bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhanced anti-HCV activity of interferon alpha 17 subtype
Authors: Dubois Aurelie , François Catherine , Descamps Veronique , Fournier Carole , Wychowski Czeslaw , Dubuisson Jean , Castelain Sandrine , Duverlie Gilles 
Published: June 2009

AbstractBackgroundPegylated interferon alpha 2 (a or b) plus ribavirin is the most effective treatment of chronic hepatitis C but a large proportion of patients do not respond to therapy. So, it is interesting to improve the treatment efficacy. Interferon alpha is a type I interferon composed of 12 different subtypes. Each subtype signals by the Jak-Stat pathway but modulations in the antiviral activity was previously described.MethodsUsing the hepatitis C virus (HCV) culture system, we have tested the anti-HCV activity of each interferon alpha subtypes. We have analyzed the effect of each subtype on the HCV multiplication and the cell-signaling pathway for some subtypes.ResultsThere were divergent effects of IFN alpha subtypes against HCV. We have found that IFN alpha 17 was three times more efficient than IFN alpha 2a on HCV. This efficiency was related to a stronger stimulation of the Jak-Stat pathway.ConclusionWe suggest that IFN α17 should be tested therapeutically with a view to improving treatment efficacy.
Genetic predisposition to chikungunya – a blood group study in chikungunya affected families
Authors: Lokireddy Sudarsanareddy , Sarojamma Vemula , Ramakrishna Vadde 
Published: June 2009

Abstract
Chikungunya fever is a viral disease transmitted to humans by the bite of CHIKV virus infected Aedes mosquitoes. During monsoon outbreak of chikungunya fever, we carried out the genetic predisposition to chikungunya in disease affected 100 families by doing blood group (ABO) tests by focusing on individuals who were likely to have a risk of chikungunya and identified the blood group involved in susceptibility/resistance to chikungunya. In the present study, based on blood group antigens, the individuals were kept in four groups – A (108), B (98), AB (20) and O (243). The result obtained was showed all Rh positive blood group individuals are susceptible to chikungunya fever. Among ABO group, the blood group O +ve individuals are more susceptible to chikungunya than other blood groups. No blood group with Rh negative was affected with chikungunya, it indicates Rh -ve more resistance to chikungunya.
γ-MYN: a new algorithm for estimating Ka and Ks with consideration of variable substitution rates
Authors: Wang Da-Peng , Wan Hao-Lei , Zhang Song , Yu Jun 
Published: June 2009

Abstract

Background
Over the past two decades, there have been several approximate methods that adopt different mutation models and used for estimating nonsynonymous and synonymous substitution rates (Ka and Ks) based on protein-coding sequences across species or even different evolutionary lineages. Among them, MYN method (a Modified version of Yang-Nielsen method) considers three major dynamic features of evolving DNA sequences–bias in transition/transversion rate, nucleotide frequency, and unequal transitional substitution but leaves out another important feature: unequal substitution rates among different sites or nucleotide positions.

Results
We incorporated a new feature for analyzing evolving DNA sequences–unequal substitution rates among different sites–into MYN method, and proposed a modified version, namely γ (gamma)-MYN, based on an assumption that the evolutionary rate at each site follows a mode of γ-distribution. We applied γ-MYN to analyze the key estimator of selective pressure ω (Ka/Ks) and other relevant parameters in comparison to two other related methods, YN and MYN, and found that neglecting the variation of substitution rates among different sites may lead to biased estimations of ω. Our new method appears to have minimal deviations when relevant parameters vary within normal ranges defined by empirical data.

Conclusion
Our results indicate that unequal substitution rates among different sites have variable influences on ω under different evolutionary rates while both transition/transversion rate ratio and unequal nucleotide frequencies affect Ka and Ks thus selective pressure ω.

Reviewers
This paper was reviewed by Kateryna Makova, David A. Liberles (nominated by David H Ardell), Zhaolei Zhang (nominated by Mark Gerstein), and Shamil Sunyaev.
Abnormal autophagy, ubiquitination, inflammation and apoptosis are dependent upon lysosomal storage and are useful biomarkers of mucopolysaccharidosis VI
Authors: Tessitore Alessandra , Pirozzi Marinella , Auricchio Alberto 
Published: June 2009

Abstract

Background
Lysosomal storage diseases are characterized by intracellular accumulation of metabolites within lysosomes. Recent evidence suggests that lysosomal storage impairs autophagy resulting in accumulation of polyubiquitinated proteins and dysfunctional mitochondria, ultimately leading to apoptosis. We studied the relationship between lysosome storage and impairment of different intracellular pathways and organelle function in mucopolysaccharidosis VI, which is characterized by accumulation of dermatan sulfate and signs of visceral and skeletal but not cerebral involvement.

