bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intramuscular interferon beta-1a is effective in Japanese patients with relapsing–remitting multiple sclerosis: a pre-treatment versus treatment comparison study of gadolinium-enhanced MRI brain lesions
Authors: Saida Takahiko , Itoyama Yasuto , Tashiro Kunio , Kira Jun-ichi , Hao Qi ,   the Interferon Beta-1a Multiple Sclerosis Study Group of Japan
Published: April 2012

Background and objective: Interferon beta (IFNβ) is standard therapy for multiple sclerosis (MS). The efficacy of intramuscular (IM) IFNβ-1a (AVONEX®) was assessed in 25 Japanese patients with relapsing–remitting MS (RRMS). Methods: Patients with RRMS not previously treated with IFNβ or other disease-modifying therapies were included in this 36-week study. The primary outcome was the average total number of gadolinium-enhanced lesions detected on four brain MRI scans during the last 12 weeks of 24 weeks’ treatment with IM IFNβ-1a 30 μg once weekly compared with the number during the 12-week pre-treatment period. Lesions were counted by blinded investigators. Results: IM IFNβ-1a significantly decreased the median number of gadolinium-enhanced lesions from 2.5 to 0.3 ( p < 0.0001) compared with pre-treatment values. The median number of new gadolinium-enhanced lesions also decreased significantly from 2.0 to 0.3 ( p = 0.0002). Serum neopterin was induced in a manner similar to that observed previously in a Caucasian RRMS population. No new adverse events occurred during the study. Conclusion: This first study of IM IFNβ-1a in Japanese patients with RRMS demonstrated a level of efficacy similar to that reported in Caucasian patients based on an assessment of pre-treatment and post-treatment gadolinium-enhanced lesions.
In Pursuit of Sustainable Leadership
Authors: Perrakis Athena , Martinez Cynthia 
Published: April 2012

The Problem. The purpose of this study is to explore how tenured female faculty members with young children negotiate personal and professional roles as department chairs. In addition, this study explores how, if at all, these women’s family and childcare responsibilities have influenced their career aspirations within the academy. The Solution. Findings reveal that role management, mentorship from deans, and sustainability of a lifestyle conducive to work–life balance are critical for female department chairs with children to thrive in their roles. Family-friendly policies in organizations must be combined with mentorship and genuine efforts to holistically support women and their multiple roles, both at home and at work. The Stakeholders. The results of this study provide important perspectives for women who aspire to move up to the administrative ranks while raising a family and for senior academic leaders and others (e.g., human resource development [HRD] practitioners) who can serve as mentors to working mothers.
Outcome of relapsed adult lymphoblastic leukemia depends on response to salvage chemotherapy, prognostic factors, and performance of stem cell transplantation
Authors: Gökbuget Nicola , Stanze Daniel , Beck Joachim , Diedrich Helmut , Horst Heinz-August , Hüttmann Andreas , Kobbe Guido , Kreuzer Karl-Anton , Leimer Lothar , Reichle Albrecht , Schaich Markus , Schwartz Stefan , Serve Hubert , Starck Michael , Stelljes Matthias , Stuhlmann Reingard , Viardot Andreas , Wendelin Knut , Freund Mathias , Hoelzer Dieter 
Published: April 2012

Abstract
Despite improvements in first-line therapies, published results on the treatment of relapsed adult acute lymphoblastic leukemia (ALL) show that prognosis is still poor. The aim of the present retrospective analysis of the German Multicenter Study Group for Adult ALL was to identify prognostic factors and options for improvement. A total of 547 patients with a median age of 33 years (range, 15-55) experiencing their first relapse (406 vs 141 shorter or longer than 18 months from diagnosis) were evaluated. The aim of salvage therapy was to achieve a complete remission (CR) with subsequent a stem cell transplantation (SCT). The CR rate (assessed in Philadelphia chromosome– and BCR-ABL–negative ALL without CNS involvement) after the first salvage in relapse after chemotherapy (n = 224) was 42%. After failure of first salvage (n = 82), the CR rate after second salvage was 33%. In relapse after SCT (n = 48) the CR rate after first salvage was 23%. The median overall survival after relapse was 8.4 months and survival was 24% at 3 years. Prognostic factors for survival were relapse localization, response to salvage, performance of SCT, and age. Overall survival appeared superior compared with previously published studies, likely because of the high rate of SCT in the present study (75%). Further improvement may be achieved with earlier relapse detection and experimental approaches in early relapse. The study is registered at www.clinicaltrials.gov as NCT00199056 and NCT00198991.
EGFR protein overexpression correlates with chromosome 7 polysomy and poor prognostic parameters in clear cell renal cell carcinoma
Authors: Đorđević Gordana , Matušan Ilijaš Koviljka , Hadžisejdić Ita , Maričić Anton , Grahovac Blaženka , Jonjić Nives 
Published: April 2012

