bluuebunny/crossref_metadata_2025_split huggingface dataset:
Silencing a key gene of the common symbiosis pathway in Nicotiana attenuata specifically impairs arbuscular mycorrhizal infection without influencing the root‐associated microbiome or plant growth
Authors: Groten Karin , Nawaz Ali , Nguyen Nam H. T. , Santhanam Rakesh , Baldwin Ian T. 
Published: April 2015

AbstractWhile the biochemical function of calcium and calmodulin‐dependent protein kinase (CCaMK) is well studied, and plants impaired in the expression of CCaMK are known not to be infected by arbuscular mycorrhizal fungi (AMF) in glasshouse studies, the whole‐plant and ecological consequences of CCaMK silencing are not well understood. Here we show that three independently transformed lines of Nicotiana attenuata plants silenced in CCaMK (irCCaMK) are neither infected by Rhizophagus irregularis in the glasshouse nor by native fungal inoculum in the field. The overall fungal community of field‐grown roots did not differ significantly among empty vector (EV) and the transgenic lines, and the bacterial communities only showed minor differences, as revealed by the alpha‐diversity parameters of bacterial OTUs, which were higher in EV plants compared with two of the three transformed lines, while beta‐diversity parameters did not differ. Furthermore, growth and fitness parameters were similar in the glasshouse and field. Herbivory‐inducible and basal levels of salicylic acid, jasmonic acid and abscisic acid did not differ among the genotypes, suggesting that activation of the classical defence pathways are not affected by CCaMK silencing. Based on these results, we conclude that silencing of CCaMK has few, if any, non‐target effects.
The Impact of Limited Supply on a Firm's Bundling Strategy
Authors: Cao Qingning , Stecke Kathryn E. , Zhang Jun 
Published: April 2015

A firm's two‐product bundling decision is examined when the supply of one product is limited and consumer valuations are normally distSteckeributed. The firm can choose to sell products separately and/or through a bundle. We find that the impact of limited supply on a firm's bundling decision depends on the correlation between the consumer valuations of the two products as well as the symmetry level of the two products in terms of their attractiveness (how much they are valued by consumers). When the valuation correlation is high and the symmetry level of the two products is low, limited supply can drive bundling. When the valuation correlation is low or the symmetry level is high, limited supply can drive no bundling. When the attractiveness of both products are low or the valuation correlation is very high, limited supply has no impact on a firm's bundling decision: The firm should not bundle for all supply levels. This study offers a new driver for product bundling: the limited supply of a product. The existing bundling literature suggests that a firm should bundle symmetric products that have a low consumer valuation correlation, when bundling is driven by consumer valuation heterogeneity reduction. In contrast, when bundling is driven by limited supply, a firm should bundle asymmetric products with a high consumer valuation correlation. The benefit of supply‐driven bundling depends on the severity of supply limitation. When supply limitation is moderate, bundling creates value by expanding the market of the less attractive product. When supply limitation is severe, bundling enables a firm to extract a higher margin from the less attractive product.
Meiotic recombination hotspots – a comparative view
Authors: Choi Kyuha , Henderson Ian R. 
Published: April 2015

SummaryDuring meiosis homologous chromosomes pair and undergo reciprocal genetic exchange, termed crossover. Meiotic recombination has a profound effect on patterns of genetic variation and is an important tool during crop breeding. Crossovers initiate from programmed DNA double‐stranded breaks that are processed to form single‐stranded DNA, which can invade a homologous chromosome. Strand invasion events mature into double Holliday junctions that can be resolved as crossovers. Extensive variation in the frequency of meiotic recombination occurs along chromosomes and is typically focused in narrow hotspots, observed both at the level of DNA breaks and final crossovers. We review methodologies to profile hotspots at different steps of the meiotic recombination pathway that have been used in different eukaryote species. We then discuss what these studies have revealed concerning specification of hotspot locations and activity and the contributions of both genetic and epigenetic factors. Understanding hotspots is important for interpreting patterns of genetic variation in populations and how eukaryotic genomes evolve. In addition, manipulation of hotspots will allow us to accelerate crop breeding, where meiotic recombination distributions can be limiting.
A neural circuitry that emphasizes spinal feedback generates diverse behaviours of human locomotion
Authors: Song Seungmoon , Geyer Hartmut 
Published: April 2015

