bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correcting the Optimal Resampling‐Based Error Rate by Estimating the Error Rate of Wrapper Algorithms
Authors: Bernau Christoph , Augustin Thomas , Boulesteix Anne‐Laure 
Published: July 2013

SummaryHigh‐dimensional binary classification tasks, for example, the classification of microarray samples into normal and cancer tissues, usually involve a tuning parameter. By reporting the performance of the best tuning parameter value only, over‐optimistic prediction errors are obtained. For correcting this tuning bias, we develop a new method which is based on a decomposition of the unconditional error rate involving the tuning procedure, that is, we estimate the error rate of wrapper algorithms as introduced in the context of internal cross‐validation (ICV) by Varma and Simon (2006, BMC Bioinformatics 7, 91). Our subsampling‐based estimator can be written as a weighted mean of the errors obtained using the different tuning parameter values, and thus can be interpreted as a smooth version of ICV, which is the standard approach for avoiding tuning bias. In contrast to ICV, our method guarantees intuitive bounds for the corrected error. Additionally, we suggest to use bias correction methods also to address the conceptually similar method selection bias that results from the optimal choice of the classification method itself when evaluating several methods successively. We demonstrate the performance of our method on microarray and simulated data and compare it to ICV. This study suggests that our approach yields competitive estimates at a much lower computational price.
Mark‐Recapture with Multiple, Non‐Invasive Marks
Authors: J Bonner Simon , Holmberg Jason 
Published: July 2013

AbstractSummaryNon‐invasive marks, including pigmentation patterns, acquired scars, and genetic markers, are often used to identify individuals in mark‐recapture experiments. If animals in a population can be identified from multiple, non‐invasive marks then some individuals may be counted twice in the observed data. Analyzing the observed histories without accounting for these errors will provide incorrect inference about the population dynamics. Previous approaches to this problem include modeling data from only one mark and combining estimators obtained from each mark separately assuming that they are independent. Motivated by the analysis of data from the ECOCEAN online whale shark (Rhincodon typus) catalog, we describe a Bayesian method to analyze data from multiple, non‐invasive marks that is based on the latent‐multinomial model of Link et al. (2010, Biometrics 66, 178–185). Further to this, we describe a simplification of the Markov chain Monte Carlo algorithm of Link et al. (2010, Biometrics 66, 178–185) that leads to more efficient computation. We present results from the analysis of the ECOCEAN whale shark data and from simulation studies comparing our method with the previous approaches.
Bayesian Approach for Clinical Trial Safety Data Using an Ising Prior
Authors: McEvoy Bradley W. , Nandy Rajesh R. , Tiwari Ram C. 
Published: July 2013

SummaryIn drug safety, development of statistical methods for multiplicity adjustments has exploited potential relationships among adverse events (AEs) according to underlying medical features. Due to the coarseness of the biological features used to group AEs together, which serves as the basis for the adjustment, it is possible that a single adverse event can be simultaneously described by multiple biological features. However, existing methods are limited in that they are not structurally flexible enough to accurately exploit this multi‐dimensional characteristic of an adverse event. In order to preserve the complex dependencies present in clinical safety data, a Bayesian approach for modeling the risk differentials of the AEs between the treatment and comparator arms is proposed which provides a more appropriate clinical description of the drug's safety profile. The proposed procedure uses an Ising prior to unite medically related AEs. The proposed method and an existing Bayesian method are applied to a clinical dataset, and the signals from the two methods are presented. Results from a small simulation study are also presented.
Bayesian Quantile Regression for Censored Data
Authors: Reich Brian J. , Smith Luke B. 
Published: July 2013

AbstractSummaryIn this paper we propose a semiparametric quantile regression model for censored survival data. Quantile regression permits covariates to affect survival differently at different stages in the follow‐up period, thus providing a comprehensive study of the survival distribution. We take a semiparametric approach, representing the quantile process as a linear combination of basis functions. The basis functions are chosen so that the prior for the quantile process is centered on a simple location‐scale model, but flexible enough to accommodate a wide range of quantile processes. We show in a simulation study that this approach is competitive with existing methods. The method is illustrated using data from a drug treatment study, where we find that the Bayesian model often gives smaller measures of uncertainty than its competitors, and thus identifies more significant effects.
Decreased tissue factor pathway inhibitor (TFPI)‐dependent anticoagulant capacity in patients with cirrhosis who have decreased protein S but normal TFPI plasma levels
Authors: Potze Wilma , Arshad Freeha , Adelmeijer Jelle , Blokzijl Hans , van den Berg Arie P. , Meijers Joost C. M. , Porte Robert J. , Lisman Ton 
Published: July 2013

