bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intensive expression of Bmi-1 is a new independent predictor of poor outcome in patients with ovarian carcinoma
Authors: Yang Guo-Fen , He Wei-Peng , Cai Mu-Yan , He Li-Ru , Luo Jun-Hang , Deng Hai-Xia , Guan Xin-Yuan , Zeng Mu-Sheng , Zeng Yi-Xin , Xie Dan 
Published: April 2010

Abstract

Background
It has been suggested that the B-cell specific moloney leukemia virus insertion site 1 (Bmi-1) gene plays an oncogenic role in several types of human cancer, but the status of Bmi-1 amplification and expression in ovarian cancer and its clinical/prognostic significance are unclear.

Methods
The methods of immunohistochemistry and fluorescence in situ hybridization were utilized to examine protein expression and amplification of Bmi-1 in 30 normal ovaries, 30 ovarian cystadenomas, 40 borderline ovarian tumors and 179 ovarian carcinomas.

Results
Intensive expression of Bmi-1 was detected in none of the normal ovaries, 3% cystadenomas, 10% borderline tumors, and 37% ovarian carcinomas, respectively. Amplification of Bmi-1 was detected in 8% of ovarian carcinomas. In ovarian carcinomas, significant positive associations were found between intensive expression of Bmi-1 and the tumors ascending histological grade, later pT/pN/pM and FIGO stages (P < 0.05). In univariate survival analysis of the ovarian carcinoma cohorts, a significant association of intensive expression of Bmi-1 with shortened patient survival (mean 49.3 months versus 100.3 months, p < 0.001) was demonstrated. Importantly, Bmi-1 expression provided significant independent prognostic parameters in multivariate analysis (p = 0.005).

Conclusions
These findings provide evidence that intensive expression of Bmi-1 might be important in the acquisition of an invasive and/or aggressive phenotype of ovarian carcinoma, and serve as a independent biomarker for shortened survival time of patients.
Breast cancer treatment and ethnicity in British Columbia, Canada
Authors: Yavari Parvin , Barroetavena Maria Cristina , Hislop T Greg , Bajdik Chris D 
Published: April 2010

Abstract

Background
Racial and ethnic disparities in breast cancer incidence, stage at diagnosis, survival and mortality are well documented; but few studies have reported on disparities in breast cancer treatment. This paper compares the treatment received by breast cancer patients in British Columbia (BC) for three ethnic groups and three time periods. Values for breast cancer treatments received in the BC general population are provided for reference.

Methods
Information on patients, tumour characteristics and treatment was obtained from BC Cancer Registry (BCCR) and BC Cancer Agency (BCCA) records. Treatment among ethnic groups was analyzed by stage at diagnosis and time period at diagnosis. Differences among the three ethnic groups were tested using chi-square tests, Fisher exact tests and a multivariate logistic model.

Results
There was no significant difference in overall surgery use for stage I and II disease between the ethnic groups, however there were significant differences when surgery with and without radiation were considered separately. These differences did not change significantly with time. Treatment with chemotherapy and hormone therapy did not differ among the minority groups.

Conclusion
The description of treatment differences is the first step to guiding interventions that reduce ethnic disparities. Specific studies need to examine reasons for the observed differences and the influence of culture and beliefs.
Toward characterization and definition of fibromyalgia severity
Authors: Silverman Stuart , Sadosky Alesia , Evans Chris , Yeh Yating , Alvir Jose Ma J , Zlateva Gergana 
Published: April 2010

Abstract

Background
There are no standard criteria for defining or assessing severity of fibromyalgia (FM) as a condition as fibromyalgia is associated with multiple symptom domains. The objective of this study was to evaluate whether patient self-reported severity of FM is associated with severity of pain and sleep interference and the presence of core co-morbidities.

Methods
We recruited individuals ≥ 18 years of age with a clinician-confirmed diagnosis of FM ≥ 3 months and a current pain rating >2 on a 0-10 numeric rating scale (NRS). Patients completed a questionnaire by mail in which they self-rated their FM severity (very mild, mild, moderate, and severe), their current pain severity and extent of sleep interference (NRS; mild, 0-3; moderate, 4-6, severe, 7-10), and provided information (yes/no) on the presence of core comorbidities (symptoms of depression, anxiety, sleep problems, back pain, neck pain) and medication use for FM. The core symptoms of FM were stratified to assist with patient characterization. Analysis of variance (ANOVA) was used to explore the relationship between self-reported FM severity and continuous variables (pain severity and sleep interference), and Mantel-Haenszel chi-square analysis was used to evaluate the trend in the proportions of patients reporting use of medications and core symptoms of FM by severity of FM. To complement patient-reported FM severity and to understand physicians' perspectives, a survey was performed among 28 physician specialists (rheumatology, neurology, anesthesiology/pain management, family practice, internal medicine, and psychiatry) to determine what they assessed when evaluating FM severity in clinical practice.

