bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combined 1p/19q Loss in Oligodendroglial Tumors: Predictive or Prognostic Biomarker?
Authors:   The German Glioma Network, Weller Michael , Berger Hilmar , Hartmann Christian , Schramm Johannes , Westphal Manfred , Simon Matthias , Goldbrunner Roland , Krex Dietmar , Steinbach Joachim P. , Ostertag Christoph B. , Loeffler Markus , Pietsch Torsten , von Deimling Andreas 
Published: December 2007

Abstract
Purpose: The combined loss of genetic material on chromosomes 1p and 19q is strongly associated with favorable outcome in patients with WHO grade 3 anaplastic oligodendroglial tumors. The prognostic value of 1p/19q loss in WHO grade 2 oligodendroglial tumors is less well defined. Importantly, the possible effect of combined 1p/19q loss has not been studied in patients who were not treated with radiotherapy or chemotherapy.
Experimental Design: Seventy-six patients with oligodendroglioma (n = 33), oligoastrocytoma (n = 30), anaplastic oligodendroglioma (n = 6), or anaplastic oligoastrocytoma (n = 7) were identified who had not received radiotherapy or chemotherapy after their first operation until the end of follow-up or until the first progression and had tissue for 1p/19q status available. 1p/19q status was assessed by multiplex ligation–dependent probe amplification.
Results: After a median follow-up of 3.8 years, progressive disease was documented in 34 patients. The estimated median progression-free survival was 4.6 years. Fifty-eight of the 76 patients had a combined loss of 1p and 19q. The absence or presence of combined 1p/19q loss was not prognostic for progression-free survival using multivariate adjustment for histology, extent of resection, and gender.
Conclusions: Combined 1p/19q loss is not a sensitive prognostic biomarker in patients with oligodendroglial tumors who do not receive radiotherapy or chemotherapy. The gene products lost as a consequence of this codeletion may include mediators of resistance to genotoxic therapies. Alternatively, 1p/19q loss might be an early oncogenic lesion promoting the formation of glial neoplasms, which retain high sensitivity to genotoxic stress.
Plasma, Tumor, and Tissue Disposition of STEALTH Liposomal CKD-602 (S-CKD602) and Nonliposomal CKD-602 in Mice Bearing A375 Human Melanoma Xenografts
Authors: Zamboni William C. , Strychor Sandra , Joseph Erin , Walsh Dustin R. , Zamboni Beth A. , Parise Robert A. , Tonda Margaret E. , Yu Ning Y. , Engbers Charles , Eiseman Julie L. 
Published: December 2007

Abstract
Purpose: S-CKD602 is a STEALTH liposomal formulation of CKD-602, a camptothecin analogue. The cytotoxicity of camptothecin analogues is related to the duration of exposure in the tumor. STEALTH liposomal formulations contain lipid conjugated to methoxypolyethylene glycol and have been designed to prolong drug circulation time, increase tumor delivery, and improve the therapeutic index. For STEALTH liposomal formulations of anticancer agents to achieve antitumor effects, the active drug must be released into the tumor extracellular fluid (ECF).
Experimental Design: S-CKD602 at 1 mg/kg or nonliposomal CKD-602 at 30 mg/kg was administered once via tail vein to mice bearing A375 human melanoma xenografts. Mice (n = 3 per time point) were euthanized at 0.083 to 24 h, 48 h, and 72 h after S-CKD02 and from 0.083 to 24 h after nonliposomal CKD-602. Plasma samples were processed to measure encapsulated, released, and sum total (encapsulated plus released) CKD-602, and tumor and tissue samples were processed to measure sum total CKD-602. Microdialysis samples of tumor ECF were obtained from 0 to 2 h, 4 to 7 h, and 20 to 24 h after nonliposomal CKD-602 and from 0 to 2 h, 24 to 27 h, 48 to 51 h, and 72 to 75 h after S-CKD602. A liquid chromatography-mass spectrometry assay was used to measure the total (sum of lactone and hydroxyl acid) CKD-602. The area under the concentration-versus-time curves (AUC) from 0 to infinity and time &gt;1 ng/mL in tumor were estimated.
Results: For S-CKD602, the CKD-602 sum total AUC in plasma and tumor and the CKD-602 AUC in tumor ECF were 201,929, 13,194, and 187 ng/mL h, respectively. For S-CKD602, 82% of CKD-602 remains encapsulated in plasma. For nonliposomal CKD-602, the CKD-602 AUC in plasma and tumor and the CKD-602 AUC in tumor ECF were 9,117, 11,661, and 639 ng/mL·h, respectively. The duration of time the CKD-602 concentration was &gt;1 ng/mL in tumor ECF after S-CKD602 and nonliposomal CKD-602 was &gt;72 and ∼20 h, respectively. For S-CKD602, the CKD-602 sum total exposure was 1.3-fold higher in fat as compared with muscle. The ratio of CKD-602 sum total exposure in fat to muscle was 3.8-fold higher after administration of S-CKD602 compared with nonliposomal CKD-602.
Conclusion: S-CKD602 provides pharmacokinetic advantages in plasma, tumor, and tumor ECF compared with nonliposomal CKD-602 at 1/30th of the dose, which is consistent with the improved antitumor efficacy of S-CKD602 in preclinical studies. The distribution of S-CKD602 is greater in fat compared with muscle whereas the distribution of nonliposomal CKD-602 is greater in muscle compared with fat. These results suggest that the body composition of a patient may affect the disposition of S-CKD602 and released CKD-602.
A Switch from E-Cadherin to N-Cadherin Expression Indicates Epithelial to Mesenchymal Transition and Is of Strong and Independent Importance for the Progress of Prostate Cancer
Authors: Gravdal Karsten , Halvorsen Ole J. , Haukaas Svein A. , Akslen Lars A. 
Published: December 2007

