bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hydrogels With Integrin-Binding Angiopoietin-1–Derived Peptide, QHREDGS, for Treatment of Acute Myocardial Infarction
Authors: Reis Lewis A. , Chiu Loraine L.Y. , Wu Jun , Feric Nicole , Laschinger Carol , Momen Abdul , Li Ren-Ke , Radisic Milica 
Published: January 2015

Background—
Hydrogels are being actively investigated for direct delivery of cells or bioactive molecules to the heart after myocardial infarction (MI) to prevent cardiac functional loss. We postulate that immobilization of the prosurvival angiopoietin-1–derived peptide, QHREDGS, to a chitosan-collagen hydrogel could produce a clinically translatable thermoresponsive hydrogel to attenuate post-MI cardiac remodeling.

Methods and Results—

In a rat MI model, QHREDGS-conjugated hydrogel (QHG213H), control gel, or PBS was injected into the peri-infarct/MI zone. By in vivo tracking and chitosan staining, the hydrogel was demonstrated to remain in situ for 2 weeks and was cleared in ≈3 weeks. By echocardiography and pressure–volume analysis, the QHG213H hydrogel significantly improved cardiac function compared with the controls. Scar thickness and scar area fraction were also significantly improved with QHG213H gel injection compared with the controls. There were significantly more cardiomyocytes, determined by cardiac troponin-T staining, in the MI zone of the QHG213H hydrogel group; and hydrogel injection did not induce a significant inflammatory response as assessed by polymerase chain reaction and an inflammatory cytokine assay. The interaction of cardiomyocytes and cardiac fibroblasts with QHREDGS was found to be mediated by β
1
-integrins.

Conclusions—
We demonstrated for the first time that the QHG213H peptide–modified hydrogel can be injected in the beating heart where it remains localized for a clinically effective period. Moreover, the QHG213H hydrogel induced significant cardiac functional and morphological improvements after MI relative to the controls.
Antiandrogenic Therapy With Finasteride Attenuates Cardiac Hypertrophy and Left Ventricular Dysfunction
Authors: Zwadlo Carolin , Schmidtmann Elisa , Szaroszyk Malgorzata , Kattih Badder , Froese Natali , Hinz Hebke , Schmitto Jan Dieter , Widder Julian , Batkai Sandor , Bähre Heike , Kaever Volkhard , Thum Thomas , Bauersachs Johann , Heineke Joerg 
Published: January 2015

Background—
In comparison with men, women have a better prognosis when experiencing aortic valve stenosis, hypertrophic cardiomyopathy, or heart failure. Recent data suggest that androgens like testosterone or the more potent dihydrotestosterone contribute to the development of cardiac hypertrophy and failure. Therefore, we analyzed whether antiandrogenic therapy with finasteride, which inhibits the generation of dihydrotestosterone by the enzyme 5-α-reductase, improves pathological ventricular remodeling and heart failure.

Methods and Results—
We found a strongly induced expression of all 3 isoforms of the 5-α-reductase (Srd5a1 to Srd5a3) in human and mouse hearts with pathological hypertrophy, which was associated with increased myocardial accumulation of dihydrotestosterone. Starting 1 week after the induction of pressure overload by transaortic constriction, mice were treated with finasteride for 2 weeks. Cardiac function, hypertrophy, dilation, and fibrosis were markedly improved in response to finasteride treatment in not only male, but also in female mice. In addition, finasteride also very effectively improved cardiac function and mortality after long-term pressure overload and prevented disease progression in cardiomyopathic mice with myocardial Gαq overexpression. Mechanistically, finasteride, by decreasing dihydrotestosterone, potently inhibited hypertrophy and Akt-dependent prohypertrophic signaling in isolated cardiac myocytes, whereas the introduction of constitutively active Akt blunted these effects of finasteride.

