bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aortic Stiffness Measurement Improves the Prediction of Asymptomatic Coronary Artery Disease in Stroke/Transient Ischemic Attack Patients
Authors: Calvet David , Touzé Emmanuel , Laurent Stéphane , Varenne Olivier , Sablayrolles Jean-Louis , Boutouyrie Pierre , Mas Jean-Louis 
Published: July 2013

Background Aortic stiffness is an independent predictor of coronary events. Aims We assessed the predictive value of aortic stiffness for ⩾50% asymptomatic coronary artery disease in a stroke/transient ischemic attack population. Methods We enrolled 300 consecutive patients aged 45–75 years with nondisabling, noncardioembolic ischemic stroke or transient ischemic attack, and no prior history of coronary artery disease. Coronary artery disease was assessed with 64-section computed tomography coronary angiography and all patients had a detailed cervicocephalic arterial work-up. Aortic stiffness was determined from carotid-femoral pulse wave velocity with 9·6 m/s as cutoff value. The predictive value of aortic stiffness was assessed by logistic regression and reclassification tables method after adjustment for the Framingham Risk Score and the presence of cervicocephalic stenosis, which were previously shown to be independent predictor of ⩾50% asymptomatic coronary artery disease. Results Among the 274 included patients who had computed tomography coronary angiography, 26% (95% CI, 21%–32%) had an increased stiffness (pulse wave velocity > 9·6 m/s) and 18% (14%–23%) had ⩾50% asymptomatic coronary artery disease. Increased aortic stiffness was associated with the presence of ⩾50% asymptomatic coronary artery disease, both in univariate (odds ratio = 3·4 [1·8–6·4]) and multivariate analyses (odds ratio = 2·3 [1·2–4·7]) after adjustment for Framingham Risk Score and presence of cervicocephalic stenosis. After carotid-femoral pulse wave velocity was added to the standard model including Framingham Risk Score and the presence of cervicocephalic stenosis, net reclassification improvement was 12·6% ( P < 0·005), integrated discrimination index was 2·51% ( P = 0·025), and model fit was improved (likelihood ratio = 4·99, P = 0·025). Conclusions In stroke/transient ischemic attack patients, aortic pulse wave velocity improves the prediction of ⩾50% asymptomatic coronary artery disease beyond classical risk factors.
Loss of β‐arrestin 2 exacerbates experimental autoimmune encephalomyelitis with reduced number of Foxp3+ CD4+ regulatory T cells
Authors: Zhang Yu , Liu Chang , Wei Bin , Pei Gang 
Published: July 2013

Summaryβ‐Arrestins are well‐known regulators and mediators of G protein‐coupled receptor signalling, and accumulating evidence reveals that they are functionally involved in inflammation and autoimmune diseases. Of the two β‐arrestins, β‐arrestin 1 is documented to play regulatory roles in an animal model of multiple sclerosis (MS), whereas the role of β‐arrestin 2 is less clear. Here, we show that β‐arrestin 2‐deficient mice displayed the exacerbated and sustained symptoms of experimental autoimmune encephalomyelitis (EAE), an animal model of MS. At the cellular level, deficiency of β‐arrestin 2 led to a decreased number of Foxp3+ CD4+ regulatory T (Treg) cells in peripheral lymphoid organs of EAE mice. Consistently, our in vitro observations also revealed that loss of β‐arrestin 2 impaired the conversion of Foxp3− CD4+ T cells into Foxp3+ CD4+ inducible Treg cells. Taken together, our data suggest that β‐arrestin 2 plays a regulatory role in MS, that is opposite to that of β‐arrestin 1, in autoimmune diseases such as MS, which is at least partially through regulation of iTreg cell differentiation.
Influenza and respiratory syncytial virus are the major respiratory viruses detected from prospective testing of pediatric and adult coronial autopsies
Authors: Speers David J. , Moss Daniel M. , Minney‐Smith Cara , Levy Avram , Smith David W. 
Published: July 2013

