bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endothelial cell metabolism and tumour angiogenesis: glucose and glutamine as essential fuels and lactate as the driving force
Authors: Polet F. , Feron O. 
Published: April 2013

AbstractAngiogenic endothelial cells and tumour cells can survive under hypoxic conditions and even proliferate and migrate in a low‐oxygen environment. In both cell types, high rates of glycolysis (i.e. conversion of glucose to lactate) and glutaminolysis provide most of the required biosynthetic intermediates and energy to support sprouting and cell division without coupling to oxidative phosphorylation. This metabolic preference is observed under hypoxic conditions, but also in situations in which oxygen is present. In the case of tumour cells, this is known as the Warburg effect and is largely governed by oncogenes. In endothelial cells lining tumour blood vessels, the option of respiration‐independent metabolism allows the neovasculature to resist the hostile environment of fluctuating oxygen tension (ranging from severe hypoxia to quasi‐normal levels of oxygen). In addition, accumulation in tumours of lactate, the end‐product of glycolysis, largely contributes to the angiogenic phenotype through inhibition of prolyl hydroxylase 2 and the activation of HIF1α and NFκB. Activation of the latter in a hypoxia‐independent manner leads to the increased production of interleukin‐8/CXCL8 which drives the autocrine stimulation of endothelial cell proliferation and maturation of neovessels. In conclusion, the addiction of proliferating endothelial cells for glucose and glutamine as fuels and the driving force of lactate to promote angiogenesis provide novel potential treatment options without the disadvantages of conventional anti‐angiogenic drugs.
VEGFA and tumour angiogenesis
Authors: Claesson‐Welsh L. , Welsh M. 
Published: April 2013

AbstractIn this review we summarize the current understanding of signal transduction downstream of vascular endothelial growth factor A (VEGFA) and its receptor VEGFR2, and the relationship between these signal transduction pathways and the hallmark responses of VEGFA, angiogenesis and vascular permeability. These physiological responses involve a number of effectors, including extracellular signal‐regulated kinases (ERKs), Src, phosphoinositide 3 kinase (PI3K)/Akt, focal adhesion kinase (FAK), Rho family GTPases, endothelial NO and p38 mitogen‐activated protein kinase (MAPK). Several of these factors are involved in the regulation of both angiogenesis and vascular permeability. Tumour angiogenesis primarily relies on VEGFA‐driven responses, which to a large extent result in a dysfunctional vasculature. The reason for this remains unclear, although it appears that certain aspects of the VEGFA‐stimulated angiogenic milieu (high level of microvascular density and permeability) promote tumour expansion. The high degree of redundancy and complexity of VEGFA‐driven tumour angiogenesis may explain why tumours commonly develop resistance to anti‐angiogenic therapy targeting VEGFA signal transduction.
Clinical characteristics of a novel subgroup of chronic fatigue syndrome patients with postural orthostatic tachycardia syndrome
Authors: Lewis I. , Pairman J. , Spickett G. , Newton J. L. 
Published: April 2013

