bluuebunny/crossref_metadata_2025 huggingface dataset:
A Computational Approach for the Identification of Small GTPases Based on Preprocessed Amino Acid Sequences
Authors: Heider Dominik , Appelmann Jessica , Bayro Tuygun , Dreckmann Winfried , Held Andreas , Winkler Jonas , Barnekow Angelika , Borschbach Markus
Published: October 2014

The prediction of essential biological features based on a given protein sequence is a challenging task in computational biology. To limit the amount of in vitro verification, the prediction of essential biological activities gives the opportunity to detect so far unknown sequences with similar properties. Besides the application within the identification of proteins being involved in tumorigenesis, other functional classes of proteins can be predicted. The prediction accuracy depends on the selected machine learning approach and even more on the composition of the descriptor set used. A computational approach based on feedforward neural networks was applied for the prediction of small GTPases. Consequently, this was realized by taking secondary structure and hydrophobicity information as a preprocessing architecture and thus, as descriptors for the neural networks. We developed a neural network cluster, which consists of a filter network and four subfamily networks. The filter network was trained to identify small GTPases and the subfamily networks were trained to assign a small GTPase to one of the subfamilies. The accuracy of the prediction, whether a given sequence represents a small GTPase is very high (98.25%). The classifications of the subfamily networks yield comparable accuracy. The high prediction accuracy of the neural network cluster developed, gives the opportunity to suggest the use of hydrophobicity and secondary structure prediction in combination with a neural network cluster, as a promising method for the prediction of essential biological activities.
Megavoltage CT in Helical Tomotherapy — Clinical Advantages and Limitations of Special Physical Characteristics
Authors: Sterzing Florian , Kalz Jörn , Sroka-Perez Gabriele , Schubert Kai , Bischof Marc , Röder Falk , Debus Jürgen , Herfarth Klaus
Published: October 2014

Helical tomotherapy is a form of image-guided intensity-modulated radiotherapy that introduces the ring gantry concept into radiation oncology. The system is a combination of a therapeutic linear accelerator and a megavoltage CT-scanner. This work describes the clinical experience with megavoltage CT with 456 patients in more than 11000 fractions. It also provides a review of the current literature of the possibilities and limitations of megavoltage CT. Between July 2006 and October 2008 456 patients were treated with helical tomotherapy and a pretreatment megavoltage CT was performed in 98.1% of the 11821 fractions to perform position control and correction. CT image acquisition was done with 3.5 MV x-rays in the helical tomotherapy machine. MVCT was used for dose recalculations to quantify doses distributions in cases of changing geometry, tumor shrinkage or presence of metal implants. Inverse treatment planning for prostate cancer patients with bilateral hip replacements was performed based upon an MVCT.

A mean 3D-correction vector of 7.1mm with a considerable variation was detected and immediately corrected. Mean shifts were lateral 0.9mm (sd 5.0mm), mean longitudinal shift 1.0mm (sd 5.1mm) and mean vertical shift 3.2mm (sd 5.2mm). The MVCT enables imaging of anatomical structures in the presence of dental metal or orthopedic implants. Especially in these cases, dose recomputations can increase the precision of dose calculations. Due to a mean 3d correction vector of more than 7mm and a variation of corrections of more than 5mm daily image-guidance is recommended to achieve a precise dose application. The MVCT shows evident advantages in cases with metal implants but has limitations due to a reduced soft tissue contrast. Compared with megavoltage cone-beam-CT the tomotherapy fan beam CT adds less extra dose fore the patient and has a better soft tissue contrast.
Helical Tomotherapy with Simultaneous Integrated Boost for High-Risk and Lymph Node-Positive Prostate Cancer: Early Report on Acute and Late Toxicity
Authors: Engels Benedikt , Soete Guy , Tournel Koen , Bral Samuel , De Coninck Peter , Verellen Dirk , Storme Guy
Published: October 2014

The use of whole pelvic radiotherapy (WPRT) for high-risk and lymph node-positive prostate cancer (PC) remains controversial. The purpose of this study was to evaluate the acute toxicity associated with helical tomotherapy in the treatment of high-risk and lymph node-positive prostate cancer. To do so, twenty-eight patients were treated to a dose of 54 Gy in daily fractions of 1.8 Gy to the pelvic lymph node area, while the prostate and the seminal vesicles received a simultaneous integrated boost (SIB) to a dose of 70.5 Gy. A SIB to a dose of 60 Gy was delivered to the involved lymph node region(s) in 8 patients with pelvic lymph node metastases. All patients received concurrent hormonal treatment. The incidence of grade 2 and 3 acute gastrointestinal (GI) toxicity was 7% and 0% respectively. Grade 2 and 3 acute genito-urinary (GU) side effects were observed in 14% and 4% of the patients respectively. No grade 4 side effects occurred. No increased toxicity was observed in the 8 lymph node-positive patients receiving a simultaneous pelvic nodal dose escalation. In conclusion, WPRT with a SIB to the prostate and seminal vesicles by helical tomotherapy resulted in a favourable toxicity profile. Pelvic nodal dose escalation in node-positive patients is feasible without increasing toxicity.
Stereotactic Body Radiotherapy: An Emerging Treatment Approach for Localized Prostate Cancer
Authors: Friedland Jay L. , Freeman Debra E. , Masterson-McGary Mary Ellen , Spellberg David M.
Published: October 2014

