bluuebunny/crossref_metadata_2025_split huggingface dataset:
An evaluation of the appropriateness and safety of nurse and midwife prescribing in Ireland
Authors: Naughton Corina , Drennan Jonathan , Hyde Abbey , Allen Deirdre , O'Boyle Kathleen , Felle Patrick , Butler Michelle 
Published: September 2012

AbstractAimTo evaluate the clinical appropriateness and safety of nurse and midwife prescribing practice.BackgroundThe number of countries introducing nurse and midwife prescribing is increasing; however, concerns over patient safety remain.DesignA multi‐site documentation evaluation was conducted using purposeful and random sampling. The sample included 142 patients' records and 208 medications prescribed by 25 Registered Nurse Prescribers.MethodsData were extracted from patient and prescription records between March–May 2009. Two expert reviewers applied the modified Medication Appropriate Index tool (8 criteria) to each drug. The percentage of appropriate or inappropriate responses for each criterion was reported. Reviewer concordance was measured using the Cohen's kappa statistic (inter‐rater reliability).ResultsNurse or midwife prescribers from eight hospitals working in seventeen different areas of practice were included. The reviewers judged that 95–96% of medicines prescribed were indicated and effective for the diagnosed condition. Criteria relating to dosage, directions, drug–drugs or disease–condition interaction, and duplication of therapy were judged appropriate in 87–92% of prescriptions. Duration of therapy received the lowest value at 76%. Overall, reviewers indicated that between 69 (reviewer 2)−80% (reviewer 1) of prescribing decisions met all eight criteria.ConclusionThe majority of nurse and midwife prescribing decisions were deemed safe and clinically appropriate. However, risk of inappropriate prescribing with the potential for drug errors was detected. Continuing education and evaluation of prescribing practice, especially related to drug and condition interactions, is required to maximize appropriate and safe prescribing.
A discussion of HIV/AIDS family interventions: implications for family‐focused nursing practice
Authors: Eustace Rosemary W. 
Published: September 2012

AbstractAimThis article presents a discussion on the role of family interventions in HIV/AIDS disease prevention and care.BackgroundAlthough HIV/AIDS epidemic and its impact on the society traditionally has been measured in terms of individual risk behaviours and individual‐level HIV prevention, HIV/AIDS family‐focused prevention and management strategies are increasingly becoming a priority. However, little is known as to what constitutes a HIV/AIDS family intervention.Data sourcesThe search was limited to English and published literature starting in the year 1983 to date. CINAHL and PubMed were emphasized using a combination of text words and subject headings. Cochrane Library, PsycInfo, Scopus, and the ISI Web of Science databases were also searched using keywords and in the case of PsycInfo, subject headings were used. The main keywords were ‘nurse’, or ‘nursing’, ‘HIV/AIDS’, ‘family interventions’, ‘family support’ and ‘family education’, and/or ‘family subsystems’.DiscussionThe process of theorizing about ‘family interventions’ and ‘HIV/AIDS‐family interventions’ is critical for putting forth essential components unique for designing culturally specific HIV/AIDS family interventions. In addition, any proposed design of HIV/AIDS family intervention should consider the impact of HIV/AIDS on the family across the family life span, disease trajectory, and from an interdisciplinary perspective.ConclusionTraining needs of family nurses should be met when designing multidisciplinary HIV/AIDS‐FIs. Furthermore, nurses should be proactive in advocating for HIV/AIDS family intervention and HIV/AIDS family policies to improve outcomes in family functioning, processes, and relationships. More needs to be done in regard to research on families, family interventions, effectiveness, and cost of family‐focused approaches.
Binding of Aldolase and Glyceraldehyde-3-Phosphate Dehydrogenase to the Cytoplasmic Tails of Plasmodium falciparum Merozoite Duffy Binding-Like and Reticulocyte Homology Ligands
Authors: Pal-Bhowmick Ipsita , Andersen John , Srinivasan Prakash , Narum David L. , Bosch Jürgen , Miller Louis H. 
Published: September 2012