Results
We show lysosomal storage, impaired autophagy, accumulation of polyubiquitinated proteins, and mitochondrial dysfunction in fibroblasts from mucopolysaccharidosis VI patients. We observe similar anomalies, along with inflammation and cell death, in association with dermatan sulfate storage in the visceral organs of mucopolysaccharidosis VI rats, but not in their central nervous system where dermatan sulfate storage is absent. Importantly, we show that prevention of dermatan sulfate storage in the mucopolysaccharidosis VI rat visceral organs by gene transfer results in correction of abnormal autophagy, inflammation, and apoptosis, suggesting that dermatan sulfate accumulation impairs lysosomal ability to receive and degrade molecules and organelles from the autophagic pathway, thus leading to cell toxicity.

Conclusion
These results indicate that the non-lysosomal degradation pathways we found activated in mucopolysaccharidosis VI can be both targets of new experimental therapies and biomarkers for follow-up of existing treatments.
International Foot and Ankle Biomechanics Community (i‐FAB): past, present and beyond
Authors: Nester Christopher J , Leardini Alberto , Cavanagh Peter R , Rosenbaum Dieter , Burns Joshua 
Published: June 2009

AbstractThe International Foot and Ankle Biomechanics Community (i‐FAB) is an international collaborative activity which will have an important impact on the foot and ankle biomechanics community. It was launched on July 2nd 2007 at the foot and ankle session of the International Society of Biomechanics (ISB) meeting in Taipei, Taiwan. i‐FAB is driven by the desire to improve our understanding of foot and ankle biomechanics as it applies to health, disease, and the design, development and evaluation of foot and ankle surgery, and interventions such as footwear, insoles and surfaces.
Unusual presentation of Lynch Syndrome
Authors: Yu Veronica PCC , Novelli Marco , Payne Stewart J , Fisher Sam , Barnetson Rebecca A , Frayling Ian M , Barrett Ann , Goudie David , Ardern-Jones Audrey , Eeles Ros , Shanley Susan 
Published: June 2009

Abstract
Lynch Syndrome/HNPCC is a syndrome of cancer predisposition linked to inherited mutations of genes participating in post-replicative DNA mismatch repair (MMR). The spectrum of cancer associated with Lynch Syndrome includes tumours of the colorectum, endometrium, ovary, upper gastrointestinal tract and the urothelium although other cancers are rarely described. We describe a family of Lynch Syndrome with an hMLH1 mutation, that harbours an unusual tumour spectrum and its diagnostic and management challenges.
Extended adjuvant hormonal therapy with exemestane has no detrimental effect on the lipid profile of postmenopausal breast cancer patients: final results of the ATENA lipid substudy
Authors: Markopoulos Christos , Dafni Urania , Misitzis John , Zobolas Vasilios , Tzoracoleftherakis Evagelos , Koukouras Dimitrios , Xepapadakis Grigorios , Papadiamantis John , Venizelos Basileios , Antonopoulou Zoh , Gogas Helen 
Published: June 2009

Abstract
Introduction
Extended adjuvant endocrine therapy for breast cancer with aromatase inhibitors may potentially alter the lipid profile of postmenopausal patients and thus increase the risk of developing cardiovascular disease. In this study, a subprotocol of the ATENA (Adjuvant post-Tamoxifen Exemestane versus Nothing Applied) trial, we compared the effect of the steroidal aromatase inactivator exemestane on the lipid profile of postmenopausal patients with operable breast cancer, in the adjuvant setting, with that of observation alone after completion of 5 to 7 years of primary treatment with tamoxifen.

Methods
In this open-label, randomized, parallel-group study, 411 postmenopausal patients with operable breast cancer, who had been treated with tamoxifen for 5 to 7 years, were randomized to either 5 additional years of exemestane (25 mg/day; n = 211) or observation only (n = 200). Assessments of total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and total serum triglycerides (TRG) were performed at baseline and then during each follow-up visit, performed at either 6 or 12 months, according to the center's clinical practice, until completing 24 months in the study.

Results
TC and LDL levels increased significantly across time for both arms; TC increase was more pronounced for the observation arm, and that was sustained up to 24 months. HDL levels decreased significantly across time for the exemestane arm, whereas no significant change was detected across time for the observation arm. Triglyceride levels decreased significantly across time on both arms, with no difference detected in changes from baseline between the exemestane and the observation arms.

