bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell-Autonomous Regulation of Neutrophil Migration by the D6 Chemokine Decoy Receptor
Authors: Rot Antal , McKimmie Clive , Burt Claire L. , Pallas Kenneth J. , Jamieson Thomas , Pruenster Monika , Horuk Richard , Nibbs Robert J. B. , Graham Gerard J. 
Published: May 2013

Abstract
Chemokines, acting on their cognate receptors on infiltrating leukocytes, drive the inflammatory response. We have been interested in determining roles and potential mechanisms for the atypical chemokine-scavenging receptor D6 in the regulation of inflammation. In this study, we show that a psoriasis-like pathology that arises in inflamed skins of D6-deficient mice is characterized by a massive and aberrant localization of neutrophils to the dermal/epidermal junction, which is associated with development of the pathology. Such misplacement of neutrophils is also seen with D6-deficient mice in other inflammatory models, suggesting a role for D6 in the spatial positioning of neutrophils within inflamed sites. We further show that D6 functions cell autonomously in this context and that D6, expressed by neutrophils, limits their migrational responses to CCR1 ligands such as CCL3. Our data therefore indicate that D6 is able to play a cell-autonomous role as a migratory rheostat restricting migration of D6-expressing cells such as neutrophils toward ligands for coexpressed inflammatory chemokine receptors. These data have important implications for our understanding of the roles for D6 in regulating inflammation and for our understanding of the control of spatial positioning of leukocytes at inflamed sites.
« Industries créatives » et « économie créative » : de la conception de notions opératoires au référentiel d’action publique locale
Authors: Le Corf Jean-Baptiste 
Published: May 2013

Cet article cherche à saisir l’incorporation des notions d’« industrie créative » et d’« économie créative » dans l’action publique locale. Sont analysées les médiations qui se réalisent au travers de la mobilisation de ces notions, à partir de l’analyse de rapports produits par des organismes internationaux et de l’observation directe de certaines manifestations rassemblant experts et décideurs territoriaux. Puis l’étude porte sur le déploiement d’actions locales en faveur des industries culturelles et créatives et sur les stratégies opportunistes des principaux acteurs engagés dans l’action partenariale : d’une part, les experts intermédiaires en charge de clusters qui défendent les intérêts des acteurs industriels ; d’autre part, les villes cherchant à renouveler leurs politiques de communication.
Complete response to low-dose sorafenib in a patient with metastatic renal cell carcinoma: A case report
Authors: Morita Jun , Naoe Michio , Ogawa Yu , Nakasato Takehiko , Sugahara Motoko , Morita Masashi , Fuji Kohzo , Fukagai Takashi , Sasaki Haruaki , Ogawa Yoshio 
Published: May 2013

We present a case of a patient with metastatic renal cell carcinoma (mRCC) who was treated solely with low-dose sorafenib and achieved a complete response (CR). A 79-year-old man with cytokine-refractory mRCC involving the lung, abdominal wall, and lymph nodes was treated with low-dose sorafenib (400 mg/day) as a second-line therapy. Five months into sorafenib administration, CR was confirmed by follow-up computed tomography. No severe adverse events were observed and sorafenib treatment has been continued without appearance of new lesions. Although sorafenib has been approved for mRCC treatment, complete clinical recovery is uncommon and has rarely been described. In this case, low-dose sorafenib appears to be sufficient for achieving CR while suppressing toxicity. Furthermore, long-term continuous administration induces the patient to obtain disease stabilization. However, considering toxicity and treatment costs, it is currently a debate whether treatment should be discontinued or sustained after CR.
Unanticipated intra-operative finding of pulmonary artery tumour thromboembolism during radical nephrectomy and caval thrombectomy: Case report and management
Authors: Sharda Rajan , Deutscher Raymond , Christodoulou Chris , Horne David , Freed Darren H. , McGregor Thomas 
Published: May 2013