Conclusions—
Finasteride, which is currently used in patients to treat prostate disease, potently reverses pathological cardiac hypertrophy and dysfunction in mice and might be a therapeutic option for heart failure.
Dysfunction in the βII Spectrin–Dependent Cytoskeleton Underlies Human Arrhythmia
Authors: Smith Sakima A. , Sturm Amy C. , Curran Jerry , Kline Crystal F. , Little Sean C. , Bonilla Ingrid M. , Long Victor P. , Makara Michael , Polina Iuliia , Hughes Langston D. , Webb Tyler R. , Wei Zhiyi , Wright Patrick , Voigt Niels , Bhakta Deepak , Spoonamore Katherine G. , Zhang Chuansheng , Weiss Raul , Binkley Philip F. , Janssen Paul M. , Kilic Ahmet , Higgins Robert S. , Sun Mingzhai , Ma Jianjie , Dobrev Dobromir , Zhang Mingjie , Carnes Cynthia A. , Vatta Matteo , Rasband Matthew N. , Hund Thomas J. , Mohler Peter J. 
Published: January 2015

Background—
The cardiac cytoskeleton plays key roles in maintaining myocyte structural integrity in health and disease. In fact, human mutations in cardiac cytoskeletal elements are tightly linked to cardiac pathologies, including myopathies, aortopathies, and dystrophies. Conversely, the link between cytoskeletal protein dysfunction and cardiac electric activity is not well understood and often overlooked in the cardiac arrhythmia field.

Methods and Results—
Here, we uncover a new mechanism for the regulation of cardiac membrane excitability. We report that βII spectrin, an actin-associated molecule, is essential for the posttranslational targeting and localization of critical membrane proteins in heart. βII spectrin recruits ankyrin-B to the cardiac dyad, and a novel human mutation in the ankyrin-B gene disrupts the ankyrin-B/βII spectrin interaction, leading to severe human arrhythmia phenotypes. Mice lacking cardiac βII spectrin display lethal arrhythmias, aberrant electric and calcium handling phenotypes, and abnormal expression/localization of cardiac membrane proteins. Mechanistically, βII spectrin regulates the localization of cytoskeletal and plasma membrane/sarcoplasmic reticulum protein complexes, including the Na/Ca exchanger, ryanodine receptor 2, ankyrin-B, actin, and αII spectrin. Finally, we observe accelerated heart failure phenotypes in βII spectrin–deficient mice.

Conclusions—
Our findings identify βII spectrin as critical for normal myocyte electric activity, link this molecule to human disease, and provide new insight into the mechanisms underlying cardiac myocyte biology.
Reactive Oxygen Metabolites are Closely Associated With the Diagnosis and Prognosis of Coronary Artery Disease
Authors: Hirata Yoshihiro , Yamamoto Eiichiro , Tokitsu Takanori , Kusaka Hiroaki , Fujisue Koichiro , Kurokawa Hirofumi , Sugamura Koichi , Maeda Hirofumi , Tsujita Kenichi , Kaikita Koichi , Hokimoto Seiji , Sugiyama Seigo , Ogawa Hisao 
Published: January 2015

Background

Reactive oxygen species (
ROS
) are associated with development of coronary artery disease (
CAD
). However, there's no useful biomarker of
ROS
in
CAD
.

