bluuebunny/crossref_metadata_2025_split huggingface dataset:
Defining localities of inadequate treatment for childhood asthma: A GIS approach
Authors: Peled Ronit , Reuveni Haim , Pliskin Joseph S , Benenson Itzhak , Hatna Erez , Tal Asher 
Published: January 2006

Abstract

Background
The use of Geographic Information Systems (GIS) has great potential for the management of chronic disease and the analysis of clinical and administrative health care data. Asthma is a chronic disease associated with substantial morbidity, mortality, and health care use. Epidemiologic data from all over the world show an increasing prevalence of asthma morbidity and mortality despite the availability of effective treatment. These facts led to the emergence of strategies developed to improve the quality of asthma care.

The objective
To develop an efficient tool for quality assurance and chronic disease management using a Geographic Information System (GIS).

Geographic location
The southern region of Israel. January 1998 – October 2000.

Databases
Administrative claims data of the largest HMO in Israel: drug dispensing registry, demographic data, Emergency Room visits, and hospitalization data bases.

Methods
We created a list of six markers for inadequate pharmaceutical treatment of childhood asthma from the Israeli clinical guidelines. We used this list to search the drug dispensing registry to identify asthmatic children who received inadequate treatment and to assess their health care utilization and bad outcomes: emergency room visits and hospitalizations. Using GIS we created thematic maps on which we located the clinics with a high percentage of children for whom the treatment provided was not in adherence with the clinical guidelines.

Results
81% of the children were found to have at least one marker for inadequate treatment; 17.5% were found to have more than one marker. Children with markers were found to have statistically significant higher rates of Emergency Room visits, hospitalizations and longer length of stay in hospital compared with children without markers. The maps show in a robust way which clinics provided treatment not in accord with the clinical guidelines. Those clinics have high rates of Emergency Room visits, hospitalizations and length of stay.

Conclusion
Integration of clinical guidelines, administrative data and GIS can create an efficient interface between administrative and clinical information. This tool can be used for allocating sites for quality assurance interventions.
BRAF mutations are associated with distinctive clinical, pathological and molecular features of colorectal cancer independently of microsatellite instability status
Authors: Qi Li Wei , Kawakami Kazuyuki , Ruszkiewicz Andrew , Bennett Graeme , Moore James , Iacopetta Barry 
Published: January 2006

Abstract

Background
BRAF is a member of RAF family of serine/threonine kinases and mediates cellular responses to growth signals through the RAS-RAF-MAP kinase pathway. Activating mutations in BRAF have recently been found in about 10% of colorectal cancers, with the vast majority being a V600E hotspot mutation. The aim of the present study was to evaluate the clinical, pathological and molecular phenotype of colorectal tumors with BRAF mutations.

Results
Mutations in BRAF were identified in 8% (23/275) of colorectal cancers. They were 5–10-fold more frequent in tumors with infiltrating lymphocytes, location in the proximal colon, poor histological grade and mucinous appearance (P < 0.002 for each). Tumors with BRAF mutation were also 10-fold more likely to show microsatellite instability and frequent DNA methylation (P < 0.0001) compared to tumors without this mutation. The characteristic morphological features of tumors with BRAF mutation (infiltrating lymphocytes, poor grade, mucinous) remained after stratification according to microsatellite instability and methylator phenotypes. Mutations in BRAF were mutually exclusive with mutations in KRAS but showed no clear association with the presence of TP53 mutation.

Conclusion

BRAF mutation identifies a colorectal cancer subgroup with distinctive phenotypic properties independent of microsatellite instability status and thus could be a valuable marker for studies into the clinical properties of these tumors.
Hypoxia-inducible factor-1α polymorphisms and TSC1/2 mutations are complementary in head and neck cancers
Authors: Hebert Carla , Norris Kathleen , Parashar Pallavi , Ord Robert A , Nikitakis Nikolaos G , Sauk John J 
Published: January 2006

Abstract

Background
Polymorphisms or mutations in hypoxia inducible factor-1 alpha (HIF-1alpha) that increases its activity and stability under normoxia have recently been identified. Likewise, disruption of the TSC1/TSC2 complex through loss of TSC1 or TSC2 has been shown to result in abnormal accumulation of HIF-1α. Here, we investigate the novel polymorphisms in exon 12, that approximate the oxygen-dependent degradation domain of HIF-1alpha in five cell lines and 28 patients with oral squamous carcinomas. Moreover, we assess for the presence of polymorphisms and mutations in TSC1 and TSC2, to ascertain if dysregulation of such might complement HIF-1alpha expression.