AbstractObjectivesA significant proportion of patients with chronic fatigue syndrome (CFS) also have postural orthostatic tachycardia syndrome (POTS). We aimed to characterize these patients and differentiate them from CFS patients without POTS in terms of clinical and autonomic features.MethodsA total of 179 patients with CFS (1994 Centers for Disease Control and Prevention criteria) attending one of the largest Department of Health‐funded CFS clinical services were included in this study. Outcome measures were as follows: (i) symptom assessment tools including the fatigue impact scale, Chalder fatigue scale, Epworth sleepiness scale (ESS), orthostatic grading scale (OGS) and hospital anxiety and depression scale (HADS‐A and ‐D, respectively), (ii) autonomic function analysis including heart rate variability and (iii) haemodynamic responses including left ventricular ejection time and systolic blood pressure drop upon standing.ResultsCFS patients with POTS (13%, n = 24) were younger (29 ± 12 vs. 42 ± 13 years, P < 0.0001), less fatigued (Chalder fatigue scale, 8 ± 4 vs. 10 ± 2, P = 0.002), less depressed (HADS‐D, 6 ± 4 vs. 9 ± 4, P = 0.01) and had reduced daytime hypersomnolence (ESS, 7 ± 6 vs. 10 ± 5, P = 0.02), compared with patients without POTS. In addition, they exhibited greater orthostatic intolerance (OGS, 11 ± 5; P < 0.0001) and autonomic dysfunction. A combined clinical assessment tool of ESS ≤9 and OGS ≥9 identifies accurately CFS patients with POTS with 100% positive and negative predictive values.ConclusionsThe presence of POTS marks a distinct clinical group of CFS patents, with phenotypic features differentiating them from those without POTS. A combination of validated clinical assessment tools can determine which CFS patients have POTS with a high degree of accuracy, and thus potentially identify those who require further investigation and consideration for therapy to control heart rate.
At the heart of the arterial baroreflex: a physiological basis for a new classification of carotid sinus hypersensitivity
Authors: Wieling W. , Krediet C. T. P. , Solari D. , de Lange F. J. , van Dijk N. , Thijs R. D. , van Dijk J. G. , Brignole M. , Jardine D. L. 
Published: April 2013

AbstractThe aim of this review is to provide an update of the current knowledge of the physiological mechanisms underlying reflex syncope. Carotid sinus syncope will be used as the classical example of an autonomic reflex with relatively well‐established afferent, central and efferent pathways. These pathways, as well as the pathophysiology of carotid sinus hypersensitivity (CSH) and the haemodynamic effects of cardiac standstill and vasodilatation will be discussed. We will demonstrate that continuous recordings of arterial pressure provide a better understanding of the cardiovascular mechanisms mediating arterial hypotension and cerebral hypoperfusion in patients with reflex syncope. Finally we will demonstrate that the current criteria to diagnoseCSHare too lenient and that the conventional classification of carotid sinus syncope as cardioinhibitory, mixed and vasodepressor subtypes should be revised because isolated cardioinhibitoryCSH(asystole without a fall in arterial pressure) does not occur. Instead, we suggest that all patients withCSHshould be thought of as being ‘mixed’, between cardioinhibition and vasodepression. The proposed stricter set of criteria forCSHshould be evaluated in future studies.
The role of mitochondrial DNA mutations and free radicals in disease and ageing
Authors: Lagouge M. , Larsson N.‐G. 
Published: April 2013

AbstractConsiderable efforts have been made to understand the role of oxidative stress in age‐related diseases and ageing. The mitochondrial free radical theory of ageing, which proposes that damage to mitochondrial DNA (mtDNA) and other macromolecules caused by the production of reactive oxygen species (ROS) during cellular respiration drives ageing, has for a long time been the central hypothesis in the field. However, in contrast with this theory, evidence from an increasing number of experimental studies has suggested that mtDNA mutations may be generated by replication errors rather than by accumulated oxidative damage. Furthermore, interventions to modulate ROS levels in humans and animal models have not produced consistent results in terms of delaying disease progression and extending lifespan. A number of recent experimental findings strongly question the mitochondrial free radical theory of ageing, leading to the emergence of new theories of how age‐associated mitochondrial dysfunction may lead to ageing. These new hypotheses are mainly based on the underlying notion that, despite their deleterious role, ROS are essential signalling molecules that mediate stress responses in general and the stress response to age‐dependent damage in particular. This novel view of ROS roles has a clear impact on the interpretation of studies in which antioxidants have been used to treat human age‐related diseases commonly linked to oxidative stress.
Cutaneous lupus erythematosus: clinical aspects and molecular pathogenesis
Authors: Oke V. , Wahren‐Herlenius M. 
Published: April 2013

