bluuebunny/crossref_metadata_2025_split huggingface dataset:
Part 1: Background, Methodology, and Clinical Adoption of Pharmacogenetics
Authors: Deenen Maarten J. , Cats Annemieke , Beijnen Jos H. , Schellens Jan H.M. 
Published: June 2011

Abstract

Learning Objectives
After completing this course, the reader will be able to: Differentiate the candidate gene and genome-wide approaches to pharmacogenetic research and the impact of each on clinical study results.Describe the clinical implications of pharmacogenetic variability and its potential role in individualized treatment of patients with cancer.
This article is available for continuing medical education credit at CME.TheOncologist.com
Equivalent drug doses may lead to wide interpatient variability with regard to drug response, reflected by differences in drug activity and normal tissue toxicity. A major factor responsible for this variability is variation among patients in their genetic constitution. Genetic polymorphism may affect the activity of proteins encoded, which in turn may lead to changes in the pharmacokinetic and pharmacodynamic behavior of a drug, observed as differences in drug transport, drug metabolism, and pharmacodynamic drug effects. Recent insights into the functional effect of polymorphism in genes that are involved in the pharmacokinetics and pharmacodynamics of anticancer drugs have provided opportunities for patient-tailored therapy in oncology. Individualized pharmacotherapy based on genotype will help to increase treatment efficacy while reducing unnecessary toxicity, especially of drugs characterized by a narrow therapeutic window, such as anticancer drugs.
We provide a series of four reviews aimed at implementing pharmacogenetic-based drug and dose prescription in the daily clinical setting for the practicing oncologist. This first part in the series describes the functional impact of genetic polymorphism and provides a general background to and insight into possible clinical consequences of pharmacogenetic variability. It also discusses different methodologies for clinical pharmacogenetic studies and provides a concise overview about the different laboratory technologies for genetic mutation analysis that are currently widely applied. Subsequently, pharmacogenetic association studies in anticancer drug transport, phase I and II drug metabolism, and pharmacodynamic drug effects are discussed in the rest of the series. Opportunities for patient-tailored pharmacotherapy are highlighted.
Targeting Angiogenesis in Esophagogastric Adenocarcinoma
Authors: Okines Alicia F.C. , Reynolds Andrew R. , Cunningham David 
Published: June 2011

Abstract

Learning Objectives
After completing this course, the reader will be able to: Describe the receptors and ligands with identified roles in tumor angiogenesis and the mechanism of action of established and investigational antiangiogenic agents.Describe aspects of antiangiogenic agents that are incompletely understood and need further investigation to define their role in esophagogastric cancer.
This article is available for continuing medical education credit at CME.TheOncologist.com
The possibility of targeting tumor angiogenesis was postulated almost 40 years ago. The vascular endothelial growth factor (VEGF) family and its receptors have since been characterized and extensively studied. VEGF overexpression is a common finding in solid tumors, including esophagogastric cancer, and frequently correlates with poor prognosis. Monoclonal antibodies, soluble receptors, and small-molecule tyrosine kinase inhibitors have been developed to inhibit tumor angiogenesis, and antiangiogenic therapy is now a component of standard treatment for advanced renal cell, hepatocellular, colorectal, breast, and non-small cell lung carcinomas. The small-molecule tyrosine kinase inhibitors sunitinib and sorafenib have been evaluated in phase II studies in esophagogastric cancer but appear to have only modest activity. Similarly, despite promising efficacy signals from phase II studies, the addition of the anti-VEGF-A monoclonal antibody bevacizumab to cisplatin plus capecitabine failed to result in a longer overall survival duration than with the chemotherapy doublet plus placebo. The response rate and progression-free survival interval were significantly greater with bevacizumab, confirming some efficacy in advanced gastric cancer, but with inadequate benefit to justify the high cost of treatment. Evaluation of bevacizumab in the neoadjuvant and perioperative settings continues, hypothesizing that a higher response rate will translate into longer survival in patients with operable disease. Despite extensive research, the discovery of a reliable predictive biomarker for antiangiogenic therapy continues to elude the scientific and oncology communities, and mechanisms of primary and acquired resistance are incompletely understood. We are therefore currently unable to personalize antiangiogenic therapy for established indications, or use molecular selection for clinical trials evaluating novel indications.
Tumor Status at 12 Weeks Predicts Survival in Advanced Colorectal Cancer: Findings from NCCTG N9741
Authors: Heun James M. , Grothey Axel , Branda Megan E. , Goldberg Richard M. , Sargent Daniel J. 
Published: June 2011