Abstract
Purpose: Cell adhesion molecules are of crucial importance in cancer invasion and metastasis. Epithelial to mesenchymal transition, characterized by reduced E-cadherin and increased N-cadherin expression, has been recognized as a feature of aggressive tumors, but the importance of this phenotype has not been settled in human prostate cancer. We here present novel data, with special focus on the independent relationship between an E-cadherin to N-cadherin switch (EN-switch) and patient prognosis.
Experimental Design: Tissue microarray sections from a consecutive series of 104 radical prostatectomies during 1988 to 1994 with detailed clinicopathologic data and long follow-up were studied immunohistochemically for the expression of E-cadherin, N-cadherin, P-cadherin, β-catenin, and p120CTN.
Results: Low E-cadherin expression was significantly associated with adverse clinicopathologic features, whereas other biomarkers were mostly related to Gleason score. In univariate survival analyses, cadherin switching (high N-cadherin and low E-cadherin) showed strong and significant associations with multiple end points of progression and cancer-specific death. Expression of the “basal cell marker” P-cadherin was associated with shorter time to skeletal metastasis (P = 0.036). In multivariate analysis of time to clinical recurrence, the “EN-switch” (hazard ratio, 4.3; P &lt; 0.0005) had strong and independent prognostic effect, together with Gleason score.
Conclusion: These novel data unravel the importance of epithelial to mesenchymal transition for prostate cancer progression, and demonstration of a switch from E-cadherin to N-cadherin expression could have significant effect on the care of prostate cancer patients.
Lack of Association of Single-Nucleotide Polymorphisms in Pregnane X Receptor, Hepatic Nuclear Factor 4α, and Constitutive Androstane Receptor with Docetaxel Pharmacokinetics
Authors: Tham Lai-San , Holford Nicholas H.G. , Hor Sok-Ying , Tan Theresa , Wang Lingzhi , Lim Rui-Chen , Lee How-Sung , Lee Soo-Chin , Goh Boon-Cher 
Published: December 2007

Abstract
Purpose: This study aims to describe a population pharmacokinetic model for docetaxel in Asian breast cancer patients and to evaluate the effects of single-nucleotide polymorphisms (SNP) in the cytochrome P450 3A (CYP3A) gene expression regulators, constitutive androstane receptor (CAR), pregnane X receptor (PXR), and hepatic nuclear factor 4α (HNF4α), on the pharmacokinetics of docetaxel.
Experimental Design: Docetaxel was given as an i.v. infusion of 75 mg/m2 over 1 h to 101 female breast cancer patients. CAR, PXR, and HNF4α were comprehensively sequenced. Docetaxel concentrations were measured using a liquid chromatography/tandem mass spectrometry method and its population pharmacokinetic variables, and the covariate effects of clearance predictors were estimated using a nonlinear mixed effects model.
Results: Final estimates for docetaxel clearance was 47.1 L/h/70 kg/1.75 m. Between subject variability in docetaxel clearance was 22.5%. Covariates that showed significant association with docetaxel clearance included body size, α1 acid glycoprotein and liver function. SNPs identified in the coding regions of CAR and HNF4α and 5′ untranslated region of PXR in this Asian breast cancer cohort did not seem to improve predictability of docetaxel clearance.
Conclusions: SNPs identified in CYP3A gene expression regulators CAR, HNF4α, and PXR in the Asian female breast cancer population do not seem to have any significant effect on the clearance of docetaxel, a CYP3A substrate.
First in Human Phase I Trial of 852A, a Novel Systemic Toll-like Receptor 7 Agonist, to Activate Innate Immune Responses in Patients with Advanced Cancer
Authors: Dudek Arkadiusz Z. , Yunis Carla , Harrison Lester I. , Kumar Sandeep , Hawkinson Ronald , Cooley Sarah , Vasilakos John P. , Gorski Kevin S. , Miller Jeffrey S. 
Published: December 2007

