bluuebunny/crossref_metadata_2025_split huggingface dataset:
Management of anaemia and blood transfusion in critical care - implementing national guidelines in ICU
Authors: Watson Sethina , Kendrick Kate 
Published: June 2014

AbstractAnaemia in intensive care is common, with approximately 50% of patients receiving a red cell transfusion. Recognised complications from transfusion include 'transfusion associated lung injury', infection, and organ failure progression. Most cohort studies show a positive relationship between red cell transfusion and adverse outcomes. In 2012, the British Committee for Standards in Haematology issued guidelines for red cell (RBC) transfusion in critical care. They recommend a haemoglobin transfusion trigger of below 70 g/dL unless the patient is bleeding, has acute sepsis, neurological injury, or an acute coronary syndrome.RBC transfusions in a single intensive care unit (ICU) were prospectively assessed for compliance with national guidance. Each transfusion was categorised with a traffic light system: red for inappropriate, green for appropriate, and amber for those that were not clearly appropriate or inappropriate.The quality improvement project began with a clinical effectiveness audit of doctors' knowledge of critical care transfusion thresholds. Two quality improvement interventions were used: 1) a local blood transfusion guideline was produced and posters were placed in the ICU 2) this guidance was attached to the transfusion prescriptions. Data was collected after each intervention. A total of 30 random adult RBC transfusions were analysed between August 2013 and February 2014.Despite good results from the effectiveness audit an assessment of RBC transfusions demonstrated room for improvement. Prior to introduction of the guideline intervention, a total of two transfusions were green, one red and seven amber. Following both interventions there were seven green transfusions and three amber. No transfusions were classed as inappropriate. According to additional trust based ICU transfusion records, there was approximately a 50% reduction (41 to 18 RBC transfusions) in overall blood transfusions following the first intervention in October 2013.Simple interventions to raise awareness such as surveys, posters, and reminders can dramatically improve RBC prescribing in accordance to evidence based guidelines. Making prescribers aware of guidelines can dramatically reduce the total number of overall transfusions and increase transfusion appropriateness.
On metric characterizations of the Radon–Nikodým and related properties of Banach spaces
Authors: Ostrovskii Mikhail I. 
Published: June 2014

We find a class of metric structures which do not admit bilipschitz embeddings into Banach spaces with the Radon–Nikodým property. Our proof relies on Chatterji's (1968) martingale characterization of the RNP and does not use the Cheeger's (1999) metric differentiation theory. The class includes the infinite diamond and both Laakso (2000) spaces. We also show that for each of these structures there is a non-RNP Banach space which does not admit its bilipschitz embedding.We prove that a dual Banach space does not have the RNP if and only if it admits a bilipschitz embedding of the infinite diamond.The paper also contains related characterizations of reflexivity and the infinite tree property.
Chemogenetic Evaluation of the Mitotic Kinesin CENP-E Reveals a Critical Role in Triple-Negative Breast Cancer
Authors: Kung Pei-Pei , Martinez Ricardo , Zhu Zhou , Zager Michael , Blasina Alessandra , Rymer Isha , Hallin Jill , Xu Meirong , Carroll Christopher , Chionis John , Wells Peter , Kozminski Kirk , Fan Jeffery , Guicherit Oivin , Huang Buwen , Cui Mei , Liu Chaoting , Huang Zhongdong , Sistla Anand , Yang Jennifer , Murray Brion W. 
Published: June 2014

