bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nonreciprocal complementation of KNOX gene function in land plants
Authors: Frangedakis Eftychios , Saint‐Marcoux Denis , Moody Laura A. , Rabbinowitsch Ester , Langdale Jane A. 
Published: November 2016

Summary

Class I KNOTTED‐LIKE HOMEOBOX (KNOX) proteins regulate development of the multicellular diploid sporophyte in both mosses and flowering plants; however, the morphological context in which they function differs.

In order to determine how Class I KNOX function was modified as land plants evolved, phylogenetic analyses and cross‐species complementation assays were performed.

Our data reveal that a duplication within the charophyte sister group to land plants led to distinct Class I and Class II KNOX gene families. Subsequently, Class I sequences diverged substantially in the nonvascular bryophyte groups (liverworts, mosses and hornworts), with moss sequences being most similar to those in vascular plants. Despite this similarity, moss mutants were not complemented by vascular plant KNOX genes. Conversely, the Arabidopsis brevipedicellus (bp‐9) mutant was complemented by the PpMKN2 gene from the moss Physcomitrella patens. Lycophyte KNOX genes also complemented bp‐9 whereas fern genes only partially complemented the mutant. This lycophyte/fern distinction is mirrored in the phylogeny of KNOX‐interacting BELL proteins, in that a gene duplication occurred after divergence of the two groups.

Together, our results imply that the moss MKN2 protein can function in a broader developmental context than vascular plant KNOX proteins, the narrower scope having evolved progressively as lycophytes, ferns and flowering plants diverged.
Immune reactivity after adenoviral‐mediated aquaporin‐1 cDNA transfer to human parotid glands
Authors: Alevizos I , Zheng C , Cotrim AP , Goldsmith CM , McCullagh L , Berkowitz T , Strobl SL , Malyguine A , Kopp WC , Chiorini JA , Nikolov NP , Neely M , Illei GG , Baum BJ 
Published: November 2016

ObjectivesThe purpose of this study was to examine the humoral and cellular immune reactivity to adenoviral vector (AdhAQP1) administration in the human parotid gland over the first 42 days of a clinical gene therapy trial.MethodsOf eleven treated subjects, five were considered as positive responders (Baum et al, 2012). Herein, we measured serum neutralizing antibody titers, circulating cytotoxic lymphocytes, and lymphocyte proliferation in peripheral blood mononuclear cells. Additionally, after adenoviral vector stimulation of lymphocyte proliferation, we quantified secreted cytokine levels.ResultsResponders showed little to modest immune reactivity during the first 42 days following gene transfer. Additionally, baseline serum neutralizing antibody titers to serotype 5‐adenovirus generally were not predictive of a subject's response to parotid gland administration of AdhAQP1. Cytokine profiling from activated peripheral blood mononuclear cells could not distinguish responders and non‐responders.ConclusionsThe data are the first to describe immune responses after adenoviral vector administration in a human parotid gland. Importantly, we found that modest (2–3 fold) changes in systemic cell‐mediated immune reactivity did not preclude positive subject responses to gene transfer. However, changes beyond that level likely impeded the efficacy of gene transfer.
Selective gene dosage by CRISPR‐Cas9 genome editing in hexaploid Camelina sativa
Authors: Morineau Céline , Bellec Yannick , Tellier Frédérique , Gissot Lionel , Kelemen Zsolt , Nogué Fabien , Faure Jean‐Denis 
Published: November 2016

AbstractIn many plant species, gene dosage is an important cause of phenotype variation. Engineering gene dosage, particularly in polyploid genomes, would provide an efficient tool for plant breeding. The hexaploid oilseed crop Camelina sativa, which has three closely related expressed subgenomes, is an ideal species for investigation of the possibility of creating a large collection of combinatorial mutants. Selective, targeted mutagenesis of the three delta‐12‐desaturase (FAD2) genes was achieved by CRISPR‐Cas9 gene editing, leading to reduced levels of polyunsaturated fatty acids and increased accumulation of oleic acid in the oil. Analysis of mutations over four generations demonstrated the presence of a large variety of heritable mutations in the three isologous CsFAD2 genes. The different combinations of single, double and triple mutants in the T3 generation were isolated, and the complete loss‐of‐function mutants revealed the importance of delta‐12‐desaturation for Camelina development. Combinatorial association of different alleles for the three FAD2 loci provided a large diversity of Camelina lines with various lipid profiles, ranging from 10% to 62% oleic acid accumulation in the oil. The different allelic combinations allowed an unbiased analysis of gene dosage and function in this hexaploid species, but also provided a unique source of genetic variability for plant breeding.
Everyday emotion word and personal pronoun use reflects dyadic adjustment among couples coping with breast cancer
Authors: KARAN ALEXANDER , WRIGHT ROBERT C. , ROBBINS MEGAN L. 
Published: November 2016

