bluuebunny/crossref_metadata_2025_split huggingface dataset:
Wellington's Men: The British Soldier of the Napoleonic Wars
Authors: Linch Kevin , McCormack Matthew 
Published: June 2015

AbstractThe bicentenary of the Battle of Waterloo offers an opportunity to think critically about the historiography of the Napoleonic Wars. This article argues that orthodox military histories of the period have tended to neglect the experience of the common soldier. By contrast, the article offers an overview of recent work on the history of war, which applies techniques from social and cultural history in order to explore the perspective of the combatant. By thinking about the social origins and experiences of soldiers and how those experiences were handled in cultural terms, this work sheds new light on the humble redcoat who fought under Wellington at Waterloo.
The effect of water on morning bad breath: a randomized clinical trial
Authors: Van der Sluijs E , Slot DE , Bakker EWP , Van der Weijden GA 
Published: June 2015

AbstractObjectivesTo assess the effects of water on the parameters of ‘morning bad breath’ (MBB) and to evaluate whether there is a difference between rinsing with water and drinking a glass of water.Materials and methodsA total of 50 participants were recruited and were randomly divided into two equal groups. One group rinsed with 15 ml of water for 30 s, and another group drank 200 ml of water within 30 s. Clinical assessments were carried out during one visit between 7:30 am and 12:00 pm. Pre‐ and post‐intervention measures were assessed organoleptically as primary outcome parameters, and a secondary outcome parameter was assessed using both the Halimeter® and OralChroma™ apparatuses to evaluate volatile sulphur compounds (VSCs), hydrogen sulphide (H2S), methyl mercaptan (CH3SH) and dimethyl sulphide ((CH3)2S). In addition, the presence of tongue coating (discoloration/thickness) and tongue fissures was assessed.ResultsAll 50 participants completed the study. In both groups, a significant reduction in the organoleptic score and the OralChroma™ H2S and CH3SH readings was obtained after the intervention. Both regimens resulted in a CH3SH reduction of approximately 60%, whereas the reduction in H2S was between 30% and 50%. The acceptable change between pre‐ and post‐assessments of the clinical parameters was not significantly different between the drinking and rinsing groups.ConclusionRinsing with water or drinking a glass of water had a statistically significant effect on the MBB parameters. No significant difference was obtained between the two regimens.
Clinical and Cost Effectiveness of Enhanced Oral Healthcare in Stroke Care Settings (SOCLE II): A Pilot, Stepped Wedge, Cluster Randomized, Controlled Trial Protocol
Authors: Brady Marian C. , Stott David , Weir Christopher J. , Chalmers Campbell , Sweeney Petrina , Donaldson Cam , Barr John , Barr Marion , Pollock Alex , McGowan Sheena , Bowers Naomi , Langhorne Peter 
Published: June 2015

Rationale Stroke-associated pneumonia, a leading cause of hospital-acquired infection after stroke, affects a fifth of stroke survivors annually. Associated with increased risk of death and poorer rehabilitation outcomes, research suggests a possible relationship between stroke-associated pneumonia and patients' oral health. Aim The aim of this study is to evaluate the feasibility of a randomized controlled trial of the clinical and cost effectiveness of enhanced oral healthcare vs. usual oral healthcare for people in stroke care settings. Design Our pilot, multicentered, pragmatic, stepped wedge, cluster randomized controlled trial oral healthcare [Stroke Oral healthCare pLan Evaluation (SOCLE II)] will compare enhanced oral healthcare intervention and usual oral healthcare. Over 13 months, across 4 wards, we seek to recruit 400 patients (estimating an average of 23 beds per site and a 50% recruitment rate) and 60 nursing staff (estimating an average of 20 members of staff per site and a 75% recruitment rate). Initially, control data (usual oral healthcare) will be collected from all sites. In a randomized, stepped manner, wards will convert to deliver the enhanced oral healthcare intervention. Study outcome(s) Outcomes will be captured across dimensions of care (as recommended for evaluations of complex interventions) at baseline and weekly thereafter. Primary outcomes are pneumonia (patients), knowledge and attitudes (staff), and specialist dental referrals (service). Secondary outcomes include oral health quality of life, plaque, antibiotics, length of stay, death (patients), use of oral healthcare equipment and products, completed assessments, and documented oral healthcare plans (staff). Discussion As one of the first stepped wedge, cluster randomized, controlled trials in stroke care mapping of the complex intervention, our choice of primary and secondary outcomes and choice of trial design are described.
Safety and Efficacy of Intensive vs. Guideline Antiplatelet Therapy in High-Risk Patients with Recent Ischemic Stroke or Transient Ischemic Attack: Rationale and Design of the Triple Antiplatelets for Reducing Dependency after Ischaemic Stroke (TARDIS) Trial (ISRCTN47823388)
Authors:   The TARDIS Trial Investigators
Published: June 2015

