bluuebunny/crossref_metadata_2025_split huggingface dataset:
Which walking capacity tests to use in multiple sclerosis? A multicentre study providing the basis for a core set
Authors: Gijbels Domien , Dalgas Ulrik , Romberg Anders , de Groot Vincent , Bethoux Francois , Vaney Claude , Gebara Benoit , Medina Carme Santoyo , Maamâgi Heigo , Rasova Kamila , de Noordhout Benoit Maertens , Knuts Kathy , Feys Peter 
Published: September 2011

Background: Many different walking capacity test formats are being used. It is unclear whether walking speed, obtained from short tests, and walking distance, obtained from long tests, provide different clinical information. Objectives: To determine the differential effect of various short and long walk test formats on gait velocity, and the actual relationship between walking speed and walking distance in multiple sclerosis (MS) patients with diverse ambulation status. Methods: A cross-sectional multicentre study design was applied. Ambulatory MS patients (Expanded Disability Status Scale (EDSS) 0–6.5; n = 189) were tested at 11 sites. Short tests consisted of the Timed 25-Foot Walk (static start, fastest speed) and 10-Metre Walk Test (dynamic start, usual and fastest speed). Long tests consisted of the 2- and 6-Minute Walk Tests (fastest speed). Subjects were divided into mild (EDSS 0–4; n = 99) or moderate (EDSS 4.5–6.5; n = 79) disability subgroups. Results: In both subgroups, the start protocol, instructed pace and length of test led to significantly different gait velocities. Fastest walking speed and 6-Minute walking distance showed the strongest correlation ( R2 = 0.78 in mild and R2 = 0.81 in moderate MS; p < 0.01). Short tests’ relative estimation errors for 6-Minute walking distance were 8–12% in mildly and 15–16% in moderately affected subjects. Based on the 2-Minute Walk Test, estimation errors significantly reduced to approximately 5% in both subgroups. Conclusions: A single short test format at fastest speed accurately describes an MS patient’s general walking capacity. For intervention studies, a long test is to be considered. We propose the Timed 25-Foot Walk and 2-Minute Walk Test as standards. Further research on responsiveness is needed.
Sunlight exposure and sun sensitivity associated with disability progression in multiple sclerosis
Authors: D’hooghe MB , Haentjens P , Nagels G , Garmyn M , De Keyser J 
Published: September 2011

Background: Sunlight and vitamin D have been inversely associated with the risk of multiple sclerosis (MS). Objective: We investigated sunlight exposure and sun sensitivity in relation to disability progression in MS. Methods: We conducted a survey among persons with MS, registered by the Flemish MS society, Belgium, and stratified data according to relapsing-onset and progressive-onset MS. We used Kaplan–Meier survival and Cox proportional hazard regression analyses with time to Expanded Disability Status Scale (EDSS) 6 as outcome measure. Hazard ratios for the time from onset and from birth were calculated for the potentially predictive variables, adjusting for age at onset, gender and immunomodulatory treatment. Results: 704 (51.3%) of the 1372 respondents had reached EDSS 6. In relapsing-onset MS, respondents reporting equal or higher levels of sun exposure than persons of the same age in the last 10 years had a decreased risk of reaching EDSS 6. In progressive-onset MS, increased sun sensitivity was associated with an increased hazard of reaching EDSS 6. Conclusion: The association of higher sun exposure with a better outcome in relapsing-onset MS may be explained by either a protective effect or reverse causality. Mechanisms underlying sun sensitivity might influence progression in progressive-onset MS.
A physical map of Brassica oleracea shows complexity of chromosomal changes following recursive paleopolyploidizations
Authors: Wang Xiyin , Torres Manuel J , Pierce Gary , Lemke Cornelia , Nelson Lisa K , Yuksel Bayram , Bowers John E , Marler Barry , Xiao Yongli , Lin Lifeng , Epps Ethan , Sarazen Heidi , Rogers Carl , Karunakaran Santhosh , Ingles Jennifer , Giattina Emily , Mun Jeong-Hwan , Seol Young-Joo , Park Beom-Seok , Amasino Richard M , Quiros Carlos F , Osborn Thomas C , Pires J Chris , Town Christopher , Paterson Andrew H 
Published: September 2011

Abstract

Background
Evolution of the Brassica species has been recursively affected by polyploidy events, and comparison to their relative, Arabidopsis thaliana, provides means to explore their genomic complexity.

