bluuebunny/crossref_metadata_2025_split huggingface dataset:
Baseline predictors of response and discontinuation of tumor necrosis factor-alpha blocking therapy in ankylosing spondylitis: a prospective longitudinal observational cohort study
Authors: Arends Suzanne , Brouwer Elisabeth , van der Veer Eveline , Groen Henk , Leijsma Martha K , Houtman Pieternella M , Th A Jansen Tim L , Kallenberg Cees GM , Spoorenberg Anneke 
Published: June 2011

Abstract
Introduction
Identifying ankylosing spondylitis (AS) patients who are likely to benefit from tumor necrosis factor-alpha (TNF-α) blocking therapy is important, especially in view of the costs and potential side effects of these agents. Recently, the AS Disease Activity Score (ASDAS) has been developed to assess both subjective and objective aspects of AS disease activity. However, data about the predictive value of the ASDAS with respect to clinical response to TNF-α blocking therapy are lacking. The aim of the present study was to identify baseline predictors of response and discontinuation of TNF-α blocking therapy in AS patients in daily clinical practice.

Methods
AS outpatients who started TNF-α blocking therapy were included in the Groningen Leeuwarden Ankylosing Spondylitis (GLAS) study, an ongoing prospective longitudinal observational cohort study with follow-up visits according to a fixed protocol. For the present analysis, patients were excluded if they had previously received anti-TNF-α treatment. Predictor analyses of response and treatment discontinuation were performed using logistic and Cox regression models, respectively.

Results
Between November 2004 and April 2010, 220 patients started treatment with infliximab (n = 32), etanercept (n = 137), or adalimumab (n = 51). At three and six months, 68% and 63% of patients were Assessments in Ankylosing Spondylitis (ASAS)20 responders, 49% and 46% ASAS40 responders, and 49% and 50% Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)50 responders, respectively. Baseline predictors of response were younger age, male gender, higher ASDAS score, higher erythrocyte sedimentation rate (ESR) level, higher C-reactive protein (CRP) level, presence of peripheral arthritis, higher patient's global assessment of disease activity, and lower modified Schober test. In August 2010, 64% of patients were still using their TNF-α blocking agent with a median follow-up of 33.1 months (range 2.4 to 68.2). Baseline predictors of discontinuation of TNF-α blocking therapy were female gender, absence of peripheral arthritis, higher BASDAI, lower ESR level, and lower CRP level.

Conclusions
Besides younger age and male gender, objective variables such as higher inflammatory markers or ASDAS score were identified as independent baseline predictors of response and/or continuation of TNF-α blocking therapy. In contrast, higher baseline BASDAI score was independently associated with treatment discontinuation. Based on these results, it seems clinically relevant to include more objective variables in the evaluation of anti-TNF-α treatment.
Potent anti-inflammatory and antinociceptive activity of the endothelin receptor antagonist bosentan in monoarthritic mice
Authors: Imhof Anne-Katja , Glück Laura , Gajda Mieczyslaw , Bräuer Rolf , Schaible Hans-Georg , Schulz Stefan 
Published: June 2011

Abstract
Introduction
Endothelins are involved in tissue inflammation, pain, edema and cell migration. Our genome-wide microarray analysis revealed that endothelin-1 (ET-1) and endothelin-2 (ET-2) showed a marked up-regulation in dorsal root ganglia during the acute phase of arthritis. We therefore examined the effects of endothelin receptor antagonists on the development of arthritis and inflammatory pain in monoarthritic mice.

Methods
Gene expression was examined in lumbar dorsal root ganglia two days after induction of antigen-induced arthritis (AIA) using mRNA microarray analysis. Effects of drug treatment were determined by repeated assessment of joint swelling, pain-related behavior, and histopathological manifestations during AIA.

Results
Daily oral administration of the mixed ETA and ETB endothelin receptor antagonist bosentan significantly attenuated knee joint swelling and inflammation to an extent that was comparable to dexamethasone. In addition, bosentan reduced inflammatory mechanical hyperalgesia. Chronic bosentan administration also inhibited joint swelling and protected against inflammation and joint destruction during AIA flare-up reactions. In contrast, the ETA-selective antagonist ambrisentan failed to promote any detectable antiinflammatory or antinociceptive activity.

