bluuebunny/crossref_metadata_2025_split huggingface dataset:
ICSH guidelines for the evaluation of blood cell analysers including those used for differential leucocyte and reticulocyte counting
Authors:   International Council for Standardization in Haematology, Writing Group:, Briggs C. , Culp N. , Davis B. , d'Onofrio G. , Zini G. , Machin S. J. ,   the International Council for Standardization of Haematology
Published: March 2014

SummaryThis revision is intended to update the 1994 ICSH guidelines. It is based on those guidelines but is updated to include new methods, such as digital image analysis for blood cells, a flow cytometric method intended to replace the reference manual 400 cell differential, and numerous new cell indices not identified morphologically are introduced. Haematology analysers are becoming increasingly complex and with technological advancements in instrumentation with more and more quantitative parameters are being reported in the complete blood count. It is imperative therefore that before an instrument is used for testing patient samples, it must undergo an evaluation by an organization or laboratory independent of the manufacturer. The evaluation should demonstrate the performance, advantages and limitations of instruments and methods. These evaluations may be performed by an accredited haematology laboratory where the results are published in a peer‐reviewed journal and compared with the validations performed by the manufacturer. A less extensive validation/transference of the equipment or method should be performed by the local laboratory on instruments prior to reporting of results.
Financial Management of a Large Multisite Randomized Clinical Trial
Authors: Sheffet Alice J. , Flaxman Linda , Tom MeeLee , Hughes Susan E. , Longbottom Mary E. , Howard Virginia J. , Marler John R. , Brott Thomas G. ,   for the CREST Investigators
Published: March 2014

Background The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) received five years' funding ($21 112 866) from the National Institutes of Health to compare carotid stenting to surgery for stroke prevention in 2500 randomized participants at 40 sites. Aims Herein we evaluate the change in the CREST budget from a fixed to variable-cost model and recommend strategies for the financial management of large-scale clinical trials. Methods Projections of the original grant's fixed-cost model were compared to the actual costs of the revised variable-cost model. The original grant's fixed-cost budget included salaries, fringe benefits, and other direct and indirect costs. For the variable-cost model, the costs were actual payments to the clinical sites and core centers based upon actual trial enrollment. We compared annual direct and indirect costs and per-patient cost for both the fixed and variable models. Differences between clinical site and core center expenditures were also calculated. Results Using a variable-cost budget for clinical sites, funding was extended by no-cost extension from five to eight years. Randomizing sites tripled from 34 to 109. Of the 2500 targeted sample size, 138 (5·5%) were randomized during the first five years and 1387(55·5%) during the no-cost extension. The actual per-patient costs of the variable model were 9% ($13 845) of the projected per-patient costs ($152 992) of the fixed model. Conclusions Performance-based budgets conserve funding, promote compliance, and allow for additional sites at modest additional cost. Costs of large-scale clinical trials can thus be reduced through effective management without compromising scientific integrity.
The Relevance of Living Supports on Antiplatelet Adherence and Trial Participation: The SPS3 Trial
Authors: Lewis Brandy L. , Pearce Lesly A. , Field Thalia S. , White Carole L. , Benavente Oscar R. 
Published: March 2014

