bluuebunny/crossref_metadata_2025_split huggingface dataset:
Subcellular forms and biochemical events triggered in human cells by HCV polyprotein expression from a viral vector
Authors: Vandermeeren Andrée M , Gómez Carmen Elena , Patiño Cristina , Domingo-Gil Elena , Guerra Susana , González Jose Manuel , Esteban Mariano 
Published: July 2012

Abstract
To identify the subcellular forms and biochemical events induced in human cells after HCV polyprotein expression, we have used a robust cell culture system based on vaccinia virus (VACV) that efficiently expresses in infected cells the structural and nonstructural proteins of HCV from genotype 1b (VT7-HCV7.9). As determined by confocal microscopy, HCV proteins expressed from VT7-HCV7.9 localize largely in a globular-like distribution pattern in the cytoplasm, with some proteins co-localizing with the endoplasmic reticulum (ER) and mitochondria. As examined by electron microscopy, HCV proteins induced formation of large electron-dense cytoplasmic structures derived from the ER and containing HCV proteins. In the course of HCV protein production, there is disruption of the Golgi apparatus, loss of spatial organization of the ER, appearance of some "virus-like" structures and swelling of mitochondria. Biochemical analysis demonstrate that HCV proteins bring about the activation of initiator and effector caspases followed by severe apoptosis and mitochondria dysfunction, hallmarks of HCV cell injury. Microarray analysis revealed that HCV polyprotein expression modulated transcription of genes associated with lipid metabolism, oxidative stress, apoptosis, and cellular proliferation. Our findings demonstrate the uniqueness of the VT7-HCV7.9 system to characterize morphological and biochemical events related to HCV pathogenesis.
Avian influenza: genetic evolution under vaccination pressure
Authors: Escorcia Magdalena , Vázquez Lourdes , Méndez Sara T , Rodríguez-Ropón Andrea , Lucio Eduardo , Nava Gerardo M 
Published: July 2012

Abstract
Antigenic drift of avian influenza viruses (AIVs) has been observed in chickens after extended vaccination program, similar to those observed with human influenza viruses. To evaluate the evolutionary properties of endemic AIV under high vaccination pressure (around 2 billion doses used in the last 12 years), we performed a pilot phylogenic analysis of the hemagglutinin (HA) gene of AIVs isolated from 1994 to 2006. This study demonstrates that Mexican low pathogenicity (LP) H5N2-AIVs are constantly undergoing genetic drifts. Recent AIV isolates (2002–2006) show significant molecular drifts when compared with the H5N2 vaccine-strain or other field isolates (1994–2000). This study also demonstrates that molecular drifts in the HA gene lineages follow a yearly trend, suggesting gradually cumulative sequence mutations. These findings might explain the increasing incidence of LP H5N2 AIV isolated from commercial avian farms. These findings support recent concerns about the challenge of AIV antigenic drift and influenza epidemics.
Genetic Variation in the Catechol-O-Methyltransferase (COMT) Gene and Morphine Requirements in Cancer Patients with Pain
Authors: Rakvåg Trude T , Ross Joy R , Sato Hiroe , Skorpen Frank , Kaasa Stein , Klepstad Pål 
Published: July 2012

Background: Genetic variation contributes to differences in pain sensitivity and response to different analgesics. Catecholamines are involved in the modulation of pain and are partly metabolized by the catechol-O-methyltransferase (COMT) enzyme. Genetic variability in the COMT gene may therefore contribute to differences in pain sensitivity and response to analgesics. It is shown that a polymorphism in the COMT gene, Rs4680 (Val158Met), influence pain sensitivity in human experimental pain and the efficacy for morphine in cancer pain treatment. In this study we wanted to investigate if variability in other regions in the COMT gene also contributes to interindividual variability in morphine efficacy. Results: We genotyped 11 single nucleotide polymorphisms (SNPs) throughout the COMT gene, and constructed haplotypes from these 11 SNPs, which were in Hardy-Weinberg equilibrium. We compared both genotypes and haplotypes against pharmacological, demographical and patient symptoms measurements in a Caucasian cancer patient cohort (n = 197) receiving oral morphine treatment for cancer pain. There were two frequent haplotypes (34.5% and 17.8%) in our cohort. Multivariate analyses showed that patients carrying the most frequent haplotype (34.5%) needed lower morphine doses than patients not carrying the haplotype, with a reduction factor of 0.71 (p = 0.005). On the allele level, carriers of alleles for six of the SNPs show weak associations in respect to morphine dose and the alleles associated with the lowest morphine doses constitute part of the most frequent haplotype. Conclusion: This study suggests that genetic variability in the COMT gene influence the efficacy of morphine in cancer patients with pain, and that increased understanding of this variability is reached by expanding from analyses of single SNPs to haplotype construction and analyses.
Use acupuncture to treat functional constipation: study protocol for a randomized controlled trial
Authors: Li Ying , Zheng Hui , Zeng Fang , Zhou Si-yuan , Zhong Feng , Zheng Hua-bing , Chen Min , Jing Xiang-hong , Cai Yu-ying , Jia Bao-hui , Zhu Bing , Liu Zhi-shun 
Published: July 2012