Results
Denaturing high pressure liquid chromatography (DHPLC) analysis on PCR fragments in exon 12 of HIF-1alpha from 28 patients with OSCC revealed that 6 of 28 patients had mismatched heteroduplex patterns. Genomic DNA was extracted from peripheral blood leukocytes and direct sequencing showed that in 5 of the six cases these changes represented polymorphisms while, one case was a somatic mutation. Analyses of TSC1 and TSC2 revealed heteroduplexes in exons: TSC1 exon 17; TSC2 exons 36,40, and 41. The relative levels of HIF-1alpha were significantly greater for tumors possessing a HIF-1alpha polymorphism or mutation within exon 12, whereas tumors possessing a deletion or polymorphism in TSC1/TSC2 displayed a trend for higher levels of HIF-1alpha. Western blot analyses for HIF-1alpha, TSC1 and TSC2 in five SCC cell lines revealed high levels of HIF-1alpha in SCC cells possessing TSC1 and/or TSC2 mutations. Wild-type TSC2 cells targeted with siRNA to TSC2 exhibited increased levels of HIF-1alpha. Transfection of a HIF-1alpha mutant produced higher levels of HIF-1alpha in TSC1/TSC2 mutant cell lines than in wild type cells. TSC1/TSC2 mutant cell lines administered Rapamycin blocked S6 phorphorylation and diminished the levels of HIF-1alpha to those observed in cell lines with wild type TSC1/TSC2.

Conclusion
Dysregulation of the TSC1/TSC2 complex by mutation compliments HIF-1α polymorphisms in the expression of HIF-1alpha in SCC of the head and neck, and may provide biomarkers to predict responses to specific therapies and overall disease prognosis.
The tumor suppressor DAL-1/4.1B and protein methylation cooperate in inducing apoptosis in MCF-7 breast cancer cells
Authors: Jiang Wei , Newsham Irene F 
Published: January 2006

Abstract

Background
DAL-1 (Differentially Expressed in Adenocarcinoma of the Lung)/4.1B is a member of the protein 4.1 superfamily that has been shown to suppress growth in lung, breast and brain tumor cells. In the case of the caspase-3 deficient MCF-7 breast cancer cells, this growth suppression has been shown to be partially mediated by the induction of apoptosis. However the exact mechanism of action of DAL-1/4.1B is unknown. Recently, protein arginine N-methyltransferase 3 (PRMT3) was identified as a DAL-1/4.1B interacting protein. Protein arginine methyltransferases (PRMTs) posttranslationally methylate the arginine residues of proteins, a modification which has been implicated in the regulation of multiple cellular processes including nuclear-cytoplasmic transport, signal transduction, and transcription.

Results
To investigate the role of protein methylation in cell death induced by DAL-1/4.1B, DAL-1/4.1B-inducible MCF-7 cells were examined for apoptosis and caspase activation in the absence and presence of the protein methylation inhibitor adenosine dialdehyde (AdOX). Flow cytometry analysis revealed that apoptosis was primarily associated with the activation of caspase 8, and inhibition of this activation blocked the ability of DAL-1/4.1B to induce cell death.

Conclusion
These results suggest that protein methylation cooperates with DAL-1/4.1B-associated caspase 8-specific activation to induce apoptosis in breast cancer cells.
Mining literature for a comprehensive pathway analysis: A case study for retrieval of homocysteine related genes for genetic and epigenetic studies
Authors: Sharma Priyanka , Senthilkumar RD , Brahmachari Vani , Sundaramoorthy Elayanambi , Mahajan Anubha , Sharma Amitabh , Sengupta Shantanu 
Published: January 2006

