bluuebunny/crossref_metadata_2025_split huggingface dataset:
scribblemutants promote aPKC and JNK-dependent epithelial neoplasia independently of Crumbs
Authors: Leong Gregory R , Goulding Karen R , Amin Nancy , Richardson Helena E , Brumby Anthony M 
Published: September 2009

Abstract

Background

Metastatic neoplasias are characterized by excessive cell proliferation and disruptions to apico-basal cell polarity and tissue architecture. Understanding how alterations in cell polarity can impact upon tumour development is, therefore, a central issue in cancer biology. The Drosophila gene scribble (scrib) encodes a PDZ-domain scaffolding protein that regulates cell polarity and acts as a tumour suppressor in flies. Increasing evidence also implicates the loss of human Scrib in cancer. In this report, we investigate how loss of Scrib promotes epithelial tumourigenesis in Drosophila, both alone and in cooperation with oncogenic mutations.

Results

We find that genetically distinct atypical protein kinase C (aPKC)-dependent and Jun N-terminal kinase (JNK)-dependent alterations in scrib mutants drive epithelial tumourigenesis. First, we show that over-expression of the apical cell polarity determinants Crumbs (Crb) or aPKC induces similar cell morphology defects and over-proliferation phenotypes as scrib loss-of-function. However, the morphological and proliferative defects in scrib mutants are independent of Crb function, and instead can be rescued by a dominant negative (kinase dead) aPKC transgene. Secondly, we demonstrate that loss of Scrib promotes oncogene-mediated transformation through both aPKC and JNK-dependent pathways. JNK normally promotes apoptosis of scrib mutant cells. However, in cooperation with oncogenic activated Ras or Notch signalling, JNK becomes an essential driver of tumour overgrowth and invasion. aPKC-dependent signalling in scrib mutants cooperates with JNK to significantly enhance oncogene-mediated tumour overgrowth.

Conclusion

These results demonstrate distinct aPKC and JNK-dependent pathways through which loss of Scrib promotes tumourigenesis in Drosophila. This is likely to have a direct relevance to the way in which human Scrib can similarly restrain an oncogene-mediated transformation and, more generally, on how the outcome of oncogenic signalling can be profoundly perturbed by defects in apico-basal epithelial cell polarity.
Large A-Fiber Activity is Required for Microglial Proliferation and P38 MAPK Activation in the Spinal Cord: Different Effects of Resiniferatoxin and Bupivacaine on Spinal Microglial Changes after Spared Nerve Injury
Authors: Suter Marc R , Berta Temugin , Gao Yong-Jing , Decosterd Isabelle , Ji Ru-Rong 
Published: September 2009

BackgroundAfter peripheral nerve injury, spontaneous ectopic activity arising from the peripheral axons plays an important role in inducing central sensitization and neuropathic pain. Recent evidence indicates that activation of spinal cord microglia also contributes to the development of neuropathic pain. In particular, activation of p38 mitogen-activated protein kinase (MAPK) in spinal microglia is required for the development of mechanical allodynia. However, activity-dependent activation of microglia after nerve injury has not been fully addressed. To determine whether spontaneous activity from C- or A-fibers is required for microglial activation, we used resiniferatoxin (RTX) to block the conduction of transient receptor potential vanilloid subtype 1 (TRPV1) positive fibers (mostly C- and Aδ-fibers) and bupivacaine microspheres to block all fibers of the sciatic nerve in rats before spared nerve injury (SNI), and observed spinal microglial changes 2 days later.ResultsSNI induced robust mechanical allodynia and p38 activation in spinal microglia. SNI also induced marked cell proliferation in the spinal cord, and all the proliferating cells (BrdU+) were microglia (Iba1+). Bupivacaine induced a complete sensory and motor blockade and also significantly inhibited p38 activation and microglial proliferation in the spinal cord. In contrast, and although it produced an efficient nociceptive block, RTX failed to inhibit p38 activation and microglial proliferation in the spinal cord.Conclusion(1) Blocking peripheral input in TRPV1-positive fibers (presumably C-fibers) is not enough to prevent nerve injury-induced spinal microglial activation. (2) Peripheral input from large myelinated fibers is important for microglial activation. (3) Microglial activation is associated with mechanical allodynia.
The control of hookworm infection in China
Authors: Zheng Qi , Chen Ying , Zhang Hao-Bing , Chen Jia-Xu , Zhou Xiao-Nong 
Published: September 2009