Here we report results from the first cohort of over 100 patients treated with hypofractionated, stereotactic body radiotherapy (SBRT) for early stage prostate cancer. Between February 2005 and December 2006, 112 patients with localized, biopsy-proven adenocarcinoma of the prostate (clinical stage T1cN0M0 to T2cN0M0) were treated in Naples, FL on a CyberKnife system (Accuray Incorporated, Sunnyvale, CA). Eighty-one patients had a Gleason score of 3+3. Mean initial PSA was 6.0, and mean initial prostate volume was 46.3cc. Implanted gold fiducials were used for image-guided targeting and tracking. Patients received 35–36 Gy administered in 5 consecutive fractions to the prostate and the proximal seminal vesicles, as identified on CT and MRI scans. At a median follow-up of 24 months, the mean PSA value was 0.78 ng/ml. Two patients have developed biopsy-confirmed local relapse; one developed distant metastases. Acute side effects were generally mild and resolved shortly after treatment. A single Grade 3 rectal complication was reported (bleeding). Eighty-two percent of patients who were sexually potent before treatment maintained erectile function post-treatment. Additional follow-up is required to better evaluate potential late toxicity and long-term PSA outcomes.
Detection and Identification of Potential Biomarkers of Non-small Cell Lung Cancer
Authors: Yang Yang , Zhao Song , Fan Yuxia , Zhao Feng , Liu Quan , Hu Wei , Liu Donglei , Fan Kai , Wang Jiaxiang , Wang Jianjun
Published: October 2014

The aim of this study was to discover and identify potential protein biomarkers specific for non-small cell lung cancer (NSCLC). Two hundred and thirty five (235) Serum samples with 112 NSCLC and 123 controls were randomly divided into a training set and a blind testing set. Serum proteomic profiles were analyzed using surface-enhanced laser desorption/ionization time-of-flight mass spectroscopy (SELDI-TOF-MS). Candidate protein biomarkers were purified by high Performance Liquid Chromatography (HPLC) and identified by liquid chromatography tandem mass spectrometry (LC-MS/MS) and validated using ProteinChip immunoassays. A total of 3 peaks ( m/z with 6628, 9191 and 11412 Da) were screened out by SVM to construct the classification model with the high discriminatory power in the training set. The sensitivity and specificity of the model were 96.56% and 94.79% respectively in the blind testing set. The candidate biomarker with m/z of 6628 Da was found down-regulated in NSCLC patients, and identified as apolipoprotein C-I. Another two candidate biomarkers (9191 and 11412 Da) were found up-regulated in serum of NSCLC patients and identified as haptoglobin alpha-1 chain and S100A4, respectively. We have identified a set of biomarkers that could discriminate NSCLC from non-cancer controls. An efficient strategy, including SELDI-TOF-MS analysis, HPLC purification, MALDI-TOF-MS trace and LC-MS/MS identification, has been proved successfully.
Expression of p-Akt and COX-2 in Gastric Adenocarcinomas and Adenovirus Mediated Akt1 and COX-2 ShRNA Suppresses SGC-7901 Gastric Adenocarcinoma and U251 Glioma Cell Growth In Vitro and In Vivo
Authors: Zhang Jing , Zhang Qing-Yu , Fu Yan-Chao , Wang Tao , Zhang Jie , Xu Peng , Zhou Xuan , Pu Pei-yu , Kang Chun-Sheng
Published: October 2014

Cyclooxygenase-2 (COX-2) and Protein kinase B (PKB/Akt) play a crucial role in the formation of many malignant tumors and have been shown to be the important therapeutic targets. In the present study, we examined immunohistochemical expression of phosphorylated Akt (p-Akt) and COX-2 in 45 gastric adenocarcinomas with different tumor grades. Then, adenovirus-mediated small hairpin RNA (shRNA) expression vectors rAd5-Akt1+COX-2 (rAd5-A+C) that target sequences of human COX-2 and Akt1 were used to examine the inhibitory effects on cell proliferation, invasion and apoptosis in SGC7901 gastric adenocarcinoma and U251 glioma cells. Cell growth was inhibited by over 70%, as indicated by a MTT assay, and was accompanied by G1/G0 phase arrest in the rAd5-A+C treated group, indicating poor cell growth activities. The number of cells invading through the matrigel in the rAd5-A+C treated group was significantly decreased (36.2±3.1) compared with that of the control group SGC7901 (105.0±4.0) and the nonsense sequence group rAd5-HK (102.5±6.4). In addition, the tumor volumes in the SGC7901 subcutaneous nude mouse model treated with rAd5-A+C was significantly smaller than those of the control group and nonsense sequence group rAd5-HK. When COX-2 and Akt1 were dramatically downregulated, Ki-67, CyclinD1, MMP-2, MMP-9 and Bcl-2 were also downregulated. Our results demonstrated that p-Akt and COX-2 were overexpressed in gastric adenocarcinomas and their expression levels were elevated with the ascending order of tumor malignancy; rAd5-A+C targeting COX-2 and Akt1 down-regulated their expression significantly in a sequence-specific manner, exerting inhibitory effects on SGC7901 and U251 cell proliferation, invasion and apoptosis. In conclusion, our data suggest a novel mechanism for the regulation of malignant tumor cell growth and provide evidence for combined gene therapy for malignant tumors.
An Automatic Occlusion Device for Remote Control of Tumor Tissue Ischemia
Authors: El-Dahdah Hamid , Wang Bei , He Guanglong , Xu Ronald X.
Published: October 2014

