bluuebunny/crossref_metadata_2025_split huggingface dataset:
Homocysteine up‐regulates vascular transmembrane chemokine CXCL16 and induces CXCR6+ lymphocyte recruitment in vitro and in vivo
Authors: Postea O. , Koenen R. R. , Hristov M. , Weber C. , Ludwig A. 
Published: October 2008

AbstractObjective: Hyperhomocysteinemia induces endothelial dysfunction and promotes atherosclerotic vascular disease. Infiltrates of activated macrophages and lymphocytes are observed in human and experimental atherosclerotic lesions, their emigration being guided by endothelial‐leukocyte adhesion molecules and chemoattractants. The CXC‐chemokine CXCL16 functions as an adhesion molecule by interacting with its receptor (CXCR6) and also as a scavenger for oxidized low density lipoprotein (oxLDL). We investigated the modulation of CXCL16 on cultured endothelial cells (EC) and the recruitment of CXCR6+ lymphocytes in response to homocysteine (Hcy), in vitro and in vivo. Methods and Results: Hcy‐stimulated EC show a significant increase in CXCL16 mRNA and protein expression. Incubation of EC with d,l‐Hcy and l‐Hcy significantly increased CXCR6+ lymphocyte adhesion to EC while l‐Cysteine (l‐Cys) had no effect. Furthermore, EC stimulation with Hcy increased uptake of DiI‐oxLDL. An anti‐CXCL16 monoclonal antibody, antioxidants (Tiron) and PPAR‐γ agonists (Pioglitazone) considerably reduced CXCR6+ lymphocyte adhesion and uptake of DiI‐oxLDL. Upon injection in the peritoneal cavities of mice, l‐Hcy and not l‐Cys, increased the number of CXCR6+ lymphocytes, which was reduced by coinjection with Pioglitazone or anti‐human CXCL16 antibody. Conclusions: Hyperhomocysteinemia up‐regulates CXCL16 leading to increased recruitment of CXCR6+ lymphocytes and scavenging of modified lipids via a potential involvement of a PPAR‐γ‐dependent mechanism. CXCL16 may therefore contribute to the formation and progression of atherosclerotic lesions under conditions of hyperhomocysteinemia.
Genetics, epigenetics and pharmaco‐(epi)genomics in angiogenesis
Authors: Buysschaert Ian , Schmidt Thomas , Roncal Carmen , Carmeliet Peter , Lambrechts Diether 
Published: October 2008

Introduction
Angiogenesis is genetically pre‐determined
Mutations causing vascular anomalies
Translocations reveal novel angiogenic genes
Single nucleotide polymorphisms shape the angio‐genome
Copy number variability affects angiogenesis
Epigenetic regulation of angiogenesis
Micromanagers of angiogenesis
Perspectives
AbstractAngiogenesis is controlled by a balance between pro‐ and anti‐angiogenic factors. Studies in mice and human beings have shown that this balance, as well as the general sensitivity of the endothelium to these factors, is genetically pre‐determined. In an effort to dissect this genetic basis, different types of genetic variability have emerged: mutations and translocations in angiogenic factors have been linked to several vascular malformations and haemangiomas, whereas SNPs have been associated with complex genetic disorders, such as cancer, neurodegeneration and diabetes. In addition, copy number alterations of angiogenic factors have been reported in several tumours. More recently, epigenetic changes caused by aberrant DNA methylation or histone acetylation of anti‐angiogenic molecules have been shown to determine angiogenesis as well. Initial studies also revealed a crucial role for microRNAs in stimulating or reducing angiogenesis. So far, most of these genetic studies have focused on tumour angiogenesis, but future research is expected to improve our understanding of how genetic variants determine angiogenesis in other diseases. Importantly, these genetic insights might also be of important clinical relevance for the use of anti‐angiogenic strategies in cancer or macular degeneration.
Implementation of a guideline for computed tomography head imaging in head injury: A prospective study
Authors: Fong Christina , Chong Winston , Villaneuva Elmer , Segal Ahuva Yocheved 
Published: October 2008

