bluuebunny/crossref_metadata_2025_split huggingface dataset:
An 18-year follow-up of seizure outcome after surgery for temporal lobe epilepsy and hippocampal sclerosis
Authors: Hemb Marta , Palmini Andre , Paglioli Eliseu , Paglioli Eduardo Beck , Costa da Costa Jaderson , Azambuja Ney , Portuguez Mirna , Viuniski Verena , Booij Linda , Nunes Magda Lahorgue 
Published: February 2013

ObjectivesTo evaluate the very long-term clinical outcome of surgery for mesial temporal lobe epilepsy and unilateral hippocampal sclerosis (MTLE/HS) without atypical features. The impact of surgical technique and postoperative reduction of medication on this outcome was investigated.DesignProspective longitudinal cohort follow-up study for up to18 years.SettingEpilepsy surgery centre in a university hospital.Patients108 patients who underwent unilateral MTLE/HS.InterventionSurgery for MTLE/HS.Main outcome measureEngel classification (I). Clinical evaluations were based on systematic interviews in person or by phone. Kaplan-Maier survival curves estimated the probability of remaining seizure free. The impact of medication management in the postoperative outcome was analysed using Cox regression.ResultsThe probability of remainingcompletelyseizure-free at 12 and 18 years after MTLE/HS surgery was 65% and 62%, respectively. The risk of having any recurrence was 22% during the first 24 months and increased 1.4% per year afterwards. Type of surgical technique (selective amygdalohippocampectomy vs anterior temporal lobectomy) did not impact on outcome. Remaining on antiepileptic drugs and history of generalised clonic seizure diminished the probability of remaining seizure free.ConclusionsMTLE/HS surgery is able to keep patients seizure free for almost up to two decades. Removal of the neocortex besides the mesial portion of the temporal lobe does not lead to better chances of seizure control. These findings are applicable to the typical unilateral MTLE/HS syndrome and cannot be generalised for all types of TLE. Future longitudinal randomised controlled studies are needed to replicate these findings.
A history of detachable coils: 1987–2012
Authors: Hui Ferdinand K , Fiorella David , Masaryk Thomas J , Rasmussen Peter A , Dion Jacques E 
Published: February 2013

BackgroundThe development of detachable coils is one of the most pivotal developments in neurointervention, providing a tool that could be used to treat a wide variety of hemorrhagic stroke. From the original Guglielmi detachable coil, a number of different coil designs and delivery designs have evolved. This article reviews the history of commercially available detachable coils.MethodsA timeline of detachable coils was constructed and coil design philosophies were reviewed.ResultsA complete list of commercially available coils is presented in a timeline format.ConclusionsDetachable coil technology continues to evolve. Advances in construction and design have yielded products which may benefit patients in terms of safety, radiation dose reduction and cost of treatment. Continued evolution is expected, irrespective of competing disruptive technologies.
Non-disclosure of HIV status in UK sexual health clinics—a pilot study to identify non-disclosure within a national unlinked anonymous seroprevalence survey
Authors: Sullivan Ann Kathleen , Savage Emma J , Lowndes Catherine M , Paul George , Murphy Gary , Carne Simon , Back David J , Gill O Noel 
Published: February 2013

ObjectivesTo identify if HIV-infected individuals attending genitourinary clinics in the UK are not disclosing their HIV status, and to examine the potential utility of drug detection as a method to indicate non-disclosure.MethodsHIV-positive samples from the unlinked anonymous seroprevalence survey from one London centre in 2009 had viral load (VL) assays performed to identify samples with VL below the level of detection (50 copies/ml, VLBLD) or <1000 copies/ml. After data matching, known HIV positives were excluded and the remaining samples analysed for the presence of a panel of antiretroviral drugs.ResultsOf 130 HIV-positive samples with sufficient clinical information and not undergoing an HIV test, 18 were classified as remaining undiagnosed after the clinic visit. Thirteen (72%, 95% CI: 47% to 90%) had a VLBLD (n=11) or VL <1000 copies/ml (n=2). Eight had sufficient volume to undergo ARV testing, and all were positive for the presence of drug; all with therapeutic levels of clinically appropriate combinations.ConclusionsNon-disclosure of HIV status occurs among individuals attending sexual health services in the UK. This study demonstrates the feasibility and utility of using both VL and ARV assays in serum samples. Furthermore, the close correlation of detection of ARV with VLBLD suggests drug detection would be a useful tool to monitor non-disclosure prospectively, thus enabling the use of stored serum samples in future studies. The extent to which these findings can be extrapolated to other settings, and the potential impact of non-disclosure on undiagnosed estimates warrants urgent prospective study.
Molecular Pathways: Mitogen-Activated Protein Kinase Pathway Mutations and Drug Resistance
Authors: Pritchard Antonia L. , Hayward Nicholas K. 
Published: February 2013

