bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validation of an educational program balancing surgeon training and surgical quality control during robot‐assisted radical prostatectomy
Authors: Fujimura Tetsuya , Menon Mani , Fukuhara Hiroshi , Kume Haruki , Suzuki Motofumi , Yamada Yuta , Niimi Aya , Nakagawa Tohru , Igawa Yasuhiko , Homma Yukio 
Published: October 2015

ObjectivesTo establish a mentoring program that allows novice surgeons to use robotics while maintaining surgical quality during robot‐assisted radical prostatectomy.MethodsA total of 242 cases of robot‐assisted radical prostatectomy for patients with localized prostate cancer were considered for this study. Each novice surgeon carried out a step‐by‐step robot‐assisted radical prostatectomy procedure by following technical checkpoints and time limits that were established on the basis of previous surgical performance by a mentor. If technical checkpoints could not be accomplished, or the times were being exceeded, a mentor replaced the novice surgeon to finish the operative step or the surgery. Furthermore, if total blood loss exceeded 500 mL, a mentor completed the surgery. The primary end‐point was the number of cases required for a new surgeon to successfully complete the entire robot‐assisted radical prostatectomy procedure. Clinicopathological outcomes and any cases that deviated more than the standard deviation were also analyzed.ResultsMedian patient age, serum prostate‐specific antigen level (ng/mL), and Gleason score at diagnosis were 68 years, 7.6 and 7, respectively. Mean console and total operative times were 184 and 237 min, respectively. Mean perioperative blood loss was 300 mL. Seven out of eight new surgeons finished the total procedure after 10.7 cases (range 8–12). Four cases (1.7%) exceeded perioperative total blood loss and operative time. Positive surgical margin rates for total, T2, and T3 were 22, 9.3 and 47%, respectively. Positive surgical margin localized at bladder neck 19%, lateral lobe 39%, apex 32% and peripheral fat 9.4%.ConclusionsHerein we demonstrate an institutional mentoring program that effectively balances surgeon robot‐assisted radical prostatectomy training and surgical quality control.
Regulatory T‐cell neutralization in mice during filariasis helps in parasite clearance by enhancing T helper type 17‐mediated pro‐inflammatory response
Authors: Pathak Manisha , Sharma Pankaj , Sharma Aditi , Verma Meenakshi , Srivastava Mrigank , Misra‐Bhattacharya Shailja 
Published: October 2015

SummaryLymphatic filariasis leads to profound impairment of parasite‐specific T helper type 1 (Th1) and Th2 immune responses and significantly increases the expression of regulatory networks and regulatory effectors like transforming growth factor‐β, CD25, cytotoxic T‐lymphocyte antigen 4, glucocorticoid‐induced tumour necrosis factor receptor (GITR) and regulatory T (Treg) cells, which together play an important role in immunosuppression. While Treg cells suppress the activity of effector cells, monocyte dysfunction, characterized by an alternatively activated immunoregulatory phenotype, is one hypothesis that explains the lack of an antigen‐specific T‐cell response in infected individuals. In the present study, we administered neutralizing antibodies against the Treg cell‐associated markers CD25 and GITR and observed its effects on filaria‐induced immunosuppression. Our results show that administration of anti‐CD25 and anti‐GITR in infected animals not only arrested the accumulation of Treg cells and reduced arginase activity, but also led to an increase in the percentages of Th17 cells in the secondary lymphoid organs of mice. Elevated levels of interferon‐γ and decreased levels of interleukin‐10 were also noted in the culture supernatants of mouse splenocytes that were treated with neutralizing antibodies. Furthermore, treatment with neutralizing antibodies enhanced the expression of inducible nitric oxide synthase on host macrophages and CD40 on host dendritic cells with concomitant decreased expression of alternative activation markers Arg1, Ym1 and Fizz1, which together lead to reduced parasite burden in treated animals. In summary, administration of neutralizing antibodies helps in breaking the regulatory network in mice and limits parasite‐induced immunosuppression at the earliest host–parasite interface.
Fc receptor inside‐out signaling and possible impact on antibody therapy
Authors: Brandsma Arianne M. , Jacobino Shamir R. , Meyer Saskia , ten Broeke Toine , Leusen Jeanette H. W. 
Published: October 2015

