bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic factors after salvage radiotherapy alone in patients with biochemical recurrence after radical prostatectomy
Authors: Song Wan , Jeon Hwang Gyun , Sung Hyun Hwan , Jeong Byong Chang , Seo Seong Il , Jeon Seong Soo , Choi Han Yong , Lee Hyun Moo 
Published: October 2015

ObjectivesTo evaluate the oncological outcome and to assess prognostic factors of salvage radiotherapy alone in patients with biochemical recurrence after radical prostatectomy.MethodsWe reviewed our single institution, prospectively maintained database of 2043 patients who underwent radical prostatectomy between September 1995 and December 2011. In this cohort, 149 patients who developed biochemical recurrence after radical prostatectomy and received salvage radiotherapy alone after pelvic magnetic resonance imaging were included. Three‐dimensional conformal radiotherapy or intensity‐modulated radiotherapy was delivered with a median dose of 70.0 Gy (66.0–78.0 Gy) or 67.2 Gy (64.8–70.0 Gy). Kaplan–Meier and Cox regression analyses were carried out.ResultsWith a median follow up of 82 months (range 20–153 months), 55 patients (36.9%) failed salvage radiotherapy. The 5‐year salvage radiotherapy failure‐free probability was 53.6%. On multivariate analysis, pre‐salvage radiotherapy prostate‐specific‐ antigen ≥1.0 ng/mL (P = 0.003, hazard ratio 3.592, 95% confidence interval 1.522–8.579), pathological stage ≥T3a (P = 0.004, hazard ratio 2.261, 95% confidence interval 1.290–3.833), pathological Gleason score ≥7 (P = 0.018, hazard ratio 5.501, 95% confidence interval 1.577–21.221), prostate‐specific antigen doubling time <12 months (P = 0.014, hazard ratio 2.243, 95% confidence interval 1.177–4.275) and no visible lesion on pelvic magnetic resonance imaging (P = 0.016, hazard ratio 2.068, 95% confidence interval 1.268–3.501) were independent prognostic factors of salvage radiotherapy failure after radical prostatectomy.ConclusionsPre‐salvage radiotherapy prostate‐specific antigen ≥1.0 ng/mL, pathological stage ≥T3a, pathological Gleason score ≥7, prostate‐specific antigen doubling time <12 months and no visible lesion on pelvic magnetic resonance imaging are prognostic factors of salvage radiotherapy failure after radical prostatectomy. We should consider additional treatment in patients with these factors for favorable outcomes.
The multiple facets of FcRn in immunity
Authors: Stapleton Nigel M. , Einarsdóttir Helga K. , Stemerding Annette M. , Vidarsson Gestur 
Published: October 2015

SummaryThe neonatal Fc receptor, FcRn, is best known for its role in transporting IgG in various tissues, providing newborns with humoral immunity, and for prolonging the half‐life of IgG. Recent findings implicate the involvement of FcRn in a far wider range of biological and immunological processes, as FcRn has been found to bind and extend the half‐life of albumin; to be involved in IgG transport and antigen sampling at mucosal surfaces; and to be crucial for efficient IgG‐mediated phagocytosis. Herein, the function of FcRn will be reviewed, with emphasis on its recently documented significance for IgG polymorphisms affecting the half‐life and biodistribution of IgG3, on its role in phagocyte biology, and the subsequent role for the presentation of antigens to lymphocytes.
The many faces of FcγRI: implications for therapeutic antibody function
Authors: Swisher Jennifer F. A. , Feldman Gerald M. 
Published: October 2015

SummaryFcγ receptor I (FcγRI or CD64) is the sole human Fc receptor with high affinity for monovalent IgG. While it contains an immunoreceptor tyrosine‐based activation motif in its cytoplasmic domain, binding of FcγRI can result in a complex array of activating and inhibitory outcomes. For instance, binding of monomeric IgG provides a low‐intensity tonic signal through FcγRI that is necessary for full interferon γ receptor signaling in the same cell. Interaction of FcγRI with larger high‐avidity complexes can result in phagocytosis, the generation of reactive oxygen species, as well as the synthesis and release of inflammatory cytokines. However, numerous reports also document potent anti‐inflammatory effects brought about by FcγRI engagement with immune complexes such as the inhibition of IFNγ and TLR4 signaling, and secretion of interleukin‐10. This has led to conflicting hypotheses regarding the function of FcγRI, especially with regard to its role in the efficacy of several therapeutic monoclonal antibodies. While many of these issues are still unclear, continued characterization of the regulation and context dependence of FcγRI function, as well as the molecular mechanisms responsible for these various outcomes, will improve our understanding of FcγRI biology as well as the therapeutic strategies designed to harness or constrain its actions.
Structure and dynamics of IgE–receptor interactions: FcεRI and CD23/FcεRII
Authors: Sutton Brian J. , Davies Anna M. 
Published: October 2015