AbstractBackgroundHookworm is still one of the three main soil-transmitted helminths prevalent in China, and 39 million cases infected with hookworm were estimated in China in 2006.ResultsThe main approach to the control of hookworm infections in China consists of large-scale deworming, rebuilding sanitation systems in rural areas and health education. The availability of low-cost, safe and single-dose albendazole make large-scale deworming programs possible in China. Currently, sanitary latrines with three-cells are recommended by government for the control of soil-transmitted helminths, since 35% of helminth infections and 83% of worm eggs could be reduced after using this kind of sanitary latrine. In addition, economic prosperity contributes greatly to the reduction of hookworm prevalence, but the inequity of economic and social development among different regions of China provides a scenario that the worst threat of hookworm infection is located in the poorest areas of southern and central China. Therefore, it is necessary to put more investments into prophylaxis and treatment of hookworm in these poor regions.ConclusionAlthough the prevalence of hookworm infection has fallen significantly in the last 15 years in China, the current strategy for controlling hookworm infections still needs to be strengthened along with the three-pronged approach, e.g. distributing anthelmintic drugs in schools and undertaking large-scale of hookworm deworming, improving water supplies and sanitation, and proper health education.
“Ma volonté est celle du peuple”: Voting in the Plebiscite and Parliamentary Elections during Napoléon's Hundred Days, April–May 1815
Authors: Crook Malcolm 
Published: September 2009

Histories of the Hundred Days, which followed Napoléon's bold and unexpected return from exile on Elba in 1815, have generally neglected the response of the French people, concentrating instead on the resurgent emperor himself and his definitive defeat at Waterloo. This study, part of a project exploring the elections of the Napoleonic period, aims to redress the balance by examining how French males voted in the plebiscite and parliamentary elections that accompanied this brief but vital period. It will not only map the lasting contours of Bonapartism but also suggest that the Hundred Days carried great significance, in terms of both forging the Napoleonic legend and entrenching a culture of voting in postrevolutionary France.
L'histoire des Cent-Jours en 1815, la période qui suit le retour à la fois audacieux et inattendu de Napoléon de son exil sur l'île d'Elbe, néglige en général la réponse du peuple français pour concentrer sur le personnage de l'empereur et sa défaite militaire à Waterloo. Cette étude, qui fait partie d'un projet consacré aux élections de l'ère napoléonienne, cherche à rétablir l'équilibre en examinant comment les Français votaient dans le plébiscite et les élections législatives organisées au cours de cet événement bref, mais bien significatif. Elle dresse la carte des contours durables du bonapartisme et, en même temps, souligne la grande importance des Cent-Jours qui établit la légende napoléonienne et renforce la culture du vote dans la France postrévolutionnaire.
A Novel Color Former Organogel for Radiation Detection Systems
Authors: Itoi Hiroaki , Sekine Yoshiyuki , Sekiguchi Masayuki , Tachikawa Tatsuya 
Published: September 2009

Abstract
A novel leuco phenoxazine color former containing l-phenylalanine at the protecting group was prepared for radiation detection systems. It forms elongated self-assembled fibers in common organic solvents, leading to that efficient gelation. FE-SEM and FT-IR of the xerogel showed the color former formed a three-dimensional net-like structure. The color former organogel showed sufficient sensitivity to γ rays that it can be used for imaging in heavy particle radiotherapy and has good potential for three-dimensional radiation detection systems.
Crystal Structures and Magnetic Properties of Isonicotinate- and Dicyanometallate-bridged Manganese(II) Complexes
Authors: Kawasaki Takeshi , Kanadani Chikahide , Saito Toshiaki , Kitazawa Takafumi 
Published: September 2009

Abstract
Two novel 3D network coordination polymers [Mn(H2O)(ina){M(CN)2}]·H2O (ina = isonicotinato, M=Ag (1) or Au (2)) have been synthesized and characterized crystallographically and magnetically. In both complexes, the coordination geometries of the MnII atoms have MnN3O3 octahedral coordination built up by one tridentate ina ligand, one H2O molecule, and two μ-[M(CN)2]− units. SQUID data show weak antiferromagnetic interactions among the Mn atoms bridged by the ina ligands in 1 and 2.
Evaluation of Workforce and Organizational Issues in Establishing Primary Angioplasty in England
Authors: Carter Angela , Wood Stephen , Goodacre Steve , Sampson Fiona , Stables Rod 
Published: September 2009