Results
A genome-wide physical map of a rapid-cycling strain of B. oleracea was constructed by integrating high-information-content fingerprinting (HICF) of Bacterial Artificial Chromosome (BAC) clones with hybridization to sequence-tagged probes. Using 2907 contigs of two or more BACs, we performed several lines of comparative genomic analysis. Interspecific DNA synteny is much better preserved in euchromatin than heterochromatin, showing the qualitative difference in evolution of these respective genomic domains. About 67% of contigs can be aligned to the Arabidopsis genome, with 96.5% corresponding to euchromatic regions, and 3.5% (shown to contain repetitive sequences) to pericentromeric regions. Overgo probe hybridization data showed that contigs aligned to Arabidopsis euchromatin contain ~80% of low-copy-number genes, while genes with high copy number are much more frequently associated with pericentromeric regions. We identified 39 interchromosomal breakpoints during the diversification of B. oleracea and Arabidopsis thaliana, a relatively high level of genomic change since their divergence. Comparison of the B. oleracea physical map with Arabidopsis and other available eudicot genomes showed appreciable 'shadowing' produced by more ancient polyploidies, resulting in a web of relatedness among contigs which increased genomic complexity.

Conclusions
A high-resolution genetically-anchored physical map sheds light on Brassica genome organization and advances positional cloning of specific genes, and may help to validate genome sequence assembly and alignment to chromosomes.
All the physical mapping data is freely shared at a WebFPC site (http://lulu.pgml.uga.edu/fpc/WebAGCoL/brassica/WebFPC/; Temporarily password-protected: account: pgml; password: 123qwe123.
Identification and comparative analysis of drought-associated microRNAs in two cowpea genotypes
Authors: Barrera-Figueroa Blanca E , Gao Lei , Diop Ndeye N , Wu Zhigang , Ehlers Jeffrey D , Roberts Philip A , Close Timothy J , Zhu Jian-Kang , Liu Renyi 
Published: September 2011

Abstract

Background
Cowpea (Vigna unguiculata) is an important crop in arid and semi-arid regions and is a good model for studying drought tolerance. MicroRNAs (miRNAs) are known to play critical roles in plant stress responses, but drought-associated miRNAs have not been identified in cowpea. In addition, it is not understood how miRNAs might contribute to different capacities of drought tolerance in different cowpea genotypes.

Results
We generated deep sequencing small RNA reads from two cowpea genotypes (CB46, drought-sensitive, and IT93K503-1, drought-tolerant) that grew under well-watered and drought stress conditions. We mapped small RNA reads to cowpea genomic sequences and identified 157 miRNA genes that belong to 89 families. Among 44 drought-associated miRNAs, 30 were upregulated in drought condition and 14 were downregulated. Although miRNA expression was in general consistent in two genotypes, we found that nine miRNAs were predominantly or exclusively expressed in one of the two genotypes and that 11 miRNAs were drought-regulated in only one genotype, but not the other.

Conclusions
These results suggest that miRNAs may play important roles in drought tolerance in cowpea and may be a key factor in determining the level of drought tolerance in different cowpea genotypes.
Molecular detection of fluoroquinolone-resistance in multi-drug resistant tuberculosis in Cambodia suggests low association with XDR phenotypes
Authors: Surcouf Corinne , Heng Seiha , Pierre-Audigier Catherine , Cadet-Daniel Véronique , Namouchi Amine , Murray Alan , Gicquel Brigitte , Guillard Bertrand 
Published: September 2011

Abstract

Background
Drug susceptibility testing (DST) remains an important concern for implementing treatment of MDR tuberculosis patients. Implementation of molecular tests for drug resistance identification would facilitate DST particularly in developing countries where culturing is difficult to perform. We have characterized multidrug resistant strains in Cambodia using MDTDRsl tests, drug target sequencing and phenotypic tests.

Methods
A total of 65 non-MDR and 101 MDR TB isolates collected between May 2007 and June 2009 were tested for resistance to fluoroquinolones and aminoglycosides/cyclic peptides using the GenoType® MTBDRsl assay and gene sequencing. Rifampicin resistance (RMP-R) was tested using gene sequencing and genotyping was assessed by spoligotyping.

Results
A total of 95 of the 101 MDR strains were confirmed to be RMP-R by rpoB gene sequencing. Fourteen of the 101 MDR isolates (14%) carried a gyrA mutation associated with fluoroquinolone-resistance (FQ-R) (detected by the MTBDRsl assay and sequencing) compared with only 1 (1.5%) of the 65 non-MDR strains. Only 1 (1%) of the MDR isolates was found to be XDR TB. The MDR group contained a higher proportion of Beijing or Beijing like strains (58%) than the non MDR group (28%). This percentage is higher in MDR FQ-R strains (71%).

