bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bioengineered nisin derivatives with enhanced activity in complex matrices
Authors: Rouse Susan , Field Des , Daly Karen M. , O'Connor Paula M. , Cotter Paul D. , Hill Colin , Ross R. Paul 
Published: January 2012

SummaryNisin A is the best known and most extensively characterized lantibiotic. As it is ribosomally synthesized, bioengineering‐based strategies can be used to generate variants. We have previously demonstrated that bioengineering of the hinge region of nisin A can result in the generation of variants with enhanced anti‐microbial activity against Gram‐positive pathogens. Here we created a larger bank of hinge variant producers and screened for producers that exhibit enhanced bioactivity as assessed by agar‐based assays against a selection of target strains. Further analysis of 12 ‘lead’ variants reveals that in many cases enhanced bioactivity is not attributable to enhanced specific activity but is instead as a consequence of an enhanced ability to diffuse through complex polymers. In the case of two variants, which contain the residues SVA and NAK, respectively, within the hinge region, we demonstrate that this enhanced trait enables the peptides to dramatically outperform nisin A with respect to controlling Listeria monocytogenes in commercially produced chocolate milk that contains carrageenan as a stabilizer.
Germination of Lecanicillium fungicola in the mycosphere of Agaricus bisporus
Authors: Berendsen Roeland L. , Kalkhove Stefanie I. C. , Lugones Luis G. , Wösten Han A. B. , Bakker Peter A. H. M. 
Published: January 2012

SummaryDry bubble disease is a major problem in the commercial cultivation of the white button mushroom Agaricus bisporus and is caused by the ascomycete Lecanicillium fungicola. In the casing layer, germination of L. fungicola spores is inhibited by the microflora, a phenomenon known as fungistasis. Fungistasis is annulled when the casing is colonized by A. bisporus hyphae. We demonstrated that addition of A. bisporus‐associated sugars, similarly annulled the casing fungistasis. However, casing fungistasis does not seem to be based on competition for resources as L. fungicola spores germinate regardless of nutrient availability. Pseudomonas bacteria are a dominant group of bacteria in the casing and have previously been implied to be essential for the development of fungistasis in soils. Antibiotics produced by model strain Pseudomonas fluorescens CHA0 inhibited L. fungicola spore germination. Addition of glucose desensitized spores of L. fungicola, which resulted in germination in the presence of antibiotics. We conclude that antibiotics produced by the microflora most likely cause fungistasis.
The influence of road transport on the activities of glutathione reductase, glutathione peroxidase, and glutathione‐S‐transferase in equine erythrocytes
Authors: Niedźwiedź Artur , Nicpoń Józef , Zawadzki Marcin , Służewska‐Niedźwiedź Monika , Januszewska Lidia 
Published: January 2012

BackgroundTransport of horses may have significant impact on serum biochemical and hematologic analytes and resistance to infection.ObjectiveThe aim of our study was to assess the influence of transport stress on selected enzymatic antioxidants in equine blood.MethodsThe study was conducted on a group of 60 horses of different breeds and ranging in age from 4 to 10 years. Venous blood was collected immediately before loading horses onto trailers for 8 hours of transport (I), immediately after unloading them from the trailer (II), and after subsequent stall rest for 24 hours (III). Hemolysates of blood were prepared, and hemoglobin (Hb) concentration and activities of the enzymatic antioxidants glutathione reductase (GR), glutathione‐S‐transferase (GST), and glutathione peroxidase (GPx) were measured. Enzyme activities were expressed as units of activity per gram of hemoglobin.ResultsThere were significant decreases in activities (mean ± SD U/g Hb [minimum–maximum]) of GPx between collection times I (36 ± 14 U/g Hb [9–67 U/g Hb]) and III (30 ± 11 U/g Hb [12–51 U/g Hb]) and of GR between collection times I (54 ± 28 U/g Hb [7–117 U/g Hb]) and II (40 ± 23 U/g Hb [12–145 U/g Hb]). There was no significant difference in activities of GR between collection times I and III (50 ± 27 U/g Hb [9–116 U/g Hb]). There were no differences detected in GST activity among the 3 collection times.ConclusionRoad transport has an impact on activities of the antioxidant enzymes GPx and GR, with recovery of GR activity evident by 24 hours post‐transport. Decreased activity of these enzymes may be one mechanism for increased susceptibility to infections that are manifest after shipping; alternatively, decreases may indicate utilization as these enzymes work to neutralize increases in reactive oxygen species.
CareTrack Australia: assessing the appropriateness of adult healthcare: protocol for a retrospective medical record review
Authors: Hunt Tamara D , Ramanathan Shanthi A , Hannaford Natalie A , Hibbert Peter D , Braithwaite Jeffrey , Coiera Enrico , Day Richard O , Westbrook Johanna I , Runciman William B 
Published: January 2012