Background While living with others has been associated with improved functional outcome after acute stroke, it is unclear if this affects adherence to stroke prevention measures. Aims We examined the relationship between living arrangements and adherence to antiplatelet therapy assignment and participation status in an international randomized trial for secondary stroke prevention. Method Antiplatelet therapy adherence, trial retention outcomes, and baseline characteristics for participants enrolled in the Secondary Prevention of Small Subcortical Strokes study were compared between those who lived alone vs. with others ( n = 2374). Participant status at end-of-trial was categorized into ( 1 ) on assigned antiplatelet, ( 2 ) off assigned anti-platelet by participant request, or ( 3 ) participant withdrew consent/lost to follow-up. Multivariable multivariate logistic regression was used to identify patient features at entry predictive of participant status at trial end. Results Living arrangement, alone vs. with other(s), was not significantly associated with participant status. Participants enrolled in the United States/Canada (odds ratio 3·1, confidence intervals 2·0–5·0, vs. Latin America), taking more (7+) prescription medications (odds ratio 1·7, confidence intervals 1·1–2·7, vs. 0–2 medications), and scoring lower on the Stroke Specific Quality of Life scale (odds ratio 1·3, confidence intervals 1·1–1·5, per 10 points) were more likely to withdraw or become lost to follow-up in the study vs. completing the study on assigned antiplatelet therapy. Participants enrolled in the United States/Canada (odds ratio 5·0, confidence intervals 2·4–10·0, vs. Latin America) and taking fewer (0–2) medications (odds ratio 1·9, confidence intervals 1·2–3·1 vs. 3–6 medications) were more likely to request discontinuation of assigned antiplatelet medication vs. completing the study. Conclusion Living with others was not independently predictive of protocol adherence in this cohort. Number of medications and Stroke Specific Quality of Life scale score may be more indicative of likelihood of trial participation and acceptance of long-term antiplatelet regimen.
Novel effect of the inhibitor of mitochondrial cyclophilin D activation, N‐methyl‐4‐isoleucine cyclosporin, on renal calcium crystallization
Authors: Niimi Kazuhiro , Yasui Takahiro , Okada Atsushi , Hirose Yasuhiko , Kubota Yasue , Umemoto Yukihiro , Kawai Noriyasu , Tozawa Keiichi , Kohri Kenjiro 
Published: March 2014

ObjectivesTo experimentally evaluate the clinical application of N‐methyl‐4‐isoleucine cyclosporin, a novel selective inhibitor of cyclophilin D activation.MethodsIn vitro, cultured renal tubular cells were exposed to calcium oxalate monohydrate crystals and treated with N‐methyl‐4‐isoleucine cyclosporin. The mitochondrial membrane was stained with tetramethylrhodamine ethyl ester perchlorate and observed. In vivo, Sprague–Dawley rats were divided into four groups: a control group, an ethylene glycol group (administration of ethylene glycol to induce renal calcium crystallization), a N‐methyl‐4‐isoleucine cyclosporin group (administration of N‐methyl‐4‐isoleucine cyclosporin) and an ethylene glycol + N‐methyl‐4‐isoleucine cyclosporin group (administration of ethylene glycol and N‐methyl‐4‐isoleucine cyclosporin). Renal calcium crystallization was evaluated using Pizzolato staining. Oxidative stress was evaluated using superoxide dismutase and 8‐hydroxy‐deoxyguanosine. Mitochondria within renal tubular cells were observed by transmission electron microscopy. Cell apoptosis was evaluated using cleaved caspase‐3.ResultsIn vitro, calcium oxalate monohydrate crystals induced depolarization of the mitochondrial membrane potential, which was remarkably prevented by N‐methyl‐4‐isoleucine cyclosporin. In vivo, ethylene glycol administration induced renal calcium crystallization, oxidative stress, mitochondrial collapse and cell apoptosis in rats, which were significantly prevented by N‐methyl‐4‐isoleucine cyclosporin.ConclusionsHerein we first report a new treatment agent determining renal calcium crystallization through cyclophilin D activation.
Embodied practice: rediscovering the ‘heart’ of nursing
Authors: Draper Jan 
Published: March 2014

AbstractAimThis article explores the importance of embodiment in nursing. It examines different sources of authoritative knowledge concerning the body and embodiment. It argues that dominant scientific and medical epistemologies of the body have displaced and marginalized embodied epistemologies, creating only a partial understanding of the embodied experiences of our patients and our own embodiment as nurses.BackgroundOver the last 20 years, there has been a rapid expansion of theoretical literature concerning the body and embodiment, spanning a range of disciplines. The potential of these insights to the essentially ‘body‐based’ practice of nursing is highly significant. However, although work in this area is now increasing, theoretical and empirical investigation of the body and embodiment in nursing has remained relatively neglected.DesignDiscussion paper.Data SourcesConventional approaches to systematic searching of the literature were not adopted for this conceptual paper. Seminal texts predominantly from nursing and sociology accompanied by more recent sources were used as a platform for theoretical reflection and to inform development of the conceptual arguments.Implications for NursingThe paper proposes a corporeal (re)turn to nursing practice, one that recognizes the lived embodied experience of the patient and the embodied skill and knowledge of the nurse and examines the implications for contemporary person‐centred nursing practice, research and education.ConclusionAt a significant juncture in nursing's history, when there is greater international focus on delivering higher standards of care, the paper calls for a repositioning of the place of embodiment in nursing.
Loss of K+ Currents in Heart Failure Is Accentuated in KChIP2 Deficient Mice
Authors: GRUBB SØREN , SPEERSCHNEIDER TOBIAS , OCCHIPINTI DONA , FISET CÉLINE , OLESEN SØREN‐PETER , THOMSEN MORTEN B. , CALLOE KIRSTINE 
Published: March 2014

