bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potent Immunomodulatory Effects of the Trifunctional Antibody Catumaxomab
Authors: Goéré Diane , Flament Caroline , Rusakiewicz Sylvie , Poirier-Colame Vichnou , Kepp Oliver , Martins Isabelle , Pesquet Julien , Eggermont Alexander , Elias Dominique , Chaput Nathalie , Zitvogel Laurence 
Published: June 2013

AbstractCatumaxomab (CatmAb), a trifunctional bispecific antibody directed against the epithelial cell adhesion molecule (EpCAM) and the T-cell antigen CD3, is approved as intraperitoneal therapy for the treatment of malignant ascites in patients with EpCAM-positive carcinomas. The immunomonitoring results of a phase II/III study using CatmAb revealed a tumoricidal effect associated with reduced VEGF levels, CD69-expressing T cells, and the release of T-helper cell (TH)-1 cytokines. We comprehensively dissected the immunomodulatory effects of the CatmAb on the major subsets of malignant ascites-infiltrating leukocytes and the molecular fingerprint of tumor cell death. Herein we show that in the presence of EpCAM-positive tumor targets, CatmAb markedly enhanced T-cell activation [CD69, CD107A (LAMP1), HLA-DR and PD-1(PDCD1) expression] and stimulated inflammatory CD4+ TH1 and CD8+ TH1 to release IFN-γ but failed to trigger TH17 cells. Engagement of CD16-expressing cells caused upregulation of TRAIL (TNFSF10) and costimulatory CD40 and CD80 molecules. CatmAb promoted tumor cell death associated with ATP release and strongly synergized with oxaliplatin for the exposure of the three hallmarks of immunogenic cell death (calreticulin, HMGB1, and ATP). These findings warrant validation as potential biomarkers of efficacy of CatmAb. Cancer Res; 73(15); 4663–73. ©2013 AACR.
Comparison of Manual Thrombus Aspiration With Rheolytic Thrombectomy in Acute Myocardial Infarction
Authors: Parodi Guido , Valenti Renato , Migliorini Angela , Maehara Akiko , Vergara Ruben , Carrabba Nazario , Mintz Gary S. , Antoniucci David 
Published: June 2013

Background—
Manual thrombus aspiration (MTA) is completely ineffective in 30% of cases, and the high profiles of the catheters prevent their use in tortuous and calcified vessels. The rheolytic thrombectomy (RT) device has the potential for improved thrombus removal in acute myocardial infarction as compared with MTA. No data exist on the comparison between the 2 techniques.

Methods and Results—

Randomized study, including 80 acute myocardial infarction patients allocated to RT or MTA before infarct artery stenting. Primary end point of this study is residual thrombus burden by optical coherence tomography. Secondary end points are (1) residual thrombolysis in myocardial infarction thrombus grade; (2) postintervention thrombolysis in myocardial infarction flow and myocardial blush; (3) early ST-segment resolution; (4) percentage of malapposed stent struts at 6 months; (5) 6-month restenosis; and (6) 6-month major adverse cardiovascular events. All but 1 patient had residual thrombus after manual aspiration thrombectomy or RT. The number of optical coherence tomography quadrants containing thrombus in MTA arm was higher than in the RT arm, but this difference did not reach significance (median value 65 and 53, respectively;
P
=0.083). Large residual thrombus was more frequently revealed in the manual aspiration thrombectomy arm (patients with number of quadrants above the median value 60% in the manual aspiration thrombectomy arm and 37% in the RT arm,
P
=0.039). All markers of reperfusion were better in the RT arm. At 6 months, the percentage of malapposed stent struts in the MTA arm was higher than in the RT arm (2.7±4.5% and 0.8±1.6%, respectively;
P
=0.019).

Conclusions—
MTA or RT allows only incomplete removal of thrombus in patients with acute myocardial infarction. The primary end point of the study was not met. However, RT as compared with MTA seems to be more effective in thrombus removal and myocardial reperfusion.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01281033.
Differential Effect of Ticagrelor Versus Prasugrel on Coronary Blood Flow Velocity in Patients With Non–ST-Elevation Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention
Authors: Alexopoulos Dimitrios , Moulias Athanasios , Koutsogiannis Nikolaos , Xanthopoulou Ioanna , Kakkavas Apostolos , Mavronasiou Eleni , Davlouros Periklis , Hahalis George 
Published: June 2013

Background—
Prasugrel and ticagrelor provide a superior anti-ischemic action than clopidogrel, with some of ticagrelor’s benefits possibly attributed to adenosine-mediated mechanisms. We aimed to compare the effect of maintenance dose of ticagrelor versus prasugrel on coronary blood flow velocity (CBFV) during increasing doses of intravenously administered adenosine.