We developed an automatic occlusion device for remote control of tumor tissue ischemia. The device consists of a flexible cannula encasing a shape memory alloy wire with its distal end connected to surgical suture. Regional tissue occlusion was tested on both the benchtop and the animal models. In the benchtop test, the occlusion device introduced quantitative and reproducible changes of blood flow in a tissue simulating phantom embedding a vessel simulator. In the animal test, the device generated a cyclic pattern of reversible ischemia in the right hinder leg tissue of a black male C57BL/6 mouse. We also developed a multimodal detector that integrates near infrared spectroscopy and electron paramagnetic resonance spectroscopy for continuous monitoring of tumor tissue oxygenation, blood content, and oxygen tension changes. The multimodal detector was tested on a cancer xenograft nude mouse undergoing reversible tumor ischemia. The automatic occlusion device and the multimodal detector can be potentially integrated for closed-loop feedback control of tumor tissue ischemia. Such an integrated occlusion device may be used in multiple clinical applications such as regional hypoperfusion control in tumor resection surgeries and thermal ablation processes. In addition, the proposed occlusion device can also be used as a research tool to understand tumor oxygen transport and hemodynamic characteristics.
Argon-Helium Cryosurgery for Treatment of C6 Gliomas in Rats and its Effect on Cellular Immunity
Authors: Li Ming , Zhang Shizhong , Zhou Yuan , Guo Yanwu , Jiang Xiaodan , Miao Li
Published: October 2014

Argon-helium cryosurgery has shown encouraging therapeutic effects on some solid tumors, but its application in the treatment of gliomas remains poorly documented. To explore the cell apoptosis at the glioma foci and the cellullar immunity changes following argon-helium cryosurgery, we established Wistar rat models bearing subcutaneous C6 glioma and divided the rats into the normal control (20 rats), sham-operated (32 rats), surgical resection (20 rats), and cryosurgery (32 rats) groups with corresponding treatments. The postoperative changes in the findings by magnetic resonance imaging (MRI) and tumor cell morphology were observed, and the cell apoptosis at the tumor foci was assessed with TUNEL assay. Flow cytometry was performed for analysis of the T lymphocyte subset changes following the cryosurgery. The results showed that cryosurgery induced not only destruction of the tumor cells but also cell apoptosis around the cryablation foci. Compared with surgical resction that caused significant reduction in CD3+ and CD4+ cell percentages, cryosurgery resulted in significantly increased percentages of CD3+ and CD4+ cells (P<0.05) with a relative increase of the CD4+/CD8+ cell ratio 14 days after the operation. These results demonstrate that in addition to tumor cell destruction, cryosurgy also results in enhanced cellular immunity and antitumor immune response of the C6 glioma-bearing rats, suggesting the great potential of argon-helium cryosurgery in clinical management of gliomas.
An Integrated Study of Aberrant Gene Copy Number and Gene Expression in GIST and LMS
Authors: Yang Da , Ylipää Antti , Yang Jilong , Hunt Kelly , Pollock Raphael , Trent Jonathan , Yli-Harja Olli , Shmulevich Ilya , Nykter Matti , Zhang Wei
Published: October 2014

Increased chromosomal instability that alters the gene copy numbers throughout the genome is known to have a role in molecular pathogenesis of tumors. The impact of gene dosage effect to the expression levels of genes in GIST and LMS is unknown. In this paper, we used a combination of array comparative genomic hybridization (aCGH) and gene expression data to gain insights into the interplay of structural and functional changes of the genome in GIST and LMSs. We identified specific target genes that change their expression due to the gene dosage effect. Statistical analysis identified four chromosomal regions, 1p, 14q, 15q, and 22q, where both copy number and mRNA expression were significantly different between the tumor types. Multi-dimensional scaling (MDS) analysis showed that the gene expression profiles of these four regions accurately distinguish GIST and LMS. In addition, the gene dosage sensitive genes in these regions are differently involved in several tumor growth promoting pathways, implying that there are different mechanisms underlying the GIST and LMS carcinogenesis. Integration of aCGH and gene expression data has not only provided insights into how DNA copy number variations affect the gene expression patterns in these cancers, but also proves to be a promising method to choose biologically relevant biomarkers.
Discovering Disease-specific Biomarker Genes for Cancer Diagnosis and Prognosis
Authors: Huang Hung-Chung , Zheng Siyuan , VanBuren Vincent , Zhao Zhongming
Published: October 2014

The large amounts of microarray data provide us a great opportunity to identify gene expression profiles (GEPs) in different tissues or disease states. Disease-specific biomarker genes likely share GEPs that are distinct in disease samples as compared with normal samples. The similarity of the GEPs may be evaluated by Pearson Correlation Coefficient (PCC) and the distinctness of GEPs may be assessed by Kolmogorov-Smirnov distance (KSD). In this study, we used the PCC and KSD metrics for GEPs to identify disease-specific (cancer-specific) biomarkers. We first analyzed and compared GEPs using microarray datasets for smoking and lung cancer. We found that the number of genes with highly different GEPs between comparing groups in smoking dataset was much larger than that in lung cancer dataset; this observation was further verified when we compared GEPs in smoking dataset with prostate cancer datasets. Moreover, our Gene Ontology analysis revealed that the top ranked biomarker candidate genes for prostate cancer were highly enriched in molecular function categories such as ‘cytoskeletal protein binding’ and biological process categories such as ‘muscle contraction’. Finally, we used two genes, ACTC1 (encoding an actin subunit) and HPN (encoding hepsin), to demonstrate the feasibility of diagnosing and monitoring prostate cancer using the expression intensity histograms of marker genes. In summary, our results suggested that this approach might prove promising and powerful for diagnosing and monitoring the patients who come to the clinic for screening or evaluation of a disease state including cancer.
On Correlated Sources of Uncertainty in Four Dimensional Computed Tomography Data Sets
Authors: Ehler Eric D. , Tomé Wolfgang A.
Published: October 2014