The Role of KChIP2 in Heart FailureIntroductionKV4 together with KV Channel‐Interacting Protein 2 (KChIP2) mediate the fast recovering transient outward potassium current (Ito,f) in the heart. KChIP2 is downregulated in human heart failure (HF), potentially underlying the loss of Ito,f. We investigated remodeling associated with HF hypothesizing that KChIP2 plays a central role in the modulation of outward K+ currents in HF.Methods and ResultsHF was induced by aortic banding in wild‐type (WT) and KChIP2 deficient (KChIP2–/–) mice, evaluated by echocardiography. Action potentials were measured by floating microelectrodes in intact hearts. Ventricular cardiomyocytes were isolated and whole‐cell currents were recorded by patch clamp. Left ventricular action potentials in KChIP2–/– mice were prolonged in a rate dependent manner, consistent with patch‐clamp data showing loss of a fast recovering outward K+ current and upregulation of the slow recovering Ito,s and IKur. HF decreased all outward K+ currents in WT mice and did not change the relative contribution of Ito,f in WT mice. Compared to WT HF, KChIP2–/– HF had a larger reduction of K+‐current density. However, the relative APD prolongation caused by HF was shorter for KChIP2–/– compared with WT, and the APs of the 2 HF mouse types were indistinguishable.ConclusionIto,f is just one of many K+ currents being downregulated in murine HF. The downregulation of repolarizing currents in HF is accentuated in KChIP2–/– mice. However, the prolongation of APs associated with HF is less in KChIP2–/– compared to WT, suggesting other compensatory mechanism(s) in the KChIP2–/– mouse.
Exaggerated Blood Pressure Response to Exercise Is Not Associated With Masked Hypertension in Patients With High Normal Blood Pressure Levels
Authors: Grossman Alon , Cohen Noa , Shemesh Joseph , Koren‐Morag Nira , Leibowitz Avshalom , Grossman Ehud 
Published: March 2014

The association between exaggerated blood pressure (BP) response to exercise (ExBPR) and “masked hypertension” is unclear. Medical records of patients with high‐normal BP who were evaluated in the Chaim Sheba Screening Institute Ramat Gan, Israel, during the years 2002–2007 and referred for 24‐hour ambulatory BP monitoring (ABPM) and exercise test were reviewed. Data on exercise tests performed in the preceding 5 years were retrieved. Reproducible ExBPR was defined when it was recorded at least twice. BP levels on 24‐hour ABPM were compared between patients with a normal BP response and those with an ExBPR (systolic BP ≥200 mm Hg). Sixty‐nine normotensive patients with high normal BP levels were identified. ExBPR was recorded in 43 patients and was reproducible in 28. BP levels on 24‐hour ABPM were similar in patients with and without ExBPR. In patients with high‐normal BP levels, ExBPR is not associated with masked hypertension.
Differential Item Functioning Assessment in Cognitive Diagnostic Modeling: Application of the Wald Test to Investigate DIF in the DINA Model
Authors: Hou Likun , la Torre Jimmy de , Nandakumar Ratna 
Published: March 2014

