bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Arabidopsis homeobox gene SHOOT MERISTEMLESS has cellular and meristem‐organisational roles with differential requirements for cytokinin and CYCD3 activity
Authors: Scofield Simon , Dewitte Walter , Nieuwland Jeroen , Murray James A.H. 
Published: April 2013

SummaryThe Arabidopsis class‐1 KNOX gene SHOOT MERISTEMLESS (STM) encodes a homeodomain transcription factor essential for shoot apical meristem (SAM) formation and sustained activity. STM activates cytokinin (CK) biosynthesis in the SAM, but the extent to which STM function is mediated through CK is unclear. Here we show that STM inhibits cellular differentiation and endoreduplication, acting through CK and the CK‐inducible CYCD3 cell cycle regulators, establishing a mechanistic link to cell cycle control which provides sustained mitotic activity to maintain a pool of undifferentiated cells in the SAM. Equivalent functions are revealed for the related KNOX genes KNAT1/BP and KNAT2 through ectopic expression. STM is also required for proper meristem organisation and can induce de novo meristem formation when expressed ectopically, even when CK levels are reduced or CK signaling is impaired. This function in meristem establishment and organisation can be replaced by KNAT1/BP, but not KNAT2, despite its activation of CK responses, suggesting that promotion of CK responses alone is insufficient for SAM organisation. We propose that STM has dual cellular and meristem‐organisational functions that are differentially represented in the class‐1 KNOX gene family and have differing requirements for CK and CYCD3.
Copy number variation in potato – an asexually propagated autotetraploid species
Authors: Iovene Marina , Zhang Tao , Lou Qunfeng , Buell C. Robin , Jiang Jiming 
Published: April 2013

SummaryCopy number variation (CNV) has been revealed as a significant contributor to the genetic variation in humans. Although CNV has been reported in several model animal and plant species, the presence of CNV and its biological impact in polyploid species has not yet been documented. We conducted a fluorescence in situ hybridization (FISH)‐based CNV survey in potato, a vegetatively propagated autotetraploid species (2n = 4x = 48). We conducted FISH analysis using 18 randomly selected potato bacterial artificial chromosome (BAC) clones in a set of 16 potato cultivars with diverse breeding backgrounds. Six BACs (33%) with insert sizes of 137–145 kb were found to be associated with large CNV events detectable at the cytological level. We demonstrate that the large CNVs associated with two specific BACs (RH102I10 and RH83C08) were widespread among potato cultivars developed in North America and Europe. We measured the transcript abundance of four genes associated with the CNV spanned by BAC RH102I10. All four genes displayed a dosage effect in transcription. Although potato is vegetatively propagated, we observed that female gametes lacking the RH102I10‐associated CNV were inferior to those with at least one copy of this CNV, indicating that the RH102I10‐associated CNV can impact on the growth and development of the potato plants. Our results show that CNV is highly abundant in the potato genome and may play a significant role in genetic variation of this important food crop.
Severe Skin Toxicity in Pediatric Oncology Patients Treated with Voriconazole and Concomitant Methotrexate
Authors: van Hasselt Johan G. C. , van Eijkelenburg Natasha K. A. , Huitema Alwin D. R. , Schellens Jan H. M. , Schouten-van Meeteren Antoinette Y. N. 
Published: April 2013

ABSTRACT
We report the occurrence of skin toxicities in pediatric oncology patients on concomitant treatment with voriconazole and methotrexate (MTX). Of 23 patients who received this combination, 11 patients suffered from cheilitis and/or photosensitivity. In contrast, only in 1 of 9 patients who received voriconazole without MTX was photosensitivity observed. A mechanism of action was not able to be identified. We describe two cases with severe skin toxicities. Caution is warranted when using voriconazole and concomitant MTX.
In Vitro
Activity of Novel Gyrase Inhibitors against a Highly Resistant Population of Pseudomonas aeruginosa
Authors: Tessier Pamela R. , Nicolau David P. 
Published: April 2013

