[A multicenter randomized prospective study of concurrent chemoradiation with 60 Gy versus 50 Gy for inoperable esophageal squamous cell carcinoma].

Objective: To determine whether 60 Gy is superior to standard 50 Gy for definitive concurrent chemoradiation(CCRT) in esophageal squamous cell carcinoma (ESCC) using modern radiation technology in a phase Ⅲ prospective randomized trial. Methods: From April 2013 to May 2017, 331 patients from 22 hospitals who were pathologically confirmed with stage ⅢA-ⅣA ESCC were randomized to 60 Gy or 50 Gy with random number table. Total of 305 patients were analyzed, including 152 in 60 Gy group and 153 in 50 Gy group. The median age was 63 years, 242(79.3%) males and 63(20.7%) females. The median length of primary tumor was 5.6 cm. The clinical characteristics between two groups were comparable. All patients were delivered 2 Gy per fraction, 5 fractions per week. Concurrent weekly chemotherapy with docetaxel (25 mg/m(2)) and cisplatin (25 mg/m(2)) and 2 cycles consolidation chemotherapy with docetaxel (70 mg/m(2)) and cisplatin (25 mg/m(2), d1-3) were administrated. The primary endpoint was local/regional progression-free survival (LRPFS). The data were compared with Pearson chi-square test or Fisher's exact test. Results: At a median follow-up of 27.3 months, the disease progression rate was 37.5% (57/152), 43.8% (67/153) in the high and standard-dose group, respectively (χ(2)=1.251, P=0.263). The 1, 2, 3-year LRPFS rate was 75.4%, 56.8%, 52.1% and 74.2%, 58.4%, 50.1%, respectively (HR: 0.95, 95%CI: 0.69-1.31, P=0.761). The 1, 2, 3-year overall survival rate was 84.1%, 64.8%, 54.1% and 85.4%, 62.9%, 54.0%, respectively (HR: 0.98, 95%CI: 0.71-1.38, P=0.927). The 1, 2, 3-year progression-free survival rate was 70.8%, 54.2%, 48.5% and 65.5%, 51.9%, 45.1%, respectively (HR: 0.93, 95%CI: 0.68-1.26, P=0.621). The incidence rates in toxicities between the two groups were similar except for higher rate of severe pneumonitis in high dose group (χ(2)=11.596, P=0.021). Conclusions: The efficacy in disease control is similar between 60 Gy and 50 Gy using modern radiation technology concurrent with chemotherapy for ESCC. The 50 Gy should be recommended as the regular radiation dose with CCRT for ESCC.

Correction: The atypical ubiquitin ligase RNF31 stabilizes estrogen receptor α and modulates estrogen-stimulated breast cancer cell proliferation.

Since the publication of the above article, the authors have noted that the input data in Fig. 6E is incorrect. The correct data are included in the below Fig. 6E. The mistake does not affect the conclusions of the paper as the levels of input proteins remain similar between samples. We apologise for any inconvenience caused by this error.

Prevalence of primary open-angle glaucoma among patients with obstructive sleep apnea.

OBJECTIVE: Our objective was to determine primary open-angle glaucoma (POAG) prevalence among obstructive sleep apnea (OSA) patients because the perioperative environment risks further damaging the optic nerve. STUDY DESIGN: We analyzed a "convenience sample" referred by Sleep Medicine for oral appliances because of continuous positive airway pressure intolerance. We determined the aggregate prevalence of the 3 POAG subtypes-"classic" open-angle glaucoma (COAG), normal-tension glaucoma (NTG), and open-angle glaucoma suspect (OAGS)-among the index population and compared it with that of same hospital's general population. Similarly determined were associations between OSA severity levels (apnea-hypopnea index [AHI]) and POAG subtypes. RESULTS: Among the study sample of 225 patients with OSA (96.4% male; mean age 58.5 ± 12.3 years), 47 (20.9%) had POAG, with a subtype distribution of COAG: 12 (25.5%), NTG: 8 (17.0%), and OAGS: 27 (57.4%). The POAG prevalence rate among medical center's general population was 2.5%, which was significantly less (P < .00001) than among those with comorbid OSA. Severity of the breathing disorder (AHI) failed to identify a significant correlation to any POAG subtype (P > .05). CONCLUSION: The significant prevalence of POAG among OSA sufferers suggests need for preoperative consultations from an ophthalmologist to determine eye health and possibly an anesthesiologist to avoid potential vision loss.