Abstract
Homocysteine is an independent risk factor for cardiovascular diseases. It is also known to be associated with a variety of complex disorders. While there are a large number of independent studies implicating homocysteine in isolated pathways, the mechanism of homocysteine induced adverse effects are not clear. Homocysteine-induced modulation of gene expression through alteration of methylation status or by hitherto unknown mechanisms is predicted to lead to several pathological conditions either directly or indirectly. In the present manuscript, using literature mining approach, we have identified the genes that are modulated directly or indirectly by an elevated level of homocysteine. These genes were then placed in appropriate pathways in an attempt to understand the molecular basis of homocysteine induced complex disorders and to provide a resource for selection of genes for polymorphism screening and analysis of mutations as well as epigenetic modifications in relation to hyperhomocysteinemia. We have identified 135 genes in 1137 abstracts that either modulate the levels of homocysteine or are modulated by elevated levels of homocysteine. Mapping the genes to their respective pathways revealed that an elevated level of homocysteine leads to the atherosclerosis either by directly affecting lipid metabolism and transport or via oxidative stress and/or Endoplasmic Reticulum (ER) stress. Elevated levels of homocysteine also decreases the bioavailability of nitric oxide and modulates the levels of other metabolites including S-adenosyl methionine and S-adenosyl homocysteine which may result in cardiovascular or neurological disorders. The ER stress emerges as the common pathway that relates to apoptosis, atherosclerosis and neurological disorders and is modulated by levels of homocysteine. The comprehensive network collated has lead to the identification of genes that are modulated by homocysteine indicating that homocysteine exerts its effect not only through modulating the substrate levels for various catalytic processes but also through regulation of expression of genes involved in complex diseases.
Increase of free Mg2+in the skeletal muscle of chronic fatigue syndrome patients
Authors: McCully Kevin K , Malucelli Emil , Iotti Stefano 
Published: January 2006

Abstract
In a previous study we evaluated muscle blood flow and muscle metabolism in patients diagnosed with chronic fatigue syndrome (CFS). To better understand muscle metabolism in CFS, we re-evaluated our data to calculate free Magnesium levels in skeletal muscle. Magnesium is an essential cofactor in a number of cell processes. A total of 20 CFS patients and 11 controls were evaluated. Phosphorus magnetic resonance spectroscopy from the medial gastrocnemius muscle was used to calculate free Mg2+ from the concentrations and chemical shifts of Pi, PCr, and beta ATP peaks. CFS patients had higher magnesium levels in their muscles relative to controls (0.47 + 0.07 vs 0.36 + 0.06 mM, P < 0.01), although there was no difference in the rate of phosphocreatine recovery in these subjects, as reported earlier. This finding was not associated with abnormal oxidative metabolism as measured by the rate of recovery of phosphocreatine after exercise. In summary, calculation of free Mg2+ levels from previous data showed CFS patients had higher resting free Mg2+ levels compared to sedentary controls.
Sex differences in the rate of fatigue development and recovery
Authors: Albert WJ , Wrigley AT , McLean RB , Sleivert GG 
Published: January 2006

Abstract

Background
Many musculoskeltal injuries in the workplace have been attributed to the repetitive loading of muscle and soft tissues. It is not disputed that muscular fatigue is a risk factor for musculoskeltal injury, however the disparity between gender with respect to muscular fatigability and rate of recovery is not well understood. Current health and safety guidelines do not account for sex differences in fatiguability and may be predisposing one gender to greater risk. The purpose of this study was to quantify the sex differences in fatigue development and recovery rate of lower and upper body musculature after repeated bouts of sustained isometric contractions.

Methods
Twenty-seven healthy males (n = 12) and females (n = 15) underwent bilateral localized fatigue of either the knee extensors (male: n = 8; female: n = 8), elbow flexors (male: n = 8; female: n = 10), or both muscle groups. The fatigue protocol consisted of ten 30-second sub-maximal isometric contractions. The changes in maximum voluntary contraction (MVC), electrically evoked twitches, and motor unit activation (MUA) were assessed along with the ability to control the sustained contractions (SLP) during the fatigue protocol using a mixed four-factor repeated measures ANOVA (gender × side × muscle × time) design with significance set at p < 0.05.

Results
There was a significant loss of MVC, MUA, and evoked twitch amplitude from pre- to post-fatigue in both the arms and legs. Males had greater relative loss of isometric force, a higher rate of fatigue development, and were less capable of maintaining the fatiguing contractions in the legs when compared to the females.