Conclusions
Thus, the present study reveals a pivotal role for the endothelin system in the development of arthritis and arthritic pain. We show that endothelin receptor antagonists can effectively control inflammation, pain and joint destruction during the course of arthritis. Our findings suggest that the antiinflammatory and antinociceptive effects of bosentan are predominantly mediated via the ETB receptor.
Short term Candida albicans colonization reduces Pseudomonas aeruginosa-related lung injury and bacterial burden in a murine model
Authors: Ader Florence , Jawhara Samir , Nseir Saad , Kipnis Eric , Faure Karine , Vuotto Fanny , Chemani Chanez , Sendid Boualem , Poulain Daniel , Guery Benoit 
Published: June 2011

Abstract
Introduction
Pseudomonas aeruginosa is a frequent cause of ventilator-acquired pneumonia (VAP). Candida tracheobronchial colonization is associated with higher rates of VAP related to P. aeruginosa. This study was designed to investigate whether prior short term Candida albicans airway colonization modulates the pathogenicity of P. aeruginosa in a murine model of pneumonia and to evaluate the effect of fungicidal drug caspofungin.

Methods
BALB/c mice received a single or a combined intratracheal administration of C. albicans (1 × 105 CFU/mouse) and P. aeruginosa (1 × 107 CFU/mouse) at time 0 (T0) upon C. albicans colonization, and Day 2. To evaluate the effect of antifungal therapy, mice received caspofungin intraperitoneally daily, either from T0 or from Day 1 post-colonization. After sacrifice at Day 4, lungs were analyzed for histological scoring, measurement of endothelial injury, and quantification of live P. aeruginosa and C. albicans. Blood samples were cultured for dissemination.

Results
A significant decrease in lung endothelial permeability, the amount of P. aeruginosa, and bronchiole inflammation was observed in case of prior C. albicans colonization. Mortality rate and bacterial dissemination were unchanged by prior C. albicans colonization. Caspofungin treatment from T0 (not from Day 1) increased their levels of endothelial permeability and lung P. aeruginosa load similarly to mice receiving P. aeruginosa alone.

Conclusions
P. aeruginosa-induced lung injury is reduced when preceded by short term C. albicans airway colonization. Antifungal drug caspofungin reverses that effect when used from T0 and not from Day 1.
Sniper: improved SNP discovery by multiply mapping deep sequenced reads
Authors: Simola Daniel F , Kim Junhyong 
Published: June 2011

AbstractSNP (single nucleotide polymorphism) discovery using next-generation sequencing data remains difficult primarily because of redundant genomic regions, such as interspersed repetitive elements and paralogous genes, present in all eukaryotic genomes. To address this problem, we developed Sniper, a novel multi-locus Bayesian probabilistic model and a computationally efficient algorithm that explicitly incorporates sequence reads that map to multiple genomic loci. Our model fully accounts for sequencing error, template bias, and multi-locus SNP combinations, maintaining high sensitivity and specificity under a broad range of conditions. An implementation of Sniper is freely available at http://kim.bio.upenn.edu/software/sniper.shtml.
A global transcriptional analysis of Plasmodium falciparum malaria reveals a novel family of telomere-associated lncRNAs
Authors: Broadbent Kate M , Park Daniel , Wolf Ashley R , Van Tyne Daria , Sims Jennifer S , Ribacke Ulf , Volkman Sarah , Duraisingh Manoj , Wirth Dyann , Sabeti Pardis C , Rinn John L 
Published: June 2011

Abstract
Background
Mounting evidence suggests a major role for epigenetic feedback in Plasmodium falciparum transcriptional regulation. Long non-coding RNAs (lncRNAs) have recently emerged as a new paradigm in epigenetic remodeling. We therefore set out to investigate putative roles for lncRNAs in P. falciparum transcriptional regulation.

