bluuebunny/crossref_metadata_2025_split huggingface dataset:
Guidance on guidelines: Understanding the evidence on the uptake of health care guidelines
Authors: Brennan Cathy , Greenhalgh Joanne , Pawson Ray 
Published: March 2017

AbstractRationaleRegardless of health issue, health sector, patient condition, or treatment modality, the chances are that provision is supported by “a guideline” making professionally endorsed recommendations on best practice. Against this background, research has proliferated seeking to evaluate how effectively such guidance is followed. These investigations paint a gloomy picture with many a guideline prompting lip service, inattention, and even opposition. This predicament has prompted a further literature on how to improve the uptake of guidelines, and this paper considers how to draw together lessons from these inquiries.MethodsThis huge body of material presents a considerable challenge for research synthesis, and this paper produces a critical, methodological comparison of 2 types of review attempting to meet that task. Firstly, it provides an overview of the current orthodoxy, namely, “thematic reviews,” which aggregate and enumerate the “barriers and facilitators” to guideline implementation. It then outlines a “realist synthesis,” focussing on testing the “programme theories” that practitioners have devised to improve guideline uptake.ResultsThematic reviews aim to provide a definitive, comprehensive catalogue of the facilitators and barriers to guideline implementation. As such, they present a restatement of the underlying problems rather than an improvement strategy. The realist approach assumes that the incorporation of any guideline into current practice will produce unintended system strains as different stakeholders wrestle over responsibilities. These distortions will prompt supplementary revisions to guidelines, which in turn beget further strains. Realist reviews follow this dynamic understanding of organisational change.ConclusionsHealth care decision makers operate in systems that are awash with guidelines. But guidelines only have paper authority. Managers do not need a checklist of their pros and cons, because the fate of guidelines depends on their reception rather than their production. They do need decision support on how to engineer and reengineer guidelines so they dovetail with evolving systems of health care delivery.
The cerebral basal arterial network: morphometry of inflow and outflow components
Authors: Burlakoti Arjun , Kumaratilake Jaliya , Taylor Jamie , Massy‐Westropp Nicola , Henneberg Maciej 
Published: March 2017

AbstractThe aim of this project was to study how the morphology of the incoming and outgoing arterial components of the cerebral basal arterial network influence the blood flow to the brain. The cerebral basal arterial network consists of the circulus arteriosus cerebri anteriorly and the basilar artery posteriorly. Diameters of inflow vessels (bilateral vertebral and internal carotid arteries), connecting vessels (anterior communicating, basilar and bilateral posterior communicating arteries) and outflow vessels (anterior, middle and posterior cerebral arteries) were measured and cross‐sectional areas calculated in 51 cadaveric brain specimens. The individual and the average cross‐sectional areas of inflow arteries (51.43 mm2) were significantly bigger than the major outflow arteries (37.76 mm2) but smaller than the combined cross‐sectional areas of outflow (37.76 mm2) and connecting (25.33 mm2) arteries. The difference in the size of arterial cross‐sectional area and the presence of the connecting arteries in the cerebral basal arterial network provides a mechanism for lowering peaks in pressure, and demonstrates a function of the cerebral basal arterial network.
Predictors for long‐term survival after transcatheter edge‐to‐edge mitral valve repair
Authors: Orban Mathias , Orban Martin , Lesevic Hasema , Braun Daniel , Deseive Simon , Sonne Carolin , Hutterer Lisa , Grebmer Christian , Khandoga Alexander , Pache Jürgen , Mehilli Julinda , Schunkert Heribert , Kastrati Adnan , Hagl Christian , Bauer Axel , Massberg Steffen , Boekstegers Peter , Nabauer Michael , Ott Ilka , Hausleiter Jörg 
Published: March 2017