Abstract
Breast cancer patients with tumors lacking the three diagnostic markers (ER, PR, and HER2) are classified as triple-negative (primarily basal-like) and have poor prognosis because there is no disease-specific therapy available. To address this unmet medical need, gene expression analyses using more than a thousand breast cancer samples were conducted, which identified elevated centromere protein E (CENP-E) expression in the basal-a molecular subtype relative to other subtypes. CENP-E, a mitotic kinesin component of the spindle assembly checkpoint, is shown to be induced in basal-a tumor cell lines by the mitotic spindle inhibitor drug docetaxel. CENP-E knockdown by inducible shRNA reduces basal-a breast cancer cell viability. A potent, selective CENP-E inhibitor (PF-2771) was used to define the contribution of CENP-E motor function to basal-like breast cancer. Mechanistic evaluation of PF-2771 in basal-a tumor cells links CENP-E–dependent molecular events (e.g., phosphorylation of histone H3 Ser-10; phospho-HH3-Ser10) to functional outcomes (e.g., chromosomal congression defects). Across a diverse panel of breast cell lines, CENP-E inhibition by PF-2771 selectively inhibits proliferation of basal breast cancer cell lines relative to premalignant ones and its response correlates with the degree of chromosomal instability. Pharmacokinetic–pharmacodynamic efficacy analysis in a basal-a xenograft tumor model shows that PF-2771 exposure is well correlated with increased phospho-HH3-Ser10 levels and tumor growth regression. Complete tumor regression is observed in a patient-derived, basal-a breast cancer xenograft tumor model treated with PF-2771. Tumor regression is also observed with PF-2771 in a taxane-resistant basal-a model. Taken together, CENP-E may be an effective therapeutic target for patients with triple-negative/basal-a breast cancer. Mol Cancer Ther; 13(8); 2104–15. ©2014 AACR.
In Vitro and In Vivo Activity of the Low-Immunogenic Antimesothelin Immunotoxin RG7787 in Pancreatic Cancer
Authors: Hollevoet Kevin , Mason-Osann Emily , Liu Xiu-fen , Imhof-Jung Sabine , Niederfellner Gerhard , Pastan Ira 
Published: June 2014

Abstract
Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis, and new therapies are needed. RG7787 is a novel low-immunogenic antimesothelin recombinant immunotoxin (RIT), engineered to overcome the limitations of SS1P, a RIT now in clinical trials. In vitro activity was evaluated on five established PDAC cell lines (KLM-1, AsPC-1, BxPC-3, Panc 3.014, and PK-1) and on PDAC cells directly established from a patient tumor (GUMC108). RG7787 had subnanomolar IC50s in most cell lines, and was significantly more active than SS1P in GUMC108, KLM-1, and Panc 3.014 cells. GUMC108 was most sensitive, with RG7787 killing &gt;99% of the cells. In a subcutaneous KLM-1 xenograft mouse model, two cycles of 3 × 2.5 mg/kg RG7787 QOD combined with two cycles of 1 × 50 mg/kg paclitaxel induced near-complete responses, with all tumors regressing below 5 mm3 within 30 days after therapy was initiated (&gt;95% decrease) and no significant growth increase for at least another 3 weeks. RG7787 alone gave limited but significant regressions and paclitaxel by itself arrested tumor growth. Quantifying the uptake of Alexa Fluor 647–labeled RG7787 in tumors showed that the RIT reached only 45% of KLM-1 cells, accounting in part for the limited responses. Paclitaxel did not improve RG7787 uptake, which thus cannot explain the beneficial effect of the combination therapy. In conclusion, RG7787 has high cytotoxic activity on PDAC cell lines as well as on primary patient cells. In vivo, this novel RIT gives durable near-complete tumor responses when combined with paclitaxel. RG7787 merits further evaluation for the treatment of PDAC. Mol Cancer Ther; 13(8); 2040–9. ©2014 AACR.
Expression of the miR200 Family of microRNAs in Mesothelial Cells Suppresses the Dissemination of Ovarian Cancer Cells
Authors: Sugiyama Kazuya , Kajiyama Hiroaki , Shibata Kiyosumi , Yuan Hong , Kikkawa Fumitaka , Senga Takeshi 
Published: June 2014

AbstractThe TGFβ-mediated alteration of the tumor microenvironment plays a crucial role in tumor progression. Mesothelial cells are the primary components of the tumor microenvironment for ovarian cancer cells; however, the exact role of TGFβ-stimulated mesothelial cells in ovarian cancer progression remains uncertain. In this report, we examined the effects of TGFβ-treated mesothelial cells on ovarian cancer progression. We show that TGFβ-stimulated human primary mesothelial cells (HPMC) are able to promote cancer cell attachment and proliferation and the activation of the promoter activities of MMP-2 and MMP-9, which are metalloproteinases necessary for tumor invasion. Expression of the miR200 family was downregulated in HPMCs by TGFβ stimulation, and restoration of the expression of miR200 family members in HPMCs suppressed cancer cell attachment and proliferation. Downregulation of the miR200 family by TGFβ induced fibronectin 1 production, which promoted cancer cell attachment to HPMCs. Finally, we demonstrated that the delivery of the miR200s to mesothelial cells in mice inhibited ovarian cancer cell implantation and dissemination. Our results suggest that alteration of the tumor microenvironment by the miR200 family could be a novel therapeutic strategy for ovarian cancer treatment. Mol Cancer Ther; 13(8); 2081–91. ©2014 AACR.
Postsystolic Shortening by Myocardial Deformation Imaging as a Sign of Cardiac Adaptation to Pressure Overload in Fetal Growth Restriction
Authors: Crispi Fàtima , Bijnens Bart , Sepulveda-Swatson Eduardo , Cruz-Lemini Monica , Rojas-Benavente Juan , Gonzalez-Tendero Anna , Garcia-Posada Raul , Rodriguez-Lopez Merida , Demicheva Elena , Sitges Marta , Gratacós Eduard 
Published: June 2014