Methods and Results—

In a prospective, single-center, single-blind, crossover study, 56 patients with non–ST-elevation acute coronary syndrome undergoing percutaneous coronary intervention were randomized to receive either ticagrelor 90 mg BID or prasugrel 10 mg OD with a 15-day treatment period. At the end of each treatment period, CBFV by transthoracic Doppler echocardiography was assessed at baseline and under incremental doses (50 μg/kg per minute, 80 μg/kg per minute, 110 μg/kg per minute, and 140 μg/kg per minute) of adenosine infusion. Maximal CBFV area under the curve was higher for ticagrelor-treated than for prasugrel-treated patients, with a least squares mean difference of 7.16 (95% confidence interval, 2.61–11.7;
P
=0.003). Maximal CBFV/baseline CBFV ratio was higher with ticagrelor than prasugrel at 50, 80, and 110 μg/kg per minute but not at 140 μg/kg per minute adenosine infusion rate, with mean difference (95% confidence interval) of 0.17 (0.08–0.26;
P
<0.001), 0.21 (0.02–0.41;
P
=0.03), 0.24 (0.01–0.47;
P
=0.04), and 0.14 (−0.12 to 0.4;
P
=0.3), respectively.

Conclusions—
In patients with non–ST-elevation acute coronary syndrome undergoing percutaneous coronary intervention, ticagrelor augments CBFV to a greater extent than prasugrel when incremental doses of adenosine are administered. Although exploratory, these results may represent a pleiotropic action of ticagrelor, possibly contributing to its beneficial effects in such patients.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01642966
Multicenter Prospective Cohort Study on Volume Management After Subarachnoid Hemorrhage
Authors: Yoneda Hiroshi , Nakamura Takumi , Shirao Satoshi , Tanaka Nobuhiro , Ishihara Hideyuki , Suehiro Eiichi , Koizumi Hiroyasu , Isotani Eiji , Suzuki Michiyasu 
Published: June 2013

Background and Purpose—
Systemic circulation management has not been established for patients with poor grade aneurysmal subarachnoid hemorrhage (SAH) or delayed cerebral ischemia (DCI) after SAH. The aims of the study were to examine hemodynamic variables in these patients and to establish treatment strategies.

Methods—
A multicenter prospective cohort study of hemodynamic variables from days 1 to 14 was performed using a transpulmonary thermodilution system (PiCCO Plus). Parameters were analyzed by Mann–Whitney test. Multivariate analysis was performed to identify parameters involved in onset of DCI.

Results—

The subjects were 204 patients, including 138 with poor grade SAH (World Federation of Neurological Surgeons grades IV and V) and 52 who developed DCI. The extravascular lung water index, pulmonary vascular permeability index, and systemic vascular resistance index were significantly greater in patients with poor grade SAH compared with those with good grade SAH (World Federation of Neurological Surgeons I–III) on day 2 (
P
=0.049,
P
=0.039, and
P
=0.038). Cardiac index was significantly lower in patients with poor grade SAH on days 1 and 2 (
P
=0.027 and
P
=0.011). In patients with DCI, the global end-diastolic volume index was significantly lower than in those without DCI on days 3 to 5 (
P
=0.0053;
P
=0.048; and
P
=0.048). In multivariate analysis, median global end-diastolic volume index, cardiac index, and systemic vascular resistance index at an early stage of SAH (days 3–6) were independently related to onset of DCI (
P
=0.023,
P
=0.013, and
P
=0.003).

Conclusions—
Patients with poor grade SAH developed heart failure–like afterload mismatch at an early stage, and those with DCI had decreased global end-diastolic volume index (hypovolemia) in the early stage of SAH.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: UMIN000003794.
How Plotinus’ Soul Animates his Body: The Argument for the Soul-Trace at Ennead 4.4.18.1-9
Authors: Noble Christopher Isaac 
Published: June 2013