ObjectivesTo determine predictors for long‐term outcome in high‐risk patients undergoing transcatheter edge‐to‐edge mitral valve repair (TMVR) for severe mitral regurgitation (MR).BackgroundThere is no data on predictors of long‐term outcome in high‐risk real‐world patients.MethodsFrom August 2009 to April 2011, 126 high‐risk patients deemed inoperable were treated with TMVR in two high‐volume university centers.ResultsMR could be successfully reduced to grade ≤2 in 92.1% of patients (116/126 patients). Long‐term clinical follow‐up up to 5 years (95.2% follow‐up rate) revealed a mortality rate of 35.7% (45/126 patients). Repeat mitral valve treatment (surgery or intervention) was needed in 19 patients (15.1%). Long‐term clinical improvement was demonstrated with 69% of patients being in NYHA class ≤II. In a multivariable Cox regression analysis, the post‐procedural grade of MR (hazard ratio [HR] 1.55 per grade, P = 0.035), the left ventricular ejection fraction (HR 0.58 for difference between 75th and 25th percentile, P = 0.031) and the glomerular filtration rate (HR 0.33 for 75th vs 25th percentile, P < 0.001) were independent predictors for long‐term mortality. Patients with primary MR and a post‐procedural MR grade ≤1 had the most favorable long‐term outcome.ConclusionsThis study determines predictors of long‐term clinical outcome after TMVR and demonstrates that the grade of residual MR determines long‐term survival. Our data suggest that it might be of benefit reducing residual MR to the lowest possible MR grade using TMVR—especially in selected high‐risk patients with primary MR who are not considered as candidates for surgical MVR.
Role of deferred stenting in patients with ST elevation myocardial infarction treated with primary percutaneous coronary intervention: A systematic review and meta‐analysis
Authors: De Maria Giovanni Luigi , Alkhalil Mohammad , Oikonomou Evangelos K. , Wolfrum Mathias , Choudhury Robin P. , Banning Adrian P. 
Published: March 2017

ObjectivesWe conducted a meta‐analysis of studies comparing deferred stenting strategy versus the conventional approach with immediate stenting in patients with ST elevation myocardial infarction.BackgroundDeferring stent after mechanical flow restoration has been proposed as a strategy to reduce the risk of “no reflow” in patients with STEMI undergoing primary percutaneous coronary intervention (pPCI). Conflicting evidence is available currently, especially after the recent publication of three randomized clinical trials.MethodsSearches in electronic databases were performed. Comparisons between the two strategies were performed for both hard clinical endpoints (all cause‐mortality, cardiovascular mortality, unplanned revascularization, myocardial infarction and readmission for heart failure) and surrogate angiographic endpoints (TIMI flow < 3 and myocardial blush grade (MBG) < 2).ResultsEight studies (three randomized and five non‐randomized) were deemed eligible, accounting for a total of 2101 patients. No difference in terms of hard clinical endpoints was observed between deferred and immediate stenting (OR [95% CI]: 0.79 [0.54‐1.15], for all‐cause mortality; odds ratio (OR) [95% CI]: 0.79 [0.47‐1.31] for cardiovascular mortality; OR [95% CI]: 0.95 [0.64‐1.41] for myocardial infarction; OR [95% CI]: 1.37 [0.87‐2.16], for unplanned revascularization and OR [95% CI]: 0.50 [0.21‐1.17] for readmission for heart failure). Notably, the deferred stenting approach was associated with improved outcome of the surrogate angiographic endpoints (OR [95% CI]: 0.43 [0.18‐0.99] of TIMI flow < 3 and OR [95% CI]: 0.25 [0.11‐0.57] for MBG < 2.ConclusionsA deferred stenting strategy could be a feasible alternative to the conventional approach with immediate stenting in “selected” STEMI patients undergoing pPCI.
Brassinosteroids act as a positive regulator for resistance against root‐knot nematode involving RESPIRATORY BURST OXIDASE HOMOLOG‐dependent activation of MAPKs in tomato
Authors: Song Liu‐Xia , Xu Xue‐Chen , Wang Fa‐Nan , Wang Yu , Xia Xiao‐Jian , Shi Kai , Zhou Yan‐Hong , Zhou Jie , Yu Jing‐Quan 
Published: March 2017