AbstractPurpose: Recent advances in the understanding of innate immunity suggest that an orchestrated sequence of events is required to elicit a productive immune response against cancer. We studied the systemic administration of the Toll-like receptor 7 agonist 852A, a small-molecule imidazoquinoline, in patients with advanced cancer. Preclinical studies showed that 852A stimulates plasmacytoid dendritic cells to produce multiple cytokines, such as IFN-α, interleukin-1 receptor antagonist, and IFN-inducible protein-10. Our goal was to define the tolerated dose, pharmacokinetics, pharmacodynamics, and immunologic effects of 852A in humans.Experimental Design: Eligible adult patients with refractory solid organ tumors received i.v. 852A thrice weekly for 2 weeks. Patients who had responses or stable disease were eligible for additional cycles.Results: Twenty-five patients (median age, 55.0 years; 72% male) were enrolled in six cohorts at dose levels of 0.15 to 2.0 mg/m2. Serum drug levels showed dose proportionality and no evidence of drug accumulation. The maximum tolerated dose was 1.2 mg/m2; higher doses were limited by fatigue and constitutional symptoms. Increases in IFN-α, interleukin-1 receptor antagonist, and IFN-inducible protein-10, immunologic activity, and clinical symptoms were observed in all patients receiving dose levels ≥0.6 mg/m2. Significant correlations were found between pharmacodynamic biomarkers and pharmacokinetic variables, and an objective clinical response was seen.Conclusions: 852A was safely administered i.v. at doses up to 1.2 mg/m2 thrice weekly for 2 weeks with transient or reversible adverse effects. This novel Toll-like receptor 7 agonist is biologically active and holds promise for stimulating innate immune responses. Future trials are warranted to assess its therapeutic role in patients with cancer.
The Muslim Surgeon and Contemporary Ethical Dilemmas Surrounding the Restoration of Virginity
Authors: Rispler-Chaim Vardit 
Published: December 2007

AbstractIn the last few decades surgeons have been able to perform an operation that repairs a torn hymen, and thus allows young women and girls whose hymen is not intact to reappear as virgins. Most of the ethical issues related to hymen repair surgery concern the conduct of the surgeon and the question of whether restoration of virginity is a way to deceive husbands. The status of hymen restoration surgery has been the subject of several fatwas issued by leading religious authorities and articles written by Muslim lawyers, physicians and ethicists. Virginity restoration, based on the above sources, appears to have its supporters and opponents. The study of hymen restoration is also related to the status of women in society and their rights, to ancient social taboos, and to the impact of modern scientific technology on society at large.
Neo-Traditional Salafi Qur'an-Sunnah Hermeneutic and the Construction of a Normative Muslimah Image
Authors: Duderija Adis 
Published: December 2007

AbstractThe aim of this article is to outline and analyse the delineating features of the Neo-Traditional Salafi model of interpreting Qur'an and Sunnah indicants and the interpretational implications of this model in relation to constructing a "normative" concept of a Muslimah (model for a Muslim woman). The author argues that the NTS interpretational model is based on a range of epistemological and methodological assumptions pertaining to the conceptualisation and interpretation of the nature and the scope of the Qur'an and Sunnah.
Een negentiende-eeuws Gents collegedictaat over het ius publicum Belgicum
Authors: van Kappen O. Moorman 
Published: December 2007

AbstractThis contribution deals with a manuscript, containing lecture notes made in 1827–1828 by a Ghent student named Callenfels and relating to the lectures on ius publicum universale et Belgicum, given by Jacob Joseph Haus (1796–1881), professor of jurisprudence at Ghent University and native of Würzburg. As the course programme of the law faculties in the southern provinces required courses in natural law as well as in ius publicum and ius gentium, the assumption has been put forward these lectures would be restricted to the ius publicum universale such as lectured in many German law faculties in the 18th century. On further examination of the manuscript under consideration this presumption proves to be wrong. After the first 13 sections, which refer in fact to the ius publicum naturale in an enlightened sense, the remaining 253 sections outline the then positive constitutional law of the Netherlands, mainly on the basis of the Dutch written constitution of 1815.
De politieke verantwoordelijkheid voor koninklijke genadebesluiten in België tijdens de 20ste eeuw
Authors: Monballyu J. 
Published: December 2007