ABSTRACT

Invasion of erythrocytes by
Plasmodium falciparum
requires a connection between the cytoplasmic tail of the parasite’s ligands for its erythrocyte receptors and the actin-myosin motor of the parasite. For the thromobospondin-related anonymous protein (TRAP) ligand on
Plasmodium
sporozoites, aldolase forms this connection and requires tryptophan and negatively charged amino acids in the ligand’s cytoplasmic tail. Because of the importance of the Duffy binding-like (DBL) and the reticulocyte homology (RH) ligand families in erythrocyte binding and merozoite invasion, we characterized the ability of their cytoplasmic tails to bind aldolase and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), both of which bind actin. We tested the binding of the cytoplasmic peptides of the two ligand families to aldolase and GAPDH. Only the cytoplasmic peptides of some RH ligands showed strong binding to aldolase, and the binding depended on the presence of an aromatic amino acid (phenylalanine or tyrosine), rather than tryptophan, in the context of negatively charged amino acids. The binding was confirmed by surface plasmon resonance analysis and was found to represent affinity similar to that seen with TRAP. An X-ray crystal structure of aldolase at 2.5 Å in the presence of RH2b peptide suggested that the binding site location was near the TRAP-binding site. GAPDH bound to some of the cytoplasmic tails of certain RH and DBL ligands in an aromatic amino acid-dependent manner. Thus, the connection between
Plasmodium
merozoite ligands and erythrocyte receptors and the actin motor can be achieved through the activity of either aldolase or GAPDH by mechanisms that do not require tryptophan but, rather, other aromatic amino acids.

IMPORTANCE
The invasion of the
Plasmodium
merozoite into erythrocytes is a critical element in malaria pathogenesis. It is important to understand the molecular details of this process, as this machinery can be a target for both vaccine and drug development. In
Plasmodium
sporozoites and
Toxoplasma
tachyzoites, invasion involves a glycolytic enzyme aldolase, linking the cytoplasmic tail domains of the parasite ligands to the actin-myosin motor that drives invasion. This binding requires a tryptophan that cannot be replaced by other aromatic residues. Here we show that aldolase binds the cytoplasmic tails of some
P. falciparum
merozoite erythrocyte-binding ligands but that the binding involves aromatic residues other than tryptophan. The biological relevance of aldolase binding to cytoplasmic tails of parasite ligands in invasion is demonstrated by our observation that RH2b but not RH2a binds to aldolase and, as previously shown, that RH2b but not RH2a is required for
P. falciparum
invasion of erythrocytes.
The burden of non-acute dying on society: dying of cancer and chronic disease in the European Union
Authors: Hasselaar Jeroen , Engels Yvonne , Menten Johan , Jaspers Birgit , Vissers Kris 
Published: September 2012

ObjectivesDue to the ageing of the European population, the burden of non-acute dying on society is expected to increase. The aim of this study is to estimate the number of persons dying of cancer and chronic disease in Europe, including regional differences.MethodsDeath certificates of deceased persons in the European Union (EU)-27 countries in 2007 (some countries 2006 or 2004) were analysed and primary death causes were listed. These data were prepared for the general population and for the population of 65 years and older. Crude death rates (CDRs) were calculated for both groups and for all included countries.ResultsOf 480 million deceased European people, 202 million died of cancer and chronic disease in 2007 (42%). The CDR of the EU-27 countries was 409 (95% CI 370 to 451) for cancer and other chronic diseases per 100 000 inhabitants in 2007. For the 65+ population, the CDR for the EU-27 was 1783 (95% CI 1701 to 1868) for cancer and chronic disease. Large differences across countries appeared. An inverse relationship was shown for country-specific CDRs for cancer and chronic disease versus CDRs for other death causes (R=−0.41; p=0.04).ConclusionsDying of cancer and chronic diseases involves a considerable burden on the European society. Future research should relate this information to the prevalence of symptoms and the use of palliative care services. European policy makers should take into account regional variations in developing long- and short-term palliative care strategies.
Viral RNA Patterns and High Viral Load Reliably Define Oropharynx Carcinomas with Active HPV16 Involvement
Authors: Holzinger Dana , Schmitt Markus , Dyckhoff Gerhard , Benner Axel , Pawlita Michael , Bosch Franz X. 
Published: September 2012