Objective To assess workforce and organizational issues in establishing a primary angioplasty service in England. Methods Staff associated with the heart attack pathway at seven acute hospitals participating in the National Infarct Angioplasty Project (NIAP) completed a questionnaire, participated in focus groups and interviews, and observations were undertaken in catheter laboratories. Results All seven hospitals implemented primary angioplasty though not all provided a 24-hour service. Hospitals varied in size, number of staff involved in the delivery of angioplasty and the volume of cases. Hospitals that developed the service by incremental expansion encountered more problems than hospitals that planned for a full service at the outset. Simple, direct access to a catheter laboratory reduced delays and could be facilitated by an angioplasty gatekeeper. Little attention was paid to later cardiac rehabilitation. Multiskilling and the ability to work across traditional professional boundaries appeared to provide substantial advantages. Building relationships with key staff and auditing the heart attack pathway were critical to successful service development. Differences in remuneration and rest for staff undertaking out-of-hours working threatened sustainability. Conclusions Primary angioplasty was feasible in varied settings and generally supported by staff. However, the participating hospitals were selected enthusiasts, only some implemented a 24-hour service and activity levels were relatively low. Organizational and workforce issues need to be addressed to achieve an efficient and sustainable service.
Comparing Generic and Innovator Drugs: A Review of 12 Years of Bioequivalence Data from the United States Food and Drug Administration
Authors: Davit Barbara M , Nwakama Patrick E , Buehler Gary J , Conner Dale P , Haidar Sam H , Patel Dewrat T , Yang Yongsheng , Yu Lawrence X , Woodcock Janet 
Published: September 2009

Background: In the US, manufacturers seeking approval to market a generic drug product must submit data demonstrating that the generic formulation provides the same rate and extent of absorption as (ie, is bioequivalent to) the innovator drug product. Thus, most orally administered generic drug products in the US are approved based on results of one or more clinical bioequivalence studies. Objective: To evaluate how well the bioequivalence measures of generic drugs approved in the US over a 12-year period compare with those of their corresponding innovator counterparts. Methods: This retrospective analysis compared the generic and innovator bioequivalence measures from 2070 single-dose clinical bioequivalence studies of orally administered generic drug products approved by the Food and Drug Administration (FDA) from 1996 to 2007 (12 y). Bioequivalence measures evaluated were drug peak plasma concentration (Cmax) and area under the plasma drug concentration versus time curve (AUC), representing drug rate and extent of absorption, respectively. The generic/innovator Cmax and AUC geometric mean ratios (GMRs) were determined from each of the bioequivalence studies, which used from 12 to 170 subjects. The GMRs from the 2070 studies were averaged. In addition, the distribution of differences between generic means and innovator means was determined for both Cmax and AUC. Results: The mean ± SD of the GMRs from the 2070 studies was 1.00 ± 0.06 for Cmax and 1.00 ± 0.04 for AUC. The average difference in Cmax and AUC between generic and innovator products was 4.35% and 3.56%, respectively. In addition, in nearly 98% of the bioequivalence studies conducted during this period, the generic product AUC differed from that of the innovator product by less than 10%. Conclusions: The criteria used to evaluate generic drug bioequivalence studies support the FDA's objective of approving generic drug formulations that are therapeutically equivalent to their innovator counterparts.
Efficacy of Fluconazole for the Treatment of Onychomycosis
Authors: Brown Sherrill J 
Published: September 2009