AbstractDuring the 20th century, Ministers of the Department of Justice in Belgium have been politically accountable for the pardons granted by the King. As a result, they had to answer questions on issues of pardons asked by members of both chambers of Parliament, viz. the Chamber of Representatives and the Senate. When responding to these questions, they would choose between two possible approaches: either they refused to disclose the specific reasons for a pardon because of the principle that the Crown's position had to remain protected by ministerial responsibility, or they stated the specific reasons on purely political grounds. On two occasions, the latter approach resulted in the Minister's enforced resignation.
A family-specific use of the Measure of Processes of Care for Service Providers (MPOC-SP)
Authors: Siebes RC , Nijhuis BJG , Boonstra AM , Ketelaar M. , Wijnroks L. , Reinders-Messelink HA , Postema K. , Vermeer A. 
Published: December 2007

Objective: To examine the validity and utility of the Dutch Measure of Processes of Care for Service Providers (MPOC-SP) as a family-specific measure. Design: A validation study. Setting: Five paediatric rehabilitation settings in the Netherlands. Main measures: The MPOC-SP was utilized in a general (reflecting on services provided for all clients and clients' families) and family-specific way (filled out in reference to a particular child and his or her family). Subjects: Professionals providing rehabilitation and educational services to children with cerebral palsy. Methods: For construct validity, Pearson's product-moment correlation coefficients (r ) between the scales were calculated. The ability of service providers to discriminate between general and family-specific ratings was examined by exploration of absolute difference scores. Results: One hundred and sixteen service professionals filled out 240 family-specific MPOC-SPs. In addition, a subgroup of 81 professionals filled out a general MPOC-SP. For each professional, family-specific and general scores were paired, resulting in 151 general—family-specific MPOC-SP pairs. The construct validity analyses confirmed the scale structure: 21 items (77.8%) loaded highest in the original MPOC-SP factors, and all items correlated best and significantly with their own scale score (r 0.565 to 0.897; P<0.001). Intercorrelations between the scales ranged from r = 0.159 to r = 0.522. In total, 94.4% of the mean absolute difference scores between general and family-specific scale scores were larger than the expected difference. Conclusion: Service providers were able to discriminate between general and family-specific MPOC-SP item ratings. The family-specific MPOC-SP is a valid measure that can be used for individual evaluation of family-centred services and can be the impetus for family-related quality improvement.
Factors associated with a second hip fracture: a systematic review
Authors: Egan Mary , Jaglal Susan , Byrne Kerry , Wells Jennie , Stolee Paul 
Published: December 2007

Objective: To provide a systematic review of factors associated with subsequent hip fracture among individuals who have fractured a hip.Data sources: We searched Ageline, CINAHL, EMBASE and MEDLINE, from database inceptions to the week of 5 June 2006.Review methods: Studies were selected if they provided information regarding risk of subsequent hip fracture among individuals who had fractured a hip. Study quality was assessed using the Jadad criteria for randomized controlled trials (RCTs) and a simple scale based on the MOOSE criteria for cohort studies.Results: Four RCTs and seven cohort studies were identified. Older age, cognitive impairment and lower bone mass appear to increase the risk of subsequent fracture, as did impaired depth perception, impaired mobility, previous falls, dizziness and poor or fair self-perceived health. Pharmacologic treatment for osteoporosis decreased the risk of subsequent fracture. Use of hip protectors by community-dwelling seniors did not appear to protect against a second fracture.Conclusion: A number of easily observed risk factors may help identify those individuals at higher risk for subsequent fracture.
Nanoparticle-driven DNA damage mimics irradiation-related carcinogenesis pathways
Authors: Mroz R. M. , Schins R. P. F. , Li H. , Jimenez L. A. , Drost E. M. , Holownia A. , MacNee W. , Donaldson K. 
Published: December 2007