AbstractDyadic adjustment is integral for couples facing breast cancer; therefore, it is important to identify its everyday indicators. A total of 52 couples coping with breast cancer wore the Electronically Activated Recorder (EAR) for one weekend and completed the Dyadic Adjustment Scale to investigate how dyadic adjustment manifests in noncancer‐related word use. Multilevel models revealed that partners', rather than one's own, positive emotion words positively related to dyadic adjustment. Conversely, spouses' negative emotion words and patients' anger words were negatively related to dyadic adjustment. Furthermore, focus on spouses rather than patients (spouses “I” and patients “you”) positively related to dyadic adjustment. Results revealed that dyadic adjustment can be reflected in couples' everyday word use, serving as an objective indicator of marital quality.
Phenotypic and genetic characterization of Pseudomonas syringae strains associated with the recent citrus bacterial blast and bacterial black pit epidemics in Tunisia
Authors: Abdellatif E. , Kałużna M. , Janse J. D. , Sobiczewski P. , Helali F. , Lamichhane J. R. , Rhouma A. 
Published: November 2016

In the spring of 2012, symptoms of a disease resembling citrus blast and citrus black pit were observed in some orchards in Tunisia. The epidemic spread rapidly in the following years. Twenty‐four commercial citrus orchards from four Tunisian regions showing characteristic symptoms of bacterial diseases were surveyed during a 3‐year study. Eighty‐eight Pseudomonas‐like bacterial isolates were successfully obtained from the northeast and west of Tunisia. No isolates were recovered from the central region. Overall, 46 isolates were identified as Pseudomonas syringae pv. syringae and most of them showed similar phenotypic and genetic profiles. The virulence of three selected isolates differed from one plant cultivar to another as well as from the type of plant organ used for the inoculation. In a bioassay test, all isolates produced syringomycin, which was confirmed by molecular detection based on the syrB and syrD genes. Only EC122 possessed syrD but not syrB. DNA fingerprints, based on repetitive sequence‐based polymerase chain reaction (rep‐PCR) and PCR melting profile (PCR MP), were used to determine the potential genetic diversity among strains. Clustering of PCR MP fingerprinting data matched with rep‐PCR fingerprinting data. The generated distribution tree showed that Tunisian isolates were closely related to the citrus reference strain LMG5496. In contrast, EC112, isolated from citrus, and the almond isolate EC122 were distantly related to the type strain LMG1247T isolated from lilac. Such studies have not been reported until now for P. syringae from citrus.
Cryopreservation of feline oocytes by vitrification using commercial kits and slush nitrogen technique
Authors: Fernandez‐Gonzalez L , Jewgenow K 
Published: November 2016

ContentsAssisted reproductive techniques are a valuable tool for conservation breeding of endangered species. Cryopreservation methods are the basis of gamete banks, supporting genetic diversity preservation. Unfortunately, cryopreservation of feline oocytes is still considered an experimental technique. The aim of this study was to compare two commercial kits, with our protocol for vitrification of cat oocytes (IZW), which comprises a three‐step method with ethylene glycol, DMSO, fetal calf serum, trehalose and Ficoll PM‐70. Furthermore, we applied slush nitrogen (SN2) for ultra‐rapid freezing to improve survival rates. Cumulus–oocyte complexes were collected from domestic cat ovaries by slicing and vitrified at immature stage using Cryotop as storage device. Vit Kit® Freeze/Thaw (n = 89) showed the lowest maturation percentage obtained after warming (10.1%). A significant difference in maturation percentage of oocytes was found between Kitazato® kit (38.7%, n = 137) and IZW protocol (24.5%, n = 143). The cleavage after ICSI of warmed and matured oocytes (20.7% and 28.6%, respectively) and the morula percentage (18. 2% and 22.5%, respectively), however, did not reveal any significant difference between the two methods. Application of SN2 did not result in any improvement of oocytes’ cryopreservation. Maturation percentage of the oocytes vitrified by IZW method with SN2 (n = 144) decreased until 6.1%, without any cleavage after fertilization. For Kitazato® (n = 62), only 17.7% were able to undergo maturation and cleavage percentage dropped to 18.2%, not reaching morula stage. These data demonstrate that feline oocytes can be vitrified either by our IZW method or by commercial Kitazato® kit, but the use of SN2 is improving neither maturation nor cleavage percentages when combined with these procedures.
Center‐Periphery Bargaining in the Age of Democracy
Authors: Siroky David S. , Mueller Sean , Hechter Michael 
Published: November 2016