SummaryFc receptors (FcR) are expressed on immune cells and bind to the Fc tail of antibodies. This interaction is essential for FcR‐mediated signaling and triggering of cellular effector functions. FcR activation is tightly regulated to prevent immune responses by non‐antigen bound antibodies or in the absence of ‘danger signals’. FcR activity may be modulated at the plasma membrane via cross‐talk with integrins. In addition, cytokines at the site of infection/inflammation can increase FcR avidity, a process referred to as inside‐out signaling. This regulatory mechanism has been described for FcγRI (CD64), FcγRIIa (CD32a), and FcαRI (CD89) and is also well‐known for integrins. Key cellular events during inside‐out signaling are (de)phosphorylation, clustering, cytoskeleton rearrangements, and conformational changes. The latter can be studied with antibodies that specifically recognize epitopes exposed by the active (high affinity) or inactive (low affinity) state of the FcR. These antibodies are important tools to investigate the role of FcR activation in disease settings. Research on FcR has gained momentum with the rise of monoclonal antibodies (mAb) entering the clinic for the treatment of cancer and other diseases. The clinical outcome of mAb therapy may be improved by increasing FcR avidity by cytokine stimulation.
Of ITIMs, ITAMs, and ITAMis: revisiting immunoglobulin Fc receptor signaling
Authors: Getahun Andrew , Cambier John C. 
Published: October 2015

SummaryReceptors for immunoglobulin Fc regions play multiple critical roles in the immune system, mediating functions as diverse as phagocytosis, triggering degranulation of basophils and mast cells, promoting immunoglobulin class switching, and preventing excessive activation. Transmembrane signaling associated with these functions is mediated primarily by two amino acid sequence motifs, ITAMs (immunoreceptor tyrosine‐based activation motifs) and ITIMs (immunoreceptor tyrosine‐based inhibition motifs) that act as the receptors’ interface with activating and inhibitory signaling pathways, respectively. While ITAMs mobilize activating tyrosine kinases and their consorts, ITIMs mobilize opposing tyrosine and inositol‐lipid phosphatases. In this review, we will discuss our current understanding of signaling by these receptors/motifs and their sometimes blurred lines of function.
The role of Fc receptors in HIV prevention and therapy
Authors: Boesch Austin W. , Brown Eric P. , Ackerman Margaret E. 
Published: October 2015

AbstractOver the past decade, a wealth of experimental evidence has accumulated supporting the importance of Fc receptor (FcR) ligation in antibody‐mediated pathology and protection in many disease states. Here we present the diverse evidence base that has accumulated as to the importance of antibody effector functions in the setting of HIV prevention and therapy, including clinical correlates, genetic associations, viral evasion strategies, and a rapidly growing number of compelling animal model experiments. Collectively, this work identifies antibody interactions with FcR as important to both therapeutic and prophylactic strategies involving both passive and active immunity. These findings mirror those in other fields as investigators continue to work toward identifying the right antibodies and the right effectors to be present at the right sites at the right time.
Fcγ receptor pathways during active and passive immunization
Authors: Bournazos Stylianos , Ravetch Jeffrey V. 
Published: October 2015

