bluuebunny/crossref_metadata_2025_split huggingface dataset:
SPIKE – a database, visualization and analysis tool of cellular signaling pathways
Authors: Elkon Ran , Vesterman Rita , Amit Nira , Ulitsky Igor , Zohar Idan , Weisz Mali , Mass Gilad , Orlev Nir , Sternberg Giora , Blekhman Ran , Assa Jackie , Shiloh Yosef , Shamir Ron 
Published: February 2008

AbstractBackgroundBiological signaling pathways that govern cellular physiology form an intricate web of tightly regulated interlocking processes. Data on these regulatory networks are accumulating at an unprecedented pace. The assimilation, visualization and interpretation of these data have become a major challenge in biological research, and once met, will greatly boost our ability to understand cell functioning on a systems level.ResultsTo cope with this challenge, we are developing the SPIKE knowledge-base of signaling pathways. SPIKE contains three main software components: 1) A database (DB) of biological signaling pathways. Carefully curated information from the literature and data from large public sources constitute distinct tiers of the DB. 2) A visualization package that allows interactive graphic representations of regulatory interactions stored in the DB and superposition of functional genomic and proteomic data on the maps. 3) An algorithmic inference engine that analyzes the networks for novel functional interplays between network components.SPIKE is designed and implemented as a community tool and therefore provides a user-friendly interface that allows registered users to upload data to SPIKE DB. Our vision is that the DB will be populated by a distributed and highly collaborative effort undertaken by multiple groups in the research community, where each group contributes data in its field of expertise.ConclusionThe integrated capabilities of SPIKE make it a powerful platform for the analysis of signaling networks and the integration of knowledge on such networks withomicsdata.
Quantitative Single-letter Sequencing: a method for simultaneously monitoring numerous known allelic variants in single DNA samples
Authors: Monsion Baptiste , Duborjal Hervé , Blanc Stéphane 
Published: February 2008

Abstract

Background
Pathogens such as fungi, bacteria and especially viruses, are highly variable even within an individual host, intensifying the difficulty of distinguishing and accurately quantifying numerous allelic variants co-existing in a single nucleic acid sample. The majority of currently available techniques are based on real-time PCR or primer extension and often require multiplexing adjustments that impose a practical limitation of the number of alleles that can be monitored simultaneously at a single locus.

Results
Here, we describe a novel method that allows the simultaneous quantification of numerous allelic variants in a single reaction tube and without multiplexing. Quantitative Single-letter Sequencing (QSS) begins with a single PCR amplification step using a pair of primers flanking the polymorphic region of interest. Next, PCR products are submitted to single-letter sequencing with a fluorescently-labelled primer located upstream of the polymorphic region. The resulting monochromatic electropherogram shows numerous specific diagnostic peaks, attributable to specific variants, signifying their presence/absence in the DNA sample. Moreover, peak fluorescence can be quantified and used to estimate the frequency of the corresponding variant in the DNA population.
Using engineered allelic markers in the genome of Cauliflower mosaic virus, we reliably monitored six different viral genotypes in DNA extracted from infected plants. Evaluation of the intrinsic variance of this method, as applied to both artificial plasmid DNA mixes and viral genome populations, demonstrates that QSS is a robust and reliable method of detection and quantification for variants with a relative frequency of between 0.05 and 1.

Conclusion
This simple method is easily transferable to many other biological systems and questions, including those involving high throughput analysis, and can be performed in any laboratory since it does not require specialized equipment.
Role of sulphated polysaccharides from Sargassum Wightii in Cyclosporine A-induced oxidative liver injury in rats
Authors: Josephine Anthony , Nithya Kalaiselvam , Amudha Ganapathy , Veena Coothan Kandaswamy , Preetha Sreenivasan P , Varalakshmi Palaninathan 
Published: February 2008

Abstract

Background
Seaweeds or marine algae have long been made up a key part of the Asian diet, and as an antioxidant, sulphated polysaccharides have piqued the interest of many researchers as one of the ocean's greatest treasures. The present investigation suggests the therapeutic potential of sulphated polysaccharides from marine brown algae "Sargassum wightii" in Cyclosporine A (CsA)- induced liver injury. CsA is a potent immunosuppressive agent used in the field of organ transplantations and various autoimmune disorders. However, hepatotoxicity due to CsA remains to be one of the major clinical challenges.

