bluuebunny/crossref_metadata_2025_split huggingface dataset:
Imaging Steps of Lymphatic Metastasis Reveals That Vascular Endothelial Growth Factor-C Increases Metastasis by Increasing Delivery of Cancer Cells to Lymph Nodes: Therapeutic Implications
Authors: Hoshida Tohru , Isaka Naohide , Hagendoorn Jeroen , di Tomaso Emmanuelle , Chen Yen-Lin , Pytowski Bronislaw , Fukumura Dai , Padera Timothy P. , Jain Rakesh K. 
Published: August 2006

Abstract
Preclinical and clinical studies positively correlate the expression of vascular endothelial growth factor (VEGF)-C in tumors and the incidence of lymph node metastases. However, how VEGF-C regulates individual steps in the transport of tumor cells from the primary tumor to the draining lymph nodes is poorly understood. Here, we image and quantify these steps in tumors growing in the tip of the mouse ear using intravital microscopy of the draining lymphatic vessels and lymph node, which receives spontaneously shed tumor cells. We show that VEGF-C overexpression in cancer cells induces hyperplasia in peritumor lymphatic vessels and increases the volumetric flow rate in lymphatics at the base of the ear by 40%. The increases in lymph flow rate and peritumor lymphatic surface area enhance the rate of tumor cell delivery to lymph nodes, leading to a 200-fold increase in cancer cell accumulation in the lymph node and a 4-fold increase in lymph node metastasis. In our model, VEGF-C overexpression does not confer any survival or growth advantage on cancer cells. We also show that an anti-VEGF receptor (VEGFR)-3 antibody reduces both lymphatic hyperplasia and the delivery of tumor cells to the draining lymph node, leading to a reduction in lymph node metastasis. However, this treatment is unable to prevent the growth of tumor cells already seeded in lymph nodes. Collectively, our results indicate that VEGF-C facilitates lymphatic metastasis by increasing the delivery of cancer cells to lymph nodes and therapies directed against VEGF-C/VEGFR-3 signaling target the initial steps of lymphatic metastasis. (Cancer Res 2006; 66(16): 8065-75)
Functional Interaction of the Retinoblastoma and Ini1/Snf5 Tumor Suppressors in Cell Growth and Pituitary Tumorigenesis
Authors: Guidi Cynthia J. , Mudhasani Rajini , Hoover Kathleen , Koff Andrew , Leav Irwin , Imbalzano Anthony N. , Jones Stephen N. 
Published: August 2006

Abstract
The Ini1 subunit of the SWI/SNF chromatin remodeling complex suppresses formation of malignant rhabdoid tumors in humans and mice. Transduction of Ini1 into Ini1-deficient tumor-derived cell lines has indicated that Ini1 arrests cell growth, controls chromosomal ploidy, and suppresses tumorigenesis by regulating components of the retinoblastoma (Rb) signaling pathway. Furthermore, conditional inactivation of Ini1 in mouse fibroblasts alters the expression of various Rb-E2F-regulated genes, indicating that endogenous Ini1 levels may control Rb signaling in cells. We have reported previously that loss of one allele of Ini1 in mouse fibroblasts results only in a 15% to 20% reduction in total Ini1 mRNA levels due to transcriptional compensation by the remaining Ini1 allele. Here, we examine the effects of Ini1 haploinsufficiency on cell growth and immortalization in mouse embryonic fibroblasts. In addition, we examine pituitary tumorigenesis in Rb-Ini1 compound heterozygous mice. Our results reveal that heterozygosity for Ini1 up-regulates cell growth and immortalization and that exogenous Ini1 down-regulates the growth of primary cells in a Rb-dependent manner. Furthermore, loss of Ini1 is redundant with loss of Rb function in the formation of pituitary tumors in Rb heterozygous mice and leads to the formation of large, atypical Rb+/− tumor cells lacking adrenocorticotropic hormone expression. These results confirm in vivo the relationship between Rb and Ini1 in tumor suppression and indicate that Ini1 plays a role in maintaining the morphologic and functional differentiation of corticotrophic cells. (Cancer Res 2006; 66(16): 8076-82)
Multiple Acquired Renal Carcinoma Tumor Capabilities Abolished upon Silencing of ADAM17
Authors: Franovic Aleksandra , Robert Isabelle , Smith Karlene , Kurban Ghada , Pause Arnim , Gunaratnam Lakshman , Lee Stephen 
Published: August 2006

