bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations between duration of untreated psychosis and domains of positive and negative symptoms
Authors: Birnbaum Michael L. , Wan Claire Ramsay , Broussard Beth , Compton Michael T. 
Published: July 2015

AbstractAimThe duration of untreated psychosis (DUP) has been established as an independent and significant predictor of negative outcomes in first‐episode psychosis samples. Whereas literature has supported the association between DUP and severity of positive and negative symptoms, surprisingly little research to date has explored specifically what types of positive and negative symptoms are most associated with DUP.MethodsDUP, Scale for the Assessment of Positive Symptoms (SAPS) and Scale for the Assessment of Negative Symptoms (SANS) data were collected in 247 first‐episode psychosis participants (mean age: 23.9 ± 4.8) between August 2008 and June 2013.ResultsDUP was significantly but modestly associated with the severity of hallucinations (ρ = 0.222; P = 0.001), delusions (r = 0.202; P = 0.003) and formal thought disorder (ρ = 0.138; P = 0.043) but was not associated with bizarre behaviour. DUP was significantly but modestly associated with SANS avolition‐apathy (ρ = 0.164; P = 0.016) and anhedonia‐asociality (r = 0.321; P < 0.001) subscales but was not associated with affective flattening or blunting, alogia or attention.ConclusionsDUP is a complex and multifaceted phenomenon that is associated with early‐course illness development. In efforts to improve early intervention services, prognoses and outcomes, it is vital to understand both the factors that contribute to lengthy untreated psychosis as well as the illness characteristics that are impacted by untreated psychosis.
Rapid rFVIIa enhanced on‐demand dosing in haemophilia inhibitor patients
Authors: Morfini Massimo 
Published: July 2015

AbstractRecombinant factor VII activated (rFVIIa) is a bypassing agent widely used in haemophilia A and B patients with antibodies against coagulation factors VIII or IX. When used according to the correct doses, rFVIIa may control bleeding, subclinical bleeding and rebleeding, avoiding the effect of neutralising inhibitors. Because of the fast action of the rFVIIa, haemostasis occurs promptly and enables a fast bleeding control with on‐demand treatment in home or in surgical setting. Rapidity is also a distinguishing feature in preparation and injection of rFVIIa to cope the restraining times of busy patients and parents. The effective haemostatic activity of rFVIIa enables a sustained bleeding control, which is implemented with every other day (eod) administration and suited for enhanced on‐demand therapy and short‐term repeated infusions use of rFVIIa to prevent microhaemorrhages or rebleeding. Comprehensive appreciation of these pharmacological and pharmacodynamic’ characteristics will likely be a further stimulus to the wider enhanced on‐demand use of rFVIIa.
Recommendations on the clinical use of bendamustine in lymphoproliferative syndromes and multiple myeloma
Authors: Peñalver Francisco Javier , Delgado Julio , Loscertales Javier , Sastre Jose Luis , Peña Asunción , Olave María Teresa , Osorio Santiago , de la Fuente Adolfo , Salar Antonio , Grande Carlos , Pérez Ceballos Elena , Debén Guillermo , Echeveste Asunción , Casado Felipe , de la Rubia Javier , Lahuerta Juan José , Mateos María Victoria 
Published: July 2015

AbstractBendamustine is an increasingly used hybrid alkylating agent that is active in lymphoid neoplasias via a novel mechanism of action. There are some pending questions about its use in clinical practice because of its developmental features. A consensus panel of several leading Spanish hematologists with broad experience in the clinical use of bendamustine has established recommendations for the management and treatment of hematological patients with bendamustine based on available clinical data and the experience of the participants. These recommendations address the dose and treatment regimen for different clinical indications, the management of toxicity, and support therapy. This article contains the conclusions of this consensus panel, which are intended to serve as guidelines for the use of bendamustine.
The neural basis of value accumulation in intertemporal choice
Authors: Rodriguez Christian A. , Turner Brandon M. , Van Zandt Trisha , McClure Samuel M. 
Published: July 2015