[Study of gonadotropin releasing hormone on suppressing migrationg and invationg of human nasopharyngeal carcinoma cells CNE2].

Objective:The aim of this study is to investigate the effect of gonadotropin releasing hormone (GnRH) on suppressing cell viability, apoptosis, migrationg and invationg of human nasopharyngeal carcinoma cells CNE2. Method:Nasopharyngeal carcinoma tissues and postnasal catarrh tissues were collected, the expression of GnRH positive cells and GnRH mRNA were detected by immunohistochemical staining and qRT-PCR. The human nasopharyngeal carcinoma CNE2 cells and immortalized nasopharyngeal epithelial cell line NP69 were cultured in vitro, and the expression of GnRH positive cells and GnRH mRNA were detected by immunohistochemical staining and qRT-PCR. The CNE2 cells were treated with GnRH with various concentrations 0 (Blank group), 10⁻², 10⁻¹, 10° nmol/L. The effects of GnRH on the viability, apoptosis, migration and invasion of CNE2 cells were detected by cell Counting Kit (CCK-8), flow cytometry, wound healing assay and transwell chamber assay in vitro. Result:The expression of GnRH positive cells and GnRH mRNA in nasopharyngeal carcinoma tissues were markedly down regulated than postnasal catarrh tissues (P<0.05). The expression of GnRH positive cells and GnRH mRNA in CNE2 cells were markedly down regulated than NP69 cells (P<0.05). Compared with blank group, GnRH can significantly inhibite the cell viability cells, apoptosis, migration and invasive ability (P<0.05 or P<0.01). Conclusion:GnRH significantly inhibited the cell viability, apoptosis, migration and invasive ability of CNE2 cells.

RING finger protein 31 promotes p53 degradation in breast cancer cells.

The atypical E3 ubiquitin ligase RNF31 is highly expressed in human breast cancer, the most frequent neoplastic lethality among women. Here, RNF31 depletion in breast cancer cells in combination with global gene expression profiling revealed p53 (TP53) signaling as a potential RNF31 target. Interestingly, RNF31 decreased p53 stability, whereas depletion of RNF31 in breast cancer cells caused cell cycle arrest and cisplatin-induced apoptosis in a p53-dependent manner. Furthermore, RNF31 associated with the p53/MDM2 complex and facilitated p53 polyubiquitination and degradation by stabilizing MDM2, suggesting a molecular mechanism by which RNF31 regulates cell death. Analysis of publically available clinical data sets displayed a negative correlation between RNF31 and p53 target genes, including IGFBP3 and BTG1, consistent with RNF31 regulating p53 function in vivo as well. Together, our findings suggest RNF31 as a potential therapeutic target to restore p53 function in breast cancer.

Submandibular gland sparing in intensity-modulated radiotherapy for N0-stage nasopharyngeal carcinoma.

OBJECTIVE: This study evaluated and quantified the feasibility of submandibular gland (SMG) sparing in intensity-modulated radiotherapy (IMRT) for N0-stage nasopharyngeal carcinoma (NPC). METHODS: Ten patients with N0-stage NPC were enrolled in the study. Four IMRT plans were produced for each, with different limiting conditions. In plan A, SMG sparing was ignored; in plans B, C and D, the mean dose to SMGs was restricted to 39 Gy. In addition, at least 95% of planning target volume (PTV)-IIa (PTV of clinical target volume involving level IIa lymph node) in plan C and 90% of PTV-IIa in plan D were required to have a 60 Gy covering. RESULTS: The average mean dose to SMGs was 54.6 ± 3.6 Gy in plan A and was lower 39.3 ± 0.3, 49.3 ± 1.9 and 46.7 ± 2.8 Gy in plans B, C and D, respectively. The volume of PTV-IIa covered by 60 Gy was 98.9%, 81.6%, 95.2% and 90.8% in plans A, B, C and D, respectively, and showed a parallel association between dose reduction to SMGs and the covering deficit of PTV-IIa. CONCLUSION: Reducing the mean dose received by SMG to 39 Gy or less in IMRT for N0-stage NPC is feasible.