AbstractThis paper introduces the key concepts used in this special issue – center, periphery, and vertical bargaining – and inquires why some national groups within democratic states demand outright independence, while others mobilize for regional autonomy and still others settle for even less. It then specifies a theoretical framework that tries to explain cross‐sectional differences and temporal changes in both peripheral demands and central responses. The building blocks of that framework include cultural distinctiveness, credibility of the exit threat and central dependence on the periphery. As an empirical illustration, the paper discusses the case of the Bernese Jura in Switzerland, and then briefly introduces the contributions to this special issue.
Herbal medicines for the treatment of otitis media with effusion: a systematic review of randomised controlled trials
Authors: Son Mi Ju , Choi Songie , Kim Young-Eun , Kim Yun Hee 
Published: November 2016

ObjectivesThis systematic review aimed to assess the clinical evidence supporting the use of herbal medicines (HMs) for the treatment of otitis media with effusion (OME).DesignSystematic review and meta-analysis.Data sourcesMEDLINE, EMBASE, Cochrane Library, AMED, CINAHL and three trial registries were searched up to January 2015. We also searched five Korean medical databases (KoreaMed, RISS, OASIS, DBPIA and KISS) and three Chinese databases (CNKI, Wanfang and VIP).Study eligibility criteriaThis study included randomised clinical trials that reported the effects of HM for OME. The primary outcome was the complete resolution of OME at 2 or 3 months post randomisation. Secondary outcomes included the partial or complete resolution at all possible time points and hearing test. Three authors independently screened the titles and abstracts, selected studies and extracted the data relating to trial quality, characteristics and results.ResultsA total of 2141 potentially relevant studies were identified, of which 17 randomised clinical trials met our inclusion criteria. Most were evaluated as having a high or unclear risk of bias. Tongqiao tablets, Tongqiao huoxue decoctions and Tsumura-Saireito were associated with a lower complete or partial resolution rate when compared with conventional medicines (CMs) (p=0.02, p=0.0001, and p=0.04, respectively), and similar outcomes were observed with Huanglong tonger pills, Erzhang decoctions and Shenling baizhu powder when combined with CM versus CM alone (p<0.00001, p=0.02, and p=0.05, respectively). Tongqiao huoxue decoction plus CM appeared to be more effective than CM in terms of improving the pure tone threshold levels (p=0.0007). Tsumura-Saireito was found to affect the proportion of patients with normalised tympanometry (p=0.03).ConclusionsDespite some indications of potential symptom improvement, the evidence regarding the effectiveness and efficacy of HMs for OME is of poor quality and therefore inconclusive.Protocol registration numberCRD42013005430.
Traumatic brain injury in England and Wales: prospective audit of epidemiology, complications and standardised mortality
Authors: Lawrence T , Helmy A , Bouamra O , Woodford M , Lecky F , Hutchinson P J 
Published: November 2016