BackgroundTo ascertain the full mortality of influenza and other respiratory viruses, the testing of community autopsy specimens is essential.MethodsRespiratory virus PCR and culture were performed on 2418 fresh unfrozen respiratory samples collected from 1611 coronial cases where the death was either unknown or infection was suspected, from July 2007 to June 2011, to detect the common respiratory viruses in children and adults, using standardized microbiological testing.ResultsThe respiratory virus positive rate was 8·3% (134 cases) with a peak of 28% (42 of 151 cases) in children under 10 years of age. Influenza virus was the commonest respiratory virus (50 cases, 3%), followed by respiratory syncytial virus (RSV) (30 cases, 2%). All tested respiratory viruses were found in children, most commonly adenovirus, enterovirus and RSV, and influenza A and RSV predominated in those over 60 years, but coinfection was uncommon. Almost all influenza cases occurred when influenza was widely circulating in the community but few were diagnosed pre‐mortem. Influenza and RSV detection was associated with bronchitis or bronchiolitis in 7 (9%) of the 80 cases and caused pneumonia in 14 (0·8%) deaths overall.ConclusionsOur prospective review of respiratory viruses using standardized testing found a single lower respiratory tract autopsy specimen for respiratory virus PCR would detect most community infections at the time of death.
A century of chasing the ice: delayed colonisation of ice‐free sites by ground beetles along glacier forelands in the Alps
Authors: Brambilla Mattia , Gobbi Mauro 
Published: July 2013

Climate change is affecting species distribution, composition of biological communities, and species traits. Despite the growing body of knowledge on the reaction of species to climate change, the potentially delayed response of species is still severely understudied.In this paper we modelled the time needed by ground‐living invertebrates to effectively react to habitat modification induced by climate change in relation to dispersal abilities. We analyzed the occurrence pattern of alpine ground beetles (carabids) along areas recently freed by retreating glaciers in the central‐eastern Italian Alps, to test how the synergic effects of time since deglaciation and environmental factors may affect the colonisation process.Different times of response to climate change in ground beetles were found. Sites already hosting the land cover type suitable for our study taxon, but ice‐free for less than 100 yr, are mainly colonised by winged carabid beetles (which have high dispersal abilities and are mostly habitat generalists). No, or very few, wingless species (slow colonizers and ecologically specialized) occur within those sites. The overall pattern suggests that within a site, suitable land cover is established prior to colonization, due to a strong joint effect of time since deglaciation and land cover type.Long‐lasting habitat development at the fine scale is likely to result in a lack of specific resources (e.g. food items, or microhabitat), which is likely to contribute to delayed colonisation, which potentially could be tied also to dispersal abilities. Whatever the reason, the existence of a time‐lag often equal to or greater than 100 yr in species colonisation implies caution in predicting species’ occurrence shifts following climate change.
Inhibition of checkpoint kinase 2 (CHK2) enhances sensitivity of pancreatic adenocarcinoma cells to gemcitabine
Authors: Duong Hong‐Quan , Hong Young Bin , Kim Jung Soon , Lee Hee‐Seok , Yi Yong Weon , Kim Yeon Jeong , Wang Antai , Zhao Wenjing , Cho Chi Heum , Seong Yeon‐Sun , Bae Insoo 
Published: July 2013

AbstractCheckpoint kinase 2 (CHK2) plays pivotal function as an effector of cell cycle checkpoint arrest following DNA damage. Recently, we found that co‐treatment of NSC109555 (a potent and selective CHK2 inhibitor) potentiated the cytotoxic effect of gemcitabine (GEM) in pancreatic cancer MIA PaCa‐2 cells. Here, we further examined whether NSC109555 could enhance the antitumour effect of GEM in pancreatic adenocarcinoma cell lines. In this study, the combination treatment of NSC109555 plus GEM demonstrated strong synergistic antitumour effect in four pancreatic cancer cells (MIA PaCa‐2, CFPAC‐1, Panc‐1 and BxPC‐3). In addition, the GEM/NSC109555 combination significantly increased the level of intracellular reactive oxygen species (ROS), accompanied by induction of apoptotic cell death. Inhibition of ROS generation by N‐acetyl cysteine (NAC) significantly reversed the effect of GEM/NSC109555 in apoptosis and cytotoxicity. Furthermore, genetic knockdown of CHK2 by siRNA enhanced GEM‐induced apoptotic cell death. These findings suggest that inhibition of CHK2 would be a beneficial therapeutic approach for pancreatic cancer therapy in clinical treatment.
Cancer, stem cell misplacement and cancer stem cells
Authors: Liao Yong 
Published: July 2013