Abstract

Background
The role of epidermal growth factor (EGF) and its receptor (EGFR) in the pathogenesis and progression of various malignant tumors has long been known, but there is still disagreement concerning prognostic significance of EGFR expression in clear cell renal cell carcinoma (CCRCC). The present study was designed to analyze more objectively the protein EGFR expression in CCRCC and to compare its value with EGFR gene copy number changes and clinicopathologic characteristics including patient survival.

Methods
The protein EGFR expression was analyzed immunohistochemically on 94 CCRCC, and gene copy number alterations of EGFR by FISH analysis on 41 CCRCC selected according to distinct membrane EGFR staining.

Results
Membrane EGFR expression in tumor cells was heterogeneous with respect to the proportion of positive cells and staining intensity. FISH analysis did not reveal EGFR gene amplification, while polysomy of chromosome 7 found in 41% was associated with higher EGFR membrane expression. Moreover, EGFR overexpression was associated with a higher nuclear grade, larger tumor size and shorter patient's survival, while there was no connection with pathological stage.

Conclusion
In conclusion, the protein expression of EGFR had an impact on prognosis in patients with CCRCC, while an increased copy number of chromosome 7 could be the possible reason for EGFR protein overexpression in the absence of gene amplification.
Disruption of the folate pathway in zebrafish causes developmental defects
Authors: Lee Marina S , Bonner Jenna R , Bernard David J , Sanchez Erica L , Sause Eric T , Prentice R Reid , Burgess Shawn M , Brody Lawrence C 
Published: April 2012

Abstract

Background
Folic acid supplementation reduces the risk of neural tube defects and congenital heart defects. The biological mechanisms through which folate prevents birth defects are not well understood. We explore the use of zebrafish as a model system to investigate the role of folate metabolism during development.

Results
We first identified zebrafish orthologs of 12 human folate metabolic genes. RT-PCR and in situ analysis indicated maternal transcripts supply the embryo with mRNA so that the embryo has an intact folate pathway. To perturb folate metabolism we exposed zebrafish embryos to methotrexate (MTX), a potent inhibitor of dihydrofolate reductase (Dhfr) an essential enzyme in the folate metabolic pathway. Embryos exposed to high doses of MTX exhibited developmental arrest prior to early segmentation. Lower doses of MTX resulted in embryos with a shortened anterior-posterior axis and cardiac defects: linear heart tubes or incomplete cardiac looping. Inhibition of dhfr mRNA with antisense morpholino oligonucleotides resulted in embryonic lethality. One function of the folate pathway is to provide essential one-carbon units for dTMP synthesis, a rate-limiting step of DNA synthesis. After 24 hours of exposure to high levels of MTX, mutant embryos continue to incorporate the thymidine analog BrdU. However, additional experiments indicate that these embryos have fewer mitotic cells, as assayed with phospho-histone H3 antibodies, and that treated embryos have perturbed cell cycles.

Conclusions
Our studies demonstrate that human and zebrafish utilize similar one-carbon pathways. Our data indicate that folate metabolism is essential for early zebrafish development. Zebrafish studies of the folate pathway and its deficiencies could provide insight into the underlying etiology of human birth defects and the natural role of folate in development.
Association between GNRHR, LHR and IGF1 polymorphisms and timing of puberty in male Angus cattle
Authors: Lirón Juan P , Prando Alberto J , Fernández María E , Ripoli María V , Rogberg-Muñoz Andrés , Goszczynski Daniel E , Posik Diego M , Peral-García Pilar , Baldo Andrés , Giovambattista Guillermo 
Published: April 2012

Abstract

Background
In bovines, there are significant differences within and among beef breeds in the time when bulls reach puberty. Although the timing of puberty is likely to be a multigenic trait, previous studies indicate that there may also be single genes that exert major effects on the timing of puberty within the general population. Despite its economic importance, there are not many SNPs or genetic markers associated with the age of puberty in male cattle. In the present work, we selected three candidate genes, GNRHR, LHR and IGF1, and associated their polymorphisms with the age of puberty in Angus male cattle.

