bluuebunny/crossref_metadata_2025_split huggingface dataset:
Eligibility for Randomized Trials of Treatments Specifically for Intracerebral Hemorrhage
Authors: Fonville Arthur F. , Samarasekera Neshika , Hutchison Aidan , Perry David , Roos Yvo B. , Al-Shahi Salman Rustam 
Published: July 2013

Background and Purpose—
Acute treatments specifically for intracerebral hemorrhage (ICH) are being sought in randomized controlled trials. The treatment effect sizes in ongoing and future trials are likely to be small, necessitating large sample sizes.

Methods—
We searched online trial registries for randomized controlled trials investigating an acute treatment for ICH. For the trials whose eligibility criteria could be assessed in a prospective, community-based ICH cohort study (2010–2011), we quantified the proportions of patients who were eligible and investigated influences on these proportions.

Results—

We applied the eligibility criteria of 17 trials to 166 adults with ICH, of whom between 0.6% (95% confidence interval, 0.1–3.3) to 40% (95% confidence interval, 33–48) were eligible for each trial. Fewer patients were eligible for trials restricted to patients randomized within 12 hours of ICH onset (versus trials with a longer time window;
P
=0.03) and trials restricting eligibility according to premorbid disability (versus trials without this restriction;
P
=0.046). Each additional eligibility criterion reduced the portion of eligible patients by 1.3% (95% confidence interval, 0.4–2.2; adjusted
R
2
=0.47;
P
=0.004).

Conclusions—

Less than half of patients with ICH were eligible for current randomized controlled trials. Future trials could maximize enrollment by minimizing the number of eligibility criteria, maximizing the time window for recruiting patients after ICH onset, permitting premorbid disability, and using a simulator to assess the impact of other eligibility critiera (
www.dcn.ed.ac.uk/ICHsimulator/
).
Lesion Location Predicts Transient and Extended Risk of Aspiration After Supratentorial Ischemic Stroke
Authors: Galovic Marian , Leisi Natascha , Müller Marlise , Weber Johannes , Abela Eugenio , Kägi Georg , Weder Bruno 
Published: July 2013

Background and Purpose—
To assess the association of lesion location and risk of aspiration and to establish predictors of transient versus extended risk of aspiration after supratentorial ischemic stroke.

Methods—
Atlas-based localization analysis was performed in consecutive patients with MRI-proven first-time acute supratentorial ischemic stroke. Standardized swallowing assessment was carried out within 8±18 hours and 7.8±1.2 days after admission.

Results—

In a prospective, longitudinal analysis, 34 of 94 patients (36%) were classified as having acute risk of aspiration, which was extended (≥7 days) or transient (<7 days) in 17 cases. There were no between-group differences in age, sex, cause of stroke, risk factors, prestroke disability, lesion side, or the degree of age-related white-matter changes. Correcting for stroke volume and National Institutes of Health Stroke Scale with a multiple logistic regression model, significant adjusted odds ratios in favor of acute risk of aspiration were demonstrated for the internal capsule (adjusted odds ratio, 6.2;
P
<0.002) and the insular cortex (adjusted odds ratio, 4.8;
P
<0.003). In a multivariate model of extended versus transient risk of aspiration, combined lesions of the frontal operculum and insular cortex was the only significant independent predictor of poor recovery (adjusted odds ratio, 33.8;
P
<0.008).

Conclusions—
Lesions of the insular cortex and the internal capsule are significantly associated with acute risk of aspiration after stroke. Combined ischemic infarctions of the frontal operculum and the insular cortex are likely to cause extended risk of aspiration in stroke patients, whereas risk of aspiration tends to be transient in subcortical stroke.
G. K. Chesterton: Theologian?
Authors: Collins Peter M. 
Published: July 2013