AbstractThe cell of origin of cancer as well as cancer stem cells is still a mystery. In a recent issue of JCMM, Wang et al. challenged the conventional somatic genetic mutation model of multi‐stage carcinogenesis of breast cancer and proposed that ‘Invasive cancers are not necessary from preformed in situ tumours—an alternative way of carcinogenesis from misplaced stem cells’. If this stem cell misplacement theory could withstand future experimental evaluation, it may provide a paradigm shift in the prevention and management of cancer in the clinic.
Nitric oxide production, systemic inflammation and lipid metabolism in periodontitis patients: possible gender aspect
Authors: Andrukhov Oleh , Haririan Hady , Bertl Kristina , Rausch Wolf‐Dieter , Bantleon Hans‐Peter , Moritz Andreas , Rausch‐Fan Xiaohui 
Published: July 2013

AbstractAimNitric oxide (NO) plays a crucial role in vascular tone regulation and is involved in pathogenesis of periodontitis. In this cross‐sectional study, we investigated the serum and saliva levels of NO metabolites in periodontal disease and their relationship with serum C‐reactive protein (CRP) levels, lipids metabolism and periodontal disease severity.Material and MethodsSerum and saliva were collected from non‐smoking patients with generalized severe periodontitis (n = 89) and healthy controls (n = 56). Serum and salivary levels of NO metabolites, serum levels of high density lipoproteins (HDL), low density lipoproteins (LDL), triglycerides, cholesterol and CRP were measured. Data were analysed in whole population and in different gender groups.ResultsPeriodontitis patients exhibited significantly lower serum and saliva levels of NO metabolites and significantly higher LDL, cholesterol and CRP levels than control group. Similar findings were observed within male but not within female population. Serum NO metabolites levels exhibited significant negative correlation with CRP in whole population and in male population. Significant positive correlation of serum NO metabolite levels with HDL levels was observed in whole population.ConclusionNO production is reduced in periodontitis, especially in male population. Gender might be an important factor in assessing risk of cardiovascular disease in periodontitis.
Vascular biology of the biliary epithelium
Authors: Morell Carola M , Fabris Luca , Strazzabosco Mario 
Published: July 2013

AbstractgraphicCholangiocytes are involved in a variety of processes essential for liver pathophysiology. To meet their demanding metabolic and functional needs, bile ducts are nourished by their own arterial supply, the peribiliary plexus. This capillary network originates from the hepatic artery and is strictly arranged around the intrahepatic bile ducts. Biliary and vascular structures are linked by a close anatomic and functional association necessary for liver development, normal organ physiology, and liver repair. This strong association is finely regulated by a range of angiogenic signals, enabling the cross talk between cholangiocytes and the different vascular cell types. This review will briefly illustrate the “vascular” properties of cholangiocytes, their underlying molecular mechanisms and the relevant pathophysiological settings.
Hepatoprotective and anti‐fibrotic functions of interleukin‐22: Therapeutic potential for the treatment of alcoholic liver disease
Authors: Kong Xiaoni , Feng Dechun , Mathews Stephanie , Gao Bin 
Published: July 2013

AbstractgraphicInterleukin‐22 (IL‐22) plays a key role in promoting antimicrobial immunity and tissue repair at barrier surfaces by binding to the receptors IL‐22R1, which is generally thought to be expressed exclusively in epithelial cells, and IL‐10R2. Our laboratory previously demonstrated that IL‐22 plays an important role in ameliorating liver injury in many rodent models by targeting hepatocytes that express high levels of IL‐22R1 and IL‐10R2. Recently, we have identified high expression levels of IL‐22R1 and IL‐10R2 in liver progenitor cells and hepatic stellate cells (HSCs). Overexpression of IL‐22 in vivo or treatment with IL‐22 in vitro promotes proliferation of liver progenitor cells via a signal transducer and activator of transcription 3 (STAT3)‐dependent mechanism. IL‐22 treatment also prevents HSC apoptosis in vitro and in vivo. Surprisingly, overexpression of IL‐22, via either gene targeting or exogenous administration of adenovirus expressing IL‐22, reduces liver fibrosis and accelerates the resolution of liver fibrosis during recovery. The anti‐fibrotic effects of IL‐22 are mediated via the activation of STAT3 in HSCs and subsequent induction of suppressor of cytokine signaling 3, which induces HSC senescence. Taken together, the hepatoprotective, mitogenic, and anti‐fibrotic effects of IL‐22 are beneficial in ameliorating alcoholic liver injury. Importantly, due to the restricted expression of IL‐22R1, IL‐22 therapy is expected to have few side effects, thus making IL‐22 a potential candidate for treatment of alcoholic liver disease.
Reversal of hepatitis B virus‐induced systemic immune tolerance by intrinsic innate immune stimulation
Authors: Han Qiuju , Lan Peixiang , Zhang Jian , Zhang Cai , Tian Zhigang 
Published: July 2013