Rationale The risk of recurrence following a stroke or transient ischemic attack is high, especially immediately after the event. Hypothesis Because two antiplatelet agents are superior to one in patients with non-cardioembolic events, more intensive treatment might be even more effective. Sample size estimates The sample size of 4100 patients will allow a shift to less recurrence, and less severe recurrence, to be detected (odds ratio 0·68) with 90% power at 5% significance. Methods and design Triple Antiplatelets for Reducing Dependency after Ischaemic Stroke (ISRCTN47823388) is comparing the safety and efficacy of intensive (combined aspirin, clopidogrel, and dipyridamole) vs. guideline antiplatelet therapy, both given for one-month. This international collaborative parallel-group prospective randomized open-label blinded-end-point phase III trial plans to recruit 4100 patients with acute ischemic stroke or transient ischemic attack. Randomization and data collection are performed over a secure Internet site with real-time data validation and concealment of allocation. Outcomes, serious adverse events, and neuroimaging are adjudicated centrally with blinding to treatment allocation. Study outcome The primary outcome is stroke recurrence and its severity (‘ordinal recurrence’ based on modified Rankin Scale) at 90 days, with masked assessment centrally by telephone. Secondary outcomes include vascular events, functional measures (disability, mood, cognition, quality of life), and safety (bleeding, death, serious adverse events). Discussion The trial has recruited more than 50% of its target sample size (latest number: 2399) and is running in 104 sites in 4 countries. One-third of patients presented with a transient ischemic attack.
Learning on the Job? EU Enlargement and the Assignment of (Shadow) Rapporteurships in the European Parliament
Authors: Hurka Steffen , Kaeding Michael , Obholzer Lukas 
Published: June 2015

AbstractThis article investigates the determinants of assignments to European Parliament negotiating teams comprising both rapporteurs and shadow rapporteurs. We re‐examine the argument that under‐representation of MEPs (Members of the European Parliament) from new Member States on these key posts after enlargement might have been due to a 'learning phase'. We find that MEPs from newer Member States remain considerably less likely to act as rapporteurs during the second term after enlargement (2009–14). Most importantly, this trend also holds for shadow rapporteurships under the co‐decision procedure, which is when they matter most. This structural under‐representation entails important implications for European integration, most importantly that MEPs from newer Member States are less able to influence legislation. We suggest that the patterns we find could be the result of reduced willingness, a more limited skill set, or a structural disadvantage of MEPs from the accession states in the report allocation process.
Context‐dependent effects of yolk androgens on nestling growth and immune function in a multibrooded passerine
Authors: Muriel J. , Salmón P. , Nunez‐Buiza A. , de Salas F. , Pérez‐Rodríguez L. , Puerta M. , Gil D. 
Published: June 2015

AbstractFemale birds may adjust their offspring phenotype to the specific requirements of the environment by differential allocation of physiologically active substances into yolks, such as androgens. Yolk androgens have been shown to accelerate embryonic development, growth rate and competitive ability of nestlings, but they can also entail immunological costs. The balance between costs and benefits of androgen allocation is expected to depend on nestling environment. We tested this hypothesis in a multibrooded passerine, the spotless starling,Sturnus unicolor. We experimentally manipulated yolk androgen levels using a between‐brood design and evaluated its effects on nestling development, survival and immune function. Both in first and replacement broods, the embryonic development period was shorter for androgen‐treated chicks than controls, but there were no differences in second broods. In replacement broods, androgen‐treated chicks were heavier and larger than those hatched from control eggs, but this effect was not observed in the other breeding attempts. Androgen exposure reduced survival with respect to controls only in second broods. Regarding immune function, we detected nonsignificant trends for androgen treatment to activate two important components of innate and adaptive immunity (IL‐6 and Ig‐A levels, respectively). Similarly, androgen‐treated chicks showed greater lymphocyte proliferation than controls in the first brood and an opposite trend in the second brood. Our results indicate that yolk androgen effects on nestling development and immunity depend on the environmental conditions of each breeding attempt. Variation in maternal androgen allocation to eggs could be explained as the result of context‐dependent optimal strategies to maximize offspring fitness.
Is geographic variation within species related to macroevolutionary patterns between species?
Authors: Fisher‐Reid M. C. , Wiens J. J. 
Published: June 2015