Conclusion
The nature of the induced fatigue was a combination of central and peripheral fatigue that did not fully recover over a 45-minute period. The results appear to reflect sex differences that are peripheral, and partially support the muscle mass hypothesis for explaining differences in muscular fatigue.
Cellular transfer and AFM imaging of cancer cells using Bioimprint
Authors: Muys JJ , Alkaisi MM , Melville DOS , Nagase J , Sykes P , Parguez GM , Evans JJ 
Published: January 2006

Abstract
A technique for permanently capturing a replica impression of biological cells has been developed to facilitate analysis using nanometer resolution imaging tools, namely the atomic force microscope (AFM). The method, termed Bioimprint™, creates a permanent cell 'footprint' in a non-biohazardous Poly (dimethylsiloxane) (PDMS) polymer composite. The transfer of nanometer scale biological information is presented as an alternative imaging technique at a resolution beyond that of optical microscopy. By transferring cell topology into a rigid medium more suited for AFM imaging, many of the limitations associated with scanning of biological specimens can be overcome. Potential for this technique is demonstrated by analyzing Bioimprint™ replicas created from human endometrial cancer cells. The high resolution transfer of this process is further detailed by imaging membrane morphological structures consistent with exocytosis. The integration of soft lithography to replicate biological materials presents an enhanced method for the study of biological systems at the nanoscale.
Weekly induction intraperitoneal chemotherapy after primary surgical cytoreduction in patients with advanced epithelial ovarian cancer
Authors: Yu Zang Rong , Li Zi Ting , Tang Jie , Huang Xiao , Mo Cai Shu 
Published: January 2006

Abstract

Background
Traditional intraperitoneal (IP) therapy administered simultaneously with intravenous (IV) chemotherapy in the primary setting has been well documented. This retrospective study was conducted to investigate the role of weekly IP therapy as an inducing intervention before front-line IV chemotherapy, particularly in patients with bulky residual disease after surgery.

Methods
A total of 426 patients with advanced ovarian cancer treated between 1990 and 1999, were reviewed. Follow-up data were available in 409 patients. Of whom, 230 patients received postoperative weekly IP therapy with a median cycles of 4, other 179 patients who did not receive any IP therapy were used as the control group.

Results
The median age of the patients was 51 years (range, 20–77 years). One hundred eighty-nine patients with stage III disease and 41 patients with stage IV disease were treated with postoperative IP therapy, respectively. Complications and toxicity were observed in 68 patients (29.5%), but there were no grade 4 toxicities and no patients died of complications or toxicities. In patients with residual disease > 1 cm, the median survival of those with IP delivery of chemotherapy and those without was 21.6 months and 18.8 months, respectively (hazard ratio [HR]= 0.69, P = 0.02). Whereas, in patients with residual disease ≤ 1 cm, the median survival was 46.8 months and 37.6 months, respectively (HR= 0.73, P = 0.09). Multivariate analysis suggested that the factors age ≤ 60 years, stage III, IP therapy and paclitaxel as front-line chemotherapy were associated with a better prognosis for patients with advanced ovarian cancer.

Conclusion
Weekly postoperative IP therapy as an inducing intervention is practical for both physicians and patients with acceptable complications and associated with a lengthened survival of patients with advanced ovarian cancer. Whether this arm can be used in lieu of a traditional one needs further randomized trial to confirm the preliminary results.
Cyclin D1 and Rb protein expression and their correlation with prognosis in patients with colon cancer
Authors: Kouraklis Gregory , Theocharis Stamos , Vamvakas Panayiotis , Vagianos Costas , Glinavou Andromahi , Giaginis Costas , Sioka Crysoula 
Published: January 2006

Abstract

Background
Cyclin D1 plays a major role as a potential contributor to the multistep process of oncogenesis; nevertheless its prognostic significance in colon cancer has already been examined in a few studies and needs to be further delineated. The aim of this study was to assess the expression of cyclin D1 and pRb and to correlate them with tumor histological stage and grade, proliferative capacity (Ki-67 labeling index) and clinical parameters, in order to delineate their impact on prognosis.

Methods
One hundred and eleven patients, who underwent surgical resection of the colon for colon cancer constituted the group of our study. The immunohistochemical expression of cyclin D1, Rb and Ki-67 proteins was examined and correlated with clinico-pathological parameters and survival.