Abstract
The subject of this review essay is Aidan Nichols’ book G. K. Chesterton, Theologian. Nichols has used Chesterton’s two best known books, Orthodoxy (1908) and The Everlasting Man (1925) (especially the latter), in explaining five “theological” Chestertonian themes, following an explication of various principles characterizing Chesterton’s authorship. The author, a well-known theologian, seems to view the first part of his book as focused upon philosophy and the second part being essentially theological. He not only is “speaking theologically” in the latter but also maintaining that Chesterton is doing theology as well. For example, he refers to The Everlasting Man as the “theological masterpiece” of Chesterton’s maturity.
In the first section of this commentary, the message of G. K. Chesterton, Theologian is summarized briefly. In the second section, there is a question raised of whether Chesterton was really a theologian despite the Christian orientation of his writings. The purpose in raising this question is not to answer it decisively, but to notice some factors that must be considered in order to answer it, at least in a preliminary manner. Much of my own inquiry in this second section is addressed to the general nature and some principles of Orthodoxy and The Everlasting Man, attempting to view them in accord with Chesterton.
Universal Salvation in a Universal Language? Trevor Steele’s Kaj staros tre alte
Authors: Hale Frederick 
Published: July 2013

Abstract
Extensive secularisation in Europe and several other parts of the world in recent decades has not diminished the attractiveness of Jesus as a theme in contemporary fiction internationally. Fictional biographies of him continue to appear in many languages. Among the novelists who have tapped their imaginations to fill in gaps in the canonical gospels and construct a Jesus who fits their own agenda is the Australian Trevor Steele. His work of 2006, Kaj staros tre alte, presents Jesus as essentially a supernaturally gifted healer but also as a teacher of universal brotherhood. Steele argues that the effectiveness of Jesus was severely limited by contemporary notions of Jewish apocalypticism and Messianism. Steele’s literary device for providing extra-biblical information about Jesus is a manuscript purportedly written by a Roman tax officer who was stationed in Caesarea approximately a decade after the Crucifixion. Discovered in 2001, this Greek text forms the fictional basis of Kaj staros tre alte.
Pharmacometabonomics and personalized medicine
Authors: Everett Jeremy R , Loo Ruey Leng , Pullen Francis S 
Published: July 2013

Background Pharmacometabonomics is a new branch of science, first described in 2006 and defined as ‘the prediction of the effects of a drug on the basis of a mathematical model of pre-dose metabolite profiles’. Pharmacometabonomics has been used to predict drug metabolism, pharmacokinetics (PK), drug safety and drug efficacy in both animals and humans and is complementary to both pharmacogenomics (PGx) and pharmacoproteomics. Methods A literature review using the search terms pharmacometabonomics, pharmacometabolomics, pharmaco-metabonomics, pharmaco-metabolomics and the singular form of all those terms was conducted in October 2012 using PubMed and Web of Science. The review was updated until mid April 2013. Results Since the original description of pharmacometabonomics in 2006, 21 original publications and eight reviews have emerged, covering a broad range of applications from the prediction of PK to the prediction of drug metabolism, efficacy and safety in humans and animals. Conclusions Pharmacometabonomics promises to be an important new approach to the delivery of personalized medicine to improve both drug efficacy and safety for patients in the future. Pharmacometabonomics is particularly powerful as it is sensitive to both genetic and environmental factors such as diet, drug intake and most importantly, a person’s microbiome. PGx is now over 50 years old and although it has not achieved as much as some hoped, it is starting to have important applications in personalized medicine. We predict that pharmacometabonomics will be equally important in the next few decades and will be both valuable in its own right and complementary to pharmacoproteomics and PGx.
Education and the public’s desire for social distance from people with depression and schizophrenia: The contribution of emotional reactions and causal attributions
Authors: von dem Knesebeck Olaf , Angermeyer Matthias C , Kofahl Christopher , Makowski Anna Christin , Mnich Eva 
Published: July 2013

Background: Association between education and desire for social distance from people with mental illness is unclear. Aims: (1) Is there an association between education and social distance from people with a depression or schizophrenia? (2) Can this association be explained by beliefs about causes of and emotional reactions to the mental disorders? (3) Are there differences between the two mental disorders? Methods: Analyses are based on a telephone survey in two large German cities (Hamburg and Munich, N = 2,014, response rate 51%). Vignettes with typical signs and symptoms suggestive of depression and schizophrenia were presented. Respondents were asked about beliefs about causes of the mental disorders, their emotional reactions and their desire for social distance. Results: Lower education is significantly associated with a stronger tendency for social distance in the case of depression but not in case of schizophrenia, when age and gender are controlled. In case of depression, the association decreases when beliefs about possible causes are additionally controlled. In terms of schizophrenia, associations between education and social distance become stronger when emotional reactions are introduced. Conclusions: Our results underline that campaigns aimed at reducing stigma and social distance should consider specific emotional reactions and information needs of people with low education regarding different mental disorders.
Sclerosis and varicocele embolization with N-butyl cyanoacrylate: experience in 41 patients
Authors: Urbano José , Cabrera Manuel , Alonso-Burgos Alberto 
Published: July 2013