AbstractOropharyngeal squamous cell carcinomas (OPSCC) that are associated with human papilloma virus (HPV) infection carry a more favorable prognosis than those that are HPV-negative. However, it remains unclear which biomarker(s) can reliably determine which OPSCC specimens are truly driven by HPV infection. In this study, we analyzed 199 fresh-frozen OPSCC specimens for HPV DNA, viral load, RNA expression patterns typical for cervical carcinomas (CxCaRNA+), and the HPV-targeted tumor suppressor protein p16INK4a as markers for HPV infection. In this set of specimens, there was a 49% prevalence of DNA for the cancer-associated HPV type 16 (HPV+). However, there was only a 16% prevalence of high viral load and only a 20% prevalence of CxCaRNA+, a marker of HPV16 carcinogenic activity. Among the CxCaRNA+ tumors, 78% of the specimens exhibited overexpression of p16INK4a, which also occurred in 14% of the HPV-negative tumors. Using a multivariate survival analysis with HPV negativity as the reference group, CxCaRNA+ as a single marker conferred the lowest risk of death [HR = 0.28, 95% confidence interval (CI), 0.13–0.61] from oropharyngeal cancer, closely followed by high viral load (HR = 0.32, 95% CI, 0.14–0.73). In contrast, a weaker inverse association was found for OPSCC that were HPV+ and p16INK4a high (HR = 0.55, 95% CI, 0.29–1.08). In summary, our findings argued that viral load or RNA pattern analysis is better suited than p16INK4a expression to identify HPV16-driven tumors in OPSCC patient populations. Cancer Res; 72(19); 4993–5003. ©2012 AACR.
ColoGuidePro: A Prognostic 7-Gene Expression Signature for Stage III Colorectal Cancer Patients
Authors: Sveen Anita , Ågesen Trude H. , Nesbakken Arild , Meling Gunn Iren , Rognum Torleiv O. , Liestøl Knut , Skotheim Rolf I. , Lothe Ragnhild A. 
Published: September 2012

AbstractPurpose: Improved prognostic stratification of patients with stage II and III colorectal cancer is warranted for postoperative clinical decision making. This study was conducted to develop a clinically feasible and robust prognostic classifier for these patients independent of adjuvant treatment.Experimental Design: Global gene expression profiles from altogether 387 stage II and III colorectal cancer tissue samples from three independent patient series were included in the study. ColoGuidePro, a seven-gene prognostic classifier, was developed from a selected Norwegian learning series (n = 95; no adjuvant treatment) using lasso-penalized multivariate survival modeling with cross-validation.Results: The expression signature significantly stratified patients in a consecutive Norwegian test series, in which patients were treated according to current standards [HR, 2.9 (1.1–7.5); P = 0.03; n = 77] and an external validation series [HR, 3.7 (2.0–6.8); P &lt; 0.001; n = 215] according to survival. ColoGuidePro was also an independent predictor of prognosis in multivariate models including tumor stage in both series (HR, ≥3.1; P ≤ 0.03). In the validation series, which consisted of patients from other populations (United States and Australia), 5-year relapse-free survival was significantly predicted for stage III patients only (P &lt; 0.001; n = 107). Here, prognostic stratification was independent of adjuvant treatment (P = 0.001).Conclusions: We present ColoGuidePro, a prognostic classifier developed for patients with stage II and III colorectal cancer. The test is suitable for transfer to clinical use and has best prognostic prediction potential for stage III patients. Clin Cancer Res; 18(21); 6001–10. ©2012 AACR.
MRI-Based Liver Iron Content Predicts for Nonrelapse Mortality in MDS and AML Patients Undergoing Allogeneic Stem Cell Transplantation
Authors: Wermke Martin , Schmidt Anne , Middeke Jan Moritz , Sockel Katja , von Bonin Malte , Schönefeldt Claudia , Mair Sabine , Plodeck Verena , Laniado Michael , Weiss Günter , Schetelig Johannes , Ehninger Gerhard , Theurl Igor , Bornhäuser Martin , Platzbecker Uwe 
Published: September 2012

Abstract
Purpose: Retrospective, surrogate marker–based studies have found inconsistent associations between systemic iron overload (SIO) and adverse outcome in patients undergoing allogeneic stem cell transplantation (allo-SCT). As a consequence, the impact of SIO in this context remains under debate. The aim of this study was to test whether the objective pretransplant quantification of liver-iron content (LIC) by magnetic resonance imaging (MRI) could circumvent these limitations and conclusively define the prognostic relevance of SIO.
Experimental Design: The correlation between pretransplant LIC and surrogate parameters as well as the impact of SIO on posttransplant outcome was assessed within an observational study of patients (n = 88) with either myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) undergoing allo-SCT.
Results: Ferritin levels of 1,000 ng/mL or more provided only poor specificity (31.8%) for predicting elevated LIC (≥125 μmol/g) and even higher thresholds (≥2,500 ng/mL) lacked an association with nonrelapse mortality (NRM). In contrast, LIC 125 μmol/g or more was a significant risk factor for NRM in uni- and multivariate analysis (HR = 2.98; P = 0.016). Multivariate Cox-regression further showed that LIC 125 μmol/g or more was associated with a decreased overall survival (HR = 2.24, P = 0.038), whereas ferritin or transfusion burden were not.
Conclusions: SIO reflected by LIC is an independent negative prognostic factor for posttransplant outcome in patients with AML and MDS undergoing allo-SCT. Therefore, MRI-based LIC, and not interference-prone serum markers such as ferritin, should be preferred for pretransplant risk stratification and patient selection in future clinical trials. Clin Cancer Res; 18(23); 6460–8. ©2012 AACR.
Multiple Isoforms of CDC25 Oppose ATM Activity to Maintain Cell Proliferation during Vertebrate Development
Authors: Verduzco Daniel , Dovey Jennifer Shepard , Shukla Abhay A. , Kodym Elisabeth , Skaug Brian A. , Amatruda James F. 
Published: September 2012