Abstract

Background
Whether acupuncture is effective for patients with functional constipation is still unclear. Therefore, we report the protocol of a randomized controlled trial of using acupuncture to treat functional constipation.

Design
A randomized, controlled, four-arm design, large-scale trial is currently undergoing in China. Seven hundred participants are randomly assigned to three acupuncture treatment groups and Mosapride Citrate control group in a 1:1:1:1 ratio. Participants in acupuncture groups receive 16 sessions of acupuncture treatment, and are followed up for a period of 9 weeks after randomization. The acupuncture groups are: (1) Back-Shu and Front-Mu acupoints of Large Intestine meridians (Shu-Mu points group); (2) He-Sea and Lower He-Sea acupoints of Large Intestine meridians (He points group); (3) Combining used Back-Shu, Front-Mu, He-Sea, and Lower He-Sea acupoints of Large Intestine meridians (Shu-Mu-He points group). The control group is Mosapride Citrate group. The primary outcome is frequency of defecation per week at the fourth week after randomization. The secondary outcomes include Bristol stool scale, the extent of difficulty during defecating, MOS 36-item Short Form health survey (SF-36), Self-Rating Anxiety Scale (SAS), and Self-rating Depression Scale (SDS). The first two of second outcomes are measured 1 week before randomization and 2, 4, and 8 weeks after randomization. Other second outcomes are measured 1 week before randomization and 2 and 4 weeks after randomization, but SF-36 is measured at randomization and 4 weeks after randomization.

Discussion
The result of this trial (which will be available in 2012) will confirm whether acupuncture is effective to treat functional constipation and whether traditional acupuncture theories play an important role in it.

Trials registration
Clinical Trials.gov NCT01411501
A concept for trial institutions focussing on randomised controlled trials in surgery
Authors: Rahbari Nuh N , Diener Markus K , Fischer Lars , Wente Moritz N , Kienle Peter , Büchler Markus W , Seiler Christoph M 
Published: July 2012

Abstract

Background
Although considered the reference standard for generating valid scientific evidence of a treatment's benefits and harms, the number of Randomised Controlled Trials (RCT) comparing surgical techniques remains low. Much effort has been made in order to overcome methodological issues and improve quality of RCTs in surgery. To the present there has been, however, only little emphasis on development and maintenance of institutions for implementation of adequately designed and conducted surgical RCTs.

Mehods/Design
Description of the developments in surgical RCT infrastructure in Germany between 2001 and 2006. Cross sectional evaluation of completed and ongoing surgical RCTs within the German Surgical Society and the Clinical Study Centre, Department of Surgery, University of Heidelberg.

Results
Foundation of a national Clinical Trial Centre (CTC) for the organisation of multi-centre RCTs in the surgical setting (Study Center of the German Surgical Society, SDGC). Establishment of a network of CTCs with affiliated Clinical Sites (CSs) to enhance patient recruitment and shorten the duration of RCTs. Since its foundation four surgical RCTs with a total sample size of 1650 patients (1006 of these randomised) have been supervised by the SDGC with 35 CSs involved in patient recruitment. Five further CTCs were set up in 2006. Together with their affiliated CSs a network has been organised providing improved conditions for the conduction of surgical RCTs.

