bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential regulation of the p70 S6 kinase pathway by interferon α (IFNα) and imatinib mesylate (STI571) in chronic myelogenous leukemia cells
Authors: Parmar Simrit , Smith Jessica , Sassano Antonella , Uddin Shahab , Katsoulidis Efstratios , Majchrzak Beata , Kambhampati Suman , Eklund Elizabeth A. , Tallman Martin S. , Fish Eleanor N. , Platanias Leonidas C. 
Published: March 2005

AbstractThe precise mechanisms by which imatinib mesylate (STI571) and interferon α (IFNα) exhibit antileukemic effects are not known. We examined the effects of IFNs or imatinib mesylate on signaling pathways regulating initiation of mRNA translation in BCR-ABL-expressing cells. Treatment of IFN-sensitive KT-1 cells with IFNα resulted in phosphorylation/activation of mammalian target of rapamycin (mTOR) and downstream activation of p70 S6 kinase. The IFN-activated p70 S6 kinase was found to regulate phosphorylation of S6 ribosomal protein, which regulates translation of mRNAs with oligopyrimidine tracts in the 5′-untranslated region. In addition, IFNα treatment resulted in an mTOR- and/or phosphatidyl-inositol 3′(PI 3′) kinase-dependent phosphorylation of 4E-BP1 repressor of mRNA translation on sites that are required for its deactivation and dissociation from the eukaryotic initiation factor-4E (eIF4E) complex. In contrast to the effects of IFNs, imatinib mesylate suppressed p70 S6 kinase activity, consistent with inhibition of BCR-ABL-mediated activation of the mTOR/p70 S6 kinase pathway. Moreover, the mTOR inhibitor rapamycin enhanced the suppressive effects of imatinib mesylate on primary leukemic granulocyte macrophage-colony-forming unit (CFU-GM) progenitors from patients with chronic myelogenous leukemia (CML). Taken altogether, our data demonstrate that IFNs and imatinib mesylate differentially regulate PI 3′ kinase/mTOR-dependent signaling cascades in BCR-ABL-transformed cells, consistent with distinct effects of these agents on pathways regulating mRNA translation. They also support the concept that combined use of imatinib mesylate with mTOR inhibitors may be an appropriate future therapeutic strategy for the treatment of CML. (Blood. 2005;106:2436-2443)
Accelerated probabilistic inference of RNA structure evolution
Authors: Holmes Ian 
Published: March 2005

Abstract
Background
Pairwise stochastic context-free grammars (Pair SCFGs) are powerful tools for evolutionary analysis of RNA, including simultaneous RNA sequence alignment and secondary structure prediction, but the associated algorithms are intensive in both CPU and memory usage. The same problem is faced by other RNA alignment-and-folding algorithms based on Sankoff's 1985 algorithm. It is therefore desirable to constrain such algorithms, by pre-processing the sequences and using this first pass to limit the range of structures and/or alignments that can be considered.

Results
We demonstrate how flexible classes of constraint can be imposed, greatly reducing the computational costs while maintaining a high quality of structural homology prediction. Any score-attributed context-free grammar (e.g. energy-based scoring schemes, or conditionally normalized Pair SCFGs) is amenable to this treatment. It is now possible to combine independent structural and alignment constraints of unprecedented general flexibility in Pair SCFG alignment algorithms. We outline several applications to the bioinformatics of RNA sequence and structure, including Waterman-Eggert N-best alignments and progressive multiple alignment. We evaluate the performance of the algorithm on test examples from the RFAM database.

Conclusion
A program, Stemloc, that implements these algorithms for efficient RNA sequence alignment and structure prediction is available under the GNU General Public License.
Compliance and toxicity of adjuvant CMF in elderly breast cancer patients: a single-center experience
Authors: De Maio Ermelinda , Gravina Adriano , Pacilio Carmen , Amabile Gerardo , Labonia Vincenzo , Landi Gabriella , Nuzzo Francesco , Rossi Emanuela , D'Aiuto Giuseppe , Capasso Immacolata , Rinaldo Massimo , Morrica Brunello , Elmo Massimo , Di Maio Massimo , Perrone Francesco , de Matteis Andrea 
Published: March 2005

Abstract
Background
Few data are available on compliance and safety of adjuvant chemotherapy when indicated in elderly breast cancer patients; CMF (cyclophosphamide, methotrexate, fluorouracil) can be reasonably considered the most widely accepted standard of treatment.