Methods
The effect of sulphated polysaccharides on CsA-induced hepatotoxicity was studied in adult male albino rats of Wistar strain, and the animals were randomized into four groups with six rats in each. Group I served as vehicle control. Group II rats were given CsA at a dosage of 25 mg/kg body weight, orally for 21 days. Group III rats were given sulphated polysaccharides at a dosage of 5 mg/kg body weight, subcutaneously for 21 days. Group IV rats were given sulphated polysaccharides simultaneously along with CsA, as mentioned in Group II for 21 days.

Results
CsA provoked hepatotoxicity was evident from the decreased activities of hepatic marker enzymes. A significant rise in the level of oxidants, along with a striking decline in both the enzymic and non-enzymic antioxidants, marks the severity of oxidative stress in CsA-induced rats. This in turn led to enhanced levels of lipid peroxidation, 8-hydroxy-2-deoxy guanosine and protein carbonyls, along with a decrease in ATPase activities and alterations in lipid profile. Histopathological changes also strongly support the above aberrations. However, concomitant treatment with sulphated polysaccharides restored the above deformities to near control and prevented the morphological alterations significantly.

Conclusion
Thus, the present study highlights that sulphated polysaccharides can act therapeutically against CsA-induced hepatotoxicity.

Key Words
Cyclosporine A; hepatic markers; antioxidants; hyperlipidemia; macromolecules; sulphated polysaccharides.
K-rasmutations in sinonasal cancers in relation to wood dust exposure
Authors: Bornholdt Jette , Hansen Johnni , Steiniche Torben , Dictor Michael , Antonsen Annemarie , Wolff Henrik , Schlünssen Vivi , Holmila Reetta , Luce Danièle , Vogel Ulla , Husgafvel-Pursiainen Kirsti , Wallin Håkan 
Published: February 2008

Abstract

Background
Cancer in the sinonasal tract is rare, but persons who have been occupationally exposed to wood dust have a substantially increased risk. It has been estimated that approximately 3.6 million workers are exposed to inhalable wood dust in EU. In previous small studies of this cancer, ras mutations were suggested to be related to wood dust exposure, but these studies were too limited to detect statistically significant associations.

Methods
We examined 174 cases of sinonasal cancer diagnosed in Denmark in the period from 1991 to 2001. To ensure uniformity, all histological diagnoses were carefully reviewed pathologically before inclusion. Paraffin embedded tumour samples from 58 adenocarcinomas, 109 squamous cell carcinomas and 7 other carcinomas were analysed for K-ras codon 12, 13 and 61 point mutations by restriction fragment length polymorphisms and direct sequencing. Information on occupational exposure to wood dust and to potential confounders was obtained from telephone interviews and from registry data.

Results
Among the patients in this study, exposure to wood dust was associated with a 21-fold increased risk of having an adenocarcinoma than a squamous cell carcinoma compared to unexposed [OR = 21.0, CI = 8.0–55.0]. K-ras was mutated in 13% of the adenocarcinomas (seven patients) and in 1% of squamous cell carcinomas (one patient). Of these eight mutations, five mutations were located in the codon 12. The exact sequence change of remaining three could not be identified unambiguously. Among the five identified mutations, the G→A transition was the most common, and it was present in tumour tissue from two wood dust exposed adenocarcinoma patients and one patient with unknown exposure. Previously published studies of sinonasal cancer also identify the GGT → GAT transition as the most common and often related to wood dust exposure.

