bluuebunny/crossref_metadata_2025 huggingface dataset:
Non-Negative Intensity for Structures with Inhomogeneous Damping
Authors: Liu Daipei , Marburg Steffen , Geweth Christian , Kessissoglou Nicole
Published: August 2018

In this work, numerical methods to identify the surface areas of a vibrating structure that radiate sound are implemented for cases of structures with inhomogeneous distributions of viscous Rayleigh damping. The intensity-based techniques correspond to acoustic intensity evaluated in terms of the acoustic pressure and particle velocity, non-negative intensity evaluated in terms of the acoustic impedance matrix obtained at the structural surface, and back-calculated non-negative intensity evaluated in terms of the acoustic impedance matrix obtained at a far-field receiver surface. Different configurations of inhomogeneous damping are applied to two elastic structures corresponding to a plate and a cylindrical shell. To examine the influence of inhomogeneous damping on sound radiation, the acoustic intensity on the structural surface, the acoustic intensity on several different far-field receiver surfaces, non-negative intensity and back-calculated non-negative intensity are numerically compared for different inhomogeneous damping cases.
Origin of basin-scale syn-extensional synclines on the southern margin of the Northern Carnarvon Basin, Western Australia
Authors: McHarg Sam , Elders Chris , Cunneen Jane
Published: August 2018

Fault geometry exerts a dominant structural control on the deformation of hanging wall sequences during extension and contraction. Numerical, kinematic and sandbox modelling studies have demonstrated that characteristic anticline–syncline pairs are produced during the extension of ramp-flat faults. These features are commonly recognized in smaller fault-scale structures, but remain underappreciated in larger, basin-scale settings. The Lewis Trough, situated within the Northern Carnarvon Basin, Western Australia, is a basin-scale, largely unfaulted syncline with an associated anticline along its western flank, rather than the fault-related graben typical of the region. We present kinematic models demonstrating that a SE-dipping, ramp-flat fault geometry can produce relative highs and lows in Jurassic strata as well as honouring the asymmetrical onlap pattern within the Lewis Trough. This study indicates that the Lewis Trough formed during the Early Jurassic, a period typically associated with high rates of extension and not during the Late Triassic Fitzroy Compression Event. This study also highlights the importance of the Locker Shale in partitioning deformation of the Permian and Mesozoic fault systems and as a diffuse zone that variably partitions displacement between stacked Permian and Mesozoic fault systems.
Gradient Estimation for Real-time Adaptive Temporal Filtering
Authors: Schied Christoph , Peters Christoph , Dachsbacher Carsten
Published: August 2018

With the push towards physically based rendering, stochastic sampling of shading, e.g. using path tracing, is becoming increasingly important in real-time rendering. To achieve high performance, only low sample counts are viable, which necessitates the use of sophisticated reconstruction filters. Recent research on such filters has shown dramatic improvements in both quality and performance. They exploit the coherence of consecutive frames by reusing temporal information to achieve stable, denoised results. However, existing temporal filters often create objectionable artifacts such as ghosting and lag. We propose a novel temporal filter which analyzes the signal over time to derive adaptive temporal accumulation factors per pixel. It repurposes a subset of the shading budget to sparsely sample and reconstruct the temporal gradient. This allows us to reliably detect sudden changes of the sampled signal and to drop stale history information. We create gradient samples through forward-projection of surface samples from the previous frame into the current frame and by reevaluating the shading samples using the same random sequence. We apply our filter to improve real-time path tracers. Compared to previous work, we show a significant reduction of lag and ghosting as well as improved temporal stability. Our temporal filter runs in 2 ms at 1080p on modern graphics hardware and can be integrated into deferred renderers.
A High-Resolution Compression Scheme for Ray Tracing Subdivision Surfaces with Displacement
Authors: Lier Alexander , Martinek Magdalena , Stamminger Marc , Selgrad Kai
Published: August 2018

Subdivision surfaces, especially with displacement, are one of the key modeling primitives used in high-quality rendering environments, such as, e.g., movie production. While their use easily maps to rasterization-based frameworks, they pose a significant challenge for ray tracing environments. This is due to the fact that incoherent access patterns require storing or caching fully tessellated and displaced meshes for efficient intersection computations. In this paper we use a two-tier hierarchy built on a scene's patches. It relies on compressed and quantized bounding volumes on the second tier to reduce the size of the BVH itself. Based on this acceleration structure, we propose a quantized, compact approximation for leaf nodes while being faithful to the underlying patch-geometry. We build on recent advances and present a system that shows competitive performance regarding run-time speed, which is close to full-resolution pre-tessellation methods as well as to previous compression approaches. Ultimately, we provide strong compression of up to a factor of 5: 1 compared to state-of-the-art methods while maintaining high geometrical fidelity surpassing similarly compact approximations and getting close to uncompressed geometry.
PLOCTree
Authors: Viitanen Timo , Koskela Matias , Jääskeläinen Pekka , Tervo Aleksi , Takala Jarmo
Published: August 2018