IntroductionIn recent years in keeping with international best practice, clinical guidelines for common conditions have been developed, endorsed and disseminated by peak national and professional bodies. Yet evidence suggests that there remain considerable gaps between the care that is regarded as appropriate by such guidelines and the care received by patients. With an ageing population and increasing treatment options and expectations, healthcare is likely to become unaffordable unless more appropriate care is provided. This paper describes a study protocol that seeks to determine the percentage of healthcare encounters in which patients receive appropriate care for 22 common clinical conditions and the reasons why variations exist from the perspectives of both patients and providers.Methods/designA random stratified sample of at least 1000 eligible participants will be recruited from a representative cross section of the adult Australian population. Participants' medical records from the years 2009 and 2010 will be audited to assess the appropriateness of the care received for 22 common clinical conditions by determining the percentage of healthcare encounters at which the care provided was concordant with a set of 522 indicators of care, developed for these conditions by a panel of 43 disease experts. The knowledge, attitudes and beliefs of participants and healthcare providers will be examined through interviews and questionnaires to understand the factors influencing variations in care.Ethics and disseminationPrimary ethics approvals were sought and obtained from the Hunter New England Local Health Network. The authors will submit the results of the study to a relevant journal as well as undertaking oral presentations to researchers, clinicians and policymakers.
Clinical evaluation of intradermal vaccination against porcine enzootic pneumonia (Mycoplasma hyopneumoniae)
Authors: Tassis P. D. , Papatsiros V. G. , Nell T. , Maes D. , Alexopoulos C. , Kyriakis S. C. , Tzika E. D. 
Published: January 2012

The aim of the present study was to investigate the efficacy of single‐dose intradermal vaccination against Mycoplasma hyopneumoniae on a commercial swine unit. A total of 1051 healthy suckling piglets of 28±3 days of age were randomly assigned to one of three experimental groups: (a) intradermal: 346 piglets vaccinated intradermally (Porcilis M Hyo ID Once, Intervet SPAH), (b) intramuscular : 351 piglets vaccinated intramuscularly (Porcilis M1 Intervet SPAH) and (c) controls: 354 piglets injected with a placebo (adjuvant only). Performance parameters such as average daily weight gain (ADG), as well as health parameters and lung lesion scores were monitored from four weeks of age until slaughter. The improvement in ADG over the controls, during the finishing phase, was 27 g/day for the intradermal group and 17 g/day for the intramuscular group. Both intradermal and intramuscular vaccinations were effective in reducing clinical signs and lung lesions caused by M hyopneumoniae. Compared with the controls, approximately 10.4 per cent fewer clinical cases were diagnosed in the intradermal group, and 6 per cent fewer in the intramuscular group, during the finishing period. In conclusion, performance results were better in the vaccinated groups than in the control group, while intradermal vaccination afforded greater protection than intramuscular vaccination, especially with regard to morbidity, lung lesion and pleuritis scores.
Integrative Survival-Based Molecular Profiling of Human Pancreatic Cancer
Authors: Donahue Timothy R. , Tran Linh M. , Hill Reginald , Li Yunfeng , Kovochich Anne , Calvopina Joseph H. , Patel Sanjeet G. , Wu Nanping , Hindoyan Antreas , Farrell James J. , Li Xinmin , Dawson David W. , Wu Hong 
Published: January 2012