Background—
Fetal growth restriction (FGR) is associated with global adverse cardiac remodeling in utero and increased cardiovascular mortality in adulthood. Prenatal myocardial deformation has not been evaluated in FGR to date. We aimed to evaluate prenatal cardiac remodeling comprehensively in FGR including myocardial deformation imaging.

Methods and Results—

Echocardiography was performed in 37 consecutive FGR (defined as birthweight <10th centile) and 37 normally grown fetuses. A comprehensive fetal echocardiography was performed including tissue Doppler and 2-dimensional–derived strain and strain rate. Postnatal blood pressure measurement at 6 months of age was also performed. FGR cases showed signs of more globular hearts with decreased longitudinal motion (left systolic annular peak velocity: controls mean 6 cm/s [SD 1.2] versus FGR 5.3 [1]) and diastolic dysfunction (isovolumic relaxation time: controls 44 ms [6] versus FGR 52 [9]). Peak strain and strain rate values of the left ventricle were not significantly different; however, a postsystolic shortening in the basal segment of the septal ventricular wall was observed in 57% of the FGR cases and in none of controls (
P
<0.001). FGR cases with postsystolic shortening had absence of a hypertrophic response, a poorer perinatal outcome (lower gestational age and birthweight, containing all cases of perinatal mortality [8%]), and higher values of blood pressure.

Conclusions—
Myocardial deformation imaging revealed a postsystolic shortening in 57% of FGR, which supports increased pressure overload as a mechanism for cardiovascular programming in FGR. Postsystolic shortening was associated with severity and with higher blood pressure postnatally.
Myocardial Contractile Dysfunction Is Associated With Impaired Mitochondrial Function and Dynamics in Type 2 Diabetic but Not in Obese Patients
Authors: Montaigne David , Marechal Xavier , Coisne Augustin , Debry Nicolas , Modine Thomas , Fayad Georges , Potelle Charlotte , El Arid Jean-Marc , Mouton Stéphanie , Sebti Yasmine , Duez Hélène , Preau Sébastien , Remy-Jouet Isabelle , Zerimech Farid , Koussa Mohamed , Richard Vincent , Neviere Remi , Edme Jean-Louis , Lefebvre Philippe , Staels Bart 
Published: June 2014

Background—
Obesity and diabetes mellitus are independently associated with the development of heart failure. In this study, we determined the respective effects of obesity, insulin resistance, and diabetes mellitus on the intrinsic contraction and mitochondrial function of the human myocardium before the onset of cardiomyopathy.

Methods and Results—

Right atrial myocardium was obtained from 141 consecutive patients presenting no sign of cardiomyopathy. We investigated ex vivo isometric contraction, mitochondrial respiration and calcium retention capacity, and respiratory chain complex activities and oxidative stress status. Diabetes mellitus was associated with a pronounced impairment of intrinsic contraction, mitochondrial dysfunction, and increased myocardial oxidative stress, regardless of weight status. In contrast, obesity was associated with less pronounced contractile dysfunction without any significant perturbation of mitochondrial function or oxidative stress status. Tested as continuous variables, glycated hemoglobin A
1C
, but neither body mass index nor the insulin resistance index (homeostasis model assessment–insulin resistance), was independently associated with cardiac mitochondrial function. Furthermore, diabetes mellitus was associated with cardiac mitochondrial network fragmentation and significantly decreased expression of the mitochondrial fusion related protein MFN1. Myocardial MFN1 content was inversely proportional to hemoglobin A
1C
.