Conclusions
The new GenoType® MTBDRsl assay combined with molecular tests to detect RMP-R and isoniazid resistance (INH-R) represents a valuable tool for the detection of XDR TB. In Cambodia there is a low rate of XDR amongst MDR TB including MDR FQ-R TB. This suggests a low association between FQ-R and XDR TB. Strain spoligotyping confirms Beijing strains to be more prone to accumulate antibiotic resistance.
Chronic instability of the anterior tibiofibular syndesmosis of the ankle. Arthroscopic findings and results of anatomical reconstruction
Authors: Wagener Marc L , Beumer Annechien , Swierstra Bart A 
Published: September 2011

Abstract

Background
The arthroscopic findings in patients with chronic anterior syndesmotic instability that need reconstructive surgery have never been described extensively.

Methods
In 12 patients the clinical suspicion of chronic instability of the syndesmosis was confirmed during arthroscopy of the ankle. All findings during the arthroscopy were scored. Anatomical reconstruction of the anterior tibiofibular syndesmosis was performed in all patients. The AOFAS score was assessed to evaluate the result of the reconstruction. At an average of 43 months after the reconstruction all patients were seen for follow-up.

Results
The syndesmosis being easily accessible for the 3 mm transverse end of probe which could be rotated around its longitudinal axis in all cases during arthroscopy of the ankle joint, confirmed the diagnosis. Cartilage damage was seen in 8 ankles, of which in 7 patients the damage was situated at the medial side of the ankle joint. The intraarticular part of anterior tibiofibular ligament was visibly damaged in 5 patients. Synovitis was seen in all but one ankle joint. After surgical reconstruction the AOFAS score improved from an average of 72 pre-operatively to 92 post-operatively.

Conclusions
To confirm the clinical suspicion, the final diagnosis of chronic instability of the anterior syndesmosis can be made during arthroscopy of the ankle. Cartilage damage to the medial side of the tibiotalar joint is often seen and might be the result of syndesmotic instability. Good results are achieved by anatomic reconstruction of the anterior syndesmosis, and all patients in this study would undergo the surgery again if necessary.
In vitro activities of novel 4-HPR derivatives on a panel of rhabdoid and other tumor cell lines
Authors: Smith Melissa E , Das Bhaskar C , Kalpana Ganjam V 
Published: September 2011

Abstract

Background
Rhabdoid tumors (RTs) are aggressive pediatric malignancies with poor prognosis. N-(4-hydroxy phenyl) retinamide (4-HPR or fenretinide) is a potential chemotherapeutic for RTs with activity correlated to its ability to down-modulate Cyclin D1. Previously, we synthesized novel halogen-substituted and peptidomimetic-derivatives of 4-HPR that retained activity in MON RT cells. Here we analyzed the effect of 4-HPR in inhibiting the growth of several RT, glioma, and breast cancer cell lines and tested their effect on cell cycle, apoptosis and Cyclin D1 expression.

Methods
Effect of compounds on RT cell cycle profiles, and cell death were assessed by MTS cell survival assays and FACS analysis. The effects of treatment on Cyclin D1 expression were determined by immunoblotting. The efficacy of these compounds on glioma and breast cancer cell lines was also determined using MTS assays.

Results
Low micromolar concentrations of 4-HPR derivatives inhibited cell survival of all RT cells tested. The 4-HPR derivatives altered RT cell cycle profiles and induced high levels of cell death that was correlated with their potency. ATRA exhibited high IC50 values in all cell lines tested and did not cause cell death. In MON RT cells, the iodo-substituted compounds were more active than 4-HPR in inducing cell cycle arrest and apoptosis. Additionally, the activity of the compounds correlated with their ability to down-modulate Cyclin D1: while active compounds reduced Cyclin D1 levels, inactive ATRA did not. In glioma and breast cancer cell lines, 4-HPR and 4-HPR derivatives showed variable efficacy.