Abstract

Learning Objectives
After completing this course, the reader will be able to: Explain the difference in survival prediction between response criteria (WHO) when used as a two-level variable (CR/PR vs. other) and as a three-level variable (CR/PR vs. SD vs. PD).Describe the limited benefit of using actual tumor measurements over traditional criteria (as a three-level variable) in predicting survival in colorectal cancer.
This article is available for continuing medical education credit at CME.TheOncologist.com

Purpose.
We explored the prognostic value of actual tumor measurements (TM) versus World Health Organization (WHO) criteria as three-level (responder, stable, and progression) and two-level (responder and non-responder) variables at 12 and 24 weeks as predictors of survival in Intergroup Trial N9741, a phase III trial in metastatic colorectal cancer (CRC).

Methods.
All patients with measurable disease (N = 1,188) were included. The percentage changes in TM from baseline to 12 and 24 weeks were calculated. The prognostic values of TM versus WHO criteria (as three- and two-level variables) at 12 and 24 weeks were compared, using Cox models for overall survival (OS) in a landmark analysis, adjusting for baseline tumor size, performance status, and treatment arm.

Results.
Tumor status at 12 weeks by WHO criteria (three or two levels) or actual TM were all strongly associated with OS. Actual TM provided no meaningful additional benefit compared with the three-level WHO criteria. Tumor status at 24 weeks was also strongly associated with survival, but added no additional prognostic value compared with the 12-week assessment. At 12 weeks, actual TM improved prognostic characterization of patients with WHO status of response, but provided no additional value in patients with stable disease or progression.

Conclusions.
In N9741, the use of actual TM, or following tumor status beyond 12 weeks, did not improve survival prediction compared with a single three-level response assessment at 12 weeks, suggesting that 12-week tumor status could be an appropriate phase II trial endpoint in metastatic CRC.
Evolution of Renal Hyperfiltration and Arterial Stiffness From Adolescence Into Early Adulthood in Type 1 Diabetes
Authors: Cherney David Z.I. , Sochett Etienne B. 
Published: June 2011

OBJECTIVE
To determine, in a small but carefully physiologically characterized cohort of subjects with uncomplicated type 1 diabetes, the changes in renal hemodynamic function and arterial stiffness that occur over time as the participants transitioned from adolescence into early adulthood. The classical paradigm for type 1 diabetes suggests that glomerular filtration rate (GFR) declines in patients with renal hyperfiltration, but the natural history of peripheral vascular function abnormalities in uncomplicated type 1 diabetes is less well understood, particularly as patients transition from adolescence to early adulthood.

RESEARCH DESIGN AND METHODS
Renal hemodynamic function (inulin and p-aminohippuric acid clearance), blood pressure, arterial stiffness (radial augmentation index), albumin excretion, and circulating renin-angiotensin system measures were obtained during clamped euglycemia at baseline and at follow-up 6.8 ± 2.5 years later in 10 patients with hyperfiltration (GFR ≥135 mL/min/1.73 m2) and in 8 with normofiltration.

RESULTS
Compared with baseline values, GFR (171 ± 20 to 120 ± 15 mL/min/1.73 m2) and filtration fraction (FF, 0.24 ± 0.06 to 0.18 ± 0.03) declined in hyperfilterers (ANOVA P ≤ 0.033), and renal vascular resistance increased (0.0678 ± 0.0135 to 0.0783 ± 0.0121 mmHg/L/min, P = 0.017). GFR and FF did not change in normofiltering subjects. In contrast, the radial augmentation index decreased in hyperfiltering (1.2 ± 11.7 to −11.0 ± 7.8%) and normofiltering (14.3 ± 14.0 to 2.5 ± 14.6%) subjects (within-group changes, ANOVA P ≤ 0.030). The decline in circulating aldosterone levels was similar in both groups.