Conclusion—
Worsening of intrinsic myocardial contraction in the transition from obesity to diabetes mellitus is likely related to worsening of cardiac mitochondrial function because impaired mitochondrial function and dynamics and contractile dysfunction are observed in diabetic patients but not in “metabolically healthy” obese patients at early stage in insulin resistance.
From Ministry Towards Spiritual Competence. Changing Perspectives in Spiritual Care in the Netherlands
Authors: Smeets Wim , Morice-Calkhoven Tessa 
Published: June 2014

In the ‘crisis of ministry’ alternatives are considered to a worldview-based spiritual positioning of spiritual caregivers. One of the concepts in this discussion is that of spiritual competence. We addressed the question: what are the attitudes of spiritual caregivers (and their educators) towards ministry and spiritual competence? In terms of the volume the question is: to what extent does a specific denominational concept such as ministry still relate to religion as it is lived in contemporary society, more specifically in healthcare systems?Ministry we defined as worldview representation in public and semi-public settings. There is a tension between representation and communication of religion, or, between authorisation and competence in the role of the minister. Quantitative empirical research clarified that spiritual caregivers regard the ministry positively. But they doubt their representation task, and have a multiple worldview orientation towards communication.Spiritual competence can be situated on the level of the person, professional practice, professional identity and legitimation. This analysis can be related to, e.g. the competence profile of medical specialists and praxis-oriented models of spiritual care. Semi-structured interviews with educators of spiritual caregivers put forward a balance in personal and professional spirituality, the role of reflexivity and some basic —, core — and heuristic competencies.Spiritual competence is at the core of the identity of spiritual care. Further research should reveal the extent to which this concept is an umbrella term, an alternative or even a substitute for ministry, conceptually and organisationally.
Caregivers Confronted With the Withdrawal of Artificial Nutrition at the End of Life
Authors: Piot Elise , Leheup Benoît F. , Goetz Christophe , Quilliot Didier , Niemier Jean-Yves , Wary Bernard , Ducrocq Xavier 
Published: June 2014

Background: Withdrawing artificial nutrition in palliative care is an issue that often leads to ethical dilemmas among health care providers, despite clinical guidelines. Objectives: To describe the experience of health care providers confronted with the withdrawing of artificial nutrition at the end of life and identifying the factors related to the level of ethical dilemmas. Methods: Cross-sectional survey questionnaire of all the nurses and nurses’ aides working in medicine, surgery, and palliative care departments of a regional hospital and who have already been confronted with the withdrawal of artificial nutrition. Results: Of 818 questionnaires sent, 274 were returned (response rate 33.5%); 60% (163) of the care providers who responded were involved in withdrawing artificial nutrition at the end of life. Among these, 42 (25.8%) had always or often been affected with ethical dilemmas, and 97 (60%) responded that withdrawing artificial nutrition had always or often been preceded by a multidisciplinary discussion. Items significantly associated with a high level of ethical dilemmas were (1) existence of differences in opinion within the health care team, (2) lack of information regarding the indication of the withdrawal of artificial nutrition, (3) feeling uncomfortable with the patient and his or her relatives, (4) guilt, (5) feeling of abandonment of care, and (6) uneasiness. Conclusion: Health care providers seem to have a lack of information and consensus regarding the withdrawal of artificial nutrition at the end of life. The ethical dimension of withdrawing artificial nutrition in palliative care has a strong impact on care providers, regardless of the circumstances of the withdrawal.
Computing the Surveillance Error Grid Analysis
Authors: Kovatchev Boris P. , Wakeman Christian A. , Breton Marc D. , Kost Gerald J. , Louie Richard F. , Tran Nam K. , Klonoff David C. 
Published: June 2014

Introduction: The surveillance error grid (SEG) analysis is a tool for analysis and visualization of blood glucose monitoring (BGM) errors, based on the opinions of 206 diabetes clinicians who rated 4 distinct treatment scenarios. Resulting from this large-scale inquiry is a matrix of 337 561 risk ratings, 1 for each pair of (reference, BGM) readings ranging from 20 to 580 mg/dl. The computation of the SEG is therefore complex and in need of automation. Methods: The SEG software introduced in this article automates the task of assigning a degree of risk to each data point for a set of measured and reference blood glucose values so that the data can be distributed into 8 risk zones. The software’s 2 main purposes are to (1) distribute a set of BG Monitor data into 8 risk zones ranging from none to extreme and (2) present the data in a color coded display to promote visualization. Besides aggregating the data into 8 zones corresponding to levels of risk, the SEG computes the number and percentage of data pairs in each zone and the number/percentage of data pairs above/below the diagonal line in each zone, which are associated with BGM errors creating risks for hypo- or hyperglycemia, respectively. Results: To illustrate the action of the SEG software we first present computer-simulated data stratified along error levels defined by ISO 15197:2013. This allows the SEG to be linked to this established standard. Further illustration of the SEG procedure is done with a series of previously published data, which reflect the performance of BGM devices and test strips under various environmental conditions. Conclusions: We conclude that the SEG software is a useful addition to the SEG analysis presented in this journal, developed to assess the magnitude of clinical risk from analytically inaccurate data in a variety of high-impact situations such as intensive care and disaster settings.
Bone marrow stromal cell–derived exosomes as communicators in drug resistance in multiple myeloma cells
Authors: Wang Jinheng , Hendrix An , Hernot Sophie , Lemaire Miguel , De Bruyne Elke , Van Valckenborgh Els , Lahoutte Tony , De Wever Olivier , Vanderkerken Karin , Menu Eline 
Published: June 2014