Conclusion
Patients exposed to wood dust seemed more likely to develop adenocarcinoma compared to squamous cell carcinomas. K-ras mutations were detected in 13% of adenocarcinomas. In this study and previously published studies of sinonasal cancer the found K-ras mutations, were almost exclusively G → A transitions. In conclusion, our study, based on a large representative collection of human SNC tumours, indicates that K-ras mutations are relatively infrequent, and most commonly occur in adenocarcinomas. Wood dust exposure alone was not found to be explanatory for the G→A mutations, but combination of exposure to tobacco, wood dust, and possibly other occupational agents may be a more likely explanation. Overall, the study suggests a limited role for K-ras mutations in development of sinonasal cancer.
Safety and immunogenicity of an MF59™-adjuvanted subunit influenza vaccine in elderly Chinese subjects
Authors: Li Rongcheng , Fang Hanhua , Li Yanping , Liu Youping , Pellegrini Michele , Podda Audino 
Published: February 2008

Abstract

Background
The safety and immunogenicity of an MF59™-adjuvanted subunit influenza vaccine (Sub/MF59™; FLUAD®, Novartis Vaccines) was evaluated among elderly Chinese subjects (≥ 60 years of age). After a preliminary Phase I, open-label study (n = 25) to assess safety 1–14 days post-vaccination, a comparative observer-blind, randomised, controlled clinical trial (n = 600) was performed to assess safety and immunogenicity versus a non-adjuvanted subunit influenza vaccine (Subunit; Agrippal®, Novartis Vaccines). Subjects were randomised (2:1) to receive Sub/MF59™ or Subunit.

Results
Both vaccines were well tolerated, with no vaccine-related serious adverse events reported during the Phase I trial. During the observer-blind study, local and systemic reactions were generally similar for both vaccines 1–22 days post-vaccination; however, injection-site induration was more frequent among the Subunit group (P < 0.05), and mild pain at the injection site and fever were more frequent among Sub/MF59™ recipients (P ≤ 0.005). Both vaccines induced a significant (P < 0.001) increase in geometric mean titres (GMTs) for the three strains tested, versus baseline; GMTs against A/H1N1, A/H3N2 and B were significantly higher in the Sub/MF59™ group (P = 0.034, P < 0.001 and P = 0.005, respectively). GMT ratios against A/H1N1, A/H3N2 and B were also significantly higher in the Sub/MF59™ group (P = 0.038, P < 0.001 and P = 0.006, respectively). Similarly, the percentage of subjects achieving seroprotection or seroconversion on Day 22 was greater for Sub/MF59™ recipients, reaching significance for A/H3N2 (P < 0.001).

Conclusion
MF59™-adjuvanted subunit influenza vaccine is well tolerated by elderly Chinese subjects and induces a higher level of immunogenicity than a non-adjuvanted subunit influenza vaccine in this population that is at high risk of influenza-related complications.

Clinical trial registry

http://www.clinicaltrials.gov, NCT00310648
Effect of medial arch-heel support in inserts on reducing ankle eversion: a biomechanics study
Authors: Fong Daniel TP , Lam Mak-Ham , Lao Miko LM , Chan Chad WN , Yung Patrick SH , Fung Kwai-Yau , Lui Pauline PY , Chan Kai-Ming 
Published: February 2008

Abstract

Background
Excessive pronation (or eversion) at ankle joint in heel-toe running correlated with lower extremity overuse injuries. Orthotics and inserts are often prescribed to limit the pronation range to tackle the problem. Previous studies revealed that the effect is product-specific. This study investigated the effect of medial arch-heel support in inserts on reducing ankle eversion in standing, walking and running.

Methods
Thirteen pronators and 13 normal subjects participated in standing, walking and running trials in each of the following conditions: (1) barefoot, and shod condition with insert with (2) no, (3) low, (4) medium, and (5) high medial arch-heel support. Motions were captured and processed by an eight-camera motion capture system. Maximum ankle eversion was calculated by incorporating the raw coordinates of 15 anatomical positions to a self-compiled Matlab program with kinematics equations. Analysis of variance with repeated measures with post-hoc Tukey pairwise comparisons was performed on the data among the five walking conditions and the five running conditions separately.