AbstractThe relationship between microevolution and macroevolution is a central topic in evolutionary biology. An aspect of this relationship that remains very poorly studied in modern evolutionary biology is the relationship between within‐species geographic variation and among‐species patterns of trait variation. Here, we tested the relationship between climate and morphology among and within species in the salamander genus Plethodon. We focus on a discrete colour polymorphism (presence and absence of a red dorsal stripe) that appears to be related to climatic distributions in a common, wide‐ranging species (Plethodon cinereus). We find that this trait has been variable among (and possibly within) species for >40 million years. Furthermore, we find a strong relationship among species between climatic variation and within‐species morph frequencies. These between‐species patterns are similar (but not identical) to those in the broadly distributed Plethodon cinereus. Surprisingly, there are no significant climate–morphology relationships within most other polymorphic species, despite the strong between‐species patterns. Overall, our study provides an initial exploration of how within‐species geographic variation and large‐scale macroevolutionary patterns of trait variation may be related.
The deubiquitinating enzyme USP46 regulates AMPA receptor ubiquitination and trafficking
Authors: Huo Yuda , Khatri Natasha , Hou Qingming , Gilbert James , Wang Guan , Man Heng‐Ye 
Published: June 2015

AbstractAlpha‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptor (AMPARs) are the primary mediators for inter‐neuronal communication and play a crucial role in higher brain functions including learning and memory. Our previous work demonstrated that AMPARs are subject to ubiquitination by the E3 ligase Nedd4, resulting in EPS15‐mediated receptor internalization and Ubiquitin (Ub)–proteasome pathway (UPP)‐dependent degradation. Protein ubiquitination is a highly dynamic and reversible process, achieved via the balance between ubiquitination and deubiquitination. However, deubiquitination of mammalian AMPARs and the responsible deubiquitinating enzymes remain elusive. In this study, we identify USP46 as the deubiquitinating enzyme for AMPARs. We find that AMPARs are subject to K63 type ubiquitination, and USP46 is able to deubiquitinate AMPARs in vivo and in vitro. In heterologous cells and neurons, expression of USP46 results in a significant reduction in AMPAR ubiquitination, accompanied by a reduced rate in AMPAR degradation and an increase in surface AMPAR accumulation. By contrast, knockdown of USP46 by RNAi leads to elevated AMPAR ubiquitination and a reduction in surface AMPARs at synapses in neurons. Consistently, miniature excitatory postsynaptic currents recordings show reduced synaptic strength in neurons expressing USP46‐selective RNAi. These results demonstrate USP46‐mediated regulation of AMPAR ubiquitination and turnover, which may play an important role in synaptic plasticity and brain function.
image
Protein ubiquitination is a highly dynamic and reversible process, achieved via the balance between ubiquitination and deubiquitination. The glutamatergic AMPARs, which mediate most of the excitatory synaptic transmission in the brain, are known to be subjected to Nedd4‐mediated ubiquitination; however, the deubiquitination process and the responsible deubiquitinating enzymes (DUBs) for mammalian AMPARs remain elusive. We find that AMPARs are subject to K63‐type ubiquitination, and identify USP46 as the DUB for AMPARs. USP46 deubiquitinates AMPARs in vitro and in vivo. Up‐ or down‐regulation of USP46 leads to changes in AMPAR ubiquitination, surface expression, and trafficking, as well as the strength of synaptic transmission. USP46‐mediated regulation of AMPAR ubiquitination and turnover may play an important role in synaptic plasticity and brain function.
Longitudinal changes in dental services provided by Australian dentists
Authors: Ju Xiangqun , Brennan David S. , Spencer A. John , Teusner Dana N. 
Published: June 2015