ObjectivesTo provide a comprehensive assessment of the management of traumatic brain injury (TBI) relating to epidemiology, complications and standardised mortality across specialist units.DesignThe Trauma Audit and Research Network collects data prospectively on patients suffering trauma across England and Wales. We analysed all data collected on patients with TBI between April 2014 and June 2015.SettingData were collected on patients presenting to emergency departments across 187 hospitals including 26 with specialist neurosurgical services, incorporating factors previously identified in the Ps14 multivariate logistic regression (Ps14n) model multivariate TBI outcome prediction model. The frequency and timing of secondary transfer to neurosurgical centres was assessed.ResultsWe identified 15 820 patients with TBI presenting to neurosurgical centres directly (6258), transferred from a district hospital to a neurosurgical centre (3682) and remaining in a district general hospital (5880). The commonest mechanisms of injury were falls in the elderly and road traffic collisions in the young, which were more likely to present in coma. In severe TBI (Glasgow Coma Score (GCS) ≤8), the median time from admission to imaging with CT scan is 0.5 hours. Median time to craniotomy from admission is 2.6 hours and median time to intracranial pressure monitoring is 3 hours. The most frequently documented complication of severe TBI is bronchopneumonia in 5% of patients. Risk-adjusted W scores derived from the Ps14nmodel indicate that no neurosurgical unit fell outside the 3 SD limits on a funnel plot.ConclusionsWe provide the first comprehensive report of the management of TBI in England and Wales, including data from all neurosurgical units. These data provide transparency and suggests equity of access to high-quality TBI management provided in England and Wales.
Prevalence and determinants of carotid plaque in the cross-sectional REFINE-Reykjavik study
Authors: Sturlaugsdottir Ran , Aspelund Thor , Bjornsdottir Gudlaug , Sigurdsson Sigurdur , Thorsson Bolli , Eiriksdottir Gudny , Gudnason Vilmundur 
Published: November 2016

ObjectiveCarotid plaque and intima-media thickness are non-invasive arterial markers that are used as surrogate end points for cardiovascular disease. The aim was to assess the prevalence and severity of carotid plaque, and examine its determinant risk factors and their association to the common carotid artery intima-media thickness (CCA-IMT) in a general population.MethodsWe examined 6524 participants aged 25–69 years in the population-based REFINE (Risk Evaluation For INfarct Estimates)-Reykjavik study. Plaques at the bifurcation and internal carotid arteries were evaluated. Mean CCA-IMT was measured in the near and far walls of the common carotid arteries.ResultsThe prevalence of minimal, moderate and severe plaque was 35.0%, 8.9% and 1.1%, respectively, and the mean CCA-IMT was 0.73 (SD 0.14) mm. Age, sex, smoking and type 2 diabetes mellitus (T2DM) were the strongest risk factors associated with plaque, followed by systolic blood pressure, total cholesterol, body mass index and family history of myocardial infarct. Low educational level was also strongly and independently associated with plaque. CCA-IMT shared the same risk factors except for a non-significant association with T2DM and family history of myocardial infarction (MI). Participants with T2DM had greater plaque prevalence, 2-fold higher in those <50 years and 17–30% greater in age groups 50–54 to 60–64, and more significant plaques (moderate or severe) were the difference in prevalence was 24% in age group 50–54 and ≥60% in older age groups, compared with non-T2DM.ConclusionsCarotid plaque and CCA-IMT have mostly common determinants. However, T2DM and family history of MI were associated with plaque but not with CCA-IMT. Greater prevalence and more severe plaques in individuals with T2DM raise the concern that with increasing prevalence of T2DM we may expect an increase in atherosclerosis and its consequences.
Are differences in travel time or distance to healthcare for adults in global north countries associated with an impact on health outcomes? A systematic review
Authors: Kelly Charlotte , Hulme Claire , Farragher Tracey , Clarke Graham 
Published: November 2016

ObjectivesTo investigate whether there is an association between differences in travel time/travel distance to healthcare services and patients' health outcomes and assimilate the methodologies used to measure this.DesignSystematic Review. We searched MEDLINE, Embase, Web of Science, Transport database, HMIC and EBM Reviews for studies up to 7 September 2016. Studies were excluded that included children (including maternity), emergency medical travel or countries classed as being in the global south.SettingsA wide range of settings within primary and secondary care (these were not restricted in the search).Results108 studies met the inclusion criteria. The results were mixed. 77% of the included studies identified evidence of a distance decay association, whereby patients living further away from healthcare facilities they needed to attend had worse health outcomes (eg, survival rates, length of stay in hospital and non-attendance at follow-up) than those who lived closer. 6 of the studies identified the reverse (a distance bias effect) whereby patients living at a greater distance had better health outcomes. The remaining 19 studies found no relationship. There was a large variation in the data available to the studies on the patients' geographical locations and the healthcare facilities attended, and the methods used to calculate travel times and distances were not consistent across studies.ConclusionsThe review observed that a relationship between travelling further and having worse health outcomes cannot be ruled out and should be considered within the healthcare services location debate.
Diagnostic and Prognostic Biomarkers in the Rational Assessment of Mesothelioma (DIAPHRAGM) study: protocol of a prospective, multicentre, observational study
Authors: Tsim Selina , Kelly Caroline , Alexander Laura , McCormick Carol , Thomson Fiona , Woodward Rosie , Foster John E , Stobo David B , Paul Jim , Maskell Nick A , Chalmers Anthony , Blyth Kevin G 
Published: November 2016