Results
Results showed that the inserts with medial arch-heel support were effective in dynamics trials but not static trials. In walking, they successfully reduced the maximum eversion by 2.1 degrees in normal subjects and by 2.5–3.0 degrees in pronators. In running, the insert with low medial arch support significantly reduced maximum eversion angle by 3.6 and 3.1 degrees in normal subjects and pronators respectively.

Conclusion
Medial arch-heel support in inserts is effective in reducing ankle eversion in walking and running, but not in standing. In walking, there is a trend to bring the over-pronated feet of the pronators back to the normal eversion range. In running, it shows an effect to restore normal eversion range in 84% of the pronators.
Lack of CCR5 on dendritic cells promotes a proinflammatory environment in submandibular glands of the NOD mouse
Authors: Wildenberg Manon E , van Helden-Meeuwsen Cornelia G , van de Merwe Joop P , Moreno Christophe , Drexhage Hemmo A , Versnel Marjan A 
Published: February 2008

AbstractSjögren’s syndrome is an autoimmune disease characterized by lymphocytic infiltration of the salivary glands. In the NOD mouse, a model for this disease, the development of lymphocytic infiltrates in the salivary glands is preceded by an accumulation of dendritic cells (DC). Given the key importance of DC in regulating the immune response, we characterized the DC isolated from NOD salivary glands. These DC lacked membrane expression of CCR5, whereas DC from control salivary glands did express this molecule. The lack of expression was present already prior to the onset of lymphocytic infiltration, indicating that this was not the result of ongoing inflammation. DC from other sources in the NOD mouse also showed a decrease in CCR5 expression. The lack of CCR5 expression in the NOD salivary gland was accompanied by an increase in inflammatory chemokines. Furthermore, DC from CCR5−/− animals or DC treated with a CCR5 antagonist showed increased secretion of IL-12. Interestingly, in Sjögren’s syndrome patients, CCR5 expression on circulating monocytes was decreased and correlated to increased levels of IL-12. These data indicate that CCR5 has regulatory properties and that the lack of CCR5 in NOD DC contributes to the proinflammatory environment in the salivary glands.
Review of Phase II Trial Designs Used in Studies of Molecular Targeted Agents: Outcomes and Predictors of Success in Phase III
Authors: El-Maraghi Robert H. , Eisenhauer Elizabeth A. 
Published: February 2008

Purpose Because the appropriate design and end points for phase II evaluation of targeted anticancer agents are unclear, we undertook a review of recent reports of phase II trials of targeted agents to determine the types of designs used, the planned end points, the outcomes, and the relationship between trial outcomes and regulatory approval. Methods We retrieved reports of single-agent phase II trials in six solid tumors for 19 targeted drugs. For each, we abstracted data regarding planned design and actual results. Response rates were examined for any relationship to eventual success of the agents, as determined by US Food and Drug Administration approval for at least one indication. Results Eighty-nine trials were identified. Objective response was the primary or coprimary end point in the majority of trials (61 of 89 trials). Fourteen reports were of randomized studies generally evaluating different doses of agents, not as controlled experiments. Enrichment for target expression was uncommon. Objective responses were seen in 38 trials; in 19 trials, response rates were more than 10%, and in eight, they were more than 20%. Agents with high response rates tended to have high nonprogression rates; renal cell carcinoma was the exception to this. Higher overall response rates were predictive of regulatory approval in the tumor types reviewed (P = .005). Conclusion In practice, phase II design for targeted agents is similar to that for cytotoxics. Objective response seems to be a useful end point for screening new targeted agents because, in our review, its observation predicted for eventual success. Improvements in design are recommended, as is more frequent inclusion of biological questions as part of phase II trials.
Estrogen Receptor, Progesterone Receptor, HER-2, and Response to Postmastectomy Radiotherapy in High-Risk Breast Cancer: The Danish Breast Cancer Cooperative Group
Authors: Kyndi Marianne , Sørensen Flemming B. , Knudsen Helle , Overgaard Marie , Nielsen Hanne Melgaard , Overgaard Jens 
Published: February 2008