Background Embolization is an established treatment for varicocele. Coils are most frequently used in the procedure. Liquid embolic and sclerosing agents seem to have a number of advantages over coils. Purpose To report our experience and explain the technique of using N-2-butyl-cyanoacrylate (N2BCA) in varicocele treatment. Material and Methods From January 2010 to July 2011, 42 gonadal veins in 41 consecutive patients (age range, 11–41 years; mean, 18 years) with a diagnosis of varicocele were treated with N2BCA as an embolic agent. The clinical diagnosis was confirmed by Doppler ultrasound in all patients. Institutional review board approval was obtained, and all the patients signed informed consent for this retrospective review. In all cases, a 4-F hydrophilic catheter was used to catheterize the distal portion of the gonadal vein through which N2BCA, emulsified with lipiodol, was injected. Results The technical success was 100%. No complications or non-targeted embolizations were reported. Seven patients reported moderate post-embolization pain that required oral analgesic treatment for 7–10 days. After 12-month follow-up, all patients exhibited varicocele resolution in the Doppler ultrasound examination as well as relief of all previous symptoms. We have no fertility-related data for patients treated for this condition. Conclusion N2BCA as an embolic agent is a therapeutic alternative for the endovascular treatment of varicocele. This technique is uncomplicated, inexpensive, efficient, and safe.
Poor specific antibody response immunodeficiency (dysgammaglobulinemia) predates systemic lupus erythematosus
Authors: Hamzi H Al , Shaikh A Al , Arnaout RK 
Published: July 2013

Poor specific antibody response is a well-known primary immunodeficiency that is related to hypogammaglobulinemia or common variable immunodeficiency (CVID). The co-existence of CVID or hypogammaglobulinemia and systemic lupus erythematosus (SLE) has been rarely described. In all reported cases, the diagnosis of SLE antedates CVID. We report a 15-year-old Saudi girl who was diagnosed with poor specific antibody response at age 6 years in the form of poor or no antibody response and dysgammaglobulinemia. She developed SLE with musculoskeletal and hematological manifestations, positive antinuclear antibody and high anti-dsDNA nine years later. She was treated with rituximab with good response.
Reverse causality behind the association between reproductive history and MS
Authors: Hedström AK , Hillert J , Olsson T , Alfredsson L 
Published: July 2013

Background: Possible associations between childbearing patterns and multiple sclerosis (MS) risk have been studied for a long time, with conflicting results. We aimed to investigate the influence of reproductive history on MS risk. Methods: Using a Swedish population-based case-control study involving incident cases of MS (1798 cases, 3907 controls), we calculated odds ratios (OR) for MS comparing parents with childless subjects together with 95% confidence intervals (CI) employing logistic regression. Results: Overall, there was an association between having children and reduced MS risk among both sexes. Subjects who had become parents within five years prior to the index year had a substantially reduced risk of developing MS (OR 0.6, 95% CI 0.5–0.8 for women, and OR 0.4, 95% CI 0.3–0.6 for men). No association between having children and MS risk was observed when more than 10 years had passed since the birth of the last child. We found no association between increasing offspring number and MS risk. Conclusions: The observed association between reproductive history and MS risk is restricted to a limited time period preceding the index year, with similar findings in both sexes, which contradicts biologic impact of pregnancy on MS risk and argues in favor of reverse causality, i.e. that fecundity is affected by yet-undiagnosed MS.
Tumor necrosis factor is elevated in progressive multiple sclerosis and causes excitotoxic neurodegeneration
Authors: Rossi Silvia , Motta Caterina , Studer Valeria , Barbieri Francesca , Buttari Fabio , Bergami Alessandra , Sancesario Giulia , Bernardini Sergio , De Angelis Gottardo , Martino Gianvito , Furlan Roberto , Centonze Diego 
Published: July 2013