Abstract
In this paper I offer an analysis of Plotinus’ argument for the existence of a quasi-psychic entity, the so-called ‘trace of soul’, that functions as an immanent cause of life for an organism’s body. I argue that Plotinus posits this entity primarily in order to account for the body’s possession of certain quasi-psychic states that are instrumental in his account of soul-body interaction. Since these quasi-psychic states imply that an organism’s body has vitality of its own (a claim for which Plotinus also finds support in the Phaedo), and Platonic souls are no part or aspect of any body, Plotinus draws the conclusion that the soul must be a cause of the body’s life by imparting a quasi-psychic qualification to it. In so doing, Plotinus introduces elements of hylomorphism into Platonist psychology, and addresses a problem for the animation of the body that Platonic soul-body dualism may plausibly be thought to face.
Jerome’s Understanding of Old Testament Quotations in the New Testament
Authors: Kato Teppei 
Published: June 2013

Abstract
Jerome compares Old Testament quotations in the New Testament with the Hebrew text and LXX in seven texts, for example in Ep. 57, written c.395. He adopts different opinions when the LXX disagrees with the Hebrew text and when the quotations disagree with the Hebrew text. In the first case, he demands a strict rendering of words, whereas in the second, he considers the quotations and the Hebrew text to have the same meaning even if their wordings differ. In other words, Jerome attributes more authority to the Evangelists and Paul than to the LXX translators. In this paper, I will explain two reasons—one negative and the other positive—for this dichotomy in Jerome’s approach.
Fundamental Rights Protection for Third Country Nationals and Citizens of the Union: Principles for Enhancing Coherence
Authors: Sánchez Sara Iglesias 
Published: June 2013

Abstract
The definition of the legal contours of a citizenship status is intrinsically bound to the determination of a differentiated status for non-citizens. Nonetheless, European citizenship has been designed in a non-exclusionary fashion. This is not so much the result of a conscious exercise of inclusiveness, as the result of the indeterminacy of the EU Treaties. The progressive construction of a common European immigration policy is happening within a constitutional scenario deprived of principles suitable to guide the relationship between the citizenship status and the several newly created status for third-country nationals, who now derive their EU rights not only from their relationships with EU citizens nor from agreements mirroring the fundamental freedoms. For this reason, there is a growing need to make explicit the principles that should govern this relationship. The main purpose of this paper is to discern and analyse the emerging lines of this relationship, which are being unveiled by EU immigration norms, particularly as they are being interpreted in recent judgements of the ECJ. It will be argued that the new EU rules on immigration are helping to uncover the shortcomings and incoherencies of the EU citizenship status since, paradoxically, the structure of EU competences allows for a deeper involvement of EU law in the determination of the rights of third country nationals than of the rights of citizens.
Risk profile and clinical outcome of symptomatic subsegmental acute pulmonary embolism
Authors: den Exter Paul L. , van Es Josien , Klok Frederikus A. , Kroft Lucia J. , Kruip Marieke J. H. A. , Kamphuisen Pieter Willem , Büller Harry R. , Huisman Menno V. 
Published: June 2013

Key Points
Patients with subsegmental PE appear to mimic those with more proximally located PE regarding their VTE risk profile and clinical outcome. Patients with subsegmental PE significantly differ from patients without PE in terms of both VTE risk profile and clinical outcome.
Integral analysis of p53 and its value as prognostic factor in sporadic colon cancer
Authors: Fariña Sarasqueta Arantza , Forte Giusi Irma , Corver Wim E , de Miranda Noel F , Ruano Dina , van Eijk Ronald , Oosting Jan , Tollenaar Rob AEM , van Wezel Tom , Morreau Hans 
Published: June 2013

AbstractBackgroundp53 (encoded byTP53) is involved in DNA damage repair, cell cycle regulation, apoptosis, aging and cellular senescence.TP53is mutated in around 50% of human cancers. Nevertheless, the consequences of p53 inactivation in colon cancer outcome remain unclear. Recently, a new role of p53 together with CSNK1A1 in colon cancer invasiveness has been described in mice.MethodsBy combining data on different levels of p53 inactivation, we aimed to predict p53 functionality and to determine its effects on colon cancer outcome. Moreover, survival effects ofCSNK1A1together with p53 were also studied.Eighty-three formalin fixed paraffin embedded colon tumors were enriched for tumor cells using flow sorting, the extracted DNA was used in a custom SNP array to determine chr17p13-11 allelic state; p53 immunostaining,TP53exons 5, 6, 7 and 8 mutations were determined in combination with mRNA expression analysis on frozen tissue.ResultsPatients with a predicted functional p53 had a better prognosis than patients with non functional p53 (Log Rank p=0.009). Expression ofCSNK1A1modified p53 survival effects. Patients with lowCSNK1A1expression and non-functional p53 had a very poor survival both in the univariate (Log Rank p<0.001) and in the multivariate survival analysis (HR=4.74 95% CI 1.45 – 15.3 p=0.009).ConclusionThe combination of mutational, genomic, protein and downstream transcriptional activity data predicted p53 functionality which is shown to have a prognostic effect on colon cancer patients. This effect was specifically modified byCSKN1A1expression.
A low-complexity user selection scheme in a multicell MIMO environment
Authors: Kim Doohee , Shin Oh-Soon , Lee Kwang Bok 
Published: June 2013