Results
The population (N = 129) of FM patients was predominantly female (89.1%), with a mean age of 49.4 ± 11.0 years, and 81.4% reported duration ≥ 2 years. Self-reported FM severity was moderate/severe in 86.0% of patients; mean current pain score was 6.40 ± 2.19 (moderate), and mean sleep interference score was 7.28 ± 2.23 (severe). Greater FM severity was significantly associated with higher levels of current pain and sleep interference (p < 0.0001), the proportion of patients reporting FM medication use (p = 0.0001), and the presence of core comorbidities (p < 0.05). Pain, functional disability, and fatigue severity were ranked as the top three criteria by the highest proportion of physicians when evaluating FM severity.

Conclusion
With higher self-reported FM severity, patients have greater pain and sleep interference as well as increased frequency of core comorbidities. Further investigation into understanding FM severity is warranted.
Can treatment of malaria be restricted to parasitologically confirmed malaria? A school-based study in Benin in children with and without fever
Authors: Faucher Jean-François , Makoutode Patrick , Abiou Grace , Béhéton Todoégnon , Houzé Pascal , Ouendo Edgard , Houzé Sandrine , Deloron Philippe , Cot Michel 
Published: April 2010

Abstract

Background
Applying the switch from presumptive treatment of malaria to new policies of anti-malarial prescriptions restricted to parasitologically-confirmed cases is a still unsolved challenge. Pragmatic studies can provide data on consequences of such a switch. In order to assess whether restricting anti-malarials to rapid diagnostic test (RDT)-confirmed cases in children of between five and 15 years of age is consistent with an adequate management of fevers, a school-based study was performed in Allada, Benin.

Methods
Children in the index group (with fever and a negative RDT) and the matched control group (without fever and a negative RDT) were not prescribed anti-malarials and actively followed-up during 14 days. Blood smears were collected at each assessment. Self-medication with chloroquine and quinine was assessed with blood spots. Malaria attacks during the follow-up were defined by persistent or recurrent fever concomitant to a positive malaria test.

Results
484 children were followed-up (242 in each group). At day 3, fever had disappeared in 94% of children from the index group. The incidence of malaria was similar (five cases in the index group and seven cases in the control group) between groups. Self-medication with chloroquine and quinine in this cohort was uncommon.

Conclusions
Applying a policy of restricting anti-malarials to RDT-confirmed cases is consistent with an adequate management of fevers in this population. Further studies on the management of fever in younger children are of upmost importance.
MicroRNA-184 inhibits neuroblastoma cell survival through targeting the serine/threonine kinase AKT2
Authors: Foley Niamh H. , Bray Isabella M. , Tivnan Amanda , Bryan Kenneth , Murphy Derek M. , Buckley Patrick G. , Ryan Jacqueline , O'Meara Anne , O'Sullivan Maureen , Stallings Raymond L. 
Published: April 2010

Abstract

Background
Neuroblastoma is a paediatric cancer of the sympathetic nervous system. The single most important genetic indicator of poor clinical outcome is amplification of the MYCN transcription factor. One of many down-stream MYCN targets is miR-184, which is either directly or indirectly repressed by this transcription factor, possibly due to its pro-apoptotic effects when ectopically over-expressed in neuroblastoma cells. The purpose of this study was to elucidate the molecular mechanism by which miR-184 conveys pro-apoptotic effects.

Results
We demonstrate that the knock-down of endogenous miR-184 has the opposite effect of ectopic up-regulation, leading to enhanced neuroblastoma cell numbers. As a mechanism of how miR-184 causes apoptosis when over-expressed, and increased cell numbers when inhibited, we demonstrate direct targeting and degradation of AKT2, a major downstream effector of the phosphatidylinositol 3-kinase (PI3K) pathway, one of the most potent pro-survival pathways in cancer. The pro-apoptotic effects of miR-184 ectopic over-expression in neuroblastoma cell lines is reproduced by siRNA inhibition of AKT2, while a positive effect on cell numbers similar to that obtained by the knock-down of endogenous miR-184 can be achieved by ectopic up-regulation of AKT2. Moreover, co-transfection of miR-184 with an AKT2 expression vector lacking the miR-184 target site in the 3'UTR rescues cells from the pro-apoptotic effects of miR-184.