AbstractgraphicSystemic immune tolerance induced by chronic hepatitis B virus (HBV) infection is a significant question, but the mechanism of which remains unclear. In this mini‐review, we summarize the impaired innate and adaptive immune responses involved in immune tolerance in chronic HBV infection. Furthermore, we delineate a novel dual functional small RNA to inhibit HBV replication and stimulate innate immunity against HBV, which proposed a promising immunotherapeutic intervention to interrupt HBV‐induced immunotolerance. A mouse model of HBV persistence was established and used to observe the immune tolerant to HBV vaccination, the cell‐intrinsic immune tolerance of which might be reversed by chemically synthesized dual functional small RNA (3p‐hepatitis B Virus X gene [HBx]‐small interfering RNA) in vitro experiments and by biologically constructed dual functional vector (single‐stranded RNA‐HBx‐ short hairpin RNA) in vivo experiment using HBV‐carrier mice.
Immunocompetent nontransgenic mouse models for studying hepatitis B virus immune responses
Authors: Tzeng Horng‐Tay , Hsu Ping‐Ning , Chen Pei‐Jer 
Published: July 2013

AbstractgraphicAlthough the chronicity of hepatitis B virus (HBV) infection is the result of impaired HBV‐specific immune responses that cannot eliminate or clear the infected hepatocytes efficiently, many issues remained unsettled. It is thus crucial to have a suitable laboratory animal to study the immunopathogenesis of HBV infection and the mechanisms of HBV persistence. To meet the requirement of a mouse model resembling natural chronic HBV infection in human, there are several approaches in the development of mouse animal model by using hydrodynamic‐based transfection of HBV DNA, delivery of adenovirus or adeno‐associated viral vectors containing HBV DNA for studying HBV immune responses. These immunocompetent nontransgenic mouse animal models will provide new approaches to investigate the mechanisms of immune pathogenesis in HBV infection.
Liver immune‐pathogenesis and therapy of human liver tropic virus infection in humanized mouse models
Authors: Bility Moses T , Li Feng , Cheng Liang , Su Lishan 
Published: July 2013

AbstractgraphicHepatitis B virus (HBV) and hepatitis C virus (HCV) infect and replicate primarily in human hepatocytes. Few reliable and easy accessible animal models are available for studying the immune system's contribution to the liver disease progression during hepatitis virus infection. Humanized mouse models reconstituted with human hematopoietic stem cells (HSCs) have been developed to study human immunology, human immunodeficiency virus 1 infection, and immunopathogenesis. However, a humanized mouse model engrafted with both human immune and human liver cells is needed to study infection and immunopathogenesis of HBV/HCV infection in vivo. We have recently developed the humanized mouse model with both human immune and human liver cells (AFC8‐hu HSC/Hep) to study immunopathogenesis and therapy of HCV infection in vivo. In this review, we summarize the current models of HBV/HCV infection and their limitations in immunopathogenesis. We will then present our recent findings of HCV infection and immunopathogenesis in the AFC8‐hu HSC/Hep mouse, which supports HCV infection, human T‐cell response and associated liver pathogenesis. Inoculation of humanized mice with primary HCV isolates resulted in long‐term HCV infection. HCV infection induced elevated infiltration of human immune cells in the livers of HCV‐infected humanized mice. HCV infection also induced HCV‐specific T‐cell immune response in lymphoid tissues of humanized mice. Additionally, HCV infection induced liver fibrosis in humanized mice. Anti‐human alpha smooth muscle actin (αSMA) staining showed elevated human hepatic stellate cell activation in HCV‐infected humanized mice. We discuss the limitation and future improvements of the AFC8‐hu HSC/Hep mouse model and its application in evaluating novel therapeutics, as well as studying both HCV and HBV infection, human immune responses, and associated human liver fibrosis and cancer.
Bermuda Triangle for the liver: Alcohol, obesity, and viral hepatitis
Authors: Zakhari Samir 
Published: July 2013