Results
We used a high-resolution DNA tiling microarray to survey transcriptional activity across 22.6% of the P. falciparum strain 3D7 genome. We identified 872 protein-coding genes and 60 putative P. falciparum lncRNAs under developmental regulation during the parasite's pathogenic human blood stage. Further characterization of lncRNA candidates led to the discovery of an intriguing family of lncRNA telomere-associated repetitive element transcripts, termed lncRNA-TARE. We have quantified lncRNA-TARE expression at 15 distinct chromosome ends and mapped putative transcriptional start and termination sites of lncRNA-TARE loci. Remarkably, we observed coordinated and stage-specific expression of lncRNA-TARE on all chromosome ends tested, and two dominant transcripts of approximately 1.5 kb and 3.1 kb transcribed towards the telomere.

Conclusions
We have characterized a family of 22 telomere-associated lncRNAs in P. falciparum. Homologous lncRNA-TARE loci are coordinately expressed after parasite DNA replication, and are poised to play an important role in P. falciparum telomere maintenance, virulence gene regulation, and potentially other processes of parasite chromosome end biology. Further study of lncRNA-TARE and other promising lncRNA candidates may provide mechanistic insight into P. falciparum transcriptional regulation.
Association of Diagnostic Radiation Exposure and Second Abdominal-Pelvic Malignancies After Testicular Cancer
Authors: van Walraven Carl , Fergusson Dean , Earle Craig , Baxter Nancy , Alibhai Shabbir , MacDonald Blair , Forster Alan J. , Cagiannos Ilias 
Published: June 2011

Purpose The evidence associating cancer risk with diagnostic radiation exposure is unclear. Men recovering from low-grade testicular cancer frequently undergo serial abdominal-pelvic computerized tomography (CT) scanning to monitor for recurrent disease. Methods We used population-based administrative data sets to identify every incident case of testicular cancer between 1991 and 2004 in Ontario, Canada. We excluded those with previous cancer, concurrent radiation therapy, retroperitoneal lymph node dissection, or fewer than 5 years observation. Patients were observed until the occurrences of death or development of a second abdominal-pelvic malignancy or until December 31, 2009. Results A total of 2,569 men (mean age, 34.7 years; standard deviation, 10.2) were observed for a median of 11.2 years (interquartile range [IQR], 8.3 to 14.3). During the first 5 years after diagnosis, men underwent a median of 10 computed tomography (CT) scans (IQR, 4 to 18) of the abdominal-pelvic area, and they were exposed to a median of 110 mSv of radiation from radiologic investigations (IQR, 44 to 190). After this, 14 men were diagnosed with a second abdominal-pelvic malignancy (rate, five per 10,000 patient-years observation, 95% CI, three to eight); the most common diagnoses were colorectal and kidney malignancies. Radiation exposure was not associated with an excess risk of second cancers (hazard ratio per 10 mSv increase, 0.99; 95% CI, 0.95 to 1.04). This association did not change if men observed for fewer than 5 years were included in the analysis (hazard ratio, 1.00; 95% CI, 0.96 to 1.04). Conclusion Second malignancies of the abdomen-pelvis are uncommon in men with low-grade testicular cancer. In this study, the risk of second cancer was not associated with the amount of diagnostic radiation exposure.
Diagnostische Pfade bei Nierenerkrankungen1) / Diagnostic pathways for renal diseases
Authors: Hofmann Walter , Ehrich Jochen H.H. , Guder Walter G. , Keller Frieder , Scherberich Jürgen 
Published: June 2011

Zusammenfassung
Die Deutsche Vereinte Gesellschaft für Klinische Chemie und Laboratoriumsmedizin hat 2006 eine Arbeitsgruppe aus der Taufe gehoben, die gemeinsam mit Mitgliedern der Deutschen Gesellschaft für Nephrologie die bisher verfügbaren Empfehlungen zum Ausschluss, zur Erfassung und Differenzierung von Nierenerkrankungen als diagnostische Pfade strukturiert niederlegen. Die so geschaffene Grundlage soll dann mit EDV-Unterstützung als ein entsprechendes Konzept in der Klinik verfügbar bzw. anforderbar gemacht werden. Die vorliegende Arbeit enthält die Inhalte dieser Pfade betreffend die glomeruläre Filtrationsrate, Hämaturie, Leukozyturie und Proteinurie.
Hirnwelt oder Lebenswelt? Zur Kritik des Neurokonstruktivismus
Authors: Fuchs Thomas 
Published: June 2011

