bluuebunny/crossref_metadata_2025_split huggingface dataset:
Profile of vemurafenib‐induced severe skin toxicities
Authors: Peuvrel L. , Quéreux G. , Saint‐Jean M. , Brocard A. , Nguyen J.M. , Khammari A. , Knol A.C. , Varey E. , Dréno B. 
Published: November 2015

AbstractBackgroundVemurafenib, a BRAF inhibitor, is commonly associated with skin toxicity. The impact of severe forms is unknown.ObjectiveTo determine the rate of permanent vemurafenib discontinuation due to grade 3–4 skin toxicity, features of these toxicities, their recurrence rate after a switch to dabrafenib and their impact on overall survival.MethodsRetrospective cohort study of 131 patients treated with vemurafenib for melanoma between November 2010 and December 2014. Data on skin toxicities, the need for vemurafenib adjustment and the impact of switching to dabrafenib were collected. Regarding survival analysis, a conditional landmark analysis was performed to correct lead‐time bias.ResultsAmong the 131 vemurafenib‐treated patients, 26% developed grade 3–4 skin toxicity. Forty‐four percent of them permanently discontinued their treatment, mainly due to rash and classic skin adverse reactions (Steven–Johnson syndrome, Drug Reaction with Eosinophilia and Systemic Symptoms). Conversely, photosensitivity and carcinomas rarely required treatment adjustment. Grade 3–4 rashes were associated with clinical or biological abnormalities in 94% of patients. Among the 10 patients who subsequently switched to dabrafenib, skin toxicity recurred only in one patient. Overall survival was significantly prolonged in case of severe skin toxicity emerging within the first 4 (P = 0.014) and 8 weeks (P = 0.038) on vemurafenib, with only a trend at 12 weeks (P = 0.052). Median overall survival was also prolonged in case of severe rash.ConclusionIn this study, vemurafenib was continued in 56% of patients with grade 3–4 skin toxicity, which was associated with prolonged overall survival when emerging within the first 4 and 8 weeks of treatment. While developing severe skin adverse reactions permanently contraindicates vemurafenib use, other rashes should lead to retreatment attempts with dose reduction. In case of recurrence, dabrafenib seems to be an interesting option. For other skin toxicities, including photosensitivity and cutaneous carcinoma, treatment adjustment is usually not needed.
Effect of Hot Boning and Elevated Brine Temperature on the Processing, Storage and Eating Quality of Cured Beef Hindquarter (M. biceps femoris) and Forequarter (M. pectoralis profundus) Muscles
Authors: Keenan D.F. , Hayes J.E. , Kenny T.A. , Kerry J.P. 
Published: November 2015

AbstractEating quality, processing and storage attributes were examined in hot‐ and cold‐boned beef (90 min and 24 h postmortem, respectively) post from two muscles (M. biceps femoris [BF] and M. pectoralis profundus [PP]) injected with curing brines at conventionally chilled (2–4C) and elevated temperature (15–17C) curing brines, stored over 21 days (4C). The pH/temperature profiles showed all hot‐boned experimental treatments were outside of the reported ranges for the occurrence of cold or heat shortening. Hot‐boned beef did not exhibit any significant added or reduced functionality compared to conventionally‐boned beef i.e., cook loss and final yield unaffected in BF and PP muscles. Cold‐boned BF products were harder (P < 0.05) than hot‐boned; however, this was not supported by sensory analysis. Samples prepared with elevated brine temperatures had a detrimental effect on the sensory characteristics of PP hams. Principal component and hierarchical cluster analyses (PCA and HCA, respectively) were used to better visualize the underlying structure between the quality measurements and samples, showing gradual product deterioration over storage. Although the combination of hot boning and higher brine temperature led to expected higher bacterial numbers, microbial stability of the product was maintained after 21 days.Practical ApplicationsCommercial demands for reduced energy usage and chill requirements were the primary factors for the development of hot boning. Hot‐boned meat also has the advantage of being in a pre‐rigor state which is known for its improved functional qualities. While it is practiced in some countries, predominantly Australia and New Zealand, it still remains underdeveloped in some territories, such as Ireland. Concerns over its widespread adoption center on: (1) training costs; (2) improved hygiene standards; and (3) increased risk of toughness due to the contraction of some muscles when they are removed from skeletal restraint. However, it is estimated that a reduction in chill space requirements could be as much as 50%, resulting in cumulative savings in refrigeration energy, capital costs and quicker plant turnover. The outcomes of this work were to develop products using techniques that would be a huge economic benefit to the meat industry.
Bacillus cereus AR156 primes induced systemic resistance by suppressing miR825/825* and activating defense‐related genes in Arabidopsis
Authors: Niu Dongdong , Xia Jing , Jiang Chunhao , Qi Beibei , Ling Xiaoyu , Lin Siyuan , Zhang Weixiong , Guo Jianhua , Jin Hailing , Zhao Hongwei 
Published: November 2015

