bluuebunny/crossref_metadata_2025_split huggingface dataset:
Initial and cumulative recurrence patterns of glioblastoma after temozolomide-based chemoradiotherapy and salvage treatment: a retrospective cohort study in a single institution
Authors: Ogura Kengo , Mizowaki Takashi , Arakawa Yoshiki , Ogura Masakazu , Sakanaka Katsuyuki , Miyamoto Susumu , Hiraoka Masahiro 
Published: April 2013

Abstract

Purpose
To analyze initial recurrence patterns in patients with newly diagnosed glioblastoma after radiotherapy plus concurrent and adjuvant temozolomide, and to investigate cumulative recurrence patterns after salvage treatment, including surgery, stereotactic radiotherapy, and chemotherapy.

Methods
Twenty-one patients with glioblastoma that recurred after concurrent temozolomide and localized radiotherapy were retrospectively analyzed (11 male, 10 female; median age, 57 years; range, 27–74). Disease progression was assessed by new response criteria proposed by the Response Assessment in Neuro-Oncology Working Group of the American Society of Clinical Oncology. The pattern of recurrence was determined by relationships between locations of recurrent tumors and irradiated doses. Central, in-field, marginal, and out-field recurrences were defined relative to the prescribed isodose line. Distant recurrence was operationally defined as subependymal or disseminated disease. Initial and cumulative patterns of recurrence were evaluated in each patient.

Results
The median follow-up of the recurrent patients was 501 (range, 217–1815) days after initial surgery. Initial recurrences were central in 14 patients (66.7%), in-field in four patients (19.0%), marginal in no patient (0%), out-field in two patients (9.5%), and distant in four patients (19.0%). One patient had both central and in-field recurrences simultaneously, and two had both central and distant recurrences. In the analysis of cumulative recurrence patterns, five patients, who had no scans after initial recurrences, were excluded and the remaining 16 were included. Cumulative recurrences were central in 11 patients (68.8%), in-field in five patients (31.3%), marginal in three patients (18.8%), out-field in five patients (31.3%), and distant in 14 patients (87.5%). Regarding salvage treatments, 11 (52.4%), 11 (52.4%) and 17 (81.0%) patients underwent surgery, stereotactic radiotherapy and chemotherapy, respectively. Eighteen (85.7%) patients had died at the time of analysis, and 16 of them (88.9%) had suffered distant recurrences, which could have been the immediate causes of death.

Conclusions
Recurrence patterns of glioblastoma after radiotherapy plus concomitant and adjuvant temozolomide were mainly central at first, and distant recurrences were often detected during the clinical course. Much better local control and prevention of distant recurrence, including effective salvage treatment, seem to be important.
Early-born neurons in type II neuroblast lineages establish a larval primordium and integrate into adult circuitry during central complex development in Drosophila
Authors: Riebli Nadia , Viktorin Gudrun , Reichert Heinrich 
Published: April 2013

Abstract

Background
The central complex is a multimodal information-processing center in the insect brain composed of thousands of neurons representing more than 50 neural types arranged in a stereotyped modular neuroarchitecture. In Drosophila, the development of the central complex begins in the larval stages when immature structures termed primordia are formed. However, the identity and origin of the neurons that form these primordia and, hence, the fate of these neurons during subsequent metamorphosis and in the adult brain, are unknown.

Results
Here, we used two pointed-Gal4 lines to identify the neural cells that form the primordium of the fan-shaped body, a major component of the Drosophila central complex. We found that these early-born primordium neurons are generated by four identified type II neuroblasts that amplify neurogenesis through intermediate progenitors, and we demonstrate that these neurons generate the fan-shaped body primordium during larval development in a highly specific manner. Moreover, we characterize the extensive growth and differentiation that these early-born primordium neurons undergo during metamorphosis in pupal stages and show that these neurons persist in the adult central complex, where they manifest layer-specific innervation of the mature fan-shaped body.

