bluuebunny/crossref_metadata_2025_split huggingface dataset:
Audiovisual biofeedback improves motion prediction accuracy
Authors: Pollock Sean , Lee Danny , Keall Paul , Kim Taeho 
Published: March 2013

Purpose:The accuracy of motion prediction, utilized to overcome the system latency of motion management radiotherapy systems, is hampered by irregularities present in the patients’ respiratory pattern. Audiovisual (AV) biofeedback has been shown to reduce respiratory irregularities. The aim of this study was to test the hypothesis that AV biofeedback improves the accuracy of motion prediction.Methods:An AV biofeedback system combined with real‐time respiratory data acquisition and MR images were implemented in this project. One‐dimensional respiratory data from (1) the abdominal wall (30 Hz) and (2) the thoracic diaphragm (5 Hz) were obtained from 15 healthy human subjects across 30 studies. The subjects were required to breathe with and without the guidance of AV biofeedback during each study. The obtained respiratory signals were then implemented in a kernel density estimation prediction algorithm. For each of the 30 studies, five different prediction times ranging from 50 to 1400 ms were tested (150 predictions performed). Prediction error was quantified as the root mean square error (RMSE); the RMSE was calculated from the difference between the real and predicted respiratory data. The statistical significance of the prediction results was determined by the Student'st‐test.Results:Prediction accuracy was considerably improved by the implementation of AV biofeedback. Of the 150 respiratory predictions performed, prediction accuracy was improved 69% (103/150) of the time for abdominal wall data, and 78% (117/150) of the time for diaphragm data. The average reduction in RMSE due to AV biofeedback over unguided respiration was 26% (p < 0.001) and 29% (p < 0.001) for abdominal wall and diaphragm respiratory motion, respectively.Conclusions:This study was the first to demonstrate that the reduction of respiratory irregularities due to the implementation of AV biofeedback improves prediction accuracy. This would result in increased efficiency of motion management techniques affected by system latencies used in radiotherapy.
Accuracy verification of infrared marker‐based dynamic tumor‐tracking irradiation using the gimbaled x‐ray head of the Vero4DRT (MHI‐TM2000)a)
Authors: Mukumoto Nobutaka , Nakamura Mitsuhiro , Sawada Akira , Suzuki Yasunobu , Takahashi Kunio , Miyabe Yuki , Kaneko Shuji , Mizowaki Takashi , Kokubo Masaki , Hiraoka Masahiro 
Published: March 2013

Purpose:To verify the accuracy of an infrared (IR) marker‐based dynamic tumor‐tracking irradiation system (IR tracking) using the gimbaled x‐ray head of the Vero4DRT (MHI‐TM2000).Methods:The gimbaled 6‐MV C‐band x‐ray head of the Vero4DRT can swing along the pan‐and‐tilt direction to track a moving target. During beam delivery, the Vero4DRT predicts the future three‐dimensional (3D) target position in real time using a correlation model [four‐dimensional (4D) model] between the target and IR marker motion, and then continuously transfers the corresponding tracking orientation to the gimbaled x‐ray head. The 4D‐modeling error (E4DM) and the positional tracking error (EP) were defined as the difference between the predicted and measured positions of the target in 4D modeling and as the difference between the tracked and measured positions of the target during irradiation, respectively. For the clinical application of IR tracking, we assessed the relationship between E4DM and EP for three 1D sinusoidal (peak‐to‐peak amplitude [A]: 20–40 mm, breathing period [T]: 2–4 s), five 1D phase‐shifted sinusoidal (A: 20 mm, T: 4 s, phase shift [τ]: 0.2–2 s), and six 3D patient respiratory patterns.Results:The difference between the 95th percentile of the absoluteEP () and the mean (μ) + two standard deviations (SD) of absolute E4DM () was within ±1 mm for all motion patterns. As the absolute correlation between the target and IR marker motions decreased from 1.0 to 0.1 for the 1D phase‐shifted sinusoidal patterns, the and increased linearly, from 0.4 to 3.0 mm (R = −0.98) and from 0.5 to 2.2 mm (R = −0.95), respectively. There was a strong positive correlation between and in each direction [(lateral, craniocaudal, anteroposterior) = (0.99, 0.98, 1.00)], even for the 3D respiratory patterns; thus, was readily estimated from .Conclusions:Positional tracking errors correlated strongly with 4D‐modeling errors in IR tracking. Thus, the accuracy of the 4D model must be verified before treatment, and margins are required to compensate for the 4D‐modeling error.
Quantification of speed-up and accuracy of multi-CPU computational flow dynamics simulations of hemodynamics in a posterior communicating artery aneurysm of complex geometry
Authors: Karmonik Christof , Yen Christopher , Gabriel Edgar , Partovi Sasan , Horner Marc , Zhang Yi J , Klucznik Richard P , Diaz Orlando , Grossman Robert G 
Published: March 2013