IntroductionMalignant pleural mesothelioma (MPM) is an asbestos-related cancer, which is difficult to diagnose. Thoracoscopy is frequently required but is not widely available. An accurate, non-invasive diagnostic biomarker would allow early specialist referral, limit diagnostic delays and maximise clinical trial access. Current markers offer insufficient sensitivity and are not routinely used. The SOMAmer proteomic classifier and fibulin-3 have recently demonstrated sensitivity and specificity exceeding 90% in retrospective studies. DIAPHRAGM (Diagnostic and Prognostic Biomarkers in the Rational Assessment of Mesothelioma) is a suitably powered, multicentre, prospective observational study designed to determine whether these markers provide clinically useful diagnostic and prognostic information.Methods and analysisSerum and plasma (for SOMAscan and fibulin-3, respectively) will be collected at presentation, prior to pleural biopsy/pleurodesis, from 83 to 120 patients with MPM, at least 480 patients with non-MPM pleural disease and 109 asbestos-exposed controls. Final numbers of MPM/non-MPM cases will depend on the incidence of MPM in the study population (estimated at 13–20%). Identical sampling and storage protocols will be used in 22 recruiting centres and histological confirmation sought in all cases. Markers will be measured using the SOMAscan proteomic assay (SomaLogic) and a commercially available fibulin-3 ELISA (USCN Life Science). The SE in the estimated sensitivity and specificity will be <5% for each marker and their performance will be compared with serum mesothelin. Blood levels will be compared with paired pleural fluid levels and MPM tumour volume (using MRI) in a nested substudy. The prognostic value of each marker will be assessed and a large bioresource created.Ethics and disseminationThe study has been approved by the West of Scotland Research Ethics Committee (Ref: 13/WS/0240). A Trial Management Group meets on a monthly basis. Results will be published in peer-reviewed journals, presented at international meetings and disseminated to patient groups.Trial registration numberISRCTN10079972, Pre-results.
Gyejibongneyong-hwan, a herbal medicine for the treatment of dysmenorrhoea with uterine fibroids: a protocol for a randomised controlled trial
Authors: Jung Jeeyoun , Lee Ju Ah , Ko Mi Mi , You Sooseong , Lee Eunhee , Choi Jiae , Kang Byoung-Kab , Lee Myeong Soo 
Published: November 2016

IntroductionGyejibongneyong-hwan (GBH), or the Guizhi Fuling Formula in Chinese, is widely used to treat uterine fibroids in East Asian countries including Korea, China and Japan. This study will assess the efficacy and safety of the GBH formula for the treatment of dysmenorrhoea.Methods and analysisThis study will be a randomised double-blind controlled trial with two parallel arms: the GBH group and the placebo group. This trial will recruit 38 women between 18 and 45 years of age with secondary dysmenorrhoea with uterine fibroids. The investigational drugs, either GBH or placebo, will be administered to the participants three times per day for two menstrual periods (8 weeks). The participants will be followed up for three menstrual cycles after administration of the drugs. The primary outcome will be the Numeric Rating Scale score of average menstrual pain. All analyses will be performed with SAS (V.9.1.3; SAS Institute, Cary, North Carolina, USA) by a statistician blinded to the allocation of the groups. Statistical analysis will be undertaken on the intent-to-treat (ITT) basis with a 95% CI using the last observation carried forward for missing values. The ITT analysis will include all randomised patients.Ethics and disseminationThis research protocol has been reviewed and approved by the institutional review boards of the trial centre (number WSOH IRB 1606-03). Written informed consent will be obtained from all study participants prior to enrolment in the study. The results will be published in a peer-reviewed journal and will be disseminated electronically and in print.Trial registration numberKCT0001967.