Conclusions
Taken together, these findings indicate that early-born neurons from type II neuroblast lineages have dual roles in the development of a complex brain neuropile. During larval stages they contribute to the formation of a specific central complex primordium; during subsequent pupal development they undergo extensive growth and differentiation and integrate into the modular circuitry of the adult brain central complex.
Parents of young people with self-harm or suicidal behaviour who seek help – a psychosocial profile
Authors: Morgan Sophia , Rickard Eóin , Noone Martha , Boylan Carole , Carthy Andreé , Crowley Sinead , Butler John , Guerin Suzanne , Fitzpatrick Carol 
Published: April 2013

Abstract

Background
Deliberate Self-Harm (DSH) is a common problem among children and adolescents in clinical and community populations, and there is a considerable amount of literature investigating factors associated with DSH risk and the effects of DSH on the child. However, there is a dearth of research examining the impact of DSH on parents, and there are few support programmes targeted at this population. This cross-sectional study examines the profile of a sample of parents of young people with DSH who participated in a support programme (Supporting Parents and Carers of young people with self-harm: the SPACE programme), with the goal of investigating pre-test parental well-being, family communication, parental satisfaction, perceived parental social support, and child strengths and difficulties.

Methods
Participants were 130 parents who attended the SPACE programme between 2009 and 2012, and who completed six questionnaires at baseline: the General Health Questionnaire-12, Strengths and Difficulties Questionnaire, Kansas Parenting Satisfaction Scale, General Functioning Scale of the McMaster Family Assessment Device, Multidimensional Scale of Perceived Social Support, and a demographic questionnaire.

Results
The majority of parents met criteria for minor psychological distress (86%) and rated the quantity and severity of their children’s difficulties as being in the abnormally high range (74%) at baseline. A majority of participants (61%) rated their perceived social support as being poor. Lower parental well-being was significantly correlated with poorer family communication, poorer parenting satisfaction, and a greater number of difficulties for the child. Perceived social support was not significantly correlated with parental well-being. Parents whose children were not attending school at baseline had significantly lower well-being scores than those whose children were. Parents whose children had received a formal diagnosis of a mental health disorder also had significantly lower well-being scores than those whose children had not.

Conclusions
Parents of young people with DSH behaviours face considerable emotional and practical challenges; they have low levels of well-being, parenting satisfaction, social support, and experience poor family communication. Given the importance of parental support for young people with DSH behaviours, consideration should be given to the need for individual or group support for such parents.
Lipophilic versus hydrophilic statin therapy for heart failure: a protocol for an adjusted indirect comparison meta-analysis
Authors: Bonsu Kwadwo Osei , Kadirvelu Amudha , Reidpath Daniel Diamond 
Published: April 2013

Abstract

Background
Statins are known to reduce cardiovascular morbidity and mortality in primary and secondary prevention studies. Subsequently, a number of nonrandomised studies have shown statins improve clinical outcomes in patients with heart failure (HF). Small randomised controlled trials (RCT) also show improved cardiac function, reduced inflammation and mortality with statins in HF. However, the findings of two large RCTs do not support the evidence provided by previous studies and suggest statins lack beneficial effects in HF. Two meta-analyses have shown statins do not improve survival, whereas two others showed improved cardiac function and reduced inflammation in HF. It appears lipophilic statins produce better survival and other outcome benefits compared to hydrophilic statins. But the two types have not been compared in direct comparison trials in HF.

Methods/design
We will conduct a systematic review and meta-analysis of lipophilic and hydrophilic statin therapy in patients with HF. Our objectives are:

To determine the effects of lipophilic statins on (1) mortality, (2) hospitalisation for worsening HF, (3) cardiac function and (4) inflammation.

To determine the effects of hydrophilic statins on (1) mortality, (2) hospitalisation for worsening HF, (3) cardiac function and (4) inflammation.

To compare the efficacy of lipophilic and hydrophilic statins on HF outcomes with an adjusted indirect comparison meta-analysis.

We will conduct an electronic search of databases for RCTs that evaluate statins in patients with HF. The reference lists of all identified studies will be reviewed. Two independent reviewers will conduct the search. The inclusion criteria include:

RCTs comparing statins with placebo or no statin in patients with symptomatic HF.

RCTs that employed the intention-to-treat (ITT) principle in data analysis.

Symptomatic HF patients of all aetiologies and on standard treatment.

Statin of any dose as intervention.

Placebo or no statin arm as control.

The exclusion criteria include:

RCTs involving cerivastatin in HF patients.

RCTs with less than 4 weeks of follow-up.