AbstractObjectiveTo estimate the longitudinal change in number of patients per year (PPY) per dentist by age and sex of dentists in Australia.MethodDentists were selected randomly from Australian dental registers, the baseline collection was in 1983 and repeated approximately every 5 years until 2009. Dentist's practice activity was collected by mailed questionnaire. Number of PPY was calculated from work hours and number of patients per week per dentist. Mixed‐effects regression was applied to estimate both individual random effects and population averaged fixed effects for the number of PPY provided by age, time, and sex.ResultsA total of 1,449 dentists completed 2,822 questionnaires from six waves of data collection (1983 to 2010). The average PPY decreased over the time of the study. The rate of change in PPY accelerated during younger ages and reached a peak when they moved into 50 years old (B = 86.04, P < 0.0001), and then decelerated (B = −0.90, P = 0.0002) across time. The mean number of PPY was higher in male dentists than female dentists in the same 10‐year age group. The pattern of PPY change with aging was an inverted U‐shape for male dentists. In contrast, there was a U‐shape for female dentists.ConclusionsThe longitudinal change in PPY with aging was an inverted U‐shape, which accelerated during younger age, and decelerated after reaching a peak at 50 years old. Males had higher PPY than female dentists at the same age. The pattern of PPY was different between male and female dentists.
Galloyl benzamide-based compounds modulating tumour necrosis factor α-stimulated c-Jun N-terminal kinase and p38 mitogen-activated protein kinase signalling pathways
Authors: Leo Valentina , Stefanachi Angela , Nacci Carmela , Leonetti Francesco , de Candia Modesto , Carotti Angelo , Altomare Cosimo D , Montagnani Monica , Cellamare Saverio 
Published: June 2015

Abstract

Objectives
The aim of this work is to investigate whether and how two newly synthesized 3,4,5-trimethoxygalloyl-containing compounds 1 and 3 interfere with the mitogen-activated protein kinase (MAPK) signalling pathways involved in several pathological events, ranging from inflammatory diseases to cancer.

Methods
The effects on the phosphorylation of MAP kinases (c-Jun N-terminal kinases (JNKs), p38) and activation of nuclear factor-kappa B (NF-κB) pathways of 1 and its 1H-indazole-containing analogue 3, compared with those elicited by the known Adenosine Triphosphate (ATP)-competitive JNK inhibitor SP600125, were evaluated through Western blot analysis in murine fibroblasts NIH-3T3 and human endothelial cells EA.hy926 acutely treated with tumour necrosis factor-α (TNF-α). Their effects on cell viability were also assessed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay.

Key findings
In cultured murine fibroblasts, 1 inhibited JNK signalling with a different mechanism from SP600125. It reduced c-Jun phosphorylation without altering phosphorylation levels of JNK protein. Compound 3, showing a profile similar to SP600125, inhibited JNK phosphorylation and partially inhibited p38 MAPK at 50 μm concentration. Compound 3 and SP600125 showed similar behaviour in both cell cultures. In contrast, compound 1 in EA.hy926 cells significantly interfered with JNK phosphorylation, did not decrease phosphorylation of c-Jun (Ser73), whereas significantly suppressed phosphorylation of p38 MAPK and reversed degradation of NF-κB signalling components.

Conclusions
3,4,5-Trimethoxygalloyl-based compounds 1 and 3, which did not show significant cell toxicity, modulate the TNF-α-induced activation of MAPK signalling, mainly inhibiting phosphorylation of JNK, c-Jun and p38 MAPK, in murine fibroblasts and human endothelial cells with different MAPK selectivity profiles. These compounds deserve future investigation in specific cell-based disease models and in-vivo pharmacology.
1118-20, an indazole diarylurea compound, inhibits hepatocellular carcinoma HepG2 proliferation and tumour angiogenesis involving Wnt/β-catenin pathway and receptor tyrosine kinases
Authors: Lu Yu-Yin , Wang Jing-Jing , Zhang Xin-Ke , Li Wen-Bao , Guo Xiu-Li 
Published: June 2015

Abstract

Objectives
Sorafenib is a first multi-kinase inhibitor and one of the most widely used small-molecule oral-targeted drugs. It has been widely used for the treatment of patients with advanced renal cell carcinoma and hepatocellular carcinoma. However, some common adverse effects of sorafenib may impact quality of life. In this study, we evaluated the inhibitory effect on the growth of hepatocellular carcinoma cell line (HepG2) and suppression on angiogenesis of 1118-20, a newly synthesized indazole diarylurea compound.