The purpose of this work is to estimate the degree of uncertainty inherent to a given four dimensional computed tomography (4D-CT) imaging modality and to test for interaction of the investigated factors ( i.e., object displacement, velocity, and the period of motion) when determining the object motion coordinates, motion envelope, and the confomality in which it can be defined within a time based data series. A motion phantom consisting of four glass spheres imbedded in low density foam on a one dimensional moving platform was used to investigate the interaction of uncertainty factors in motion trajectory that could be used in comparison of trajectory definition, motion envelope definition and conformality in an optimal 4D-CT imaging environment. The motion platform allowed for a highly defined motion trajectory that could be as the ground truth in the comparison with observed motion in 4D-CT data sets. 4D-CT data sets were acquired for 9 different motion patterns. Multifactor analysis of variance (ANOVA) was performed where the factors considered were the phantom maximum velocity, object volume, and the image intensity used to delineate the high density objects. No statistical significance was found for three factor interaction for definition of the motion trajectory, motion envelope, or Dice Similarity Coefficient (DSC) conformality. Two factor interactions were found to be statistically significant for the DSC for the interactions of 1) object volume and the HU threshold used for delineation and 2) the object velocity and object volume. Moreover, a statistically significant single factor direct proportionality was observed between the maximum velocity and the mean tracking error. In this work multiple factors impacting on the uncertainty in 4D data sets have been considered and some statistically significant two-factor interactions have been identified. Therefore, the detailed evaluation of errors and uncertainties in 4D imaging modalities is recommended in order to assess the clinical implications of interaction among the various uncertainty factors.
Functional MRI for Radiotherapy of Gliomas
Authors: Chang Jenghwa , Narayana Ashwatha
Published: October 2014

In this paper, we review the applications of functional magnetic resonance imaging (MRI) for target delineation and critical organ avoidance for brain radiotherapy. In this article we distinguish functional MRI from brain functional MRI (fMRI). Functional MRI includes magnetic resonance spectroscopic imaging (MRSI), perfusion MRI, diffusion tensor imaging (DTI) and brain fMRI. These functional MRI modalities can provide unique metabolic, pathological and physiological information that are not available in anatomic MRI and can potentially improve the treatment outcomes of brain tumors. For example, both choline (Cho) to N-acetylaspartate (NAA) and Cho to creatine (Cr) ratios from MRSI increase with increasing tumor malignancy and can be used to grade gliomas. Relative cerebral blood volume (rCBV) measurements from dynamic susceptibility contrast perfusion magnetic resonance imaging (DSC MRI) are superior to conventional contrast-enhanced MRI in predicting tumor biology and may be even superior to pathologic assessment in predicting patient clinical outcomes. Brain fMRI can help identify and avoid functionally critical areas when constructing treatment plans for brain radiotherapy. In the past, functional MRI measurements have not been routinely used in a clinical arena due to the experimental nature of these imaging modalities. As these methods become more commonly used and effective image co-registration algorithms become available, integration of functional MRI into the treatment process of brain radiotherapy now appears to be clinically feasible, at least in major medical centers.
The CyberKnife® Robotic Radiosurgery System in 2010
Authors: Kilby W. , Dooley J. R. , Kuduvalli G. , Sayeh S. , Maurer C. R.
Published: October 2014

This review provides a complete technical description of the CyberKnife® VSI™ System, the latest addition to the CyberKnife product family, which was released in September 2009. This review updates the previous technical reviews of the original system version published in the late 1990s. Technical developments over the last decade have impacted virtually every aspect of the CyberKnife System. These developments have increased the geometric accuracy of the system and have enhanced the dosimetric accuracy and quality of treatment, with advanced inverse treatment planning algorithms, rapid Monte Carlo dose calculation, and post-processing tools that allow trade-offs between treatment efficiency and dosimetric quality to be explored. This review provides a system overview with detailed descriptions of key subsystems. A detailed review of studies of geometric accuracy is also included, reporting a wide range of experiments involving phantom tests and patient data. Finally, the relationship between technical developments and the greatly increased range of clinical applications they have allowed is reviewed briefly.
Image-Guided Stereotactic Body Radiation Therapy for Clinically Localized Prostate Cancer: Preliminary Clinical Results
Authors: Bolzicco Giampaolo , Favretto Maria Silvia , Scremin Enrico , Tambone Carmelo , Tasca Andrea , Guglielmi Rosabianca
Published: October 2014