AbstractSmall RNAs play an important role in plant immune responses. However, their regulatory function in induced systemic resistance (ISR) is nascent. Bacillus cereus AR156 is a plant growth‐promoting rhizobacterium that induces ISR in Arabidopsis against bacterial infection. Here, by comparing small RNA profiles of Pseudomonas syringae pv. tomato (Pst) DC3000‐infected Arabidopsis with and without AR156 pretreatment, we identified a group of Arabidopsis microRNAs (miRNAs) that are differentially regulated by AR156 pretreatment. miR825 and miR825* are two miRNA generated from a single miRNA gene. Northern blot analysis indicated that they were significantly downregulated in Pst DC3000‐infected plants pretreated with AR156, in contrast to the plants without AR156 pretreatment. miR825 targets two ubiquitin‐protein ligases, while miR825* targets toll‐interleukin‐like receptor (TIR)‐nucleotide binding site (NBS) and leucine‐rich repeat (LRR) type resistance (R) genes. The expression of these target genes negatively correlated with the expression of miR825 and miR825*. Moreover, transgenic plants showing reduced expression of miR825 and miR825* displayed enhanced resistance to Pst DC3000 infection, whereas transgenic plants overexpressing miR825 and miR825* were more susceptible. Taken together, our data indicates that Bacillus cereus AR156 pretreatment primes ISR to Pst infection by suppressing miR825 and miR825* and activating the defense related genes they targeted.
Sox13 functionally complements the related Sox5 and Sox6 as important developmental modulators in mouse spinal cord oligodendrocytes
Authors: Baroti Tina , Schillinger Anja , Wegner Michael , Stolt C. Claus 
Published: November 2015

AbstractThe role of transcription factor Sox13, which together with Sox5 and Sox6 belongs to the SoxD family, is only poorly characterized in central nervous system development. Therefore, we analysed whether Sox13 expression and function overlaps with or differs from that of its close relatives Sox5 and Sox6. In the developing mouse spinal cord, we found Sox13 predominantly expressed in neuroepithelial precursors, oligodendroglial and astroglial cells. The substantially overlapping expression with Sox5 and Sox6 in oligodendroglial cells prompted us to study potential roles during specification, lineage progression and differentiation of oligodendrocytes. In contrast to Sox5 and Sox6, Sox13 expression continues after differentiation and even increases in myelinating oligodendrocytes. Sox13 deletion did not interfere with oligodendroglial development, which was normal in Sox13‐deficient mice. However, the premature differentiation of oligodendrocyte precursors triggered by loss of Sox6 was slightly more prominent in Sox6/Sox13 double‐deficient mice. Sox13 can bind to the same sites in myelin gene promoters as Sox5 and Sox6 in vitro. Reporter gene assays furthermore reveal a similar antagonizing effect on Sox10‐dependent transactivation of myelin gene promoters as previously shown for Sox5 and Sox6. This argues that Sox13 is functionally redundant with the other SoxD proteins and complements Sox5 and Sox6 in their role as important modulators of oligodendrocyte development.
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The transcription factor Sox13 is co‐expressed with the related Sox5 and Sox6 in cells of the oligodendroglial lineage. By itself, it has little impact on oligodendrocyte development but supports Sox5 and Sox6 during the process as a functionally redundant transcription factor.
Functional interplay between ganglioside GM1 and cross‐linking galectin‐1 induces axon‐like neuritogenesis via integrin‐based signaling and TRPC5‐dependent Ca2+ influx
Authors: Wu Gusheng , Lu Zi‐Hua , André Sabine , Gabius Hans‐Joachim , Ledeen Robert W. 
Published: November 2015