Discussion
We will perform an adjusted indirect comparison meta-analysis of lipophilic versus hydrophilic statins in patients with HF using placebo or no statin arm as common comparator.
Novel design of combinational and sequential logical structures in quantum dot cellular automata
Authors: Ghosh Bahniman , Gupta Shoubhik , Kumari Smriti , Salimath Akshaykumar 
Published: April 2013

Abstract
Quantum dot cellular automata (QCA) is a emerging nanotechnology that promises smaller size and lower power consumption, with faster speed compared to the transistor-based technology. In this paper, we have proposed novel 8-into-3 bit simple encoder, 4-into-2 bit priority encoder, scan flip-flop, and pseudo-random bit sequence generator designs in QCA. These circuits are useful components for the design of many logical and functional circuits. Simulation results of the proposed QCA circuits are obtained by using the QCA designer tool. The correctness of the proposed circuits is hence confirmed.
Correlations between angiogenic factors and capillaroscopic patterns in systemic sclerosis
Authors: Avouac Jérôme , Vallucci Maeva , Smith Vanessa , Senet Patricia , Ruiz Barbara , Sulli Alberto , Pizzorni Carmen , Frances Camille , Chiocchia Gilles , Cutolo Maurizio , Allanore Yannick 
Published: April 2013

Abstract
Introduction
We sought to assess whether nailfold videocapillaroscopy (NVC) patterns are associated with levels of angiogenic factors in systemic sclerosis (SSc).

Methods
Circulating endothelial progenitor cells (EPCs) and circulating endothelial cells (CECs) were measured in the peripheral blood of 60 consecutive SSc patients. Serum levels of eight endothelial markers were measured first in these 60 patients, and then in an independent replication cohort of 43 SSc patients in case of association with NVC patterns. NVC patterns were determined by four independent investigators blinded to vascular markers.

Results
Patients with the late-NVC pattern exhibited lower EPC levels (P < 0.0001) and higher VEGF levels (P = 0.03). Higher VEGF levels were confirmed to be associated with the late-NVC pattern in the replication cohort (P = 0.01). By multivariate analysis focused on biomarkers, lower EPC (P = 0.03) and higher VEGF levels (P = 0.001) were independently associated with the late-NVC pattern. In an alternate multivariate model including these two factors and SSc-related disease characteristics, lower EPC counts (P = 0.005), higher VEGF levels (P = 0.01), a history of digital ulcers (P = 0.04), and a modified Rodnan skin score > 14 (P < 0.0001) were independently associated with the late-NVC pattern.

Conclusion
Our data revealed decreased EPC counts and increased VEGF levels in patients with the late-NVC pattern. Further studies are now needed to determine the role of VEGF and EPCs in endothelial injury and repair in SSc.
Balanced versus chloride-rich solutions for fluid resuscitation in brain-injured patients: a randomised double-blind pilot study
Authors: Roquilly Antoine , Loutrel Olivier , Cinotti Raphael , Rosenczweig Elise , Flet Laurent , Mahe Pierre Joachim , Dumont Romain , Marie Chupin Anne , Peneau Catherine , Lejus Corinne , Blanloeil Yvonnick , Volteau Christelle , Asehnoune Karim 
Published: April 2013

Abstract
Introduction
We sought to investigate whether the use of balanced solutions reduces the incidence of hyperchloraemic acidosis without increasing the risk for intracranial hypertension in patients with severe brain injury.

Methods
We conducted a single-centre, two-arm, randomised, double-blind, pilot controlled trial in Nantes, France. Patients with severe traumatic brain injury (Glasgow Coma Scale score ≤8) or subarachnoid haemorrhage (World Federation of Neurosurgical Society grade III or higher) who were mechanically ventilated were randomised within the first 12 hours after brain injury to receive either isotonic balanced solutions (crystalloid and hydroxyethyl starch; balanced group) or isotonic sodium chloride solutions (crystalloid and hydroxyethyl starch; saline group) for 48 hours. The primary endpoint was the occurrence of hyperchloraemic metabolic acidosis within 48 hours.

Results
Forty-two patients were included, of whom one patient in each group was excluded (one consent withdrawn and one use of forbidden therapy). Nineteen patients (95%) in the saline group and thirteen (65%) in the balanced group presented with hyperchloraemic acidosis within the first 48 hours (hazard ratio = 0.28, 95% confidence interval [CI] = 0.11 to 0.70; P = 0.006). In the saline group, pH (P = .004) and strong ion deficit (P = 0.047) were lower and chloraemia was higher (P = 0.002) than in the balanced group. Intracranial pressure was not different between the study groups (mean difference 4 mmHg [-1;8]; P = 0.088). Seven patients (35%) in the saline group and eight (40%) in the balanced group developed intracranial hypertension (P = 0.744). Three patients (14%) in the saline group and five (25%) in the balanced group died (P = 0.387).

