bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell adhesion molecules contribute to Alzheimer’s disease: multiple pathway analyses of two genome‐wide association studies
Authors: Liu Guiyou , Jiang Yongshuai , Wang Ping , Feng Rennan , Jiang Nan , Chen Xiaoyun , Song Hui , Chen Zugen 
Published: October 2011

J. Neurochem. (2012) 120, 190–198.AbstractAlzheimer’s disease (AD) is a kind of complex neurological disorder. The complex genetic architecture of AD makes genetic analysis difficult. Fortunately, a pathway‐based method to study the existing genome‐wide association studies datasets has been applied into AD. However, no shared Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway was reported. In this study, we performed multiple pathway analyses of French AD genome‐wide association studies dataset (discovery dataset, n = 7360, 2032 cases and 5328 controls) and Pfizer dataset (validation dataset, n = 2220, 1034 cases and 1186 controls). First, we performed multiple pathway analyses by Hypergeometric test, improved gene set enrichment analysis (IGSEA) and Z‐statistic test in KEGG. Using Hypergeometric test, we identified 54 and 25 significant pathways (p < 0.05) in discovery dataset and validation dataset, respectively. Using IGSEA method, we identified three significant pathways in both discovery and validation datasets, respectively. Using Z‐statistic test, we identified 19 significant pathways in validation dataset. Among the significant pathways, cell adhesion molecules (CAM) pathway was identified to be the only consistent signal emerging across multiple analyses in KEGG. After permutation and multiple testing corrections, CAM pathway was significant with p = 2.40E−05 (Hypergeometric test) and p = 3.00E−03 (IGSEA) in discovery dataset. In validation dataset, CAM pathway was significant with p = 1.84E−06 (Hypergeometric test), p = 1.00E−02 (IGSEA) and p = 2.81E−03 (Z‐statistic test). We replicated the association by multiple pathway analyses in Gene Ontology using Hypergeometric test (WebGestalt), modified Fisher’s exact test (DAVID) and Binomial test (PANTHER). Our findings provided further evidence on the association between CAM pathway and AD susceptibility, which would be helpful to study the genetic mechanisms of AD and may significantly assist in the development of therapeutic strategies.
Why are hippocampal CA1 neurons vulnerable but motor cortex neurons resistant to transient ischemia?
Authors: Zhu Hong , Yoshimoto Tanihiro , Imajo‐Ohmi Shinobu , Dazortsava Maryia , Mathivanan Arumugam , Yamashima Tetsumori 
Published: October 2011

J. Neurochem. (2012) 120, 574–585.AbstractIt is well‐known that heat‐shock protein 70.1 (Hsp70.1), a major protein of the human Hsp70 family, plays cytoprotective roles by both its chaperone function and stabilization of lysosomal membranes. Recently, we found that calpain‐mediated cleavage of carbonylated Hsp70.1 in the hippocampal cornu Ammonis1 (CA1) contributes to neuronal death after transient global ischemia. This study aims to elucidate the differential neuronal vulnerability between the motor cortex and CA1 sector against ischemia/reperfusion. Fluoro‐Jade B staining and terminal deoxynucleotidyl transferase‐mediated dUTP‐nick‐end‐labeling analysis of the monkey brain undergoing 20 min whole brain ischemia followed by reperfusion, showed that the motor cortex is significantly resistant to the ischemic insult compared with CA1. Up‐regulation of Hsp70.1 but absence of its cleavage by calpain facilitated its binding with NF‐κB p65/IκBα complex to minimize NF‐κB p65 activation, which contributed to a neuroprotection in the motor cortex. In contrast, because activated μ‐calpain cleaved carbonylated Hsp70.1 in CA1, the resultant Hsp70.1 dysfunction not only destabilized lysosomal membrane but also induced a sustained activation of NF‐κB p65, both of which resulted in delayed neuronal death. We propose that the cascades underlying lysosomal stabilization and regulating NF‐κB activation by Hsp70.1 may influence neuronal survival/death after the ischemia/reperfusion.
Double blockade of angiotensin II (AT1)‐receptors and ACE does not improve weight gain and glucose homeostasis better than single‐drug treatments in obese rats
Authors: Miesel Anja , Müller‐Fielitz Helge , Jöhren Olaf , Vogt Florian M , Raasch Walter 
Published: October 2011