We report a case of an unanticipated intra-operative transesophageal echocardiography (TEE) finding of pulmonary artery thromboembolism in a 72yr woman being prepared for radical nephrectomy and caval thrombectomy. Intra-operative TEE performed to evaluate the extent of caval thrombus found the presence of pulmonary artery tumor thromboembolism in an otherwise asymptomatic patient after induction and prior to commencing surgery. A chest Computed Tomography (CT) scan confirmed a large saddle tumor thromboembolus. A multidisciplinary approach was utilized to facilitate radical nephrectomy with caval thrombectomy and pulmonary artery thromboembolectomy. This case shows the importance of adequate perioperative imaging and utilization of intra-operative TEE to evaluate the extent of disease. To our knowledge, we are the first to present a case of RCC with cava tumour thrombus in which the pulmonary artery tumour thromboembolism was detected incidentally on intraoperative TEE.
L’herméneutique théologique de Hans-Georg Gadamer : une dérogation à son herméneutique philosophique ?
Authors: Rodier Dany 
Published: May 2013

Cet article propose une analyse détaillée des considérations de Hans-Georg Gadamer sur l’herméneutique théologique proprement dite. Pensée dans et pour la foi chrétienne, la conception de l’herméneutique théologique qu’il met en avant se veut essentiellement une herméneutique du texte biblique. Les réflexions de Gadamer sur ce thème nous conduisent cependant tout droit dans sa théorie de la littérature. La question directrice devient celle de la nature du texte religieux (entendons : du texte biblique, reçu en son unité canonique) en tant que texte éminent, dont la structure singulière est mise en relief au moyen d’une éclairante comparaison avec les textes poétique, philosophie et juridique. L’Écriture, en tant qu’elle répond à la structure textuelle de la promesse, exige du lecteur une forme particulière d’appropriation qui trouve sa réalisation exemplaire dans la prédication. Toutefois, contre une lecture (Ommen, Eberhard, etc.) qui insiste sur la discontinuité de l’herméneutique théologique de Gadamer avec sa propre oeuvre philosophique, je soutiens la thèse de leur foncière cohérence.
Vatican II entre catholicisme et catholicité
Authors: Siegwalt Gérard 
Published: May 2013

Face aux trois tentations majeures du catholicisme traditionnel (mais dont il n’a pas le monopole), à savoir le particularisme absolutisé de la compréhension qu’il a de lui-même, le supranaturalisme de sa compréhension de Dieu, l’an-historisme de la théologie mystique, face ainsi à la théologie dualiste de la délimitation par rapport à ce qui n’est pas lui, le concile Vatican II représente, dans sa visée, l’ouverture au réel tel qu’il est, dans un esprit non de discrimination mais de discernement, avec la question : qu’est-ce qui dans le réel est constructeur, qu’est-ce qui est destructeur ? Il est mû par la conscience que Dieu est le Dieu du réel et la foi, foi au coeur du réel. Il marque l’ouverture à une théologie de la récapitulation selon laquelle toutes choses sont récapitulées par Dieu en Christ, et ainsi à une intégration critique du réel, dépassant par là l’exclusivisme du catholicisme traditionnel et accédant à l’exigence d’une théologie critique — exclusive et inclusive à la fois — de la catholicité.
Alpha‐Spending Function
Authors: DeMets David L. , Lan K. K. Gordon 
Published: May 2013

AbstractRandomized clinical trials are typically monitored periodically for early evidence of convincing benefit or of potential harm for both scientific and ethical reasons by a data monitoring committee. After increments in the number of patients randomized or in the number of observed events, interim statistical analyses may be conducted to evaluate emerging results. This process may be referred to as a group sequential design. However, repeated analysis of accumulating data with conventional statistical testing can lead to substantially increased Type I or false positive error rates. The alpha spending function provides a flexible approach to control the Type I error while allowing the data monitoring committee to review the data as needed without having to specifya prioriwhen and how many such interim analyses will be conducted. Other earlier group sequential methods had these somewhat restrictive requirements. This alpha spending function approach can be applied to several spending functions that approximate some of these earlier methods.
Application of New Designs in PhaseITrials
Authors: Garrett‐Mayer Elizabeth 
Published: May 2013

