bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell senescence, apoptosis and DNA damage cooperate in the remodeling processes accounting for heart morphogenesis
Authors: Lorda‐Diez Carlos I. , Solis‐Mancilla Michelle E. , Sanchez‐Fernandez Cristina , Garcia‐Porrero Juan A. , Hurle Juan M. , Montero Juan A. 
Published: March 2019

AbstractDuring embryonic development, organ morphogenesis requires major tissue rearrangements that are tightly regulated at the genetic level. A large number of studies performed in recent decades assigned a central role to programmed cell death for such morphogenetic tissue rearrangements that often sculpt the shape of embryonic organs. However, accumulating evidence indicates that far from being the only factor responsible for sculpting organ morphology, programmed cell death is accompanied by other tissue remodeling events that ensure the outcome of morphogenesis. In this regard, cell senescence has been recently associated with morphogenetic degenerative embryonic processes as an early tissue remodeling event in development of the limbs, kidney and inner ear. Here, we have explored cell senescence by monitoring β‐galactosidase activity during embryonic heart development where programmed cell death is believed to exert an important morphogenetic function. We report the occurrence of extensive cell senescence foci during heart morphogenesis. These foci overlap spatially and temporally with the areas of programmed cell death that are associated with remodeling of the outflow tract to build the roots of the great arteries and with the septation of cardiac cavities. qPCR analysis allowed us to identify a gene expression profile characteristic of the so‐called senescence secretory associated phenotype in the remodeling outflow tract of the embryonic heart. In addition, we confirmed local upregulation of numerous tumor suppressor genes including p21, p53, p63, p73 and Btg2. Interestingly, the areas of cell senescence were also accompanied by intense lysosomal activation and non‐apoptotic DNA damage revealed by γH2AX immunolabeling. Considering the importance of sustained DNA damage as a triggering factor for cell senescence and apoptosis, we propose the coordinated contribution of DNA damage, senescence and apoptotic cell death to assure tissue remodeling in the developing vertebrate heart.
Bryophytes in fir waves: Forest canopy indicator species and functional diversity decline in canopy gaps
Authors: Berdugo Monica B. , Dovciak Martin 
Published: March 2019

AbstractAimsBryophytes can cover three quarters of the ground surface, play key ecological functions, and increase biodiversity in mesic high‐elevation conifer forests of the temperate zone. Forest gaps affect species coexistence (and ecosystem functions) as suggested by the gap and gap‐size partitioning hypotheses (GPH, GSPH). Here we test these hypotheses in the context of high‐elevation forest bryophyte communities and their functional attributes.Study SiteSpruce–fir forests on Whiteface Mountain, NY, USA.MethodsWe characterized canopy openness, microclimate, forest floor substrates, vascular vegetation cover, and moss layer (cover, common species, and functional attributes) in three canopy openness environments (gap, gap edge, forest canopy) across 20 gaps (fir waves) (n = 60); the functional attributes were based on 16 morphologic, reproductive, and ecological bryophyte plant functional traits (PFTs). We tested GPH and GSPH relative to bryophyte community metrics (cover, composition), traits, and trait functional sensitivity (functional dispersion; FDis) using indicator species analysis, ordination, and regression.ResultsCanopy openness drove gradients in ground‐level temperature, substrate abundance and heterogeneity (beta diversity), and understory vascular vegetation cover. The GPH was consistent with (a) the abundance patterns of forest canopy indicator species (Dicranum fuscescens, Hypnum imponens, and Tetraphis pellucida), and (b) FDis based on three PFTs (growth form, fertility, and acidity), both increasing with canopy cover. We did not find support for GPH in the remaining species or traits, or for GSPH in general; gap width (12–44 m) was not related to environmental or bryophyte community gradients.ConclusionsThe observed lack of variation in most bryophyte metrics across canopy environments suggests high resistance of the bryophyte layer to natural canopy gaps in high‐elevation forests. However, responses of forest canopy indicator species suggest that canopy mortality, potentially increased by changing climate or insect pests, may cause declines in some forest canopy species and consequently in the functional diversity of bryophyte communities.
Sorghum tiller bud growth is repressed by contact with the overlying leaf
Authors: Liu Ruixian , Finlayson Scott A. 
Published: March 2019