AbstractgraphicDespite major progress in understanding and managing liver disease in the past 30 years, it is now among the top 10 most common causes of death globally. Several risk factors, such as genetics, diabetes, obesity, excessive alcohol consumption, viral infection, gender, immune dysfunction, and medications, acting individually or in concert, are known to precipitate liver damage. Viral hepatitis, excessive alcohol consumption, and obesity are the major factors causing liver injury. Estimated numbers of hepatitis B virus (HBV) and hepatitis C virus (HCV)‐infected subjects worldwide are staggering (370 and 175 million, respectively), and of the 40 million known human immunodeficiency virus positive subjects, 4 and 5 million are coinfected with HBV and HCV, respectively. Alcohol and HCV are the leading causes of end‐stage liver disease worldwide and the most common indication for liver transplantation in the United States and Europe. In addition, the global obesity epidemic that affects up to 40 million Americans, and 396 million worldwide, is accompanied by an alarming incidence of end‐stage liver disease, a condition exacerbated by alcohol. This article focuses on the interactions between alcohol, viral hepatitis, and obesity (euphemistically described here as the Bermuda Triangle of liver disease), and discusses common mechanisms and synergy.
Update on epidemiology of hepatitis B and C in China
Authors: Cui Yan , Jia Jidong 
Published: July 2013

AbstractgraphicA high rate of chronic hepatitis B virus (HBV) infection in China is mainly caused by perinatal or early childhood transmission. Administration of universal HBV vaccination in infants has led to a dramatic decrease in HBV epidemiology, with hepatitis B surface antigen (HBsAg) prevalence declining from 9.75% in 1992 to 7.18% in 2006. The major HBV genotypes are B and C, with B being more prevalent in the southern part and C more prevalent in the northern part of China. A national survey carried out in 1992 showed that the hepatitis C virus (HCV) infection rate was 3.20% in general population in China. After implementation of mandatory HCV screening for blood transfusion and other precautions to prevent blood‐borne disease since 1993, the new cases of HCV infection associated with blood or blood product has become very rare. Although the anti‐HCV prevalence would be much higher in high‐risk groups, a survey carried in 2006 showed that the anti‐HCV prevalence rate was only 0.43% in general population. This sharp decline in HCV infection rate was mainly due to stringent administration and monitoring of blood donors and blood products, but may also be related to the remarkably improved specificity of anti‐HCV test. The predominant HCV genotype in China is genotype 1b (60–70%), and the host interleukin‐28b rs12979860 CC genotype is very frequent in Chinese population (over 80%).
In vivo bone strain and finite element modeling of the mandible of Alligator mississippiensis
Authors: Porro Laura B. , Metzger Keith A. , Iriarte‐Diaz Jose , Ross Callum F. 
Published: July 2013

AbstractForces experienced during feeding are thought to strongly influence the morphology of the vertebrate mandible; in vivo strain data are the most direct evidence for deformation of the mandible induced by these loading regimes. Although many studies have documented bone strains in the mammalian mandible, no information is available on strain magnitudes, orientations or patterns in the sauropsid lower jaw during feeding. Furthermore, strain gage experiments record the mechanical response of bone at a few locations, not across the entire mandible. In this paper, we present bone strain data recorded at various sites on the lower jaw of Alligator mississippiensis during in vivo feeding experiments. These data are used to understand how changes in loading regime associated with changes in bite location are related to changes in strain regime on the working and balancing sides of the mandible. Our results suggest that the working side mandible is bent dorsoventrally and twisted about its long‐axis during biting, and the balancing side experiences primarily dorsoventral bending. Strain orientations are more variable on the working side than on the balancing side with changes in bite point and between experiments; the balancing side exhibits higher strain magnitudes. In the second part of this paper, we use principal strain orientations and magnitudes recorded in vivo to evaluate a finite element model of the alligator mandible. Our comparison demonstrates that strain orientations and mandibular deformation predicted by the model closely match in vivo results; however, absolute strain magnitudes are lower in the finite element model.
Financial Markets and Investment Externalities
Authors: TITMAN SHERIDAN 
Published: July 2013

ABSTRACTThis address explores the link between financial market shocks, investment choices, and various externalities that can arise from these choices. My analysis, which emphasizes differences between shocks to debt and equity markets, provides insights about some stylized facts from the macro finance literature. These insights are illustrated with a discussion of the technology boom and bust in the late 1990s and early 2000s, and the housing boom and bust in the mid‐2000s.