Objective: To evaluate the efficacy of fluconazole for the treatment of onychomycosis. Data Sources: Searches of MEDLINE (1966–May 2009) and International Pharmaceutical Abstracts (1970–May 2009) were performed. Key search terms included fluconazole and onychomycosis. In addition, reference citations from identified publications were reviewed. Study Selection and Data Extraction: All articles in English identified from the data sources were evaluated. All studies evaluating oral fluconazole for the treatment of onychomycosis were included in the review. Data Synthesis: Seven studies evaluating fluconazole treatment for onychomycosis were identified. One study used daily dosing and the rest used once-weekly dosing. Treatment doses ranged from 100 mg to 450 mg weekly and 150 mg daily, and durations ranged from 12 weeks to 12 months. Most of the studies evaluated the efficacy of fluconazole in patients with toenail onychomycosis due to dermatophyte infection. Fluconazole was superior to placebo, with mycologic eradication rates ranging from 36% to 100% in placebo-controlled studies. In one of the comparative studies, the mycologic cure rate was lower with fluconazole (31.2%) compared with terbinafine (75%) and itraconazole (61.1%). Common adverse events reported with fluconazole use were headache, gastrointestinal pain, and diarrhea. Conclusions: Fluconazole is less effective than terbinafine and itraconazole in the treatment of onychomycosis. However, fluconazole may be preferred in patients unable to tolerate other oral antifungal agents due to the dosing regimen, adverse effect profile, and drug interactions.
Impact of a Renal Drug Dosing Service on Dose Adjustment in Hospitalized Patients with Chronic Kidney Disease
Authors: Hassan Yahaya , Al-Ramahi Rowa' J , Aziz Noorizan Abd , Ghazali Rozina 
Published: September 2009

Background: Appropriate drug selection and dosing for patients with chronic kidney disease (CKD) is important to avoid unwanted drug effects and ensure optimal patient outcomes. Objective: To assess the rate of inappropriate dosing in patients with CKD in a nephrology unit and to evaluate the impact on dose adjustment, adverse drug events (ADEs), and drug cost of having a pharmacist accompany a team of physicians on their rounds. Methods: This was a comparative study with a preintervention and postintervention design. The preintervention phase served as the control; it was prospective and observational only and was conducted from the beginning of February to the end of May 2007. The second phase (intervention phase) was conducted from the beginning of March to the end of June 2008. Two random samples of 300 patients with an estimated creatinine clearance less than or equal to 50 mL/min were included. During the intervention phase, a clinical pharmacist made rounds with the nephrology unit team and gave dosing adjustment recommendations when needed. A collection of reliable and up-to-date drug information references that are commonly used globally were used during the intervention. Results: In the preintervention group, drug dosage adjustment or avoidance, based on renal function, was necessary in 607 of 2814 (21.6%) prescriptions. Of these, 322 (53.0%) did not comply with guidelines. In the intervention group, adjustment was necessary for 640 of 2981 (21.5%) prescriptions. The pharmacist made 388 recommendations related to dosing adjustment, 212 (54.6%) of which were accepted by physicians. Clinicians' noncompliance with dosing guidelines decreased to 176 (27.5%) (p < 0.001). In the preintervention group, 64 (21.3%) patients had a suspected ADE, with a total of 73 events. In the intervention group, this number was significantly lower with 49 events in 48 (16.0%) patients (p < 0.05). The intervention resulted in drug cost savings of $2250 US. Conclusions: A renal drug dosing service for patients hospitalized with CKD can increase the proportion of drug dosing that is adjusted to take into account renal function. This can save drug costs and may prevent ADEs.
Analysis of Medications Returned to Community Pharmacies
Authors: James Tess H , Helms Margaret L , Braund Rhiannon 
Published: September 2009

Background: There are many causes of medication waste, including excess supply, treatment changes, and patient nonadherence to therapy. Investigating medication returns may indicate areas for targeting interventions to reduce waste. Objective: To identify and quantify the types and amounts of medications returned to community pharmacies and, specifically, to quantify the percentage of medication returned from the original dispensing, its therapeutic category, and reasons for not being used. Methods: Unsolicited medication returned for disposal to the 24 community pharmacies in the Taranaki region (~ 37,000 households) of New Zealand over a 6-week period was analyzed. The results were entered into a database, recording medication, amount originally issued (if known), date of issue, Anatomical Therapeutic Chemical (ATC) classification, and reason for nonuse. Cross-tabulation of ATC category versus percentage returned as well as ATC category versus reason for returns was performed. Adjusted standardized residuals were investigated to determine specific cells that were in excess of the expected counts. Results: Complete information was available for 2704 items. The majority (51%) of returns contained 75–100% of the original dispensed amount of medication. For the respiratory category, 77% of the returns were in the 75–100% group, significantly more than for any other therapeutic group. Reasons for returns were recorded as bereavement (22%), surplus to requirements (17%), expired (8%), medication change (11%), dose change (3%), and unknown (39%). The cardiovascular group and respiratory groups had a higher rate of returned drugs due to medication changes and surplus to requirements, respectively. Conclusions: The majority of returned medications contained greater than 75% of the original amount issued. Identification of therapeutic groups having higher rates of returns due to medication changes or surplus to requirements may suggest areas to target to reduce medication waste.
Serum 25-hydroxyvitamin D levels modulate the acute-phase response associated with the first nitrogen-containing bisphosphonate infusion
Authors: Bertoldo Francesco , Pancheri Serena , Zenari Sonia , Boldini Stefania , Giovanazzi Benedetta , Zanatta Mirko , Valenti Maria Teresa , Carbonare Luca Dalle , Cascio Vincenzo Lo 
Published: September 2009

