bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterisation of lymphocyte subpopulations in infantile haemangioma
Authors: Tan Elysia M S , Itinteang Tinte , Chudakova Daria A , Dunne Jonathan C , Marsh Reginald , Brasch Helen D , Davis Paul F , Tan Swee T 
Published: June 2015

AimsInterstitial CD45+ cells and T lymphocytes have previously been demonstrated within infantile haemangioma (IH). This study investigated the expression of B and T lymphocyte markers by the CD45+ population, and the expression of Thy-1, a marker of thymocyte progenitors, which have the ability to give rise to both B and T cells.MethodsImmunohistochemical (IHC) staining was performed on proliferating and involuted IHs for the expression of CD45, CD3, CD20, CD79a, Thy-1 and CD34. The presence of mRNA corresponding toCD45, CD3G, CD20andThy-1was confirmed by reverse transcriptase-polymerase chain reaction in snap-frozen IH tissues. Cell counting of 3,3-diaminobenzidine IHC-stained slides was performed on CD45+ only cells and dually stained CD45+/CD3+ cells or CD45+/CD20+ cells and analysed statistically. In situ hybridisation and mass spectrometry were also performed to confirm the presence and abundance of Thy-1, respectively.ResultsIHC staining showed a subpopulation of CD45+ interstitial cells that expressed the T lymphocyte marker, CD3, and another subpopulation that expressed the B lymphocyte marker, CD20, in proliferating and diminished in involuted IHs. The abundant expression of Thy-1 on the endothelium of proliferating, but not involuted IH, was demonstrated by IHC staining and confirmed by in situ hybridisation and mass spectrometry.ConclusionsBoth B and T lymphocytes are present within the interstitium of proliferating and involuted IH. The expression of Thy-1 by the endothelium suggests that B and T cells in IH may have originated from within the lesion, rather than migrating from the peripheral circulation.
Altered gut–liver axis and hepatic adiponectin expression in OSAS: novel mediators of liver injury in paediatric non-alcoholic fatty liver
Authors: Nobili Valerio , Alisi Anna , Cutrera Renato , Carpino Guido , De Stefanis Cristiano , D'Oria Valentina , De Vito Rita , Cucchiara Salvatore , Gaudio Eugenio , Musso Giovanni 
Published: June 2015

BackgroundMechanism(s) connecting obstructive sleep apnoea syndrome (OSAS) to liver injury in paediatric non-alcoholic fatty liver disease (NAFLD) are unknown. We hypothesised alterations in gut–liver axis and in the pool and phenotype of hepatic progenitor cells (HPCs) may be involved in OSAS-associated liver injury in NAFLD.MethodsEighty biopsy-proven NAFLD children (age, mean±SD, 11.4±2.0 years, 56% males, body mass indexz-score 1.95±0.57) underwent a clinical–biochemical assessment, with measurement of insulin sensitivity, plasma cytokines, lipopolysaccharide (LPS), an intestinal permeability test and a standard polysomnography. Hepatic toll-like receptor (TLR)-4 expression by liver-resident cells and overall number and expression of resistin and adiponectin by HPCs were assessed by immunofluorescence and immunohistochemistry. OSAS was defined by an apnoea/hypopnoea index ≥1.ResultsOSAS was characterised by an increased intestinal permeability and endotoxemia, coupled with TLR-4 upregulation in hepatocytes, Kupffer and hepatic stellate cells (HSCs) and by an expansion of an adiponectin-deficient HPC pool, key features of steatohepatitis and fibrosis.The duration of haemoglobin desaturation (SaO2<90%) independently predicted intestinal permeability (β: 0.396; p=0.026), plasma LPS (β: 0.358; p=0.008) and TLR-4 expression by hepatocytes (β: 0.332; p=0.009), Kupffer cells (β: 0.357; p=0.006) and HSCs (β:0.445; p=0.002).SaO2<90% predicted also HPC number (β: 0.471; p=0.001) and impaired adiponectin expression by HPC pool (β: −0.532; p=0.0009).These relationships were observed in obese and non-obese children.ConclusionsIn paediatric NAFLD, OSAS is associated with increased endotoxemia coupled with impaired gut barrier function, with increased TLR-4-mediated hepatic susceptibility to endotoxemia and with an expansion of an adiponectin-deficient HPC pool. These alterations may represent a novel pathogenic link and a potential therapeutic target for OSAS-associated liver injury in NAFLD.
Cooperative Resource Allocation in Open Systems of Systems
Authors: Anders Gerrit , Schiendorfer Alexander , Siefert Florian , Steghöfer Jan-Philipp , Reif Wolfgang 
Published: June 2015