BackgroundTowards the translation of computational fluid dynamics (CFD) techniques into the clinical workflow, performance increases achieved with parallel multi-central processing unit (CPU) pulsatile CFD simulations in a patient-derived model of a bilobed posterior communicating artery aneurysm were evaluated while simultaneously monitoring changes in the accuracy of the solution.MethodsSimulations were performed using 2, 4, 6, 8, 10 and 12 processors. In addition, a baseline simulation was obtained with a dual-core dual CPU computer of similar computational power to clinical imaging workstations. Parallel performance indices including computation speed-up, efficiency (speed-up divided by number of processors), computational cost (computation time × number of processors) and accuracy (velocity at four distinct locations: proximal and distal to the aneurysm, in the aneurysm ostium and aneurysm dome) were determined from the simulations and compared.ResultsTotal computation time decreased from 9 h 10 min (baseline) to 2 h 34 min (10 CPU). Speed-up relative to baseline increased from 1.35 (2 CPU) to 3.57 (maximum at 10 CPU) while efficiency decreased from 0.65 to 0.35 with increasing cost (33.013 to 92.535). Relative velocity component deviations were less than 0.0073% and larger for 12 CPU than for 2 CPU (0.004±0.002%, not statistically significant, p=0.07).ConclusionsWithout compromising accuracy, parallel multi-CPU simulation reduces computing time for the simulation of hemodynamics in a model of a cerebral aneurysm by up to a factor of 3.57 (10 CPUs) to 2 h 34 min compared with a workstation with computational power similar to clinical imaging workstations.
Performance of concrete buildings in the 22 February 2011 Christchurch earthquake and implications for Canadian codes
Authors: Elwood Kenneth J. 
Published: March 2013

At 12:51 pm local time on 22 February 2011, a M 6.2 aftershock of the 4 September 2010, Darfield earthquake shook the city of Christchurch, New Zealand. The aftershock occurred on an unmapped fault less than 10 km from the city centre resulting in significant damage, particularly in the Central Business District (CBD). The earthquake resulted in the collapse of two reinforced concrete office buildings, one parking garage, and numerous unreinforced masonry buildings, including many heritage structures, leading to 185 deaths. Liquefaction was wide spread in the CBD and the eastern suburbs, resulting in foundation movement for housing and office buildings alike. Many buildings in the CBD experienced severe damage, some requiring demolition, necessitating careful controlled access to the CBD in the months following the earthquake. This paper summarizes the recorded earthquake shaking and observed damage to concrete buildings in CBD, with a specific focus on identifying future research and possible changes for seismic design practice and codes in Canada to address the Christchurch observations.
Abstract A15: Snail upregulation of SPARC leads to increased invasion in models of both early-and late-stage NSCLC
Authors: Grant Jeanette L. , Walser Tonya C. , Minna John D. , Shay Jerry W. , Dubinett Steven M. 
Published: March 2013