Key points
It is often assumed that central pattern generators, which generate rhythmic patterns without rhythmic inputs, play a key role in the spinal control of human locomotion.
We propose a neural control model in which the spinal control generates muscle stimulations mainly through integrated reflex pathways with no central pattern generator.
Using a physics‐based neuromuscular human model, we show that this control network is sufficient to compose steady and transitional 3‐D locomotion behaviours, including walking and running, acceleration and deceleration, slope and stair negotiation, turning, and deliberate obstacle avoidance.
The results suggest feedback integration to be functionally more important than central pattern generation in human locomotion across behaviours.
In addition, the proposed control architecture may serve as a guide in the search for the neurophysiological origin and circuitry of spinal control in humans.
AbstractNeural networks along the spinal cord contribute substantially to generating locomotion behaviours in humans and other legged animals. However, the neural circuitry involved in this spinal control remains unclear. We here propose a specific circuitry that emphasizes feedback integration over central pattern generation. The circuitry is based on neurophysiologically plausible muscle‐reflex pathways that are organized in 10 spinal modules realizing limb functions essential to legged systems in stance and swing. These modules are combined with a supraspinal control layer that adjusts the desired foot placements and selects the leg that is to transition into swing control during double support. Using physics‐based simulation, we test the proposed circuitry in a neuromuscular human model that includes neural transmission delays, musculotendon dynamics and compliant foot–ground contacts. We find that the control network is sufficient to compose steady and transitional 3‐D locomotion behaviours including walking and running, acceleration and deceleration, slope and stair negotiation, turning, and deliberate obstacle avoidance. The results suggest feedback integration to be functionally more important than central pattern generation in human locomotion across behaviours. In addition, the proposed control architecture may serve as a guide in the search for the neurophysiological origin and circuitry of spinal control in humans.
Implementing a structured education program for children with diabetes: lessons learnt from an integrated process evaluation
Authors: Sawtell Mary , Jamieson Liz , Wiggins Meg , Smith Felicity , Ingold Anne , Hargreaves Katrina , Khatwa Meena , Brooks Lucy , Thompson Rebecca , Christie Deborah 
Published: April 2015

BackgroundThere is recognition of an urgent need for clinic-based interventions for young people with type 1 diabetes mellitus that improve glycemic control and quality of life. The Child and Adolescent Structured Competencies Approach to Diabetes Education (CASCADE) is a structured educational group program, using psychological techniques, delivered primarily by diabetes nurses. Composed of four modules, it is designed for children with poor diabetic control and their parents. A mixed methods process evaluation, embedded within a cluster randomized control trial, aimed to assess the feasibility, acceptability, fidelity, and perceived impact of CASCADE.Methods28 pediatric diabetes clinics across England participated and 362 children aged 8–16 years, with type 1 diabetes and a mean glycosylated hemoglobin (HbA1c) of 8.5 or above, took part. The process evaluation used a wide range of research methods.ResultsOf the 180 families in the intervention group, only 55 (30%) received the full program with 53% attending at least one module. Only 68% of possible groups were run. Staff found organizing the groups burdensome in terms of arranging suitable dates/times and satisfactory group composition. Some staff also reported difficulties in mastering the psychological techniques. Uptake, by families, was influenced by the number of groups run and by school, work and other commitments. Attendees described improved: family relationships; knowledge and understanding; confidence; motivation to manage the disease. The results of the trial showed that the intervention did not significantly improve HbA1c at 12 or 24 months.ConclusionsClinic-based structured group education delivered by staff using psychological techniques had perceived benefits for parents and young people. Staff and families considered it a valuable intervention, yet uptake was poor and the burden on staff was high. Recommendations are made to inform issues related to organization, design, and delivery in order to potentially enhance the impact of CASCADE and future programs.Current Controlled TrialsISRCTN52537669.
Does quality of life improve in octogenarians following cardiac surgery? A systematic review
Authors: Abah Udo , Dunne Mike , Cook Andrew , Hoole Stephen , Brayne Carol , Vale Luke , Large Stephen 
Published: April 2015