Conclusion
Improvement of infrastructure substantially facilitates integration of RCTs into routine surgical practice. A network of collaborating CTCs and CSs can provide an adequate infrastructure for the conduction of multi-centre RCTs.
Gadd45β expression in chondrosarcoma: A pilot study for diagnostic and biological implications in histological grading
Authors: Zenmyo Michihisa , Tanimoto Akihide , Sakakima Harutoshi , Yokouchi Masahiro , Nagano Satoshi , Yamamoto Takuya , Ishido Yasuhiro , Komiya Setsuro , Ijiri Kosei 
Published: July 2012

Abstract

Background
Although the diagnosis of chondrosarcoma, especially the distinction between enchondroma and low-grade chondrosarcoma or low-grade chondrosarcoma and high-grade chondrosarcoma, is pathologically difficult, differential diagnosis is very important because the treatment strategies for these diseases are completely different. The grading system is crucial in predicting biologic behavior and prognosis, however, exact pathological grading is difficult using only routine examinations because the criteria of the grading system are not necessarily definitive. Growth arrest and DNA damage-inducible protein 45β (GADD45β) is an essential molecule for chondrocytes during terminal differentiation. In the present study, we investigated the immunohistochemical expression of GADD45β in enchondroma, and chondrosarcoma of histological grades I, II, and III, to clarify the diagnostic significance of GADD45β in pathological grading of chondrosarcoma.

Methods
Twenty samples (enchondroma = 6, chondrosarcoma grade I = 7, grade II = 6, grade III = 1) were used for immunohistochemical analysis to investigate the expression of GADD45β. Quantitative analysis was performed to compare the number of GADD45β positive cells and pathological grading.

Results
Over 70% of the cells in enchondromas expressed GADD45β. On the other hand, the expression of GADD45β decreased significantly according to the histological grade of chondrosarcoma (grade I: 45%; grade II: 13.8%; and grade III: 3.8%).

Conclusions
The association of GADD45β expression and pathological grading of chondrosarcoma in the present study suggests that the immunohistochemical study of GADD45β may be a specific diagnostic parameter for chondrosarcoma cell differentiation.
The abdomen of Drosophila: does planar cell polarity orient the neurons of mechanosensory bristles?
Authors: Fabre Caroline CG , Casal José , Lawrence Peter A 
Published: July 2012

Abstract
Background
In the adult abdomen of Drosophila, the shafts of mechanosensory bristles point consistently from anterior to posterior. This is an example of planar cell polarity (PCP); some genes responsible for PCP have been identified. Each adult bristle is made by a clone of four cells, including the neuron that innervates it, but little is known as to how far the formation or positions of these cells depends on PCP. The neurons include a single dendrite and an axon; it is not known whether the orientation of these processes is influenced by PCP.

Results
We describe the development of the abdominal mechanosensory bristles in detail. The division of the precursor cell gives two daughters, one (pIIa) divides to give rise to the bristle shaft and socket cell and the other (pIIb) generates the neuron, the sheath and the fifth cell. Although the bristles and their associated shaft and socket cells are consistently oriented, the positioning and behaviour of the neuron, the sheath and the fifth cell, as well as the orientation of the axons and the dendritic paths, depend on location. For example, in the anterior zone of the segment, the axons grow posteriorly, while in the posterior zone, they grow anteriorly. Manipulating the PCP genes can reverse bristle orientation, change the path taken by the dendrite and the position of the cell body of the neuron. However, the paths taken by the axon are not affected.

Conclusion
PCP genes, such as starry night and dachsous orient the bristles and position the neuronal cell body and affect the shape of the dendrites. However, these PCP genes do not appear to change the paths followed by the sensory axons, which must, therefore, be polarised by other factors.
Semaphorin-6A controls guidance of corticospinal tract axons at multiple choice points
Authors: Rünker Annette E , Little Graham E , Suto Fumikazu , Fujisawa Hajime , Mitchell Kevin J 
Published: July 2012

Abstract
Background
The trajectory of corticospinal tract (CST) axons from cortex to spinal cord involves a succession of choice points, each of which is controlled by multiple guidance molecules. To assess the involvement of transmembrane semaphorins and their plexin receptors in the guidance of CST axons, we have examined this tract in mutants of Semaphorin-6A (Sema6A), Plexin-A2 (PlxnA2) and Plexin-A4 (PlxnA4).

Results
We describe defects in CST guidance in Sema6A mutants at choice points at the mid-hindbrain boundary (MHB) and in navigation through the pons that dramatically affect how many axons arrive to the hindbrain and spinal cord and result in hypoplasia of the CST. We also observe defects in guidance within the hindbrain where a proportion of axons aberrantly adopt a ventrolateral position and fail to decussate. This function in the hindbrain seems to be mediated by the known Sema6A receptor PlxnA4, which is expressed by CST axons. Guidance at the MHB, however, appears independent of this and of the other known receptor, PlxnA2, and may depend instead on Sema6A expression on CST axons themselves at embryonic stages.