Methods and Results

We recruited 395 consecutive
CAD
patients who were performed coronary angiography (262 male and 133 female, age 70.2±10), and we measured serum derivatives of reactive oxidative metabolites (
DROM
) were measured. Two hundred twenty‐seven non‐
CAD
patients were also enrolled. We performed follow‐up study in these 395
CAD
patients and case‐control study after risk factor and 1:1 pair matching (both, n=163). As subgroup analysis,
DROM
were also measured at the aortic root and the coronary sinus in 59
CAD
patients.
DROM
were significantly higher in
CAD
patients (n=163, median [inter‐quartile range,
IQR
]=338 [302 to 386]) than in risk factor‐matched non‐
CAD
patients (n=163, 311 [282 to 352.5], effect size=0.33,
P
<0.001). During a mean follow‐up period of 20 months of 395
CAD
patients, 83 cardiovascular events were recorded. Kaplan‐Meier analysis showed a higher probability of cardiovascular events in the high‐
DROM
group (>346 U.CARR) than in the low‐
DROM
group (≤346 U.CARR) (
P
=0.001 [log‐rank test]). Multivariate Cox hazard analysis identified ln‐
DROM
as an independent predictor for cardiovascular events (hazard ratio: 10.8, 95% confidence interval: 2.76 to 42.4,
P
=0.001). The transcardiac gradient of
DROM
was significantly higher in
CAD
patients than in non‐
CAD
patients (−2.0 [−9.0 to 9.0] versus 8 [−8.0 to 28.3], effect size=0.21,
P
=0.04), indicating that
DROM
production in coronary circulation is associated with development of
CAD
.

Conclusion

DROM
are increased in
CAD
patients and associated with future cardiovascular events.
DROM
might provide clinical benefits for risk stratification of
CAD
.

Clinical Trial Registration

URL:
http://www.umin.ac.jp/ctr/
. Unique identifier: UMIN000012990.
The Effects of Short-term and Long-term Learning on the Responses of Lateral Intraparietal Neurons to Visually Presented Objects
Authors: Sigurdardottir Heida M. , Sheinberg David L. 
Published: January 2015

Abstract
The lateral intraparietal area (LIP) is thought to play an important role in the guidance of where to look and pay attention. LIP can also respond selectively to differently shaped objects. We sought to understand to what extent short-term and long-term experience with visual orienting determines the responses of LIP to objects of different shapes. We taught monkeys to arbitrarily associate centrally presented objects of various shapes with orienting either toward or away from a preferred spatial location of a neuron. The training could last for less than a single day or for several months. We found that neural responses to objects are affected by such experience, but that the length of the learning period determines how this neural plasticity manifests. Short-term learning affects neural responses to objects, but these effects are only seen relatively late after visual onset; at this time, the responses to newly learned objects resemble those of familiar objects that share their meaning or arbitrary association. Long-term learning affects the earliest bottom–up responses to visual objects. These responses tend to be greater for objects that have been associated with looking toward, rather than away from, LIP neurons' preferred spatial locations. Responses to objects can nonetheless be distinct, although they have been similarly acted on in the past and will lead to the same orienting behavior in the future. Our results therefore indicate that a complete experience-driven override of LIP object responses may be difficult or impossible. We relate these results to behavioral work on visual attention.
Papuadocus blodiwai gen. nov., sp. nov. (Crustacea: Amphipoda: Maeridae), a new bathyal species associated with sunken wood in the Bismarck Sea (Papua New Guinea)
Authors: CORBARI LAURE , SORBE JEAN CLAUDE 
Published: January 2015

A new species belonging to a new genus of Maeridae, Papuadocus blodiwai gen. nov., sp. nov., is described from bathyal bottoms of the Bismarck Sea (Papua New Guinea). This genus/species can be distinguished from most other known maerids by right and left maxillas 1 with asymmetrical palps and by gnathopod 2 not sexually dimorphic. Its closest relative is the genus Bathyceradocus also characterized by asymmetrical maxillas 1, but differing by the presence of gill on coxae 7. These observations lead to the conclusion that the diagnosis of the family Maeridae has to be amended to receive both Bathyceradocus and Papuadocus genera. All the collected specimens lived in association with sunken wood, at 500–580 m depth.
Evaluating Light Rain from Satellite- and Ground-Based Remote Sensing Data over the Subtropical North Atlantic
Authors: Burdanowitz Jörg , Nuijens Louise , Stevens Bjorn , Klepp Christian 
Published: January 2015