SummaryProtein S acts as a cofactor for tissue factor pathway inhibitor (TFPI) in the down regulation of thrombin generation, and acquired and congenital protein S deficiencies are associated with a concomitant TFPI deficiency. In contrast, in patients with liver diseases, decreased protein S, but normal or increased levels of TFPI have been reported. We compared TFPI and protein S plasma levels between 26 patients with cirrhosis and 20 healthy controls and found that TFPI levels were comparable between patients (111 ± 38%) and controls (108 ± 27%), despite reduced protein S levels (74 ± 23% in patients vs. 98 ± 10% in controls). Subsequently, we quantified the activity of the TFPI‐protein S system by measuring thrombin generation in the absence and presence of neutralizing antibodies to protein S or TFPI. Ratios of peak thrombin generation in the absence and presence of these antibodies were calculated. Both the protein S and the TFPI ratios were increased in patients with cirrhosis compared to controls. Protein S ratios were (0·62 [0·08–0·93] in patients vs. 0·32 [0·20–0·54] in controls; TFPI ratios were 0·50 [0·05–0·90] in patients vs. 0·18 [0·11–0·49] in controls). Thus, although the acquired protein S deficiency in patients with cirrhosis is not associated with decreased TFPI levels, the TFPI/protein S anticoagulant system is functionally impaired.
Copper(I) (Pseudo)Halide Complexes with Neocuproine and Aminomethylphosphines Derived from Morpholine and Thiomorpholine – In Vitro Cytotoxic and Antimicrobial Activity and the Interactions with DNA and Serum Albumins
Authors: Starosta Radosław , Bykowska Aleksandra , Kyzioł Agnieszka , Płotek Michał , Florek Magdalena , Król Jarosław , Jeżowska‐Bojczuk Małgorzata 
Published: July 2013

Herein, a series of CuI or CuNCS complexes with neocuproine (2,9‐dimethyl‐1,10‐phenanthroline: dmp) and two tris(aminomethyl)phosphines derived from morpholine (P(CH2N(CH2CH2)2O)3) or thiomorpholine (P(CH2N(CH2CH2)2S)3) were tested as cytotoxic agents in vitro towards mouse colon carcinoma (CT26) and human lung adenocarcinoma (A549). The studies showed that the complexes exhibit potential antitumor properties, displayed by IC50 values below 10 μm towards the tested cell lines, in the case of 4‐h incubation time with the examined compounds. Moreover, a high antimicrobial activity of all the complexes was observed against Staphylococcus aureus and Candida albicans with minimal inhibitory concentrations equal to 1–2 μg/mL. To gain insight into the molecular mechanism of biological activity of the complexes, we investigated also their interactions with plasmid DNA (pUC18) and the human and bovine serum albumins. Gel electrophoresis experiments demonstrated that all the compounds were comparably efficient in DNA degradation process; however, luminescence quenching showed surprising dependence on the interactions strength of the used compounds with the albumins. Apart from exceptionally effective [CuI(dmp)P(CH2N(CH2CH2)2O)3], the complexes with P(CH2N(CH2CH2)2O)3 quenched more strongly luminescence of bovine serum albumin, while the complexes with P(CH2N(CH2CH2)2S)3 were more active in the quenching of human serum albumin luminescence.
Alveolar macrophages in pulmonary host defence – the unrecognized role of apoptosis as a mechanism of intracellular bacterial killing
Authors: Aberdein J D , Cole J , Bewley M A , Marriott H M , Dockrell D H 
Published: July 2013

Summary
Alveolar macrophages play an essential role in clearing bacteria from the lower airway, as the resident phagocyte alveolar macrophages must both phagocytose and kill bacteria, and if unable to do this completely must co-ordinate an inflammatory response. The decision to escalate the inflammatory response represents the transition between subclinical infection and the development of pneumonia. Alveolar macrophages are well equipped to phagocytose bacteria and have a large phagolysosomal capacity in which ingested bacteria are killed. The rate-limiting step in control of extracellular bacteria, such as Streptococcus pneumoniae, is the capacity of alveolar macrophages to kill ingested bacteria. Therefore, alveolar macrophages complement canonical microbicidal strategies with an additional level of apoptosis-associated killing to help kill ingested bacteria.
An immunodominant La/SSB autoantibody proteome derives from public clonotypes
Authors: Thurgood L A , Arentz G , Lindop R , Jackson M W , Whyte A F , Colella A D , Chataway T K , Gordon T P 
Published: July 2013