Key Points
BMSCs and MM cells mutually communicate through exosomes, which carry selective cytokines. BMSC-derived exosomes favor MM cell proliferation, migration, and survival and induce drug resistance to bortezomib.
Magnetic resonance direct thrombus imaging differentiates acute recurrent ipsilateral deep vein thrombosis from residual thrombosis
Authors: Tan Melanie , Mol Gerben C. , van Rooden Cornelis J. , Klok Frederikus A. , Westerbeek Robin E. , Iglesias del Sol Antonio , van de Ree Marcel A. , de Roos Albert , Huisman Menno V. 
Published: June 2014

Key Points
Diagnostic management of ipsilateral recurrent DVT of the leg is complicated because residual DVT is common and mimics acute DVT on CUS. MRDTI is able to reproducibly distinguish acute ipsilateral recurrent DVT from 6-month-old chronic residual thrombi in the leg veins.
von Willebrand factor, Jedi knight of the bloodstream
Authors: Springer Timothy A. 
Published: June 2014

AbstractWhen blood vessels are cut, the forces in the bloodstream increase and change character. The dark side of these forces causes hemorrhage and death. However, von Willebrand factor (VWF), with help from our circulatory system and platelets, harnesses the same forces to form a hemostatic plug. Force and VWF function are so closely intertwined that, like members of the Jedi Order in the movie Star Wars who learn to use “the Force” to do good, VWF may be considered the Jedi knight of the bloodstream. The long length of VWF enables responsiveness to flow. The shape of VWF is predicted to alter from irregularly coiled to extended thread-like in the transition from shear to elongational flow at sites of hemostasis and thrombosis. Elongational force propagated through the length of VWF in its thread-like shape exposes its monomers for multimeric binding to platelets and subendothelium and likely also increases affinity of the A1 domain for platelets. Specialized domains concatenate and compact VWF during biosynthesis. A2 domain unfolding by hydrodynamic force enables postsecretion regulation of VWF length. Mutations in VWF in von Willebrand disease contribute to and are illuminated by VWF biology. I attempt to integrate classic studies on the physiology of hemostatic plug formation into modern molecular understanding, and point out what remains to be learned.
Validation of a guideline-based decision support system for the diagnosis of primary headache disorders based on ICHD-3 beta
Authors: Dong Zhao , Yin Ziming , He Mianwang , Chen Xiaoyan , Lv Xudong , Yu Shengyuan 
Published: June 2014

Abstract

Background
China may have the largest population of headache sufferers and therefore the most serious burden of disease worldwide. However, the rate of diagnosis for headache disorders is extremely low, possibly due to the relative complexity of headache subtypes and diagnostic criteria. The use of computerized clinical decision support systems (CDSS) seems to be a better choice to solve this problem.

Methods
We developed a headache CDSS based on ICHD-3 beta and validated it in a prospective study that included 543 headache patients from the International Headache Center at the Chinese PLA General hospital, Beijing, China.

Results
We found that the CDSS correctly recognized 159/160 (99.4%) of migraine without aura, 36/36 (100%) of migraine with aura, 20/21 (95.2%) of chronic migraine, and 37/59 (62.7%) of probable migraine. This system also correctly identified 157/180 (87.2%) of patients with tension-type headache (TTH), of which infrequent episodic TTH was diagnosed in 12/13 (92.3%), frequent episodic TTH was diagnosed in 99/101 (98.0%), chronic TTH in 18/20 (90.0%), and probable TTH in 28/46 (60.9%). The correct diagnostic rates of cluster headache and new daily persistent headache (NDPH) were 90.0% and 100%, respectively. In addition, the system recognized 32/32 (100%) of patients with medication overuse headache.

Conclusions
With high diagnostic accuracy for most of the primary and some types of secondary headaches, this system can be expected to help general practitioners at primary hospitals improve diagnostic accuracy and thereby reduce the burden of headache in China.