Conclusions
Here we demonstrate, for the first time, that the inhibitory activities of novel halogen-substituted and peptidomimetic derivatives of 4-HPR are correlated to their ability to induce cell death and down-modulate Cyclin D1. These 4-HPR derivatives showed varied potencies in breast cancer and glioma cell lines. These data indicate that further studies are warranted on these derivatives of 4-HPR due to their low IC50s in RT cells. These derivatives are of general interest, as conjugation of halogen radioisotopes such as 18F, 124I, or 131I to 4-HPR will allow us to combine chemotherapy and radiotherapy with a single drug, and to perform PET/SPECT imaging studies in the future.
Ligand-dependent differences in estrogen receptor beta-interacting proteins identified in lung adenocarcinoma cells corresponds to estrogenic responses
Authors: Ivanova MM , Abner SM , Pierce WM , Klinge CM 
Published: September 2011

Abstract

Background
A recent epidemiological study demonstrated a reduced risk of lung cancer mortality in breast cancer patients using antiestrogens. These and other data implicate a role for estrogens in lung cancer, particularly nonsmall cell lung cancer (NSCLC). Approximately 61% of human NSCLC tumors express nuclear estrogen receptor β (ERβ); however, the role of ERβ and estrogens in NSCLC is likely to be multifactorial. Here we tested the hypothesis that proteins interacting with ERβ in human lung adenocarcinoma cells that respond proliferatively to estradiol (E2) are distinct from those in non-E2-responsive cells.

Methods
FLAG affinity purification of FLAG-ERβ-interacting proteins was used to isolate ERβ-interacting proteins in whole cell extracts from E2 proliferative H1793 and non-E2-proliferative A549 lung adenocarcinoma cell lines. Following trypsin digestion, proteins were identified using liquid chromatography electrospray ionization tandem mass spectrometry (LC-MS/MS). Proteomic data were analyzed using Ingenuity Pathway Analysis. Select results were confirmed by coimmunoprecipitation.

Results
LC-MS/MS identified 27 non-redundant ERβ-interacting proteins. ERβ-interacting proteins included hsp70, hsp60, vimentin, histones and calmodulin. Ingenuity Pathway Analysis of the ERβ-interacting proteins revealed differences in molecular and functional networks between H1793 and A549 lung adenocarcinoma cells. Coimmunoprecipitation experiments in these and other lung adenocarcinoma cells confirmed that ERβ and EGFR interact in a gender-dependent manner and in response to E2 or EGF. BRCA1 interacted with ERβ in A549 cell lines and in human lung adenocarcinoma tumors, but not normal lung tissue.

Conclusion
Our results identify specific differences in ERβ-interacting proteins in lung adenocarcinoma cells corresponding to ligand-dependent differences in estrogenic responses.
Parotid gland-recovery after radiotherapy in the head and neck region - 36 months follow-up of a prospective clinical study
Authors: Hey Jeremias , Setz Juergen , Gerlach Reinhard , Janich Martin , Hildebrandt Guido , Vordermark Dirk , Gernhardt Christian R , Kuhnt Thomas 
Published: September 2011

Abstract

Background
The aim of the present study was to evaluate the recovery potential of the parotid glands after using either 3D-conformal-radiotherapy (3D-CRT) or intensity-modulated radiotherapy (IMRT) by sparing one single parotid gland.

Methods
Between 06/2002 and 10/2008, 117 patients with head and neck cancer were included in this prospective, non-randomised clinical study. All patients were treated with curative intent. Salivary gland function was assessed by measuring stimulated salivary flow at the beginning, during and at the end of radiotherapy as well as 1, 6, 12, 24, and 36 months after treatment. Measurements were converted to flow rates and normalized relative to rates before treatment. Mean doses (Dmean) were calculated from dose-volume histograms based on computed tomographies of the parotid glands.

Results
Patients were grouped according to the Dmean of the spared parotid gland having the lowest radiation exposure: Group I - Dmean < 26 Gy (n = 36), group II - Dmean 26-40 Gy (n = 45), and group III - Dmean > 40 Gy (n = 36). 15/117 (13%) patients received IMRT. By using IMRT as compared to 3D-CRT the Dmean of the spared parotid gland could be significantly reduced (Dmean IMRT vs. 3D-CRT: 21.7 vs. 34.4 Gy, p < 0.001). The relative salivary flow rates (RFSR) as a function of the mean parotid dose after 24 and 36 months was in group I 66% and 74%, in group II 56% and 49%, and in group III 31% and 24%, respectively. Multiple linear regression analyses revealed that the parotid gland dose and the tumor site were the independent determinants 12 and 36 months after the end of RT. Patients of group I and II parotid gland function did recover at 12, 24, and 36 months after the end of RT.