CONCLUSIONS
During the transition from adolescence to early adulthood, hyperfiltration is not sustained in subjects with type 1 diabetes, whereas GFR remains stable in normofiltering subjects. Our findings suggest early normofiltration may predict stable renal function. In contrast, arterial stiffness decreased in all patients regardless of filtration status, suggesting that age-related increases in arterial stiffness occur at older ages.
Vibrational calculations in formaldehyde: the CH stretch system
Authors: Rashev Svetoslav , Moule David 
Published: June 2011

Abstract
An alternative procedure for the calculation of highly excited vibrational levels in S0 formaldehyde was developed to apply to larger molecules. It is based on a new set of symmetrized vibrational valence coordinates. The fully symmetrized vibrational kinetic energy operator is derived in these coordinates using the Handy expression [Molec. Phys. 61, 207 (1987)]. The potential energy surface is expressed as a fully symmetrized quartic expansion in the coordinates. We have performed ab initio electronic computations using GAMESS to obtain all force constants of the S0 formaldehyde quartic force field. Our large scale vibrational calculations are based on a fully symmetrized vibrational basis set, in product form. The vibrational levels are calculated one by one using an artificial intelligence search/selection procedure and subsequent Lanczos iteration, providing access to extremely high vibrational energies. In this work special attention has been given to the CH stretch system by calculating the energies up to the fifth CH stretch overtone at ∼16000 cm−1, but the method has also been tested on two highly excited combination levels including other lower frequency modes.
The role of Mg2FeH6 formation on the hydrogenation properties of MgH2-FeFx composites
Authors: Malka Iwona , Czujko Tomasz , Bystrzycki Jerzy , Jaroszewicz Leszek 
Published: June 2011

Abstract
The hydrogenation properties of magnesium hydride mechanically milled with iron fluorides (FeF2 and FeF3), were investigated by Temperature Programmed Desorption (TPD) and volumetric methods using a Sieverts-type apparatus, as prepared upon dehydrogenation and finally upon subsequent hydrogenation. The activation energy of hydrogen desorption (Ea), calculated from the Kissinger formula using TPD measurements obtained with different heating rates, showed significant decreases of Ea in comparison to that of milled MgH2 without any dopants. Moreover, the influence of these metal fluorides on the thermodynamics of the decomposition process was also examined. In the case of the FeF2 dopant, rehydrogenation following desorption caused the complete decomposition of the iron fluoride to BCC iron and the formation of a predominant MgH2 phase. In contrast to FeF2, the addition of FeF3 led to the formation of β-MgH2 as a major phase coexisting with Mg2FeH6 and MgF2 compounds. The presence of pure Fe in the MgH2+FeF2 composite, as opposed to MgH2+FeF3 containing Mg2FeH6 and MgF2, did not cause any significant influence on the sorption properties of MgH2. Moreover, the original material doped with FeF3 predominantly showed iron in the Mg2FeH6 compound, while the FeF2 dopant iron mostly showed the nearly pure BCC metallic phase
Crystallographic and structural characterisation of heterometallic platinum compounds: Part I. Heterobinuclear Pt compounds
Authors: Holloway Clive , Melnik Milan 
Published: June 2011

Abstract
This review covers almost 290 heterobinuclear Pt derivatives. When the heterometals (M) are non transition and the binuclear are found both with and without a metal to metal bond. Where M is a transition metal or actinide, only those with a metal-metal bond have been included here. There are thirteen non-transition metals (Sn, Hg, Ge, Sb, Tl, Zn, Pb, Cd, Na, K, Ga, Ca and In). The shortest Pt-M bond distance is 235.2(1) (Pt-Ge). There are eighteen transition metals (Fe, W, Rh, Re, Pd, Ag, Ir, Mo, Mn, Re, Co, Cu, Cr, Au, Ni, Ti, Ta and V). The shortest Pt-M bond distance is 249.5(2) pm (Pt-Cr). There is one example of an actinide, Pt-Th at 298.4(1) pm. The Pt atom has oxidation numbers 0, +2 and +4. The Pt coordination geometries include square planar (most common), trigonal bipyramidal, pseudo octahedral (Pt(IV)) and a few prevalently capped trigonal prismatic seven coordinate species. There are at least two types of isomerism distortion and polymerisation. Factors affecting bond lengths and angles are discussed and some ambiguities in coordination polyhedra are outlined.
Arthroscopic Capsular Shrinkage for Chronic Ankle Instability with Thermal Radiofrequency: Prospective Multicenter Trial
Authors: de Vries Jasper S. , Krips Rover , Blankevoort Leendert , Fievez Alex W.F.M. , van Dijk C. Niek 
Published: June 2011