SummaryImmunoglobulin E (IgE) is well known for its role in allergic disease, the manifestations of which are mediated through its two Fc receptors, FcεRI and CD23 (FcεRII). IgE and its interactions with these receptors are therefore potential targets for therapeutic intervention, and exciting progress has been made in this direction. Furthermore, recent structural studies of IgE‐Fc, the two receptors, and of their complexes, have revealed a remarkable degree of plasticity at the IgE–CD23 interface and an even more remarkable degree of dynamic flexibility within the IgE molecule. Indeed, there is allosteric communication between the two receptor‐binding sites, which we now know are located at some distance from each other in IgE‐Fc (at opposite ends of the Cε3 domain). The conformational changes associated with FcεRI and CD23 binding to IgE‐Fc ensure that their interactions are mutually incompatible, and it may be that this functional imperative has driven IgE to evolve such a dynamic structure. Appreciation of these new structural data has revised our view of IgE structure, shed light on the co‐evolution of antibodies and their receptors, and may open up new therapeutic opportunities.
FcγR requirements leading to successful immunotherapy
Authors: Dahal Lekh N. , Roghanian Ali , Beers Stephen A. , Cragg Mark S. 
Published: October 2015

SummaryMonoclonal antibody (mAb) immunotherapy is currently experiencing an unprecedented amount of success, delivering blockbuster sales for the pharmaceutical industry. Having experienced several false dawns and overcoming technical issues which limited progress, we are now entering a golden period where mAbs are becoming a mainstay of treatment regimes for diseases ranging from cancer to autoimmunity. In this review, we discuss how these mAbs are most likely working and focus in particular on the key receptors that they interact with to precipitate their therapeutic effects. Although their targets may vary, their engagement with Fcγ receptors (FcγRs) on numerous immune effector cells is almost universal, and here we review their roles in delivering successful immunotherapy.
Structural analysis of Fc/FcγR complexes: a blueprint for antibody design
Authors: Caaveiro Jose M. M. , Kiyoshi Masato , Tsumoto Kouhei 
Published: October 2015

SummaryThe number of studies and the quality of the structural data of Fcγ receptors (FcγRs) has rapidly increased in the last few years. Upon critical examination of the literature, we have extracted general conclusions that could explain differences in affinity and selectivity of FcγRs for immunoglobulin G (IgG) based on structural considerations. FcγRs employ a little conserved asymmetric surface of domain D2 composed of two distinct subsites to recognize the well‐conserved lower hinge region of IgG1‐Fc. The extent of the contact interface with the antibody in subsite 1 of the receptor (but not in subsite 2), the geometrical complementarity between antibody and receptor, and the number of polar interactions contribute decisively toward strengthening the binding affinity of the antibody for the receptor. In addition, the uncertain role of the N‐linked glycan of IgG for the binding and effector responses elicited by FcγRs is discussed. The available data suggest that not only the non‐covalent interactions between IgG and FcγRs but also their dynamic features are essential for the immune response elicited through these receptors. We believe that the integration of structural, thermodynamic, and kinetic data will be critical for the design and validation of the next generation of therapeutic antibodies with enhanced effector capabilities.
Fc receptors in antibody‐dependent enhancement of viral infections
Authors: Taylor Adam , Foo Suan‐Sin , Bruzzone Roberto , Vu Dinh Luan , King Nicholas J. C. , Mahalingam Suresh 
Published: October 2015