Conclusion
These data identify Sema6A as a major contributor to the guidance of CST axons at multiple choice points. They highlight the active control of guidance at the MHB and also implicate the inferior olive as an important structure in the guidance of CST axons within the hindbrain. They also suggest that Sema6A, which is strongly expressed by oligodendrocytes, may affect CST regeneration in adults.
Long-term alterations of striatal parvalbumin interneurons in a rat model of early exposure to alcohol
Authors: De Giorgio Andrea , Comparini Sara E , Intra Francesca Sangiuliano , Granato Alberto 
Published: July 2012

Abstract

Background
Exposure to alcohol in utero is a known cause of mental retardation. Although a certain degree of motor impairment is always associated with fetal alcohol spectrum disorder, little is known about the neurobiological basis of the defective motor control. We have studied the striatal interneurons containing parvalbumin in a rat model of fetal alcohol spectrum disorder.

Methods
Newborn rats received ethanol by inhalation from postnatal day two through six and parvalbumin striatal neurons were labeled by immunohistochemistry on postnatal day 60. The spatial distribution of parvalbumin interneurons was studied using Voronoi spatial tessellation and their dendritic trees were completely reconstructed.

Results
Parvalbumin interneurons of ethanol-treated animals showed a clustered spatial distribution similar to that observed in control animals. The dendritic tree of parvalbumin interneurons was significantly reduced in ethanol-treated animals, as compared with controls.

Conclusions
Striatal parvalbumin interneurons are crucial components of the brain network serving motor control. Therefore, the shrinkage of their dendrites could contribute to the motor and cognitive symptoms observed in fetal alcohol spectrum disorder.
A short‐term educational program improved physicians’ adherence to guidelines for COPD and asthma in Shanghai
Authors: Fang Xiaocong , Li Shanqun , Gao Lei , Zhao Naiqing , Wang Xiangdong , Bai Chunxue 
Published: July 2012

AbstractBackgroundChronic pulmonary diseases such as chronic obstructive pulmonary disease (COPD) and asthma exert increasing burden on society while the management of them is far from adequate. The objective of this study is to evaluate adherence to guidelines through a patient study, and then investigate the effects of a short‐term quality improvement educational program among clinicians in Shanghai, China.MethodsA prescription survey was performed in a random sample of 100 COPD and asthma outpatients to assess their pharmacological therapy. Then, an educational program was conducted in young pulmonary physicians from 83 hospitals in Shanghai. The training course was divided into 7 sessions of 2 hours delivered over 4 days from July 2010 to August 2011. Three months later, all of the participants were asked to take a written examination to assess the efficiency of training.ResultsPrescription survey among the patients indicated the prescriptions are not consistent with the recommendations of current GOLD and GINA guidelines. The mainly existing issue is the overuse of inhaled glucocorticosteroid. For the educational program, 161 pulmonary physicians have attended the training course, and 110 clinicians finished the tests with an attendance rate of 68.3%. Although most of the clinicians recognized the increasing burden of COPD and asthma, they do not know well about the core elements of guidelines and their clinical practice is not fully in agreement with current recommendations. Through crossover comparison, our results suggested clinicians’ knowledge of the guidelines was improved after training.ConclusionsWe concluded that application of continuous educational programs among physicians might promote their adherence to guidelines, and by that improve the quality of healthcare.
Defining cut-off values for disease activity states and improvement scores for patient-reported outcomes: the example of the Rheumatoid Arthritis Impact of Disease (RAID)
Authors: Dougados Maxime , Brault Yves , Logeart Isabelle , van der Heijde Désirée , Gossec Laure , Kvien Tore 
Published: July 2012

Abstract

Introduction

The Rheumatoid Arthritis Impact of Disease (RAID) is a patient-reported outcome measure evaluating the impact of rheumatoid arthritis (RA) on patient quality of life. It comprises 7 domains that are evaluated as continuous variables from 0 (best) to 10 (worst). The objective was to define and identify cut-off values for disease activity states as well as improvement scores in order to present results at the individual level (for example, patient in acceptable state, improved patient).

Methods

Patients with definite active RA requiring anti-tumour necrosis factor (anti-TNF) therapy were seen at screening, baseline and after 4 and 12 weeks of etanercept therapy. Answers to "Gold standard" questions on improvement (MCII: Minimum Clinically Important Improvement) and an acceptable status (PASS: Patient Acceptable Symptom State) were collected as well as the RAID score and Disease Activity Score 28- erythrocyte sedimentation rate (DAS28-ESR). Cut-offs were defined by different techniques including empirical, measurement error and gold standard anchors. The external validity of these cut-offs was evaluated using the positive likelihood ratio (LR) based on the patient's perspective (for example, patient's global) and on low disease activity status (such as DAS28-ESR).