Methods
We evaluated the activity of 1118-20 against HepG2 cells growth and tumour angiogenesis of human umbilical vascular endothelial cell line (HUVECs) with sorafenib as a positive control.

Key findings
The cytotoxic efficacy of 1118-20 was higher in HepG2 cells than human normal liver cell line (HL-7702). 1118-20 significantly suppressed the proliferation of HepG2 cells by apoptosis induction via Bcl-2 family-mediated mitochondria pathway and inhibition on Wnt/β-catenin signalling pathway. 1118-20 effectively blunt the motility and migration, and inhibited the formation of capillary tube of HUVECs through suppression of angiogenic factors expression. Moreover, the results indicated that 1118-20 exerted higher efficacy than sorafenib on tumour cell proliferation and angiogenesis.

Conclusions
Compared with its parent drug sorafenib, we found that 1118-20 possessed more potential on inhibition of angiogenesis and cancer cells growth. Inhibitory effect of 1118-20 on non-tumour liver cell HL-7702 was lower than that on hepatoma carcinoma cell HepG2. These results suggest that 1118-20 is a promising candidate compound that could be developed to a potent anticancer agent.
The use of water-soluble mucoadhesive gels for the intravesical delivery of epirubicin to the bladder for the treatment of non-muscle-invasive bladder cancer
Authors: Chatta Dani , Cottrell Lewis , Burnett Bruce , Laverty Garry , McConville Christopher 
Published: June 2015

Abstract

Objectives
To develop an epirubicin-loaded, water-soluble mucoadhesive gels that have the correct rheological properties to facilitate their delivery into the bladder via a catheter, while allowing for their spread across the bladder wall with limited expansion of the bladder and increasing the retention of epirubicin in the bladder and flushing with urine.

Methods
Epirubicin-loaded hydroxyl ethyl cellulose (HEC) and hydroxy propyl methyl cellulose (HPMC) gels were manufactured and tested for their rheological properties. Their ability to be pushed through a catheter was also assessed as was their in-vitro drug release, spreading in a bladder and retention of epirubicin after flushing with simulated urine.

Key findings
Epirubicin drug release was viscosity-dependent. The 1 and 1.5% HEC gels and the 1, 1.5 and 2% HPMC gels had the correct viscosity to be administered through a model catheter and spread evenly across the bladder wall under the pressure of the detrusor muscle. The epirubicin-loaded gels had an increased retention time in the bladder when compared with a standard intravesical solution of epirubicin, even after successive flushes with simulated urine.

Conclusion
The increased retention of epirubicin in the bladder by the HEC and HPMC gels warrant further investigation, using an in-vivo model, to assess their potential for use as treatment for non-muscle-invasive bladder cancer.
Immune system transcriptome in gingival tissues of young nonhuman primates
Authors: Gonzalez O. A. , Nagarajan R. , Novak M. J. , Orraca L. , Gonzalez‐Martinez J. A. , Kirakodu S. S. , Ebersole J. L. 
Published: June 2015

Background and ObjectiveYoung/adolescent humans harbor many microorganisms associated with periodontal disease in adults and show substantial gingival inflammatory responses. However, younger individuals do not demonstrate the soft‐ and hard‐tissue destruction that hallmark periodontitis.Material and MethodsThis study evaluated responses to the oral microbial ecology in gingival tissues from clinically healthy young Macaca mulatta (< 3 years of age) compared with older animals (5–23 years of age). RNA was isolated from the tissues and analyzed for the transcriptome using the Rhesus Macaque GeneChip (Affymetrix).ResultsGlobal transcriptional profiling of four age groups revealed a subset of 159 genes that were differentially expressed across at least one of the age comparisons. Correlation metrics generated a relevance network abstraction of these genes. Partitioning of the relevance network revealed seven distinct communities comprising functionally related genes associated with host inflammatory and immune responses. A group of genes was identified that were selectively increased/decreased or positively/negatively correlated with gingival profiles in the animals. A principal components analysis created metagenes of expression profiles for classifying the 23 animals.ConclusionThe results provide novel system‐level insights into gene‐expression differences in gingival tissues from healthy young animals, weighted toward host responses associated with anti‐inflammatory biomolecules or those linked with T‐cell regulation of responses. The combination of the regulated microenvironment may help to explain the apparent ‘resistance’ of younger individuals to developing periodontal disease.