Conclusions
This study provides evidence that balanced solutions reduce the incidence of hyperchloraemic acidosis in brain-injured patients compared to saline solutions. Even if the study was not powered sufficiently for this endpoint, intracranial pressure did not appear different between groups.

Trial registration
EudraCT 2008-004153-15 andNCT00847977
The work in this trial was performed at Nantes University Hospital in Nantes, France.
Biological activity and magnetic resonance imaging of superparamagnetic iron oxide nanoparticles-labeled adipose-derived stem cells
Authors: Fan Jingjing , Tan Yanbin , Jie Liyong , Wu Xinying , Yu Risheng , Zhang Minming 
Published: April 2013

Abstract
Introduction
No comparative study of adipose-derived stem cells (ADSCs) and bone marrow mesenchymal stem cells (BMSCs) by using superparamagnetic iron oxide nanoparticles (SPIOs)-labeling and magnetic resonance imaging (MRI) has been performed.

Methods
We studied the biological activity and MRI of ADSCs by labeling them with SPIOs and comparing them with BMSCs. After incubating the cells in culture medium with different levels of SPIOs (control group: 0 μg/ml; Groups 1 to 3: 25, 50, and 100 μg/ml) for 24 hours, we compared ADSCs with BMSCs in terms of intracellular iron content, labeling efficiency, and cell viability. Stem cells in the culture medium containing 50 μg/ml SPIOs were induced into osteoblasts and fat cells. Adipogenic and osteogenic differentiation potentials were compared. R2* values of MRI in vitro were compared.

Results
The results showed that labeling efficiency was highest in Group 2. Intracellular iron content and R2* values increased with increasing concentrations of SPIOs, whereas cell viability decreased with increasing concentrations of SPIOs, and adipogenic and osteogenic differentiation potentials decreased. However, we found no significant difference between the two kinds of cells for any of these indexes.

Conclusions
ADSCs can be labeled and traced as easily as BMSCs in vitro. Given their abundance and higher proliferative capacity, as was previously shown, ADSCs may be better suited to stem cell therapy than are BMSCs.
Role of BAFF in Opsoclonus-Myoclonus syndrome, a bridge between cancer and autoimmunity
Authors: Raffaghello Lizzia , Fuhlhuber Verena , Bianchi Giovanna , Conte Massimo , Blaes Franz , Gambini Claudio , Pistoia Vito 
Published: April 2013

ABSTRACT
OMS is a rare paraneoplastic disorder that affects adults and children. Pediatric OMS is often associated with NB, a common, solid tumor of childhood, derived from the sympathetic nervous system. The detection of autoantibodies and lymphocytic infiltration in NB patients led to advance an autoimmune hypothesis for the pathogenesis of OMS-related NB. BAFF is a potent modulator of B cell growth and survival upon interaction with its receptors BAFF-R and BCMA. The aim of this study was to investigate mechanism(s) involved in ectopic lymphoid neogenesis in OMS-associated NB. We investigated BAFF, BAFF-R, and BCMA expression in NB tumors associated or not with OMS. Furthermore, we evaluated BAFF expression and secretion in NB cell lines, treated or untreated with differentiating agents. Immunohistochemically, lymphocytes infiltrating NB tumors from patients, with or without OMS, expressed BAFF, BAFF-R, and BCMA, whereas neuroblasts expressed BAFF and BCMA but not BAFF-R. By flow cytometry, BAFF was found to be consistently expressed in NB cell lines. Similarly to the results obtained in tissue lesions, BCMA but not BAFF-R was detected on the surface of all NB cell lines under basal conditions. De novo synthesis of BAFF-R and up-regulation of BCMA were observed in NB cell lines upon treatment with IFN-γ or 13-cis retinoic acid. This study provides new insights in the mechanisms driving the neogenesis of lymphoid follicles and in the functional interactions between tumor and immune cells in OMS-associated NB.
Dual regulation of osteopontin production by TLR stimulation in dendritic cells
Authors: Salvi Valentina , Scutera Sara , Rossi Silvia , Zucca Mario , Alessandria Manuela , Greco Deborah , Bosisio Daniela , Sozzani Silvano , Musso Tiziana 
Published: April 2013