Abstract
Purpose: To carry out an integrative profile of human pancreatic ductal adenocarcinoma (PDAC) to identify prognosis-significant genes and their related pathways.
Experimental Design: A concordant survival-based whole genome in silico array analysis of DNA copy number, and mRNA and miRNA expression in 25 early-stage PDAC was carried out. A novel composite score simultaneously integrated gene expression with regulatory mechanisms to identify the signature genes with the most levels of prognosis-significant evidence. The predominant signaling pathways were determined via a pathway-based approach. Independent patient cohorts (n = 148 and 42) were then used as in vitro validation of the array findings.
Results: The composite score identified 171 genes in which expressions were able to define two prognosis subgroups (P = 3.8e-5). Eighty-eight percent (151 of 171) of the genes were regulated by prognosis-significant miRNAs. The phosphoinositide 3-kinase/AKT pathway and SRC signaling were densely populated by prognosis-significant genes and driven by genomic amplification of SRC and miRNA regulation of p85α and CBL. On tissue microarray validation (n = 148), p85α protein expression was associated with improved survival for all patients (P = 0.02), and activated P-SRC (Y418) was associated shorter survival for patients with low-grade histology tumors (P = 0.04). Interacting P-SRC and p85α revealed that they define two distinct PDAC patient subgroups (P = 0.0066). Furthering the importance of these pathways, CBL protein expression was associated with improved survival (P = 0.03) on a separate cohort (n = 42).
Conclusions: These pathways and related genes may represent putative clinical biomarkers and possible targets of individualized therapy in the distinct patient subgroups they define. Clin Cancer Res; 18(5); 1352–63. ©2012 AACR.
Sunitinib Therapy for Melanoma Patients with KIT Mutations
Authors: Minor David R. , Kashani-Sabet Mohammed , Garrido Maria , O'Day Steven J. , Hamid Omid , Bastian Boris C. 
Published: January 2012

Abstract
Purpose: Recent studies have shown activating KIT mutations in melanoma originating from mucosa, acral, or cumulative sun-damaged skin sites. We aimed to assess the predictive role of KIT mutation, amplification, or overexpression for response to treatment with the kinase inhibitor sunitinib.
Experimental Design: Tumor tissues from 90 patients with stage III or IV acral, mucosal, or cumulative sun-damaged skin melanoma underwent sequencing of KIT, BRAF, NRAS, and GNAQ genes, FISH analysis for KIT amplification, and immunohistochemistry of KIT protein (CD117). Patients with mutations, amplifications, or overexpression of KIT were treated with sunitinib and responses measured by Response Evaluation Criteria in Solid Tumors (RECIST).
Results: Eleven percent of the melanomas tested had mutations in KIT, 23% in BRAF, 14% in NRAS, and none in GNAQ. Of 12 patients treated with sunitinib, 10 were evaluable. Of the 4 evaluable patients with KIT mutations, 1 had a complete remission for 15 months and 2 had partial responses (1- and 7-month duration). In contrast, only 1 of the 6 patients with only KIT amplification or overexpression alone had a partial response. In 1 responder with rectal melanoma who later progressed, the recurring tumor had a previously undetected mutation in NRAS, which was found in addition to the persisting mutation in KIT. Interestingly, among patients with manifest stage IV disease, KIT mutations were associated with a significantly shortened survival time (P &lt; 0.0001).
Conclusions: Sunitinib may have activity in patients with melanoma and KIT mutations; more study is needed. KIT mutations may represent an adverse prognostic factor in metastatic melanoma. Clin Cancer Res; 18(5); 1457–63. ©2012 AACR.
CD26 Overexpression Is Associated with Prolonged Survival and Enhanced Chemosensitivity in Malignant Pleural Mesothelioma
Authors: Aoe Keisuke , Amatya Vishwa Jeet , Fujimoto Nobukazu , Ohnuma Kei , Hosono Osamu , Hiraki Akio , Fujii Masanori , Yamada Taketo , Dang Nam H. , Takeshima Yukio , Inai Kouki , Kishimoto Takumi , Morimoto Chikao 
Published: January 2012