The atypical ubiquitin ligase RNF31 stabilizes estrogen receptor α and modulates estrogen-stimulated breast cancer cell proliferation.

Estrogen receptor α (ERα) is initially expressed in the majority of breast cancers and promotes estrogen-dependent cancer progression by regulating the transcription of genes linked to cell proliferation. ERα status is of clinical importance, as ERα-positive breast cancers can be successfully treated by adjuvant therapy with antiestrogens or aromatase inhibitors. Complications arise from the frequent development of drug resistance that might be caused by multiple alterations, including components of ERα signaling, during tumor progression and metastasis. Therefore, insights into the molecular mechanisms that control ERα expression and stability are of utmost importance to improve breast cancer diagnostics and therapeutics. Here we report that the atypical E3 ubiquitin ligase RNF31 stabilizes ERα and facilitates ERα-stimulated proliferation in breast cancer cell lines. We show that depletion of RNF31 decreases the number of cells in the S phase and reduces the levels of ERα and its downstream target genes, including cyclin D1 and c-myc. Analysis of data from clinical samples confirms correlation between RNF31 expression and the expression of ERα target genes. Immunoprecipitation indicates that RNF31 associates with ERα and increases its stability and mono-ubiquitination, dependent on the ubiquitin ligase activity of RNF31. Our data suggest that association of RNF31 and ERα occurs mainly in the cytosol, consistent with the lack of RNF31 recruitment to ERα-occupied promoters. In conclusion, our study establishes a non-genomic mechanism by which RNF31 via stabilizing ERα levels controls the transcription of estrogen-dependent genes linked to breast cancer cell proliferation.

SU-E-T-486: Volume and Location Dependence on the Difference Between Monte Carlo and Pencil Beam Dose Calculations for Lung Stereotactic Body Radiation Therapy.

PURPOSE: Stereotactic body radiotherapy has been an efficacious treatment modality for early stage non-small cell lung cancer. The accuracy of dose calculations is in question due to the presence of inhomogeneity. It was required in several clinical trials to calculate dose without heterogeneity correction. However, to better correlate the outcomes with the planned dose, accurate dose calculation with heterogeneity correction is highly desirable. METHODS: We compared the recalculated dose with Monte Carlo (MC) algorithm to the original Pencil Beam (PB) calculations for clinical lung SBRT plans. Thirty-one clinical plans that followed protocol guidelines were retrospectively investigated. Dosimetric parameters D1, D95 and D99 for the PTV and D1 for organs at risk were compared. Correlations of mean lung dose and V20 of lungs between two calculations were investigated. RESULTS: Compared to the PB calculations without heterogeneity correction in clinical plans, we found that in terms of D95 of PTV, (1) the two calculations resulted in similar D95 for edge tumors with volumes greater than 25.1cc; (2) an average overestimation of 5% in PB calculations for edge tumors with volumes less than 25.1cc; and (3) an average overestimation of 9% or underestimation of 3% in PB calculations for island tumors with volumes smaller or greater than 22.6 cc, respectively. With heterogeneity correction, the PB calculation resulted in an average reduction of 23.8% and 15.3% in D95 for island and edge lesions respectively compared to the MC calculation. For organs at risks, no clinical meaningful differences were found among all the comparisons. Excellent correlations for mean dose and V20 of lungs were observed between the two calculations. CONCLUSIONS: Using a single scaling factor to account for the differences in using heterogeneity correction may not be sufficient. To understand dose-response relation in Lung SBRT, accurate dose calculation such as the Monte Carlo algorithms is highly recommended.

SU-E-J-10: Accuracy of Image Guidance Using Cone-Beam CT with Multiple Breath Hold Using Active Breathing Coordination.