AbstractMaking intertemporal choices (choosing between rewards available at different points in time) requires determining and comparing the subjective values of available rewards. Several studies have found converging evidence identifying the neural systems that encode subjective value in intertemporal choice. However, the neural mechanisms responsible for the process that produces intertemporal decisions on the basis of subjective values have not been investigated. Using model‐based and connectivity analyses of functional magnetic resonance imaging data, we investigated the neural mechanisms underlying the value‐accumulation process by which subjective value guides intertemporal decisions. Our results show that the dorsomedial frontal cortex, bilateral posterior parietal cortex, and bilateral lateral prefrontal cortex are all involved in the accumulation of subjective value for the purpose of action selection. Our findings establish a mechanistic framework for understanding frontoparietal contributions to intertemporal choice and suggest that value‐accumulation processes in the frontoparietal cortex may be a general mechanism for value‐based choice.
Improvement of cold injury‐induced mouse brain edema by endothelin ETB antagonists is accompanied by decreases in matrixmetalloproteinase 9 and vascular endothelial growth factor‐A
Authors: Michinaga Shotaro , Seno Naoki , Fuka Mayu , Yamamoto Yui , Minami Shizuho , Kimura Akimasa , Hatanaka Shunichi , Nagase Marina , Matsuyama Emi , Yamanaka Daisuke , Koyama Yutaka 
Published: July 2015

AbstractBrain edema is a potentially fatal pathological state that often occurs after brain injuries such as ischemia and trauma. However, therapeutic agents that fundamentally treat brain edema have not yet been established. We previously found that endothelin ETB receptor antagonists attenuate the formation and maintenance of vasogenic brain edema after cold injury in mice. In this study, the effects of ETB antagonists on matrixmetalloproteinase (MMP)9 and vascular endothelial growth factor (VEGF)‐A expression were examined in the cold injury model. Cold injury was performed in the left brain of male ddY mice (5–6 weeks old) for the induction of vasogenic edema. Expression of MMP9 and VEGF‐A mRNA in the mouse cerebrum was increased by cold injury. Immunohistochemical observations showed that the MMP9 and VEGF‐A were mainly produced in reactive astrocytes in the damaged cerebrum. Intracerebroventricular administration of BQ788 (10 μg) or IRL‐2500 (10 μg) (selective ETB antagonists) attenuated brain edema and disruption of the blood–brain barrier after cold injury. BQ788 and IRL‐2500 reversed the cold injury‐induced increases in MMP9 and VEGF‐A expression. The induction of reactive astrocytes producing MMP9 and VEGF‐A in the damaged cerebrum was attenuated by BQ788 and IRL‐2500. These results suggest that attenuations of astrocytic MMP9 and VEGF‐A expression by ETB antagonists may be involved in the amelioration of vasogenic brain edema.
Assessment of soil water repellency as a function of soil moisture with mixed modelling
Authors: Fishkis O. , Wachten M. , Hable R. 
Published: July 2015

SummaryAn understanding of the relation between soil water repellency (SWR) and soil moisture is a prerequisite of water‐flow modelling in water‐repellent soil. Here, the relation between SWR and soil moisture was investigated with intact cores of soil taken from three types of soil with different particle‐size distributions. The SWR was measured by a sessile drop contact angle (CA) during drying at soil pF values that ranged from −∞ to 4.2. From the measured CA, the work of adhesion (Wa) was calculated and its relation with the pF‐value was explored. Mixed modelling was applied to evaluate the effects of pF, soil type and soil depth on CA and Wa. For all soil types, a positive relation was observed between CA and the pF‐value that could be represented by a linear model for the pF‐range of 1–4.2. The variation in slope and intercept of the CA–pF relationship caused by heterogeneity of the samples taken from a single soil horizon was quantified. In addition, the relation between CA and water content (WC) showed hysteresis, with significantly larger CAs during drying than during wetting.
Geography, assortative mating, and the effects of sexual selection on speciation with gene flow
Authors: Servedio Maria R. 
Published: July 2015