Abstract
Purpose: Malignant pleural mesothelioma (MPM) is an aggressive and therapy-resistant neoplasm arising from the pleural mesothelial cells, without established indicators to predict responsiveness to chemotherapy.
Experimental Design: Our study involving 79 MPM patients showed that 73.4% of MPM expressed CD26 on cell membrane.
Results: The majority of epithelioid and biphasic types of MPM expressed CD26 on the cell membrane, whereas the sarcomatoid type showed a lack of CD26 surface expression. Although the sarcomatoid type was associated with poor prognosis (P &lt; 0.0001), no significant relationship between CD26 expression and survival was observed. On the contrary, there was a trend for an association between response rate to chemotherapy and CD26 expression (P = 0.053), with a higher level of CD26 expression more likely to be linked to better response to chemotherapy. Moreover, CD26 expression was a significant factor associated with improved survival in patients who received chemotherapy [median survival time (MST), 18.6 vs. 10.7 months, P = 0.0083]. Furthermore, CD26 expression was significantly associated with better prognosis in patients receiving non–pemetrexed-containing regimens (MST, 14.2 vs. 7.4 months, P = 0.0042), whereas there was no significant association between CD26 expression and survival time for patients receiving pemetrexed-containing regimens. Our in vitro and microarray studies showed that mesothelioma cells expressing high CD26 displayed high proliferative activity, and CD26 expression was closely linked to cell-cycle regulation, apoptosis, and chemotherapy resistance.
Conclusions: Our results strongly suggest that CD26 is a clinically significant biomarker for predicting response to chemotherapy for MPM. Clin Cancer Res; 18(5); 1447–56. ©2012 AACR.
A Functional, New Short Isoform of Death Receptor 4 in Ewing's Sarcoma Cell Lines May be Involved in TRAIL Sensitivity/Resistance Mechanisms
Authors: Picarda Gaëlle , Surget Sylvanie , Guiho Romain , Téletchéa Stéphane , Berreur Martine , Tirode Franck , Pellat-Deceunynck Catherine , Heymann Dominique , Trichet Valérie , Rédini Françoise 
Published: January 2012

Abstract
Ewing's sarcoma (ES) is a high-grade neoplasm arising in bones of children and adolescents. Survival rate decreases from greater than 50% to only 20% after 5 years for patients not responding to treatment or presenting metastases at diagnosis. TRAIL, which has strong antitumoral activity, is a promising therapeutic candidate. To address TRAIL sensitivity, 7 human ES cell lines were used. Cell viability experiments [3′[1-(phenylaminocarbonyl)-3,4-tetrazolium]-bis(4-methoxy-6-nitro-)benzene sulfonic acid hydrate (XTT) assay] showed that 4 of the 7 ES cell lines were resistant to TRAIL. Western blotting and flow cytometry analyses revealed that DR5 was uniformly expressed by all ES cell lines, whereas DR4 levels were higher in sensitive cell lines. In TRAIL-sensitive TC-71 cells, knockdown of TNFRSF10A/DR4 by short hairpin RNA (shRNA) was associated with a loss of sensitivity to TRAIL, in spite of DR5 presence. Interestingly, we identified a new transcript variant that results from an alternative splicing and encodes a 310–amino acid protein which corresponds to the 468 aa of DR4 original isoform but truncated of aa 11 to 168 within the extracellular TRAIL-binding domain. According to modeling studies, the contact of this new DR4 isoform (bDR4) with TRAIL seemed largely preserved. The overexpression of bDR4 in a TRAIL-resistant cell line restored TRAIL sensitivity. TRAIL resensitization was also observed after c-FLIP knockdown by shRNA in two TRAIL-resistant cell lines, as shown by XTT assay and caspase-3 assay. The results presented in this study showed that DR4, both as the complete form or as its new short isoform, is involved in TRAIL sensitivity in ES. Mol Cancer Res; 10(3); 336–46. ©2012 AACR.
Conduction Abnormalities in Pediatric Patients With Restrictive Cardiomyopathy
Authors: Walsh Mark A. , Grenier Michelle A. , Jefferies John L. , Towbin Jeffrey A. , Lorts Angela , Czosek Richard J. 
Published: January 2012

Background—
Pediatric restrictive cardiomyopathy carries a poor prognosis secondary to a high risk of sudden death previously attributed to ventricular tachyarrhythmias. The extent of conduction abnormalities in this population and their relationship to life-threatening events has not been previously reported.

Methods and Results—

A retrospective study of pediatric patients with restrictive cardiomyopathy diagnosed between April 1994 and May 2011 was performed. Demographic, cardiac, and ECG characteristics and the mechanisms of serious arrhythmic events (death or episode of acute hemodynamic compromise thought to be secondary to arrhythmia) were evaluated. Sixteen patients (1–17 years of age) were reviewed, with 5 sudden cardiac events noted, including 4 deaths. Two deaths were caused by development of acute heart block; another patient with syncope had intermittent heart block and survived as the result of pacing features of an implanted defibrillator system. The median PR interval (222 versus 144 ms;
P
<0.01) and the QRS duration (111 versus 74;
P
=0.01) were significantly longer in those who had an acute cardiac event. Older age at presentation was associated with sudden cardiac events (
P
<0.01). No other functional or echocardiographic variables were associated with a sudden cardiac event.