The study was designed as a prospective multicenter longitudinal trial. Adult patients with symptomatic mechanical chronic ankle instability, not improving with conservative therapy, were included and underwent surgery. Primary outcome measures were radiological and manually tested mechanical laxity. Secondary outcome measures were number of complications, reoperations and symptoms, range of motion, and functional (ankle) scores (Karlsson and SF-36 score). The latest follow-up was 9 months for each patient.
Thirty-nine patients underwent surgery (19 male patients; 16 right ankles; median age, 27 years). Mechanical stability showed no clinically relevant improvement whereas most secondary outcome measures showed a substantial and statistically significant improvement. One surgery-related complication occurred without functional consequences, and 3 patients underwent a secondary procedure. One was considered a treatment failure, requiring an open anatomic ligament reconstruction. The second patient sustained a severe supination trauma by starting intensive training too early, also requiring an open anatomic reconstruction. The third patient had posterior ankle pain, which was successfully treated by posterior ankle arthroscopy.
Arthroscopic thermal capsular shrinkage of the ankle is a safe procedure, leading to resolution of symptoms in the majority of patients with chronic ankle instability.
Increased Cell Surface Fas Expression Is Necessary and Sufficient To Sensitize Lung Fibroblasts to Fas Ligation-Induced Apoptosis: Implications for Fibroblast Accumulation in Idiopathic Pulmonary Fibrosis
Authors: Wynes Murry W. , Edelman Benjamin L. , Kostyk Amanda G. , Edwards Michael G. , Coldren Christopher , Groshong Steve D. , Cosgrove Gregory P. , Redente Elizabeth F. , Bamberg Alison , Brown Kevin K. , Reisdorph Nichole , Keith Rebecca C. , Frankel Stephen K. , Riches David W. H. 
Published: June 2011

Abstract
Idiopathic pulmonary fibrosis (IPF) is associated with the accumulation of collagen-secreting fibroblasts and myofibroblasts in the lung parenchyma. Many mechanisms contribute to their accumulation, including resistance to apoptosis. In previous work, we showed that exposure to the proinflammatory cytokines TNF-α and IFN-γ reverses the resistance of lung fibroblasts to apoptosis. In this study, we investigate the underlying mechanisms. Based on an interrogation of the transcriptomes of unstimulated and TNF-α– and IFN-γ–stimulated primary lung fibroblasts and the lung fibroblast cell line MRC5, we show that among Fas-signaling pathway molecules, Fas expression was increased ∼6-fold in an NF-κB– and p38mapk-dependent fashion. Prevention of the increase in Fas expression using Fas small interfering RNAs blocked the ability of TNF-α and IFN-γ to sensitize fibroblasts to Fas ligation-induced apoptosis, whereas enforced adenovirus-mediated Fas overexpression was sufficient to overcome basal resistance to Fas-induced apoptosis. Examination of lung tissues from IPF patients revealed low to absent staining of Fas in fibroblastic cells of fibroblast foci. Collectively, these findings suggest that increased expression of Fas is necessary and sufficient to overcome the resistance of lung fibroblasts to Fas-induced apoptosis. Our findings also suggest that approaches aimed at increasing Fas expression by lung fibroblasts and myofibroblasts may be therapeutically relevant in IPF.
Finding a Place for Critical Thinking and Self-voice in College English as a Foreign Language Writing Classrooms
Authors: Barnawi Osman 
Published: June 2011

Although the concepts of critical thinking and self-voice have been extensively discussed in a second language writing, little attention has been given, on the pedagogical level, to critical thinking and self-voice in college EFL writing instruction. To fill such a void, this paper attempts to propose some pedagogical tasks namely: persuasive writing tasks, draft workshops one-on-one mentoring approaches for finding a place for critical thinking and self-voice in EFL classrooms. In doing so, this paper provides the operational definitions of critical thinking and self-voice concepts. It then discusses how these two concepts are closely related to complement EFL writing learning. In what follows, it presents the rationale for finding a place for critical thinking and self-voice in EFL writing. It then touches on some pedagogical practices for developing critical thinking and self-voice in classrooms. Lastly, it addresses some challenges related to implementing critical thinking and self-voice tasks in EFL classrooms.
The Effects of Portfolio Assessment on Writing of EFL Students
Authors: Nezakatgoo Behzad 
Published: June 2011