AbstractTheoretical and empirical research on the evolution of reproductive isolation have both indicated that the effects of sexual selection on speciation with gene flow are quite complex. As part of this special issue on the contributions of women to basic and applied evolutionary biology, I discuss my work on this question in the context of a broader assessment of the patterns of sexual selection that lead to, versus inhibit, the speciation process, as derived from theoretical research. In particular, I focus on how two factors, the geographic context of speciation and the mechanism leading to assortative mating, interact to alter the effect that sexual selection through mate choice has on speciation. I concentrate on two geographic contexts: sympatry and secondary contact between two geographically separated populations that are exchanging migrants and two mechanisms of assortative mating: phenotype matching and separate preferences and traits. I show that both of these factors must be considered for the effects of sexual selection on speciation to be inferred.
Macrolide‐induced hyperthermia in foals: Role of impaired sweat responses
Authors: Stieler A. L. , Sanchez L. C. , Mallicote M. F. , Martabano B. B. , Burrow J. A. , MacKay R. J. 
Published: July 2015

SummaryReasons for performing studyThe mechanism of hyperthermia, a potentially fatal adverse effect of erythromycin treatment of foals, is unknown.ObjectivesTo determine the cause of erythromycin‐associated hyperthermia. It was hypothesised that the normal sweat response of foals is impaired by treatment with erythromycin.Study designBlinded, crossover study in 10 healthy pony foals.MethodsFoals kept in stalls were given either erythromycin (25 mg/kg bwt orally, 3 times daily) or control for 10 days then turned out for a further 10 days. Quantitative intradermal terbutaline sweat tests were performed on Days 1 (baseline), 3, 10 and 20. The effects on terbutaline‐induced sweating of erythromycin, terbutaline concentration and treatment day were analysed by repeated‐measures ANOVA with Bonferroni‐corrected pairwise post hoc comparisons. Peak temperatures were compared by Wilcoxon's signed rank test and proportions by McNemar's related samples test. Significance was set at P<0.05.ResultsThere were significant 2‐factor interactions for treatment × terbutaline after baseline, treatment × day at every terbutaline concentration, and day × terbutaline for erythromycin (P<0.001) but not control (P = 0.9) treatment. Sweating was significantly reduced from baseline in erythromycin‐treated foals at all subsequent days. Erythromycin‐treated foals produced less sweat at all time‐points than did control‐treated foals (P<0.05). Peak rectal temperatures of erythromycin‐treated foals were significantly higher (P = 0.02) than those of controls. During the first 3 days outside more erythromycin‐treated than control‐treated foals required treatment for hyperthermia (6 vs. 0; P = 0.03).ConclusionsWe believe drug‐induced anhidrosis is the likely cause of hyperthermia in some foals treated with erythromycin.
Self‐maintenance of neurogenic inflammation contributes to a vicious cycle in skin
Authors: Gouin Olivier , Lebonvallet Nicolas , L'Herondelle Killian , Le Gall‐Ianotto Christelle , Buhé Virginie , Plée‐Gautier Emmanuelle , Carré Jean‐Luc , Lefeuvre Luc , Misery Laurent 
Published: July 2015

AbstractCutaneous neurogenic inflammation (CNI) is frequently associated with skin disorders. CNI is not limited to the retrograde signalling of nociceptive sensory nerve endings but can instead be regarded as a multicellular phenomenon. Thus, soluble mediators participating in communication among sensory nerves, skin and immune cells are key components of CNI. These interactions induce the self‐maintenance of CNI, promoting a vicious cycle. Certain G protein‐coupled receptors (GPCRs) play a prominent role in these cell interactions and contribute to self‐maintenance. Protease‐activated receptors 2 and 4 (PAR‐2 and PAR‐4, respectively) and Mas‐related G protein‐coupled receptors (Mrgprs) are implicated in the synthesis and release of neuropeptides, proteases and soluble mediators from most cutaneous cells. Regulation of the expression and release of these mediators contributes to the vicious cycle of CNI. The authors propose certain hypothetical therapeutic options to interrupt this cycle, which might reduce skin symptoms and improve patient quality of life.
Suppressor of cytokine signalling‐1 induces significant preclinical antitumor effect in malignant melanoma cells
Authors: Tagami‐Nagata Naoko , Serada Satoshi , Fujimoto Minoru , Tanemura Atsushi , Nakatsuka Rie , Ohkawara Tomoharu , Murota Hiroyuki , Kishimoto Tadamitsu , Katayama Ichiro , Naka Tetsuji 
Published: July 2015