AbstractBasal branching in grasses, or tillering, is an important trait determining both form and function of crops. Although similarities exist between eudicot and grass branching programs, one notable difference is that the tiller buds of grasses are covered by the subtending leaf, whereas eudicot buds are typically unconstrained. The current study shows that contact with the leaf sheath represses sorghum bud growth by providing a mechanical signal that cues the bud to refrain from rapid growth. Leaf removal resulted in massive reprogramming of the bud transcriptome that included signatures of epigenetic modifications and also implicated several hormones in the response. Bud abscisic acid transiently increased, then decreased following leaf removal relative to controls, and abscisic acid was necessary to repress bud growth in the presence of the leaf. Jasmonic acid (JA) levels and signalling increased in buds following leaf removal. Remarkably, application of JA to buds in situ promoted growth. The repression of bud growth by leaf contact shares characteristics of thigmomorphogenic responses in other systems, including the involvement of JA, though the JA effect is opposite. The repression of bud growth by leaf contact may represent a mechanism to time tillering to an appropriate developmental stage of the plant.
A simple score can identify kidney transplant recipients at high risk of severe infection over the following 2 years
Authors: Dendle Claire , Polkinghorne Kevan R. , Mulley William R. , Gan Poh‐Yi , Kanellis John , Stuart Rhonda L. , Thursky Karin , Holdsworth Stephen R. 
Published: March 2019

AbstractBackgroundThe aim of this study was to determine whether a composite score of simple immune biomarkers and clinical characteristics could predict severe infections in kidney transplant recipients.MethodsWe conducted a prospective study of 168 stable kidney transplant recipients who underwent measurement of lymphocyte subsets, immunoglobulins, and renal function at baseline and were followed up for 2 years for the development of any severe infections, defined as infection requiring hospitalization. A point score was developed to predict severe infection based on logistic regression analysis of factors in baseline testing.ResultsFifty‐nine (35%) patients developed severe infection, 36 (21%) had two or more severe infections, and 3 (2%) died of infection. A group of 19 (11%) patients had the highest predicted infectious risk (>60%), as predicted by the score. Predictive variables were mycophenolate use, graft function, CD4+, and natural killer cell number. The level of immunosuppression score had an area under the receiver operating curve of 0.75 (95% CI: 0.67‐0.83).ConclusionOur level of immunosuppression score for predicting the development of severe infection over 2 years has sufficient prognostic accuracy for identification of high‐risk patients. This data can inform research that examines strategies to reduce the risks of infection.
Quantitative assessment of the anticoagulant in plasma units collected by plasmapheresis
Authors: Vurro Filippo , Merolle Lucia , Marraccini Chiara , Parisi Maura , Canovi Laura , Erta Barbara , Santachiara Annalisa , Bonvicini Laura , Giorgi Rossi Paolo , Baricchi Roberto , Pertinhez Thelma A. 
Published: March 2019

BACKGROUNDTo date, the quantification of the anticoagulant (ACD‐A) in plasma units has been based on theoretical calculations. An accurate quantification could help minimize the risks associated with plasmapheresis, given that the total ACD‐A used during the procedure is distributed between the donor and the plasma unit.Our aim was to experimentally quantify the volume of ACD‐A in units collected by plasmapheresis.STUDY DESIGN AND METHODSWe used proton nuclear magnetic resonance spectroscopy to measure the ACD‐A volume in 295 plasma units collected by the Azienda USL‐IRCCS of Reggio Emilia, Italy. We analyzed the determinants of the differences between estimated and measured ACD‐A through multivariate regression models.RESULTSThe experimentally measured ACD‐A in plasma units was variable, with 45% of the samples showing a discrepancy of more than 15 mL compared to the manufacturer's estimate.ACD‐A was underestimated for higher density of the units (p < 0.0005); a weak association was also observed with triglycerides (underestimated for higher levels, p = 0.015) and sex (overestimated in females, p = 0.008), but our model explained only 35% of the individual variability.CONCLUSIONThe manufacturer's algorithms do not accurately estimate the ACD‐A in units collected by plasmapheresis. Donor‐related characteristics may affect ACD‐A distribution between donor and plasma unit, thereby explaining the discrepancies between estimate and measurement.Errors in the estimate of the ACD‐A actually received by donors could hamper studies on dose–response relationship between anticoagulant and adverse reactions. Our work should stimulate research on tailored procedures aimed at minimizing the anticoagulant received by donors and increasing plasmapheresis safety.
A standardized kodecyte method to quantify ABO antibodies in undiluted plasma of patients before ABO‐incompatible kidney transplantation
Authors: Perry Holly , Bovin Nicolai , Henry Stephen 
Published: March 2019