SummaryIgG antibodies are actively produced in response to antigenic challenge or passively administered as an effective form of immunotherapy to confer immunity against foreign antigens. Their protective activity is mediated through their bifunctional nature: a variable Fab domain mediates antigen‐binding specificity, whereas the constant Fc domain engages Fcγ receptors (FcγRs) expressed on the surface of leukocytes to mediate effector functions. While traditionally considered the invariant domain of an IgG molecule, the Fc domain displays remarkable structural heterogeneity determined primarily by differences in the amino acid sequence of the various IgG subclasses and by the composition of the complex, Fc‐associated biantennary N‐linked glycan. These structural determinants regulate the conformational flexibility of the IgG Fc domain and affect its capacity to interact with distinct types of FcγRs (type I or type II FcγRs). FcγR engagement activates diverse downstream immunomodulatory pathways with pleiotropic functional consequences including cytotoxicity and phagocytosis of IgG‐coated targets, differentiation and activation of antigen presenting cells, modulation of T‐cell activation, plasma cell survival, and regulation of antibody responses. These functions highlight the importance of FcγR‐mediated pathways in the modulation of adaptive immune responses and suggest a central role for IgG–FcγR interactions during active and passive immunization.
Human IgG4: a structural perspective
Authors: Davies Anna M. , Sutton Brian J. 
Published: October 2015

SummaryIgG4, the least represented human IgG subclass in serum, is an intriguing antibody with unique biological properties, such as the ability to undergo Fab‐arm exchange and limit immune complex formation. The lack of effector functions, such as antibody‐dependent cell‐mediated cytotoxicity and complement‐dependent cytotoxicity, is desirable for therapeutic purposes. IgG4 plays a protective role in allergy by acting as a blocking antibody, and inhibiting mast cell degranulation, but a deleterious role in malignant melanoma, by impeding IgG1‐mediated anti‐tumor immunity. These findings highlight the importance of understanding the interaction between IgG4 and Fcγ receptors. Despite a wealth of structural information for the IgG1 subclass, including complexes with Fcγ receptors, and structures for intact antibodies, high‐resolution crystal structures were not reported for IgG4‐Fc until recently. Here, we highlight some of the biological properties of human IgG4, and review the recent crystal structures of IgG4‐Fc. We discuss the unexpected conformations adopted by functionally important Cγ2 domain loops, and speculate about potential implications for the interaction between IgG4 and FcγRs.
TRIM21: a cytosolic Fc receptor with broad antibody isotype specificity
Authors: Foss Stian , Watkinson Ruth , Sandlie Inger , James Leo C. , Andersen Jan Terje 
Published: October 2015

SummaryAntibodies are key molecules in the fight against infections. Although previously thought to mediate protection solely in the extracellular environment, recent research has revealed that antibody‐mediated protection extends to the cytosolic compartment of cells. This postentry viral defense mechanism requires binding of the antibody to a cytosolic Fc receptor named tripartite motif containing 21 (TRIM21). In contrast to other Fc receptors, TRIM21 shows remarkably broad isotype specificity as it does not only bind IgG but also IgM and IgA. When viral pathogens coated with these antibody isotypes enter the cytosol, TRIM21 is rapidly recruited and efficient neutralization occurs before the virus has had the time to replicate. In addition, inflammatory signaling is induced. As such, TRIM21 acts as a cytosolic sensor that engages antibodies that have failed to protect against infection in the extracellular environment. Here, we summarize our current understanding of how TRIM21 orchestrates humoral immunity in the cytosolic environment.
Accelerating antibody discovery using transgenic animals overexpressing the neonatal Fc receptor as a result of augmented humoral immunity
Authors: Cervenak Judit , Kurrle Roland , Kacskovics Imre 
Published: October 2015

SummaryIn recent years, there has been an increasing demand for the development of faster and more efficient technologies for the generation of monoclonal antibodies against challenging targets that are weakly immunogenic or available only in limited amounts. Typical classes of such targets are cell surface antigens such as G‐protein related receptors (GPCRs) or ion channels. We have developed transgenic (Tg) mice and rabbits that overexpress the neonatal Fc receptor (FcRn), resulting in an augmented humoral immune response even if challenging antigens are used for immunization. The impressively enhanced FcRn‐mediated immune reactions are characterized by improved IgG protection and enhanced antigen presentation leading to greater number of antigen‐specific T‐helper and B‐cell activation in lymphoid organs. Notably, these animals do not show any sign of autoimmunity and can be efficiently bred. FcRn overexpression thus leads to a number of practical benefits for improved generation of monoclonal and polyclonal antibodies against multiple antigens, including weakly immunogenic epitopes or tiny amounts of proteins. This review summarizes our current understanding about the mechanisms by which FcRn overexpression leads to such a significantly enhanced humoral immune response.
The platelet Fc receptor, FcγRIIa
Authors: Qiao Jianlin , Al‐Tamimi Mohammad , Baker Ross I. , Andrews Robert K. , Gardiner Elizabeth E. 
Published: October 2015