AbstractMalignant melanoma is the most aggressive form of skin cancer, responsible for the majority of skin cancer‐related deaths. Metastatic melanoma is resistant to surgery, radiation or chemotherapy, and an effective therapy has not yet been established. Our study investigated the therapeutic potential of the suppressor of cytokine signalling‐1 (SOCS‐1), an endogenous inhibitor of the intracellular cytokine signalling pathway, for treating melanoma. Adenovirus vectors encoding the SOCS‐1 gene were used to overexpress SOCS‐1 in three melanoma cell lines (G361, SK‐MEL5 and SK‐MEL28). In G361 and SK‐MEL5, overexpression of SOCS‐1 significantly reduced cell proliferation and induced apoptosis in vitro and in vivo. Furthermore, we indicated that the antiproliferative effect of SOCS‐1 correlated not only with decreased levels of the activation of signal transducer and activator of transcription (STAT)3 but also with increased levels of p53 expression and phosphorylation. These findings indicate the potential for clinical use of SOCS‐1 for melanoma treatment.
Dual oxidase 2 is essential for house dust mite‐induced pro‐inflammatory cytokine production in human keratinocytes
Authors: Ko Eunbi , Choi Hyun , Park Kkot‐Nara , Park Ju‐Yearl , Lee Tae Ryong , Shin Dong Wook , Bae Yun Soo 
Published: July 2015

AbstractHouse dust mites (HDMs) are known to trigger chronic inflammation through Toll‐like receptors (TLRs) and their signalling cascades. In this study, we found that TLR2 ligation by HDMs induced the activation of dual oxidase 2 (Duox2) and nuclear factor‐κB (NF‐κB), leading to the production of pro‐inflammatory cytokines in human keratinocytes. Stimulation of human keratinocytes with HDMs resulted in increases in interleukin‐8 (IL‐8) and chemokine (C–C motif) ligand 20 (CCL20) levels. However, pro‐inflammatory cytokine production was abolished in keratinocytes transfected with TLR2 siRNA, indicating that HDM‐induced cytokine production was mediated via TLR2 signalling. We also examined the function of Duox1/2 isozymes, which are primarily expressed in keratinocytes, in HDM‐mediated pro‐inflammatory cytokine production. Human keratinocytes transfected with control siRNA or Duox1 siRNA showed no inhibition of IL‐8 or CCL20 production in response to HDMs, whereas the silencing of Duox2 expression resulted in a failure to induce cytokine production. Moreover, the phosphorylation and nuclear localization of RelA/p65, a component of NF‐κB, were induced by HDMs in human keratinocytes. Transfection of human keratinocytes with TLR2 siRNA or Duox2 siRNA resulted in the complete abolishment of RelA/p65 nuclear localization in response to HDMs. Taken together, these results indicate that the HDM‐dependent TLR2‐Duox2 signalling axis indeed promotes NF‐κB activation, which induces IL‐8 and CCL20 production and mediates epidermal keratinocyte inflammation.
Novel pppGpp binding site at the C‐terminal region of the Rel enzyme from Mycobacterium smegmatis
Authors: Syal Kirtimaan , Joshi Himanshu , Chatterji Dipankar , Jain Vikas 
Published: July 2015

Mycobacterium tuberculosis elicits the stringent response under unfavorable growth conditions, such as those encountered by the pathogen inside the host. The hallmark of this response is production of guanosine tetra‐ and pentaphosphates, collectively termed (p)ppGpp, which have pleiotropic effects on the bacterial physiology. As the stringent response is connected to survival under stress, it is now being targeted for developing inhibitors against bacterial persistence. The Rel enzyme in mycobacteria has two catalytic domains at its N‐terminus that are involved in the synthesis and hydrolysis of (p)ppGpp, respectively. However, the function of the C‐terminal region of the protein remained unknown. Here, we have identified a binding site for pppGpp in the C‐terminal region of Rel. The binding affinity of pppGpp was quantified by isothermal titration calorimetry. The binding site was determined by crosslinking using the nucleotide analog azido‐pppGpp, and examining the crosslink product by mass spectrometry. Additionally, mutations in the Rel protein were created to confirm the site of pppGpp binding by isothermal titration calorimetry. These mutants showed increased pppGpp synthesis and reduced hydrolytic activity. We believe that binding of pppGpp to Rel provides a feedback mechanism that allows the protein to detect and adjust the (p)ppGpp level in the cell. Our work suggests that such sites should also be considered while designing inhibitors to target the stringent response.
Warming and drought differentially influence the production and resorption of elemental and metabolic nitrogen pools inQuercus rubra
Authors: Suseela Vidya , Tharayil Nishanth , Xing Baoshan , Dukes Jeffrey S. 
Published: July 2015