Conclusions

MYCN contributes to tumorigenesis, in part, by repressing miR-184, leading to increased levels of AKT2, a direct target of miR-184. Thus, two important genes with positive effects on cell growth and survival, MYCN and AKT2, can be linked into a common genetic pathway through the actions of miR-184. As an inhibitor of AKT2, miR-184 could be of potential benefit in miRNA mediated therapeutics of MYCN amplified neuroblastoma and other forms of cancer.
Genomic alterations of primary tumor and blood in invasive ductal carcinoma of breast
Authors: Bae Ja Seong , Choi Jin Soo , Baik Seung Ho , Park Woo Chan , Song Byung Joo , Kim Jeong Soo , Lim Young , Jung Sang Seol 
Published: April 2010

Abstract

Background
Genomic alterations are important events in the origin and progression of various cancers, with DNA copy number changes associated with progression and treatment response in cancer. Array CGH is potentially useful in the identification of genomic alterations from primary tumor and blood in breast cancer patients. The aim of our study was to compare differences of DNA copy number changes in blood and tumor tissue in breast cancer.

Methods
DNA copy number changes in blood were compared to those in tumor tissue using array-comparative genomic hybridization in samples obtained from 30 breast cancer patients. The relative degree of chromosomal changes was analyzed using log2 ratios and data was validated by real-time polymerase chain reaction.

Results
Forty-six regions of gains present in more than 30% of the tissues and 70 regions of gains present in more than 30% of blood were identified. The most frequently gained region was chromosome 8q24. In total, agreement of DNA copy numbers between primary tumor and blood was minimal (Kappa = 0.138, p < 0.001).

Conclusion
Although there was only a slight agreement of DNA copy number alterations between the primary tumor and the blood samples, the blood cell copy number variation may have some clinical significance as compared to the primary tumor in IDC breast cancer patients.
Differential sensitivity of melanoma cell lines with BRAF
V600E
mutation to the specific Raf inhibitor PLX4032
Authors: Søndergaard Jonas N , Nazarian Ramin , Wang Qi , Guo Deliang , Hsueh Teli , Mok Stephen , Sazegar Hooman , MacConaill Laura E , Barretina Jordi G , Kehoe Sarah M , Attar Narsis , von Euw Erika , Zuckerman Jonathan E , Chmielowski Bartosz , Comin-Anduix Begoña , Koya Richard C , Mischel Paul S , Lo Roger S , Ribas Antoni 
Published: April 2010

Abstract
Blocking oncogenic signaling induced by the BRAF
V600E mutation is a promising approach for melanoma treatment. We tested the anti-tumor effects of a specific inhibitor of Raf protein kinases, PLX4032/RG7204, in melanoma cell lines. PLX4032 decreased signaling through the MAPK pathway only in cell lines with the BRAF
V600E mutation. Seven out of 10 BRAF
V600E mutant cell lines displayed sensitivity based on cell viability assays and three were resistant at concentrations up to 10 μM. Among the sensitive cell lines, four were highly sensitive with IC50 values below 1 μM, and three were moderately sensitive with IC50 values between 1 and 10 μM. There was evidence of MAPK pathway inhibition and cell cycle arrest in both sensitive and resistant cell lines. Genomic analysis by sequencing, genotyping of close to 400 oncogeninc mutations by mass spectrometry, and SNP arrays demonstrated no major differences in BRAF locus amplification or in other oncogenic events between sensitive and resistant cell lines. However, metabolic tracer uptake studies demonstrated that sensitive cell lines had a more profound inhibition of FDG uptake upon exposure to PLX4032 than resistant cell lines. In conclusion, BRAF
V600E mutant melanoma cell lines displayed a range of sensitivities to PLX4032 and metabolic imaging using PET probes can be used to assess sensitivity.
Chiropractic management of patients post-disc arthroplasty: eight case reports
Authors: O'Shaughnessy Julie , Drolet Marc , Roy Jean-François , Descarreaux Martin 
Published: April 2010

Abstract

Background
When conservative therapies for low back pain (LBP) are not effective, elective surgery may be proposed to these patients. Over the last 20 years, a new technology, disc replacement, has become increasingly popular because it is believed to maintain or restore the integrity of spinal movement and minimize the side-effects compared to fusion. Although disc replacement may relieve a patient from pain and related disability, soreness and stiffness of the lumbopelvic region seem to be common aftermaths of the surgery. This prospective case series was undertaken to identify and describe potential adverse events of lumbar spinal manipulation, a common therapy for low back pain, in a group of patients with symptoms after disc prostheses.