Methods
We retrospectively reviewed compliance and safety of adjuvant CMF in patients older than 60. The treatment was indicated if patients had no severe comorbidity, a high-risk of recurrence, and were younger than 75. Toxicity was coded by NCI-CTC. Toxicity and compliance were compared between two age subgroups (<65, ≥ 65) by Fisher exact test and exact Wilcoxon rank-sum test.

Results
From March 1991 to March 2002, 180 patients were identified, 100 older than 60 and younger than 65, and 80 aged 65 or older. Febrile neutropenia was more frequent among older patients (p = 0.05). Leukopenia, neutropenia, nausea, cardiac toxicity and thrombophlebitis tended to be more frequent or severe among elderlies, while mucositis tended to be more evident among younger patients, all not significantly. Almost one half (47%) of the older patients receiving concomitant radiotherapy experienced grade 3–4 haematological toxicity. Compliance was similar in the two groups, with 6 cycles administered in 86% and 79%, day-8 chemotherapy omitted at least once in 36% and 39%, dose reduction in 27% and 38%, prolonged treatment duration (≥ 29 weeks) in 10% and 11% and need of G-CSF in 9% and 18%, among younger and older patients, respectively.

Conclusion
Our data show that, in a highly selected population of patients 65 or more years old, CMF is as feasible as in patients older than 60 and younger than 65, but with a relevant burden of toxicity. We suggest that prospective trials in elderly patients testing less toxic treatment schemes are mandatory before indicating adjuvant chemotherapy to all elderly patients with significant risk of breast cancer recurrence.
Casodex treatment induces hypoxia-related gene expression in the LNCaP prostate cancer progression model
Authors: Rothermund Christy A , Gopalakrishnan Velliyur K , Eudy James D , Vishwanatha Jamboor K 
Published: March 2005

Abstract
Background
The changes in gene expression profile as prostate cancer progresses from an androgen-dependent disease to an androgen-independent disease are still largely unknown.

Methods
We examined the gene expression profile in the LNCaP prostate cancer progression model during chronic treatment with Casodex using cDNA microarrays consisting of 2305 randomly chosen genes.

Results
Our studies revealed a representative collection of genes whose expression was differentially regulated in LNCaP cells upon treatment with Casodex. A set of 15 genes were shown to be highly expressed in Casodex-treated LNCaP cells compared to the reference sample. This set of highly expressed genes represents a signature collection unique to prostate cancer since their expression was significantly greater than that of the collective pool of ten cancer cell lines of the reference sample. The highly expressed signature collection included the hypoxia-related genes membrane metallo-endopeptidase (MME), cyclin G2, and Bcl2/adenovirus E1B 19 kDa (BNIP3). Given the roles of these genes in angiogenesis, cell cycle regulation, and apoptosis, we further analyzed their expression and concluded that these genes may be involved in the molecular changes that lead to androgen-independence in prostate cancer.

Conclusion
Our data indicate that one of the mechanisms of Casodex action in prostate cancer cells is induction of hypoxic gene expression.
Acne and smoking: is there a relationship?
Authors: Firooz Alireza , Sarhangnejad Reza , Davoudi Seyyed Massoud , Nassiri-Kashani Mansour 
Published: March 2005

Abstract
Background
There are contradictory reports on the relationship between acne vulgaris and cigarette smoking. The objective of this study was to examine the relation between acne and cigarette smoking in a case-control study.

Methods
A questionnaire on smoking habits was offered to 350 patients with acne vulgaris and 350 patients suffering from skin diseases other than acne, aged 15 – 40 years, attending in a skin clinic in Tehran, Iran. The patients completed the questionnaires anonymously in the waiting room.

Results
Two hundred and ninety-three patients with acne (response rate 83.7 %) and 301 patients with other skin diseases (response rate 86.0 %) completed the questionnaires. Twelve acne patients (4.1 %) and 27 control patients (9.0 %) were current smokers (odds ratio = 0.43, 95% confidence limits 0.22 – 0.87, p < 0.05). But after adjustment for sex, this difference was not significant (odds ratio: 0.61, 95% CI: 0.30–1.26, p > 0.05, Mantel-Haenszel test).

Conclusion
An association between acne and cigarette smoking was not found in this study.
A topological model of biofeedback based on catecholamine interactions
Authors: Basak Tapas K , Halder Suman , Kumar Madona , Sharma Renu , Midya Bijoylaxmi 
Published: March 2005

Abstract
Background
The present paper describes a topological model of biofeedback. This model incorporates input from a sensory organ and a transduction phase mediated through catecholamine production in the feedback path. The transduction phase comprises both conservative and dissipative systems, from which the appropriate output is combined in a closed loop.