Resource allocation is a common problem in many technical systems. In multi-agent systems, the decentralized or regionalized solution of this problem usually requires the agents to cooperate due to their limited resources and knowledge. At the same time, if these systems are of large scale, scalability issues can be addressed by a self-organizing hierarchical system structure that enables problem decomposition and compartmentalization. In open systems, various uncertainties—introduced by the environment as well as the agents’ possibly self-interested or even malicious behavior—have to be taken into account to be able to allocate the resources according to the actual demand.
In this article, we present a trust- and cooperation-based algorithm that solves a dynamic resource allocation problem in open systems of systems. To measure and deal with uncertainties imposed by the environment and the agents at runtime, the algorithm uses the social concept of trust. In a hierarchical setting, we additionally show how agents create constraint models by learning the capabilities of subordinate agents if these are not able or willing to disclose this information. Throughout the article, the creation of power plant schedules in decentralized autonomous power management systems serves as a running example.
Amplification of Long Noncoding RNA ZFAS1 Promotes Metastasis in Hepatocellular Carcinoma
Authors: Li Tao , Xie Junjie , Shen Chuan , Cheng Dongfeng , Shi Yuan , Wu Zhichong , Deng Xiaxing , Chen Hao , Shen Baiyong , Peng Chenghong , Li Hongwei , Zhan Qian , Zhu Zhecheng 
Published: June 2015

Abstract
Despite progress in the diagnostics and treatment of hepatocellular carcinoma (HCC), its prognosis remains poor. In this study, we globally assessed long noncoding RNAs (lncRNA) for contributions to HCC using publicly available microarray data, in vitro and in vivo assays. Here, we report that ZFAS1, encoding a lncRNA that is frequently amplified in HCC, is associated with intrahepatic and extrahepatic metastasis and poor prognosis of HCC. ZFAS1 functions as an oncogene in HCC progression by binding miR-150 and abrogating its tumor-suppressive function in this setting. miR-150 repressed HCC cell invasion by inhibiting ZEB1 and the matrix metalloproteinases MMP14 and MMP16. Conversely, ZFAS1 activated ZEB1, MMP14, and MMP16 expression, inhibiting these effects of miR-150. Our results establish a function for ZFAS1 in metastatic progression and suggest its candidacy as a new prognostic biomarker and target for clinical management of HCC. Cancer Res; 75(15); 3181–91. ©2015 AACR.
Comorbidity and Survival in Lung Cancer Patients
Authors: Islam K.M. Monirul , Jiang Xiaqing , Anggondowati Trisari , Lin Ge , Ganti Apar Kishor 
Published: June 2015

Abstract
Background: As the population of the United States ages, there will be increasing numbers of lung cancer patients with comorbidities at diagnosis. Comorbid conditions are important factors in both the choice of the lung cancer treatment and outcomes. However, the impact of individual comorbid conditions on patient survival remains unclear.
Methods: A population-based cohort study of 5,683 first-time diagnosed lung cancer patients was captured using the Nebraska Cancer Registry (NCR) linked with the Nebraska Hospital Discharge Data (NHDD) between 2005 and 2009. A Cox proportional hazards model was used to analyze the effect of comorbidities on the overall survival of patients stratified by stage and adjusting for age, race, sex, and histologic type.
Results: Of these patients, 36.8% of them survived their first year after lung cancer diagnosis, with a median survival of 9.3 months for all stages combined. In this cohort, 26.7% of the patients did not have any comorbidity at diagnosis. The most common comorbid conditions were chronic pulmonary disease (52.5%), diabetes (15.7%), and congestive heart failure (12.9%). The adjusted overall survival of lung cancer patients was negatively associated with the existence of different comorbid conditions such as congestive heart failure, diabetes with complications, moderate or severe liver disease, dementia, renal disease, and cerebrovascular disease, depending on the stage.
Conclusions: The presence of comorbid conditions was associated with worse survival. Different comorbid conditions were associated with worse outcomes at different stages.
Impact: Future models for predicting lung cancer survival should take individual comorbid conditions into consideration. Cancer Epidemiol Biomarkers Prev; 24(7); 1079–85. ©2015 AACR.
St. John's Wort Attenuates Colorectal Carcinogenesis in Mice through Suppression of Inflammatory Signaling
Authors: Manna Soumen K. , Golla Srujana , Golla Jaya Prakash , Tanaka Naoki , Cai Yan , Takahashi Shogo , Krausz Kristopher W. , Matsubara Tsutomu , Korboukh Ilia , Gonzalez Frank J. 
Published: June 2015