ABSTRACT

The activity of five novel gyrase inhibitors was evaluated against 303 nonduplicate
Pseudomonas aeruginosa
strains collected from 53 North American institutions. The most active compound, GP-2, displayed MIC
50
and MIC
90
values of 1 and 2 μg/ml, respectively. Cross-resistance to other commercially available antipseudomonal compounds was not evident, as no major change was observed in the gyrase inhibitor MIC distribution when stratified by nonsusceptible phenotypes, including the fluoroquinolones and those isolates classified as multidrug resistant (MDR).
Comparison of a High-Throughput High-Content Intracellular Leishmania donovani Assay with an Axenic Amastigote Assay
Authors: De Rycker Manu , Hallyburton Irene , Thomas John , Campbell Lorna , Wyllie Susan , Joshi Dhananjay , Cameron Scott , Gilbert Ian H. , Wyatt Paul G. , Frearson Julie A. , Fairlamb Alan H. , Gray David W. 
Published: April 2013

ABSTRACTVisceral leishmaniasis is a neglected tropical disease with significant health impact. The current treatments are poor, and there is an urgent need to develop new drugs. Primary screening assays used for drug discovery campaigns have typically used free-living forms of theLeishmaniaparasite to allow for high-throughput screening. Such screens do not necessarily reflect the physiological situation, as the disease-causing stage of the parasite resides inside human host cells. Assessing the drug sensitivity of intracellular parasites on scale has recently become feasible with the advent of high-content screening methods. We describe here a 384-well microscopy-based intramacrophageLeishmania donovaniassay and compare it to an axenic amastigote system. A panel of eight reference compounds was tested in both systems, as well as a human counterscreen cell line, and our findings show that for most clinically used compounds both axenic and intramacrophage assays report very similar results. A set of 15,659 diverse compounds was also screened using both systems. This resulted in the identification of seven new antileishmanial compounds and revealed a high false-positive rate for the axenic assay. We conclude that the intramacrophage assay is more suited as a primary hit-discovery platform than the current form of axenic assay, and we discuss how modifications to the axenic assay may render it more suitable for hit-discovery.
Microdialysis Study of Cefotaxime Cerebral Distribution in Patients with Acute Brain Injury
Authors: Dahyot-Fizelier Claire , Frasca Denis , Grégoire Nicolas , Adier Christophe , Mimoz Olivier , Debaene Bertrand , Couet William , Marchand Sandrine 
Published: April 2013

ABSTRACT

Central nervous system (CNS) antibiotic distribution was described mainly from cerebrospinal fluid data, and only few data exist on brain extracellular fluid concentrations. The aim of this study was to describe brain distribution of cefotaxime (2 g/8 h) by microdialysis in patients with acute brain injury who were treated for a lung infection. Microdialysis probes were inserted into healthy brain tissue of five critical care patients. Plasma and unbound brain concentrations were determined at steady state by high-performance liquid chromatography.
In vivo
recoveries were determined individually using retrodialysis by drug. Noncompartmental and compartmental pharmacokinetic analyses were performed. Unbound cefotaxime brain concentrations were much lower than corresponding plasma concentrations, with a mean cefotaxime unbound brain-to-plasma area under the curve ratio equal to 26.1 ± 12.1%. This result was in accordance with the brain input-to-brain output clearances ratio (CL
in,brain
/CL
out,brain
). Unbound brain concentrations were then simulated at two dosing regimens (4 g every 6 h or 8 h), and the time over the MICs (T>MIC) was estimated for breakpoints of susceptible and resistant
Streptococcus pneumoniae
strains. T>MIC was higher than 90% of the dosing interval for both dosing regimens for susceptible strains and only for 4 g every 6 h for resistant ones. In conclusion, brain distribution of cefotaxime was well described by microdialysis in patients and was limited.
The Emergence of Human Coronavirus EMC: How Scared Should We Be?
Authors: Chan Renee W. Y. , Poon Leo L. M. 
Published: April 2013