Abstract
An efficient user selection scheme for the downlink of multiuser MIMO systems is proposed in a multicell environment. In a multicell environment, the intercell interference is one of the most influential factors limiting the performance. Thus, a user selection scheme that considers intercell interference is essential to increase the sum rate. The proposed scheme is based on an interference-aware precoding. It sequentially selects users such that the sum rate is maximized. In particular, we develop a simple incremental metric for the sum rate. The use of the derived metric enables a significant reduction in the computational complexity of the user selection process, as compared to the optimal exhaustive search. Numerical results show that the proposed scheme provides near-optimal performance with substantially reduced complexity.
Conditionally-live attenuated SIV upregulates global T effector memory cell frequency under replication permissive conditions
Authors: Manoussaka Maria S , Berry Neil , Ferguson Deborah , Stebbings Richard , Robinson Mark , Ham Claire , Page Mark , Li Bo , Das Atze T , Berkhout Ben , Almond Neil , Cranage Martin P 
Published: June 2013

Abstract

Background
Live attenuated SIV induces potent protection against superinfection with virulent virus; however the mechanism of this vaccine effect is poorly understood. Such knowledge is important for the development of clinically acceptable vaccine modalities against HIV.

Results
Using a novel, doxycycline dependent, replication-competent live-attenuated SIVmac239Δnef (SIV-rtTAΔnef), we show that under replication-permissive conditions SIV-rtTAΔnef is fully viable. Twelve rhesus macaques were infected with a peak plasma vRNA on average two log10 lower than in 6 macaques infected with unconditionally replication-competent SIVΔnef. Consistent with the attenuated phenotype of the viruses the majority of animals displayed low or undetectable levels of viraemia by 42-84 days after infection. Next, comparison of circulating T cells before and after chronic infection with parental SIVΔnef revealed a profound global polarisation toward CD28-CCR7- T-effector memory 2 (TEM2) cells within CD95+CD4+ and CD95+CD8+ populations. Critically, a similar effect was seen in the CD95+ CD4+ population and to somewhat lesser extent in the CD95+ CD8+ population of SIV-rtTAΔnef chronically infected macaques that were maintained on doxycycline, but was not seen in animals from which doxycycline had been withdrawn. The proportions of gut-homing T-central memory (TCM) and TEM defined by the expression of α4β7 and CD95 and differential expression of CD28 were increased in CD4 and CD8 cells under replication competent conditions and gut-homing CD4 TCM were also significantly increased under non-permissive conditions. TEM2 polarisation was seen in the small intestines of animals under replication permissive conditions but the effect was less pronounced than in the circulation. Intracellular cytokine staining of circulating SIV-specific T cells for IL-2, IFN-γ, TNF-α and IL-17 showed that the extent of polyfunctionality in CD4 and CD8 T cells was associated with replication permissivity; however, signature patterns of cytokine combinations were not distinguishable between groups of macaques.

Conclusion
Taken together our results show that the global T memory cell compartment is profoundly skewed towards a mature effector phenotype by attenuated SIV. Results with the replication-conditional mutant suggest that maintenance of this effect, that may be important in vaccine design, might require persistence of replicating virus.
Molecular topography of the MED12-deleted region in smooth muscle tumors: a possible link between non-B DNA structures and hypermutability
Authors: Markowski Dominique Nadine , Nimzyk Rolf , Belge Gazanfer , Löning Thomas , Helmke Burkhard Maria , Bullerdiek Jörn 
Published: June 2013

Abstract

Background
Deletions of the gene encoding mediator subcomplex 12 (MED12) in human smooth muscle tumors rank among the most frequent genomic alterations in human tumors at all. In a minority of these cases, small deletions are found. In an attempt to delineate key features of the deletions aimed at a better understanding of the molecular pathogenesis of uterine smooth muscle tumors we have analyzed 70 MED12 deletions including 46 cases from the literature and 24 own unpublished cases.