Cases presentation
Eight patients who underwent lumbar spine total disc replacement were referred by an orthopaedic surgeon for chiropractic treatments. These patients had 1 or 2 total lumbar disc replacements and were considered stable according to the surgical protocol but presented persistent, post-surgical, non-specific LBP or pelvic pain. They were treated with lumbar spine side posture manipulations only and received 8 to 10 chiropractic treatments based on the clinical evolution and the chiropractor's judgment. Outcome measures included benign, self-limiting, and serious adverse events after low back spinal manipulative therapy. The Oswestry Disability Index, a pain scale and the fear avoidance belief questionnaire were administered to respectively assess disability, pain and fear avoidance belief about work and physical activity. This prospective case series comprised 8 patients who all had at least 1 total disc replacement at the L4/L5 or L5/S1 level and described persistent post-surgical LBP interfering with their daily activities. Commonly-reported side-effects of a benign nature included increased pain and/or stiffness of short duration in nearly half of the chiropractic treatment period. No major or irreversible complication was noted.

Conclusions
During the short treatment period, no major complication was encountered by the patients. Moreover, the benign side-effects reported after lumbar spine manipulation were similar in nature and duration to those frequently experienced by the general population.
Protocol: a simple gel-free method for SNP genotyping using allele-specific primers in rice and other plant species
Authors: Hirotsu Naoki , Murakami Naomi , Kashiwagi Takayuki , Ujiie Kazuhiro , Ishimaru Ken 
Published: April 2010

AbstractBackgroundGenotype analysis using multiple single nucleotide polymorphisms (SNPs) is a useful but labor-intensive or high-cost procedure in plant research. Here we describe an alternative genotyping method that is suited to multi-sample or multi-locus SNP genotyping and does not require electrophoresis or specialized equipment.ResultsWe have developed a simple method for multi-sample or multi-locus SNP genotyping using allele-specific primers (ASP). More specifically, we (1) improved the design of allele-specific primers, (2) established a method to detect PCR products optically without electrophoresis, and (3) standardized PCR conditions for parallel genomic assay using various allele-specific primers. As an illustration of multi-sample SNP genotyping using ASP, we mapped the locus for lodging resistance in a typhoon (lrt5). Additionally, we successfully tested multi-locus ASP-PCR analysis using 96 SNPs located throughout the genomes of rice (Oryza sativa) cultivars 'Koshihikari' and 'Kasalath', and demonstrated its applicability to other diverse cultivars/subspecies, including wild rice (O. rufipogon).ConclusionOur ASP methodology allows characterization of SNPs genotypes without electrophoresis, expensive probes or specialized equipment, and is highly versatile due to the flexibility in the design of primers. The method could be established easily in any molecular biology laboratory, and is applicable to diverse organisms.
ApoE mimetic peptide decreases Aβ production in vitro and in vivo
Authors: Minami S Sakura , Cordova Antoinette , Cirrito John R , Tesoriero Joseph A , Babus Lenard W , Davis Gary C , Dakshanamurthy Sivanesan , Turner R Scott , Pak Daniel TS , Rebeck G William , Paige Mikell , Hoe Hyang-Sook 
Published: April 2010

Abstract

Background
Apolipoprotein E (apoE) is postulated to affect brain Aβ levels through multiple mechanisms--by altering amyloid precursor protein (APP) processing, Aβ degradation, and Aβ clearance. We previously showed that an apoE-derived peptide containing a double repeat of the receptor-binding region was similarly effective in increasing APP processing in vivo. Here, we further examined whether peptides containing tandem repeats of the apoE receptor-binding region (amino acids 141-149) affected APP trafficking, APP processing, and Aβ production.