BACKGROUND AND PURPOSE Combination therapies are becoming increasingly important for the treatment of high blood pressure. Little is known about whether double blockade of angiotensin II (AT1) receptors and angiotensin‐converting enzyme (ACE) exert synergistic metabolic effects.EXPERIMENTAL APPROACH Spontaneously hypertensive rats were allowed to choose between palatable chocolate bars and standard chow and were simultaneously treated with the AT1 blocker telmisartan (8 mg·kgbw−1·day−1), the ACE inhibitor ramipril (4 mg·kgbw−1·day−1) or a combination of the two (8 + 4 mg·kgbw−1·day−1) for 12 weeks.KEY RESULTS Although food‐dependent energy intake was increased by telmisartan and telmisartan + ramipril compared with ramipril or controls, body weight gain, abundance of fat and plasma leptin levels were decreased. Increased insulin levels in response to an oral glucose tolerance test were comparably attenuated by telmisartan and telmisartan + ramipril, but not by ramipril. During an insulin tolerance test, glucose utilization was equally as effectively improved by telmisartan and telmisartan + ramipril. In response to a stress test, ACTH, corticosterone and glucose increased in controls. These stress reactions were attenuated by telmisartan and telmisartan + ramipril.CONCLUSIONS AND IMPLICATIONS The combination of telmisartan + ramipril was no more efficacious in regulating body weight and glucose homeostasis than telmisartan alone. However, telmisartan was more effective than ramipril in improving metabolic parameters and in reducing body weight. The association between the decrease in stress responses and the diminished glucose levels after stress supports our hypothesis that the ability of telmisartan, as an AT1 receptor blocker, to alleviate stress reactions may contribute to its hypoglycaemic actions.
Potent mechanism‐based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates
Authors: Filppula AM , Laitila J , Neuvonen PJ , Backman JT 
Published: October 2011

BACKGROUND AND PURPOSEImatinib, a cytochrome P450 2C8 (CYP2C8) and CYP3A4 substrate, markedly increases plasma concentrations of the CYP3A4/5 substrate simvastatin and reduces hepatic CYP3A4/5 activity in humans. Because competitive inhibition of CYP3A4/5 does not explain these in vivo interactions, we investigated the reversible and time‐dependent inhibitory effects of imatinib and its main metabolite N‐desmethylimatinib on CYP2C8 and CYP3A4/5 in vitro.EXPERIMENTAL APPROACHAmodiaquine N‐deethylation and midazolam 1′‐hydroxylation were used as marker reactions for CYP2C8 and CYP3A4/5 activity. Direct, IC50‐shift, and time‐dependent inhibition were assessed with human liver microsomes.KEY RESULTSInhibition of CYP3A4 activity by imatinib was pre‐incubation time‐, concentration‐ and NADPH‐dependent, and the time‐dependent inactivation variables KI and kinact were 14.3 µM and 0.072 min−1 respectively. In direct inhibition experiments, imatinib and N‐desmethylimatinib inhibited amodiaquine N‐deethylation with a Ki of 8.4 and 12.8 µM, respectively, and midazolam 1′‐hydroxylation with a Ki of 23.3 and 18.1 µM respectively. The time‐dependent inhibition effect of imatinib was predicted to cause up to 90% inhibition of hepatic CYP3A4 activity with clinically relevant imatinib concentrations, whereas the direct inhibition was predicted to be negligible in vivo.CONCLUSIONS AND IMPLICATIONSImatinib is a potent mechanism‐based inhibitor of CYP3A4 in vitro and this finding explains the imatinib–simvastatin interaction and suggests that imatinib could markedly increase plasma concentrations of other CYP3A4 substrates. Our results also suggest a possibility of autoinhibition of CYP3A4‐mediated imatinib metabolism leading to a less significant role for CYP3A4 in imatinib biotransformation in vivo than previously proposed.
Krüppel‐like factor 4 is induced by rapamycin and mediates the anti‐proliferative effect of rapamycin in rat carotid arteries after balloon injury
Authors: Wang Ying , Zhao Beilei , Zhang Yi , Tang Zhihui , Shen Qiang , Zhang Youyi , Zhang Weizhen , Du Jie , Chien Shu , Wang Nanping 
Published: October 2011