ABSTRACT

A novel betacoronavirus, human coronavirus (HCoV-EMC), has recently been detected in humans with severe respiratory disease. Further characterization of HCoV-EMC suggests that this virus is different from severe acute respiratory syndrome coronavirus (SARS-CoV) because it is able to replicate in multiple mammalian cell lines and it does not use angiotensin-converting enzyme 2 as a receptor to achieve infection. Additional research is urgently needed to better understand the pathogenicity and tissue tropism of this virus in humans. In their recent study published in
mBio
, Kindler et al. shed some light on these important topics (E. Kindler, H. R. Jónsdóttir, M. Muth, O. J. Hamming, R. Hartmann, R. Rodriguez, R. Geffers, R. A. Fouchier, C. Drosten, M. A. Müller, R. Dijkman, and V. Thiel, mBio 4[1]:e00611-12, 2013). These authors report the use of differentiated pseudostratified human primary airway epithelial cells, an
in vitro
model with high physiological relevance to the human airway epithelium, to characterize the cellular tropism of HCoV-EMC. More importantly, the authors demonstrate the potential use of type I and type III interferons (IFNs) to control viral infection.
Right ventricular ejection fraction during exercise as a predictor of mortality in patients awaiting lung transplantation: a cohort study
Authors: Selimovic Nedim , Andersson Bert , Bech-Hanssen Odd , Lomsky Milan , Riise Gerdt C , Rundqvist Bengt 
Published: April 2013

ObjectiveThe occurrence of right ventricular dysfunction is a well-known indicator of poor prognosis in patients with chronic cardiopulmonary disease. The role of right ventricular ejection fraction (RVEF) at rest and during exercise as predictors of outcome in patients awaiting lung transplantation (LTx) is unclear.DesignWe performed a retrospective analysis of lung transplant candidates who had undergone equilibrium radionuclide angiography (ERNA), to determine baseline and exercise RVEF. Lung function, gas exchange and pulmonary haemodynamics were also assessed.Patients and main outcome measures152 patients (mean age 47±11 years; 59% women) were included in the study. Primary endpoint was death on the waiting list for LTx. Main diagnoses were α-1 antitrypsin deficiency (n=35), chronic obstructive pulmonary disease (n=41), cystic fibrosis (n=10), interstitial lung disease (n=34) and pulmonary arterial hypertension (n=32). Twenty-five patients died (16, 4%). LTx was performed in 121 patients. The mean RVEF at rest was equal to mean RVEF during exercise (38±12%). In univariate analysis RVEF at rest, RVEF during exercise, heart rate and forced volume capacity (FVC) % of predicted were factors significantly associated with risk of death. In multivariate analysis RVEF during exercise and FVC% of predicted were independent predictors of death.ConclusionsIn lung transplant candidates, right ventricular function during exercise is a stronger predictor of outcome than right ventricular function at rest. RVEF during exercise assessed by ERNA could be incorporated into priority-based allocation algorithms for LTx.
Amputations and socioeconomic position among persons with diabetes mellitus, a population-based register study
Authors: Venermo Maarit , Manderbacka Kristiina , Ikonen Tuija , Keskimäki Ilmo , Winell Klas , Sund Reijo 
Published: April 2013

ObjectiveLow socioeconomic position is a known health risk. Our study aims to evaluate the association between socioeconomic position (SEP) and lower limb amputations among persons with diabetes mellitus.DesignPopulation-based register study.SettingFinland, nationwide individual-level data.ParticipantsAll persons in Finland with any record of diabetes in the national health and population registers from 1991 to 2007 (FinDM II database).MethodsThree outcome indicators were measured: the incidence of first major amputation, the ratio of first minor/major amputations and the 2-year survival with preserved leg after the first minor amputation. SEP was measured using income fifths. The data were analysed using Poisson and Cox regression as well as age-standardised ratios.ResultsThe risk ratio of the first major amputation in the lowest SEP group was 2.16 (95% CI 1.95 to 2.38) times higher than the risk in the highest SEP group (p<0.001). The incidence of first major amputation decreased by more than 50% in all SEP groups from 1993 to 2007, but there was a stronger relative decrease in the highest compared with the lowest SEP group (p=0.0053). Likewise, a clear gradient was detected in the ratio of first minor/major amputations: the higher the SEP group, the higher the ratio. After the first minor amputation, the 2-year and 10-year amputation-free survival rates were 55.8% and 9.3% in the lowest and 78.9% and 32.3% in the highest SEP group, respectively.ConclusionsAccording to all indicators used, lower SEP was associated with worse outcomes in the population with diabetes. Greater attention should be paid to prevention of diabetes complications, adherence to treatment guidelines and access to the established pathways for early expert assessment when diabetic complications arise, with a special attention to patients from lower SEP groups.
Haemodynamic and structural correlates of the first and second heart sounds in pulmonary arterial hypertension: an acoustic cardiography cohort study
Authors: Chan William , Woldeyohannes Maryam , Colman Rebecca , Arand Patti , Michaels Andrew D , Parker John D , Granton John T , Mak Susanna 
Published: April 2013