The primary focus of this study was to determine the effect of portfolio assessment on final examination scores of EFL students’ writing skill. To determine the impact of portfolio-based writing assessment 40 university students who enrolled in composition course were initially selected and divided randomly into two experimental and control groups. A quasi-experimental research design was adopted in this study. In order to appraise the homogeneity of the experimental and control groups Comprehensive English Language Test (CELT) was employed at the beginning of the study. The pre-test was applied to both the experimental group and control group. Later in the study, a post-test of dependent variables was implemented for both groups. Data analysis was carried out by SPSS 16 statistical computer program .The statistical techniques being applied were the Levene statistic of One-Way ANOVA and the Paired-sample T-test. The results of the study revealed that that students whose work was evaluated by a portfolio system (portfolio-based assessment) had improved in their writing and gained higher scores in final examination when compared to those students whose work was evaluated by the more traditional evaluation system (non-portfolio-based assessment).The findings of the present study highlighted the fact that portfolio assessment could be used as a complementary alternative along with traditional assessment to shed new light on the process of writing.
Recent Progress in DNA Origami Technology
Authors: Endo Masayuki , Sugiyama Hiroshi 
Published: June 2011

AbstractDNA origami is an emerging technology for designing defined two‐dimensional DNA nanostructures. In this review, we focus on and describe several types of DNA origami‐related studies, as follows: (1) programmed DNA origami assembly, (2) DNA origami‐templated molecular assembly, (3) design and construction of various three‐dimensional DNA origami structures, (4) programmed functionalization of DNA origami and combination with top‐down nanotechnology, (5) single molecular observation on a designed DNA origami, and (6) DNA nanomachines working on a DNA origami. Curr. Protoc. Nucleic Acid Chem. 45:12.8.1‐12.8.19. © 2011 by John Wiley & Sons, Inc.
Residue K556‐A Light Triggerable Gatekeeper to Sterically Control Translocation in FhuA
Authors: Güven Arcan , Dworeck Tamara , Fioroni Marco , Schwaneberg Ulrich 
Published: June 2011

AbstractThe general aim of our work is to build a set of engineered protein channels to be used in liposome and polymersome technology with a special emphasis in delivery applications. The channel proteins FhuA and OmpF are modified to answer to chemical (Angew. Chem. Int. Ed., 2008), pH (Soft Matter, 2011), and light stimuli. In this study a first light triggered release system is developed by employing the photo‐cleavable label 6‐nitroveratryloxycarbonyl chloride (NVOC‐Cl) and FhuA variants with six, five, and only one lysine in the barrel. Kinetic studies on liposome inserted FhuA variants, using 3,3′,5,5′‐tetramethylbenzidine (TMB)/horseradish peroxidase (HRP) as detection system led to the discovery of a single labeled amino acid position, K556, that is sufficient to act as a gate and that controls TMB translocation through the FhuA Δ1‐160 pore. Background conversion of TMB in the absence of FhuA Δ1‐160 ranges from 13 (non‐photo‐irradiated) to 27 (photo‐irradiated) n · s−1. A “fully” open FhuA Δ1‐160 channel reaches TMB conversions up to 113 × 10−9 M · s−1; a “fully” labeled FhuA Δ1‐160 shows a TMB conversion of 29 × 10−9 M · s−1 which is close to background levels. The engineered FhuA Δ1‐160 with only one lysine in the barrel interior (K556) shows a TMB conversion of 33 × 10−9 M · s−1 after labeling and after NVOC photo‐cleavage a conversion of 94 × 10−9 M · s−1. The latter proves the gate keeping role of position 556 in sterically modulating TMB fluxes. CD spectra, cryogenic TEM, and DLS experiments were performed to characterize the employed liposomes with embedded FhuA Δ1‐160 variants.
3D Out‐of‐Plane Rotational Etching with Pinned Catalysts in Metal‐Assisted Chemical Etching of Silicon
Authors: Hildreth Owen J. , Brown Devin , Wong Ching P. 
Published: June 2011

AbstractPinned structures in conjunction with shaped catalysts are used in metal‐assisted chemical etching (MACE) of silicon to induce out‐of‐plane rotational etching. Sub‐micro‐ and nanostructures are fabricated in silicon, which include scooped‐out channels and curved subsurface horns, along with vertically oriented thin metal structures. Five different etching modes induced by catalyst and pinning geometry are identified: 1) fully pinned–no etching, 2) rotation via twist, 3) rotation via delamination, 4) in‐plane bending, and 5) swinging. The rotation angle is roughly controlled through catalyst geometry. The force and pressure experienced by the catalyst are calculated from the deformation of the catalyst and range between 0.5–3.5 μN and 0.5–3.9 MPa, respectively. This is a new, simple method to fabricate 3D, heterogeneous sub‐micro‐ and nanostructures in silicon with high feature fidelity on the order of tens of nanometers while providing a method to measure the forces responsible for catalyst motion during MACE.