Abstract
From a neuroconstructivistic point of view, the human brain produces an internal simulation of the external world which appears in conscious experience as the phenomenal world. This concept implies in particular that the subjective body and the organic or objective body belong to fundamentally different realms, i.e. to the mental and the physical world. The spatiality of the subject-body has then to be declared an illusion, which is done by pointing to dissociations of the subject- and object-body as in the rubber hand illusion or in phantom limbs. This alleged virtuality of body experience may be refuted, however, namely by referring to the intersubjectivity of perception which certifies the coextensivity of subject-body and object-body. Subjectivity is thus shown to be embodied as well as spatially extended, that means, as bodily being-in-the-world.
Begegnungen im Vorraum der Macht. Carl Schmitt und Niklas Luhmann
Authors: Scholz Leander 
Published: June 2011

Abstract
Following Carl Schmitt′s diagnosis that the area of politics is becoming diffuse, this article analyses the transformation of the relationship between the powerholders and the subordinates under the condition of an increasing numbers of observers representing a powerful factor in their own right. In the perspective of Schmitt this factor threatens the relation of protection and obedience and therefore the whole fundament of politics. By contrast this article understands the system theory of power by Niklas Luhmann as an answer to the problem: including the observers in the process of the execution of power and transforming them into managers of political risk renders the reproduction of power possible under the condition of increasing observation.
Perspektiven einer kritischen Philosophie der Neurowissenschaften
Authors: Slaby Jan 
Published: June 2011

Abstract
This text presents a survey of problem areas surrounding recent developments in the cognitive, social and affective neurosciences and analyzes them from a critical philosophical perspective. Issues discussed include the public circulation of brain images, the stabilizing of types of persons on the grounds of alleged brain types, the re-formatting of humanities disciplines under the imperatives of scientific research and funding structures, the widespread construals of cerebral subjectivity and the tacit naturalization of social categories and conditions in the name of neural plasticity. A brief outline of the interdisciplinary initiative of critical neuroscience is provided to suggest a perspective for further analyses of these debated issues.
Rechtsverhältnis und aufrechter Gang. Rechtsethik im zweiten Versuch
Authors: Somek Alexander 
Published: June 2011

Abstract
The concept of law presupposes the concept of the legal relationship. Law authorizes, potentially or actually, the use of coercion in order to guarantee freedom from interference by others. But coercive norms also constitute internal negative liberty for their addressees. A legal obligation cannot require adopting, let alone endorsing, the internal perspective of the law-giver. Legal subjects remain strangers to one another. Reconciling legality with autonomy involves, therefore, conceiving of one′s self-determination from the perspective of someone whose reasoning remains ultimately secluded from others. Realizing this type of relation to oneself gives rise to the ethical legal obligation to assert oneself as a morally self-reliant individual.
Literary Experimentation in Rowland Hill's Village Dialogues: Transcending "Critical Attitudes" in the Face of Societal Ruination
Authors: Wallbank Adrian J. 
Published: June 2011

Adrian J. Wallbank, "Literary Experimentation in Rowland Hill's Village Dialogues: Transcending 'Critical Attitudes' in the Face of Societal Ruination" (pp. 1–36)
In the aftermath of the French "Revolution Controversy," middle-class evangelical writers made a concerted effort to rehabilitate the moral fabric of British society. Hannah More's Cheap Repository Tracts (1795–98) are recognized as pivotal within this program, but in this essay I question whether they were really as influential as has been supposed. I argue that autobiographical evidence from the period demonstrates an increasing skepticism toward overt didacticism, and that despite their significant and undeniable penetration within working-class culture, the Cheap Repository Tracts, if not all "received ideologies," were increasingly being rejected by their readers. This essay examines the important contribution that Rowland Hill's Village Dialogues (1801) made to this arena. Hill, like many of his contemporaries, felt that British society was facing ruination, but he also recognized that overt moralizing and didacticism was no longer palatable or effective. I argue that Hill thus experimented with an array of literary techniques—many of which closely intersect with developments occurring within the novel and sometimes appear to contradict or undermine the avowed seriousness of evangelicalism—that not only attempt to circumvent what Jonathan Rose has described as the "critical attitudes" of early-nineteenth-century readers, but also effectively map the "transitional" nature of the shifting literary and social terrains of the period. In so doing, Hill contributed signally to the evolution of the dialogue form (which is often synonymous with mentoring and didacticism), since his use of conversational mimesis and satire predated the colloquialism of John Wilson's Noctes Ambrosianae (1822–35) and Walter Savage Landor's Imaginary Conversations (1824–29).
Implementation of a Multicenter Rapid Response System in Pediatric Academic Hospitals Is Effective
Authors: Kotsakis Afrothite , Lobos Anna-Theresa , Parshuram Christopher , Gilleland Jonathan , Gaiteiro Rose , Mohseni-Bod Hadi , Singh Ram , Bohn Desmond ,   on behalf of the Ontario Pediatric Critical Care Response Team Collaborative
Published: June 2011