Abstract
The acute-phase response (APR) is the most frequent side effect after the first dose of intravenous nitrogen-containing bisphosphonates (N-BPs). It has been demonstrated in vitro that N-BPs stimulate γδ T-cell proliferation and production of cytokines and that vitamin D is able to modulate them. Therefore, we have studied the relationship between bone metabolism parameters, particularly for 25-hydroxyvitamin D [25(OH)D], and APR in patients treated with 5 mg zoledronic acid intravenously. Ninety N-BP-naive osteoporotic women (63.7 ± 10.6 years of age) were stratified for the occurrence of APR (APR+) or not (APR–) and quantified by body temperature and C-reactive protein (CRP). The APR+ women had significantly lower 25(OH)D levels than the APR– women. Levels of 25(OH)D were normal (&gt;30 ng/mL) in 31% of APR+ women and in 76% of APR– women. The odds ratio (OR) to have APR in 25(OH)D-depleted women was 5.8 [95% confidence interval (CI) 5.30–6.29; p &lt; .0002] unadjusted and 2.38 (95% CI 1.85–2.81; p &lt; .028) after multiple adjustments (for age, body mass index, CRP, calcium, parathyroid hormone, and C-telopeptide of type I collagen). Levels of 25(OH)D were negatively correlated with postdose body temperature (r = −0.64, p &lt; .0001) and CRP (r = −0.79, p &lt; .001). An exponential increase in fever and CRP has been found with 25(OH)D levels lower than 30 ng/mL and body temperature less than 37 °C, whereas normal CRP was associated with 25(OH)D levels above 40 ng/mL. The association between post-N-BPs APR and 25(OH)D suggests an interesting interplay among N-BPs, 25(OH)D, and the immune system, but a causal role of 25(OH)D in APR has to be proven by a randomized, controlled trial. However, if confirmed, it should have some practical implications in preventing APR. © 2010 American Society for Bone and Mineral Research.
Scanning Electron Microscope Characterization of the Surfaces of ASTM C 109 Standard Ottawa Sand Grains
Authors: Barnes BD , Diamond S , Dolch WL 
Published: September 2009

Abstract
Surface microstructural features of Ottawa sand prescribed for mortar strength tests of portland cements in ASTM C 109 have been examined by scanning electron microscopy. The observed features include large areas of rounded grain surface that appear etched or frosted at low magnification and are seen to consist of sharp hills and valleys on a scale of a few micrometres; some areas of smooth planar surfaces representing cleavage planes; a number of large dish-shaped concavities thought to arise through conchoidal fractures associated with violent grain-to-grain contact; and incised lines separating some of the frosted surface into roughly polygonal blocks about 50 μm across. The frosted areas probably represent the results of repeated local dissolution and reprecipitation of silica.
Low-Void Concrete Mixtures
Authors: Rahal AS , Havens JH 
Published: September 2009

Abstract
The purpose of this study was to modify concrete mix design formulas so that all water over and above that needed for hydration could be replaced with a nonevaporable liquid material or a super water-reducer or superplasticizer, thus producing a low-void concrete. A water cement ratio of 0.244 to 0.30 was presumed minimal for hydration of the cement. Several polymeric materials, asphalts, oils, and superplasticizers were used. Success was achieved with two latexes, one epoxy, and several superplasticizers. The use of these materials in concrete resulted in improved strength, reduction of air voids and permeability, and improved resistance to corrosive chloride salts.