Conclusions
If a Dmean < 26 Gy for at least one parotid gland can be achieved then this is sufficient to reach complete recovery of pre-RT salivary flow rates. The radiation volume which depends on tumor site did significantly impact on the Dmean of the parotids, and thus on the saliva flow and recovery of parotid gland.
Estimating the budget impact of orphan medicines in Europe: 2010 - 2020
Authors: Schey Carina , Milanova Tsveta , Hutchings Adam 
Published: September 2011

Abstract

Background
Orphan drugs are a growing issue of importance to European healthcare policy makers. The success of orphan drug legislation in Europe has resulted in an increasing number of licensed medicines for rare diseases, and many more yet unlicensed products have received orphan drug designation. Increasingly the concerns amongst policy makers relate to issues of patient access and affordability, yet few studies have sought to estimate the future budget impact of orphan drugs. The aim of this study was to predict the total cost of orphan medicines in Europe between 2010 and 2020 as a percentage of total European pharmaceutical expenditure.

Methods
A disease-based epidemiological model was created based upon trends in the designation and approval of new orphan medicines, prevalence estimates for orphan diseases, and historical price and sales data for orphan drugs in Europe (defined as Eurozone + UK). The analysis incorporated two stages:
1) Predicting the number of diseases for which new orphan drugs will be approved over the next decade, based on an analysis of trends from the EU registry of orphan medicines;
2) stimating the average ex-factory drug cost across an orphan disease life cycle, from the year in which the first orphan medicine is launched to the point where the first medicine loses marketing exclusivity.
The two sets of information were combined to quantify the annual cost of orphan drugs from 2010 through 2020.

Results
The results from the model predicted a steady increase in the cumulative number of diseases for which an orphan drug is approved, averaging just over 5 new diseases per year over the next 10 years. The annual per patient cost of existing orphan drugs was seen to vary between €1,251 and €407,631, with the median cost being €32,242 per year. The share of the total pharmaceutical market represented by orphan drugs is predicted to increase from 3.3% in 2010 to a peak of 4.6% in 2016 after which it is expected to level off through 2020, as growth falls into line with that in the wider pharmaceutical market. In sensitivity analysis peak-year orphan drug budget impact ranged between 3% - 6.6%.

Conclusions
Although European orphan drug legislation has led to an increase in the number of approved orphan drugs, the growth in cost, as a proportion of total pharmaceutical expenditure, is likely to plateau over the next decade as orphan growth rates converge on those in the broader pharmaceutical market. Given the assumptions and simplifications inherent in such a projection, there is uncertainty around the base case forecast and further research is needed to monitor how trends develop. However, fears that growth in orphan drug expenditure will lead to unsustainable cost escalation do not appear to be justified. Furthermore, based on the results of this budget impact forecast, the European orphan drug legislation is not leading to a disproportionate impact on pharmaceutical expenditure.
Non-small cell lung carcinoma in an adolescent manifested by acute paraplegia due to spinal metastases: a case report
Authors: Ackert Ulrike , Haffner Dieter , Classen Carl Friedrich 
Published: September 2011

Abstract

Introduction
Bronchial carcinomas in childhood and adolescence are extremely rare; only individual cases have been reported previously.

Case presentation
We report on a 16-year-old Caucasian German boy with non-small cell lung carcinoma (squamous cell non-small cell lung carcinoma) stage IV, T4N2M1, without epidermal growth factor receptor overexpression and/or mutation or k-ras mutation. He presented with paraplegia due to spinal metastases of the bronchial carcinoma. No familial predisposition or toxin exposure was identified. Treatment following adult protocols consisted of surgical intervention for spinal metastases, first-line cisplatinum and gemcitabine, irradiation and second-line docetaxel. After a transient response our patient experienced disease progression and died about 10 months later.

Conclusion
Response and survival in our 16-year-old patient were similar to adult patients with stage IV non-small cell lung carcinoma.
Effective detection of rare variants in pooled DNA samples using Cross-pool tailcurve analysis
Authors: Niranjan Tejasvi S , Adamczyk Abby , Bravo Héctor Corrada , Taub Margaret A , Wheelan Sarah J , Irizarry Rafael , Wang Tao 
Published: September 2011

AbstractSequencing targeted DNA regions in large samples is necessary to discover the full spectrum of rare variants. We report an effective Illumina sequencing strategy utilizing pooled samples with novel quality (Srfim) and filtering (SERVIC
4
E) algorithms. We sequenced 24 exons in two cohorts of 480 samples each, identifying 47 coding variants, including 30 present once per cohort. Validation by Sanger sequencing revealed an excellent combination of sensitivity and specificity for variant detection in pooled samples of both cohorts as compared to publicly available algorithms.