AbstractThree state-of-the-art satellite climatologies are analyzed for their ability to observe light rain from predominantly shallow, warm clouds over the subtropical North Atlantic Ocean trade winds (1998–2005). HOAPS composite (HOAPS-C), version 3.2; TMPA, version 7; and GPCP 1 Degree Daily (1DD), version 1.2, are compared with ground-based S-Pol radar data from the Rain in Cumulus over the Ocean (RICO; winter 2004/05) campaign and Micro Rain Radar data from the Barbados Cloud Observatory (2010–12). Winter rainfall amounts to one-third of annual rainfall, whereby light rain from warm clouds dominates. Daily rain occurrence and rain intensity during RICO largely differ among the satellite climatologies. TMPA best captures the frequent light rain events, only missing 7% of days on which the S-Pol radar detects rain, whereas HOAPS-C misses 33% and GPCP 1DD misses 56%. Algorithm constraints mainly cause these differences. In HOAPS-C also few available passive microwave (PMW) sensor overpasses limit its performance. TMPA outperforms HOAPS-C when only comparing nonmissing time steps, yet HOAPS-C can detect rain for S-Pol rain-covered areas down to 2%. In GPCP 1DD’s algorithm, the underestimated rain occurrence derived from PMW scanners is linked to the overestimated rain intensity, being constrained by the GPCP monthly satellite–gauge combination, whereby IR sensors determine the timing. Algorithm improvements in version 1.2 increased the rain occurrence by 50% relative to version 1.1. In version 7 of TMPA, algorithm corrections in PMW sounder data largely improved the rain detection relative to version 6. TMPA best represents light rain in the North Atlantic trades, followed by HOAPS-C and GPCP 1DD.
Modelled Rainfall Response to Strong El Niño Sea Surface Temperature Anomalies in the Tropical Pacific
Authors: Chung Christine T. Y. , Power Scott B. 
Published: January 2015

AbstractEl Niño–Southern Oscillation strongly influences the interannual variability of rainfall over the Pacific, shifting the position and orientation of the South Pacific convergence zone (SPCZ) and intertropical convergence zone (ITCZ). In 1982/83 and 1997/98, very strong El Niño events occurred, during which time the SPCZ and ITCZ merged into a single zonal convergence zone (szCZ) extending across the Pacific at approximately 5°S. The sea surface temperature anomalies (SSTAs) reached very large values and peaked farther east compared to other El Niño events. Previous work shows that tropical Pacific precipitation responds nonlinearly to changing the amplitude of the El Niño SSTA even if the structure of the SSTA remains unchanged, but large canonical El Niño SSTAs cannot reproduce the szCZ precipitation pattern. This study conducts idealized, SST-forced experiments, starting with a large-amplitude canonical El Niño SSTA and gradually adding a residual pattern until the full (1982/83) and (1997/98) mean SST is reproduced. Differences between the canonical and strong El Niño SSTA patterns are crucial in generating an szCZ event. Three elements influence the precipitation pattern: (i) the local meridional SST maxima influences the ITCZ position and western Pacific precipitation, (ii) the total zonal SST maximum influences the SPCZ position, and (iii) the equatorial Pacific SST influences the total amount of precipitation. In these experiments, the meridional SST gradient increases as the SSTAs approach szCZ conditions. Additionally, the precipitation changes evident in szCZ years are primarily driven by changes in the atmospheric circulation, rather than thermodynamic changes. The addition of a global warming SST pattern increases the precipitation along the equator and shifts the ITCZ farther equatorward.
Arctic Ocean Water Mass Transformation in S–T Coordinates
Authors: Pemberton Per , Nilsson Johan , Hieronymus Magnus , Meier H. E. Markus 
Published: January 2015