Abstract
The zinc-finger protein Snail is upregulated in human non-small cell lung cancer (NSCLC) tissues and is associated with poor patient prognosis. We have shown that Snail upregulation in lung cancer cell lines leads to morphologic changes indicative of epithelial-mesenchymal transition (EMT) in vitro and tumor progression in vivo. Snail overexpression is associated with differential gene expression related to diverse aspects of lung cancer progression. One gene upregulated by Snail in both NSCLC and histologically normal human bronchial epithelial cell lines is secreted protein, acidic and rich in cysteine (SPARC). Expression of SPARC modulates reversible interactions between cells and their extracellular matrix and is known to play an important role in the wound healing process of normal epithelial cells. Its upregulation in several cancer types is associated with increased migration, invasion, and poor patient prognosis. Here, we show that overexpression of Snail leads to increased invasion in a modified Boyden chamber assay in models of both early and late stage NSCLC. Knockdown of SPARC by shRNA leads to a reversal of invasion, indicating that SPARC is at least partially responsible for the effect of Snail on invasion. Computational analysis indicates that Snail does not directly enhance the transcription of SPARC; therefore, we have investigated the indirect mechanism for this relationship. Both ERK1/2 and the chaperone protein HSP27 have emerged as potential components of the pathway. Snail overexpression also leads to activation of ERK1/2, and chemical inhibition of this pathway leads to a decrease in SPARC protein. Snail-overexpressing cell lines show increased transcription of HSP27 mRNA. As Snail has been shown to be overexpressed in the inflammatory microenvironment of premalignancy and in established tumors, SPARC-driven invasion supports both the parallel and linear models of tumor progression. Delineating pathways involved in Snail-dependent and SPARC-mediated tumor progression may yield new targets for lung cancer prevention and treatment.
Abstract A19: Lung cancers taken from autopsies express more tumor antigens than those taken from surgical resections: Implications for immunoprevention
Authors: Ge Lisheng , Lambrecht Nils , Ouyang Yi , Hoa Neil , Chen Longchaun , Deng Xiamong , Dacosta-Iyer Maria , Szabo Sandor , Jadus Martin Robert 
Published: March 2013

Abstract
Lung cancers are fatal cancers, even if caught early, since some cancer cells have spread by the time they are detected. Some lung cancer patients treated by immunotherapy have improved their survival. A limited number of tumor-associated antigens (TA), both humoral-based and cell-mediated antigens, are known for lung cancers. The identification of more relevant antigens will allow better immunotherapies to be developed. We analyzed adenocarcinomas and small cell lung cancers taken from surgical resections or from autopsies to determine the prevalent antigens by using quantitative real time PCR techniques for 43 putative tumor antigens. We compared these tumor-derived profiles with normal lung cell expression. The data fell into 3 profiles where: 1) both tumors were positive for 18 TA; 2) only SCLC expressed 14 TA; 3) a group of 10 TA that had no differences. The lung tumor samples taken at autopsy, expressed a higher number of TA and expressed more mRNA TA than those taken from surgical resections. Blotting techniques using the specimens from the lung cancer autopsies confirmed increased expression of the tumor antigen precursor proteins when compared to the normal lung. Use of two lung cancer cell lines also independently confirmed the presence of these proteins. These data suggest that human lung cancers at the time of death are more antigenic than those taken at an earlier stage. This type of tumor taken at autopsy might provide more targets for vaccine generation and allow the concept of immunoprevention to be used in lung cancer patients.
Abstract A21: Tissue platinum concentration and tumor response in non-small cell lung cancer
Authors: Kim Eric S. , He Guangan , Chow Chi-Wan , Fujimoto Junya , Lee Jack J. , Kalhor Neda , Swisher Stephen G. , Wistuba Ignacio I. , Stewart David J. , Siddik Zahid H. 
Published: March 2013

Abstract
Background: Platinum resistance is a major limitation in the treatment of advanced non-small cell lung cancer (NSCLC). Reduced intracellular drug accumulation is one of the most consistently identified features of platinum-resistant cell lines, but clinical data are limited. We assessed effects of tissue platinum concentrations on tumor response, time to recurrence, progression-free survival (PFS) and overall survival (OS) in patients with early-stage NSCLC following neoadjuvant platinum-based chemotherapy.
Methods: We measured total platinum concentrations in 44 archived fresh frozen NSCLC specimens from patients who received neoadjuvant platinum-based chemotherapy. Samples were analyzed by flameless atomic absorption spectrophotometry to assess absorbance reading associated with platinum concentration. Four specimens from patients who underwent surgery only and one patient who received pemetrexed as neoadjuvant chemotherapy were analyzed as negative controls. Absorbance value per mg of tissue was correlated with percent reduction in tumor size on post- vs prechemotherapy CT scans. Kaplan-Meier curves and log-rank tests were used to evaluate differences in time to recurrence and survival between two groups divided by median platinum concentration.
Results: Platinum absorbance values in 44 neoadjuvant specimens were easily detectable and ranged from 0.6 to 6.7 × 10−3 per mg of tissue while five negative controls demonstrated absorbance readings similar to 0.1N HCL. Platinum absorbance correlated significantly with percent reduction in tumor size (R2 = 0.48, P&lt;0.00001). The same correlations were seen in cisplatin (P = 0.0003), carboplatin (P = 0.0013), adenocarcinoma (P = 0.0003) and squamous cell carcinoma (P = 0.019) groups. Furthermore, there was no significant impact of potential variables such as the type of platinum compound, number of cycles, pre-treatment tumor diameter and time lapse from last chemotherapy on platinum concentration. Patients with lower Pt concentration also had shorter time to recurrence (P = 0.0494), progression free survival (P = 0.0366) and overall survival (P = 0.035).
Conclusion: This is the first tissue-based study to establish a relationship between tissue platinum concentrations and response in NSCLC. Reduced intratumoral platinum accumulation may constitute a significant mechanism of platinum resistance even in clinical specimens. Further studies investigating factors that modulate intracellular platinum concentration are warranted (Supported by National Foundation of Cancer Research 90088436, Department of Defense W81XWH-07-1-0306, National Institute of Health CA127263, CA160687 and CA16672).
Abstract A22: Clinical implication of microscopic anthracotic pigment in mediastinal staging of non-small cell lung cancer by endobronchial ultrasound-guided transbronchial needle aspiration
Authors: Kim Young Whan , Park Young Sik , Lee Jinwoo , Lee Sang-Min , Yim Jae-Joon , Han Sung Koo , Pang Jin Chul , Chung Doo Hyun , Yang Seok-Chul 
Published: March 2013