ObjectivesCurrent outcome measures in cardiac surgery are largely described in terms of mortality. Given the changing demographic profiles and increasingly aged populations referred for cardiac surgery this may not be the most appropriate measure. Postoperative quality of life is an outcome of importance to all ages, but perhaps particularly so for those whose absolute life expectancy is limited by virtue of age. We undertook a systematic review of the literature to clarify and summarise the existing evidence regarding postoperative quality of life of older people following cardiac surgery. For the purpose of this review we defined our population as people aged 80 years of age or over.MethodsA systematic review of MEDLINE, EMBASE, Cochrane Library, trial registers and conference abstracts was undertaken to identify studies addressing quality of life following cardiac surgery in patients 80 or over.ResultsForty-four studies were identified that addressed this topic, of these nine were prospective therefore overall conclusions are drawn from largely retrospective observational studies. No randomised controlled data were identified.ConclusionsOverall there appears to be an improvement in quality of life in the majority of elderly patients following cardiac surgery, however there was a minority in whom quality of life declined (8–19%). There is an urgent need to validate these data and if correct to develop a robust prediction tool to identify these patients before surgery. Such a tool could guide informed consent, policy development and resource allocation.
Public health implications of molecular point-of-care testing for chlamydia and gonorrhoea in remote primary care services in Australia: a qualitative study
Authors: Natoli L , Guy R J , Shephard M , Whiley D , Tabrizi S N , Ward J , Regan D G , Badman S G , Anderson D A , Kaldor J , Maher L 
Published: April 2015

ObjectivesWith accurate molecular tests now available for diagnosis of chlamydia and gonorrhoea (Chlamydia trachomatis(CT)/Neisseria gonorrhoeae(NG)) at the point-of-care (POC), we aimed to explore the public health implications (benefits and barriers) of their integration into remote primary care in Australia.MethodsQualitative interviews were conducted with a purposively selected group of 18 key informants reflecting sexual health, primary care, remote Aboriginal health and laboratory expertise.ResultsParticipants believed that POC testing may decrease community prevalence of sexually transmitted infections (STIs), and associated morbidity by reducing the time to treatment and infectious period and expediting partner notification. Also, POC testing could improve acceptability of STI testing, increase testing coverage and result in more targeted prescribing, thereby minimising the risk of antibiotic resistance. Conversely, some felt the immediacy of diagnosis could deter certain young people from being tested. Participants also noted that POC testing may reduce the completeness of communicable disease surveillance data given the current dependence on reporting from pathology laboratories. Others expressed concern about the need to maintain and improve the flow of NG antibiotic sensitivity data, already compromised by the shift to nucleic acid-based testing. This is particularly relevant to remote areas where culture viability is problematic.ConclusionsResults indicate a high level of support from clinicians and public health practitioners for wider access to CT/NG POC tests citing potential benefits, including earlier, more accurate treatment decisions and reductions in ongoing transmission. However, the data also highlight the need for new systems to avoid adverse impact on disease surveillance.Trial registration numberAustralian and New Zealand Clinical Trials Registry: ACTRN12613000808741.
The stability of weight status through the early to middle childhood years in Australia: a longitudinal study
Authors: Wheaton Nikita , Millar Lynne , Allender Steven , Nichols Melanie 
Published: April 2015