ObjectiveTo examine the relationship between acoustic characteristics of the first and second heart sounds (S1 and S2) and underlying cardiac structure and haemodynamics in patients with isolated pulmonary arterial hypertension (PAH) and controls.DesignProspective multicentre cohort study.SettingTertiary referral and community hospitals.ParticipantsWe prospectively evaluated 40 PAH patients undergoing right-heart catheterisation with contemporaneous digital acoustic cardiography (intensity and complexity) and two-dimensional transthoracic echocardiography. To normalise for differences in body habitus, acoustic variables were also expressed as a ratio (S2/S1). 130 participants (55 also had haemodynamic and/or echocardiographic assessment) without clinical or haemodynamic evidence of PAH or congestive heart failure acted as controls.ResultsPatients with PAH had higher mean pulmonary artery pressure (mPA; 40±13 vs 16±4 mm Hg, p<0.0001) and pulmonary vascular resistance (9±6 vs 1±1 Wood Units, p<0.0001) compared with controls, but cardiac index and mean pulmonary capillary wedge pressure were similar. More PAH patients had evidence of right ventricular (RV) dilation (50% vs 19%) and RV systolic dysfunction (41% vs 9%) in the moderate–severe range (all p<0.05). Compared with controls, the acoustic profiles of PAH patients were characterised by increased S2 complexity, S2/S1 complexity and S2/S1 intensity (all p<0.05). In the PAH cohort, S2 complexity was inversely related to S1 complexity. mPA was the only independent multivariate predictor of S2 complexity. The severity of RV enlargement and systolic impairment had reciprocal effects on the complexity of S2 (increased) and S1 (decreased). Decreased S1 complexity was also related to evidence of a small left ventricular cavity.ConclusionsAcoustic characteristics of both S1 and S2 are related to the severity of PAH and are associated with RV enlargement and systolic dysfunction. The reciprocal relationship between S2 and S1 complexity may also reflect the underlying ventricular interaction associated with PAH.
Recruiting ethnic minority participants to a clinical trial: a qualitative study
Authors: MacNeill Virginia , Nwokoro Chinedu , Griffiths Chris , Grigg Jonathan , Seale Clive 
Published: April 2013

ObjectivesTo compare the motives and experiences of different ethnic groups participating in a randomised double blind placebo-controlled trial of montelukast in preschool wheeze, and to assess parents’ or guardians’ understanding of trial procedures and their implications, including the collection of genetic material.DesignQualitative interviews with parents or guardians.SettingInterviews occurred in the homes of London children recruited to a national multicentre clinical trial following primary and secondary care attendance with wheeze.Participants42 parents (20 of Bangladeshi origin, 10 white UK, 12 other ethnicities) of preschool children enrolled in a clinical trial.ResultsBangladeshi families were relatively reluctant to participate in the qualitative study, despite strong engagement with the parent study. Anxiety related to wheezing was a common primary motive for trial enrolment. Parents viewed the trial as a route to improved treatment. Verbal delivery of trial information appeared more effective than study literature, especially for Bangladeshi families, with low parental literacy and high levels of trust in medical professionals potential contributors to this effect. All ethnic groups expressed a low understanding and/or retention of essential study concepts such as randomisation and genetic testing.ConclusionsBangladeshi families are particularly motivated to participate in clinical trials despite variable comprehension of study concepts. This motivation is more strongly contingent on strong researcher-subject rapport than on the quality of study literature. Trial teams seeking to recruit from South Asian populations should emphasise face-to-face verbal explanation of trial concepts and procedures and consider modified trial literature.
Midlife dietary patterns and mortality in the population-based study of Swedish twins
Authors: Granic A , Andel R , Dahl A K , Gatz M , Pedersen N L 
Published: April 2013