AbstractMalignancy is a manifestation of acquired defects in regulatory circuits that direct normal cell proliferation and homeostasis. Most of these circuits operate through cell autonomous pathways, whereas others potentially involve the neighboring microenvironment. We report that the metalloprotease ADAM17 plays a pivotal role in several acquired tumor cell capabilities by mediating the availability of soluble transforming growth factor-α, an epidermal growth factor receptor (EGFR) ligand, and thus the establishment of a key autocrine signaling pathway. Silencing of ADAM17 in human renal carcinoma cell lines corrects critical features associated with cancer cells, including growth autonomy, tumor inflammation, and tissue invasion. Highly malignant renal carcinoma cancer cells fail to form in vivo tumors in the absence of ADAM17, confirming the essential function of this molecule in tumorigenesis. These data show that ligand shedding is a crucial step in endogenous EGFR activation and endorse prospective therapeutic strategies targeting ADAM17 in human cancer. (Cancer Res 2006; 66(16): 8083-90)
Comprehensive quality control utilizing the prehybridization third-dye image leads to accurate gene expression measurements by cDNA microarrays
Authors: Wang Xujing , Jia Shuang , Meyer Lisa , Xiang Bixia , Chen Li-Yen , Jiang Nan , Moreno Carol , Jacob Howard J , Ghosh Soumitra , Hessner Martin J 
Published: August 2006

Abstract

Background
Gene expression profiling using microarrays has become an important genetic tool. Spotted arrays prepared in academic labs have the advantage of low cost and high design and content flexibility, but are often limited by their susceptibility to quality control (QC) issues. Previously, we have reported a novel 3-color microarray technology that enabled array fabrication QC. In this report we further investigated its advantage in spot-level data QC.

Results
We found that inadequate amount of bound probes available for hybridization led to significant, gene-specific compression in ratio measurements, increased data variability, and printing pin dependent heterogeneities. The impact of such problems can be captured through the definition of quality scores, and efficiently controlled through quality-dependent filtering and normalization. We compared gene expression measurements derived using our data processing pipeline with the known input ratios of spiked in control clones, and with the measurements by quantitative real time RT-PCR. In each case, highly linear relationships (R2>0.94) were observed, with modest compression in the microarray measurements (correction factor<1.17).

Conclusion
Our microarray analytical and technical advancements enabled a better dissection of the sources of data variability and hence a more efficient QC. With that highly accurate gene expression measurements can be achieved using the cDNA microarray technology.
Validation and functional annotation of expression-based clusters based on gene ontology
Authors: Steuer Ralf , Humburg Peter , Selbig Joachim 
Published: August 2006

Abstract

Background
The biological interpretation of large-scale gene expression data is one of the paramount challenges in current bioinformatics. In particular, placing the results in the context of other available functional genomics data, such as existing bio-ontologies, has already provided substantial improvement for detecting and categorizing genes of interest. One common approach is to look for functional annotations that are significantly enriched within a group or cluster of genes, as compared to a reference group.

Results
In this work, we suggest the information-theoretic concept of mutual information to investigate the relationship between groups of genes, as given by data-driven clustering, and their respective functional categories. Drawing upon related approaches (Gibbons and Roth, Genome Research 12:1574-1581, 2002), we seek to quantify to what extent individual attributes are sufficient to characterize a given group or cluster of genes.

Conclusion
We show that the mutual information provides a systematic framework to assess the relationship between groups or clusters of genes and their functional annotations in a quantitative way. Within this framework, the mutual information allows us to address and incorporate several important issues, such as the interdependence of functional annotations and combinatorial combinations of attributes. It thus supplements and extends the conventional search for overrepresented attributes within a group or cluster of genes. In particular taking combinations of attributes into account, the mutual information opens the way to uncover specific functional descriptions of a group of genes or clustering result. All datasets and functional annotations used in this study are publicly available. All scripts used in the analysis are provided as additional files.
Cell organisation, sulphur metabolism and ion transport-related genes are differentially expressed in Paracoccidioides brasiliensis mycelium and yeast cells
Authors: Andrade Rosângela V , Paes Hugo C , Nicola André M , de Carvalho Maria José A , Fachin Ana Lúcia , Cardoso Renato S , Silva Simoneide S , Fernandes Larissa , Silva Silvana P , Donadi Eduardo A , Sakamoto-Hojo Elza T , Passos Geraldo AS , Soares Célia MA , Brígido Marcelo M , Felipe Maria Sueli S 
Published: August 2006