BACKGROUND AND PURPOSE The transcription factor, Krüppel‐like factor 4 (KLF4), plays an important role in regulating the proliferation of vascular smooth muscle cells. This study aimed to examine the effect of rapamycin on the expression of KLF4 and the role of KLF4 in arterial neointimal formation.EXPERIMENTAL APPROACH Expression of KLF4 was monitored using real‐time PCR and immunoblotting in cultured vascular smooth muscle cells. and in rat carotid arteries in vivo after balloon injury. Adenovirus‐mediated overexpression and siRNA‐mediated knockdown of KLF4 were used to examine the role of KLF4 in mediating the anti‐proliferative role of rapamycin . KLF4‐regulated genes were identified using cDNA microarray.KEY RESULTS Rapamycin induced the expression of KLF4 in vitro and in vivo. Overexpression of KLF4 inhibited cell proliferation and the activity of mammalian target of rapamycin (mTOR) and its downstream pathways, including 4EBP‐1 and p70S6K in vascular smooth muscle cells and prevented the neointimal formation in the balloon‐injured arteries. KLF4 up‐regulated the expression of GADD45β, p57kip2 and p27kip1. Furthermore, knockdown of KLF4 attenuated the anti‐proliferative effect of rapamycin both in vitro and in vivo.CONCLUSIONS AND IMPLICATIONS KLF4 plays an important role in mediating the anti‐proliferative effect of rapamycin in VSMCs and balloon‐injured arteries. Thus, it is a potential target for the treatment of proliferative vascular disorders such as restenosis after angioplasty.
An Image of Possibility: Illustrating a Pedagogic Encounter with Culture
Authors: Michael Maureen K. 
Published: October 2011

AbstractAn Image of Possibility is an interplay between image‐making and interpretation. It explores author‐created illustration as an art‐based tool for educational inquiry and is designed further to inform the creative research practice of the author. The illustration ‘Meeting People’ is created by the author to render an event of learning and culture pictorially evident. In a description of the process and content of the image it becomes clear that the creation of the image rehearses known ideas and literally re‐presents them. However, what is more interesting is that in a critical rereading of the image unintended ideas are revealed to the author. Illustration, the act of drawing and its manipulation, reveals meaning as an active component in research discovery through creative practice. The illustration encapsulates characteristics of Bourriaud's relational aesthetics and Atkinson's notion of the learning event. The ‘truth’ of the learning event is revealed not in the relationship between the students and culture, as at first assumed, but in the relationship between the author/artist and the illustration. From the perspective of the author/artist, the article explores the question: ‘To what extent can illustration illuminate pedagogic encounters with culture?’ An Image of Possibility presents a metonymical representation of an educational encounter and offers illustration as a tool for educational inquiry.
Moments of Intensity: Affect and the Making and Teaching of Art
Authors: Addison Nicholas 
Published: October 2011

AbstractAffect often arises unexpectedly within the process of making art (along with other creative activities). In this article I argue for affect as a necessary and constructive dynamic within educational processes specifically for art and design. After a consideration of its recent neglect within art education, I revisit the notion of affect with reference to a number of thinkers who provide different perspectives, but particularly through the lens of the US psychologist Silvan Tomkins. Through him and others I seek to understand how affect can be recognised and cultivated in pedagogic situations. I do so by reflecting on the making and teaching experiences of students following an MA in Art and Design in Education and a practice‐based PhD, as witnessed by me (supervisor/co‐tutor), as recounted by students and as discussed in post‐event conversation/semi‐structured interviews.
Can a decision‐making model be justified in the management of hepatocellular adenoma?
Authors: van Aalten Susanna M. , Witjes Caroline D. M. , de Man Robert A. , Ijzermans Jan N. M. , Terkivatan Türkan 
Published: October 2011

AbstractDuring recent years, there was a great development in the area of hepatocellular adenomas (HCA), especially regarding the pathological subtype classification, radiological imaging and management during pregnancy. This review discusses the current knowledge about diagnosis and treatment modalities of HCA and proposes a decision‐making model for HCA. A Medline search of studies relevant to epidemiology, histopathology, complications, imaging and management of HCA lesions was undertaken. References from identified articles were hand‐searched for further relevant articles.
Public Health Nursing—Indispensible and Economical for Everyone if Organized
Authors: Emerson Haven 
Published: October 2011

AbstractIn August 1930, the editors of the original Public Health Nursing published an article derived from a speech made by Dr. Haven Emerson, then professor of public health administration at Columbia University, on the topic of the distribution and use of public health nurses. The speech was made before an audience of lay board members from hospitals and public health nursing organizations in Chicago, February 17, 1930. Emerson reported the results of a data analysis in which the numbers and credentials of public health nurses in 24 cities across the United States were reported. Excerpts from this report and Dr. Emerson's conclusions are powerful reminders that while there were issues of labor supply and distribution, the power of nurses to effect social transformation was central to the role as conceived by those administering public health services.
Randomized Controlled Trial of Mailed Personalized Feedback for Problem Drinkers in the Emergency Department: The Short‐Term Impact
Authors: Havard Alys , Shakeshaft Anthony P. , Conigrave Katherine M. , Doran Christopher M. 
Published: October 2011