SummaryThe La/SSB autoantigen is a major target of long-term humoral autoimmunity in primary Sjögren's Syndrome (SS) and systemic lupus erythematosus. A majority of patients with linked anti-Ro60/Ro52/La responses target an NH2-terminal epitope designated LaA that is expressed on Ro/La ribonucleoprotein complexes and the surface membrane of apoptotic cells. In this study, we used high-resolution Orbitrap mass spectrometry to determine the clonality, isotype and V-region sequences of LaA-specific autoantibodies in seven patients with primary SS. Anti-LaA immunoglobulin (Ig)Gs purified from polyclonal sera by epitope-specific affinity chromatography were analysed by combined database and de-novo mass spectrometric sequencing. Autoantibody responses comprised two heavily mutated IgG1 kappa-restricted monoclonal species that were shared (public) across unrelated patients; one clonotype was specified by an IGHV3-30 heavy chain paired with IGKV3-15 light chain and the second by an IGHV3-43/IGKV3-20 pairing. Shared amino acid replacement mutations were also seen within heavy and light chain complementarity-determining regions, consistent with a common breach of B cell tolerance followed by antigen-driven clonal selection. The discovery of public clonotypic autoantibodies directed against an immunodominant epitope on La, taken together with recent findings for the linked Ro52 and Ro60 autoantigens, supports a model of systemic autoimmunity in which humoral responses against protein–RNA complexes are mediated by public sets of autoreactive B cell clonotypes.
Premature ageing of the immune system relates to increased anti-lymphocyte antibodies (ALA) after an immunization in HIV-1-infected and kidney-transplanted patients
Authors: Cagigi A , Rinaldi S , Santilli V , Mora N , C. Manno E , Cotugno N , Zangari P , Aquilani A , Guzzo I , Dello Strologo L , Rossi P , Palma P 
Published: July 2013

Summary
Low-affinity immunoglobulin (Ig)G with potential autoreactivity to lymphocytes and hypergammaglobulinaemia have been described previously in HIV-1-infected patients. Whether such antibodies increase after challenging the immune system, for example with an immunization, is not known. In the present study, the modulation of antibodies with low affinity and potential autoreactivity was evaluated after 2012–13 seasonal flu vaccination with a simple empirical laboratory test measuring the titres of anti-lymphocyte antibodies (ALA) in two different models of secondary immunodeficiency: HIV-1 vertically infected patients (HIV) and patients treated with immunosuppressive therapies after kidney transplantation (KT) compared to healthy individuals (HC). In parallel, the activation status of B cells and their degree of immune senescence was evaluated by measuring the B cell interleukin (IL)-21R expression/plasma IL-21 levels and the frequencies of mature-activated (MA) and double-negative (DN) B cells. A significant increase of ALA titres was observed after vaccination in HIV and KT but not in HC, and this correlated directly with the frequencies of both MA and DN and inversely with the B cell IL-21R expression. This suggests that the quality of an immune response triggered by flu vaccination in HIV and KT may depend upon the activation status of B cells and on their degree of immune senescence. Further investigations are needed to verify whether high frequencies of MA and DN may also relate to increase autoimmunity after immunization in high-risk populations.
Protective creams fail to prevent solvent‐induced cumulative skin irritation – results of a randomized double‐blind study
Authors: Schliemann Sibylle , Kleesz Peter , Elsner Peter 
Published: July 2013