AbstractAxon‐like neuritogenesis in neuroblastoma (NG108‐15) cells and primary cerebellar granular neurons is furthered by the presence of ganglioside GM1. We describe here that galectin‐1 (Gal‐1), a homobivalent endogenous lectin, is an effector by cross‐linking the ganglioside and its associated glycoprotein α5β1‐integrin. The thereby triggered signaling cascade involves autophosphorylation of focal adhesion kinase and activation of phospholipase Cγ and phosphoinositide‐3 kinase. This leads to a transient increase in the intracellular Ca2+ concentration by opening of TRPC5 channels, which belong to the signal transduction‐gated cation channels. Controls with GM1‐defective cells (NG‐CR72 and neurons from ganglio‐series KO mice) were retarded in axonal growth, underscoring the relevance of GM1 as functional counterreceptor for Gal‐1. The lectin's presence was detected in the NG108‐15 cells, suggesting an autocrine mechanism of action, and in astrocytes in situ. Gal‐1, as cross‐linking lectin, can thus translate metabolic conversion of ganglioside GD1a to GM1 by neuraminidase action into axon growth.
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Galectin‐1 (Gal‐1) was shown an effector of axonogenesis in cerebellar granule neurons (CGNs) and NG108‐15 cells by cross‐linking GM1 ganglioside and its associated glycoprotein α5β1‐integrin. The resulting signaling led to a transient increase in intracellular Ca2+ by opening TRPC5 channels. CGNs deficient in GM1 showed retarded axonogenesis, underscoring the relevance of GM1 as functional counterreceptor for Gal‐1 in this process. This Gal‐1/GM1‐induced signaling was manifest only at the earliest, initiating stage of axon development.
24‐hour pH‐impedance monitoring on therapy to select patients with refractory reflux symptoms for antireflux surgery. A single center retrospective study
Authors: Desjardin M. , Luc G. , Collet D. , Zerbib F. 
Published: November 2015

AbstractBackgroundTreatment of gastro‐esophageal reflux refractory symptoms is challenging. This monocenter retrospective study assessed the value of preoperative pH‐impedance monitoring ‘on’ therapy to predict functional outcome after laparoscopic fundoplication in patients with refractory reflux symptoms.MethodsPatients with a preoperative pH‐impedance monitoring ‘on’ proton pump inhibitors (PPIs) twice daily were assessed at least 6 months after a laparoscopic fundoplication for refractory reflux symptoms. Failure of fundoplication was defined by a Visick score > 2. Postoperative symptoms were assessed by the reflux disease questionnaire (RDQ). The pH‐impedance parameters analyzed were the number of reflux events (total, acid, non‐acid), esophageal acid exposure time, esophageal bolus exposure time, and symptom‐reflux association defined by symptom index (SI) >50% and symptom association probability (SAP) >95%.Key ResultsThirty‐three patients (18 female patients, median age 46 years) were assessed after a mean follow‐up of 41.3 (range 7–102.2) months. Seven (21.2%) patients were considered as failures. Compared to patients with favorable outcome, these patients were more often ‘on’ PPI therapy (86% vs 23%, p < 0.05) and had higher RDQ scores in each domain: heartburn (p < 0.05), regurgitation (p < 0.05) and dyspepsia (p < 0.05). A positive SAP was the only pH‐impedance parameter statistically associated with successful postoperative outcome (p = 0.004).Conclusions & InferencesOn therapy, a preoperative positive symptom association probability is the only pH‐impedance parameter associated with favorable outcome after laparoscopic fundoplication for refractory reflux symptoms. These results should be confirmed by prospective studies.
Tests for Multiple Breaks in the Trend with Stationary or Integrated Shocks
Authors: Sobreira Nuno , Nunes Luis C. 
Published: November 2015