Abstract
Introduction: Microscopic anthracotic pigment is frequently observed in EBUS-TBNA specimen from non-small cell lung cancer, but the clinical interpretation is not known. The aim of this study was to evaluate the clinical implication of microscopic anthracotic pigment in mediastinal staging of non-small cell lung cancer by EBUS-TBNA.
Methods: From May 2010 to July 2011, Consecutive potentially operable non-small cell lung cancer patients who underwent EBUS-TBNA for mediastinal staging were recruited in this retrospective study.
Results: Total 133 patients, male were 102 (76.7%). Median age was 68. Squamous cell carcinoma (59, 44.4%) and adenocarcinoma (57, 42.9%) were most common. Clinical stages after EBUS-TBNA were as followed; IA (18.8%), IB (17.3%), IIA (6.0%), IIB (9.0%), IIIA (36.8%), IIIB (12.0%). Total 281 mediastinal lymph nodes were sampled by EBUS-TBNA, station 4R (100, 35.8%) and station 7 (86, 30.8%) were most common sites. Malignant lymph nodes were 100 (35.8%). Microscopic anthracotic pigment was observed in 61 (21.7%) lymph nodes, and among them malignant lymph nodes were only 3 (P&lt;0.001). The lymph nodes with microscopic anthracotic pigment were small (9.0 vs. 10.8 mm, P = 0.001) and low SUV on FDG-PET (5.4 vs. 6.7, P = 0.120). In multivariable analysis, microscopic anthracotic pigment was statistically significant associated with benign lymph node (adjusted OR, 14.3; 95% CI, 3.6–57.3; P&lt;0.001).
Conclusion: In potentially operable non-small cell lung cancer patients, microscopic anthracotic pigment in endobronchial ultrasound-guided transbronchial needle aspiration specimen was strongly associated with benign mediastinal lymph node.
Abstract A24: CpG island methylation of microRNAs is associated with tumor size and the recurrence of non-small cell lung cancer
Authors: Kitano Kentaro , Goto Akiteru , Fukayama Masashi , Yatomi Yutaka , Ohishi Nobuya , Takai Daiya , Watanabe Kousuke , Emoto Noriko , Kage Hidenori , Hamano Emi , Nagase Takahide , Sano Atsushi , Murakawa Tomohiro , Nakajima Jun 
Published: March 2013

Abstract
We investigated whether the CpG island methylation of certain microRNAs was associated with the clinicopathological features and the prognosis of non-small cell lung cancer. The methylation of mir-152, -9-3, -124-1, -124-2, and -124-3 was analyzed in 96 non-small cell lung cancer specimens using a combined bisulfite restriction analysis. The median observation period was 49.5 months. The methylation of mir-9-3, -124-2, and -124-3 was individually associated with an advanced T factor independently of age, sex, and smoking habit. Moreover, the methylation of multiple microRNA loci was associated with a poorer progression-free survival in a univariate analysis. Our result enlightens the accumulation of aberrant DNA methylation which occurs in concordance with the tumor progression.
Abstract A27: Expression of the EGFR suppressor LRIG1 is associated with survival in non-small cell lung cancer
Authors: Kvarnbrink Samue , Edlund Karolina , Botling Johan , Micke Patrick , Hedman Håkan , Johansson Mikael 
Published: March 2013