AbstractObjective:  To improve appropriate ordering of head computed tomography (CT) in patients presenting with a head injury by applying an evidence‐based head injury guideline.Methods:  This was a comparison observational study of CT head ordering in the setting of head trauma between two groups of patients. There was a pre‐guideline implementation group and a post‐guideline implementation group. Our Southernhealth Head Injury Guideline was largely based on the Canadian CT Head Rule by Steill et al. 2001.We also applied the Canadian CT Head Rule to our post‐guideline implementation group.Results:  CT ordering rate in the pre‐guideline group was 31.6% compared with 59% in the post‐guideline group with a relative risk of 1.88 (95% confidence interval [CI]: 1.56–2.27). Abnormal head CT were reported in 6.8% in the pre‐guideline group and 5% in the post‐guideline group (relative risk 0.88, 95% CI 0.44–1.51). When we applied the Canadian CT Head Rule to the prospective group, four patients with clinically significant abnormal head CT would not have been scanned. The sensitivity of the guideline was 100% (95% CI 79–100%), with a specificity of 43.22% (95% CI 37–48%) in diagnosing a significant head injury on CT.Conclusion:  The Southernhealth Head Injury Guideline is safe and easy to apply to minor and major head injuries.
Rapid risk stratification in suspected acute coronary syndrome using serial multiple cardiac biomarkers: A pilot study
Authors: Macdonald Stephen PJ , Nagree Yusuf 
Published: October 2008

AbstractObjective:  To determine the feasibility of using a biomarker panel of myoglobin, creatinine kinase MB (CK‐MB) and cardiac troponin I (cTnI) to identify patients with suspected acute coronary syndrome (ACS) who are suitable for discharge within 2 h.Methods:  We took blood at presentation and at 2 h from patients with suspected ACS and non‐diagnostic electrocardiogram who were admitted to the ED short stay ward for serial electrocardiogram and troponin testing. We used a point‐of‐care device that gives rapid estimation of myoglobin, CK‐MB and cTnI (Triage cardiac panel). These results were compared with the results of our standard hospital cardiac troponin T assay. Patients were followed up by telephone at 30 days.Results:  The study group comprised 100 patients (61 men) with mean age of 58 years. Six had a troponin‐positive ACS during their ED stay. One additional patient died of a myocardial infarction within the follow‐up period. The Triage panel at 2 h after presentation predicted 12‐h cardiac troponin T elevation (sensitivity 100%, negative predictive value 99%) and 30‐day events (sensitivity 86%, negative predictive value 97%). The majority of patients were ultimately suitable for discharge.Conclusion:  Serial myoglobin, CK‐MB and cTnI have the potential to identify patients who are suitable for early discharge and outpatient work‐up. A large multicentre study is required.
SDSS J084539.17+225728.0: the first DBZ white dwarf with a metal-rich gaseous debris disc
Authors: Gänsicke B. T. , Koester D. , Marsh T. R. , Rebassa-Mansergas A. , Southworth J. 
Published: October 2008

Abstract
We report the discovery of a third white dwarf hosting a gaseous debris disc, SDSS J084539.17+225728.0. The typical double-peaked Ca ii 8498,8542,8662 Å emission lines can be modelled in terms of a Keplerian gas disc with a radial extent from ∼0.5 to ∼1.0 R⊙. The effective temperature of SDSS 0845+2257, Teff≃ 18 600 ± 500 K, is comparable to the two other white dwarfs with gaseous discs, SDSS 1043+0855 and SDSS 1228+1040, and hence substantially hotter than the bulk of white dwarfs where dusty debris discs were identified through the presence of infrared excess flux. This may suggest that the conditions to produce emission lines from debris discs in the optical wavelength range are only met for a relatively narrow range in Teff. The observed asymmetry in the line profiles indicates a substantial eccentricity in the disc. Two spectra obtained four years apart reveal a significant change in the shapes and equivalent widths of the line profiles, implying that the circumstellar disc evolves on relatively short time-scales. In contrast to SDSS 1043+0855 and SDSS 1228+1040, SDSS 0845+2257 has a helium-dominated atmosphere. We detect photospheric absorption lines of He, Ca, Mg and Si in the Sloan Digital Sky Survey spectrum, and hence classify SDSS 0845+2257 as DBZ white dwarf. The abundances for the three metals determined from model atmosphere fits are Ca/He ≃ 1.3 × 10−7, Mg/He ≃ 6.0 × 10−6 and Si/He ≃ 8.0 × 10−6. From the non-detection of Hα, we derive H/He &lt; 3 × 10−5, which implies that the hydrogen-to-metal abundance ratio of the circumstellar material is ≳1000 times lower than in the Sun. This lends strong support to the hypothesis that the gaseous and dusty debris discs found around roughly a dozen white dwarfs originate from the disruption of rocky planetary material.
Self‐Reported Substance Use and Sexual Behaviors Among Adolescents in a Rural State
Authors: Dunn Michael S , Ilapogu Varaprasad , Taylor LaShan , Naney C. , Blackwell Roger , Wilder Regina , Givens C. 
Published: October 2008