Abstract
Receptor tyrosine kinases are a diverse family of transmembrane proteins that can activate multiple pathways upon ligation of the receptor, one of which is the series of mitogen-activated protein kinase (MAPK) signaling cascades. The MAPK pathways play critical roles in a wide variety of cancer types, from hematologic malignancies to solid tumors. Aberrations include altered expression levels and activation states of pathway components, which can sometimes be attributable to mutations in individual members. The V600E mutation of BRAF was initially described in 2002 and has been found at particularly high frequency in melanoma and certain subtypes of colorectal cancer. In the relatively short time since this discovery, a family of drugs has been developed that specifically target this mutated BRAF isoform, which, after results from phase I/II and III clinical trials, was granted U.S. Food and Drug Administration approval in August 2011. Although these drugs produce clinically meaningful increases in progression-free and overall survival, due to acquired resistance they have not improved mortality rates. New drugs targeting other members of the MAPK pathways are in clinical trials or advanced stages of development. It is hoped that combination therapies of these new drugs in conjunction with BRAF inhibitors will counteract the mechanisms of resistance and provide cures. The clinical implementation of next-generation sequencing is leading to a greater understanding of the genetic architecture of tumors, along with acquired mechanisms of drug resistance, which will guide the development of tumor-specific inhibitors and combination therapies in the future. Clin Cancer Res; 19(9); 2301–9. ©2013 AACR.
Establishment and Characterization of the First Pediatric Adrenocortical Carcinoma Xenograft Model Identifies Topotecan as a Potential Chemotherapeutic Agent
Authors: Pinto Emilia M. , Morton Christopher , Rodriguez-Galindo Carlos , McGregor Lisa , Davidoff Andrew M. , Mercer Kimberly , Debelenko Larisa V. , Billups Catherine , Ribeiro Raul C. , Zambetti Gerard P. 
Published: February 2013

Abstract
Purpose: Pediatric adrenocortical carcinoma (ACC) is a rare and highly aggressive malignancy. Conventional chemotherapeutic agents have shown limited utility and are largely ineffective in treating children with advanced ACC. The lack of cell lines and animal models of pediatric ACC has hampered the development of new therapies. Here we report the establishment of the first pediatric ACC xenograft model and the characterization of its sensitivity to selected chemotherapeutic agents.
Experimental Design: A tumor from an 11-year-old boy with previously untreated ACC was established as a subcutaneous xenograft in immunocompromised CB17 scid−/− mice. The patient harbored a germline TP53 G245C mutation, and the primary tumor showed loss of heterozygosity with retention of the mutated TP53 allele. Histopathology, DNA fingerprinting, gene expression profiling, and biochemical analyses of the xenograft were conducted and compared with the primary tumor and normal adrenal cortex. The second endpoint was to assess the preliminary antitumor activity of selected chemotherapeutic agents.
Results: The xenograft maintained the histopathologic and molecular features of the primary tumor. Screening the xenograft for drug responsiveness showed that cisplatin had a potent antitumor effect. However, etoposide, doxorubicin, and a panel of other common cancer drugs had little or no antitumor activity, with the exception of topotecan, which was found to significantly inhibit tumor growth. Consistent with these preclinical findings, topotecan as a single agent in a child with relapsed ACC resulted in disease stabilization.
Conclusion: Our study established a novel TP53-associated pediatric ACC xenograft and identified topotecan as a potentially effective agent for treating children with this disease. Clin Cancer Res; 19(7); 1740–7. ©2013 AACR.
Reduced antiplatelet effect of aspirin is associated with low-grade inflammation in patients with coronary artery disease
Authors: Larsen Sanne , Grove Erik , Kristensen Steen , Hvas Anne-Mette 
Published: February 2013