Stereotactic body radiotherapy (SBRT) is a new treatment modality for prostate cancer. The current study evaluates CyberKnife® SBRT and reports toxicity and early Prostate-Specific Antigen (PSA) kinetics. From June 2006 to August 2009, 45 low-and intermediate-risk prostate cancer patients received Cyberknife SBRT of 35 Gy in five fractions with 95% minimum target coverage. Median follow-up was 20-months (range 6–42-months). Seventeen patients received androgen-deprivation therapy also. Acute complications were mild, short-lived and no greater than Grade 2 by RTOG scale. Late toxicities consisted of one patient (2.2%) experiencing Grade 2 rectal, one patient (2.2%) Grade 3 and four patients (8.8%) with Grade 1 urinary toxicity. PSA in all patients progressively declined from a mean 4.7 ng/ml baseline to 1.48 ng/ml at three months, to 0.68 ng/ml at 12 months and to 0, 35 ng/ml at 24 months. The 28 hormon-naive patients had the mean PSA value of 1.1 ng/ml at one year from a mean 6.65 ng/ml baseline. There was a significant PSA value reduction in 11 hormone therapy patients with low baseline PSA value (< 1 ng/ml) from 0.37 down 0.14 ng/ml (p value 0.0068) at one year. Moreover, 14 low risk patients gave better results of mean PSA value than 17 Intermediate risk patients 0.43 ng/ml vs. 0.93 ng/ml (p value 0.02) at one year. No patient had biochemical failure at last follow-up. Hypofractionated SBRT appears to have potential against prostate cancer. Low toxicity and encouraging biochemical control support its use in early-stage prostate cancer. Results encourage further follow-up and larger studies.
Hypofractionated Stereotactic Radiotherapy for Brain Metastases: A Dosimetric and Treatment Efficiency Comparison between Volumetric Modulated Arc Therapy and Intensity Modulated Radiotherapy
Authors: Ma Yidong , Li Minghuan , Yin Yong , Kong Li , Sun Xindong , Lin Xiutong , Yu Jinming
Published: October 2014

A treatment planning comparison study was performed to evaluate the dosimetric characteristic and treatment efficiency of volumetric modulated arc therapy with step-and-shoot intensity modulated radiotherapy (IMRT) for the hypofractionated stereotactic radiotherapy (HFSRT) in patients with multiple brain metastases. CT datasets of 10 patients with two to four brain metastases were selected for the comparison. Three plans were generated for each case: seven-field step-and-shoot IMRT, single (RA1) and double (RA2) arcs with RapidArc technique (RA, Varian Medical System). The prescribed dose was 50 Gy in 10 fractions and plans were all normalized to the mean dose to the PTV. For PTV, plans aim to achieve at least 98% of PTV was covered with the 95% of prescription dose, at least 95% of PTV was encompassed by the prescription dose, and an over-dosage of 110% of the prescription dose was allowed to 5% volume of the PTV. The plans generated using three techniques were clinically acceptable. The target conformity and homogeneity were improved slightly with RA2 compared to IMRT and RA1. The Paddick CI was 0.868 (IMRT), 0.863 (RA1) and 0.895 (RA2), and HI was 7.7 (IMRT), 7.5 (RA1) and 6.5 (RA2), respectively. Compared with IMRT, the maximum dose in RA2 plans to the brainstem, left and right optic nerves, left and right lens was reduced by 1.6 Gy, 6 Gy, 3 Gy, 1.5 Gy, 1.3 Gy, respectively. The percentage of healthy tissue volume receiving 5 Gy was larger with RA1 (56.7%) and RA2 (57.1%) than with IMRT (52.9%), while the percentages of volume receiving 15 Gy and 20 Gy were smaller with RA1 (27.1%, 18.7%) and RA2 (25%, 16.3%) than with IMRT (28.8%, 19.1%). No significant difference was observed between RA1 and RA2. The mean number of MU per fraction of 5 Gy was 1944 ± 374 (IMRT), 1199 ± 173 (RA1) and 1387 ± 186 (RA2), respectively. Compared with IMRT, the MUs were reduced by 36.8% and 27.2% with RA1 and RA2. The pure beam-on time needed per fraction was 6.5 ± 1.2 min (IMRT), 1.25 min (RA1) and 2.5 min (RA2), respectively. The beam-on time for RA1 and RA2 was approximately 80% and 40% less compared to IMRT. In conclusion, RA, single arc or double arcs, is a feasible technique with highly conformal dose distribution for the HFSRT in patients with oligo brain metastases. Compared with IMRT, RA1 provides similar plan quality, while RA2 achieves slight improvements in PTV coverage and sparing of organs at risk. The treatment efficiency, using less monitor units and shorter treatment delivery time, is the most obvious advantage.
Toolkit for Determination of Dose-response Relations, Validation of Radiobiological Parameters and Treatment Plan Optimization Based on Radiobiological Measures
Authors: Mavroidis Panayiotis , Tzikas Athanasios , Papanikolaou Nikos , Lind Bengt K.
Published: October 2014

Accurately determined dose-response relations of the different tumors and normal tissues should be estimated and used in the clinic. The aim of this study is to demonstrate developed tools that are necessary for determining the dose-response parameters of tumors and normal tissues, for clinically verifying already published parameter sets using local patient materials and for making use of all this information in the optimization and comparison of different treatment plans and radiation techniques.

One of the software modules (the Parameter Determination Module) is designed to determine the dose-response parameters of tumors and normal tissues. This is accomplished by performing a maximum likelihood fitting to calculate the best estimates and confidence intervals of the parameters used by different radiobiological models. Another module of this software (the Parameter Validation Module) concerns the validation and compatibility of external or reported dose-response parameters describing tumor control and normal tissue complications. This is accomplished by associating the expected response rates, which are calculated using different models and published parameter sets, with the clinical follow-up records of the local patient population. Finally, the last module of the software (the Radiobiological Plan Evaluation Module) is used for estimating and optimizing the effectiveness a treatment plan in terms of complication-free tumor control, P+.

The use of the Parameter Determination Module is demonstrated by deriving the dose-response relation of proximal esophagus from head & neck cancer radiotherapy. The application of the Parameter Validation Module is illustrated by verifying the clinical compatibility of those dose-response parameters with the examined treatment methodologies. The Radiobiological Plan Evaluation Module is demonstrated by evaluating and optimizing the effectiveness of head & neck cancer treatment plans. The results of the radiobiological evaluation are compared against dosimetric criteria.