Background: Chronic inflammation leads to gray matter damage in progressive multiple sclerosis (MS), but the mechanism linking inflammation and neurodegeneration is unclear. Objective: The objective of this paper is to investigate the synaptic mechanism of inflammatory neurodegeneration in progressive forms of MS. Methods: Cytokine and neurofilament-light were determined in cerebrospinal fluid (CSF) of MS patients. In vitro electrophysiology and cell swelling experiments were performed to measure the effects of inflammatory cytokines in the CSF of MS patients on synaptic transmission and neuronal integrity. Results: Tumor necrosis factor-α (TNF) was higher in CSF of progressive MS subjects, and caused excitotoxic neuronal death in vitro. In murine brain slices incubated in the presence of CSF from progressive MS, in fact, we observed increased spontaneous excitatory postsynaptic currents (sEPSCs) and glutamate-mediated neuronal swelling through a mechanism dependent on enhanced TNF signaling. We also suggested a pathogenic role of B cells in TNF CSF increase, exacerbation of glutamatergic transmission and neuronal damage, since CNS depletion of B cells with intrathecal rituximab caused a dramatic reduction of TNF levels, of TNF-induced sEPSC alterations, and of neurofilament CSF concentrations in a patient with progressive MS. Conclusion: Our results point to TNF as a primary neurotoxic molecule in progressive forms of MS.
Combining HLA-DR risk alleles and anti-Epstein-Barr virus antibody profiles to stratify multiple sclerosis risk
Authors: Strautins K , Tschochner M , James I , Choo L , Dunn DS , Pedrini M , Kermode A , Carroll W , Nolan D 
Published: July 2013

Background: Risk factors for multiple sclerosis (MS) include human leukocyte antigen (HLA)-DR and Epstein-Barr virus (EBV)-specific antibody responses, including an epitope within EBV nuclear antigen 1 (EBNA-1) that is of recent interest. Objective: The objective of this paper is to assess case-control associations between MS risk and anti-EBV antibody levels as well as HLA-DR profiles, gender and age in a population-based cohort. Methods: Serological responses to EBV were measured in 426 MS patients and 186 healthy controls. HLA-DR typing was performed using sequence-based methods. Results: MS patients had significantly higher levels of antibodies against epitope-specific and polyspecific EBNA-1 and viral capsid antigen (VCA), compared with controls (all p < 10−15). In regression analyses, anti-EBNA-1 and anti-VCA antibody levels, protective HLA-DR*04/07/09 alleles and gender (all p < 0.003) contributed independently to a model that classified cases and controls with an odds ratio > 20 (sensitivity 92%, specificity 64%). Notably, the strong influence of high-risk HLA-DR alleles was abrogated after inclusion of EBV serology results. Conclusions: The ability to discriminate MS cases and controls can be substantially enhanced by including anti-EBV serology as well as HLA-DR risk profiles. These findings support the relevance of EBV-specific immunity in MS pathogenesis, and implicate both HLA-dependent and HLA-independent immune responses against EBNA-1 as prominent disease risk factors.
Impact of the Data Collection on Adverse Events of Anti-HIV Drugs Cohort Study on Abacavir Prescription among Treatment-Naive, HIV-Infected Patients in Canada
Authors: Antoniou Tony , Gillis Jennifer , Loutfy Mona R. , Cooper Curtis , Hogg Robert S. , Klein Marina B. , Machouf Nima , Montaner Julio S. G. , Rourke Sean B. , Tsoukas Chris , Raboud Janet M. ,   Canadian Observational Cohort (CANOC) collaboration
Published: July 2013

Objective: To evaluate the trends in abacavir (ABC) prescription among antiretroviral (ARV) medication-naive individuals following the presentation of the Data Collection on Adverse Events of Anti-HIV Drugs (DAD) cohort study. Methods: We conducted a retrospective cohort study of ARV medication-naive individuals in the Canadian Observational Cohort (CANOC). Results: Between January 1, 2000, and February 28, 2010, a total of 7280 ARV medication-naive patients were included in CANOC. We observed a significant change in the proportion of new ABC prescriptions immediately following the release of DAD (−11%; 95% confidence interval [CI]: −20% to −2.4%) and in the months following the presentation of these data (−0.66% per month; 95% CI: −1.2% to −0.073%). A post-DAD presentation decrease in the odds of being prescribed ABC versus tenofovir (TDF) was observed (adjusted odds ratio, 0.72 per year, 95% CI: 0.54-0.97). Conclusions: Presentation of the DAD was associated with a significant decrease in ABC use among ARV medication-naive, HIV-positive patients initiating therapy.
Experimental and theoretical evidence of zinc structurally bound in vermiculite from naturally metal-enriched soils
Authors: Fernández-Caliani J. C. , Timón V. , Rivera M. B. , Giráldez I. , Pérez-Ló pez R. 
Published: July 2013