The epidemiological association between cancer and exposure to ambient air pollution particles (particles with a 50% cut-off aerodynamic diameter of 10 μm (PM10)) has been related to the ability of PM10and its constituent nanoparticles (NPs) to cause reactive oxidative species (ROS)-driven DNA damage. However, there are no data on the molecular response to these genotoxic effects.In order to assess whether PM10, NP and ROS-driven DNA damage induce carcinogenesis pathways, A549 cells were treated with tert-butyl-hyperperoxide (Tbh), urban dust (UD), carbon black (CB), nanoparticulate CB (NPCB), benzo(a)pyrene (BaP) and NPCB coated with BaP for ≤24 h. Single- and double-strand breakage of DNA was determined by comet assay; cell cycle status was analysed using flow cytometry. Nuclear extracts or acid-extracted histones were used for Western blot analysis of p-ser15-p53 (p53 phosphorylated at ser15), p53 binding protein (53BP) 1, phospho-histone H2A.X (p-H2A.X) and phospho-BRCA1 (p-BRCA1).UD caused both single- and double-strand DNA breaks, while other tested NPs caused only single-strand DNA breaks. NPs significantly altered cell cycle kinetics. Tbh enhanced p-H2A.X after 1 and 6 h (2.1- and 2.2-fold, respectively). NP increased 53BP1 expression at 1 h (2.4–8.7-fold) and p-BRCA1 at 1–6 h.N-acetylcysteine blocked NP-driven p-ser15-p53 response.In conclusion, nanoparticles and reactive oxidative species induce DNA damage, activating p53 and proteins related to DNA repair, mimicking irradiation-related carcinogenesis pathways.
Exhaled nitric oxide and asthma control: a longitudinal study in unselected patients
Authors: Michils A. , Baldassarre S. , Van Muylem A. 
Published: December 2007

Controlled studies have shown that monitoring of the exhaled nitric oxide fraction (FeNO) improves asthma management. However, the studies seldom consider the full range of patients seen in clinical practise. In the present study, the ability ofFeNOto reflect asthma control over time is investigated in a regular clinical setting, and meaningfulFeNOcut-off points and changes are identified.Answers to the Asthma Control Questionnaire andFeNOwere recorded at least once in 341 unselected asthma patients. The whole population and subgroups were considered,i.e.both inhaled corticosteroid (ICS)-naïve and low or high-to-medium (≤ or >500 μg beclomethasone dipropionate equivalents·day−1) ICS-dose groups.AnFeNOdecrease <40% or increase <30% precludes asthma control optimisation or deterioration, respectively (negative predictive value 79 and 82%, respectively). In the present study’s low-dose group, a decrease >40% indicated asthma control optimisation (positive predictive value (PPV) 83%). In ICS-naïve patients,FeNO>35 ppb predicted asthma control improvement in response to ICS (PPV 68%). In most cases, forced expiratory volume in one second assessments were not useful.In conclusion, in a given patient, exhaled nitric oxide fraction was found to be significantly related to asthma control over time. The overall ability of exhaled nitric oxide fraction to reflect asthma control was reduced in patients using high doses of inhaled corticosteroids. Forced expiratory volume in one second had little additional value in assessing asthma control.
Multidisciplinary interobserver agreement in the diagnosis of idiopathic pulmonary fibrosis
Authors: Thomeer M. , Demedts M. , Behr J. , Buhl R. , Costabel U. , Flower C. D. R. , Verschakelen J. , Laurent F. , Nicholson A. G. , Verbeken E. K. , Capron F. , Sardina M. , Corvasce G. , Lankhorst I. 
Published: December 2007

The purpose of the present study was to evaluate the accuracy of the diagnosis of idiopathic pulmonary fibrosis (IPF) by respiratory physicians in six European countries, and to calculate the interobserver agreement between high-resolution computed tomography reviewers and histology reviewers in IPF diagnosis.The diagnosis of usual interstitial pneumonia (UIP) was assessed by a local investigator, following the American Thoracic Society/European Respiratory Society consensus statement, and confirmed when a minimum of two out of three expert reviewers from each expert panel agreed with the diagnosis. The level of agreement between readers within each expert panel was calculated by weighted kappa.The diagnosis of UIP was confirmed by the expert panels in 87.2% of cases. A total of 179 thoracic high-resolution computed tomography scans were independently reviewed, and an interobserver agreement of 0.40 was found. Open or thoracoscopic lung biopsy was performed in 97 patients, 82 of whom could be reviewed by the expert committee. The weighted kappa between histology readers was 0.30.It is concluded that, although the level of agreement between the readers within each panel was only fair to moderate, the overall accuracy of a clinical diagnosis of idiopathic pulmonary fibrosis in expert centres is good (87.2%).