SummaryInflammation has been proposed to modify platelet function. This may lead to increased platelet reactivity and reduced antiplatelet drug efficacy in patients with coronary artery disease (CAD). However, this hypothesis has not been investigated in stable CAD patients receiving aspirin as mono antiplatelet therapy. It was the objective of this study to investigate the association between platelet reactivity, the inflammatory markers high-sensitive C-reactive protein (hs-CRP) and interleukin-6 (IL-6), and platelet activation. We performed a cross-sectional study on 524 stable high-risk CAD patients. Among these, 91% had a history of myocardial infarction, 23% had type 2 diabetes, and 13% had both. All patients received 75 mg aspirin daily as mono antiplatelet therapy. Platelet reactivity was assessed by multiple electrode aggregometry (Multiplate®, MEA) and VerifyNow®. Inflammation was evaluated by hs-CRP and IL-6. Platelet activation was assessed by soluble P-selectin (sP-selectin), and cyclooxygenase-1 inhibition was evaluated by measurement of serum thromboxane B2. Hs-CRP levels were significantly higher in upper platelet reactivity tertile patients than in lower platelet reactivity tertile patients (p≤0.02). Similar results were obtained with IL-6, though not statististically significant (p≥0.15). Platelet activation evaluated by sP-selectin was significantly higher in patients with MEA reactivity levels in the upper tertile than in the lower tertile (p=0.0001). Optimal compliance was confirmed by low serum thromboxane B2 levels in all patients. In conclusion, increased levels of hs-CRP were associated with augmented platelet reactivity in stable high-risk CAD patients receiving aspirin as mono antiplatelet therapy. These findings may suggest that chronic low-grade inflammation reduce the antiplatelet effect of aspirin.
Platelet apoptosis and agonist-mediated activation in myelodysplastic syndromes
Authors: Jiménez-Yuste Víctor , Bello Ihosvany , Salgado Elena García , Álvarez María , Martín Mónica , de Paz Raquel , Butta Nora V. 
Published: February 2013

SummaryPatients with myelodysplastic syndromes (MDS) have a defect in the differentiation of bone marrow multipotent progenitor cells. Thrombocytopenia in MDS patients may be due to premature megakaryocyte death, but platelet apoptotic mechanisms may also occur. This study aimed to study function and apoptotic state of platelets from MDS patients with different platelet count. Reticulated platelets, platelet activation, activated caspases and annexin-V binding were evaluated by flow cytometry. Pro-apoptotic Bax and Bak proteins were determined by western blots and plasma thrombopoietin by ELISA. Microparticle-associated procoagulant activity and thrombin generation capacity of plasma were determined by an activity kit and calibrated automated thrombography, respectively. High plasma thrombopoietin levels and low immature circulating platelet count showed a pattern of hypoplastic thrombocytopenia in MDS patients. Platelets from MDS patients showed reduced activation capacity and more apoptosis signs than controls. Patients with the lowest platelet count showed less platelet activation and the highest extent of platelet apoptosis. On this basis, patients with thrombocytopenia should suffer more haemorrhagic episodes than is actually observed. Consequently, we tested whether there were some compensatory mechanisms to counteract their expected bleeding tendency. Microparticle-associated procoagulant activity was enhanced in MDS patients with thrombocytopenia, whereas their plasma thrombin generation capacity was similar to control group. This research shows a hypoplastic thrombocytopenia that platelets from MDS patients possess an impaired ability to be stimulated and more apoptosis markers than those from healthy controls, indicating that MDS is a stem cell disorder, and then, both number and function of progeny cells, might be affected.
Phenotypic and molecular characterisation of type 3 von Willebrand disease in a cohort of Indian patients
Authors: Budde Ulrich , Jan Rifat , Oyen Florian , Kannan Meganathan , Schneppenheim Reinhard , Ahmad Firdos , Saxena Renu 
Published: February 2013