Abstract

Background
Mycelium-to-yeast transition in the human host is essential for pathogenicity by the fungus Paracoccidioides brasiliensis and both cell types are therefore critical to the establishment of paracoccidioidomycosis (PCM), a systemic mycosis endemic to Latin America. The infected population is of about 10 million individuals, 2% of whom will eventually develop the disease. Previously, transcriptome analysis of mycelium and yeast cells resulted in the assembly of 6,022 sequence groups. Gene expression analysis, using both in silico EST subtraction and cDNA microarray, revealed genes that were differential to yeast or mycelium, and we discussed those involved in sugar metabolism. To advance our understanding of molecular mechanisms of dimorphic transition, we performed an extended analysis of gene expression profiles using the methods mentioned above.

Results
In this work, continuous data mining revealed 66 new differentially expressed sequences that were MIPS(Munich Information Center for Protein Sequences)-categorised according to the cellular process in which they are presumably involved. Two well represented classes were chosen for further analysis: (i) control of cell organisation – cell wall, membrane and cytoskeleton, whose representatives were hex (encoding for a hexagonal peroxisome protein), bgl (encoding for a 1,3-β-glucosidase) in mycelium cells; and ags (an α-1,3-glucan synthase), cda (a chitin deacetylase) and vrp (a verprolin) in yeast cells; (ii) ion metabolism and transport – two genes putatively implicated in ion transport were confirmed to be highly expressed in mycelium cells – isc and ktp, respectively an iron-sulphur cluster-like protein and a cation transporter; and a putative P-type cation pump (pct) in yeast. Also, several enzymes from the cysteine de novo biosynthesis pathway were shown to be up regulated in the yeast form, including ATP sulphurylase, APS kinase and also PAPS reductase.

Conclusion
Taken together, these data show that several genes involved in cell organisation and ion metabolism/transport are expressed differentially along dimorphic transition. Hyper expression in yeast of the enzymes of sulphur metabolism reinforced that this metabolic pathway could be important for this process. Understanding these changes by functional analysis of such genes may lead to a better understanding of the infective process, thus providing new targets and strategies to control PCM.
An examination of factors influencing the choice of therapy for patients with coronary artery disease
Authors: Hirani Shashivadan P , Hyam Jonathan A , Shaefi Shahzad , Walker John M , Walesby Robin K , Newman Stanton P 
Published: August 2006

Abstract

Background
A diverse range of factors influence clinicians' decisions regarding the allocation of patients to different treatments for coronary artery disease in routine cardiology clinics. These include demographic measures, risk factors, co-morbidities, measures of objective cardiac disease, symptom reports and functional limitations. This study examined which of these factors differentiated patients receiving angioplasty from medication; bypass surgery from medication; and bypass surgery from angioplasty.

Methods
Univariate and multivariate logistic regression analyses were conducted on patient data from 214 coronary artery disease patients who at the time of recruitment had been received a clinical assessment and were reviewed by their cardiologist in order to determine the form of treatment they were to undergo: 70 would receive/continue medication, 71 were to undergo angioplasty and 73 were to undergo bypass surgery.

Results
Analyses differentiating patients receiving angioplasty from medication produced 9 significant univariate predictors, of which 5 were also multivariately significant (left anterior descending artery disease, previous coronary interventions, age, hypertension and frequency of angina). The analyses differentiating patients receiving surgery from angioplasty produced 12 significant univariate predictors, of which 4 were multivariately significant (limitations in mobility range, circumflex artery disease, previous coronary interventions and educational level). The analyses differentiating patients receiving surgery from medication produced 14 significant univariate predictors, of which 4 were multivariately significant (left anterior descending artery disease, previous cerebral events, limitations in mobility range and circumflex artery disease).