Results

Ninety-seven (97) of the 108 recruited patients (age: 54 ± 13 years old, female gender: 75%, rheumatoid factor positive: 81%, disease duration: 8 ± 7 years, CRP: 18 ± 30 mg/l, DAS28-ESR: 5.4 ± 0.8) completed the 12 weeks of the study. The different techniques suggested thresholds ranging from 0.2 to 3 (absolute change) and from 6 to 50% (relative change) for defining MCII and thresholds from less than 1 to less than 4.2 for defining PASS. The evaluation of external validity (LR+) showed the highest LR+ was obtained with thresholds of 3 for absolute change; 50% for relative change and less than 2 for an acceptable status.

Conclusions

This study showed that thresholds defined for continuous variables are closely related to the methodological technique, justifying a systematic evaluation of their validity. Our results suggested that a change of at least 3 points (absolute) or 50% (relative) in the RAID score should be used to define a MCII and that a maximal value of 2 defines an acceptable status.

Trial Registration

Clinicaltrial.gov: NCT004768053
Variation in breast cancer risk associated with factors related to pregnancies according to truncating mutation location, in the French National BRCA1 and BRCA2 mutations carrier cohort (GENEPSO)
Authors: Lecarpentier Julie , Noguès Catherine , Mouret-Fourme Emmanuelle , Gauthier-Villars Marion , Lasset Christine , Fricker Jean-Pierre , Caron Olivier , Stoppa-Lyonnet Dominique , Berthet Pascaline , Faivre Laurence , Bonadona Valérie , Buecher Bruno , Coupier Isabelle , Gladieff Laurence , Gesta Paul , Eisinger François , Frénay Marc , Luporsi Elisabeth , Lortholary Alain , Colas Chrystelle , Dugast Catherine , Longy Michel , Pujol Pascal , Tinat Julie ,   GENEPSO, Lidereau Rosette , Andrieu Nadine 
Published: July 2012

Abstract
Introduction
Mutations in BRCA1 and BRCA2 confer a high risk of breast cancer (BC), but the magnitude of this risk seems to vary according to the study and various factors. Although controversial, there are data to support the hypothesis of allelic risk heterogeneity.

Methods
We assessed variation in BC risk according to factors related to pregnancies by location of mutation in the homogeneous risk region of BRCA1 and BRCA2 in 990 women in the French study GENEPSO by using a weighted Cox regression model.

Results
Our results confirm the existence of the protective effect of an increasing number of full-term pregnancies (FTPs) toward BC among BRCA1 and BRCA2 mutation carriers (≥3 versus 0 FTPs: hazard ratio (HR) = 0.51, 95% confidence interval (CI) = 0.33 to 0.81). Additionally, the HR shows an association between incomplete pregnancies and a higher BC risk, which reached 2.39 (95% CI = 1.28 to 4.45) among women who had at least three incomplete pregnancies when compared with women with zero incomplete pregnancies. This increased risk appeared to be restricted to incomplete pregnancies occurring before the first FTP (HR = 1.77, 95% CI = 1.19 to 2.63). We defined the TMAP score (defined as the Time of Breast Mitotic Activity during Pregnancies) to take into account simultaneously the opposite effect of full-term and interrupted pregnancies. Compared with women with a TMAP score of less than 0.35, an increasing TMAP score was associated with a statistically significant increase in the risk of BC (P trend = 0.02) which reached 1.97 (95% CI = 1.19 to 3.29) for a TMAP score >0.5 (versus TMAP ≤0.35). All these results appeared to be similar in BRCA1 and BRCA2. Nevertheless, our results suggest a variation in BC risk associated with parity according to the location of the mutation in BRCA1. Indeed, parity seems to be associated with a significantly decreased risk of BC only among women with a mutation in the central region of BRCA1 (low-risk region) (≥1 versus 0 FTP: HR = 0.27, 95% CI = 0.13 to 0.55) (Pinteraction <10-3).

Conclusions
Our findings show that, taking into account environmental and lifestyle modifiers, mutation position might be important for the clinical management of BRCA1 and BRCA2 mutation carriers and could also be helpful in understanding how BRCA1 and BRCA2 genes are involved in BC.