Results
After weaning, 276 Angus males were measured every month for weight (W), scrotal circumference (SC), sperm concentration (C) and percentage of motility (M). A total of 4 SNPs, two within GNRHR, one in LHR and one in IGF1 were genotyped using the pyrosequencing technique. IGF1-SnaBI SNP was significant associated (P < 0.01) with age at SC 28 cm, but it were not associated with age at M 10% and C 50 million. Genotype CC exhibited an average age at SC 28 cm of 7 and 11 days higher than CT (p = 0.037) and TT (p = 0.012), respectively. This SNP explained 1.5% of the genetic variance of age of puberty at SC28. LHR-I499L, GNRHR-SNP5 and GNRHR-SNP6 were not associated with any of the measurements. However, GNRHR haplotypes showed a suggestive association with age at SC 28 cm.

Conclusions
The findings presented here could support the hypothesis that IGF1 is a regulator of the arrival to puberty in male calves and is involved in the events that precede and initiate puberty in bull calves. Given that most studies in cattle, as well as in other mammals, were done in female, the present results are the first evidence of markers associated with age at puberty in male cattle.
Riluzole neuroprotection in a parkinson's disease model involves suppression of reactive astrocytosis but not GLT-1 regulation
Authors: Carbone Marica , Duty Susan , Rattray Marcus 
Published: April 2012

Abstract

Background
Riluzole is a neuroprotective drug used in the treatment of motor neurone disease. Recent evidence suggests that riluzole can up-regulate the expression and activity of the astrocyte glutamate transporter, GLT-1. Given that regulation of glutamate transport is predicted to be neuroprotective in Parkinson's disease, we tested the effect of riluzole in parkinsonian rats which had received a unilateral 6-hydroxydopamine injection into the median forebrain bundle.

Results
Rats were treated with intraperitoneal riluzole (4 mg/kg or 8 mg/kg), 1 hour before the lesion then once daily for seven days. Riluzole produced a modest but significant attenuation of dopamine neurone degeneration, assessed by suppression of amphetamine-induced rotations, preservation of tyrosine hydroxylase positive neuronal cell bodies in the substantia nigra pars compacta and attenuation of striatal tyrosine hydroxylase protein loss. Seven days after 6-hydroxydopamine lesion, reactive astrocytosis was observed in the striatum, as determined by increases in expression of glial fibrillary acidic protein, however the glutamate transporter, GLT-1, which is also expressed in astrocytes was not regulated by the lesion.

Conclusions
The results confirm that riluzole is a neuroprotective agent in a rodent model of parkinson's disease. Riluzole administration did not regulate GLT-1 levels but significantly reduced GFAP levels, in the lesioned striatum. Riluzole suppression of reactive astrocytosis is an intriguing finding which might contribute to the neuroprotective effects of this drug.
The impact of a bariatric rehabilitation service on weight loss and psychological adjustment - study protocol
Authors: Hollywood Amelia , Ogden Jane , Pring Christopher 
Published: April 2012

Abstract

Background
Bariatric surgery is currently the most effective form of obesity management for those whose BMI is greater than 40 (or 35 with co morbidities). A minority of patients, however, either do not show the desired loss of excess weight or show weight regain by follow up. Research highlights some of the reasons for this variability, most of which centres on the absence of any psychological support with patients describing how although surgery fixes their body, psychological issues relating to dietary control, self esteem, coping and emotional eating remain neglected.
The present study aims to evaluate the impact of a health psychology led bariatric rehabilitation service (BRS) on patient health outcomes. The bariatric rehabilitation service will provide information, support and mentoring pre and post surgery and will address psychological issues such as dietary control, self esteem, coping and emotional eating. The package reflects the rehabilitation services now common place for patients post heart attack and stroke which have been shown to improve patient health outcomes.

Methods/Design
The study is a randomised control trial and patients will be allocated to receive either usual care or the bariatric rehabilitation service pre and post bariatric surgery. Follow up measures of weight loss and psychological issues will be taken at baseline (2 weeks preoperatively), 3, 6 and 12 months postoperatively. The contents of the bariatric service and the follow up measures are based on previous pilot work and have been developed further by the research team working closely with two patient support groups (BOSPA & WLSinfo). This study will take place in St Richard's Hospital in Chichester in the UK.

Discussion
It is predicted that a bariatric rehabilitation service will improve weight loss following surgery and will also facilitate changes in other psychological variables such as quality of life, dietary control, self esteem, coping and emotional eating. This also has cost implications for the NHS and other healthcare providers as improved effectiveness of bariatric surgery reduces the health costs of obese patients in the longer term.