SummarySensitization of the humoral immune response to invading viruses and production of antiviral antibodies forms part of the host antiviral repertoire. Paradoxically, for a number of viral pathogens, under certain conditions, antibodies provide an attractive means of enhanced virus entry and replication in a number of cell types. Known as antibody‐dependent enhancement (ADE) of infection, the phenomenon occurs when virus‐antibody immunocomplexes interact with cells bearing complement or Fc receptors, promoting internalization of the virus and increasing infection. Frequently associated with exacerbation of viral disease, ADE of infection presents a major obstacle to the prevention of viral disease by vaccination and is thought to be partly responsible for the adverse effects of novel antiviral therapeutics such as intravenous immunoglobulins. There is a growing body of work examining the intracellular signaling pathways and epitopes responsible for mediating ADE, with a view to aiding rational design of antiviral strategies. With in vitro studies also confirming ADE as a feature of infection for a growing number of viruses, challenges remain in understanding the multilayered molecular mechanisms of ADE and its effect on viral pathogenesis.
Population genetic structure of the stony coral Acropora tenuis shows high but variable connectivity in East Africa
Authors: van der Ven Rosa M. , Triest Ludwig , De Ryck Dennis J. R. , Mwaura Jelvas M. , Mohammed Mohammed S. , Kochzius Marc 
Published: October 2015

AbstractAimThe aim of this study is to determine the genetic diversity, population structure and connectivity of the broadcast‐spawning coral Acropora tenuis (Cnidaria; Scleractinia; Acroporidae). Based on the long pelagic larval duration (PLD) of the species, long‐distance dispersal resulting in high connectivity among populations is hypothesized.LocationEast Africa (Kenya and Tanzania; 2.5°S ~ 10°S)MethodsA total of 269 samples were collected from 11 sample sites in Kenya and Tanzania spanning a distance of 900 km. The coral fragments were genotyped using seven microsatellite markers. Analyses included population genetic estimations of diversity and population differentiation, principal coordinate analysis (PCoA), Bayesian clustering approaches and testing for isolation by distance (IBD).ResultsModerate, but significant, genetic structure was found when comparing all sample sites, but IBD could not be detected. Based on Bayesian cluster analyses three groups of samples sites could be identified: (1) Kenya and northern Tanzania, (2) southern Tanzania and (3) sample sites located in the Zanzibar and Pemba channels.Main conclusionsHigh connectivity can be explained by the long‐distance dispersal capacity of A. tenuis and by the influence of the northbound East African Coastal Current facilitating dispersal by effectively spreading larvae along the coast. Oceanographic characteristics rather than distance are factors that determine connectivity among populations of A. tenuis in Kenya and Tanzania. No clear genetic break was identified. However, variable connectivity between sample sites does occur, with limited connectivity of the sample sites Misali and Stonetown.
Whose Plaza Is It, Anyway? Chávez's Bolivarianism and Contested Public Spaces in Caracas
Authors: Servigna Ana 
Published: October 2015

ResumenDurante los catorce años (1999–2013) de gobierno del fallecido Presidente Hugo Chávez, los espacios públicos en Venezuela se convirtieron en lugares de significado moral. Este artículo analiza cómo los seguidores de Chávez perciben, interpretan y hablan de los espacios públicos y sus significados morales, en particular los lugares que honran a Simón Bolívar. Analizando la Plaza Bolívar de Caracas y sus imaginarios sociales sostengo que la noción de Bolivarianismo ha sido utilizada como referente para institucionalizar una geografía moral y construir nuevas formas de exclusión en los espacios públicos de Caracas. Los resultados muestran como los seguidores de Chávez han transformado la Plaza Bolívar—discursiva y espacialmente—en un santuario secular para articular las diferencias políticas y reforzar las divisiones sociales.
Quantification of structural changes in acute inflammation by fractal dimension, angular second moment and correlation
Authors: STANKOVIC MARIJA , PANTIC IGOR , DE LUKA SILVIO R. , PUSKAS NELA , ZALETEL IVAN , MILUTINOVIC‐SMILJANIC SANJA , PANTIC SENKA , TRBOVICH ALEXANDER M. 
Published: October 2015