In the near future, GPUs are expected to have hardware support for real-time ray tracing in order to, e.g., help render complex lighting effects in video games and enable photorealistic augmented reality. One challenge in real-time ray tracing is dynamic scene support, that is, rebuilding or updating the spatial data structures used to accelerate rendering whenever the scene geometry changes. This paper proposes PLOCTree, an accelerator for tree construction based on the Parallel Locally-Ordered Clustering (PLOC) algorithm. Tree construction is highly memory-intensive, thus for the hardware implementation, the algorithm is rewritten into a bandwidth-economical form which converts most of the external memory traffic of the original software-based GPU implementation into streaming on-chip data traffic. As a result, the proposed unit is 3.9 times faster and uses 7.7 times less memory bandwidth than the GPU implementation. Compared to state-of-the-art hardware builders, PLOCTree gives a superior performance-quality tradeoff: it is nearly as fast as a state-of-the-art low-quality linear builder, while producing trees of similar Surface Area Heuristic (SAH) cost as a comparatively expensive binned SAH sweep builder.
Temporal changes in myocardial collagen, matrix metalloproteinases, and their tissue inhibitors in the left ventricular myocardium in experimental chronic mitral regurgitation in rodents
Authors: Corporan Daniella , Onohara Daisuke , Hernandez-Merlo Roberto , Sielicka Alicja , Padala Muralidhar
Published: August 2018

Mitral regurgitation (MR) imposes left ventricular volume overload, triggering rapid ventricular dilatation, increased myocardial compliance, and, ultimately, cardiac dysfunction. Breakdown of the extracellular matrix has been hypothesized to drive these rapid changes, partially from an imbalance in the matrix metalloproteinases (MMPs) and their tissue inhibitors [tissue inhibitors of metalloproteinase (TIMPs)]. In the present study, we developed a rat model of severe MR that mimics the human condition and investigated the temporal changes in extracellular matrix-related genes, collagen biosynthesis proteins, and proteolytic enzymes over a 20-wk period. Male Sprague-Dawley rats were anesthetized to a surgical plane with mechanical ventilation, and a thoracotomy was performed to expose the apex. Using transesophageal ultrasound guidance, a needle was inserted into the beating heart to perforate the anterior mitral leaflet and create severe MR. Animals were survived for 20 wk, with some animals terminated at 2, 10, and 20 wk for analysis of left ventricular tissue. A sham group that underwent the same surgery without mitral leaflet perforation and MR were used as controls. At 2 wk post-MR, increased collagen gene expression was measured, but protein levels of collagen did not corroborate this finding. In parallel, MMP-1-to-TIMP-4, MMP-2-to-TIMP-1, and MMP-2-to-TIMP-3 ratios were significantly elevated, indicating a proteolytic milieu in the myocardium, possibly causing collagen degradation. By 20 wk, many of the initial differences seen in the proteolytic ratios were not observed, with an increase in collagen compared with the 2-wk time point. Altogether, this data indicates that an imbalance in the MMP-to-TIMP ratio may occur early and potentially contribute to the early dilatation and compliance observed structurally.

NEW & NOTEWORTHY In this rodent model of severe mitral regurgitation that mimics the human condition, eccentric left ventricular dilatation occurred rapidly and persisted over the 20-wk period with parallel changes in myocardial collagen and matrix metalloproteinases that may drive the extracellular matrix breakdown.
Structural and functional cardiac profile after prolonged duration of mechanical unloading: potential implications for myocardial recovery
Authors: Castillero Estibaliz , Ali Ziad A. , Akashi Hirokazu , Giangreco Nicholas , Wang Catherine , Stöhr Eric J. , Ji Ruping , Zhang Xiaokan , Kheysin Nathaniel , Park Joo-Eun S. , Hegde Sheetal , Patel Sanatkumar , Stein Samantha , Cuenca Carlos , Leung Diana , Homma Shunichi , Tatonetti Nicholas P. , Topkara Veli K. , Takeda Koji , Colombo Paolo C. , Naka Yoshifumi , Sweeney H. Lee , Schulze P. Christian , George Isaac
Published: August 2018

Clinical and experimental studies have suggested that the duration of left ventricular assist device (LVAD) support may affect remodeling of the failing heart. We aimed to 1) characterize the changes in Ca2+/calmodulin-dependent protein kinase type-IIδ (CaMKIIδ), growth signaling, structural proteins, fibrosis, apoptosis, and gene expression before and after LVAD support and 2) assess whether the duration of support correlated with improvement or worsening of reverse remodeling. Left ventricular apex tissue and serum pairs were collected in patients with dilated cardiomyopathy ( n = 25, 23 men and 2 women) at LVAD implantation and after LVAD support at cardiac transplantation/LVAD explantation. Normal cardiac tissue was obtained from healthy hearts ( n = 4) and normal serum from age-matched control hearts ( n = 4). The duration of LVAD support ranged from 48 to 1,170 days (median duration: 270 days). LVAD support was associated with CaMKIIδ activation, increased nuclear myocyte enhancer factor 2, sustained histone deacetylase-4 phosphorylation, increased circulating and cardiac myostatin (MSTN) and MSTN signaling mediated by SMAD2, ongoing structural protein dysregulation and sustained fibrosis and apoptosis (all P < 0.05). Increased CaMKIIδ phosphorylation, nuclear myocyte enhancer factor 2, and cardiac MSTN significantly correlated with the duration of support. Phosphorylation of SMAD2 and apoptosis decreased with a shorter duration of LVAD support but increased with a longer duration of LVAD support. Further study is needed to define the optimal duration of LVAD support in patients with dilated cardiomyopathy.