AbstractInterplay of hormones with reactive oxygen species (ROS) fine‐tunes the response of plants to stress; however, the crosstalk between brassinosteroids (BRs) and ROS in nematode resistance is unclear. In this study, we found that low BR biosynthesis or lack of BR receptor increased, whilst exogenous BR decreased the susceptibility of tomato plants to Meloidogyne incognita. Hormone quantification coupled with hormone mutant complementation experiments revealed that BR did not induce the defence response by triggering salicylic acid (SA), jasmonic acid/ethylene (JA/ET) or abscisic acid (ABA) signalling pathway. Notably, roots of BR‐deficient plants had decreased apoplastic ROS accumulation, transcript of RESPIRATORY BURST OXIDASE HOMOLOG1 (RBOH1) and WHITEFLY INDUCED1 (WFI1), and reduced activation of mitogen‐activated protein kinase 1/2 (MPK1/2) and MPK3. Silencing of RBOH1, WFI1, MPK1, MPK2 and MPK3 all increased the root susceptibility to nematode and attenuated BR‐induced resistance against the nematode. Significantly, suppressed transcript of RBOH1 compromised BR‐induced activation of MPK1/2 and MPK3. These results strongly suggest that RBOH‐dependent MPK activation is involved in the BR‐induced systemic resistance against the nematode.
Polyethylene versus cotton cap as an adjunct to body wrap in preterm infants
Authors: Shafie Hashim , Syed Zakaria Syed Zulkifli , Adli Ali , Shareena Ishak , Rohana Jaafar 
Published: March 2017

AbstractBackgroundOcclusive body wrap using polyethylene plastic applied immediately after birth had been shown to reduce hypothermia among preterm infants. Various adjunct methods have been studied in an attempt to further reduce the incidence of hypothermia. This study was conducted to determine whether polyethylene cap is more effective than cotton cap as an adjunct to polyethylene occlusive body wrap in reducing hypothermia in preterm infants.MethodsThe subjects consisted of preterm infants 24–34 weeks’ gestation born at Universiti Kebangsaan Malaysia Medical Centre. Infants were randomly assigned to NeoCap or control groups. Infants in both groups were wrapped in polyethylene sheets from the neck downwards immediately after birth without prior drying. Infants in the control group had their heads dried and subsequently covered with cotton caps while infants in the NeoCap group had polyethylene caps put on without drying. Axillary temperature was measured on admission to the neonatal intensive care unit (NICU), and after having been stabilized in the incubator.ResultsAmong the 80 infants recruited, admission hypothermia (axillary temperature <36.5°C) was present in 37 (92.5%) and in 40 (100%) in the NeoCap and control groups, respectively. There was no significant difference in mean temperature onNICUadmission between the two groups (35.3 vs 35.1°C,P = 0.36). Mean post‐stabilization temperature, however, was significantly higher in the NeoCap group (36.0 vs 35.5°C,P = 0.01).ConclusionCombined use of polyethylene body wrap and polyethylene cap was associated with a significantly higher mean post‐stabilization temperature compared with polyethylene body wrap and cotton cap.
Exact and Approximate Statistical Inference for Nonlinear Regression and the Estimating Equation Approach
Authors: Demidenko Eugene 
Published: March 2017

AbstractThe exact density distribution of the non‐linear least squares estimator in the one‐parameter regression model is derived in closed form and expressed through the cumulative distribution function of the standard normal variable. Several proposals to generalize this result are discussed. The exact density is extended to the estimating equation (EE) approach and the non‐linear regression with an arbitrary number of linear parameters and one intrinsically non‐linear parameter. For a very special non‐linear regression model, the derived density coincides with the distribution of the ratio of two normally distributed random variables previously obtained by Fieler almost a century ago, unlike other approximations previously suggested by other authors. Approximations to the density of the EE estimators are discussed in the multivariate case. Numerical complications associated with the non‐linear least squares are illustrated, such as non‐existence and/or multiple solutions, as major factors contributing to poor density approximation. The non‐linear Markov–Gauss theorem is formulated on the basis of the near exact EE density approximation.
Simultaneous human platelet antigen genotyping and detection of novel single nucleotide polymorphisms by targeted next‐generation sequencing
Authors: Davey Sue , Navarrete Cristina , Brown Colin 
Published: March 2017