Conclusions
Exemestane lacks the beneficial effect of tamoxifen on lipids; however, sequential adjuvant treatment with exemestane in postmenopausal breast cancer patients after cessation of 5 to 7 years of tamoxifen does not appear to alter the lipid profile significantly compared with that of an observational arm.

Trial Registration
ClinicalTrials.gov ID: NCT00810706.
Leptin-signaling inhibition results in efficient anti-tumor activity in estrogen receptor positive or negative breast cancer
Authors: Rene Gonzalez Ruben , Watters Amber , Xu Yanbo , Singh Udai P , Mann David R , Rueda Bo R , Penichet Manuel L 
Published: June 2009

Abstract
Introduction
We have shown previously that treatment with pegylated leptin peptide receptor antagonist 2 (PEG-LPrA2) reduced the expression of vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor type 2 (VEGFR2) and growth of 4T1-breast cancer (BC) in syngeneic mice. In this investigation, PEG-LPrA2 was used to evaluate whether the inhibition of leptin signaling has differential impact on the expression of pro-angiogenic and pro-proliferative molecules and growth of human estrogen receptor-positive (ER+) and estrogen receptor-negative (ER-) BC xenografts hosted by immunodeficient mice.

Methods
To test the contribution of leptin signaling to BC growth and expression of leptin-targeted molecules, PEG-LPrA2 treatment was applied to severe immunodeficient mice hosting established ER+ (MCF-7 cells; ovariectomized/supplemented with estradiol) and ER- (MDA-MB231 cells) BC xenografts. To further assess leptin and PEG-LPrA2 effects on ER+ and ER- BC, the expression of VEGF and VEGFR2 (protein and mRNA) was investigated in cell cultures.

Results
PEG-LPrA2 more effectively reduced the growth of ER+ (>40-fold) than ER- BC (twofold) and expression of pro-angiogenic (VEGF/VEGFR2, leptin/leptin receptor OB-R, and IL-1 receptor type I) and pro-proliferative molecules (proliferating cell nuclear antigen and cyclin D1) in ER+ than in ER- BC. Mouse tumor stroma in ER+ BC expressed high levels of VEGF and leptin that was induced by leptin signaling. Leptin upregulated the transcriptional expression of VEGF/VEGFR2 in MCF-7 and MDA-MB231 cells.

Conclusions
These results suggest that leptin signaling plays an important role in the growth of both ER+ and ER- BC that is associated with the leptin regulation of pro-angiogenic and pro-proliferative molecules. These data provide support for the potential use of leptin-signaling inhibition as a novel treatment for ER+ and ER- BC.
Single-Agent Bortezomib in Previously Untreated Multiple Myeloma: Efficacy, Characterization of Peripheral Neuropathy, and Molecular Correlations With Response and Neuropathy
Authors: Richardson Paul G. , Xie Wanling , Mitsiades Constantine , Chanan-Khan Asher A. , Lonial Sagar , Hassoun Hani , Avigan David E. , Oaklander Anne Louise , Kuter David J. , Wen Patrick Y. , Kesari Santosh , Briemberg Hannah R. , Schlossman Robert L. , Munshi Nikhil C. , Heffner L. Thompson , Doss Deborah , Esseltine Dixie-Lee , Weller Edie , Anderson Kenneth C. , Amato Anthony A. 
Published: June 2009

Purpose To assess efficacy and safety of single-agent bortezomib in previously untreated patients with multiple myeloma, investigate prevalence of baseline and treatment-emergent polyneuropathy, and identify molecular markers associated with response and neuropathy. Patients and Methods Patients received bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11, for up to eight 21-day cycles. A subset of patients underwent neurophysiologic evaluation pre- and post-treatment. Bone marrow aspirates were performed at baseline for exploratory whole-genome analyses. Results Among 64 patients, 41% had partial response or better, including 9% complete/near-complete responses; median duration of response was 8.4 months. Response rates did not differ in the presence or absence of adverse cytogenetics. After median follow-up of 29 months, median time to progression was 17.3 months. Median overall survival had not been reached; estimated 1-year survival was 92%. Thirty-two patients successfully underwent optional stem-cell transplantation. Bortezomib treatment was generally well tolerated. At baseline, 20% of patients had sensory polyneuropathy. Sensory polyneuropathy developed during treatment in 64% of patients (grade 3 in 3%), but proved manageable and resolved in 85% within a median of 98 days. Neurologic examination, neurophysiologic testing, and measurements of epidermal nerve fiber densities in 35 patients confirmed pretreatment sensory neuropathy in 20% and new or worsening neuropathy in 63%. Pharmacogenomic analyses identified molecular markers of response and treatment-emergent neuropathy, which will require future study. Conclusion Single-agent bortezomib is effective in previously untreated myeloma. Baseline myeloma-associated neuropathy seems more common than previously reported, and bortezomib-associated neuropathy, although a common toxicity, is reversible in most patients.
Novel TET2 Mutations Associated With UPD4q24 in Myelodysplastic Syndrome
Authors: Mohamedali Azim M. , Smith Alexander E. , Gaken Joop , Lea Nicholas C. , Mian Syed A. , Westwood Nigel B. , Strupp Corinna , Gattermann Norbert , Germing Ulrich , Mufti Ghulam J. 
Published: June 2009