Results
The average length of the deletions was 18.7 bp ranging between 2 bp and 43 bp. While in general multitudes of 3 clearly dominated leaving the transcript in frame, deletions of 21, 24, 30, and 33 nucleotides were clearly underrepresented. Within the DNA segment affected deletion breakpoints were not randomly distributed. Most breakpoints clustered within the center of the segment where two peaks of breakpoint clusters could be distinguished. Interestingly, one of these clusters coincides with the loop of a putative folded non-B DNA structure whereas a much lower number of breaks noted in the 5′ and 3′ stem of the structure forming an intramolecular B-helix. The second cluster mainly consisting of 3′ breaks was located in a region downstream adjacent to the stem.

Conclusion
The present study describes for the first time main characteristics of MED12 deletions occurring in smooth muscle tumors. Interestingly, the non-random distribution of breakpoints within the deletion hotspot region may point to a role of non-canonical DNA structures for the occurrence of these mutations and the molecular pathogenesis of uterine smooth muscle tumors, respectively.
Horizontal transfer of bacterial polyphosphate kinases to eukaryotes: implications for the ice age and land colonisation
Authors: Whitehead Michael P , Hooley Paul , W Brown Michael R 
Published: June 2013

Abstract

Background
Studies of online database(s) showed that convincing examples of eukaryote PPKs derived from bacteria type PPK1 and PPK2 enzymes are rare and currently confined to a few simple eukaryotes. These enzymes probably represent several separate horizontal transfer events. Retention of such sequences may be an advantage for tolerance to stresses such as desiccation or nutrient depletion for simple eukaryotes that lack more sophisticated adaptations available to multicellular organisms. We propose that the acquisition of encoding sequences for these enzymes by horizontal transfer enhanced the ability of early plants to colonise the land. The improved ability to sequester and release inorganic phosphate for carbon fixation by photosynthetic algae in the ocean may have accelerated or even triggered global glaciation events. There is some evidence for DNA sequences encoding PPKs in a wider range of eukaryotes, notably some invertebrates, though it is unclear that these represent functional genes.
Polyphosphate (poly P) is found in all cells, carrying out a wide range of essential roles. Studied mainly in prokaryotes, the enzymes responsible for synthesis of poly P in eukaryotes (polyphosphate kinases PPKs) are not well understood. The best characterised enzyme from bacteria known to catalyse the formation of high molecular weight polyphosphate from ATP is PPK1 which shows some structural similarity to phospholipase D. A second bacterial PPK (PPK2) resembles thymidylate kinase. Recent reports have suggested a widespread distribution of these bacteria type enzymes in eukaryotes.

Results
On – line databases show evidence for the presence of genes encoding PPK1 in only a limited number of eukaryotes. These include the photosynthetic eukaryotes Ostreococcus tauri, O. lucimarinus, Porphyra yezoensis, Cyanidioschyzon merolae and the moss Physcomitrella patens, as well as the amoeboid symbiont Capsaspora owczarzaki and the non-photosynthetic eukaryotes Dictyostelium (3 species), Polysphondylium pallidum and Thecamonas trahens. A second bacterial PPK (PPK2) is found in just two eukaryotes (O. tauri and the sea anemone Nematostella vectensis). There is some evidence for PPK1 and PPK2 encoding sequences in other eukaryotes but some of these may be artefacts of bacterial contamination of gene libraries.

Conclusions
Evidence for the possible origins of these eukaryote PPK1s and PPK2s and potential prokaryote donors via horizontal gene transfer is presented. The selective advantage of acquiring and maintaining a prokaryote PPK in a eukaryote is proposed to enhance stress tolerance in a changing environment related to the capture and metabolism of inorganic phosphate compounds. Bacterial PPKs may also have enhanced the abilities of marine phytoplankton to sequester phosphate, hence accelerating global carbon fixation.
UpSETing chromatin during non-coding RNA production
Authors: Venkatesh Swaminathan , Workman Jerry L , Smolle Michaela 
Published: June 2013

Abstract
The packaging of eukaryotic DNA into nucleosomal arrays permits cells to tightly regulate and fine-tune gene expression. The ordered disassembly and reassembly of these nucleosomes allows RNA polymerase II (RNAPII) conditional access to the underlying DNA sequences. Disruption of nucleosome reassembly following RNAPII passage results in spurious transcription initiation events, leading to the production of non-coding RNA (ncRNA). We review the molecular mechanisms involved in the suppression of these cryptic initiation events and discuss the role played by ncRNAs in regulating gene expression.