BACKGROUNDThe ABO transplantation barrier can be breached if antibody is reduced to low levels. Current serologic methods involve testing natural RBCs against dilutions of plasma to determine antibody levels, but these methods are poorly standardized and inherently error prone with consequent large inter‐ and intra laboratory variation. We evaluated the feasibility of using antigen‐standardized kodecytes and undiluted plasma as an alternative method for antibody measurement in patients preparing for ABO‐incompatible kidney transplantation.STUDY DESIGN AND METHODSA panel of five kodecytes, bearing defined levels of synthetic blood group A type 2 antigen was developed (kodecyte assay) to show reaction patterns against undiluted plasma that were indicative of anti‐A and anti‐A,B levels. This panel was evaluated against the contemporary method of testing dilutions of plasma against A1 cells to determine titer (A1 cell assay) in both column agglutination and tube techniques. Evaluation samples included reference standards, 102 group O plus 23 group B donors, and 40 pre‐ and post‐plasmapheresis samples from five prospective ABO‐incompatible kidney transplant patients.RESULTSComparisons between the kodecyte and A1 cell assays found greater than 90% correlation for all samples. Tube and column agglutination technology platform differences were observed with A1 cells and kodecytes. Discordant samples were generally found to have high ratios of IgG:IgM or vice versa.CONCLUSIONSThe kodecyte assay is a simple method that requires no sample dilution, and an optimized two‐cell kodecyte panel is potentially capable of informing ABO‐incompatible kidney transplantation decisions based on antibody levels.
The role of tonic glycinergic conductance in cerebellar granule cell signalling and the effect of gain‐of‐function mutation
Authors: McLaughlin Catherine , Clements John , Oprişoreanu Ana‐Maria , Sylantyev Sergiy 
Published: March 2019

Key points
A T258F mutation of the glycine receptor increases the receptor affinity to endogenous agonists, modifies single‐channel conductance and shapes response decay kinetics.
Glycine receptors of cerebellar granule cells play their functional role not continuously, but when the granule cell layer starts receiving a high amount of excitatory inputs.
Despite their relative scarcity, tonically active glycine receptors of cerebellar granule cells make a significant impact on action potential generation and inter‐neuronal crosstalk, and modulate synaptic plasticity in neural networks; extracellular glycine increases probability of postsynaptic response occurrence acting at NMDA receptors and decreases this probability acting at glycine receptors.
Tonic conductance through glycine receptors of cerebellar granule cells is a yet undiscovered element of the biphasic mechanism that regulates processing of sensory inputs in the cerebellum.
A T258F point mutation disrupts this biphasic mechanism, thus illustrating the possible role of the gain‐of‐function mutations of the glycine receptor in development of neural pathologies.
AbstractFunctional glycine receptors (GlyRs) have been repeatedly detected in cerebellar granule cells (CGCs), where they deliver exclusively tonic inhibitory signals. The functional role of this signalling, however, remains unclear. Apart from that, there is accumulating evidence of the important role of GlyRs in cerebellar structures in development of neural pathologies such as hyperekplexia, which can be triggered by GlyR gain‐of‐function mutations. In this research we initially tested functional properties of GlyRs, carrying the yet understudied T258F gain‐of‐function mutation, and found that this mutation makes significant modifications in GlyR response to endogenous agonists. Next, we clarified the role of tonic GlyR conductance in neuronal signalling generated by single CGCs and by neural networks in cell cultures and in living cerebellar tissue of C57Bl‐6J mice. We found that GlyRs of CGCs deliver a significant amount of tonic inhibition not continuously, but when the cerebellar granule layer starts receiving substantial excitatory input. Under these conditions tonically active GlyRs become a part of neural signalling machinery allowing generation of action potential (AP) bursts of limited length in response to sensory‐evoked signals. GlyRs of CGCs support a biphasic modulatory mechanism which enhances AP firing when excitatory input intensity is low, but suppresses it when excitatory input rises to a certain critical level. This enables one of the key functions of the CGC layer: formation of sensory representations and their translation into motor output. Finally, we have demonstrated that the T258F mutation in CGC GlyRs modifies single‐cell and neural network signalling, and breaks a biphasic modulation of the AP‐generating machinery.
Terminal Position and Orientation Coupling in Lower Mobility Robots
Authors: Hu Bo 
Published: March 2019