Background: Evidence exists for the efficacy of emergency department (ED)‐based brief alcohol interventions, but attempts to incorporate face‐to‐face interventions into routine ED practice have been hampered by time, financial, and attitudinal constraints. Mailed personalized feedback, which is likely to be more feasible, has been associated with reduced alcohol consumption in other settings, but its cost‐effectiveness in the ED has not been examined.
Methods:  The intervention was evaluated with a randomized controlled trial of patients presenting to 5 rural EDs in New South Wales, Australia. Patients aged 14 years and older were screened using the Alcohol Use Disorders Identification Test, and those scoring 8 or more were randomly allocated to the intervention or control group. Participants in the intervention group received mailed personalized feedback regarding their alcohol consumption. The control group received no feedback.
Results:  Two hundred and forty‐four (80%) participants were successfully followed up at 6 weeks. A significant effect of the mailed feedback was observed only in patients with an alcohol‐involved ED presentation. Among this subgroup of participants, those in the intervention group consumed 12.2 fewer drinks per week than the control group after controlling for baseline consumption and other covariates (effect size d = 0.59). The intervention was associated with an average cost of Australian $5.83 per patient, and among participants with an alcohol‐involved ED presentation, an incremental cost‐effectiveness ratio of 0.48.
Conclusions:  Mailed personalized feedback is efficacious in reducing quantity/frequency of alcohol consumption among patients with alcohol‐involved ED presentations. Mailed feedback has high cost‐efficacy and a low absolute cost, making it a promising candidate for integration into ED care.
In vitro quality of single‐donor platelets treated with riboflavin and ultraviolet light and stored in platelet storage medium for up to 8 days
Authors: Cookson Philip , Thomas Stephen , Marschner Susanne , Goodrich Ray , Cardigan Rebecca 
Published: October 2011

BACKGROUND: The Mirasol pathogen reduction technology system is known to increase the activation and metabolic rate of platelets (PLTs). Storage of Mirasol PLTs in PLT storage medium (PSM) has the potential to slow this accelerated PLT storage lesion. We investigated the quality of Mirasol‐treated PLTs stored in either 50% SSP+ or 50% Composol for 8 days.STUDY DESIGN AND METHODS: Single‐donor double hyperconcentrates were divided between control and Mirasol‐treated arms and after treatment were suspended in approximately 50% (vol/vol) SSP+ (n = 8) or Composol (n = 7). In vitro markers of PLT activation and/or apoptosis were measured over an 8‐day storage period.RESULTS: Mirasol treatment resulted in increased spontaneous PLT activation and glycolysis and these effects were worsened when PLTs were treated below a certain volume (150 mL). At higher treatment volumes there were no significant differences between treated units stored in either Composol or SSP+. When low‐volume units were stored in Composol the median pH fell below 6.4 on Day 5 and bicarbonate was undetectable, whereas in SSP+ the median pH value was greater than 6.9 and bicarbonate remained at detectable levels, despite other markers of in vitro function being similar to those of Composol.CONCLUSION: Mirasol treatment of PLTs followed by storage in PSM results in increased PLT activation and metabolism to a level similar to that reported for PLTs treated and stored in plasma. Units treated at a low volume (<150 mL) showed poor in vitro quality.
Transfusion safety in francophone African countries: an analysis of strategies for the medical selection of blood donors
Authors: Tagny Claude Tayou , Kouao Maxime Diané , Touré Hamane , Gargouri Jalel , Fazul Ahamada Said , Ouattara Siaka , Anani Ludovic , Othmani Habiba , Feteke Lochina , Dahourou Honorine , Mbensa Guy Olivier , Molé Simplice , Nébié Yacouba , Mbangue Madeleine , Toukam Michel , Boulahi Mahommed Ould , Andriambelo Lalatiana Valisoa , Rakoto Olivat , Baby Mounirou , Yahaya Rakia , Bokilo Amelia , Senyana Florent , Mbanya Dora , Shiboski Caroline , Murphy Edward L. , Lefrère Jean Jacques 
Published: October 2011