Abstract
The early development of vertebrate embryos is characterized by rapid cell proliferation necessary to support the embryo's growth. During this period, the embryo must maintain a balance between ongoing cell proliferation and mechanisms that arrest or delay the cell cycle to repair oxidative damage and other genotoxic stresses. The ataxia-telangiectasia mutated (ATM) kinase is a critical regulator of the response to DNA damage, acting through downstream effectors, such as p53 and checkpoint kinases (CHK) to mediate cell-cycle checkpoints in the presence of DNA damage. Mice and humans with inactivating mutations in ATM are viable but have increased susceptibility to cancers. The possible role of ATM in limiting cell proliferation in early embryos has not been fully defined. One target of ATM and CHKs is the Cdc25 phosphatase, which facilitates cell-cycle progression by removing inhibitory phosphates from cyclin-dependent kinases (CDK). We have identified a zebrafish mutant, standstill, with an inactivating mutation in cdc25a. Loss of cdc25a in the zebrafish leads to accumulation of cells in late G2 phase. We find that the novel family member cdc25d is essential for early development in the absence of cdc25a, establishing for the first time that cdc25d is active in vivo in zebrafish. Surprisingly, we find that cell-cycle progression in cdc25a mutants can be rescued by chemical or genetic inhibition of ATM. Checkpoint activation in cdc25a mutants occurs despite the absence of increased DNA damage, highlighting the role of Cdc25 proteins to balance constitutive ATM activity during early embryonic development. Mol Cancer Res; 10(11); 1451–61. ©2012 AACR.
Differential putaminal morphology in Huntington’s disease, frontotemporal dementia and Alzheimer’s disease
Authors: Looi Jeffrey CL , Rajagopalan Priya , Walterfang Mark , Madsen Sarah K , Thompson Paul M , Macfarlane Matthew D , Ching Chris , Chua Phyllis , Velakoulis Dennis 
Published: September 2012

Objective: Direct neuronal loss or deafferentation of the putamen, a critical hub in corticostriatal circuits, may result in diverse and distinct cognitive and motoric dysfunction in neurodegenerative disease. Differential putaminal morphology, as a quantitative measure of corticostriatal integrity, may thus be evident in Huntington’s disease (HD), Alzheimer’s disease (AD) and frontotemporal dementia (FTD), diseases with differential clinical dysfunction. Methods: HD ( n = 17), FTD ( n = 33) and AD ( n = 13) patients were diagnosed according to international consensus criteria and, with healthy controls ( n = 17), were scanned on the same MRI scanner. Patients underwent brief cognitive testing using the Neuropsychiatry Unit Cognitive Assessment Tool (NUCOG). Ten MRI scans from this dataset were manually segmented as a training set for the Adaboost algorithm, which automatically segmented all remaining scans for the putamen, yielding the following subset of the data: 9 left and 12 right putamen segmentations for AD; 25 left and 26 right putamina for FTD; 16 left and 15 right putamina for HD; 12 left and 12 right putamina for controls. Shape analysis was performed at each point on the surface of each structure using a multiple regression controlling for age and sex to compare radial distance across diagnostic groups. Results: Age, but not sex and intracranial volume (ICV), were significantly different in the segmentation subgroups by diagnosis. The AD group showed significantly poorer performance on cognitive testing than FTD. Mean putaminal volumes were HD < FTD < AD ≤ controls, controlling for age and ICV. The greatest putaminal shape deflation was evident in HD, followed by FTD, in regions corresponding to the interconnections to motoric cortex. Conclusions: Differential patterns of putaminal atrophy in HD, FTD and AD, with relevance to corticostriatal circuits, suggest the putamen may be a suitable clinical biomarker in neurodegenerative disease.
A theoretical analysis for fiber contacts in multilayer nanofibrous assemblies
Authors: Bagherzadeh Roohollah , Shaikhzadeh Najar Saeed , Latifi Masoud , Amani Tehran Mohammad , Kong Lingxue 
Published: September 2012