SummaryBackgroundOccupational skin contact with lipophilic substances is a risk factor for the development of irritant hand dermatitis. Skin protection creams form part of the personal protective equipment, and some are claimed to protect against lipophilic irritants. However, their benefit against solvents is under debate.ObjectivesTo evaluate the efficacy of barrier creams claimed to protect against lipophilic irritants in a newly developed repetitive irritation model.MethodsThirty‐five healthy volunteers were enrolled in a double‐blind, randomized study, and six barrier creams were evaluated against irritation induced by two occupationally relevant model solvents, n‐octane and cumene. Clinical scoring and bioengineering methods (capacitance and transepidermal water loss measurements) were used to quantify the irritant reactions.ResultsNone of the test products offered protection against n‐octane‐induced clinical irritation or stratum corneum dehydration. One test product significantly aggravated the skin irritation induced by both irritants, and a second one enhanced dehydration induced by n‐octane only.ConclusionsThe lack of efficacy and the aggravation of skin irritation induced by two of six test products stress the need for standardized efficacy testing of occupational skin protection products.
Cobalt, nickel and chromium release from dental tools and alloys
Authors: Kettelarij Jolinde A. B. , Lidén Carola , Axén Emmy , Julander Anneli 
Published: July 2013

SummaryBackgroundCobalt–chromium alloys are used as casting alloys by dental technicians when producing dental prostheses and implants. Skin exposure and metal release from alloys and tools used by the dental technicians have not been studied previously.ObjectivesTo study the release of cobalt, nickel and chromium from alloys and tools that come into contact with the skin of dental technicians.MethodsCobalt and nickel release from tools and alloys was tested with the cobalt spot test and the dimethylglyoxime test for nickel. Also, the release of cobalt, nickel and chromium in artificial sweat (EN1811) at different time‐points was assessed. Analysis was performed with inductively coupled plasma‐mass spectrometry.ResultsSixty‐one tools were spot tested; 20% released nickel and 23% released cobalt. Twenty‐one tools and five dental alloys were immersed in artificial sweat. All tools released cobalt, nickel and chromium. The ranges were 0.0047–820, 0.0051–10 and 0.010–160 µg/cm2/week for cobalt, nickel and chromium, respectively. All dental alloys released cobalt in artificial sweat, with a range of 0.0010–17 µg/cm2/week, and they also released nickel and chromium at low concentrations.ConclusionsSensitizing metals are released from tools and alloys used by dental technicians. This may cause contact allergy and hand eczema.
The prevalence of dental trauma and its association with illicit drug use among adolescents
Authors: de Oliveira Filho Paulo Messias , Jorge Kelly Oliva , Paiva Paula Cristina Pelli , Ferreira Efigênia Ferreira e , Ramos‐Jorge Maria Letícia , Zarzar Patrícia Maria 
Published: July 2013

AbstractBackground/AimDental trauma has been associated with predisposing factors such as gender and age, and biological characteristics such as overjet and socio‐economic factors. However, research literature associating the use of illicit drugs with dental trauma is scarce. The aim of this survey is to investigate the prevalence of dental trauma and the association of the same with the use of illicit drugs among adolescents.Material and MethodsA transversal analysis was conducted using a representative sample of 701 students between the ages of 14 and 19. Data were gathered by means of clinical examinations and self‐administered questionnaires. The ABA‐ABIPEME tool was adopted for the assessment of socio‐economic conditions and ASSIST (Screening Test for Involvement with Alcohol, Cigarettes, and Other Substances) as a standard for the consumption of illicit drugs.ResultsThe prevalence of dental trauma was 26.6% (183/687) and that of illicit drug use 7% (48/684). Dental trauma was more prevalent among older adolescents (P = 0.010) with overjet greater than 3 mm (P = 0.005) in males (P = 0.001) who had used marijuana and/or cocaine in their lifetime (P = 0.005). The Poisson regression results revealed that illicit drug use was still associated with dental trauma independent of other variables [PR = 1.54 (95% CI: 1.06–2.24) P = 0.022].ConclusionsThe prevalence of dental trauma was high and associated with the use of illicit drugs.
Rural and remote early psychosis intervention services: the Gordian knot of early intervention
Authors: Cheng Chiachen , Dewa Carolyn S. , Langill Gord , Fata Mirella , Loong Desmond 
Published: July 2013