AbstractLupus erythematosus (LE) is an autoimmune disease with diverse clinical manifestations ranging from limited cutaneous (CLE) to potentially life‐threatening systemic disease (SLE). Susceptibility to LE arises from genetic variation in multiple loci, and disease activity is provoked by exogenous or endogenous trigger(s), the best characterized of which is exposure to ultraviolet radiation (UVR). Amongst patients with LE, a cluster of photosensitive subjects with cutaneous lesions and positivity for anti‐Ro/SSA autoantibodies have been described. The Ro52 antigen belongs to the tripartite motif protein family and has E3 ligase activity. New data reveal that Ro52 ubiquitinates interferon regulatory factors and modulates their transcriptional activity, indicating an important role for Ro52 in inflammation as a negative feedback regulator. Our findings indicate that UVR exposure induces upregulation of Ro52 in the CLE target cell, the keratinocyte, and that Ro52 is upregulated in spontaneous and UVR‐induced CLE lesions. Recently described functional analysis of Ro52‐deficient mice revealed that loss of Ro52 results in uncontrolled inflammation in response to minor skin injury leading to an LE‐like condition. In summary, emerging data suggest that abnormal function or regulation of Ro52 contributes to the pathogenesis of UVR‐induced CLE in genetically susceptible individuals. Ro52 may thus be an interesting therapeutic target, as its activation could contribute to downregulation of the chronic inflammatory process in LE. Here, we review the available data on the pathogenesis of CLE and, in particular, the role of the Ro52 autoantigen.
Effects of individual and combined dietary weight loss and exercise interventions in postmenopausal women on adiponectin and leptin levels
Authors: Abbenhardt C. , McTiernan A. , Alfano C. M. , Wener M. H. , Campbell K. L. , Duggan C. , Foster‐Schubert K. E. , Kong A. , Toriola A. T. , Potter J. D. , Mason C. , Xiao L. , Blackburn G. L. , Bain C. , Ulrich C. M. 
Published: April 2013

AbstractBackgroundExcess body weight and a sedentary lifestyle are associated with the development of several diseases, including cardiovascular disease, diabetes and cancer in women. One proposed mechanism linking obesity to chronic diseases is an alteration in adipose‐derived adiponectin and leptin levels. We investigated the effects of 12‐month reduced calorie, weight loss and exercise interventions on adiponectin and leptin concentrations.MethodsOverweight/obese postmenopausal women (n = 439) were randomized as follows: (i) a reduced calorie, weight‐loss diet (diet; N = 118), (ii) moderate‐to‐vigorous intensity aerobic exercise (exercise; N = 117), (iii) a combination of a reduced calorie, weight‐loss diet and moderate‐to‐vigorous intensity aerobic exercise (diet + exercise; N = 117), and (iv) control (N = 87). The reduced calorie diet had a 10% weight‐loss goal. The exercise intervention consisted of 45 min of moderate‐to‐vigorous aerobic activity 5 days per week. Adiponectin and leptin levels were measured at baseline and after 12 months of intervention using a radioimmunoassay.ResultsAdiponectin increased by 9.5% in the diet group and 6.6% in the diet + exercise group (both P ≤ 0.0001 vs. control). Compared with controls, leptin decreased with all interventions (diet + exercise, −40.1%, P < 0.0001; diet, −27.1%, P < 0.0001; exercise, −12.7%, P = 0.005). The results were not influenced by the baseline body mass index (BMI). The degree of weight loss was inversely associated with concentrations of adiponectin (diet, P‐trend = 0.0002; diet + exercise, P‐trend = 0.0005) and directly associated with leptin (diet, P‐trend < 0.0001; diet + exercise, P‐trend < 0.0001).ConclusionWeight loss through diet or diet + exercise increased adiponectin concentrations. Leptin concentrations decreased in all of the intervention groups, but the greatest reduction occurred with diet + exercise. Weight loss and exercise exerted some beneficial effects on chronic diseases via effects on adiponectin and leptin.
Out‐of‐hospital cardiac arrest: 10 years of progress in research and treatment
Authors: Hollenberg J. , Svensson L. , Rosenqvist M. 
Published: April 2013