SummaryThe aim of the study was to examine alteration and possible application of fractal dimension, angular second moment, and correlation for quantification of structural changes in acutely inflamed tissue.Acute inflammation was induced by injection of turpentine oil into the right and left hind limb muscles of mice, whereas control animals received intramuscular saline injection. After 12 h, animals were anesthetised and treated muscles collected. The tissue was stained by hematoxylin and eosin, digital micrographs produced, enabling determination of fractal dimension of the cells, angular second moment and correlation of studied tissue.Histopathological analysis showed presence of inflammatory infiltrate and tissue damage in inflammatory group, whereas tissue structure in control group was preserved, devoid of inflammatory infiltrate. Fractal dimension of the cells, angular second moment and correlation of treated tissue in inflammatory group decreased in comparison to the control group.In this study, we were first to observe and report that fractal dimension of the cells, angular second moment, and correlation were reduced in acutely inflamed tissue, indicating loss of overall complexity of the cells in the tissue, the tissue uniformity and structure regularity. Fractal dimension, angular second moment and correlation could be useful methods for quantification of structural changes in acute inflammation.
Diabetes screening by telecentric digital holographic microscopy
Authors: DOBLAS A. , ROCHE E. , AMPUDIA‐BLASCO F. J. , MARTÍNEZ‐CORRAL M. , SAAVEDRA G. , GARCIA‐SUCERQUIA J. 
Published: October 2015

SummaryDiabetes is currently the world's fastest growing chronic disease and it is caused by deficient production of insulin by the endocrine pancreas or by abnormal insulin action in peripheral tissues. This results in persistent hyperglycaemia that over time may produce chronic diabetic complications. Determination of glycated haemoglobin level is currently the gold standard method to evaluate and control sustained hyperglycaemia in diabetic people. This measurement is currently made by high‐performance liquid chromatography, which is a complex chemical process that requires the extraction of blood from the antecubital vein. To reduce the complexity of that measurement, we propose a fully‐optical technique that is based in the fact that there are changes in the optical properties of erythrocytes due to the presence of glucose‐derived adducts in the haemoglobin molecule. To evaluate these changes, we propose to perform quantitative phase maps of erythrocytes by using telecentric digital holographic microscopy. Our experiments show that telecentric digital holographic microscopy allows detecting, almost in real time and from a single drop of blood, significant differences between erythrocytes of diabetic patients and healthy patients. Besides, our phase measurements are well correlated with the values of glycated haemoglobin and the blood glucose values.
Benefits and risks of antihypertensive medications in the elderly
Authors: Butt D. A. , Harvey P. J. 
Published: October 2015

AbstractHypertension is highly prevalent in older age and accounts for a large proportion of cardiovascular (CV) morbidity and mortality worldwide. Isolated systolic hypertension is more common in the elderly than younger adults and associated with poor outcomes such as cerebrovascular disease and acute coronary events. International guidelines are inconsistent in providing recommendations on optimal blood pressure targets in hypertensive elderly patients as a result of the limited evidence in this population. Evidence from clinical trials supports the use of antihypertensive drugs in hypertensive elderly patients due to benefits in reducing CV disease and mortality. However, elderly participants in these trials may not be typical of elderly patients seen in routine clinical practice, and the potential risks associated with use of antihypertensive drugs in the elderly are not as well studied as younger participants. Therefore, the purpose of this review was to provide a comprehensive summary of the benefits and risks of the use of antihypertensive drugs in elderly patients (aged ≥65 years), highlighting landmark clinical trials and observational studies. We will focus on specific outcomes relating to the benefits and risks of these medications in hypertensive elderly patients, such as CV disease, cognitive decline, dementia, orthostatic hypotension, falls, fractures, cancer and diabetes, in order to provide an update of the most relevant and current evidence to help inform clinical decision‐making.
The Clinical and Serological Effect of a Gluten‐Free Diet in Border Terriers with Epileptoid Cramping Syndrome
Authors: Lowrie M. , Garden O.A. , Hadjivassiliou M. , Harvey R.J. , Sanders D.S. , Powell R. , Garosi L. 
Published: October 2015