ABSTRACTBackground:  Research finds a strong association between substance use and risky sexual behavior but more needs to be known about this relationship. Few studies have examined this relationship among rural sixth‐ to eighth‐grade students. As such, the purposes of this study were to provide a descriptive profile of rural sixth‐ to eighth‐grade students’ substance use behavior and sexual activity and to examine the relationship between substance use behaviors and sexual activity.Methods:  Participants consisted of a convenience sample of 10,273 middle school students (sixth to eighth grade) attending 10 public schools in rural Tennessee. The middle school Youth Risk Behavior Survey was administered to these students during April and May 2004.Results:  Analysis found that a large percentage of students had tried cigarettes, alcohol, and inhalants. Additionally, it was found that sexual intercourse had been initiated by 18.8% of females and 25.4% of males. Of those students who reported ever having had sexual intercourse, 75% had reported the use of cigarettes and alcohol. In addition, approximately 50% of those students reported marijuana and inhalant use.Conclusions:  The results suggest that substance use behavior has a relationship with the likelihood of initiating sexual activity. Additional longitudinal research with this population will be needed for explaining whether these select substance use behaviors are probable risk factors predisposing young rural adolescents to report engaging in sexual behaviors or a result of other factors.
Sexual Harassment Policies in K‐12 Schools: Examining Accessibility to Students and Content
Authors: Lichty Lauren F. , Torres Jennifer M.C. , Valenti Maria T. , Buchanan NiCole T. 
Published: October 2008

ABSTRACTBackground:  Peer sexual harassment is a significant social problem with consequences for both students and schools. Four out of 5 students report experiencing sexual harassment. These experiences have been linked to poor psychological health and academic withdrawal. Recognizing the seriousness of sexual harassment in schools, Supreme Court rulings have established school liability for known instances of sexual harassment under Title IX of the Education Amendments of 1972. Federal guidelines established by the Office for Civil Rights of the US Department of Education mandate schools to develop sexual harassment policies; however, the implementation of these guidelines has not been examined. Therefore, this study assessed the degree to which sexual harassment policies in primary and secondary schools adhered to said guidelines.Methods:  This study evaluated 784 primary and secondary school sexual harassment policies across 4 states on 3 key factors: accessibility to students (ie, via the Internet), consistency with federal guidelines regarding their content and the inclusion of 10 key components, and consistency of content across educational levels.Results:  Only 14% of sexual harassment policies were available online; the majority of policies incorporated only 5 of the 10 critical components, and elementary school policies contained significantly fewer components than all other educational levels.Conclusions:  The Internet is an underused resource for disseminating school sexual harassment policies to students. When policies are available, they rarely incorporate the key elements specified in the federal guidelines. Particularly troubling are the inaccessibility and incompleteness of elementary school policies. Greater attention to policy accessibility and comprehensiveness is needed.
The cultural eutrophication of Lac la Biche, Alberta, Canada: a paleoecological study
Authors: Schindler D. W. , Wolfe Alexander P. , Vinebrooke Rolf , Crowe Angela , Blais Jules M. , Miskimmin Brenda , Freed Rina , Perren Bianca 
Published: October 2008