Purpose Cryptic chromosomal aberrations, such as regions of uniparental disomy (UPD), have been shown to harbor homozygous mutations and are a common feature in myelodysplastic syndrome (MDS). We investigated the sequence integrity of 4q24 candidate tumor suppressor gene TET2 in MDS patients with UPD on chromosome 4. Patients and Methods The coding exons of TET2 were analyzed by 454 deep sequencing and Sanger sequencing in nine patients with UPD on 4q. Four patients had refractory cytopenia with multilineage dysplasia and ringed sideroblasts (RCMD-RS) and UPD4q24, and five patients (refractory anemia with excess blasts-II, n = 1; 5q– syndrome, n = 1; RCMD-RS, n = 1; refractory anemia, n = 1; refractory cytopenia with multilineage dysplasia, n = 1) had no UPD4q24. Results Mutations on TET2 were identified in all four patients with UPD4q24. These were localized to exons 3, 6, and 9 and resulted in two premature stop codons, one frameshift mutation, and one cysteine to glycine amino acid change. Mutant clone size varied between 30% and 85%. One patient with UPD outside of q24 (UPD4q28.3) displayed additional TET2 mutations, but these were at low clonal levels (13%, 4%, and 4% for a silent mutation, a 180-base pair deletion in exon 3, and a lysine to phenylalanine substitution in exon 11, respectively). The other patients who did not have UPD4q24 did not have verifiable TET2 mutations. Conclusion Our data identify novel TET2 mutations in a dominant clone in patients with UPD4q24. The presence of UPD4q24 and mutations in RCMD-RS patients may suggest specificity to this subtype. Our preliminary results need to be confirmed in a large cohort of all MDS subtypes.
How does a standardized care plan facilitate the practice of pharmaceutical care planning in mental health settings across Scotland?
Authors: Fraser Mary , Fraser Karen , Davies Paul , Shaw Thom , Walker Andrew 
Published: June 2009

Abstract

Objectives
The aim of the project was to understand how a standardized generic pharmaceutical care plan could facilitate the practice of mental health pharmacy care planning across Scotland. Specifically, the objectives were to examine whether the plan was easy to use, collected appropriate information and enabled communication on discharge; when the plan was used in relation to multidisciplinary meetings; how useful it was to other team members; whether it changed the way pharmacists worked; and who wrote in the plan. A further objective was to examine whether there were barriers to implementing the plan and how these may be overcome.

Methods
A piloted questionnaire and diary were completed by practising pharmacists, asking them to describe their use of the generic care plan. Mental health pharmacists throughout Scotland used the care plans with adult, elderly and forensic mental health inpatients over the 2 month period.

Key findings
Forty-four mental health pharmacists participated (69.84% of practising mental health pharmacists across Scotland). They used the plan with 241 adult, 70 elderly and 16 forensic mental health patients. Many sections of the plan received positive appraisal, but changes were also widely recommended. Changes were on three levels: (1) additions or deletions to individual sections of the care plan, some of which may reflect local circumstances, (2) more radical deletions or changes to entire sections or pages and (3) to take into account the wider social and political context in which pharmacists work, with the potential for local rates of progress towards national imperatives, such as multidisciplinary working.

Conclusions
The development of a standardized care plan for mental health pharmacists should address policy issues and could enhance the role of the pharmacist within multidisciplinary teams.
Development and validation of procedures for assessment of competency of non-pharmacists in extemporaneous dispensing
Authors: Donnelly Ryan F , McNally Martin J , Barry Johanne G 
Published: June 2009

Abstract

Objectives
To develop and validate procedures that may be suitable for assessment of competency of two groups of non-pharmacist staff (pharmacy students and trainee support staff) in extemporaneous dispensing. This is important given the prospect of remote supervision of community pharmacies in the UK.