Analyzing examinees’ responses using cognitive diagnostic models (CDMs) has the advantage of providing diagnostic information. To ensure the validity of the results from these models, differential item functioning (DIF) in CDMs needs to be investigated. In this article, the Wald test is proposed to examine DIF in the context of CDMs. This study explored the effectiveness of the Wald test in detecting both uniform and nonuniform DIF in the DINA model through a simulation study. Results of this study suggest that for relatively discriminating items, the Wald test had Type I error rates close to the nominal level. Moreover, its viability was underscored by the medium to high power rates for most investigated DIF types when DIF size was large. Furthermore, the performance of the Wald test in detecting uniform DIF was compared to that of the traditional Mantel‐Haenszel (MH) and SIBTEST procedures. The results of the comparison study showed that the Wald test was comparable to or outperformed the MH and SIBTEST procedures. Finally, the strengths and limitations of the proposed method and suggestions for future studies are discussed.
Integrated metabolomic profiling of hepatocellular carcinoma in hepatitis C cirrhosis through GC/MS and UPLC/MS‐MS
Authors: Fitian Asem I. , Nelson David R. , Liu Chen , Xu Yiling , Ararat Miguel , Cabrera Roniel 
Published: March 2014

AbstractBackground & AimsThe metabolic pathway disturbances associated with hepatocellular carcinoma (HCC) remain unsatisfactorily characterized. Determination of the metabolic alterations associated with the presence of HCC can improve our understanding of the pathophysiology of this cancer and may provide opportunities for improved disease monitoring of patients at risk for HCC development. To characterize the global metabolic alterations associated with HCC arising from hepatitis C (HCV)‐associated cirrhosis using an integrated non‐targeted metabolomics methodology employing both gas chromatography/mass spectrometry (GC/MS) and ultrahigh‐performance liquid chromatography/electrospray ionization tandem mass spectrometry (UPLC/MS‐MS).MethodsThe global serum metabolomes of 30 HCC patients, 27 hepatitis C cirrhosis disease controls and 30 healthy volunteers were characterized using a metabolomics approach that combined two metabolomics platforms, GC/MS and UPLC/MS‐MS. Random forest, multivariate statistics and receiver operator characteristic analysis were performed to identify the most significantly altered metabolites in HCC patients vs. HCV‐cirrhosis controls and which therefore exhibited a close association with the presence of HCC.ResultsElevated 12‐hydroxyeicosatetraenoic acid (12‐HETE), 15‐HETE, sphingosine, γ‐glutamyl oxidative stress‐associated metabolites, xanthine, amino acids serine, glycine and aspartate, and acylcarnitines were strongly associated with the presence of HCC. Elevations in bile acids and dicarboxylic acids were highly correlated with cirrhosis.ConclusionsIntegrated metabolomic profiling through GC/MS and UPLC/MS‐MS identified global metabolic disturbances in HCC and HCV‐cirrhosis. Aberrant amino acid biosynthesis, cell turnover regulation, reactive oxygen species neutralization and eicosanoid pathways may be hallmarks of HCC. Aberrant dicarboxylic acid metabolism, enhanced bile acid metabolism and elevations in fibrinogen cleavage peptides may be signatures of cirrhosis.
A physiological framework to explain genetic and environmental regulation of tillering in sorghum
Authors: Alam Mohammad Mobashwer , Hammer Graeme L. , van Oosterom Erik J. , Cruickshank Alan W. , Hunt Colleen H. , Jordan David R. 
Published: March 2014

Summary

Tillering determines the plant size of sorghum (Sorghum bicolor) and an understanding of its regulation is important to match genotypes to prevalent growing conditions in target production environments. The aim of this study was to determine the physiological and environmental regulation of variability in tillering among sorghum genotypes, and to develop a framework for this regulation.
Diverse sorghum genotypes were grown in three experiments with contrasting temperature, radiation and plant density to create variation in tillering. Data on phenology, tillering, and leaf and plant size were collected. A carbohydrate supply/demand (S/D) index that incorporated environmental and genotypic parameters was developed to represent the effects of assimilate availability on tillering. Genotypic differences in tillering not explained by this index were defined as propensity to tiller (PTT) and probably represented hormonal effects.
Genotypic variation in tillering was associated with differences in leaf width, stem diameter and PTT. The S/D index captured most of the environmental effects on tillering and PTT most of the genotypic effects.
A framework that captures genetic and environmental regulation of tillering through assimilate availability and PTT was developed, and provides a basis for the development of a model that connects genetic control of tillering to its phenotypic consequences.
Expression of cathepsin K in periodontitis and in gingival fibroblasts
Authors: Beklen A , Al‐Samadi A , Konttinen YT 
Published: March 2014