A multiproxy paleoecological investigation of Lac la Biche, a large boreal lake in northeastern Alberta, Canada, revealed that the lake was eutrophic before European settlement but has undergone additional cultural eutrophication in the past 30 to 50 years. Annual fluxes to sediments of phosphorus, nitrogen, carbon, and inorganic sediments have increased with time. A declining N–P ratio has increasingly favored nitrogen-fixing cyanobacteria. Increased deposition of microbial pigments and diatom frustules and a recent shift in diatom species also indicate increasing eutrophication. Biogenic silica increased with time, but there is no evidence of a near-surface decline that would indicate silica limitation. Stable isotopes suggest that an increasing proportion of carbon deposited in sediments is of in-lake origin, indicating increased productivity. In the basin nearest the town of Lac La Biche, an increase in δ15N followed the construction of the sewage treatment plant, but more recently, decreased δ15N in both basins suggests that nitrogen fixation has become a more important source of nitrogen. Despite documented damage to the fishery of the lake, zooplankton fossils do not show evidence of a strong trophic cascade. The study illustrates the power of a multiproxy approach in obtaining reliable paleolimnological conclusions.
Oxygen concentration in the water boundary layer next to rainbow trout (Oncorhynchus mykiss) embryos is influenced by hypoxia exposure time, metabolic rate, and water flow
Authors: Miller Silvana C. , Reeb Shannon E. , Wright Patricia A. , Gillis Todd E. 
Published: October 2008

The objective of this study was to examine the influence of hypoxia exposure time, metabolic rate, and water flow rate on the O2concentration in the boundary layer outside and inside the chorion of rainbow trout ( Oncorhynchus mykiss ) embryos. Oxygen consumption, growth, and dissolved O2in the boundary layer were measured at 15, 22, and 29 days post fertilization (dpf) from embryos reared in normoxia (O2concentration at 100% saturation) and chronic hypoxia (>24 h, 50% saturation) and exposed to acute hypoxia (30 min, 50% saturation). Chronic and acute hypoxia exposure decreased the dissolved O2in the boundary layer to the same extent at 15 and 22 dpf; however, at 29 dpf, O2levels were significantly lower in acute relative to chronic hypoxia. At 29 dpf, O2uptake per individual was significantly lower in embryos exposed to chronic relative to acute hypoxia. In addition, mass-specific O2uptake in chronic hypoxia-exposed embryos was ~40% less than that of controls but the same as that of acutely exposed embryos. This correlates with reduced growth in embryos exposed to chronic hypoxia. We conclude that boundary layer O2is lower after 30 min of hypoxia compared with 2 weeks of hypoxia simply because embryos exposed to chronic hypoxia grow slower and consume less O2.
Marine survival of steelhead (Oncorhynchus mykiss) enhanced by a seasonally closed estuary
Authors: Bond Morgan H. , Hayes Sean A. , Hanson Chad V. , MacFarlane R. Bruce 
Published: October 2008

To investigate the role that estuaries play in the survival of steelhead, Oncorhynchus mykiss , we compared juvenile size at ocean entry with back-calculated measures of size at ocean entry for returning adults in Scott Creek, a representative California coastal stream. During the annual spring emigration, the largest smolts (>150 mm fork length (FL)) move directly to sea, while some smaller smolts remain in the estuary until sandbar formation creates a closed freshwater lagoon. High growth rates in the estuary throughout the summer result in a near doubling of fork length from the time of estuary entry (mean FL of spring migrants = 102.2 mm; mean FL of fall lagoon resident = 195.9 mm). Analysis of the scale morphology of returning adult steelhead indicates that there is strong size-dependent mortality at sea, with estuary-reared steelhead showing a large survival advantage, comprising between 87% and 95.5% (based on tag returns and scale analysis, respectively) of the returning adult population despite being between 8% and 48% of the annual downstream migrating population. Although the estuary forms less than 5% of the watershed area, it is critical nursery habitat, and steelhead population persistence in southern margin ecosystems may well depend upon healthy estuaries.
Suppression of the Negative Regulator LRIG1 Contributes to ErbB2 Overexpression in Breast Cancer
Authors: Miller Jamie K. , Shattuck David L. , Ingalla Ellen Q. , Yen Lily , Borowsky Alexander D. , Young Lawrence J.T. , Cardiff Robert D. , Carraway Kermit L. , Sweeney Colleen 
Published: October 2008