AbstractAimOne of the basic challenges of Early Psychosis Intervention (EPI) programs for rural populations is translating best practice which developed for urban high‐population density areas to rural and remote settings. This paper presents data from two different models (hub and spoke and specialist outreach) of rural EPI practice in Ontario, Canada.MethodsThis cross‐sectional study used a convenience sample of clients from two rural EPI programs between 2005 and 2007. Data about client outcomes specific to general functioning, admissions to hospital and emergency room (ER) visits were collected. For all dichotomous variables, chi‐square tests were used to test differences between two groups.ResultsThe total clients served in hub and spoke were 457 compared to 91 in specialist outreach. Although not statistically significant, the hub and spoke group showed better functioning in the community. There was a significant difference between the two groups with regard to hospital admissions. Although not significant, there was a greater percentage (58.3%) of specialist outreach clients who visited the ER in the previous 12 months as compared to clients serviced by the hub and spoke model (34.9%).ConclusionsThe observed data from these two rural models suggest that there may be differing outcomes. There are limitations to this study, and this paper does not address why there are differences. Future work needs to continue to further explore why differences exist and whether they persist so we can provide equity and quality care for rural and remote populations.
The resting‐state neurovascular coupling relationship: rapid changes in spontaneous neural activity in the somatosensory cortex are associated with haemodynamic fluctuations that resemble stimulus‐evoked haemodynamics
Authors: Bruyns‐Haylett Michael , Harris Sam , Boorman Luke , Zheng Ying , Berwick Jason , Jones Myles 
Published: July 2013

AbstractAlthough promise exists for patterns of resting‐state blood oxygen level‐dependent (BOLD) functional magnetic resonance imaging (fMRI) brain connectivity to be used as biomarkers of early brain pathology, a full understanding of the nature of the relationship between neural activity and spontaneous fMRI BOLD fluctuations is required before such data can be correctly interpreted. To investigate this issue, we combined electrophysiological recordings of rapid changes in multi‐laminar local field potentials from the somatosensory cortex of anaesthetized rats with concurrent two‐dimensional optical imaging spectroscopy measurements of resting‐state haemodynamics that underlie fluctuations in the BOLD fMRI signal. After neural ‘events’ were identified, their time points served to indicate the start of an epoch in the accompanying haemodynamic fluctuations. Multiple epochs for both neural ‘events’ and the accompanying haemodynamic fluctuations were averaged. We found that the averaged epochs of resting‐state haemodynamic fluctuations taken after neural ‘events’ closely resembled the temporal profile of stimulus‐evoked cortical haemodynamics. Furthermore, we were able to demonstrate that averaged epochs of resting‐state haemodynamic fluctuations resembling the temporal profile of stimulus‐evoked haemodynamics could also be found after peaks in neural activity filtered into specific electroencephalographic frequency bands (theta, alpha, beta, and gamma). This technique allows investigation of resting‐state neurovascular coupling using methodologies that are directly comparable to that developed for investigating stimulus‐evoked neurovascular responses.
Paradoxical increase in survival of newborn neurons in the dentate gyrus of mice with constitutive depletion of serotonin
Authors: Diaz Silvina L. , Narboux‐Nême Nicolas , Trowbridge Sara , Scotto‐Lomassese Sophie , Kleine Borgmann Felix B. , Jessberger Sebastian , Giros Bruno , Maroteaux Luc , Deneris Evan , Gaspar Patricia 
Published: July 2013

AbstractIncreased adult neurogenesis is a major neurobiological correlate of the beneficial effects of antidepressants. Indeed, selective serotonin (5‐HT) re‐uptake inhibitors, which increase 5‐HT transmission, enhance adult neurogenesis in the dentate gyrus (DG) of the hippocampus. However, the consequences of 5‐HT depletion are still unclear as studies using neurotoxins that target serotonergic neurons reached contradictory conclusions on the role of 5‐HT on DG cell proliferation. Here, we analysed two genetic models of 5‐HT depletion, the Pet1−/− and the VMAT2f/f; SERTcre/+ mice, which have, respectively, 80 and 95% reductions in hippocampal 5‐HT. In both models, we found unchanged cell proliferation of the neural precursors in the DG subgranular zone, whereas a significant increase in the survival of newborn neurons was noted 1 and 4 weeks after BrdU injections. This pro‐survival trait was phenocopied pharmacologically with 5‐HT synthesis inhibitor PCPA treatment in adults, indicating that this effect was not developmental. Furthermore, a 1‐week administration of the 5‐HT1A receptor agonist 8‐OH‐DPAT in Pet1−/− and PCPA‐treated mice normalised hippocampal cell survival. Overall, our results indicate that constitutive 5‐HT depletion does not alter the proliferation of neural precursors in the DG but promotes the survival of newborn cells, an effect which involves activation of postsynaptic 5‐HT1A receptors. The role of 5‐HT in selective neuronal elimination points to a new facet in its multiple effects in controlling neural circuit maturation.