Trial registration
ClinicalTrials.gov NCT01264120.
Inhibition of HSP27 alone or in combination with pAKT inhibition as therapeutic approaches to target SPARC-induced glioma cell survival
Authors: Schultz Chad R , Golembieski William A , King Daniel A , Brown Stephen L , Brodie Chaya , Rempel Sandra A 
Published: April 2012

Abstract

Background
The current treatment regimen for glioma patients is surgery, followed by radiation therapy plus temozolomide (TMZ), followed by 6 months of adjuvant TMZ. Despite this aggressive treatment regimen, the overall survival of all surgically treated GBM patients remains dismal, and additional or different therapies are required. Depending on the cancer type, SPARC has been proposed both as a therapeutic target and as a therapeutic agent. In glioma, SPARC promotes invasion via upregulation of the p38 MAPK/MAPKAPK2/HSP27 signaling pathway, and promotes tumor cell survival by upregulating pAKT. As HSP27 and AKT interact to regulate the activity of each other, we determined whether inhibition of HSP27 was better than targeting SPARC as a therapeutic approach to inhibit both SPARC-induced glioma cell invasion and survival.

Results
Our studies found the following. 1) SPARC increases the expression of tumor cell pro-survival and pro-death protein signaling in balance, and, as a net result, tumor cell survival remains unchanged. 2) Suppressing SPARC increases tumor cell survival, indicating it is not a good therapeutic target. 3) Suppressing HSP27 decreases tumor cell survival in all gliomas, but is more effective in SPARC-expressing tumor cells due to the removal of HSP27 inhibition of SPARC-induced pro-apoptotic signaling. 4) Suppressing total AKT1/2 paradoxically enhanced tumor cell survival, indicating that AKT1 or 2 are poor therapeutic targets. 5) However, inhibiting pAKT suppresses tumor cell survival. 6) Inhibiting both HSP27 and pAKT synergistically decreases tumor cell survival. 7) There appears to be a complex feedback system between SPARC, HSP27, and AKT. 8) This interaction is likely influenced by PTEN status. With respect to chemosensitization, we found the following. 1) SPARC enhances pro-apoptotic signaling in cells exposed to TMZ. 2) Despite this enhanced signaling, SPARC protects cells against TMZ. 3) This protection can be reduced by inhibiting pAKT. 4) Combined inhibition of HSP27 and pAKT is more effective than TMZ treatment alone.

Conclusions
We conclude that inhibition of HSP27 alone, or in combination with pAKT inhibitor IV, may be an effective therapeutic approach to inhibit SPARC-induced glioma cell invasion and survival in SPARC-positive/PTEN-wildtype and SPARC-positive/PTEN-null tumors, respectively.
Fuzzy n-Jordan *-homomorphisms in induced fuzzy C*-algebras
Authors: Park Choonkil , Ghaleh Shahram Ghaffary , Ghasemi Khatereh , Jang Sun Young 
Published: April 2012

Abstract
Using fixed point method, we prove the fuzzy version of the Hyers-Ulam stability of n-Jordan *-homomorphisms in induced fuzzy C*-algebras associated with the following functional equation

f

x
+
y
+
z

3

+
f

x
-
2
y
+
z

3

+
f

x
+
y
-
2
z

3

=
f

(

x

)

.

Mathematics Subject Classification (2010): Primary 46S40; 47S40; 39B52; 47H10; 46L05.
Deletions in chromosome 6p22.3-p24.3, including ATXN1, are associated with developmental delay and autism spectrum disorders
Authors: Celestino-Soper Patrícia BS , Skinner Cindy , Schroer Richard , Eng Patricia , Shenai Jayant , Nowaczyk Malgorzata MJ , Terespolsky Deborah , Cushing Donna , Patel Gayle S , Immken LaDonna , Willis Alecia , Wiszniewska Joanna , Matalon Reuben , Rosenfeld Jill A , Stevenson Roger E , Kang Sung-Hae L , Cheung Sau Wai , Beaudet Arthur L , Stankiewicz Pawel 
Published: April 2012