AbstractIn this paper, we propose new tests of the presence of multiple breaks in the trend of a univariate time‐series where the number and dates of the breaks are unknown and that are valid in the presence of stationary or unit root shocks. These tests can also be used to sequentially estimate the number of breaks. The behaviour of the proposed tests is studied through Monte Carlo experiments.
d‐Alanine metabolism is essential for growth and biofilm formation of Streptococcus mutans
Authors: Qiu W. , Zheng X. , Wei Y. , Zhou X. , Zhang K. , Wang S. , Cheng L. , Li Y. , Ren B. , Xu X. , Li Y. , Li M. 
Published: November 2015

SummaryPart of the d‐alanine (d‐Ala) metabolic pathway in bacteria involves the conversion of l‐alanine to d‐Ala by alanine racemase and the formation of d‐alanyl–d‐alanine by d‐alanine–d‐alanine ligase, the product of which is involved in cell wall peptidoglycan synthesis. At present, drugs that target the metabolic pathway of d‐Ala are already in clinical use – e.g. d‐cycloserine (DCS) is used as an antibiotic against Mycobacterium tuberculosis. Streptococcus mutans is the main cariogenic bacterium in the oral cavity. Its d‐Ala metabolism‐associated enzymes alanine racemase and d‐alanine–d‐alanine ligase are encoded by the genes smu.1834 and smu.599, respectively, which may be potential targets for inhibitors. In this study, the addition of DCS blocked the d‐Ala metabolic pathway in S. mutans, leading to bacterial cell wall defects, significant inhibition of bacterial growth and biofilm formation, and reductions in extracellular polysaccharide production and bacterial adhesion. However, the exogenous addition of d‐Ala could reverse the inhibitory effect of DCS. Through the means of drug regulation, our study demonstrated, for the first time, the importance of d‐Ala metabolism in the survival and biofilm formation of S. mutans. If the growth of S. mutans can be specifically inhibited by designing drugs that target d‐Ala metabolism, then this may serve as a potential new treatment for dental caries.
Are Propositions Essentially Representational?
Authors: Pickel Bryan 
Published: November 2015

AbstractJeffrey King argues that nothing has truth conditions except by being taken to be true or false by rational agents. But – for good reason – King claims that propositions possess truth conditions essentially and intrinsically. I will argue that King cannot have both: if the truth conditions of a proposition depend on the reactions of rational agents, then the possession of truth conditions can't follow from the intrinsic nature or existence of the proposition. This leaves two options. Either, nothing can do the job that motivates positing propositions. Or, there is no need to explain what bestows a truth condition on a proposition.
Hume on Mental Transparency
Authors: Qu Hsueh 
Published: November 2015

AbstractThis article investigates Hume's account of mental transparency. In this article, I will endorse Qualitative Transparency – that is, the thesis that we cannot fail to apprehend the qualitative characters of our current perceptions, and these apprehensions cannot fail to be veridical – on the basis that, unlike its competitors, it is both weak enough to accommodate the introspective mistakes that Hume recognises, and yet strong enough to make sense of his positive employments of mental transparency. Moreover, Qualitative Transparency is also philosophically satisfying in providing good philosophical reason for why the mental states that are incorrigible should in fact be so.
Testimonial Knowledge Without Knowledge of what is Said
Authors: Peet Andrew 
Published: November 2015

AbstractThis article discusses the following question: what epistemic relation must audiences bear to the content of assertions in order to gain testimonial knowledge? There is a brief discussion of why this issue is of importance, followed by two counterexamples to the most intuitive answer: that in order for an audience to gain testimonial knowledge thatpthey must know that the speaker has assertedp. It is then suggested that the argument generalises and can be made to work on different sets of assumptions about the conditions for knowledge, and the conditions under which a proposition is asserted.
Spatio‐temporal analysis of the role of faecal depositions in aggregation behaviour of the triatomine Rhodnius prolixus
Authors: Falvo Marianel L. , Lorenzo Figueiras Alicia N. , Manrique Gabriel 
Published: November 2015