Abstract
The kinematics has attracted continuous interests in the field of robotics. Terminal position and orientation coupling phenomenon is the key problem and the first consideration in the kinematics of lower mobility robots. However, this property was usually neglected or has not been well solved. This paper discusses the terminal position and orientation coupling issues in lower mobility robots, especially for the lower mobility hybrid robots. First, this paper reveals the terminal position and orientation coupling in serial and parallel robots. Then, based on elimination theory, an approach for establishing the terminal position and orientation coupling equations for hybrid robots is proposed, which is illustrated in detail by the (3-RPS) + (RR) and (3-RPS) + (3-RCR) hybrid robots. The results show that the hybrid robots have highly nonlinear terminal position and orientation coupling relations, which are more complicated than serial and parallel robots. The research of this paper is valuable in kinematics modeling of robots.
Effects of removing reimbursement restrictions on targeted therapy accessibility for non-small cell lung cancer treatment in Taiwan: an interrupted time series study
Authors: Hsu Jason C , Wei Chen-Fang , Yang Szu-Chun 
Published: March 2019

InterventionsTargeted therapies have been proven to provide clinical benefits to patients with metastatic non-small cell lung cancer (NSCLC). Gefitinib was initially approved and reimbursed as a third-line therapy for patients with advanced NSCLC by the Taiwan National Health Insurance (NHI) in 2004; subsequently it became a second-line therapy (in 2007) and further a first-line therapy (in 2011) for patients with epidermal growth factor receptor mutation-positive advanced NSCLC. Another targeted therapy, erlotinib, was initially approved as a third-line therapy in 2007, and it became a second-line therapy in 2008.ObjectivesThis study is aimed towards an exploration of the impacts of the Taiwan NHI reimbursement policies (removing reimbursement restrictions) related to accessibility of targeted therapies.SettingWe retrieved 2004–2013 claims data for all patients with lung cancer diagnoses from the NHI Research Database.Design and outcome measuresUsing an interrupted time series design and segmented regression, we estimated changes in the monthly prescribing rate by patient number and market shares by cost following each modification of the reimbursement policy for gefitinib and erlotinib for NSCLC treatment.ResultsTotally 92 220 patients with NSCLC were identified. The prescribing rate of the targeted therapies increased by 15.58%, decreased by 10.98% and increased by 6.31% following the introduction of gefitinib as a second-line treatment in 2007, erlotinib as a second-line treatment in 2008 and gefitinib as as first line treatment in 2011, respectively. The average time to prescription reduced by 65.84% and 41.59% following coverage of erlotinib by insurance and gefitinib/erlotinib as second-line treatments in 2007–2008 and following gefitinib as the first-line treatment in 2011.ConclusionsThe changes in reimbursement policies had a significant impact on the accessibility of targeted therapies for NSCLC treatment. Removing reimbursement restrictions can significantly increase the level and the speed of drug accessibility.
How do doctors in the Netherlands perceive the impact of disciplinary procedures and disclosure of disciplinary measures on their professional practice, health and career opportunities? A questionnaire among medical doctors who received a disciplinary measure
Authors: Laarman Berber S , Bouwman Renée JR , de Veer Anke JE , Hendriks Michelle , Friele Roland D 
Published: March 2019