AbstractCardiac disease is the most common cause of mortality in Western countries, with most deaths due to out‐of‐hospital cardiac arrest (OHCA). In Sweden, 5000–10 000 OHCAs occur annually. During the last decade, the time from cardiac arrest to start of cardiopulmonary resuscitation (CPR) and defibrillation has increased, whereas survival has remained unchanged or even increased. Resuscitation of OHCA patients is based on the ‘chain‐of‐survival’ concept, including early (i) access, (ii) CPR, (iii) defibrillation, (iv) advanced cardiac life support and (v) post‐resuscitation care. Regarding early access, agonal breathing, telephone‐guided CPR and the use of ‘track and trigger systems’ to detect deterioration in patients' condition prior to an arrest are all important. The use of compression‐only CPR by bystanders as an alternative to standard CPR in OHCA has been debated. Based on recent findings, guidelines recommend telephone‐guided chest compression‐only CPR for untrained rescuers, but trained personnel are still advised to give standard CPR with both compressions and ventilation, and the method of choice for this large group remains unclear and demands for a randomized study. Data have shown the benefit of public access defibrillation for dispatched rescuers (e.g. police and fire fighters) but data are not as strong for the use of automated defibrillators (AEDs) by trained or untrained rescuers. Postresuscitation, use of therapeutic hypothermia, the importance of specific prognostic survival factors in the intensive care unit and the widespread use of percutaneous coronary intervention have all been considered. Despite progress in research and improved treatment regimens, most patients do not survive OHCA. Particular areas of interest for improving survival include (i) identification of high‐risk patients prior to their arrest (e.g. early warning symptoms and genes); (ii) increased use of bystander CPR training (e.g. in schools) and simplified CPR techniques; (iii) better identification of high‐incidence sites and better recruitment of AEDs (via mobile phone solutions?); (iv) improved understanding of the use of therapeutic hypothermia; (v) determining which patients should undergo immediate coronary angiography on hospital admission; and (vi) clarifying the importance of extracorporeal membrane oxygenation during CPR.
Auditors and Corporate Governance: Evidence from the Public Sector
Authors: Schelker Mark 
Published: April 2013

SummaryCorporate auditors review and evaluate financial statements. Audit quality depends on auditor expertise and independence. To enhance auditor independence the selection process and auditor rotation requirements have been debated intensively. The available empirical evidence is not conclusive and suffers from serious endogeneity problems. I propose learning from the public sector where auditors play a similar role and present empirical evidence on the impact of auditor expertise, term length and rotation requirements on government performance at the US state level. I find evidence indicating that greater auditor expertise and rotation requirements have a positive effect on state credit ratings.
Do Consumer Tastes Evolve with Competition? The Case of the Slovenian Beer Market
Authors: Šušteršič Janez , Šušteršič Snežana 
Published: April 2013

SummaryWe use the natural experiment of EU entry to test the hypothesis that the lack of consumer tastes for diversity in beer may be responsible for slow development of small breweries in a highly concentrated beer market. Our contribution is to propose that lagged imports diversity, which increased after joining the common market, may be used as a proxy for consumer tastes development. Our reasoning is that after the EU entry, when imports soared, consumers became increasingly exposed to a much wider variety of beer styles. This might have led at least some of them to develop a taste for diversity in beer. In turn, this increased appreciation of diversity may have led them also to appreciate more the products of domestic microbreweries. Using monthly sales data, we are able to find some empirical confirmation that variety of imports indeed helps domestic small producers to cope with increasing competition. This suggest that the »taste for beer diversity« may develop as consumers are faced by a larger variety of beers. However, higher significance of domestic supply diversity compared to imported diversity may indicate that apart from actual beer tasting, there are additional channels of “taste development”, such as the general international fad for microbreweries which is developing in recent years.
Measuring Job Satisfaction withCUBModels
Authors: Gambacorta Romina , Iannario Maria 
Published: April 2013