BACKGROUND: The goal of selecting a healthy blood donor is to safeguard donors and reduce the risks of infections and immunologic complications for recipients.STUDY DESIGN AND METHODS: To evaluate the blood donor selection process, a survey was conducted in 28 blood transfusion centers located in 15 francophone African countries. Data collected included availability of blood products, risk factors for infection identified among blood donor candidates, the processing of the information collected before blood collection, the review process for the medical history of blood donor candidates, and deferral criteria for donor candidates.RESULTS: During the year 2009, participating transfusion centers identified 366,924 blood donor candidates. A mean of 13% (range, 0%‐36%) of the donor candidates were excluded based solely on their medical status. The main risk factors for blood‐borne infections were having multiple sex partners, sexual intercourse with occasional partners, and religious scarification. Most transfusion centers collected this information verbally instead of having a written questionnaire. The topics least addressed were the possible complications relating to the donation, religious scarifications, and history of sickle cell anemia and hemorrhage. Only three centers recorded the temperature of the blood donors. The deferral criteria least reported were sickle cell anemia, piercing, scarification, and tattoo.CONCLUSIONS: The medical selection process was not performed systemically and thoroughly enough, given the regional epidemiologic risks. It is essential to identify the risk factors specific to francophone African countries and modify the current medical history questionnaires to develop a more effective and relevant selection process.
French “As She Is Spoke”
Authors: Davis Edwin B. 
Published: October 2011

What authority should be adopted for the pronunciation of French? Great divergence of pronunciation not only among classes of society but among individual “authorities.” Divergence from all acknowledged standards of the great mass of Parisians. Mutual derision of each other's pronunciation by bourgeois and purists.Conclusion: There is no inviolable standard of Parisian pronunciation. Value, however, in phonetic training. Inadequacy of Grammont's description of phonemes. The student of French should be better informed of these facts
An Administrator Looks at Language Study*
Authors: Morrison J. Cayce 
Published: October 2011

Author's Summary.— The Second World War brought to the people of the United States opportunities for leadership among the peoples of the world. Obviously, such leadership can be exercised wisely only insofar as we know and understand the aspirations, the hopes, the ideals, and the thoughts of others. In the final analysis, such wisdom is gleaned only through knowledge of language as a working tool. To gain such mastery of the languages of other peoples as will be needed by Americans in the years ahead presents many problems which must be finally answered in terms of experimentation and research.Looking to the future, we shall be not less interested in the cultural values of language study, but we shall strive to attain those cultural values through teaching languages as an essential instrument in the exercise of our duties as citizens of the world.)
Lead Implant Duration Does Not Always Predict Ease of Extraction: Extraction Sheath May Be Required at < 1 Year
Authors: MAYTIN MELANIE , EPSTEIN LAURENCE M. , JOHN ROY M. 
Published: October 2011

Introduction:
Lead implant duration is a predictor of extraction sheath (ES) use in transvenous lead extraction (TLE). Most operators agree that leads with short implant durations can be extracted easily but data regarding defibrillator (implantable cardioverter‐defibrillator [ICD]) leads and newer generation leads with backfilled coils are limited.
Methods and Results:
We performed a retrospective study of consecutive patients undergoing TLE of leads with implant durations of ≤ 2 years at a single, high‐volume center. Patient and lead characteristics, indications, and ES use were analyzed. Between January 2000 and January 2011, 139 patients underwent TLE meeting inclusion criteria. Mean implant duration was 13.2 ± 6.4 months. The cohort was 67% male with a mean age of 63 years (16–93) and left ventricular ejection fraction of 36 ± 17%. Indications for extraction included infection (51%), lead malfunction (27%), device upgrade (13%), and other indications (venous occlusion, severe chronic pain at site of device or lead, advisory leads, etc., 9%). Extraction was achieved with simple traction alone in 68% of the 239 leads removed. ES assistance with laser or femoral sheaths was employed in 32% of cases. ES use increased significantly with longer implant duration (P = 0.0004). In multivariate analysis, young age, the presence of an ICD, and increasing implant duration were the strongest predictors of the need for ES assistance for successful lead removal. There was no statistically significant difference in ES use between older and newer generation ICD leads (P = 0.68).
Conclusions:
While leads with short implant durations may be extracted easily, the need for ES assistance is significant and frequently unpredictable even with newer generation ICD leads. Thus, operators should be fully prepared to use all available methods of extraction in every case regardless of implant duration. (PACE 2011; 34:1615–1620)