IntroductionDisciplinary procedures can have serious consequences for the health, personal life and professional functioning of doctors. Until recently, specific disciplinary measures (reprimands) were publicly disclosed in the Netherlands. The perceived additional impact of disclosing reprimands on the professional and personal life of doctors is unclear.MethodsAll doctors who received a disciplinary measure from the Dutch Disciplinary Board between July 2012 and August 2016 were invited to partake in a 60-item questionnaire concerning the respondents’ characteristics, the complaint, experience with the procedure and perceived impact of the procedure on health and professional functioning as reported by doctors themselves. The response rate was 43% (n=210). 21.4% received a reprimand (disclosed); the remainder received a warning (not disclosed). Differences between the two groups were calculated.ResultsRespondents with a reprimand reported significantly more negative experiences and impact on health and work than respondents with a warning. 37.8% of the doctors said their health was very good. A small percentage reported moderate-to-severe depressive complaints (3.6%), moderate-to-severe anxiety disorder (2%) or indications of burnout (10.8%). The majority reported changes in their professional practices associated with ‘defensive medicine’, such as doing more supplementary research (41%) and complying more with patients’ wishes (35%).ConclusionThe Dutch disciplinary procedure has strong negative side effects, that disclosing measures seems to increase. Dutch disciplinary law aims to contribute to the quality of professional practice. A safe environment is a basic condition for quality improvement and therefore, disclosure of disciplinary measures should be carefully considered. Disclosure of disciplinary measures has always been controversial and the results of this study has rekindled this debate. Recently, a majority in the Dutch House of Representatives has voted against disclosure of reprimands, leaving disclosure of reprimands a discretion of the disciplinary board when deemed appropriate or necessary.
Barriers and facilitators to adopting high value practices and de-adopting low value practices in Canadian intensive care units: a multimethod study
Authors: Sauro Khara , Bagshaw Sean M , Niven Daniel , Soo Andrea , Brundin-Mather Rebecca , Parsons Leigh Jeanna , Cook Deborah J , Stelfox Henry Thomas 
Published: March 2019

ObjectiveTo compare and contrast illustrative examples of the adoption of high value practices and the de-adoption of low value practices.Design(1) Retrospective, population-based audit of low molecular weight heparin (LMWH) for venous thromboembolism (VTE) prophylaxis (high value practice) and albumin for fluid resuscitation (low value practice) and (2) cross-sectional survey of healthcare providers.SettingData were collected from nine adult medical-surgical intensive care units (ICUs) in two large Canadian cities. Patients are managed in these ICUs by a group of multiprofessional and multidisciplinary healthcare providers.ParticipantsParticipants included 6946 ICU admissions and 309 healthcare providers from the same ICUs.Main outcome measures(1) The use of LMWH for VTE prophylaxis (per cent ICU days) and albumin for fluid resuscitation (per cent of patients); and (2) provider knowledge of evidence underpinning these practices, and barriers and facilitators to adopt and de-adopt these practices.ResultsLMWH was administered on 38.7% of ICU days, and 20.0% of patients received albumin.Most participants had knowledge of evidence underpinning VTE prophylaxis and fluid resuscitation (59.1% and 84.2%, respectively). Providers perceived these practices to be followed. The most commonly reported barrier to adoption was insufficient knowledge/understanding (32.8%), and to de-adoption was clinical leader preferences (33.2%). On-site education was the most commonly identified facilitator for adoption and de-adoption (67.8% and 68.6%, respectively).ConclusionsDespite knowledge of and self-reported adherence to best practices, the audit demonstrated opportunity to improve. Provider-reported barriers and facilitators to adoption and de-adoption are broadly similar.