AbstractIn this paper we present two statistical approaches for discussing and modelling job satisfaction based on data collected in theSurvey onHouseholdIncome andWealth (SHIW) conducted by theBank ofItaly. In particular, we analyse these data by means of a mixture model introduced for ordinal data and compare results with theOrdinalProbit model. The aim is to establish common outcomes and differences in the estimated patterns of global job satisfaction, but also to stress the potential for curbing the effects of measurement errors on estimates by usingCUBmodels [aCombination of discreteUniform and (shifted)Binomial distributions], allowing control for the effect of uncertainty and shelter choices in the response process.
Pathology of SSLOW, a transmissible and fatal synthetic prion protein disorder, and comparison with naturally occurring classical transmissible spongiform encephalopathies
Authors: Jeffrey M. , McGovern G. , Makarava N. , González L. , Kim Y.‐S. , Rohwer R. G. , Baskakov I. V. 
Published: April 2013

AimsNaturally occurring transmissible spongiform encephalopathies (TSEs) accumulate disease‐specific forms of prion protein on cell membranes in association with pathognomonic lesions. We wished to determine whether synthetic prion protein disorders recapitulated these and other subcellular TSE‐specific changes.MethodsSSLOW is a TSE initiated with refolded synthetic prion protein. Five terminally sick hamsters previously intracerebrally inoculated with third passage SSLOW were examined using light and immunogold electron microscopy.ResultsSSLOW‐affected hamsters showed widespread abnormal prion protein (PrPSSLOW) and amyloid plaques. PrPSSLOW accumulated on plasma lemmas of neurites and glia without pathological changes. PrPSSLOW also colocalized with increased coated vesicles and pits, coated spiral membrane invaginations and membrane microfolding. PrPSSLOW was additionally observed in lysosomes of microglial cells but not of neurones or astrocytes.ConclusionsPrPSSLOW is propagated by cell membrane conversion of normal PrP and lethal disease may be linked to the progressive growth of amyloid plaques. Cell membrane changes present in SSLOW are indistinguishable from those of naturally occurring TSEs. However, some lesions found in SSLOW are absent in natural animal TSEs and vice versa. SSLOW may not entirely recapitulate neuropathological features previously described for natural disease. End‐stage neuropathology in SSLOW, particularly the nature and distribution of amyloid plaques may be significantly influenced by the early redistribution of seeds within the inoculum and its recirculation following interstitial, perivascular and other drainage pathways. The way in which seeds are distributed and aggregate into plaques in SSLOW has significant overlap with murine APP overexpressing mice challenged with Aβ.
Adult stem cells for acute lung injury: Remaining questions and concerns
Authors: Zhu Ying‐Gang , Hao Qi , Monsel Antoine , Feng Xiao‐Mei , Lee Jae‐Woo 
Published: April 2013

AbstractAcute lung injury (ALI) or acute respiratory distress syndrome remains a major cause of morbidity and mortality in hospitalized patients. The pathophysiology of ALI involves complex interactions between the inciting event, such as pneumonia, sepsis or aspiration, and the host immune response resulting in lung protein permeability, impaired resolution of pulmonary oedema, an intense inflammatory response in the injured alveolus and hypoxemia. In multiple preclinical studies, adult stem cells have been shown to be therapeutic due to both the ability to mitigate injury and inflammation through paracrine mechanisms and perhaps to regenerate tissue by virtue of their multi‐potency. These characteristics have stimulated intensive research efforts to explore the possibility of using stem or progenitor cells for the treatment of lung injury. A variety of stem or progenitor cells have been isolated, characterized and tested experimentally in preclinical animal models of ALI. However, questions remain concerning the optimal dose, route and the adult stem or progenitor cell to use. Here, the current mechanisms underlying the therapeutic effect of stem cells in ALI as well as the questions that will arise as clinical trials for ALI are planned are reviewed.