Abstract
Despite widespread use as well as epidemiologic indications, there have been no investigations into the effect of St. John's wort (SJW) extract on colorectal carcinogenesis in vivo. This study reports a systematic evaluation of the impact of dietary supplementation of SJW extract on azoxymethane-induced colorectal carcinogenesis in mice. Mice were fed with either AIN-93G (control) diet or SJW extract–supplemented diet (SJW diet) prior to azoxymethane treatment. SJW diet was found to significantly improve the overall survival of azoxymethane-treated mice. Pretreatment with the SJW diet significantly reduced body weight loss as well as decrease of serum albumin and cholesterol levels associated with azoxymethane-induced colorectal tumorigenesis. SJW diet–fed mice showed a significant decrease in tumor multiplicity along with a decrease in incidence of large tumors and a trend toward decreased total tumor volume in a dose-dependent manner. A short-term study, which examined the effect of SJW prior to rectal bleeding, also showed decrease in colorectal polyps in SJW diet–fed mice. Nuclear factor kappa B (NF-κB) and extracellular signal–regulated kinase (ERK1/2) pathways were attenuated by SJW administration. SJW extract resulted in early and continuous attenuation of these pathways in the colon epithelium of SJW diet–fed mice under both short-term and long-term treatment regimens. In conclusion, this study demonstrated the chemopreventive potential of SJW extract against colorectal cancer through attenuation of proinflammatory processes. Cancer Prev Res; 8(9); 786–95. ©2015 AACR.
Proteome Analysis of Human Arterial Tissue Discloses Associations Between the Vascular Content of Small Leucine-Rich Repeat Proteoglycans and Pulse Wave Velocity
Authors: Lyck Hansen Maria , Beck Hans Christian , Irmukhamedov Akhmadjon , Jensen Pia Søndergaard , Olsen Michael Hecht , Rasmussen Lars Melholt 
Published: June 2015

Objectives—
We hypothesized that arterial stiffness is associated with changes in the arterial protein profile, particularly of extracellular matrix components. We aimed at determining differentially expressed proteins by quantitative proteome analysis in arterial tissue from patients with different degrees of arterial stiffness.

Approach and Results—

Arterial stiffness, assessed by carotid-femoral pulse wave velocity (PWV), central blood pressure and augmentation index by pulse wave analysis were measured the day before surgery in a group of patients undergoing coronary artery bypass grafting. Protein extracts of well-defined, homogenous, nonatherosclerotic individual samples of the left mammary artery from 10 of these patients with high PWV and 9 with low PWV were compared by quantitative proteome analysis, using tandem mass tag labeling and nano–liquid chromatography mass spectrometry/mass spectrometry. Of 418 quantified proteins, 28 were differentially expressed between the groups with high and low PWV (
P
<0.05). Three of 7 members of the extracellular matrix family of small leucine-rich repeat proteoglycans displayed significant differences between the 2 groups (
P
=0.0079; Fisher exact test). Three other ECM proteins were differentially regulated, that is, collagen, type VIII, α-1 and α-2 and collagen, type IV, α-1. Several proteins related to smooth muscle cell function and structure were also found in different amounts between the 2 groups.

Conclusions—
Changes in the arterial amounts of small leucine-rich proteoglycans, known to be involved in collagen fibrillogenesis, and of some nonfibrillar collagens in combination with alterations in proteins related to functions of the human arterial smooth muscle are associated with arterial stiffness, as determined by PWV.
Regulation of Vascular Endothelial Growth Factor Receptor Function in Angiogenesis by Numb and Numb-Like
Authors: van Lessen Max , Nakayama Masanori , Kato Katsuhiro , Kim Jung Mo , Kaibuchi Kozo , Adams Ralf H. 
Published: June 2015

Objective—
Vascular endothelial growth factor (VEGF) signaling is a major regulator of physiological and pathological angiogenesis. VEGF receptor activity is strongly controlled by endocytosis, which can terminate or enhance signal transduction in the angiogenic endothelium, but the exact molecular regulation of these processes remains incompletely understood. We have therefore examined the function of Numb family clathrin-associated sorting proteins in angiogenesis.