AbstractBackgroundWe examined midlife dietary patterns in relation to (1) sociodemographic and health-related characteristics and (2) survival.MethodsA two-step cluster analysis of a 12-item food questionnaire was used to derive dietary patterns in a cohort of 16 649 members of the Swedish Twin Registry, a prospective, population-based study of twins. The average age at baseline (1967) was 55.5 years; the follow-up for all-cause mortality extended until 2011 (26.8±12.35 years or 345 127 person-years) via death records.ResultsFour dietary patterns (classes) distinguishable by demographic and health characteristics emerged: Moderate Intake and Starch Diet (Class 1), Moderate Intake Diet with Low Flour-Based Foods (Class 2), Meat and Starch Diet (Class 3) and Low Meat Intake Diet (Class 4). Membership in Class 3 was associated with 7% increased risk of mortality compared with Class 2 independent of baseline age, cohort, sex and body mass index. These results were mostly explained by sociodemographic and lifestyle factors. When follow-up was restricted to those in the study for 20+ years, both Classes 1 and 3 conferred increased risk of mortality compared with Class 2, independent of covariates. Analyses conducted within twin pairs revealed similar results.ConclusionsMidlife diet over-represented by meat and starch-based foods may increase the risk of mortality, whereas the diet low in starch may be beneficial. These results appear to be independent of factors shared by twins, as well as at least partially a function of social and lifestyle factors, particularly marital status and smoking.
THE BOUNDARY ELEMENT METHOD
Authors: MUKHERJEE SUBRATA , LIU YIJUN 
Published: April 2013

The boundary element method (BEM), along with the finite element and finite difference methods, is commonly used to carry out numerical simulations in a wide variety of subjects in science and engineering. The BEM, rooted in classical mathematics of integral equations, started becoming a useful computational tool around 50 years ago. Many researchers have worked on computational aspects of this method during this time.This paper presents an overview of the BEM and related methods. It has three sections. The first, relatively short section, presents the governing equations for classical applications of the BEM in potential theory, linear elasticity and acoustics. The second describes specialized applications in bodies with thin features including micro-electro-mechanical systems (MEMS). The final section addresses current research. It has three subsections that present the boundary contour, boundary node and fast multipole methods (BCM, BNM and FMM), respectively. Several numerical examples are included in the second and third sections of this paper.
Prognostic Significance of Cardiac Magnetic Resonance Imaging in Children With Pulmonary Hypertension
Authors: Moledina Shahin , Pandya Bejal , Bartsota Margarita , Mortensen Kristian H. , McMillan Merlin , Quyam Sadia , Taylor Andrew M. , Haworth Sheila G. , Schulze-Neick Ingram , Muthurangu Vivek 
Published: April 2013

Background—
There are very few validated prognostic markers in pediatric pulmonary hypertension. Cardiac MRI is a useful, noninvasive method for determining prognosis in adults. The present study is the first to assess its prognostic value in children.

Methods and Results—

A total of 100 children with pulmonary hypertension (median, 10.4 years; range, 0.5–17.6 years) were evaluated (idiopathic, n=60; repaired congenital heart disease, n=22; miscellaneous, n=18). In all patients, ventricular volumes and great vessel flow were measured. Volumetric data were obtained using retrospectively gated cine imaging (n=37) or real-time imaging (n=63), depending on the patient’s ability to hold his or her breath. During a median follow-up of 1.9 years, 11 patients died and 3 received lung transplantation. Of the cardiac MR parameters measured, right ventricular ejection fraction and left ventricular stroke volume index were most strongly predictive of survival on univariate analysis (2.6- and 2.5-fold increase in mortality for every 1-SD decrease, respectively;
P
<0.05). These results were reflected in good separation of tertile-based Kaplan-Meier survival curves for these variables.

Conclusions—
Cardiac MR measures correlate with clinical status and prognosis in children with pulmonary hypertension. Cardiac MR is feasible and may be useful in clinical decision making in pediatric pulmonary hypertension.