AbstractThe ErbB2 receptor tyrosine kinase is overexpressed in ∼25% of breast tumors and contributes to poor patient prognosis and therapeutic resistance. Here, we examine the role of the recently discovered ErbB negative regulator LRIG1 in ErbB2+ breast cancer. We observe that LRIG1 protein levels are significantly suppressed in ErbB2-induced mammary tumors in transgenic mice as well as in the majority of ErbB2+ human breast tumors. These observations raise the possibility that LRIG1 loss could contribute to the initiation or growth of ErbB2+ breast tumors. RNA interference–mediated knockdown of endogenous LRIG1 in the ErbB2-overexpressing breast tumor cell lines MDA-MB-453 and BT474 further elevates ErbB2 in these cells and augments cellular proliferation. In contrast, ectopic expression of LRIG1 reverses these trends. Interestingly, we observe that LRIG1 protein levels are suppressed in response to ErbB receptor activation in breast tumor cells but are unaffected by ErbB activation in immortalized nontransformed breast epithelial cells. Our observations indicate that the suppression of LRIG1 protein levels is a common feature of breast tumors. Moreover, our observations point to the existence of a feed-forward regulatory loop in breast tumor cells where aberrant ErbB2 signaling suppresses LRIG1 protein levels, which in turn contributes to ErbB2 overexpression. [Cancer Res 2008;68(20):8286–94]
The Polarity Protein Par6 Induces Cell Proliferation and Is Overexpressed in Breast Cancer
Authors: Nolan Marissa E. , Aranda Victoria , Lee Sangjun , Lakshmi Balasubramanian , Basu Srinjan , Allred D. Craig , Muthuswamy Senthil K. 
Published: October 2008

Abstract
The polarity protein complex Par6/atypical protein kinase (aPKC)/Cdc42 regulates polarization processes during epithelial morphogenesis, astrocyte migration, and axon specification. We, as well as others, have shown that this complex is also required for disruption of apical-basal polarity during the oncogene ErbB2-induced transformation and transforming growth factor β–induced epithelial-mesenchymal transition of mammary epithelial cells. Here, we report that expression of Par6 by itself in mammary epithelial cells induces epidermal growth factor–independent cell proliferation and development of hyperplastic three-dimensional acini without affecting apical-basal polarity. This is dependent on the ability of Par6 to interact with aPKC and Cdc42, but not Lgl and Par3, and its ability to promote sustained activation of MEK/ERK signaling. Down-regulation of Cdc42 or aPKC expression suppresses the ability of Par6 to induce proliferation, demonstrating that Par6 promotes cell proliferation by interacting with aPKC and Cdc42. We also show that Par6 is overexpressed in breast cancer–derived cell lines and in both precancerous breast lesions and advanced primary human breast cancers, suggesting that Par6 overexpression regulates tumor initiation and progression. Thus, in addition to regulating cell polarization processes, Par6 is an inducer of cell proliferation in breast epithelial cells. [Cancer Res 2008;68(20):8201–9]
Ultrasound Imaging of Apoptosis in Tumor Response: Novel Preclinical Monitoring of Photodynamic Therapy Effects
Authors: Banihashemi Behzad , Vlad Roxana , Debeljevic Branislav , Giles Anoja , Kolios Michael C. , Czarnota Gregory J. 
Published: October 2008

Abstract
High-frequency ultrasound is a novel method to detect apoptotic cell death based on changes in cell morphology that cause alterations in the viscoelastic and, consequently, the acoustic properties of cell ensembles and tissues. In this study, we evaluated the first preclinical tumor-based use of high-frequency ultrasound spectroscopy to noninvasively monitor tumor treatment by following xenograft malignant melanoma tumor responses to photodynamic therapy (PDT) in vivo. We observed a time-dependant increase in ultrasound backscatter variables after treatment. The observed increases in spectroscopic variables correlated with morphologic findings, indicating increases in apoptotic cell death, which peaked at 24 hours after PDT. We analyzed the changes in spectral slope and backscatter in relation to apoptosis and histologic variations in cell nuclear size. Changes in spectral slope strongly correlated with the changes in mean nuclear size over time, associated with apoptosis, after PDT (P &lt; 0.05). At 48 hours, a decrease in ultrasound backscatter was observed, which could be explained by an increase in cell nuclear degradation. In summary, we show that high-frequency ultrasound spectroscopic variables can be used noninvasively to monitor response after treatment in a preclinical tumor cancer model. These findings provide a foundation for future investigations regarding the use of ultrasound to monitor and aid the customization of treatments noninvasively based on responses to specific interventions. [Cancer Res 2008;68(20):8590–6]