BACKGROUNDTwenty‐nine human platelet antigen systems have been described to date, but the majority of current genotyping methods are restricted to the identification of those most commonly associated with alloantibody production in a clinical context. This can result in a protracted investigation if causative human platelet antigens are rare or novel. A targeted next‐generation sequencing approach was designed to detect all known human platelet antigens with the additional capability of identifying novel mutations in the encoding genes.STUDY DESIGN AND METHODSA targeted enrichment, high‐sensitivity HaloPlex assay was designed to sequence all exons and flanking regions of the six genes known to encode human platelet antigens. Indexed DNA libraries were prepared from 47 previously human platelet antigen‐genotyped samples and subsequently combined into one of three pools for sequencing on an Illumina MiSeq platform. The generated FASTQ files were aligned and scrutinized for each human platelet antigen polymorphism using SureCall data analysis software.RESULTSForty‐six samples were successfully genotyped for human platelet antigens 1 through 29bw, with an average per base coverage depth of 1144. Concordance with historical human platelet antigen genotypes was 100%. A putative novel mutation in Exon 10 of the integrin β‐3 (ITGB3) gene from an unsolved case of fetal neonatal alloimmune thrombocytopenia was also detected.CONCLUSIONA next‐generation sequencing‐based method that can accurately define all known human platelet antigen polymorphisms was developed. With the ability to sequence up to 96 samples simultaneously, our HaloPlex design could be used for high‐throughput human platelet antigen genotyping. This method is also applicable for investigating fetal neonatal alloimmune thrombocytopenia when rare or novel human platelet antigens are suspected.
Feeling the burn: the significant burden of febrile nonhemolytic transfusion reactions
Authors: Cohen Robert , Escorcia Alioska , Tasmin Farzana , Lima Ana , Lin Yulia , Lieberman Lani , Pendergrast Jacob , Callum Jeannie , Cserti‐Gazdewich Christine 
Published: March 2017

BACKGROUNDFebrile nonhemolytic transfusion reactions (FNHTRs) are characterized by a post‐transfusion temperature rise (of ≥ 1°C, to ≥ 38°C) or chills/rigors unrelated to the underlying condition. FNHTRs are provoked by inflammatory cytokines in the product or by host antileukocyte antibodies against residual donor leukocytes. FNHTRs are among the most commonly reported transfusion disturbances and are generally deemed nonserious events. However, their impact on patients and hospitals may be underestimated.STUDY DESIGN AND METHODSA search through two hemovigilance databases identified all known possible‐to‐definite FNHTRs over 3 years (2013‐2015) at four academic hospitals using prestorage leukoreduced components. FNHTRs were assessed for frequency by product (red blood cells [RBCs], platelets [PLTs], intravenous immunoglobulin), diagnostics (bedside, chest imaging, serology, microbiology), and management (medications, disposition change). The definition of FNHTR was derived from Canada's Transfusion‐Transmitted Injuries Surveillance System.RESULTSFor 437 FNHTRs, the overall per‐product rate across all sites was 0.24%, or 0.17% with RBCs alone and 0.25% with PLTs alone. One‐third of patients had significant fevers (≥ 39.0°C or a rise by ≥ 2.0°C). Approximately one‐quarter underwent chest imaging within 48 hours, and 79% had blood cultures. A hospital admission directly attributable to the FNHTR, to exclude other causes of fever, occurred in 15% of FNHTR outpatients.CONCLUSIONAn analysis of FNHTRs reveals a substantial burden of postreaction clinical activity in addition to the disturbance itself. Efforts to avoid this adverse event may save resources, reduce patient distress, and encourage compliance with more restrictive transfusion strategies.
Infectivity of blood products containing cytomegalovirus DNA: results of a lookback study in nonimmunocompromised patients
Authors: Ziemann Malte , Juhl David , Brockmann Christian , Görg Siegfried , Hennig Holger 
Published: March 2017