A theoretical analysis is presented for the estimation of the number of contacts between fibers in random multilayer nanofibrous assemblies with arbitrary fiber diameter and orientation. The statistics of fiber contacts for single-layer nanofiber mats were considered first, and the equations were developed for three-dimensional multilayer nanofibrous assemblies by considering the superposition of the single-layer assemblies. Based on the theoretical approach presented here for multilayer nanofibrous networks, the network porosity, mean fiber diameter and a function of fiber aspect ratio contribute to a model to determine the average number of fiber contacts per unit fiber length in multilayer nanofibrous mats. The theory is studied parametrically and results compared with the work of a model presented by Samson. It is shown that the presented model compared to the existing models is more sensitive with the fiber diameter in the nano-scale. It is also believed that the presented theory for fiber-to-fiber contacts is more realistic and useful for further studies of multilayer nanofibrous assemblies.
Engulfment of hematopoietic stem cells caused by down-regulation of CD47 is critical in the pathogenesis of hemophagocytic lymphohistiocytosis
Authors: Kuriyama Takuro , Takenaka Katsuto , Kohno Kentaro , Yamauchi Takuji , Daitoku Shinya , Yoshimoto Goichi , Kikushige Yoshikane , Kishimoto Junji , Abe Yasunobu , Harada Naoki , Miyamoto Toshihiro , Iwasaki Hiromi , Teshima Takanori , Akashi Koichi 
Published: September 2012

AbstractHemophagocytic lymphohistiocytosis (HLH) is characterized by deregulated engulfment of hematopoietic stem cells (HSCs) by BM macrophages, which are activated presumably by systemic inflammatory hypercytokinemia. In the present study, we show that the pathogenesis of HLH involves impairment of the antiphagocytic system operated by an interaction between surface CD47 and signal regulatory protein α (SIRPA). In HLH patients, changes in expression levels and HLH-specific polymorphism of SIRPA were not found. In contrast, the expression of surface CD47 was down-regulated specifically in HSCs in association with exacerbation of HLH, but not in healthy subjects. The number of BM HSCs in HLH patients was reduced to approximately 20% of that of healthy controls and macrophages from normal donors aggressively engulfed HSCs purified from HLH patients, but not those from healthy controls in vitro. Furthermore, in response to inflammatory cytokines, normal HSCs, but not progenitors or mature blood cells, down-regulated CD47 sufficiently to be engulfed by macrophages. The expression of prophagocytic calreticulin was kept suppressed at the HSC stage in both HLH patients and healthy controls, even in the presence of inflammatory cytokines. These data suggest that the CD47-SIRPA antiphagocytic system plays a key role in the maintenance of HSCs and that its disruption by HSC-specific CD47 down-regulation might be critical for HLH development.
Predictive value of the 4Ts scoring system for heparin-induced thrombocytopenia: a systematic review and meta-analysis
Authors: Cuker Adam , Gimotty Phyllis A. , Crowther Mark A. , Warkentin Theodore E. 
Published: September 2012

Abstract
The 4Ts is a pretest clinical scoring system for heparin-induced thrombocytopenia (HIT). Although widely used in clinical practice, its predictive value for HIT in diverse settings and patient populations is unknown. We performed a systematic review and meta-analysis to estimate the predictive value of the 4Ts in patients with suspected HIT. We searched PubMed, Cochrane Database, and ISI Web of Science for studies that included patients with suspected HIT, who were evaluated by both the 4Ts and a reference standard against which the 4Ts could be compared. Quality of eligible studies was assessed by QUADAS-2 criteria. Thirteen studies, collectively involving 3068 patients, fulfilled eligibility criteria. A total of 1712 (55.8%) patients were classified by 4Ts score as having a low probability of HIT. The negative predictive value of a low probability 4Ts score was 0.998 (95% CI, 0.970-1.000) and remained high irrespective of the party responsible for scoring, the prevalence of HIT, or the composition of the study population. The positive predictive value of an intermediate and high probability 4Ts score was 0.14 (0.09-0.22) and 0.64 (0.40-0.82), respectively. A low probability 4Ts score appears to be a robust means of excluding HIT. Patients with intermediate and high probability scores require further evaluation.