Approach and Results—

We show that Numb proteins are expressed by endothelial cells during retinal angiogenesis in mice. Inducible inactivation of the
Numb
/
Numbl
genes in the postnatal endothelium led to impaired vessel growth, reduced endothelial proliferation and sprouting, and decreased VEGF receptor activation. Biochemistry and cell biology experiments established that Numb can interact with VEGFR2 and VEGFR3 and controls VEGF receptor activation in response to ligand stimulation. Experiments in cultured endothelial cells showed that Numb proteins counteract VEGF receptor degradation and promote VEGFR2 recycling back to the plasma membrane.

Conclusions—
Numb proteins control VEGF receptor endocytosis, signaling, and recycling in endothelial cells, which promotes the angiogenic growth of blood vessels.
Evaluation of the Necessity for Cardioverter-Defibrillator Implantation in Elderly Patients With Brugada Syndrome
Authors: Kamakura Tsukasa , Wada Mitsuru , Nakajima Ikutaro , Ishibashi Kohei , Miyamoto Koji , Okamura Hideo , Noda Takashi , Aiba Takeshi , Takaki Hiroshi , Yasuda Satoshi , Ogawa Hisao , Shimizu Wataru , Makiyama Takeru , Kimura Takeshi , Kamakura Shiro , Kusano Kengo 
Published: June 2015

Background—
The clinical characteristics and prognosis of elderly patients with Brugada syndrome (BrS) are largely unknown. The purpose of this study was to evaluate the risks and benefits of implantable cardioverter defibrillator (ICD) in elderly patients with BrS based on a long follow-up.

Methods and Results—
A total of 120 BrS patients with ICD (90 for aborted sudden cardiac arrest or syncope, mean age, 46.6±12.2 years; 50 with age ≥60 years at the last follow-up) were included in this study. During 102±68 months of follow-up, 31 patients (26%) experienced appropriate shocks. Age at the first attack of ventricular fibrillation (VF) was <70 years in all patients (mean, 45.0±12.1 years), the incidence of VF decreased with age, and VF did not recur after 70 years of age except in 2 patients with ischemic heart disease. Eleven of 28 patients with supraventricular tachycardia experienced inappropriate shocks. These inappropriate shocks increased with age and reached a peak in patients who were in their sixties. Lead failures occurred in later stages after implantation in 10 of 120 patients (8%).

Conclusions—
Long-term follow-up of high-risk BrS patients with ICD showed a low incidence of VF in those aged >70 years. Considering the increasing risk of inappropriate shocks because of the relatively late onset of supraventricular tachycardia and lead failures, avoidance of ICD implantation, or replacement may be considered in elderly BrS patients who remain free from VF until 70 years of age.
Clinical Characteristics and Outcomes of Patients With Coronary Artery Disease and Angina
Authors: Badar Athar A. , Perez-Moreno Ana Cristina , Hawkins Nathaniel M. , Jhund Pardeep S. , Brunton Alan P.T. , Anand Inder S. , McKelvie Robert S. , Komajda Michel , Zile Michael R. , Carson Peter E. , Gardner Roy S. , Petrie Mark C. , McMurray John J.V. 
Published: June 2015

Background—
The aim of our study was to investigate the relationship between coronary artery disease (CAD), angina, and clinical outcomes in patients with heart failure and preserved ejection fraction enrolled in the irbesartan in patients with heart failure and preserved systolic function (I-Preserve) trial.

Methods and Results—

The mean follow-up period for the 4128 patients enrolled in I-Preserve was 49.5 months. Patients were divided into 4 mutually exclusive groups according to history of CAD and angina: patients with no history of CAD or angina (n=2008), patients with no history of CAD but a history of angina (n=649), patients with a history of CAD but no angina (n=468), and patients with a history of CAD and angina (n=1003); patients with no known CAD or angina were the reference group. After adjustment for other prognostic variables using Cox proportional-hazard models, patients with CAD but no angina were found to be at higher risk of all-cause mortality (hazard ratio [HR], 1.58 [1.22–2.04];
P
<0.01) and sudden death (HR, 2.12 [1.33–3.39];
P
<0.01), compared with patients with no CAD or angina. Patients with CAD and angina were also at higher risk of all-cause mortality (HR, 1.29 [1.05–1.59];
P
=0.02) and sudden death (HR, 1.83 [1.24–2.69];
P
<0.01) compared with the same reference group and had the highest risk of unstable angina or myocardial infarction (HR, 5.84 [3.43–9.95];
P
<0.01).