The presented toolkit appears to be very convenient and efficient for clinical implementation of radiobiological modeling. It can also be used for the development of a clinical data and health information database for assisting the performance of epidemiological studies and the collaboration between different institutions within research and clinical frameworks.
Targeting Accuracy in Real-time Tumor Tracking via External Surrogates: A Comparative Study
Authors: Torshabi A. E. , Pella Andrea , Riboldi Marco , Baroni Guido
Published: October 2014

The use of external surrogates to predict tumor motion in real-time for extra-cranial sites requires the use of accurate correlation models. This is extremely challenging when motion prediction is to be performed over several breathing cycles, as occurs for realtime tumor tracking with Cyberknife® Synchrony®. In this work we compare three different approaches to infer tumor motion based on external surrogates, since no comparative study is available to assess the accuracy of correlation models in tumor tracking over a long time period. We selected 20 cases in a database of 130 patients treated with realtime tumor tracking by means of the Synchrony® module. The implemented correlation models comprise linear/quadratic correlation, artificial neural networks and fuzzy logic. The accuracy of each correlation model is evaluated on the basis of ground truth tumor position information acquired during treatment, as detected by means of stereoscopic X-ray imaging. Results show that the implemented models achieve an error reduction with respect to Synchrony®, measured at the 95% confidence level, up to 10.8% for the fuzzy logic approach. This latter is able to partly reduce the incidence of tumor tracking errors above 6 mm, resulting in improved accuracy for larger discrepancies. In conclusion, complex models are suggested to predict tumor motion over long time periods. This leads to an effective improvement with respect to Cyberknife® Synchrony®. Future studies will investigate the sensitivity of the implemented models to the input database, in order to define optimal strategies.
Comparison of Internal Target Volumes for Hepatocellular Carcinoma Defined Using 3DCT with Active Breathing Coordinator and 4DCT
Authors: Gong Guanzhong , Yin Yong , Xing Ligang , Guo Yujie , Chen Jinhu , Liu Tonghai , Lu Jie , Ma Changsheng , Sun Tao , Bai Tong , Zhang Guifang , Deng Wei
Published: October 2014

The aim of this paper is to study the feasibility for determining the individual internal target volume (ITV) for hepatocellular carcinoma (HCC) using 3DCT associated with active breathing coordinator (ABC), comparing the ITVs defined by 3DCT associated with ABC and 4DCT. Thirteen patients with HCC after transarterial chemoembolization (TACE) treatment underwent 4DCT simulation and 3DCT simulation associated with ABC in free breathing (FB), end inspiration hold (EIH) and end expiration hold (EEH). The 4DCT images were sorted into 10 phases according to the respiratory cycle and labeled as CT0, CT10…CT90; and CTMIP (the maximum intensity projection image) was reconstructed. GTV0, GTV10…GTV90, GTVMIP on 4DCT, and the GTVFB, GTVEIH, GTVEEH on 3DCT were contoured. GTV0,10…90, GTV0 and GTV50, GTVEIH and GTVEEH were merged into ITV1, ITV2 and ITV3. The individual margins from GTVFB to ITV1–3 were obtained and applied to ITVFB (labeled as ITVFB-1 ITVFB-2 ITVFB-3), respectively. All the target volumes were normalized by ITV1. The volume of GTVs, ITVs and the margins were compared. There was no significant difference of diaphragm mobility between 4DCT and 3DCT ( P > 0.05), nor significant difference among the volume of the GTVs. The three ITVs were larger than the GTVMIP ( P < 0.05), but there was no significant difference among three ITVs. It's similar to the differences both in the margins of three dimensions from GTVFB to ITV1–3 and in the volumes among ITVFB-1 ITVFB-2 and ITVFB-3 ( P > 0.05). This study shows that it's safe and feasible to determine the individual ITV for HCC using 3DCT associated with ABC in comparison with 4DCT.
Publication Pressure and Scientific Misconduct in Medical Scientists
Authors: Tijdink Joeri K. , Verbeke Reinout , Smulders Yvo M.
Published: October 2014

There is increasing evidence that scientific misconduct is more common than previously thought. Strong emphasis on scientific productivity may increase the sense of publication pressure. We administered a nationwide survey to Flemish biomedical scientists on whether they had engaged in scientific misconduct and whether they had experienced publication pressure. A total of 315 scientists participated in the survey; 15% of the respondents admitted they had fabricated, falsified, plagiarized, or manipulated data in the past 3 years. Fraud was more common among younger scientists working in a university hospital. Furthermore, 72% rated publication pressure as “too high.” Publication pressure was strongly and significantly associated with a composite scientific misconduct severity score.
The role of gender on the frequency of shopping with friends during adolescence: Between the need for individuation and the need for assimilation
Authors: Gentina Elodie , Chandon Jean-Louis
Published: October 2014

Very little is known about identity mechanisms underlying shopping with friends during adolescence. A quantitative study ( Ntotal n= 614) shows that the frequency of shopping with friends relies on a balance between desires for individuation (i.e. autonomy from mother) and social approbation (i.e. susceptibility to normative and informative influence from friends). Our results show that gender moderates these mechanisms: the autonomy from mother is a key variable of shopping with peers for adolescent boys, whereas the susceptibility to peers’ normative and informative influence is a key variable for adolescent girls.
Mechanisms of Selective Attention in Generalized Anxiety Disorder
Authors: Yiend Jenny , Mathews Andrew , Burns Tom , Dutton Kevin , Fernández-Martín Andrés , Georgiou George A. , Luckie Michael , Rose Alexandra , Russo Riccardo , Fox Elaine
Published: October 2014