SummaryHuman platelets express FcγRIIa, the low‐affinity receptor for the constant fragment (Fc) of immunoglobulin (Ig) G that is also found on neutrophils, monocytes, and macrophages. Engagement of this receptor on platelets by immune complexes triggers intracellular signaling events that lead to platelet activation and aggregation. Importantly these events occur in vivo, particularly in response to pathological immune complexes, and engagement of this receptor on platelets has been causally linked to disease pathology. In this review, we will highlight some of the key features of this receptor in the context of the platelet surface, and examine the functions of platelet FcγRIIa in normal hemostasis and in response to injury and infection. This review will also highlight pathological consequences of engagement of this receptor in platelet‐based autoimmune disorders. Finally, we present some new data investigating whether levels of the extracellular ligand‐binding region of platelet glycoprotein VI which is rapidly shed upon engagement of platelet FcγRIIa by autoantibodies, can report on the presence of pathological anti‐heparin/platelet factor 4 immune complexes and thus identify patients with pathological autoantibodies who are at the greatest risk of developing life‐threatening thrombosis in the setting of heparin‐induced thrombocytopenia.
The Meaning of ‘choice and control’ for People with Intellectual Disabilities who are Planning their Social Care and Support
Authors: Williams Val , Porter Sue 
Published: October 2015

BackgroundThis paper questions consumerist assumptions in current English social care policy and aims to look behind the processes of personalization to interrogate what ‘choice and control’ means in the lives of a diverse group of people with intellectual disabilities.MethodsData were from multiple interviews and direct practice recordings with nine people using personal budgets and were analysed using an interpretative approach.ResultsIdentity, other people and personal budget processes were all important for choice and control. People needed to build confidence in themselves as decision‐makers, both through peer support and through joint decisions with trusted others.ConclusionsPractitioners need to take into account the spectrum of ways in which people may make decisions. Action needs to be taken both at the micro level of support interactions and at the macro level, with a clearer articulation of independent living in policy and strategy for people with intellectual disabilities.
Effect of ICD Therapies on Mortality in the OMNI Trial
Authors: SUN SHINING , JOHNSON JAMES , DEGROOT PAUL , BROWN MARK L. , OBEL OWEN 
Published: October 2015

ICD Therapies and Mortality in OMNIBackgroundAnalyses from primary prevention trials on implantable cardioverter defibrillator (ICD) therapy have shown an association between shocks and increased mortality. Recent data suggest a similar association with antitachycardia pacing (ATP).ObjectiveThe OMNI study is an observational study of pacemaker and ICD use. We aim to examine associations between ICD therapies and mortality in this setting.MethodsA total of 2,255 OMNI patients with ICDs were included. Treated episodes were classified as appropriate or inappropriate. Patients were assigned into 1 of 3 groups depending on whether the episode required ATP only, single shock, or multiple shocks, and then followed for all‐cause mortality. Additionally, we aimed to determine the frequency with which inappropriate ATP precipitated ventricular arrhythmias that led to shock, since this has been suggested as a mechanism of harm.ResultsOver a mean follow‐up of 39 ± 19 months, there were a total of 470 deaths (21%). Compared to patients with no treated episodes, patients with appropriate therapy had greater risk of death. Hazard ratios were 1.46 (95% confidence interval [CI] 1.05–2.02; P = 0.023) for the ATP‐only group, 2.11 (95% CI 1.51–2.96; P < 0.001) for the single‐shock group, and 2.55 (95% CI 1.43–4.57; P = 0.002) for the multishock group. There was no significant association between any type of inappropriate therapy and increased mortality. We identified only 7 instances of inappropriate ATP precipitating ventricular arrhythmia resulting in shock.ConclusionsPatients receiving appropriate therapy of all types had increased mortality compared to those with no episodes. Furthermore, inappropriate ATP rarely precipitates ventricular arrhythmias.
Islands of Difference: Design, Urbanism, and Sustainable Tourism in the Anthropocene Caribbean
Authors: Moore Amelia 
Published: October 2015