AbstractIn this paper, water mass transformations in the Arctic Ocean are studied using a recently developed salinity–temperature (S–T) framework. The framework allows the water mass transformations to be succinctly quantified by computing the surface and internal diffusive fluxes in S–T coordinates. This study shows how the method can be applied to a specific oceanic region, in this case the Arctic Ocean, by including the advective exchange of water masses across the boundaries of the region. Based on a simulation with a global ocean circulation model, the authors examine the importance of various parameterized mixing processes and surface fluxes for the transformation of water across isohaline and isothermal surfaces in the Arctic Ocean. The model-based results reveal a broadly realistic Arctic Ocean where the inflowing Atlantic and Pacific waters are primarily cooled and freshened before exiting back to the North Atlantic. In the model, the water mass transformation in the T direction is primarily accomplished by the surface heat flux. However, the surface freshwater flux plays a minor role in the transformation of water toward lower salinities, which is mainly driven by a downgradient mixing of salt in the interior ocean. Near the freezing line, the seasonal melt and growth of sea ice influences the transformation pattern.
Cost of Care for Subjective Tinnitus in Relation to Patient Satisfaction
Authors: Goldstein Eric , Ho Chuan‐Xing , Hanna Rania , Elinger Clara , Yaremchuk Kathleen L. , Seidman Michael D. , Jesse Michelle T. 
Published: January 2015

ObjectiveA consistent management algorithm for subjective tinnitus remains to be elucidated. Chronic tinnitus yields approximately US$2110 in annual health care costs per patient. However, it is unclear whether spending more in the management of tinnitus equates with greater patient satisfaction. Thus, the aim of this study is to correlate patient satisfaction with patient demographics, provider recommendations, and total health care–related expenditures.Study DesignA retrospective chart review and a patient satisfaction questionnaire.SettingAll data were collected from a large Midwestern hospital.Subjects and MethodsPatients were included who presented to the tinnitus clinic during the year 2011 and were between the ages of 18 and 89 years. They were excluded with diagnoses of Ménière’s disease, pulsatile tinnitus, acoustic neuromas, or autoimmune inner ear diseases. The retrospective data and satisfaction surveys were entered by 3 of the authors. Responses were based on Likert scales.ResultsOf the 692 patients included, 230 completed and returned the satisfaction questionnaire (33.2% response rate), yielding an overall mean of $662.60 charges. The frequency of intervention recommendations per patients ranged from 0 to 13, with a median of 4. Spearman’s correlations did not result in significant correlations between patient satisfaction and number of clinic visits (P =. 499) or associated charges (P =. 453).ConclusionGiven that the variability among provider recommendations, the high overall mean of tinnitus‐related charges, and patient satisfaction was not related to costs, further research is needed examining patient preference in the treatment of tinnitus.
Altered elastase—alpha1-antitrypsin balance in the blood of patients with chronic venous disease
Authors: Budzyn-Napierala M , Iskra M , Krasinski Z , Turkiewicz W , Gryszczynska B , Kasprzak M , Urbanek T 
Published: January 2015

Objectives Although leukocyte elastase is suspected to be involved in the damage of vein wall during chronic venous disease, the equilibrium between this protease and its inhibitor, alpha1-antitrypsin, has not yet been evaluated. The aim of the present study was to determine the relationship between leukocyte elastase and alpha1-antitrypsin, in the blood of patients with chronic venous disease. Patients and methods The concentration and the activity of leukocyte elastase along with the activity of alpha1-antitrypsin were evaluated in the blood of 55 chronic venous disease patients. The results were compared with those obtained in 33 healthy age and sex-matched volunteers. Results A significant decrease in the leukocyte elastase activity that correlated with an increased alpha1-antitrypsin activity was observed in the serum of patients with mild clinical symptoms of chronic venous disease. Conclusions The results of the study did not confirm a hypothesis about an important role of proteolytic activity of leukocyte elastase in the vein wall injury mechanism. They show that the leukocyte elastase–alpha1-antitrypsin balance is rather shifted toward antiprotease activity, especially in an early stage of chronic venous disease.
Antigenic modulation limits the effector cell mechanisms employed by type I anti-CD20 monoclonal antibodies
Authors: Tipton Thomas R. W. , Roghanian Ali , Oldham Robert J. , Carter Matthew J. , Cox Kerry L. , Mockridge C. Ian , French Ruth R. , Dahal Lekh N. , Duriez Patrick J. , Hargreaves Philip G. , Cragg Mark S. , Beers Stephen A. 
Published: January 2015