Conclusions—
Patients with heart failure and preserved ejection fraction and CAD are at higher risk of all-cause mortality and sudden death when compared with those without CAD.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00095238.
Childhood Psychosocial Adversity and Adult Neighborhood Disadvantage as Predictors of Cardiovascular Disease
Authors: Halonen Jaana I. , Stenholm Sari , Pentti Jaana , Kawachi Ichiro , Subramanian S.V. , Kivimäki Mika , Vahtera Jussi 
Published: June 2015

Background—
Childhood adverse psychosocial factors (eg, parental divorce, long-term financial difficulties) and adult neighborhood disadvantage have both been linked to increased cardiovascular disease (CVD). However, their combined effects on disease risk are not known.

Methods and Results—
Participants were 37 699 adults from the Finnish Public Sector study whose data were linked to a national neighborhood disadvantage grid with the use of residential addresses between the years 2000 and 2008 and who responded to a survey on childhood psychosocial adversities and adult CVD risk behaviors in 2008 to 2009. Survey data were also linked to national registers on hospitalization, mortality, and prescriptions to assess CVD risk factors in 2008 to 2009 and to ascertain incident CVD (coronary heart disease or cerebrovascular disease) between the survey and the end of December 2011 (mean follow-up, 2.94 years; SD=0.44 years). Combined exposure to high childhood adversity and high adult disadvantage was associated with CVD risk factors (hypertension, dyslipidemia, diabetes mellitus, obesity, smoking, heavy alcohol use, and physical inactivity) and with a 2.25-fold (95% confidence interval, 1.39–3.63) hazard of incident CVD compared with a low childhood adversity and low adult disadvantage. This hazard ratio was attenuated by 16.6% but remained statistically significant after adjustment for the CVD risk factors (1.96; 95% confidence interval, 1.22–3.16). Exposure to high childhood adversity or high adult neighborhood disadvantage alone was not significantly associated with CVD in fully adjusted models.

Conclusions—
These findings suggest that individuals with both childhood psychosocial adversity and adult neighborhood disadvantage are at an increased risk of CVD. In contrast, those with only 1 of these exposures have little or no excess risk after controlling for conventional risk factors.
Comparison of Acute Stroke Preparedness Strategies to Decrease Emergency Department Arrival Time in a Multiethnic Cohort
Authors: Boden-Albala Bernadette , Stillman Joshua , Roberts Eric T. , Quarles Leigh W. , Glymour M. Maria , Chong Ji , Moats Harmon , Torrico Veronica , Parides Michael C. 
Published: June 2015

Background and Purpose—
Less than 25% of stroke patients arrive to an emergency department within the 3-hour treatment window. Stroke Warning Information and Faster Treatment (SWIFT) compared an interactive intervention (II) with enhanced educational (EE) materials on recurrent stroke arrival times in a prospective cohort of multiethnic stroke/transient ischemic attack survivors.

Methods—
A single-center randomized controlled trial (2005–2011) randomized participants to EE (bilingual stroke preparedness materials) or II (EE plus in-hospital sessions). We assessed differences by randomization in the proportion arriving to emergency department <3 hours, prepost intervention arrival <3 hours, incidence rate ratio for total events, and stroke knowledge and preparedness capacity.

Results—

SWIFT randomized 1193 participants (592 EE, 601 II): mean age 63 years; 50% female, 17% black, 51% Hispanic, 26% white. At baseline, 28% arrived to emergency department <3 hours. Over 5 years, first recurrent stroke (n=133), transient ischemic attacks (n=54), or stroke mimics (n=37) were documented in 224 participants. Incidence rate ratio=1.31 (95% confidence interval=1.05–1.63; II to EE). Among II, 40% arrived <3 hours versus 46% EE (
P
=0.33). In prepost analysis, there was a 49% increase in the proportion arriving <3 hours (
P
=0.001), greatest among Hispanics (63%,
P
<0.003). II had greater stroke knowledge at 1 month (odds ratio=1.63; 1.23–2.15). II had higher preparedness capacity at 1 month (odds ratio=3.36; 1.86, 6.10) and 12 months (odds ratio=7.64; 2.49, 23.49).

Conclusions—
There was no difference in arrival <3 hours overall between II and EE; the proportion arriving <3 hours increased in both groups and in race-ethnic minorities.

Clinical Trial Registration—
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00415389.