ResumenEste artículo introduce la idea del antropoceno como un espacio problema con importancia para la antropología del caribe y la industria turística de éste. Este término es utilizado por científicos para definir la era presente en la cual los procesos humanos operan al nivel de escala geológica y biológica en la tierra, y ha venido a justificar una gran cantidad de acciones en el nombre de la sostenibilidad. A través de la examinación de una zona dedicada a la construcción de segundos hogares en las Bahamas, identifico cambios en diseño turístico de la isla que va dejando atrás el modelo del resort como enclave del turismo en masa. Argumento que las nociones de sostenibilidad del antropoceno no sólo re‐articulan las prácticas de construcción y el “branding” del destino turístico, pero también las posibilidades analíticas para el estudio de fabricación de lugar y procesos transnacionales. Abogo por una mayor incorporación de la antropología del diseño y urbana en el estudio del turismo al caribe como una forma de mejor entender estos eventos emergentes.
Performing Participation: Mining, Power, and the Limits of Public Consultation in Bolivia
Authors: Perreault Tom 
Published: October 2015

ResumenLos mecanismos de consulta, particularmente aquellos dirigidos a los pueblos indígenas y campesinos, han sido promovidos por instituciones internacionales e incorporados a la normativa legal a lo largo de América Latina. En Bolivia, la consulta ha sido codificada legalmente desde 1991 y ha sido integrada a la normativa que gobierna la extracción minera y de hidrocarburos, así como a la Constitución Nacional de 2009 sólo recientemente. A pesar de ser un requisito legal, la consulta no se implementa con regularidad y tampoco es vinculante en términos jurídicos. Como resultado, ni las empresas privadas ni el estado están obligadas a cumplir las recomendaciones comunitarias. Asimismo, las comunidades no tienen derecho a frenar los proyectos a los que se oponen. Este artículo examina la consulta pública comunitaria en el sector minero de Bolivia. Basado en investigación etnográfica en el departamento boliviano de Oruro, propongo que los procesos de consulta pública son gestionados con fruición y circunscribiendo las opiniones emitidas a nivel local. En vez de fomentar la participación en la gobernanza de recursos naturales por parte de las poblaciones afectadas por la minería, la consulta pública circunscribe y despolitiza las relaciones sociales desiguales e injustas, con el fin de legitimar actividades extractivas. [Bolivia, minería, consulta pública, consulta previa, desarrollo participativa]
Strain mapping accuracy improvement using super‐resolution techniques
Authors: BÁRCENA‐GONZÁLEZ G. , GUERRERO‐LEBRERO M.P. , GUERRERO E. , FERNÁNDEZ‐REYES D. , GONZÁLEZ D. , MAYORAL A. , UTRILLA A.D. , ULLOA J.M. , GALINDO P.L. 
Published: October 2015

SummarySuper‐resolution (SR) software‐based techniques aim at generating a final image by combining several noisy frames with lower resolution from the same scene. A comparative study on high‐resolution high‐angle annular dark field images of InAs/GaAs QDs has been carried out in order to evaluate the performance of the SR technique. The obtained SR images present enhanced resolution and higher signal‐to‐noise (SNR) ratio and sharpness regarding the experimental images. In addition, SR is also applied in the field of strain analysis using digital image processing applications such as geometrical phase analysis and peak pairs analysis. The precision of the strain mappings can be improved when SR methodologies are applied to experimental images.