PURPOSE: To complete a CBCT for a treatment using ABC, multiple breath hold (BH) (>3) were used due to the slow gantry rotation and the short BH period. Inter-BH tumor position variability may introduce distortion in the reconstructed images. This study aims to determine a threshold of the inter-BH scan displacement so that the inconsistency can be identified from the CBCT images. METHODS: A numerical phantom was constructed to represent the thorax region of a human body. To simulate the inter-BH displacements, known magnitudes of motion (s = 0, 1, 3, 5 mm) along the longitudinal direction were introduced for the 'tumor' and 'diaphragm' in the phantom. Two different irregular motion patterns (s1=s3=/=s2 and s1=/=s2=/=s3) during CBCT scans were tested. Furthermore, a physical phantom with a movable insert was scanned using a commercial CBCT system. The insert of the phantom was programmed to move in the longitudinal direction according to the same motion patterns as designed in the numerical simulations. Subsequently, nine CBCT's in 'half-fan' mode for the physical phantom were acquired with the insert in various positions. These CBCT images were then fused to the reference CT by aligning to either the body of the phantom or the 'tumor' inside the insert. RESULTS: Based on numerical simulation, position variation >1mm can be observed from the reconstructed CBCT images. Based on acquired CBCTs of the physical phantom, position variations of >3mm or 5mm were observed, depending on the motion pattern during the data acquisition. Because of the use of half-fan mode, we observed the order of position displacements of the tumor during CBCT acquisition drastically affected the outcome of imaging registration. CONCLUSIONS: Using ABC device, the inter-BH variability during a CBCT acquisition affects accuracy of tumor localization. A patient individualized planning margin might be necessary to account for this effect.

Tradeoffs of integrating real-time tracking into IGRT for prostate cancer treatment.

This study investigated the integration of the Calypso real-time tracking system, based on implanted ferromagnetic transponders and a detector array, into the current process for image-guided radiation treatment (IGRT) of prostate cancer at our institution. The current IGRT process includes magnetic resonance imaging (MRI) for prostate delineation, CT simulation for treatment planning, daily on-board kV and CBCT imaging for target alignment, and MRI/MRS for post-treatment assessment. This study assesses (1) magnetic-field-induced displacement and radio-frequency (RF)-induced heating of transponders during MRI at 1.5 T and 3 T, and (2) image artifacts caused by transponders and the detector array in phantom and patient cases with the different imaging systems. A tissue-equivalent phantom mimicking prostate tissue stiffness was constructed and implanted with three operational transponders prior to phantom solidification. The measurements show that the Calypso system is safe with all the imaging systems. Transponder position displacements due to the MR field are minimal (<1.0 mm) for both 1.5 T and 3 T MRI scanners, and the temperature variation due to MRI RF heating is <0.2 degrees C. The visibility of transponders and bony anatomy was not affected on the OBI kV and CT images. Image quality degradation caused by the detector antenna array is observed in the CBCT image. Image artifacts are most significant with the gradient echo sequence in the MR images, producing null signals surrounding the transponders with radii approximately 1.5 cm and length approximately 4 cm. Thus, Calypso transponders can preclude the use of MRI/MRS in post-treatment assessment. Modifications of the clinical flow are required to accommodate and minimize the substantial MRI artifacts induced by the Calypso transponders.

Unintended consequence of plant transformation: biolistic transformation caused transpositional activation of an endogenous retrotransposon Tos17 in rice ssp. japonica cv. Matsumae.

Genetic instability could be provoked as an unintended consequence of genetic engineering in plants. Here, we report that the rice endogenous long terminal repeat (LTR) retrotransposon Tos17 was transpositionally activated only in transgenic calli and their regenerated plants produced by biolistic transformation in rice (Oryza sativa L.) ssp. japonica cv. Matsumae. Moreover, the transpositional activity of Tos17 was sustained after plant regeneration in the T0 generation, and produced new germinal insertions. In contrast, the element remained totally quiescent in calli and regenerated plants from tissue culture of this genotype. Nonetheless, transcriptional induction and cytosine demethylation of Tos17 were found to have occurred with no significant difference in both kinds of calli, tissue culture alone and transgenic. This suggests that callus culture is likely to have played an important role in destabilizing Tos17 in the direction towards transpositional activation, but that biolistic transformation is the direct causal factor.

A novel mixture of propofol, alfentanil, and lidocaine for regional block with monitored anesthesia care in ophthalmic surgery.