ObjectivesTo investigate the sociodemographic and behavioural factors associated with incidence, persistence or remission of obesity in a longitudinal sample of Australian children aged 4–10 years.SettingNationally representative Longitudinal Study of Australian Children (LSAC).ParticipantsThe sample for this analysis included all children in the Kinder cohort (aged 4–5 years at wave 1) who participated in all four waves of LSAC (wave 1, 2004, aged 4–5 years; wave 2, 2006, aged 6–7 years; wave 3, 2008, aged 8–9 years and wave 4, 2010, aged 10–11 years). Of the 4983 children who participated in the baseline (wave 1) survey, 4169 (83.7%) children completed all four waves of data collection.Primary and secondary outcome measuresMovement of children between weight status categories over time and individual-level predictors of weight status change (sociodemographic characteristics, selected dietary and activity behaviours).ResultsThe study found tracking of weight status across this period of childhood. There was an inverse association observed between socioeconomic position and persistence of overweight/obesity. Sugar-sweetened beverages and fruit and vegetable intake and screen time appeared to be important predictors of stronger tracking.ConclusionsOverweight and obesity established early in childhood tracks strongly to the middle childhood years in Australia, particularly among children of lower socioeconomic position and children participating in some unhealthy behaviour patterns.
Identification of stroke during the emergency call: a descriptive study of callers’ presentation of stroke
Authors: Berglund Annika , von Euler Mia , Schenck-Gustafsson Karin , Castrén Maaret , Bohm Katarina 
Published: April 2015

ObjectivesTo evaluate symptoms presented by the caller during emergency calls regarding stroke, and to assess if symptoms in the Face-Arm-Speech-Time Test (FAST) are related to identification of stroke.SettingEmergency calls to the Emergency Medical Communication Center (EMCC) concerning patients discharged with stroke diagnosis in a large teaching hospital in Stockholm, Sweden, in January–June 2011.ParticipantsThe emergency calls of 179 patients who arrived at hospital by ambulance, and who were discharged with a stroke diagnosis and consented to participate were included in the study.Outcome measuresFrequencies of stroke symptoms presented and a comparison of symptoms presented in calls with dispatch code stroke or other dispatch code.ResultsOf the 179 emergency calls analysed, 64% were dispatched as ‘Stroke’. FAST symptoms, that is, facial or arm weakness or speech disturbances, were presented in 64% of the calls and were spontaneously revealed in 90%. Speech disturbance was the most common problem (54%) in all calls, followed by fall/lying position (38%) and altered mental status (27%). For patients with dispatch codes other than stroke, the dominating problem presented was a fall or being in a lying position (66%), followed by speech disturbance (31%) and altered mental status (25%). Stroke-specific symptoms were more common in patients dispatched as stroke. FAST symptoms were reported in 80% of patients dispatched as stroke compared with 35% in those dispatched as something else.ConclusionsThis study implicates that fall/lying position and altered mental status could be considered as possible symptoms of stroke during an emergency call. Checking for FAST symptoms in these patients might uncover stroke symptoms. Future studies are needed to evaluate if actively asking for FAST symptoms in emergency calls presenting falls or a lying position can improve the identification of stroke.Trial registration numberStroke2010/703-31/2.
Influence of lifestyle on theFAIM2promoter methylation between obese and lean children: a cohort study
Authors: Wu Lijun , Zhao Xiaoyuan , Shen Yue , Huang Guimin , Zhang Meixian , Yan Yinkun , Hou Dongqing , Meng Linghui , Liu Junting , Cheng Hong , Mi Jie 
Published: April 2015

ObjectiveAn obesity-related gene, Fas apoptotic inhibitory molecule 2 (FAIM2), is regulated by nutritional state and the methylation levels of theFAIM2promoter are significantly associated with obesity. Lifestyle factors, such as sedentary behaviour and physical activity, might modify epigenetic patterns that have been related to obesity. Whether the molecular mechanisms by whichFAIM2affects obesity are involved in lifestyle is unclear. This study investigates the potential differences of theFAIM2promoter methylation with sedentary behaviour and physical activity in obese and lean children.DesignCohort study.SettingInstitute of Pediatrics in China.Participants59 obese cases and 39 lean controls aged 8–18 years recruited from a cross-sectional survey of children from Beijing in 2013.Primary and secondary outcome measuresTheFAIM2promoter methylation was quantified using the Sequenom MassARRAY platform. Sedentary behaviour and physical activity were investigated using a questionnaire. The influences of different lifestyles on methylation variations in obese and lean children were examined by multiple linear regression.ResultsThe methylation levels at seven CpG sites of theFAIM2promoter were significantly associated with sedentary behaviour, especially the methylation levels at site −975, site −413, sites −362 and −360, and sites −353 and −349 (p=0.00004, 0.00009, 0.0006 and 0.00005, respectively). There were significant differences between the methylation levels at four CpG sites in obese and lean participants with high or moderate physical activity level <150 min/week.ConclusionsThis study provides the first evidence that there are significant differences in the associations of theFAIM2promoter methylation with sedentary behaviour and physical activity between obese and lean children. Our results suggest that lifestyle may possibly be mediating the process of theFAIM2involved in obesity.
Advanced Glycation End-Products: A Biological Consequence of Lifestyle Contributing to Cancer Disparity
Authors: Turner David P. 
Published: April 2015