Results
The model has been simulated in MATLAB 6.0 R12 in order to facilitate a comprehensive understanding of the complex biofeedback phenomena concomitant with the transduction phases associated with migraine and with psychosomatic diseases involving digestive disorders.

Conclusion
The complexity of the biological system influences the transduction phase and nature of the system response, which is consequent on the activation of smooth muscles by sympathetic and parasympathetic stimulation.
Effect of risedronate on joint structure and symptoms of knee osteoarthritis: results of the BRISK randomized, controlled trial [ISRCTN01928173]
Authors: Spector Tim D , Conaghan Philip G , Buckland-Wright J Christopher , Garnero Patrick , Cline Gary A , Beary John F , Valent David J , Meyer Joan M 
Published: March 2005

AbstractTo determine the efficacy and safety of risedronate in patients with knee osteoarthritis (OA), the British study of risedronate in structure and symptoms of knee OA (BRISK), a 1-year prospective, double-blind, placebo-controlled study, enrolled patients (40–80 years of age) with mild to moderate OA of the medial compartment of the knee. The primary aims were to detect differences in symptoms and function. Patients were randomized to once-daily risedronate (5 mg or 15 mg) or placebo. Radiographs were taken at baseline and 1 year for assessment of joint-space width using a standardized radiographic method with fluoroscopic positioning of the joint. Pain, function, and stiffness were assessed using the Western Ontario and McMaster Universities (WOMAC) OA index. The patient global assessment and use of walking aids were measured and bone and cartilage markers were assessed. The intention-to-treat population consisted of 284 patients. Those receiving risedronate at 15 mg showed improvement of the WOMAC index, particularly of physical function, significant improvement of the patient global assessment (P < 0.001), and decreased use of walking aids relative to patients receiving the placebo (P = 0.009). A trend towards attenuation of joint-space narrowing was observed in the group receiving 15 mg risedronate. Eight percent (n = 7) of patients receiving placebo and 4% (n = 4) of patients receiving 5 mg risedronate exhibited detectable progression of disease (joint-space width ≥ 25% or ≥ 0.75 mm) versus 1% (n = 1) of patients receiving 15 mg risedronate (P = 0.067). Risedronate (15 mg) significantly reduced markers of cartilage degradation and bone resorption. Both doses of risedronate were well tolerated. In this study, clear trends towards improvement were observed in both joint structure and symptoms in patients with primary knee OA treated with risedronate.
Increased level of phosphorylated akt measured by chemiluminescence-linked immunosorbent assay is a predictor of poor prognosis in primary breast cancer overexpressing ErbB-2
Authors: Cicenas Jonas , Urban Patrick , Vuaroqueaux Vincent , Labuhn Martin , Küng Willy , Wight Edward , Mayhew Mark , Eppenberger Urs , Eppenberger-Castori Serenella 
Published: March 2005

Abstract
Introduction
Akt1, Akt2 and Akt3 kinases are downstream components of phosphoinositol 3-kinase derived signals from receptor tyrosine kinases, which influence cell growth, proliferation and survival. Akt2 overexpression and amplification have been described in breast, ovarian and pancreatic cancers. The present study was designed to investigate the prognostic significance of activated Akt in primary breast cancer and its association with other tumour biomarkers.

Methods
Using a two-site chemiluminescence-linked immunosorbent assay, we measured the quantitative expression levels of total phosphorylated (P-S473) Akt (Akt1/Akt2/Akt3) on cytosol fractions obtained from fresh frozen tissue samples of 156 primary breast cancer patients.

Results
Akt phosphorylation was not associated with nodal status or ErbB-2 protein expression levels. High levels of phosphorylated Akt correlated (P < 0.01) with poor prognosis, and the significance of this correlation increased (P < 0.001) in the subset of patients with ErbB-2 overexpressing tumours. In addition, phosphorylated Akt was found to be associated with mRNA expression levels of several proliferation markers (e.g. thymidylate synthase), measured using quantitative real-time RT-PCR.