STUDY OBJECTIVE: The purpose of this study is to determine the efficacy and safety of sedation/analgesia using a mixture of propofol, alfentanil, and lidocaine. DESIGN: A retrospective case review was undertaken. SETTING: This study took place at a university medical center. PATIENTS: Eighty-nine American Society of Anesthesiologists physical status 1, 2, and 3 adult patients undergoing ophthalmic surgery with regional block and monitored anesthesia care were studied. INTERVENTION: Six milliliters of propofol, 2 mL of alfentanil, and 2 mL of 2% lidocaine (6-2-2 mixture) were freshly mixed. The bolus dose was determined based on the patients' age: 5 microg/kg of alfentanil (and 0.3 mg/kg of propofol) for patients older than 75 years; the dose increased 1 mug/kg per 10-year decrease in age; and up to 9 microg/kg of alfentanil (0.54 mg/kg of propofol) for patients younger than 45 years. Regional block was performed at 1 minute after bolus completion. Blood pressure (BP), Sa(O2), electrocardiogram, capnography, clinical signs of sedation, responses to block, need for airway support, nausea and vomiting (N/V), pain due to propofol infusion, recall, and patient and surgeon satisfaction were recorded. MEASUREMENTS AND MAIN RESULTS: Seventy-eight percent of patients achieved analgesia and sedation without adverse response to the block. Twelve percent achieved good analgesia and sedation with only eyebrow movement upon needle insertion. Twenty-seven percent had respiratory depression but were able to follow commands and maintain adequate ventilation. Two percent had brief apnea alleviated by chin lift or jaw thrust. None had pain because of propofol infusion or N/V. Before sedation, average systolic BP was significantly increased (P < 0.0001) compared with baseline. After sedation and block, systolic BP decreased 6% from baseline (P < 0.005). CONCLUSION: Adjusted for age and weight, the dose of the 6-2-2 mixture met the sedation requirements for most patients. With a low incidence of need for airway support, no pain during infusion, and no N/V, this novel mixture of propofol, alfentanil, and lidocaine provided adequate analgesia and sedation as well as hemodynamic stability for ophthalmic surgery under regional block.

Mechanical shear wave induced by piezoelectric ceramics for magnetic resonance elastography.

Magnetic resonance elastography (MRE) is a noninvasive technique to measure elasticity of tissues in vivo. For MRE, an additional actuator is needed to be mounted on an observed object, and to excite the object. In this paper, an experiment is set to obtain MR mechanical shear wave images. A novel actuator is proposed to generate mechanical wave propagating inside a gel phantom. The actuator is made of piezoelectric ceramics, and is fixed on a plexiglass bracket. Both of the gel phantom and the actuator are put into a head coil in the scanner's bore. The actuator works synchronously with an imaging sequence running on the scanner. The sequence is modified from a FLASH sequence, into a motion-sensitizing phase-contrast sequence, for shear wave imaging. Wave images are presented to show the effect of those factors, such as the stiffness of the phantoms, the frequency of the actuator, the parameters of the motion-sensitizing gradient, and the oscillation of the patient bed.

Hybrid Weighted Minimum Norm Method A new method based LORETA to solve EEG inverse problem.

This Paper brings forward a new method to solve EEG inverse problem. Based on following physiological characteristic of neural electrical activity source: first, the neighboring neurons are prone to active synchronously; second, the distribution of source space is sparse; third, the active intensity of the sources are high centralized, we take these prior knowledge as prerequisite condition to develop the inverse solution of EEG, and not assume other characteristic of inverse solution to realize the most commonly 3D EEG reconstruction map. The proposed algorithm takes advantage of LORETA's low resolution method which emphasizes particularly on 'localization' and FOCUSS's high resolution method which emphasizes particularly on 'separability'. The method is still under the frame of the weighted minimum norm method. The keystone is to construct a weighted matrix which takes reference from the existing smoothness operator, competition mechanism and study algorithm. The basic processing is to obtain an initial solution's estimation firstly, then construct a new estimation using the initial solution's information, repeat this process until the solutions under last two estimate processing is keeping unchanged.

Liver CT-image retrieval based on Gabor texture.