AbstractIn recent years, novel designs have been introduced for dose‐finding studies in phase I clinical trials. Most of these are based on mathematical models of the relationship between dose and toxicity. Though these may appear more technical than more commonly used algorithmic designs, the novel designs tend be better for many reasons including smaller sample size, more precise and accurate estimate of the desired dose, fewer patients treated at unsafe levels, and more patients treated at efficacious doses. Several of these novel designs are discussed. The continual reassessment method is an adaptive approach that uses the information gathered on early patients in the trial to make decisions about the dose for patients treated later in the trial. Adaptive Bayesian designs behave in a similar way, but the framework in which they are developed differs. A design in which efficacy and toxicity are both used to determine an optimum dose is also discussed.
Global Assessment Variables
Authors: Tilley Barbara , Huang Peng , O'Brien Peter C. 
Published: May 2013

AbstractMultiple outcomes are often collected for an evaluation of a treatment's effect on disease or quality of life or other underlying condition. When multiple outcomes are being assessed, and no predefined and validated composite outcome (summary measure) exists, two classes of statistical tests have been developed that address two different scientific questions. Tests in one class are designed to test whether a treatment effect is observed for any of the outcomes. Tests in the other class are designed to test whether a treatment confers an overall benefit (or harm) to patients. We provide a brief survey of global statistical tests (GST) of the second class. Each GST is discussed in terms of its motivation, approach to conducting the test, and some basic properties of the test. To facilitate the interpretation of the GST, we use the concept of a global treatment effect (GTE) to quantify the treatment's overall effect on multiple outcomes. We provide examples of the application of GSTs to clinical trials along with recommendations for choosing outcomes to include in the GST.
Good Clinical Practice (
GCP
)
Authors: Barr David B. 
Published: May 2013

Abstract
Good Clinical Practices (GCPs) are international ethical and quality standards for the design, conduct, performance, monitoring, auditing, analysis, recording, reporting, and regulation of clinical investigations. Clinical investigations are experiments in which a medical product such as a drug is administered or dispensed to, or used involving, one or more human subjects. These standards provide assurance that the rights and confidentiality of the trial subjects are protected and that the data and reported results are credible and accurate.
Group Sequential Designs
Authors: Wassmer Gernot 
Published: May 2013

AbstractIn clinical research, a great interest in interim analyses exists for ethical, economical, and organizational or administrative reasons. Interim analyses are performed withinsequential designsthat offer the possibility to stop a trial early with a statistically significant test result. This trial will possibly need less patients than the trial with a fixed sample size in which a test decision can be made only at the end of the trial. A therapy that was shown to be superior can be applied earlier and the inferior therapy can be replaced by the better one. Furthermore, in interim analyses, the quality of the performance of the trial can be assessed and possibly be improved when necessary. Interim analyses are also carried out for the assessment of the safety of the treatments under consideration, and the observation of serious adverse events can lead to an early stopping of the trial.
Imaging Science in Medicine
Authors: Hendee William R. 
Published: May 2013

Abstract
The use of imaging technologies has expanded tremendously in medicine over the past two decades. This expansion reflects the evolution of new imaging tools that reveal human anatomy and physiology in ever‐increasing detail, as well as the development of digital data acquisition and processing techniques that extract information from human tissues in ever‐expanding degrees of subtlety. A further factor that is stimulating growth in imaging is the expansion of knowledge about biological systems at the cellular, molecular, and genetic levels. This factor is transforming medical imaging from a “technology‐push” discipline into one where fundamental biological questions, as well as important clinical issues, are the force driving development of new imaging technologies. This transformation demands enhanced knowledge about the interface between biological properties of tissues and the characteristics of imaging systems. Exploration of the existing state of knowledge about the interface, and what is needed for the immediate future, is the subject of this article.
Multiple Comparisons
Authors: Proschan Michael A. 
Published: May 2013

AbstractBecause clinical trials are very expensive, investigators often want to make several comparisons in the same trial. But, performing several statistical tests at significance level α will increase the probability of at least one false positive declaration. The situation is analogous to throwing many darts at a target; even a completely unskilled dart thrower will eventually hit the bull's eye. Many multiple comparison adjustment methods control the probability of at least one false positive by “raising the bar” for each separate comparison. However, raising the bar increases the chance of missing a true effect and increases the sample size needed to maintain the same power. The tension between controlling the chance of at least one false positive and missing a true effect makes multiplicity adjustment a subject of great controversy in clinical trials. Although clinical trialists have differing opinions about how much adjustment is needed, certain settings exist most would agree that adjustment is needed and others in which most would agree that it is not. This article attempts to shed light on situations in which multiplicity adjustments are needed and the most common methods of adjustment in different clinical trial scenarios, which include multiple arms, multiple endpoints, subgroup analysis, and interim monitoring.
Optimizing Schedule of Administration in PhaseIClinical Trials
Authors: Braun Thomas M. , Thall Peter F. 
Published: May 2013