Conclusions—
Pediatric patients with restrictive cardiomyopathy are at risk for acute high-grade heart block, and, in this cohort, bradycardic events represented a significant portion of all arrhythmic events. Aggressive ECG monitoring strategies looking for conduction system disease should be ongoing in all patients with restrictive cardiomyopathy. Implantation of a defibrillator/pacemaker should be considered as prophylactic management.
Playing a First-person Shooter Video Game Induces Neuroplastic Change
Authors: Wu Sijing , Cheng Cho Kin , Feng Jing , D'Angelo Lisa , Alain Claude , Spence Ian 
Published: January 2012

AbstractPlaying a first-person shooter (FPS) video game alters the neural processes that support spatial selective attention. Our experiment establishes a causal relationship between playing an FPS game and neuroplastic change. Twenty-five participants completed an attentional visual field task while we measured ERPs before and after playing an FPS video game for a cumulative total of 10 hr. Early visual ERPs sensitive to bottom–up attentional processes were little affected by video game playing for only 10 hr. However, participants who played the FPS video game and also showed the greatest improvement on the attentional visual field task displayed increased amplitudes in the later visual ERPs. These potentials are thought to index top–down enhancement of spatial selective attention via increased inhibition of distractors. Individual variations in learning were observed, and these differences show that not all video game players benefit equally, either behaviorally or in terms of neural change.
Why the Assessment of Causality in Brain–Behavior Relations Requires Brain Stimulation
Authors: Silvanto Juha , Pascual-Leone Alvaro 
Published: January 2012

Abstract
A central aim in cognitive neuroscience is to explain how neural activity gives rise to perception and behavior; the causal link of paramount interest is thus from brain to behavior. Functional neuroimaging studies, however, tend to provide information in the opposite direction by informing us how manipulation of behavior may affect neural activity. Although this may provide valuable insights into neuronal properties, one cannot use such evidence to make inferences about the behavioral significance of the observed activations; if A causes B, it does not necessarily follow that B causes A. In contrast, brain stimulation techniques enable us to directly modulate brain activity as the source of behavior and thus establish causal links.
Representations of Facial Identity in the Left Hemisphere Require Right Hemisphere Processing
Authors: Verosky Sara C. , Turk-Browne Nicholas B. 
Published: January 2012

Abstract
A quintessential example of hemispheric specialization in the human brain is that the right hemisphere is specialized for face perception. However, because the visual system is organized contralaterally, what happens when faces appear in the right visual field and are projected to the nonspecialized left hemisphere? We used divided field presentation and fMRI adaptation to test the hypothesis that the left hemisphere can recognize faces, but only with support from the right hemisphere. Consistent with this hypothesis, facial identity adaptation was observed in the left fusiform face area when a face had previously been processed by the right hemisphere, but not when it had only been processed by the left hemisphere. These results imply that facial identity information is transferred from the right hemisphere to the left hemisphere, and that the left hemisphere can represent facial identity but is less efficient at extracting this information by itself.
Quantitative Analysis of Factors Contributing to Urban Heat Island Intensity
Authors: Ryu Young-Hee , Baik Jong-Jin 
Published: January 2012

AbstractThis study identifies causative factors of the urban heat island (UHI) and quantifies their relative contributions to the daytime and nighttime UHI intensities using a mesoscale atmospheric model that includes a single-layer urban canopy model. A midlatitude city and summertime conditions are considered. Three main causative factors are identified: anthropogenic heat, impervious surfaces, and three-dimensional (3D) urban geometry. Furthermore, the 3D urban geometry factor is subdivided into three subfactors: additional heat stored in vertical walls, radiation trapping, and wind speed reduction. To separate the contributions of the factors and interactions between the factors, a factor separation analysis is performed. In the daytime, the impervious surfaces contribute most to the UHI intensity. The anthropogenic heat contributes positively to the UHI intensity, whereas the 3D urban geometry contributes negatively. In the nighttime, the anthropogenic heat itself contributes most to the UHI intensity, although it interacts strongly with other factors. The factor that contributes the second most is the impervious-surfaces factor. The 3D urban geometry contributes positively to the nighttime UHI intensity. Among the 3D urban geometry subfactors, the additional heat stored in vertical walls contributes most to both the daytime and nighttime UHI intensities. Extensive sensitivity experiments to anthropogenic heat intensity and urban surface parameters show that the relative importance and ranking order of the contributions are similar to those in the control experiment.