Key PointsAntigenic modulation significantly impacts natural killer cell and macrophage ability to mediate Fc γ receptor-dependent killing. hIgG1 mAbs are unable to elicit natural killer–mediated ADCC in the mouse, supporting ADCP as the dominant effector mechanism.
A novel mutation in the F5 gene (factor V Amsterdam) associated with bleeding independent of factor V procoagulant function
Authors: Cunha Marisa L. R. , Bakhtiari Kamran , Peter Jorge , Marquart J. Arnoud , Meijers Joost C. M. , Middeldorp Saskia 
Published: January 2015

Key Points
A novel gain-of-function mutation in factor V leading to increased levels of TFPI and bleeding was identified by whole exome sequencing. Factor V Amsterdam (F5 C2588G) resembles the mutation (F5 A2350G) leading to East Texas bleeding disorder.
MicroRNA-125b upregulation confers aromatase inhibitor resistance and is a novel marker of poor prognosis in breast cancer
Authors: Vilquin Paul , Donini Caterina F , Villedieu Marie , Grisard Evelyne , Corbo Laura , Bachelot Thomas , Vendrell Julie A , Cohen Pascale A 
Published: January 2015

Abstract
Introduction
Increasing evidence indicates that microRNAs (miRNAs) are important players in oncogenesis. Considering the widespread use of aromatase inhibitors (AIs) in endocrine therapy as a first-line treatment for postmenopausal estrogen receptor α–positive breast cancer patients, identifying deregulated expression levels of miRNAs in association with AI resistance is of utmost importance.

Methods
To gain further insight into the molecular mechanisms underlying the AI resistance, we performed miRNA microarray experiments using a new model of acquired resistance to letrozole (Res-Let cells), obtained by long-term exposure of aromatase-overexpressing MCF-7 cells (MCF-7aro cells) to letrozole, and a model of acquired anastrozole resistance (Res-Ana cells). Three miRNAs (miR-125b, miR-205 and miR-424) similarly deregulated in both AI-resistant cell lines were then investigated in terms of their functional role in AI resistance development and breast cancer cell aggressiveness and their clinical relevance using a cohort of 65 primary breast tumor samples.

Results
We identified the deregulated expression of 33 miRNAs in Res-Let cells and of 18 miRNAs in Res-Ana cells compared with the sensitive MCF-7aro cell line. The top-ranked Kyoto Encyclopedia of Genes and Genomes pathways delineated by both miRNA signatures converged on the AKT/mTOR pathway, which was found to be constitutively activated in both AI-resistant cell lines. We report for the first time, to our knowledge, that ectopic overexpression of either miR-125b or miR-205, or the silencing of miR-424 expression, in the sensitive MCF-7aro cell line was sufficient to confer resistance to letrozole and anastrozole, to target and activate the AKT/mTOR pathway and to increase the formation capacity of stem-like and tumor-initiating cells possessing self-renewing properties. Increasing miR-125b expression levels was also sufficient to confer estrogen-independent growth properties to the sensitive MCF-7aro cell line. We also found that elevated miR-125b expression levels were a novel marker for poor prognosis in breast cancer and that targeting miR-125b in Res-Let cells overcame letrozole resistance.

Conclusion
This study highlights that acquisition of specific deregulated miRNAs is a newly discovered alternative mechanism developed by AI-resistant breast cancer cells to achieve constitutive activation of the AKT/mTOR pathway and to develop AI resistance. It also highlights that miR-125b is a new biomarker of poor prognosis and a candidate therapeutic target in AI-resistant breast cancers.