AbstractThis paper provides evidence of appreciable amounts of Zn (up to 0.52 a.p.f.u.) residing in the crystal structure of trioctahedral vermiculite; the results were obtained by a combination of experimental methods (X-ray diffraction, energy dispersive X-ray spectrometry, electron microprobe analysis and selective chemical extractions) and theoretical studies based on density functional theory (DFT). Vermiculite occurs in size fractions ranging from 10 to 40 μm of near-neutral soils naturally enriched in Zn (up to 8110 mg kg–1) due to the weathering of carbonate-hosted Zn-Pb deposits in SW Spain. Zinc was partitioned among the various pedogenic phases during soil formation, but the larger part (>80%) was concentrated in the residual silicate fraction. The soil exchangeable Zn pool was found to be virtually negligible. The DFT calculations support the hypothesis that the role of vermiculite is an effective sink for geogenic Zn; this is consistent, in terms of energetic stability, with the assumption that most Zn is structurally bound in octahedral sheets rather than in the interlayer exchange sites. The findings conclusively indicate that the potential mobility of Zn should remain low under the present soil conditions.
A review of microbial redox interactions with structural Fe in clay minerals
Authors: Pentráková L. , Su K. , Pentrák M. , Stucki J. W. 
Published: July 2013

AbstractVirtually all 2:1 clay minerals contain some Fe in their crystal structure, which may undergo redox reaction with surrounding redox-active species causing potentially significant changes in the chemical and physical properties of the clay mineral and its surrounding matrix. This phenomenon was originally of interest mostly as a laboratory experiment using strong inorganic reduction agents, but the discovery that the structural Fe could be reduced by microorganisms in natural soils and sediments opened the way for this to become a practical method for altering the chemical and physical properties of soils and sedimentsin situ. The purpose of this report was to review the body of literature that has been published since the inception of this field of inquiry and to complement, update, and complete three other reviews that have been published during the intervening years. Studies of microbial reduction of structural Fe in smectites have revealed the extent of reduction, effects on chemical and physical properties, reversibility (or lack thereof) of microbial reduction, stoichiometry, possible reaction mechanism, and types of organisms involved. Some organisms are also capable of oxidizing structural Fe, such as in biotite or reduced smectite, while one appears to be able to do both. Illitic layers resist reduction by microorganisms, but this can be partially overcome by the presence of an electron shuttle compound such as anthraquinone-2,6-disulfonate, which also enhances the extent of reduction in smectites. Microorganisms may be employed as an in situ reducing agent to drive redox cycles for structural Fe in constituent clay minerals of soils and sediments, which in turn can serve as an abiotic source for redox-mediated remediation of environmental contaminants.
REACTIN: Regulatory activity inference of transcription factors underlying human diseases with application to breast cancer
Authors: Zhu Mingzhu , Liu Chun-Chi , Cheng Chao 
Published: July 2013

Abstract

Background
Genetic alterations of transcription factors (TFs) have been implicated in the tumorigenesis of cancers. In many cancers, alteration of TFs results in aberrant activity of them without changing their gene expression level. Gene expression data from microarray or RNA-seq experiments can capture the expression change of genes, however, it is still challenge to reveal the activity change of TFs.

Results
Here we propose a method, called REACTIN (REgulatory ACTivity INference), which integrates TF binding data with gene expression data to identify TFs with significantly differential activity between disease and normal samples. REACTIN successfully detect differential activity of estrogen receptor (ER) between ER+ and ER- samples in 10 breast cancer datasets. When applied to compare tumor and normal breast samples, it reveals TFs that are critical for carcinogenesis of breast cancer. Moreover, Reaction can be utilized to identify transcriptional programs that are predictive to patient survival time of breast cancer patients.

Conclusions
REACTIN provides a useful tool to investigate regulatory programs underlying a biological process providing the related case and control gene expression data. Considering the enormous amount of cancer gene expression data and the increasingly accumulating ChIP-seq data, we expect wide application of REACTIN for revealing the regulatory mechanisms of various diseases.