Results
The 5-years survival rate of patients presenting cyclin D1 positive tumors was 54%, while that of cyclin D1 negative ones was 67% (P = > 0.05). The survival rate of patients with pRb positive tumors was similar to that of pRb negatine ones. Significant association was observed between Ki-67 and cyclin D1 positivity (P = 0.045). Univariate analysis revealed worse survival in advanced stage patients presenting cyclin D1 positive tumors (P = 0.025). Additionally, the survival of patients aging less than 70 years old was correlated to cyclin D1 positivity (P = 0.009). Multivariate survival analysis revealed statistical significance for stage and hepatic metastasis.

Conclusion
Even though cyclin D1 and pRb have not disclosed any clear association with shorter survival, cyclin D1 positivity may be a useful predictor of subgroup patients with colon cancer being in advanced stage and early age.
Common angiotensin receptor blockers may directly modulate the immune system via VDR, PPAR and CCR2b
Authors: Marshall Trevor G , Lee Robert E , Marshall Frances E 
Published: January 2006

Abstract

Background
There have been indications that common Angiotensin Receptor Blockers (ARBs) may be exerting anti-inflammatory actions by directly modulating the immune system. We decided to use molecular modelling to rapidly assess which of the potential targets might justify the expense of detailed laboratory validation. We first studied the VDR nuclear receptor, which is activated by the secosteroid hormone 1,25-dihydroxyvitamin-D. This receptor mediates the expression of regulators as ubiquitous as GnRH (Gonadatrophin hormone releasing hormone) and the Parathyroid Hormone (PTH). Additionally we examined Peroxisome Proliferator-Activated Receptor Gamma (PPARgamma), which affects the function of phagocytic cells, and the C-CChemokine Receptor, type 2b, (CCR2b), which recruits monocytes to the site of inflammatory immune challenge.

Results
Telmisartan was predicted to strongly antagonize (Ki≈0.04nmol) the VDR. The ARBs Olmesartan, Irbesartan and Valsartan (Ki≈10 nmol) are likely to be useful VDR antagonists at typical in-vivo concentrations. Candesartan (Ki≈30 nmol) and Losartan (Ki≈70 nmol) may also usefully inhibit the VDR. Telmisartan is a strong modulator of PPARgamma (Ki≈0.3 nmol), while Losartan (Ki≈3 nmol), Irbesartan (Ki≈6 nmol), Olmesartan and Valsartan (Ki≈12 nmol) also seem likely to have significant PPAR modulatory activity. Olmesartan andIrbesartan (Ki≈9 nmol) additionally act as antagonists of a theoretical modelof CCR2b. Initial validation of this CCR2b model was performed, and a proposed model for the AngiotensinII Type1 receptor (AT2R1) has been presented.

Conclusion
Molecular modeling has proven valuable to generate testable hypotheses concerning receptor/ligand binding and is an important tool in drug design. ARBs were designed to act as antagonists for AT2R1, and it was not surprising to discover their affinity for the structurally similar CCR2b. However, this study also found evidence that ARBs modulate the activation of two key nuclear receptors-VDR and PPARgamma. If our simulations are confirmed by experiment, it is possible that ARBs may become useful as potent anti-inflammatory agents, in addition to their current indication as cardiovascular drugs.
Anti-viral RNA silencing: do we look like plants ?
Authors: Saumet Anne , Lecellier Charles-Henri 
Published: January 2006

Abstract
The anti-viral function of RNA silencing was first discovered in plants as a natural manifestation of the artificial 'co-suppression', which refers to the extinction of endogenous gene induced by homologous transgene. Because silencing components are conserved among most, if not all, eukaryotes, the question rapidly arose as to determine whether this process fulfils anti-viral functions in animals, such as insects and mammals. It appears that, whereas the anti-viral process seems to be similarly conserved from plants to insects, even in worms, RNA silencing does influence the replication of mammalian viruses but in a particular mode: micro(mi)RNAs, endogenous small RNAs naturally implicated in translational control, rather than virus-derived small interfering (si)RNAs like in other organisms, are involved. In fact, these recent studies even suggest that RNA silencing may be beneficial for viral replication. Accordingly, several large DNA mammalian viruses have been shown to encode their own miRNAs. Here, we summarize the seminal studies that have implicated RNA silencing in viral infection and compare the different eukaryotic responses.