Conclusion
Variables emphasised in clinical guidelines are clearly involved in coronary artery disease treatment decisions. However, variables beyond these may also be important factors when therapy decisions are undertaken thus their roles require further investigation.
Fungal infection-related mortality versus total mortality as an outcome in trials of antifungal agents
Authors: Due Anne K , Johansen Helle K , Gøtzsche Peter C 
Published: August 2006

AbstractBackgroundDisease specific mortality is often used as outcome rather than total mortality in clinical trials. This approach assumes that the classification of cause of death is unbiased. We explored whether use of fungal infection-related mortality as outcome rather than total mortality leads to bias in trials of antifungal agents in cancer patients.MethodsAs an estimate of bias we used relative risk of death in those patients the authors considered had not died from fungal infection. Our sample consisted of 69 trials included in four systematic reviews of prophylactic or empirical antifungal treatment in patients with cancer and neutropenia we have published previously.ResultsThirty trials met the inclusion criteria. The trials comprised 6130 patients and 869 deaths, 220 (25%) of which were ascribed to fungal infection. The relative risk of death was 0.85 (95% CI 0.75–0.96) for total mortality, 0.57 (95% CI 0.44–0.74) for fungal mortality, and 0.95 (95% CI 0.82–1.09) for mortality among those who did not die from fungal infection.ConclusionWe could not support the hypothesis that use of disease specific mortality introduces bias in antifungal trials on cancer patients as our estimate of the relative risk for mortality in those who survived the fungal infection was not increased. We conclude that it seems to be reliable to use fungal mortality as the primary outcome in trials of antifungal agents. Data on total mortality should be reported as well, however, to guard against the possible introduction of harmful treatments.
Identification of novel mutant PAX6 alleles in Indian cases of familial aniridia
Authors: Neethirajan Guruswamy , Nallathambi Jeyabalan , Krishnadas Subbaiah Ramasamy , Vijayalakshmi Perumalsamy , Shashikanth Shetty , Collinson Jon Martin , Sundaresan Periasamy 
Published: August 2006

Abstract

Background
Haploinsufficiency at the PAX6 locus causes aniridia, a panocular eye condition characterized by iris hypoplasia and a variety of other anterior and posterior eye defects leading to poor vision. This study was performed to identify novel PAX6 mutations that lead to familial aniridia in Indian patients.

Methods
Genomic DNA was isolated from affected individuals (clinically diagnosed aniridia) from nine unrelated aniridic pedigrees, unaffected family members, and unrelated normal controls. The coding regions of PAX6 were amplified and subjected to single strand conformation polymorphism (SSCP) gel analysis, and direct cloning and sequencing.

Results
SSCP band shifts, indicative of DNA base pair mutations, were observed in five of these unrelated families. Four mutations were shown to be previously unreported insertion or deletions in PAX6, leading to frameshifts. These new mutations were c.1174delTG (in exon 10), c.710delC (exon 6), c.406delTT (exon 5) and c.393insTCAGC (exon 5). The other nonsense mutation, a transition (c.1080C>T) in exon 9, has been reported previously as a mutation hotspot for PAX6 in other ethnic pedigrees. All mutant alleles transmitted through aniridic individuals in each family.

Conclusion
These new deletions and an insertion create frameshifts, which are predicted to introduce premature termination codons into the PAX6 reading frame. The genetic alterations carried by affected individuals are predicted to lead to loss-of-function mutations that would segregate in an autosomal dominant manner to subsequent generations. This is the first report of the 'hotspot' c.1080C>T transition from Indian families.
Knowledge, attitude and practices of pediatricians regarding the prevention of oral diseases in Italy
Authors: Di Giuseppe Gabriella , Nobile Carmelo GA , Marinelli Alessandra , Angelillo Italo F 
Published: August 2006

Abstract

Background
Pediatricians are in an ideal position to advise families about the prevention and management of oral diseases in children. The objective of the study was to determine knowledge, attitude, and practices regarding the prevention of oral diseases among pediatricians in Italy.

Methods
A systematic random sample of 1000 pediatricians received a questionnaire on socio-demographic and practice characteristics; knowledge on risk factors; attitude and practices towards the prevention of oral diseases.