SummarySevere type 3 VWD (VWD3) is characterised by complete absence or presence of trace amounts of non-functional von Willebrand factor (VWF). The study was designed to evaluate the VWF mutations in VWD3 patients and characterise the breakpoints of two identified homozygous novel large deletions. Patients were diagnosed by conventional tests and VWF multimer analysis. Mutation screening was performed in 19 VWD3 patients by direct sequencing of VWF including flanking intronic sequence and multiplex ligation-dependent probe amplification (MLPA) analysis. Breakpoint characterisation of two identified novel large deletions was done using walking primers and long spanning PCR. A total of 21 different mutations including 15 (71.4%) novel ones were identified in 17 (89.5%) patients. Of these mutations, five (23.8%) were nonsense (p.R1659*, p.R1779*, p.R1853*, p.Q2470*, p.Q2520*), one was a putative splice site (p.M814I) and seven (33.3%) were deletions (p.L254fs*48, p.C849fs*60, p.L1871fs*6, p.E2720fs*24) including three novel large deletions of exon 14–15, 80,830bp (−41510_657+7928A*del) and 2,231bp [1534–2072T_c.1692G*del(p.512fs*terminus)] respectively. A patient carried gene conversion comprising of pseudogene harbouring mutations. The missense mutations (p.G19R, p.K355R, p.D437Y, p.C633R, p.M771V, p.G2044D, p.C2491R) appear to play a major role and were identified in seven (36.8%) patients. In conclusion, a high frequency of novel mutations suggests the high propensity of VWF for new mutations. Missense and deletion mutations found to be a common cause of VWD3 in cohort of Indian VWD3 patients. Breakpoints characterisation of two large deletions reveals the double strand break and non-homologous recombination as deletions mechanism.
Detection of Left Atrial Appendage Thrombus by Cardiac Computed Tomography in Patients With Atrial Fibrillation
Authors: Romero Jorge , Husain Syed Arman , Kelesidis Iosif , Sanz Javier , Medina Hector M. , Garcia Mario J. 
Published: February 2013

Background—
Transesophageal echocardiogram (TEE) is considered the gold standard modality in detecting left atrial/LA appendage (LA/LAA) thrombi. However, this is a semi-invasive procedure with rare but potential life-threatening complications. Cardiac computed tomography has been proposed as an alternative method. The purpose of this meta-analysis was to evaluate the diagnostic accuracy of cardiac computed tomography assessing LA/LAA thrombi in comparison with TEE.

Methods and Results—
A systematic review of Medline, Cochrane, and Embase to look for clinical trials assessing detection of LA/LAA thrombi by cardiac computed tomography when compared with TEE in patients with a history of atrial fibrillation before electric cardioversion/pulmonary vein isolation or after cardioembolic cerebrovascular accident was performed using standard approach and bivariate analysis. Nineteen studies with 2955 patients (men, 71%; mean age, 61±4 years) fulfilled the inclusion criteria. Most studies (85%, 16 studies) used 64-slide multidetector computed tomography and 15 studies (79%) were electrocardiographic-gated. The incidence of LA/LAA thrombi was 8.9% (SD, ±7). The mean sensitivity and specificity were 96% and 92%, whereas the positive predictive value and negative predictive value were 41% and 99%, respectively. The diagnostic accuracy was 94%. In a subanalysis of studies in which delayed imaging was performed, the diagnostic accuracy significantly improved to a mean weighted sensitivity and specificity of 100% and 99%, respectively, whereas the positive predictive value and negative predictive value increased to 92% and 100%, respectively. The accuracy for this technique was 99%.

Conclusions—
Cardiac computed tomography, particularly when delayed imaging is performed, is a reliable alternative to TEE for the detection of LA/LAA thrombi/clot, avoiding the discomfort and risks associated with TEE.
Sildenafil and Diastolic Dysfunction After Acute Myocardial Infarction in Patients With Preserved Ejection Fraction
Authors: Andersen Mads J. , Ersbøll Mads , Axelsson Anna , Gustafsson Finn , Hassager Christian , Køber Lars , Borlaug Barry A. , Boesgaard Søren , Skovgaard Lene T. , Møller Jacob E. 
Published: February 2013

Background—
Diastolic dysfunction is frequently seen after myocardial infarction and is characterized by a disproportionate increase in filling pressure during exercise to maintain stroke volume. We hypothesized that sildenafil would reduce filling pressure during exercise in patients with diastolic dysfunction after myocardial infarction.