OBJECTIVES:
This is the first large multicenter study to examine the effectiveness of a pediatric rapid response system (PRRS). The primary objective was to determine the effect of a PRRS using a physician-led team on the rate of actual cardiopulmonary arrests, defined as an event requiring chest compressions, epinephrine, or positive pressure ventilation. The secondary objectives were to determine the effect of PRRSs on the rate of PICU readmission within 48 hours of discharge and PICU mortality after readmission and urgent PICU admission.

METHODS:
A PRRS was developed, implemented, and evaluated in a standardized manner across 4 pediatric academic centers in Ontario, Canada. The team responded to activations for inpatients and followed patients discharged from the PICU for 48 hours. A 2-year, prospective, observational study was conducted after implementation, and outcomes were compared with data collected 2 years before implementation.

RESULTS:
After PRRS implementation, there were 55 963 hospital admissions and a team activation rate of 44 per 1000 hospital admissions. There were 7302 patients followed after PICU discharge. Implementation of the PRRS was not associated with a reduction in the rate of actual cardiopulmonary arrests (1.9 vs 1.8 per 1000 hospital admissions; P = .68) or PICU mortality after urgent admission (1.3 vs 1.1 per 1000 hospital admissions; P = .25). There was a reduction in the PICU mortality rate after readmission (0.3 vs 0.1 death per 1000 hospital admissions; P = .05).

CONCLUSION:
The standardized implementation of a multicenter PRRS was associated with a decrease in the rate of PICU mortality after readmission but not actual cardiopulmonary arrests.
Folic Acid Use in Pregnancy and the Development of Atopy, Asthma, and Lung Function in Childhood
Authors: Magdelijns Fabienne J. H. , Mommers Monique , Penders John , Smits Luc , Thijs Carel 
Published: June 2011

BACKGROUND:
Recently, folic acid supplementation during pregnancy was implicated as a potential risk factor for atopic diseases in childhood.

OBJECTIVE:
To investigate whether folic acid supplementation and higher intracellular folic acid (ICF) levels during pregnancy increase the risk of childhood atopic diseases.

METHODS:
In the KOALA Birth Cohort Study (N = 2834), data on eczema and wheeze were collected by using repeated questionnaires at 3, 7, 12, and 24 months, 4 to 5 years, and 6 to 7 years after delivery. Atopic dermatitis and total and specific immunoglobulin E levels were determined at age 2 years and asthma and lung function at age 6 to 7 years. We defined folic acid use as stand-alone and/or multivitamin supplements according to the period of use before and/or during pregnancy. ICF levels were determined in blood samples taken at ∼35 weeks of pregnancy (n = 837). Multivariable logistic and linear regression analyses were conducted, with generalized estimating equation models for repeated outcomes.

RESULTS:
Maternal folic acid supplement use during pregnancy was not associated with increased risk of wheeze, lung function, asthma, or related atopic outcomes in the offspring. Maternal ICF level in late pregnancy was inversely associated with asthma risk at age 6 to 7 years in a dose-dependent manner (P for trend = .05).

CONCLUSIONS:
Our results do not confirm any meaningful association between folic acid supplement use during pregnancy and atopic diseases in the offspring. Higher ICF levels in pregnancy tended, at most, toward a small decreased risk for developing asthma.