A well-established literature has identified different selective attentional orienting mechanisms underlying anxiety-related attentional bias, such as engagement and disengagement of attention. These mechanisms are thought to contribute to the onset and maintenance of anxiety disorders. However, conclusions to date have relied heavily on experimental work from subclinical samples. We therefore investigated individuals with diagnosed generalized anxiety disorder (GAD), healthy volunteers, and individuals with high trait anxiety (but not meeting GAD diagnostic criteria). Across two experiments we found faster disengagement from negative (angry and fearful) faces in GAD groups, an effect opposite to that expected on the basis of the subclinical literature. Together these data challenge current assumptions that we can generalize, to those with GAD, the pattern of selective attentional orienting to threat found in subclinical groups. We suggest a decisive two-stage experiment identifying stimuli of primary salience in GAD, then using these to reexamine orienting mechanisms across groups.
Characterization of Human Anterosuperior Acetabular Depression in Correlation With Labral Tears
Authors: Kopydlowski Nathan J. , Tannenbaum Eric P. , Smith Matthew V. , Sekiya Jon K.
Published: October 2014

Background:

Labral tears often occur in the same quadrant of the acetabulum at a small depression previously referred to as the psoas valley. Understanding the anatomic variations of this depression could help us understand the etiology of labral tears.

Purpose:

To describe the location and dimensions of the depression located in the anterosuperior acetabular rim. The hypothesis was that the location of this depression would be consistent with the common location of acetabular labral tears described in the literature.

Study Design:

Controlled laboratory study.

Methods:

A total of 240 pelvic specimens were divided into 2 groups (n = 120 for each) according to age (younger age group: 21.36 ± 3.12 years [range, 14-24 years]; older age group: 42.30 ± 10.27 years, [range, 25-60 years]).Specimens were also categorized based on sex (mean age: 31.93 ± 12.31 years [male]; 32.08 ± 13.66 years [female]) and race (mean age: 31.45 ± 13.16 years [black]; 32.57 ± 12.82 years [white]). The depth and width of the acetabular depression were measured using a digital caliper, and the location was measured using a goniometer.

Results:

The psoas valley was observed in every specimen and was located in the anterosuperior quadrant of the acetabulum. Its depth was significantly greater ( P < .001) in males (5.35 ± 1.60 mm) than in females (3.95 ± 1.31 mm). The width of the psoas valley was also greater ( P < .001) in males (29.39 ± 3.98 mm) than in females (24.49 ± 4.80 mm). There were no differences in size or location of the depression between races or age groups. The psoas valley was located between 3.92 ± 0.42 o’clock anteriorly and 2.12 ± 0.77 o’clock posteriorly.

Conclusion:

The differences observed in the study data are believed to be a result of the different anatomic morphologies of the pelvis in males and females. This loss of bony support, caused by the depression, could be the underlying cause of weakening of the acetabular labrum as people age.

Clinical Relevance:

The loss of bony support in the anterosuperior acetabular depression could contribute to the labral tears that commonly occur in this area. Understanding the normal anatomy of this area could be important in determining the risk of labral tears as well as treatment options.
Interaction of platelet-derived autotaxin with tumor integrin αVβ3 controls metastasis of breast cancer cells to bone
Authors: Leblanc Raphael , Lee Sue-Chin , David Marion , Bordet Jean-Claude , Norman Derek D. , Patil Renukadevi , Miller Duane , Sahay Debashish , Ribeiro Johnny , Clézardin Philippe , Tigyi Gabor J. , Peyruchaud Olivier
Published: October 2014

Key Points

ATX stored in α-granules of resting platelets is secreted upon tumor cell-induced aggregation leading to prometastatic LPA production. Nontumoral ATX promotes early bone colonization by breast cancer cells and contributes to the progression of skeletal metastases.
Maternal High-Fat Diet and Offspring Expression Levels of Vitamin K–Dependent Proteins
Authors: Lanham S. A. , Cagampang F. R. , Oreffo R. O. C.
Published: October 2014

Studies suggest that bone growth and development and susceptibility to vascular disease in later life are influenced by maternal nutrition during intrauterine and early postnatal life. There is evidence for a role of vitamin K–dependent proteins (VKDPs) including osteocalcin, matrix Gla protein, periostin, and growth-arrest specific– protein 6, in both bone and vascular development. We have examined whether there are alterations in these VKDPs in bone and vascular tissue from offspring of mothers subjected to a nutritional challenge: a high-fat diet during pregnancy and postnatally, using 6-week-old mouse offspring. Bone site–specific and sex-specific differences across femoral and vertebral bone in male and female offspring were observed. Overall a high-fat maternal diet and offspring diet exacerbated the bone changes observed. Sex-specific differences and tissue-specific differences were observed in VKDP levels in aorta tissue from high-fat diet–fed female offspring from high-fat diet–fed mothers displaying increased levels of Gas6 and Ggcx compared with those of female controls. In contrast, differences were seen in VKDP levels in femoral bone of female offspring with lower expression levels of Mgp in offspring of mothers fed a high-fat diet compared with those of controls. We observed a significant correlation in Mgp expression levels within the femur to measures of bone structure of the femur and vertebra, particularly in the male offspring cohort. In summary, the current study has highlighted the importance of maternal nutrition on offspring bone development and the correlation of VKDPs to bone structure.
A Balance Theory of Peripheral Corticotropin-Releasing Factor Receptor Type 1 and Type 2 Signaling to Induce Colonic Contractions and Visceral Hyperalgesia in Rats
Authors: Nozu Tsukasa , Takakusaki Kaoru , Okumura Toshikatsu
Published: October 2014