AbstractThe process of nutrient retranslocation from plant leaves during senescence subsequently affects both plant growth and soil nutrient cycling; changes in either of these could potentially feed back to climate change. Although elemental nutrient resorption has been shown to respond modestly to temperature and precipitation, we know remarkably little about the influence of increasing intensities of drought and warming on the resorption of different classes of plant metabolites. We studied the effect of warming and altered precipitation on the production and resorption of metabolites inQuercus rubra. The combination of warming and drought produced a higher abundance of compounds that can help to mitigate climatic stress by functioning as osmoregulators and antioxidants, including important intermediaries of the tricarboxylic acid (TCA) cycle, amino acids including proline and citrulline, and polyamines such as putrescine. Resorption efficiencies (REs) of extractable metabolites surprisingly had opposite responses to drought and warming; drought treatments generally increased RE of metabolites compared to ambient and wet treatments, while warming decreased RE. However, RE of total N differed markedly from that of extractable metabolites such as amino acids; for instance, droughted plants resorbed a smaller fraction of elemental N from their leaves than plants exposed to the ambient control. In contrast, plants in drought treatment resorbed amino acids more efficiently (>90%) than those in ambient (65–77%) or wet (42–58%) treatments. Across the climate treatments, the RE of elemental N correlated negatively with tissue tannin concentration, indicating that polyphenols produced in leaves under climatic stress could interfere with N resorption. Thus, senesced leaves from drier conditions might have a lower nutritive value to soil heterotrophs during the initial stages of litter decomposition despite a higher elemental N content of these tissues. Our results suggest that N resorption may be controlled not only by plant demand, but also by climatic influences on the production and resorption of plant metabolites. As climate–carbon models incorporate increasingly sophisticated nutrient cycles, these results highlight the need to adequately understand plant physiological responses to climatic variables.
Is part‐night lighting an effective measure to limit the impacts of artificial lighting on bats?
Authors: Azam Clémentine , Kerbiriou Christian , Vernet Arthur , Julien Jean‐François , Bas Yves , Plichard Laura , Maratrat Julie , Le Viol Isabelle 
Published: July 2015

AbstractAs light pollution is currently considered to be a major threat to biodiversity, different lighting management options are being explored to mitigate the impact of artificial lighting on wildlife. Although part‐night lighting schemes have been adopted by many local authorities across Europe to reduce the carbon footprint and save energy, their effects on biodiversity are unknown. Through a paired, in situ experiment, we compared the activity levels of 8 bat species under unlit, part‐night, and full‐night lighting treatments in a rural area located 60 km south of Paris, France. We selected 36 study locations composed of 1 lit site and a paired unlit control site; 24 of these sites were located in areas subject to part‐night lighting schemes, and 12 sites were in areas under standard, full‐night lighting. There was significantly more activity on part‐night lighting sites compared to full‐night lighting sites for the late‐emerging, light‐sensitive Plecotus spp., and a similar pattern was observable for Myotis spp., although not significant. In contrast, part‐night lighting did not influence the activity of early emerging bat species around streetlights, except for Pipistrellus pipistrellus for which there was significantly less activity on part‐night lighting sites than on full‐night lighting sites. Overall, no significant difference in activity between part‐ and full‐night lighting sites were observed in 5 of the 8 species studied, suggesting that current part‐night lighting schemes fail to encompass the range of activity of most bat species. We recommend that such schemes start earlier at night to effectively mitigate the adverse effects of artificial lighting on light‐sensitive species, particularly along ecological corridors that are especially important to the persistence of biodiversity in urban landscapes.