Gabor schemes of image representation have shown great success in many texture related computer vision applications. This is mainly because the primitives of image representation in vision have a wavelet form similar to Gabor elementary functions (GEF's). We use Gabor approach to analyze the texture of liver CT-images and extract the corresponding feature vectors. Then, the feature vectors are used to facilitate content-based image retrieval (CBIR). In experiments, a batch of liver CT images containing several types of CT findings is collected, and retrieval results by Gabor texture are present.

[Advances of research on stereo localization in computer assisted surgery].

In this paper several kinds of localization technologies used in computer assisted surgery are analyzed, especially the optical stereo localization methods. Finally directions of research and development in the field are given.

A double-blind, placebo-controlled, randomized clinical trial of transdermal dihydrotestosterone gel on muscular strength, mobility, and quality of life in older men with partial androgen deficiency.

The efficacy and safety of androgen supplementation in older men remains controversial. Despite biochemical evidence of partial androgen deficiency in older men, controlled studies using T demonstrate equivocal benefits. Furthermore, the importance of aromatization and 5alpha reduction in androgen actions among older men remains unclear. Dihydrotestosterone is the highest potency natural androgen with the additional features that it is neither aromatizable nor susceptible to potency amplification by 5alpha reduction. Therefore, the effects of dihydrotestosterone may differ from those of T in older men. This study evaluated the efficacy and safety of 3 months treatment with transdermal dihydrotestosterone gel on muscle strength, mobility, and quality of life in ambulant, community-dwelling men aged 60 yr or older. Eligible men (plasma T < or =15 nmol/liter) were randomized to undergo daily dermal application of 70 mg dihydrotestosterone gel (n = 18) or vehicle (n = 19) and were studied before, monthly during, and 1 month after treatment. Among 33 (17 dihydrotestosterone, 16 placebo) men completing the study with a high degree of compliance, dihydrotestosterone had significant effects on circulating hormones (increased dihydrotestosterone; decreased total and free testosterone, LH, and FSH; unchanged SHBG and estradiol), lipid profiles (decreased total and low-density lipoprotein cholesterols; unchanged high-density lipoprotein cholesterol and triglycerides), hematopoiesis (increased hemoglobin, hematocrit, and red cell counts), and body composition (decreased skinfold thickness and fat mass; unchanged lean mass and waist to hip ratio). Muscle strength measured by isokinetic peak torque was increased in flexion of the dominant knee but not in knee extension or shoulder contraction, nor was there any significant change in gait, balance, or mobility tests, in cognitive function, or in quality of life scales. Dihydrotestosterone treatment had no adverse effects on prostate (unchanged prostate volumes and prostate-specific antigen) and cardiovascular (no adverse change in vascular reactivity or lipids) safety markers. We conclude that 3 months treatment with transdermal dihydrotestosterone gel demonstrates expected androgenic effects, short-term safety, and limited improvement in lower limb muscle strength but no change in physical functioning or cognitive function.

[Application of time-frequency analysis on medical signal processing].

The frequency content of many biomedical signals can change rapidly with time. Conventional Fourier spectral analysis techniques are insufficient for analyzing the time-varying spectral content of these signals. By mapping a one-dimensional function of time(or frequency), the time-frequency representation can localize the signal energy in both the time and frequency directions. It has been shown that many biomedical signal problems may benefit from time-frequency analysis. The basic method of time-frequency analysis and its application in biomedical signals processing are introduced.

Realizations of fast 2-D/3-D image filtering and enhancement.

This paper proposes a novel algorithm for multidimensional image enhancement based on a fuzzy domain enhancement method, and an implementation of a recursive and separable low-pass filter. Considering a smoothed image as a fuzzy data set, each pixel in an image is processed independently, using fuzzy domain transformation and enhancement of both the dynamic range and the local gray level variations. The algorithm has the advantages of being fast and adaptive, so it can be used in real-time image processing applications and for multidimensional data with low computational cost. It also has the ability to reduce noise and unwanted background that may affect the visualization quality of two-dimensional (2-D)/three-dimensional (3-D) data. Examples for the applications of the algorithm are given for mammograms, ultrasound 3-D images, and photographic images.