ABSTRACT
OPN, a cytokine produced, among others, by DCs, is involved in inflammation and defense against pathogens. Here, we report that the activation of the MyD88 pathway by TLR2, TLR5, and TLR7/8 agonists or IL-1β induces high levels of OPN in human DCs. Conversely, LPS and Poly I:C, two TLR3 and TLR4 agonists that engage the TRIF pathway, were ineffective. TLR2 agonists were the strongest OPN inducers, and OPN production was highly stimulated by TLR2-triggering bacteria (Staphylococcus aureus) but not by TLR4-triggering Escherichia coli. Costimulation experiments revealed that TLR3 and TLR4 agonists, beyond being inactive by themselves, sharply limited TLR2-dependent OPN production by activating a TRIF-dependent inhibition of the MyD88-dependent OPN production. MyD88 silencing impaired TLR2-dependent OPN induction, whereas TRIF pathway blockage by chloroquine, dynasore, or TRIF knockdown prevented the TLR3/4 agonist-mediated inhibition, which was independent from the endogenous production of type I IFN, IL-29, IL-10, or TGF-β. LPS and Poly I:C inhibitory activity was associated with the release of a &gt;10-kDa protein factor(s). We also demonstrated that the higher OPN levels produced by S. aureus-treated DCs compared with E. coli-treated DCs were responsible for a markedly increased production of IL-17 by CD4+ T cells. These results highlight the biological relevance of the differential OPN induction by TLR2 and TLR4 agonists and emphasize the importance of TLR cross-talk in OPN induction. This implies that OPN regulation by TLR signaling is critical in shaping inflammatory responses and may modulate IL-17 production in response to pathogens.
Identification of novel oligonucleotides from mitochondrial DNA that spontaneously induce plasmacytoid dendritic cell activation
Authors: Ries Moritz , Schuster Philipp , Thomann Sabrina , Donhauser Norbert , Vollmer Jörg , Schmidt Barbara 
Published: April 2013

ABSTRACT
This study tested the hypothesis that mtDNA fragments carry immunostimulatory motifs that naturally induce immune activation by PDC. Genomic and mtDNA induced similar IFN-α production after transfection into PBMCs using the liposomal transfection reagent DOTAP. Shortening of mtDNA to CpG islands enhanced the immunostimulatory activity, based on the presence of unmethylated CpG DNA. Further fragmentation into mtODN, which exhibited similarities to published CpG ODN, resulted in a strong immunostimulatory activity in addition to PDC maturation and migration. The addition of the human cathelicidin LL-37 to CpG islands induced spontaneous PDC IFN-α production. Notably, one phosphodiester mtODN with a double-palindromic structure induced PDC IFN-α production in the absence of DOTAP. Flow cytometry, life-cell, and confocal imaging revealed attachment and spontaneous uptake into PDC, colocalizing, in part, with TLR9 in early endosomal vesicles. This process was accompanied by a moderate but significant PDC maturation in addition to B cell and NK cell activation (P&lt;0.05). Altogether, our data indicate that fragmented mtDNA, which may be released as a consequence of apoptotic, necrotic, and necroptotic cell death, can act as a DAMP. For the first time, our study provides a mechanism how longer and shorter mtDNA fragments can be taken up naturally by the PDC and thus, may contribute to acute and chronic immune activation.
ROS production in phagocytes: why, when, and where?
Authors: Dupré-Crochet Sophie , Erard Marie , Nüβe Oliver 
Published: April 2013

ABSTRACTIn the phagocytosis field, ROS production by the phagocyte NOX has been associated with pathogen killing for the last 50 years. Since the discovery of nonphagocyte NOX, numerous other roles for ROS production have been identified. Oxidative stress and ROS-mediated signaling have received much attention in recent years. Much lower concentrations of ROS may be required for signaling compared with microbial killing. Based on the discoveries in nonphagocytic cells, it became logical to look for ROS functions distinct from pathogen killing, even in phagocytes. ROS are now linked to various forms of cell death, to chemotaxis, and to numerous modifications of cellular processes, including the NOX itself. ROS functions are clearly concentration-dependent over a wide range of concentrations. How much is required for which function? Which species are required for how much time? Is ROS signaling only a side effect of bactericidal ROS production? One major obstacle to answer these questions is the difficulty of reliable quantitative ROS detection. Signal transduction often takes place on a subcellular scale over periods of seconds or minutes, so the detection methods need to provide appropriate time and space resolution. We present examples of local ROS production, decreased degradation, signaling events, and potentially ROS-sensitive functions. We attempt to illustrate the current limitations for quantitative spatiotemporal ROS detection and point out directions for ongoing development. Probes for localized ROS detection and for combined detection of ROS, together with protein localization or other cellular parameters, are constantly improved.