Conclusion
Our findings demonstrate that, in breast cancer patients, Akt activation is associated with tumour proliferation and poor prognosis, particularly in the subset of patients with ErbB2-overexpressing tumours.
Quantitative genomics of starvation stress resistance in Drosophila
Authors: Harbison Susan T , Chang Sherman , Kamdar Kim P , Mackay Trudy FC 
Published: March 2005

Abstract
Background
A major challenge of modern biology is to understand the networks of interacting genes regulating complex traits, and the subset of these genes that affect naturally occurring quantitative genetic variation. Previously, we used P-element mutagenesis and quantitative trait locus (QTL) mapping in Drosophila to identify candidate genes affecting resistance to starvation stress, and variation in resistance to starvation stress between the Oregon-R (Ore) and 2b strains. Here, we tested the efficacy of whole-genome transcriptional profiling for identifying genes affecting starvation stress resistance.

Results
We evaluated whole-genome transcript abundance for males and females of Ore, 2b, and four recombinant inbred lines derived from them, under control and starved conditions. There were significant differences in transcript abundance between the sexes for nearly 50% of the genome, while the transcriptional response to starvation stress involved approximately 25% of the genome. Nearly 50% of P-element insertions in 160 genes with altered transcript abundance during starvation stress had mutational effects on starvation tolerance. Approximately 5% of the genome exhibited genetic variation in transcript abundance, which was largely attributable to regulation by unlinked genes. Genes exhibiting variation in transcript abundance among lines did not cluster within starvation resistance QTLs, and none of the candidate genes affecting variation in starvation resistance between Ore and 2b exhibited significant differences in transcript abundance between lines.

Conclusions
Expression profiling is a powerful method for identifying networks of pleiotropic genes regulating complex traits, but the relationship between variation in transcript abundance among lines used to map QTLs and genes affecting variation in quantitative traits is complicated.
Haemoglobin A1c: Evaluation of three point of care analysers for use in a paediatric diabetes clinic
Authors: Greaves Ronda F , Northfield Jo-Ann T , Cameron Fergus J 
Published: March 2005

Background: The measurement of haemoglobin A1c(HbA1c) by high-performance liquid chromatography (HPLC) is generally deemed unsuitable for point of care testing (POCT) due to its complexity and extended turnaround times (TAT). The aim of this project was to evaluate two new HPLC instruments, the Bio-Rad D10 and the Primus PDQ, as POCT instruments compared with Bayer's DCA2000 HbA1c immunoassay analyser in our paediatric diabetes clinic. Methods: A total of 228 samples were analysed, of which 160 analyses were performed in our paediatric diabetes clinic. HbA1c results were compared by the Passing-Bablok agreement test, the Bland-Altman difference analysis, within- and between-run imprecision, and TAT. Results: : The agreement test and difference analysis showed a correlation of r2=0.96 and a mean HbA1c difference of <0.1% between the three analysers. The PDQ and the D10 achieved the within-run target coefficient of variation (CV) of <2% at an HbA1c of 7.5%. Between-run imprecision at an HbA1c of 10.8% produced CV of 3.5%, 2.4% and 1.6% for the D10, DCA2000 and PDQ, respectively. TAT studies confirmed that the PDQ was substantially faster than the DCA2000 and D10. Conclusions: The PDQ had the shortest TAT, afforded random access and exhibited acceptable imprecision, and hence is the preferred instrument for our POCT environment.
Direct phonoplasty under local anaesthetic
Authors: Montgomery P , Sharma A , Qayyum A , Mierzwa K 
Published: March 2005

Objective: A new technique of direct phonoplasty under local anaesthetic is described.Background: Vocal-fold medialization is an accepted method to improve voice in patients with a paralysed vocal fold. Various materials have been used to inject into the paralysed vocal fold, resulting in medialization of the fold and improved phonation. The two established methods are direct injection under general anaesthetic and transcutaneous injection under local anaesthetic; both have advantages and disadvantages. Method: A Pentax 80K series flexible endoscope is used to directly inject collagen into the paralysed vocal fold via a reusable 23G endoscopic needle under local anaesthetic. Conclusion: New technology and innovation have allowed development of the new technique of direct phonoplasty under local anaesthetic. This combines the advantages of transcutaneous injection under local anaesthetic and direct injection under general anaesthetic, without their disadvantages.
Systemic cross-linked N-terminal telopeptide and procollagen I C-terminal extension peptide as markers of bone turnover after total hip arthroplasty
Authors: Savarino L. , Granchi D. , Cenni E. , Baldini N. , Greco M. , Giunti A. 
Published: March 2005