Results
A total of 507 pediatricians participated. More than half knew the main risk factors for oral diseases and this knowledge was higher in primary care pediatricians (p = 0.007), in those with a higher number of hours worked per week (p = 0.012), and who believed that oral diseases may be prevented (p = 0.017). Pediatricians with higher knowledge about the main risk factors (p = 0.006) believe that they have an important role in preventing oral diseases and that they can perform an oral examination. Almost all (89%) prescribed fluoride supplements and those younger (p = 0.016), with a higher number of patients seen in workday (p = 0.001), with longer practice activity (p = 0.004), those who believe that fluoride is effective in preventing caries (p < 0.0001), and who learned about prevention from scientific sources (p = 0.002) were more likely to prescribe fluoride. One-fourth and 40.6% provides and recommends a dental visit once a year and primary care pediatricians (p = 0.014) and those who believed that routine visit is important in preventing oral diseases (p < 0.0001) were more likely to recommend a dental visit once a year.

Conclusion
The results showed a lack of knowledge among pediatricians although almost all believed that they had an important responsibility in preventing oral diseases and provided an oral examination.
Prevalence of self-reported hypertension and its relation to dietary habits, in adults; a nutrition & health survey in Greece
Authors: Pitsavos Christos , Milias George A , Panagiotakos Demosthenes B , Xenaki Dimitra , Panagopoulos George , Stefanadis Christodoulos 
Published: August 2006

Abstract

Background
Hypertension leads to many degenerative diseases, the most common being cardiovascular in origin. This study has been designed to estimate the prevalence of self-reported hypertension in a random nationwide sample of adult Greek population, while focus was set to the assessment of participants' nutritional habits in relation to their hypertension status.

Methods
A random-digit dialed telephone survey. Based on a multistage, stratified sampling, 5003 adults (18 – 74 yr) participated (men: 48.8%, women: 51.2%). All participants were interviewed via telephone by trained personnel who used a standard questionnaire. The questionnaire included demographic and socioeconomic characteristics, medical history, lifestyle habits and nutritional assessment.

Results
The prevalence of self-reported hypertension was 13.3% in men and 17.7% in women (P < 0.001). Furthermore, women reported higher values of systolic blood pressure (180 ± 27 mmHg) than men (169 ± 24 mmHg). Positive relationships were found between hypertension status and the prevalence of the rest investigated health conditions (i.e. hypercholesterolaemia, diabetes mellitus, renal failure and obesity). Nutritional assessment showed that consumption of fish, fruits and juices, cereals, and low fat milk and yogurt was significantly higher among hypertensive subjects while the opposite was observed for food items as red meat, pork, egg, pasta and rice, full fat dairy products and desserts.

Conclusion
Hypertension seems to be a serious public health problem in Greece. It is encouraging that hypertensives may have started adopting some more healthy nutritional behaviour compared to normotensive ones. However, they can gain significant benefits regarding to blood pressure control, if they increase the level of compliance with dietary recommendations.
Emerging advantages and drawbacks of telephone surveying in public health research in Ireland and the U.K
Authors: Boland M , Sweeney MR , Scallan E , Harrington M , Staines A 
Published: August 2006

Abstract

Background
Telephone surveys have been used widely in public health research internationally and are being increasingly used in Ireland and the U.K.

Methods
This study compared three telephone surveys conducted on the island of Ireland from 2000 to 2004, examining study methodology, outcome measures and the per unit cost of each completed survey. We critically examined these population-based surveys which all explored health related attitudes and behaviours.

Results
Over the period from 2000 to 2005 the percentage of calls which succeeded in contacting an eligible member of the public fell, from 52.9% to 31.8%. There was a drop in response rates to the surveys (once contact was established) from 58.6% to 17.7%. Costs per completed interview rose from €4.48 to €15.65.
Respondents were prepared to spend 10–15 minutes being surveyed, but longer surveys yielded poorer completion rates. Respondents were willing to discuss issues of a sensitive nature. Interviews after 9 pm were less successful, with complaints about the lateness of the call. Randomisation from electronic residential telephone directory databases excluded all ex-directory numbers and thus was not as representative of the general population as number generation by the hundred-bank method. However the directory database was more efficient in excluding business and fax numbers.

Conclusion
Researchers should take cognisance of under-representativeness of land-line telephone surveys, of the increasing difficulties in contacting the public and of mounting personnel costs. We conclude that telephone surveying now requires additional strategies such as a multimode approach, or incentivisation, to be a useful, cost-effective means of acquiring data on public health matters in Ireland and the U.K.