AbstractSeveral triatomine species aggregate over conspecific faeces. In some domestic species, this behaviour might help individuals to find their refuges because faeces are usually deposited around such places. In the present study, the defaecation behaviour of the triatomine bug Rhodnius prolixus Stål (Heteroptera: Reduviidae) is described in detail, including the temporal pattern of aggregation of nymphs with different nutritional status to faeces of different post‐deposition times. First, using an experimental arena, the spatial distribution of faecal deposition spots released by nymphs, in relation to the position of a refuge, is recorded. The results show that a high density of faeces is deposited inside the refuge, and few and distant spots, in relation to the position of the refuge, are dropped outside. Second, whether the aggregation behaviour of nymphs is altered by the time elapsed from deposition of the faeces, and by the nutritional status of the insects, is determined. The post‐deposition time of the faeces strongly modulates the aggregation response of the insects. Differences in aggregation between fed and unfed insects are only marginally significant; however, different temporal windows of aggregation according to the post‐deposition times of the faeces are demonstrated between bugs of different nutritional status. The results are discussed with respect to the relevance of the aggregation signal in relation to the characteristics of the natural refuges used by R. prolixus.
The Relationship between Total Fibroid Burden and First Trimester Bleeding and Pain
Authors: Michels Kara A , Hartmann Katherine E , Archer Kristin R , Ye Fei , Velez Edwards Digna R 
Published: November 2015

AbstractBackgroundFew studies comment on the association between fibroids and symptoms among pregnant women. These studies generally are retrospective and do not to assess the influence of number of tumours or their volume on risk of symptoms.MethodsRight from the Start is a prospective cohort that enrolled pregnant women from the southeastern USA between 2000 and 2012. In the first trimester, all participants had standardised ultrasounds to determine the presence or absence of fibroids. Symptoms were queried in a telephone survey. We used polytomous logistic regression to model odds of bleeding, pain, or both symptoms in relation to increasing total fibroid number and volume among white and black women.ResultsAmong 4509 participants, the prevalence of fibroids was 11%. Among those reporting symptoms (70%), 11% reported only bleeding, 59% reported only pain, and 30% reported both symptoms. After adjusting for age, race, parity, hypertension, smoking, alcohol use, and study site, increasing number of fibroids was associated with pain [odds ratio (OR) 1.16, 95% confidence interval (CI) 1.00, 1.33] and both symptoms [OR 1.25, 95% CI 1.08, 1.45] but not with bleeding among all women. Fibroid volume was not associated with symptoms among black women, but white women with the smallest fibroid volumes were more likely to report both symptoms than those without fibroids [OR 1.79, 95% CI 1.17, 2.72].ConclusionsVery large tumours are not requisite for experiencing symptoms, as small fibroids and increasing number of tumours are associated with pain and both symptoms.
Measuring the Impact of China's Export Growth on its Asian Neighbours
Authors: Kong Yoke Fong , Kneller Richard 
Published: November 2015

AbstractThe rise of China as an economic power has led to concern in many Asian counties that this development poses a threat to their ability to export. The empirical support for this remains inconsistent, however. One explanation for these inconsistencies includes biases that follow from the use of a gravity model specified in an a‐theoretical manner. We study the effect of the Chinese exports growth using the empirical framework outlined by Baldwin and Taglioni (2006). We report evidence of a positive relationship between Chinese and its Asian neighbours’ exports, with countries with greater endowments of human capital benefiting most from this growth.
Perceived blood transfusion safety: a cross‐European comparison
Authors: Merz E.‐M. , Zijlstra B. J. H. , de Kort W. L. A. M. 
Published: November 2015

Background and ObjectivesDuring the past decades, blood transfusions have become an ever safer clinical procedure in developed countries. Extensive donor screening together with improved infectious disease testing has led to a minimization of risks for transfusion recipients. Still, the general public perceives the process of blood transfusion as risky.Materials and MethodsThis study tested variation in perceived transfusion safety across countries and explained it with individual and country factors. We examined whether individual demographic and macro‐level factors (i.e. Human Development Index and Power Distance Index) explain variation within and across European countries. We applied multilevel models to 2009 Eurobarometer data collected in 26 countries (N = 20 874).ResultsResults were largely in line with expectations derived from risk perception and power and status difference theories. Generally, women, older adults, the lower educated and those earning lower incomes perceived heightened risk. Most of the variation across Europe was explained by the Human Development Index. Risk perception regarding blood transfusions was lower in countries with higher Human Development Indices, that is countries with higher average education, life expectancy and Gross Domestic Product.ConclusionThis study provides new insights of how risk perception regarding blood transfusions is shaped within and across Europe. Both individual demographic factors and country characteristics play a role.