Results
We found that peptides containing a double or triple tandem repeat of the apoE receptor-binding region, LRKLRKRLL, increased cell surface APP and decreased Aβ levels in PS1-overexpressing PS70 cells and in primary neurons. This effect was potentiated by a sequential increase in the number of apoE receptor-binding domain repeats (trimer > dimer > monomer). We previously showed that the apoE dimer increased APP CTF in vivo; to determine whether the dimer also affected secreted APP or Aβ levels, we performed a single hippocampal injection of the apoE dimer in wild-type mice and analyzed its effect on APP processing. We found increased sAPPα and decreased Aβ levels at 24 hrs after treatment, suggesting that the apoE dimer may increase α-secretase cleavage.

Conclusions
These data suggest that small peptides consisting of tandem repeats of the apoE receptor-binding region are sufficient to alter APP trafficking and processing. The potency of these peptides increased with increasing repeats of the receptor binding domain of apoE. In addition, in vivo administration of the apoE peptide (dimer) increased sAPPα and decreased Aβ levels in wild-type mice. Overall, these findings contribute to our understanding of the effects of apoE on APP processing and Aβ production both in vitro and in vivo.
Heartworm (Dirofilaria immitis) infection in a leopard (Panthera pardus pardus) housed in a zoological park in north-eastern Italy
Authors: Mazzariol Sandro , Cassini Rudi , Voltan Laura , Aresu Luca , Frangipane di Regalbono Antonio 
Published: April 2010

Abstract
Canine heartworm (cHW) disease is now recognised as potential cause of serious disease in cats and other felids, especially in endemic areas. In March 2009, a 23-years-old male African leopard (Panthera pardus pardus) housed in a zoological park located in the Province of Padova (Veneto Region), a cHW endemic area of the north-eastern Italy, died and was immediately necropsied. A cloth completely occluding the pyloric lumen was considered the presumptive cause of death. During necropsy, six nematodes (4 males and 2 females) were found within the right ventricle of the heart and the pulmonary artery. Diagnosis of HW (Dirofilaria immitis) infection was carried out by morphological features of adult worms and microfilariae, and then confirmed by detection of circulating HW antigens using a commercial SNAP kit (IDEXX Laboratories inc., USA). D. immitis infection was also confirmed by PCR amplification of the 5S ribosomal spacer region, performed on worm fragments and microfilaraemic blood samples obtained from the right ventricle of the heart. A glomerulonephritis of immuno-mediated origin and most likely associated with the HW infection is also reported. HW chemoprophylaxis and annual serological testing on wild felids housed outdoors in endemic cHW disease areas are recommended. This is the first diagnosis of D. immitis infection in an exotic felid in Italy.
Astrocytic expression of Parkinson's disease-related A53T α-synuclein causes neurodegeneration in mice
Authors: Gu Xing-Long , Long Cai-Xia , Sun Lixin , Xie Chengsong , Lin Xian , Cai Huaibin 
Published: April 2010

Abstract

Background
Parkinson's disease (PD) is the most common movement disorder. While neuronal deposition of α-synuclein serves as a pathological hallmark of PD and Dementia with Lewy Bodies, α-synuclein-positive protein aggregates are also present in astrocytes. The pathological consequence of astrocytic accumulation of α-synuclein, however, is unclear.

Results
Here we show that PD-related A53T mutant α-synuclein, when selectively expressed in astrocytes, induced rapidly progressed paralysis in mice. Increasing accumulation of α-synuclein aggregates was found in presymptomatic and symptomatic mouse brains and correlated with the expansion of reactive astrogliosis. The normal function of astrocytes was compromised as evidenced by cerebral microhemorrhage and down-regulation of astrocytic glutamate transporters, which also led to increased inflammatory responses and microglial activation. Interestingly, the activation of microglia was mainly detected in the midbrain, brainstem and spinal cord, where a significant loss of dopaminergic and motor neurons was observed. Consistent with the activation of microglia, the expression level of cyclooxygenase 1 (COX-1) was significantly up-regulated in the brain of symptomatic mice and in cultured microglia treated with conditioned medium derived from astrocytes over-expressing A53T α-synuclein. Consequently, the suppression of COX-1 activities extended the survival of mutant mice, suggesting that excess inflammatory responses elicited by reactive astrocytes may contribute to the degeneration of neurons.

Conclusions
Our findings demonstrate a critical involvement of astrocytic α-synuclein in initiating the non-cell autonomous killing of neurons, suggesting the viability of reactive astrocytes and microglia as potential therapeutic targets for PD and other neurodegenerative diseases.