AbstractHistorically, phase I clinical trials of new agents have been designed to find a safe dose from a small set of possible doses. Typically, toxicity is defined based on one or possibly two cycles of chemotherapy so that it can be scored relatively quickly after the start of therapy. The study treats cohorts of patients according to an outcome‐adaptive statistical design or algorithm for choosing successive doses, and the resulting data are used to determine an acceptable or maximum tolerable dose (MTD). However, in most clinical settings, physicians administer multiple courses of an agent to a patient and monitor long‐term toxicity that may be related to the agent's cumulative effects. Furthermore, some patients may receive one or more modifications or delays of their planned treatment course due to low‐grade (non–dose limiting) toxicity from previous administrations. To address these situations, we have proposed a new paradigm for phase I clinical trials that determines a maximum tolerable schedule (MTS) of administration, rather than a conventional MTD (Braun, Yuan, and Thall, 14). The design is based on the time to toxicity of each patient rather than a binary indicator. The model and method account for the patient's entire sequence of administrations, with the overall hazard of toxicity modeled as the sum of a sequence of dose‐dependent hazards, each associated with one administration. As patients are enrolled, data monitoring and decision making are done continuously throughout the trial using an outcome‐adaptive Bayesian design that optimizes the schedule in terms of the overall risk of toxicity. We illustrate this new methodology with a clinical trial in allogeneic bone marrow transplantation.
Biomarkers Aid Paleoenvironment Studies of Asian Aridification
Authors: Peng Tingjiang , Li Jijun , Zhao Zhijun , Song Chunhui , Zhang Jun 
Published: May 2013

AbstractThe broad, arid region of central Asia is one of the most important dust sources on Earth, its eolian dust output being critical to global biogeochemical cycles. For example, dust contains iron, and wind transport flings the dust to the ocean, where it serves as an important nutrient for phytoplankton. In turn, phytoplankton colonies fueled by dust uptake carbon dioxide (CO2), a key greenhouse gas, from the ocean, allowing the ocean to draw more carbon from the atmosphere. As such, dust availability helps determine how much carbon gets sunk into the ocean.
Lymphocytes: Intraepithelial
Authors: Lambolez Florence , Mayans Sofia , Cheroutre Hilde 
Published: May 2013

Abstract

Intraepithelial lymphocytes (IELs) are small, round mononuclear white blood cells, which reside in the paracellular space between epithelial cells. They are found in the skin and within the epithelial layer that lines the intestine, the biliary tract, the oral cavity, the upper respiratory tract and lungs and the reproductive tract. IELs constitute a heterogeneous population of T lymphocytes that express an αβ or γδ T cell receptor (TCR) on their cell surface. IELs characteristically display an antigen‐experienced phenotype; they vary in their major histocompatibility complex restriction and TCR antigen specificity. All these characteristics are common features of the IEL pool with some variations depending on the tissue where they reside. The largest population of IELs resides within the epithelium of the small intestine, where they function to preserve the integrity of the mucosal barrier by protecting the epithelium against pathogen‐ or immune‐induced pathology.

Key Concepts:

The lymphocytes located in the epithelium are exposed to self, pathogenic and harmless nonself antigens.

The T‐cell populations that reside within the small intestinal epithelium are the most significant in number and the most diverse of all lymphocyte populations in the body.

The T‐cell populations that reside within the epithelium contain unconventional subpopulations such as the CD8αα TCRαβ
+
IELs.

Self‐specific CD8αα TCRαβ
+
IELs acquire their functional antigen‐experienced differentiation during a specific agonist selection process in the thymus.