Abstract
Leucine-rich repeats and immunoglobulin-like domains (LRIG)-1 is an endogenous inhibitor of epidermal growth factor receptor (EGFR) signaling, that is down-regulated in several forms of human cancer. The LRIG gene family also includes LRIG2 and LRIG3. EGFR signaling is important in non-small cell lung cancer (NSCLC) and EGFR tyrosine kinase inhibitors are today considered standard treatment in patients with advanced disease. Since smoking recently was reported to down-regulate LRIG1 gene expression in lung epithelium and squamous cell carcinoma of the lung, the LRIG family of proteins may be important in lung cancer.
The objective of the present study was to investigate if LRIG is a prognostic factor in non-small cell lung cancer (NSCLC). Therefore, we conducted an in silico analysis of LRIG gene expression in publicly available datasets using the Oncomine database and compared LRIG expression to clinical outcome. We also analyzed the LRIG protein expression by immunohistochemistry in a tissue micro array (TMA, n = 190) representing long- and short time survivors from a surgically treated NSCLC patient cohort.
In seven out of 11 datasets in the in silico analysis, high expression of LRIG1 correlated (p&lt;0.05) with long patient survival. This correlation was apparent both in adenocarcinoma and squamous cell carcinoma. In the TMA, LRIG1 expression was significantly higher in the long-term survival group than in the short time survival group (p&lt;0.05). LRIG2 and LRIG3 protein expression did not significantly correlate to survival.
In conclusion, both our in silico analysis of gene expression and TMA study of protein expression showed associations between high LRIG1 expression and longer NSCLC patient survival. This implicates that LRIG1 may be a prognostic factor in NSCLC and further studies on larger datasets have been initiated.
Abstract A29: Genomic alteration of E2F/Rb activates EZH2 in small cell lung cancer
Authors: Thu Kelsie L. , Hubaux Roland , Aviel-Ronen Sarit , MacAulay Calum E. , Tsao Ming-Sound , Lam Stephen , Lam Wan L. , Coe Bradley P. 
Published: March 2013

Abstract
Introduction: Small Cell Lung Cancer (SCLC) is a highly aggressive lung tumor with a 5 year survival rate of only 5% for extensive stage disease, which has only modestly improved over the last few decades. Identification of new molecular diagnostic and therapeutic targets is thus imperative. The purpose of this study was to employ genomic profiling of SCLC tumors to identify novel genomic alterations responsible for driving the aggressive biology of SCLC.
Methods: DNA was extracted from a panel of 14 formalin fixed paraffin embedded SCLC tumors and used to perform high resolution array comparative genomic hybridization (aCGH) on a tiling array to identify recurrent copy number alterations. RNA was harvested from a series of SCLC cell lines and used to perform qRT-PCR on candidate genes. Publicly available SCLC tumor microarray data was also analyzed to interrogate the expression of candidate genes.
Results: Through application of integrated genome and transcriptome microarray profiling, and comparison of SCLC to less aggressive non-small cell lung cancers (NSCLC) we have identified novel patterns of genomic alteration mediated pathway disruption specific to SCLC. This includes activation of the cell cycle through deregulation of downstream pathway components, as opposed to upstream deregulation of receptors such as EGFR which is characteristic of NSCLC.
Strikingly we observed direct genomic activation of E2F transcription factors, in addition to the classically described loss of the Rb tumor suppressor. Analysis of targets of the E2F/Rb pathway identified EZH2, a polycomb repressive complex 2 (PRC2) member involved in epigenetic silencing of genes involved in differentiation. EZH2 has been characterized as a target of genomic amplification in prostate and breast cancers, however, no genomic amplifications were detected in our SCLC samples, thus any overexpression is likely regulated by upstream elements of the E2F/Rb pathway. qRT-PCR confirmed EZH2 as being specifically hyper-activated with a mean 42 fold over-expression (range 10 to 74 fold) in SCLC compared to 13 fold in NSCLC. This pattern was verified from an analysis of an independent array study of SCLC. Moreover, shRNA-mediated knockdown demonstrated a significant reduction in cell viability in SCLC cell lines.
Conclusion: We conclude that EZH2 activation through genomic alteration of E2F/Rb contributes to the malignant phenotype of SCLC and may represent a potential therapeutic target.