BackgroundCanine epileptoid cramping syndrome (CECS) is a paroxysmal movement disorder of Border Terriers (BTs). These dogs might respond to a gluten‐free diet.ObjectivesThe objective of this study was to examine the clinical and serological effect of a gluten‐free diet in BTs with CECS.AnimalsSix client‐owned BTs with clinically confirmed CECS.MethodsDogs were prospectively recruited that had at least a 6‐month history of CECS based on the observed phenomenology (using video) and had exhibited at least 2 separate episodes on different days. Dogs were tested for anti‐transglutaminase 2 (TG2 IgA) and anti‐gliadin (AGA IgG) antibodies in the serum at presentation, and 3, 6, and 9 months after the introduction of a gluten‐free diet. Duodenal biopsies were performed in 1 dog.ResultsSerum TG2 IgA titers were increased in 6/6 BTs (P = .006) and AGA IgG titers were increased in 5/6 BTs at presentation compared to those of controls (P = .018). After 9 months, there was clinical and serological improvement in all BTs with CECS strictly adhering to a gluten‐free diet (5/5). One dog had persistently increased antibody titers. This dog scavenged horse manure. On the strict introduction of a gluten‐free diet this dog also had an improved clinical and serological response. The diet‐associated improvement was reversible in 2 dogs on completion of the study, both of which suffered a relapse of CECS on the re‐introduction of gluten.ConclusionsCanine epileptoid cramping syndrome in BTs is a gluten‐sensitive movement disorder triggered and perpetuated by gluten and thus responsive to a gluten‐free diet.
Pattern of repeatability in the movement behaviour of a long‐lived territorial species, the eagle owl
Authors: Campioni L. , Delgado M. M. , Penteriani V. 
Published: October 2015

AbstractObserved movement patterns are the response of the interaction between environmental variables and the animal internal state. Therefore, even individuals of the same species experiencing similar environmental conditions can exhibit different behavioural responses, as these responses can be highly repeatable within individuals. Here, we investigated the nocturnal movement behaviour of a territorial species, by radiotracking 26 eagle owls Bubo bubo in order to analyze within and between individual variation with respect to movement parameters and route choice. Owls showed a considerable individual consistency in all movement parameters and made repeated use of similar routes while moving within fixed home ranges. Thus, movement parameters varied much less between repeated nightly trajectories than between different individuals. Furthermore, when we compared different individuals inhabiting the same territory in different years, within‐group repeatability was low or non‐significant suggesting that the spatial configuration of habitat does not always represents one of the main drivers in animal movement behaviour. Similarly, male individuals appeared to exhibit greater repeatability than females. The overall pattern of repeatability we found seems to identify such consistent movement behaviour not only as the expression of individual response to external/internal inputs but also as an additional trait to include in the broad definition of animal personality.
Breeding status affects the expression of androgen and progesterone receptor mRNA in the brain of male Damaraland mole‐rats
Authors: Voigt C. , Leitner S. , Bennett N. C. 
Published: October 2015

AbstractThe eusocial Damaraland mole‐rat Fukomys damarensis represents an extreme example of reproductive skew, in that reproduction is completely blocked in female subordinate group members. Similarly, male subordinates within the colony show no sexual behaviour. In contrast to females, however, non‐reproductive males have functional gonads and do not differ in circulating levels of pituitary hormones and testosterone from reproductive males. Nevertheless, they have reduced numbers of follicle‐stimulating hormone (FSH) receptors in their testes and they produce fewer spermatozoa with a large proportion of immature spermatozoa and precursors. To understand the mechanism of reproductive suppression operational in subordinate males, we studied the expression of androgen receptor (AR) and progesterone receptor (PGR) genes in forebrain regions involved in the control of reproductive behaviour in male breeders and non‐breeders from intact colonies. While it is well documented that testosterone activates male‐typical behaviour, the role of progesterone in this process is less clear as previous studies have produced contradictory results. We found the expression of AR and PGR genes in several forebrain regions of male Damaraland mole‐rats. The distribution of AR in males matches our previous findings in females. This is the first report showing the distribution of PGR in mole‐rats. We found PGR in all areas which were also sensitive to androgens and oestrogens. Analysis of the optical densities of the AR and PGR hybridization signal revealed that breeding males had increased expression of AR and PGR compared to non‐breeders in most brain regions examined, which include the medial preoptic area, the bed nucleus of the stria terminalis, the ventromedial nucleus of the hypothalamus, the arcuate nucleus and the medial amygdala. These status‐related differences were more pronounced for PGR than for AR. This study shows that breeding position affects the neuroendocrine phenotype of male Damaraland mole‐rats. Furthermore, it suggests that androgens and progesterone might act synergistically in activating sexual behaviour in males.