Methods
Analytical methods were validated according to International Conference on Harmonisation specifications and procedures were optimized to allow efficient drug extraction. This permitted straightforward determination of drug content in extemporaneously prepared lidocaine hydrochloride mouthwashes and norfloxacin creams and suspensions prepared by 10 participants recruited to represent the two groups of non-pharmacist staff.

Key findings
All 10 participants had completed the extemporaneous dispensing of all three products within 90 min. Extraction and analysis took approximately 15 min for each lidocaine hydrochloride mouthwash and 30 min for each diluted norfloxacin cream and norfloxacin suspension. The mean drug concentrations in lidocaine hydrochloride mouthwashes and diluted norfloxacin creams were within what are generally accepted as being pharmaceutically acceptable limits for drug content (100 ± 5%) for both groups of participants. There was no significant difference in the mean drug concentration of norfloxacin suspensions prepared by the participant groups. However, it was notable that only one participant prepared a suspension containing a norfloxacin concentration that was within pharmaceutically acceptable limits (101.51%).

Conclusions
A laboratory possessing suitable equipment and appropriately trained staff could cope readily with the large number of products prepared, for example, by a cohort of pre-registration students. Consequently, the validated procedures developed here could usefully be incorporated into the pre-registration examination for pharmacy students and a final qualifying examination for dispensers and pharmacy technicians. We believe that this is essential if the public and the profession are to have confidence in extemporaneous dispensing carried out in the absence of a pharmacist.
Industrielle pH-Messung – Beiträge der Diffusionspotenziale zur MessunsicherheitIndustrial pH Measurement – Contribution of Diffusion Potentials to Measurement Uncertainty
Authors: Tauber Günter 
Published: June 2009

Zusammenfassung
Qualitätsmanagementsysteme stellen hohe Anforderungen an die Analytik und die Prozessführung in der chemischen und pharmazeutischen Industrie. Analysenergebnisse müssen rückführbar auf nationale Standards sein. Zur Angabe der Unsicherheit bei der wichtigen pH-Messung fehlen bisher Werte für die Liquid Junction Potentials (LJPs). Dieser Beitrag soll einen Teil dieser Lücke schließen.
2D-Echtzeit-Ultraschallverfahren zur Messung der Gewebeelastizität für die TumorfrüherkennungUltrasonic 2D-Real-Time Measurement of Tissue Elasticity for Early Tumor Detection
Authors: Eder Andreas , Kargel Christian 
Published: June 2009

Zusammenfassung
Die bildgebende Modalität “Ultraschall” besitzt eine Reihe von Vorteilen, jedoch können Gewebeveränderungen nur bei veränderten Schallstreueigenschaften sichtbar gemacht werden. Dies ist bei Tumoren leider nicht der Fall. Die Ultraschall-Elastographie verbessert die diagnostische Aussagekraft durch Messung der elasto-mechanischen Gewebeeigenschaften. Da Mediziner nur Echtzeit-Ultraschall-Verfahren akzeptieren, werden heute in der Elastographie vorwiegend numerisch effiziente 1D-Signalverarbeitungsmethoden eingesetzt. Diese unterliegen jedoch signifikanten Limitierungen, weshalb im vorliegenden Beitrag ein echtzeitfähiges 2D-Verfahren vorgestellt und mit dem besten 1D-Verfahren verglichen wird.
Kalibrierungsfreie Messung von Amplitude und Phase hochfrequenter SchwingungenCalibration-Free Measurement of Amplitude and Phase of High-Frequency Vibrations
Authors: Gollwitzer Andreas , Fischerauer Alice , Schwarzmüller Christian , Fischerauer Gerhard 
Published: June 2009

Zusammenfassung
Es wird ein neues Verfahren zur interferometrischen Erfassung von akustischen Oberflächenwellen vorgestellt. Die beschriebene Methode erlaubt die Extraktion der absoluten Amplitude und der Phase einer hochfrequenten Schwingung, unabhängig von Oberflächenreflexionsfaktoren, Variationen der Laserleistung oder Sensitivität des Interferometers. Ermöglicht wird dies durch die synchrone Erfassung des Messsignals mittels eines vektoriellen Netzwerkanalysators und eines digitalen Speicheroszilloskops. Die anschließende digitale Signalverarbeitung extrahiert die gewünschte Information aus den Messdaten. Zur Verifikation wurden Simulationen der Anregung akustischer Wellen mit dem Deltafunktionsmodell durchgeführt und mit den Messdaten verglichen. Anhand der Messdaten wird schließlich die anisotrope Slowness-Kurve konstruiert. Diese Information kann zur Bestimmung der Materialparameter von Dünnschichten verwendet werden.