There is no diagnostic, non-invasive method for the early detection of loosening after total hip arthroplasty. In a pilot study, we have analysed two serum markers of bone remodelling, procollagen I C-terminal extension peptide (PICP) and cross-linked N-terminal telopeptide (NTx), as well as the diagnostic performance of NTx for the assessment of osteolysis. We recruited 21 patients with loosening (group I), 18 with a well-fixed prosthesis (group II) and 17 at the time of primary arthroplasty for osteoarthritis (OA) (group III). Internal normal reference ranges were obtained from 30 healthy subjects (group IV). The serum PICP level was found to be significantly lower in patients with OA and those with loosening, when compared with those with stable implants, while the NTx level was significantly increased only in the group with loosening, suggesting that collagen degradation depended on the altered bone turnover induced by the implant. This hypothesis was reinforced by the finding that the values in the pre-surgery patients and stable subjects were comparable with the reference range of younger healthy subjects. A high specificity and positive predictive value for NTx provided good diagnostic evidence of agreement between the test and the clinical and radiological evaluations. The NTx level could be used to indicate stability of the implant. However, further prospective, larger studies are necessary.
The Bryan cervical disc prosthesis as an alternative to arthrodesis in the treatment of cervical spondylosis
Authors: Lafuente J. , Casey A. T. H. , Petzold A. , Brew S. 
Published: March 2005

We present data relating to the Bryan disc arthroplasty for the treatment of cervical spondylosis in 46 patients. Patients with either radiculopathy or myelopathy had a cervical discectomy followed by implantation of a cervical disc prosthesis. Patients were reviewed at six weeks, six months and one year and assessment included three outcome measures, a visual analogue scale (VAS), the short form 36 (SF-36) and the neck disability index (NDI). The results were categorised according to a modification of Odom’s criteria. Radiological evaluation, by an independent radiologist, sought evidence of movement, stability and subsidence of the prosthesis. A highly significant difference was found for all three outcome measurements, comparing the pre-operative with the post-operative values: VAS (Z = 6.42, p < 0.0001), SF-36 (mental component) (Z = −5.02, p < 0.0001), SF-36 (physical component) (Z = −5.00, p < 0.0001) and NDI (Z = 7.03, p < 0.0001). The Bryan cervical disc prosthesis seems reliable and safe in the treatment of patients with cervical spondylosis.
Dynamic Properties of Geosynthetic Interfaces
Authors: Kim J , Riemer M , Bray JD 
Published: March 2005

Abstract
An experimental study of geosynthetics was carried out on a shaking table to investigate the relationship between dynamic friction resistances and shear displacement rate and to examine other frictional characteristics of geosynthetic interfaces. A cyclic, displacement rate-controlled experimental setup was developed. The subsequent multiple rate tests showed that interfaces that involve geotextiles have unique shearing characteristics that can be differentiated from the interfaces not involving geotextiles. It was found that shear strengths of geosynthetic interfaces tend to increase with increasing displacement rate for combinations of geosynthetics that involve geotextiles; whereas, shear strengths of interfaces not involving geotextiles do not.
Mini Compaction Test Apparatus for Fine Grained Soils
Authors: Sridharan A , Sivapullaiah PV 
Published: March 2005

Abstract
The standard and modified Proctor compaction tests are devised to establish dry unit weight-water content relationships for a soil under controlled conditions, such as compactive effort, water content, etc. This paper presents a mini compaction apparatus primarily for use in fine grained soils, which requires only about 1/10th volume of soil needed for the standard and modified Proctor test. Additionally, the time and effort involved in carrying out the compaction test is much less. Also, the compacted soil sample, after trimming, can be used for strength tests.
The Map Expansion Obtained With Recombinant Inbred Strains and Intermated Recombinant Inbred Populations for Finite Generation Designs
Authors: Teuscher F , Guiard V , Rudolph P E , Brockmann G A 
Published: March 2005

Abstract
The generation of special crosses between different inbred lines such as recombinant inbred strains (RIS) and intermated recombinant inbred populations (IRIP) is being used to improve the power of QTL detection techniques, in particular fine mapping. These approaches acknowledge the fact that recombination of linked loci increases with every generation, caused by the accumulation of crossovers appearing between the loci at each meiosis. This leads to an expansion of the map distance between the loci. While the amount of the map expansion of RIS and IRIP is known for infinite inbred generations, it is not known for finite numbers of generations. This gap was closed here. Since the recursive evaluation of the map expansion factors turned out to be complex, a useful approximation was derived.