Several recent studies suggest that peripheral corticotropin-releasing factor (CRF) receptor type 1 (CRF1) and CRF2 have a counter regulatory action on gastrointestinal functions. We hypothesized that the activity balance of each CRF subtype signaling may determine the changes in colonic motility and visceral sensation. Colonic contractions were assessed by the perfused manometry, and contractions of colonic muscle strips were measured in vitro in rats. Visceromotor response was determined by measuring contractions of abdominal muscle in response to colorectal distensions (CRDs) (60 mm Hg for 10 min twice with a 30-min rest). All drugs were administered through ip route in in vivo studies. CRF increased colonic contractions. Pretreatment with astressin, a nonselective CRF antagonist, blocked the CRF-induced response, but astressin2-B, a selective CRF2 antagonist, enhanced the response by CRF. Cortagine, a selective CRF1 agonist, increased colonic contractions. In in vitro study, CRF increased contractions of muscle strips. Urocortin 2, a selective CRF2 agonist, itself did not alter the contractions but blocked this increased response by CRF. Visceromotor response to the second CRD was significantly higher than that of the first. Astressin blocked this CRD-induced sensitization, but astressin2-B or CRF did not affect it. Meanwhile, astressin2-B together with CRF significantly enhanced the sensitization. Urocortin 2 blocked, but cortagine significantly enhanced, the sensitization. These results indicated that peripheral CRF1 signaling enhanced colonic contractility and induced visceral sensitization, and these responses were modulated by peripheral CRF2 signaling. The activity balance of each subtype signaling may determine the colonic functions in response to stress.
Functional Diversification of Vitamin D Receptor Paralogs in Teleost Fish After a Whole Genome Duplication Event
Authors: Kollitz Erin M. , Hawkins Mary Beth , Whitfield G. Kerr , Kullman Seth W.
Published: October 2014

The diversity and success of teleost fishes (Actinopterygii) has been attributed to three successive rounds of whole-genome duplication (WGD). WGDs provide a source of raw genetic material for evolutionary forces to act upon, resulting in the divergence of genes with altered or novel functions. The retention of multiple gene pairs (paralogs) in teleosts provides a unique opportunity to study how genes diversify and evolve after a WGD. This study examines the hypothesis that vitamin D receptor (VDR) paralogs (VDRα and VDRβ) from two distantly related teleost orders have undergone functional divergence subsequent to the teleost-specific WGD. VDRα and VDRβ paralogs were cloned from the Japanese medaka (Beloniformes) and the zebrafish (Cypriniformes). Initial transactivation studies using 1α, 25-dihydroxyvitamin D3 revealed that although VDRα and VDRβ maintain similar ligand potency, the maximum efficacy of VDRβ was significantly attenuated compared with VDRα in both species. Subsequent analyses revealed that VDRα and VDRβ maintain highly similar ligand affinities; however, VDRα demonstrated preferential DNA binding compared with VDRβ. Protein-protein interactions between the VDR paralogs and essential nuclear receptor coactivators were investigated using transactivation and mammalian two-hybrid assays. Our results imply that functional differences between VDRα and VDRβ occurred early in teleost evolution because they are conserved between distantly related species. Our results further suggest that the observed differences may be associated with differential protein-protein interactions between the VDR paralogs and coactivators. We speculate that the observed functional differences are due to subtle ligand-induced conformational differences between the two paralogs, leading to divergent downstream functions.
The Benefits and Harms of Systemic Dehydroepiandrosterone (DHEA) in Postmenopausal Women With Normal Adrenal Function: A Systematic Review and Meta-analysis
Authors: Elraiyah Tarig , Sonbol Mohamad Bassam , Wang Zhen , Khairalseed Tagwa , Asi Noor , Undavalli Chaitanya , Nabhan Mohammad , Altayar Osama , Prokop Larry , Montori Victor M. , Murad Mohammad Hassan
Published: October 2014

Context:

Exogenous dehydroepiandrosterone (DHEA) therapy has been proposed to replenish the depletion of endogenous DHEA and its sulfate form, which occurs with advancing age and is thought to be associated with loss of libido and menopausal symptoms.

Objective:

We conducted a systematic review and meta-analysis to summarize the evidence supporting the use of systemic DHEA in postmenopausal women with normal adrenal function.

Methods:

We searched MEDLINE, EMBASE, PsycInfo, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus through January 2014. Pairs of reviewers, working independently, selected studies and extracted data from eligible randomized controlled trials (RCTs). We used the random-effects model to pool across studies and evaluated heterogeneity using the I2 statistic.

Results:

We included 23 RCTs with moderate to high risk of bias enrolling 1188 women. DHEA use was not associated with significant improvement in libido or sexual function (standardized mean difference, 0.35; 95% confidence interval, −0.02 to 0.73; P value = .06; I2 = 62%). There was also no significant effect of DHEA on serious adverse effects, serum lipids, serum glucose, weight, body mass index, or bone mineral density. This evidence warranted low confidence in the results, mostly due to imprecision, risk of bias, and inconsistency across RCTs.

Conclusions:

Evidence warranting low confidence suggests that DHEA administration does not significantly impact sexual symptoms or selected metabolic markers in postmenopausal women with normal adrenal function.