Purpose To examine the importance of estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER-2), and constructed subtypes in a large study randomly assigning patients to receive or not receive postmastectomy radiotherapy (PMRT). Patients and Methods The present analysis included 1,000 of the 3,083 high-risk breast cancer patients randomly assigned to PMRT in the Danish Breast Cancer Cooperative Group (DBCG) protocol 82 trials b and c. Tissue microarray sections were stained for ER, PgR, and HER-2. Median follow-up time for patients alive was 17 years. End points were locoregional recurrence as isolated first event, distant metastases, and overall survival. For statistical analyses four subgroups were constructed from hormonal receptors (Rec). Rec+ was defined as ER+ and/or PgR+. Rec–as both ER–and PgR–. The four subgroups were Rec+/HER-2–, Rec+/HER-2+, Rec–/HER-2–(triple negative), and Rec–/HER-2+. Results A significantly improved overall survival after PMRT was seen only among patients characterized by good prognostic markers such as hormonal receptor–positive and HER-2− patients (including the two Rec+ subtypes). No significant overall survival improvement after PMRT was found among patients with an a priori poor prognosis, the hormonal receptor–negative and HER-2+ patients, and in particular the Rec–/HER-2+ subtype. Furthermore, comparing hazard ratios and 95% CIs, significantly smaller improvements in locoregional recurrence control after PMRT were found for ER–and PgR–tumors compared with the ER+ and PgR+ tumors (P = .003 and .04, respectively), and for the triple-negative (P = .02), and the Rec–/HER-2+ subtypes (P = .003) compared with the Rec+/HER-2–subtype. Conclusion Hormonal receptor status, HER-2, and the constructed subtypes may be predictive of locoregional recurrence and survival after postmastectomy radiotherapy.
Torsional characterization of ropes used offshore
Authors: Ridge I M L 
Published: February 2008

The first part of this paper presents a general discussion of the various problems which must be addressed when combining different ropes in series or, in some cases, in using a rope in conditions where it is rotationally unrestrained. The paper will pay particular attention to the various classes of rope used in the offshore environment and their main torsional characteristics. In the second part, equipment is shown which is suitable for the measurement of the torsional response of various rope constructions at different levels of twist. Experimental data are presented for a variety of rope constructions at sizes comparable with those used in offshore applications. Comparison is made with data obtained in similar previous studies but with smaller‐diameter ropes.
What is the place of the new WHO antenatal care model in a teaching hospital setting?
Authors: Ekele B A , Shehu C E , Ahmed Y , Fache M 
Published: February 2008

The basic component of the new World Health Organization (WHO) antenatal care model prescribes reduced number of clinic visits and limited investigations for low-risk pregnant women. The objectives of this study were to determine the proportion of pregnant women seeking antenatal care in a Nigerian teaching hospital who qualify for the basic component and to document difficulties that may arise with the classifying form. In December 2004, 234 pregnant women who had initiated antenatal care were enrolled for the study. Using the classifying form, 157 (67%) were eligible for the basic component, 41 (18%) for special care, but 36 (15%) women could not be classified. Those that did not know the birth weight of their last babies accounted for most (89%) of the unclassified group. The WHO antenatal care model was the most appropriate and relevant method for our hospital where a large percentage (67%) of prenatal women were eligible for the basic component. However, we consider that the classifying form should be adapted to accommodate all pregnant women.
Does Low Vitamin D Status Contribute to “Age-Related” Morbidity?
Authors: Binkley Neil 
Published: February 2008

Abstract
It is increasingly appreciated that vitamin D plays important physiological roles beyond the musculoskeletal system. As such, it is plausible that endemic vitamin D deficiency contributes to much nonskeletal morbidity that adversely affects quality of life with advancing age among older adults. This overview will explore the evidence for, and potential involvement of, vitamin D deficiency in nonbone conditions that are currently accepted as “age-related” morbidity among older adults.