from infarcted tissue. We aimed to describe risk factors, 3-month mortality, and functional outcome in patients with the poorly understood complication of remote intracerebral hemorrhage, as well as local intracerebral hemorrhage.

Methods—
In this study, 43 494 patients treated with intravenous recombinant tissue-type plasminogen activator, with complete imaging data, were enrolled in the Safe Implementation of Treatments in Stroke-International Stroke Thrombolysis Register (SITS-ISTR) during 2002 to 2011. Baseline data were compared among 970 patients (2.2%) with remote parenchymal hemorrhage (PHr), 2325 (5.3%) with PH, 438 (1.0%) with both PH and PHr, and 39 761 (91.4%) without PH or PHr. Independent risk factors for all hemorrhage types were obtained by multivariate logistic regression.

Results—

Previous stroke (
P
=0.023) and higher age (
P
<0.001) were independently associated with PHr, but not with PH. Atrial fibrillation, computed tomographic hyperdense cerebral artery sign, and elevated blood glucose were associated with PH, but not with PHr. Female sex had a stronger association with PHr than with PH. Functional independence at 3 months was more common in PHr than in PH (34% versus 24%;
P
<0.001), whereas 3-month mortality was lower (34% versus 39%;
P
<0.001).

Conclusions—
Differences between risk factor profiles indicate an influence of previous vascular pathology in PHr and acute large-vessel occlusion in PH. Additional research is needed on the effect of pre-existing cerebrovascular disease on complications of recanalization therapy in acute ischemic stroke.
Long-Term Risk and Predictors of Recurrent Stroke Beyond the Acute Phase
Authors: Pennlert Johanna , Eriksson Marie , Carlberg Bo , Wiklund Per-Gunnar 
Published: May 2014

Background and Purpose—
Previous studies have shown heterogeneous results on predictors and rates of stroke recurrence. This study set out to investigate the long-term risk and predictors of recurrent stroke in Northern Sweden 1995 to 2008.

Methods—
In the population-based Monitoring Trends and Determinants of Cardiovascular Disease (MONICA) stroke incidence registry, stroke survivors of either ischemic stroke or intracerebral hemorrhage were followed for recurrent stroke or death. Cox regression was used to identify predictors of stroke recurrence.

Results—

The study comprised 6700 patients and 26 597 person-years. During follow-up, 928 (13.9%) patients had a recurrent stroke. Comparison between the first time period (1995–1998) and the last (2004–2008) showed declined risk of stroke recurrence (hazard ratio, 0.64 [95% confidence interval, 0.52–0.78]). Previous myocardial infarction was less prevalent in the most recent cohort (
P
<0.001). Predictors of stroke recurrence were age (hazard ratio, 1.03 [95% confidence interval, 1.02–1.04]) and diabetes mellitus (hazard ratio, 1.34 [95% confidence interval, 1.15–1.57]). After an index intracerebral hemorrhage (n=815), a major part of recurrent events were ischemic (63%), and compared with the ischemic stroke group (n=5885), a tendency toward lower risk of recurrence was observed.

Conclusions—
Despite declining recurrence rates in this relatively young stroke population, almost one third are either dead or have experienced a second stroke in 5 years.
Laryngopharyngeal Reflux
Authors: Gooi Zhen , Ishman Stacey L. , Bock Jonathan M. , Blumin Joel H. , Akst Lee M. 
Published: May 2014

Objective: This study aimed to describe current patterns for diagnosis and treatment of laryngopharyngeal reflux (LPR) and analyze differences between laryngologists and non-laryngologists. Methods: American Academy of Otolaryngology–Head and Neck Surgery and American Broncho-Esophagological Association members were invited to complete an online survey regarding evaluation, diagnosis, and treatment of LPR. Subgroup analysis was performed to identify differences between respondents who completed laryngology fellowships (LF) and those who did not (NL). Results: Of 159 respondents, 40 were LF. Video documentation of laryngopharyngeal exams was almost universal among LF (97% vs 38%, P < .0001). Use of rigid (100%, P = .002) and flexible distal-chip technologies (94%, P = .004) was more common among LF. Diagnostic criteria were similar between the groups, with symptoms of heartburn, globus, and throat clearing thought most suggestive of LPR. Adjunctive tests most commonly used were barium esophagram and dual-probe pH testing with impedance. Laryngology fellowship-trained respondents used dual pH probes with impedance more often ( P = .004). They were more likely to prescribe twice daily proton pump inhibitors with concurrent H2-blocker medication initially ( P = .004) and to treat for longer than 4 weeks ( P = .0003). Conclusion: Otolaryngologists are in agreement on symptoms and physical features of LPR; however, significant differences exist between laryngologists and non-laryngologists on the use of adjunctive testing and treatment strategies.
From FUS to Pandora syndrome
Authors: Tony Buffington C A , Westropp Jodi L , Chew Dennis J 
Published: May 2014

New concepts: Ideas about the causes of lower urinary tract signs (LUTS) in cats have changed significantly in the past 40 years. Recent research is challenging the conventional view that the bladder is always the perpetrator of LUTS, and suggests that the bladder can also be one victim of a systemic process associated with a sensitized central stress response system. Aim: In this article the authors provide their perspective on the implications of these findings for the diagnosis and treatment of cats with LUTS, provide some historical context, and suggest ways that the veterinary profession might work together to better understand the disorders underlying these signs, and possibly reduce their prevalence.
Feline dermatophytosis
Authors: Newbury Sandra , Moriello Karen A 
Published: May 2014

Practical relevance: Dermatophytosis (ringworm) is the most important infectious and contagious skin disease of cats in shelters. Its importance relates to the fact that it can affect all cats, but tends to affect those which would otherwise have good chances for adoption. Although many diseases in shelters fit this description, dermatophytosis is of particular significance because of associated public health concerns. Clinical challenges: Disease management in animal shelters is challenging because new animals are frequently entering the population, numerous animals are often housed together, and resources are almost always limited. Global relevance: Outbreaks of dermatophytosis occur worldwide and no animal shelter is completely shielded from possible introduction of the disease into the population. Audience: This article offers a flexible stepwise approach to dealing with a known or suspected outbreak of dermatophytosis in an animal shelter. It is based on the authors’ experiences spanning more than a decade of responses and/or consultations. While primarily aimed at veterinarians involved in shelter medicine, the principles largely apply to other group-housing situations, such as catteries and breeding establishments. Aims: The goals in dealing with a potential dermatophytosis outbreak are to ascertain if the ‘outbreak’ is actually an outbreak, to develop a shelter-specific outbreak management plan and to implement a long-term plan to prevent recurrences.