Abstract
Low income, poor diet, obesity, and a lack of exercise are interrelated lifestyle factors that can profoundly alter our biologic make up to increase cancer risk, growth, and development. We recently reported a potential mechanistic link between carbohydrate-derived metabolites and cancer, which may provide a biologic consequence of lifestyle that can directly affect tumor biology. Advanced glycation end-products (AGE) are reactive metabolites produced as a by-product of sugar metabolism. Failure to remove these highly reactive metabolites can lead to protein damage, aberrant cell signaling, increased stress responses, and decreased genetic fidelity. Critically, AGE accumulation is also directly affected by our lifestyle choices and shows a race-specific, tumor-dependent pattern of accumulation in cancer patients. This review will discuss the contribution of AGEs to the cancer phenotype, with a particular emphasis on their biologic links with the socioeconomic and environmental risk factors that drive cancer disparity. Given the potential benefits of lifestyle changes and the potential biologic role of AGEs in promoting cancer, opportunities exist for collaborations affecting basic, translational, epidemiologic, and cancer prevention initiatives. Cancer Res; 75(10); 1925–9. ©2015 AACR.
Myeloid-Derived Suppressor Cells as an Immune Parameter in Patients with Concurrent Sunitinib and Stereotactic Body Radiotherapy
Authors: Chen Hui-Ming , Ma Ge , Gildener-Leapman Neil , Eisenstein Samuel , Coakley Brian A. , Ozao Junko , Mandeli John , Divino Celia , Schwartz Myron , Sung Max , Ferris Robert , Kao Johnny , Wang Lu-Hai , Pan Ping-Ying , Ko Eric C. , Chen Shu-Hsia 
Published: April 2015

Abstract
Purpose: The clinical effects of sunitinib on human myeloid-derived suppressor cell (MDSC) subsets and correlation of the T-cell–mediated immune responses and clinical outcomes in patients with oligometastases treated by stereotactic body radiotherapy (SBRT) have been evaluated.
Experimental Design: The numbers of granulocytic and monocytic MDSC subsets, effector T cells, and regulatory T cells in the peripheral blood were evaluated pre- and post-sunitinib treatment and concurrent with SBRT. Correlations between MDSC, Treg, and T-cell responses and clinical outcomes were analyzed.
Results: Patients with oligometastases of various cancer types had elevated granulocytic MDSC and certain subsets of monocytic MDSC population. Sunitinib treatment resulted in a significant reduction in monocytic MDSC, phosphorylated STAT3, and arginase levels in monocytic MDSC (CD33+CD14+CD16+), and an increase in T-cell proliferative activity in cancer patients. Interestingly, the effects of sunitinib on reducing the accumulation and immune-suppressive function of MDSC were significantly correlated with Treg reduction, in responders but not in nonresponding patients. SBRT synergized the therapeutic effects of sunitinib, especially as related to decreased numbers of monocytic MDSC, Treg, and B cells, and augmented Tbet expression in primary CD4 and CD8 T cells. These effects were not observed in patients receiving radiation therapy alone. Most interestingly, the responders, defined by sunitinib-mediated reduction in CD33+CD11b+ myeloid cell populations, tend to exhibit improved progression-free survival and cause-specific survival.
Conclusions: Sunitinib treatment increased the efficacy of SBRT in patients with oligometastases by reversing MDSC and Treg-mediated immune suppression and may enhance cancer immune therapy to prevent tumor recurrence post-SBRT. Clin Cancer Res; 21(18); 4073–85. ©2015 AACR.