Methods and Results—

Seventy patients with diastolic dysfunction and near normal left ventricular ejection fraction on echocardiography were randomly assigned sildenafil 40 mg thrice daily or matching placebo for 9 weeks. Before randomization and after 9 weeks of treatment patients underwent simultaneous echocardiography and right heart catheterization at rest and during exercise. Primary end point was pulmonary capillary wedge pressure, and secondary end points comprised cardiac index and pulmonary arterial pressure at rest and during exercise after 9 weeks. After 9 weeks there were no differences in pulmonary capillary wedge pressure at rest (13±4 versus 13±3 mm Hg,
P
=0.25) or at peak exercise (35±8 mm Hg versus 31±7 mm Hg,
P
=0.07). However, with treatment cardiac index increased at rest (
P
=0.006) and peak exercise (
P
=0.02) in the sildenafil group, and systemic vascular resistance index (resting,
P
=0.0002; peak exercise,
P
=0.007) and diastolic blood pressure (resting,
P
=0.005; peak exercise,
P
=0.02) were lower in the sildenafil group. Resting left ventricular end-diastolic volume index increased (
P
=0.001) within the sildenafil group but was unchanged in the placebo group.

Conclusions—
Sildenafil did not decrease filling pressure at rest or during exercise in post–myocardial infarction patients with diastolic dysfunction. However, there were effects on secondary end points, which require further studies.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov/ct2/show/NCT01046838
. Unique identifier: NCT01046838.
Pure Creativity, 1994
Authors: Kareyan David 
Published: February 2013

Abstract
The two texts presented here were written by members of conceptual artists' group ACT operating in Armenia in 1994–1996. The group developed affirmative artistic actions and exhibitions to support the constitution of the new state based on the principles of liberal democracy and market capitalism. Its conceptual interventions and actions, both in conventional spaces of exhibition, but also on the street and in the already dysfunctional factories, were often formally minimal and austere, but almost always prescriptive in terms of offering a model of political and aesthetic participation.
Searching for the Neural Correlates of Conscious Intention
Authors: Desmurget Michel 
Published: February 2013

Abstract
It is typically assumed that the conscious experience of wanting to move is not the driving force for motor planning, but the secondary consequence of the unconscious neural processes preparing the movement. A recent study by Schneider et al. [Schneider, L., Houdayer, E., Bai, O., & Hallett, M. What we think before a voluntary movement. Journal of Cognitive Neuroscience, 25, 822–829, 2013] seems consistent with this dominant view by showing that the brain can be preparing to make voluntary movements not only “prior to the conscious appreciation that this is happening” but also “while subjects are thinking about something else.” However, an alternative hypothesis exists. It is supported by several lines of evidence and suggests that the early neural signals recorded by Schneider et al. (and others) do not reflect movement preparation per se, but rather a buildup in neural activity that ultimately leads to the emergence of a conscious intention to move. According to this view, the conscious experience of wanting to move is not the consequence but the cause of movement initiation.
Transcranial Magnetic Stimulation to the Transverse Occipital Sulcus Affects Scene but Not Object Processing
Authors: Ganaden Rachel E. , Mullin Caitlin R. , Steeves Jennifer K. E. 
Published: February 2013

Abstract
Traditionally, it has been theorized that the human visual system identifies and classifies scenes in an object-centered approach, such that scene recognition can only occur once key objects within a scene are identified. Recent research points toward an alternative approach, suggesting that the global image features of a scene are sufficient for the recognition and categorization of a scene. We have previously shown that disrupting object processing with repetitive TMS to object-selective cortex enhances scene processing possibly through a release of inhibitory mechanisms between object and scene pathways [Mullin, C. R., & Steeves, J. K. E. TMS to the lateral occipital cortex disrupts object processing but facilitates scene processing. Journal of Cognitive Neuroscience, 23, 4174–4184, 2011]. Here we show the effects of TMS to the transverse occipital sulcus (TOS), an area implicated in scene perception, on scene and object processing. TMS was delivered to the TOS or the vertex (control site) while participants performed an object and scene natural/nonnatural categorization task. Transiently interrupting the TOS resulted in significantly lower accuracies for scene categorization compared with control conditions. This demonstrates a causal role of the TOS in scene processing and indicates its importance, in addition to the parahippocampal place area and retrosplenial cortex, in the scene processing network. Unlike TMS to object-selective cortex, which facilitates scene categorization, disrupting scene processing through stimulation of the TOS did not affect object categorization. Further analysis revealed a higher proportion of errors for nonnatural scenes that led us to speculate that the TOS may be involved in processing the higher spatial frequency content of a scene. This supports a nonhierarchical model of scene recognition.