IELs function to protect the epithelium against pathogen‐induced as well as immune‐induced pathology.
Mimiviruses and Marseilleviruses, the Largest Known Viruses
Authors: Boughalmi Mondher , Colson Philippe , La Scola Bernard 
Published: May 2013

Abstract

Acanthamoeba polyphaga mimivirus
was discovered in 2003 but was isolated two decades ago during the investigation of a pneumonia outbreak, while trying to isolate
Legionella
‐like bacterial pathogens that infect and survive in amoebae.
Acanthamoeba polyphaga marseillevirus
was isolated five years thereafter. These two viruses are the founding members of two new viral families whose members are the largest known viruses based on the sizes of the capsid and the genome. Beyond being giant, mimiviruses and marseilleviruses exhibit several unexpected and remarkable features. Their genomes encode proteins involved in translation, these viruses harbour messenger ribonucleic acid in addition to their double‐stranded
deoxyribonucleic acid
(DNA) genome, and their gene repertoire indicates that they have a common ancestral origin with other large DNA viruses. Finally, mimiviruses and marseilleviruses are likely to be common in our biosphere and have begun to be isolated from humans.

Key Concepts:

Mimiviruses and marseilleviruses are giant viruses that infect phagocytic protists (Acanthamoeba spp. in most cases).

Mimiviruses are the largest known viruses, and their genomes are the largest among viruses and are larger than those of the smallest cellular life.

Mimiviruses and marseilleviruses differ greatly from ‘classical’ viruses in several respects.

Mimiviruses and marseilleviruses are linked by phylogeny based on certain genes and their core genomes to the members of the five families of nucleocytoplasmic large DNA viruses; these seven families were recently proposed to be assigned to a new viral order, Megavirales.

The mosaic gene repertoires of mimiviruses and marseilleviruses are likely linked to their sympatric lifestyle within phagocytic protistan grazers.

Mimiviruses and marseilleviruses are common in our biosphere.

Mimiviruses may cause pneumonia in humans.
Molecular Genetics of Frontotemporal Dementia
Authors: Ferrari Raffaele , Thumma Avinash , Momeni Parastoo 
Published: May 2013

Abstract

Frontotemporal dementia (FTD) is a nonAlzheimer's form of dementia. Onset age lies in the mid‐to‐late 50s. FTD affects the frontal and/or the temporal lobes and is clinically divided into two main categories: behavioural variant (bvFTD) and language variant. FTD is characterised by heterogeneous pathology defined by pathogenic protein inclusions: microtubule‐associated protein tau (MAPT), ubiquitin/transactive responses (TAR)
deoxyribonucleic acid (DNA)
‐binding protein 43 (TDP)‐43, fused in sarcoma (FUS) and p62.
MAPT
, progranulin (
PGRN
) and, recently,
C9orf72
genes represent the three main genetic markers associated with FTD. In addition, genetic variability in
TDP‐43
, charged multivesicular body protein 2B (
CHMP2B
), valosin‐containing protein (
VCP
),
FUS
and
TMEM106B
genes contribute to ⩽5% of cases. Research tools such as genome‐wide association studies and exome and genome sequencing hold promise to further uncover the genetic underpinnings of this complex disorder.

Key Concepts:

Frontotemporal dementia (FTD) is a nonAlzheimer's form of dementia; it affects behaviour, cognition and language, while memory (in the early phases).

The anatomical areas of the brain that are affected by atrophy are the frontal and the temporal lobes; based on this fact FTD is considered part of the spectrum called frontotemporal lobar degeneration (FTLD).

FTD is a complex disease with insidious onset; no therapeutic measures are available as yet.

Behavioural variant FTD (bvFTD) is the most common syndrome of FTD, which is associated with gradual deterioration of behaviour and cognition.

Different protein inclusions in the brain are used to classify the pathology associated with FTLD.

TDP‐43 and tau pathology represent the most common (∼90%) types of pathological signatures associated with FTLD.

MAPT
,
PGRN
and
C9orf72
are the major (∼95%) genetic markers associated with familial FTD.

TMEM106B regulates granulin protein levels.

Genome‐wide association studies (GWASs) and next‐generation sequencing technologies whole exome sequencing (WES) and whole genome sequencing (WGS) hold promise for dissecting the genetic aetiology of complex diseases; in molecular genetics these technologies help in screening a wide range of genetic variabilities from SNPs to CNVs in large cohorts across different populations.