BACKGROUNDDNA of human cytomegalovirus (CMV) is frequently detected in plasma of donors with primary CMV infection. It is unknown, however, whether leukoreduced blood products from these donors contain sufficient amounts of infectious virus to cause transfusion‐transmitted CMV infections (TT‐CMV).STUDY DESIGN AND METHODSDuring a 14‐year period, CMV DNA–positive donations were identified as part of several previously published studies. Additionally, further donors with seroconversion were tested for CMV DNA. The serostatus of patients who had received a CMV DNA–positive blood product was determined out of pretransfusion samples. Later samples were examined for development of CMV antibodies. Patients with a follow‐up of less than 140 days were also tested for CMV DNA.RESULTSA total of 221 blood products from CMV DNA–positive donations were transfused to 219 recipients. Pretransfusion samples were available for 179 patients, of whom 62 (34.6%) were seronegative. For 39 seronegative recipients of 40 blood products follow‐up samples drawn at least 30 days after transfusion were available. The median duration of follow‐up was 287 days (range, 38‐3784 days). Thirty‐six patients were still CMV seronegative in their last sample. Three patients were CMV seropositive due to passive antibody transfer by plasma rich products from seropositive donors, but CMV DNA negative in all tested samples.CONCLUSIONTT‐CMV was excluded in all recipients of 40 blood products from CMV DNA–positive donations. This corresponds to a 95% interval of confidence for the risk of TT‐CMV of less than 7.4%. Because no patient belonged to a typical at‐risk population, the results are only valid for immunocompetent subjects.
Use of allogeneic apheresis stem cell products as an interlaboratory proficiency challenge
Authors: Cooling Laura , Roxbury Kelly , Hoffmann Sandra , DeBusscher Joan , Kota Usha , Goldstein Steven , Davenport Robertson 
Published: March 2017

BACKGROUNDAABB Standards requires that laboratories participate in a proficiency test (PT) program for critical analytes. Institutions can purchase commercial PT materials; however, PT can also be performed through interlaboratory exchange. We investigated the utility of allogeneic hematopoietic progenitor cell apheresis (HPC‐A) products as an interlaboratory PT challenge for total nucleated cell count (TNC) and CD34 assessment.STUDY DESIGN AND METHODSThree‐year retrospective and comparative review of unrelated allogeneic HPC‐A products received by the University of Michigan between January 2011 and December 2013. Internal TNC and CD34 count were compared to the external collecting facility by paired t test and linear regression. The absolute and percent difference between external and internal counts and 95% limits of agreeability (95% LA) were determined. Results were analyzed relative to donor center location (international, domestic), time zone (domestic), and calendar year.RESULTSThere was a strong correlation between internal and external TNC, regardless of donor center location or year. For CD34, there was a good correlation between centers (R = 0.88‐0.91; slope = 0.95‐0.98x) with a median difference of −1% (95% LA, −50%, +47%). This was considerably better than commercial PT challenges, which showed a persistent negative bias for absolute CD34 and CD3 counts.CONCLUSIONAllogeneic HPC‐A products represent an interlaboratory PT exchange for all critical analytes, including TNC and CD34 count, cell viability, and sterility. Allogeneic HPC‐A products, which are fresh and transported under validated conditions, are less subject to preanalytical variables that may impact commercial PT samples such as aliquoting and sample homogeneity, commercial additives, and sample stability during manufacturing and transport.
Bosutinib, an SRC inhibitor, induces caspase‐independent cell death associated with permeabilization of lysosomal membranes in melanoma cells
Authors: Noguchi S. , Shibutani S. , Fukushima K. , Mori T. , Igase M. , Mizuno T. 
Published: March 2017

BackgroundSRC kinase (SRC proto‐oncogene, non‐receptor tyrosine kinase) is a promising target for the treatment of solid cancers including human melanoma. Bosutinib (Bosu), a SRC inhibitor, has already been applied to the treatment of human chronic myelogenous leukemia and also has been assessed its safety in dogs.AimThe aim of this study was to clarify a novel anti‐tumour mechanism of Bosu in canine and human melanoma cells.Materials and MethodsThe canine and human melanoma cells were treated with Bosu and its effects were evaluated by the cell viability, the protein expression levels such as caspase‐3 and LC3, Annexin V/Propidium iodide staining, and confocal immunostaining.ResultsBosu induced the massive caspase‐independent cell death, and blocked autophagy flux, which resulted from lysosomal dysfunction. Lysosomal dysfunction caused by Bosu was due to lysosomal membrane permeabilization (LMP), which resulted in the release of lysosomal hydrolases including cathepsin B.ConclusionOur data suggest that Bosu induces the cell death through induction of LMP in melanoma cells and is a promising therapeutic agent for treatment of melanoma in both dogs and humans.