ObjectiveTo study non‐osteoclastic sources of cathepsin K in periodontitis.Materials and MethodsTissue samples were obtained from 10 otherwise healthy periodontitis pati‐ents during routine periodontal flap operations and 10 systemically and periodontally healthy individuals who underwent extraction operations for retained third molars. Methods used were immunohistochemistry, image analysis, immunofluorescence double‐staining, gingival fibroblast culture, tumour necrosis factor‐α (TNF‐α) stimulation and Western blotting.ResultsMacrophage‐like cells, fibroblast‐like cells, vascular endothelial cells and gingival epithelial cells were more intensively stained for cathepsin K and also more frequent in periodontitis than in controls (665 ± 104 vs 258 ± 40 cells mm−2, P < 0.01). Some cathepsin K+ cells in periodontal tissues were CD68+, but some were CD68− and probably fibroblasts. Indeed, in gingival fibroblast culture, resting fibroblasts released cathepsin K, more 43 kD procathepsin K than 29 kD active cathepsin K. TNF‐α increased the release of the activated cathepsin K 4‐ to 5‐fold.ConclusionsResults suggest that GCF‐cathepsin K is not only osteoclast‐derived, but in periodontitis, also other cells contribute to it. GCF‐cathepsin K, perhaps together with intracellular, lysosomal collagenolytically active cathepsin K in fibroblasts, macrophages and gingival epithelial cells, can contribute to the loss of attachment and destruction of the periodontal ligament.
Respect for the Unworthy
Authors: Dean Richard 
Published: March 2014

AbstractThe claim that everyone ought to be treated with respect is a familiar and widely accepted prescription in recent moral philosophy, often expressed as a principle of ‘respect for persons.’ I argue that this principle need not be justified by a claim that every person possesses some feature – dignity, autonomy, value, or the like – that makes her worthy of respect. There is abundant conceptual space within many approaches to moral philosophy, including a Kantian approach, to affirm a duty of respect for all persons, while denying that the duty is justified by the respect‐worthiness of every person.
What It Is to Pretend
Authors: Langland‐Hassan Peter 
Published: March 2014

AbstractPretense is a topic of keen interest to philosophers and psychologists. But what is it, really, to pretend? What features qualify an act as pretense? Surprisingly little has been said on this foundational question. Here I defend an account of what it is to pretend, distinguishing pretense from a variety of related but distinct phenomena, such as (mere) copying and practicing. I show how we can distinguish pretense from sincerity by sole appeal to a person's beliefs, desires, and intentions – and without circular recourse to an ‘intention to pretend’ or to asui generismental state of ‘imagining.’
Global reprogramming of transcription and metabolism in Medicago truncatula during progressive drought and after rewatering
Authors: ZHANG JI‐YI , CRUZ DE CARVALHO MARIA H. , TORRES‐JEREZ IVONE , KANG YUN , ALLEN STACY N. , HUHMAN DAVID V. , TANG YUHONG , MURRAY JEREMY , SUMNER LLOYD W. , UDVARDI MICHAEL K. 
Published: March 2014

AbstractMedicago truncatula is a model legume forage crop native to the arid and semi‐arid environments of the Mediterranean. Given its drought‐adapted nature, it is an ideal candidate to study the molecular and biochemical mechanisms conferring drought resistance in plants. Medicago plants were subjected to a progressive drought stress over 14 d of water withholding followed by rewatering under controlled environmental conditions. Based on physiological measurements of plant water status and changes in morphology, plants experienced mild, moderate and severe water stress before rehydration. Transcriptome analysis of roots and shoots from control, mildly, moderately and severely stressed, and rewatered plants, identified many thousands of genes that were altered in expression in response to drought. Many genes with expression tightly coupled to the plant water potential (i.e. drought intensity) were identified suggesting an involvement in Medicago drought adaptation responses. Metabolite profiling of drought‐stressed plants revealed the presence of 135 polar and 165 non‐polar compounds in roots and shoots. Combining Medicago metabolomic data with transcriptomic data yielded insight into the regulation of metabolic pathways operating under drought stress. Among the metabolites detected in drought‐stressed Medicago plants, myo‐inositol and proline had striking regulatory profiles indicating involvement in Medicago drought tolerance.