Abstract
Interstitial deletions of the short arm of chromosome 6 are rare and have been associated with developmental delay, hypotonia, congenital anomalies, and dysmorphic features. We used array comparative genomic hybridization in a South Carolina Autism Project (SCAP) cohort of 97 subjects with autism spectrum disorders (ASDs) and identified an ~ 5.4 Mb deletion on chromosome 6p22.3-p23 in a 15-year-old patient with intellectual disability and ASDs. Subsequent database queries revealed five additional individuals with overlapping submicroscopic deletions and presenting with developmental and speech delay, seizures, behavioral abnormalities, heart defects, and dysmorphic features. The deletion found in the SCAP patient harbors ATXN1, DTNBP1, JARID2, and NHLRC1 that we propose may be responsible for ASDs and developmental delay.
Pain in the three spinal regions: the same disorder? Data from a population-based sample of 34,902 Danish adults
Authors: Leboeuf-Yde Charlotte , Fejer René , Nielsen Jan , Kyvik Kirsten O , Hartvigsen Jan 
Published: April 2012

Abstract

Background
Studies of back pain are typically based on the assumption that symptoms from different parts of the spine are distinctive entities. Recently, however, the assumption that back pain is a site-specific disorder has been challenged, suggesting that localized back pain should be seen as part of a general musculoskeletal syndrome.

Objectives
To describe and compare the patterns of reporting of pain and consequences of pain in the three spinal regions.

Methods
In all, 34,902 (74%) twin individuals representative of the general Danish population, aged 20 to 71, participated in a cross-sectional nation-wide survey. Identical questions from the Standardised Nordic Questionnaire for each of the three spinal regions were used for lumbar, mid-back and neck pain respectively: Pain past year, pain ever, radiating pain, and consequences of back pain (care-seeking, reduced physical activities, sick-leave, change of work/work duties and disability pension). The relative prevalence estimates of these variables were compared for the three spinal regions.

Results
The relative proportions of individuals with pain ever, who also reported to have had pain in the past year varied between 75% and 80%, for the three spinal regions. The proportions of individuals with pain in the past year and for various pain durations were also very similar. Regardless if pain was reported in the lumbar, thoracic or cervical regions, the proportions of individuals reporting radiating pain were equally large. The relative number of consequences was the same across the spinal regions, as were the relative proportions of each these consequences. However, low back pain resulted more often in some kind of consequence compared to the consequences of pain in the neck and mid back.

Conclusions
Back pain and its consequences share many characteristics and may, at least in a general population, be regarded as the same condition regardless of where the pain happens to manifest itself. However, because some exceptions were noted for the lumbar spine, separate entities for a smaller group of individuals with back pain cannot be ruled out.
Epithelial to Mesenchymal Transition Is Activated in Metastatic Pheochromocytomas and Paragangliomas Caused by SDHB Gene Mutations
Authors: Loriot Céline , Burnichon Nelly , Gadessaud Noémie , Vescovo Laure , Amar Laurence , Libé Rossella , Bertherat Jérôme , Plouin Pierre-François , Jeunemaitre Xavier , Gimenez-Roqueplo Anne-Paule , Favier Judith 
Published: April 2012

Context:
Pheochromocytoma and paraganglioma are rare neural-crest-derived tumors. They are metastatic in 15% of cases, and the identification of a germline mutation in the SDHB gene is a predictive risk factor for malignancy and poor prognosis. To date, the link between SDHB mutations and malignancy is still missing.

Objective:
Epithelial to mesenchymal transition (EMT) is a developmental event, reactivated in cancer cells to promote cell mobility and invasiveness. The aim of this study was to address the participation of EMT in the metastatic evolution of pheochromocytoma/paraganglioma.

Design and Patients:
Transcriptomic profiling of EMT was performed on 188 tumor samples, using a set of 94 genes implicated in this pathway. Activation of EMT was further confirmed at protein level by immunohistochemistry in a second set of 93 tumors.

Results:
Hierarchical unsupervised classification showed that most SDHB-metastatic samples clustered together, indicating that EMT is differently regulated in these tumors. Major actors of EMT, metalloproteases and components of cellular junctions, were either up-regulated (LOXL2, TWIST, TCF3, MMP2, and MMP1) or down-regulated (KRT19 and CDH2) in SDHB-metastatic tumors compared with nonmetastatic ones. Interestingly, within metastatic tumors, most of these genes (LOXL2, TWIST, TCF3, MMP2, and KRT19) also allowed us to discriminate SDHB-mutated from non-SDHB-related tumors. In the second set of tumors, we studied Snail1/2 expression by immunohistochemistry and observed its specific nuclear translocation in all SDHB-metastatic tumors.

Conclusion:
We have identified the first pathway that distinguishes SDHB-metastatic from all other types of pheochromocytomas/paragangliomas and suggest that activation of the EMT process might play a critical role in the particularly invasive phenotype of this group of tumors.