NEW & NOTEWORTHY A long duration of left ventricular assist device support may be detrimental for myocardial recovery, based on myocardial tissue experiments in patients with prolonged support showing significantly worsened activation of Ca2+/calmodulin-dependent protein kinase-IIδ, increased nuclear myocyte enhancer factor 2, increased myostatin and its signaling by SMAD2, and apoptosis as well as sustained histone deacetylase-4 phosphorylation, structural protein dysregulation, and fibrosis.
Shear stress augments mitochondrial ATP generation that triggers ATP release and Ca2+signaling in vascular endothelial cells
Authors: Yamamoto Kimiko , Imamura Hiromi , Ando Joji
Published: August 2018

Vascular endothelial cells (ECs) sense and transduce hemodynamic shear stress into intracellular biochemical signals, and Ca2+signaling plays a critical role in this mechanotransduction, i.e., ECs release ATP in the caveolae in response to shear stress and, in turn, the released ATP activates P2 purinoceptors, which results in an influx into the cells of extracellular Ca2+. However, the mechanism by which the shear stress evokes ATP release remains unclear. Here, we demonstrated that cellular mitochondria play a critical role in this process. Cultured human pulmonary artery ECs were exposed to controlled levels of shear stress in a flow-loading device, and changes in the mitochondrial ATP levels were examined by real-time imaging using a fluorescence resonance energy transfer-based ATP biosensor. Immediately upon exposure of the cells to flow, mitochondrial ATP levels increased, which was both reversible and dependent on the intensity of shear stress. Inhibitors of the mitochondrial electron transport chain and ATP synthase as well as knockdown of caveolin-1, a major structural protein of the caveolae, abolished the shear stress-induced mitochondrial ATP generation, resulting in the loss of ATP release and influx of Ca2+into the cells. These results suggest the novel role of mitochondria in transducing shear stress into ATP generation: ATP generation leads to ATP release in the caveolae, triggering purinergic Ca2+signaling. Thus, exposure of ECs to shear stress seems to activate mitochondrial ATP generation through caveola- or caveolin-1-mediated mechanisms.

NEW & NOTEWORTHY The mechanism of how vascular endothelial cells sense shear stress generated by blood flow and transduce it into functional responses remains unclear. Real-time imaging of mitochondrial ATP demonstrated the novel role of endothelial mitochondria as mechanosignaling organelles that are able to transduce shear stress into ATP generation, triggering ATP release and purinoceptor-mediated Ca2+signaling within the cells.
Neuronal (pro)renin receptor regulates deoxycorticosterone-induced sodium intake
Authors: Trebak Fatima , Li Wencheng , Feng Yumei
Published: August 2018

Increased sodium appetite is a physiological response to sodium deficiency; however, it has also been implicated in disease conditions such as congestive heart failure, kidney failure, and salt-sensitive hypertension. The central nervous system is the major regulator of sodium appetite and intake behavior; however, the neural mechanisms underlying this behavior remain incompletely understood. Here, we investigated the involvement of the (pro)renin receptor (PRR), a component of the brain renin-angiotensin system, in the regulation of sodium intake in a neuron-specific PRR knockout (PRRKO) mouse model generated previously in our laboratory. Sodium intake following deoxycorticosterone (DOCA) stimulation was tested by assessing the preference of mice for 0.9% saline or regular water in single-animal metabolic cages. Blood pressure was monitored in conscious, freely moving mice by a telemetry system. We found that saline intake and total fluid intake were significantly reduced in PRRKO mice following DOCA treatment compared with that in wild-type (WT) mice, whereas regular water intake was similar between the genotypes. Sodium preference and total sodium intake were significantly reduced in PRRKO mice compared with WT mice. PRRKO mice also excreted less urine and urinary sodium compared with WT mice following DOCA treatment, whereas potassium excretion was similar between the two groups. Finally, we found that the sodium balance, calculated by subtracting urinary sodium excretion from sodium intake, was greater in WT mice than in PRRKO mice. Collectively, these findings suggest that the neuronal PRR plays a regulatory role in DOCA-induced sodium intake.
Antibacterial Activity of Chalcone and Dihydrochalcone Compounds from Uvaria chamae Roots against Multidrug-Resistant Bacteria
Authors: Koudokpon H. , Armstrong N. , Dougnon T. V. , Fah L. , Hounsa E. , Bankolé H. S. , Loko F. , Chabrière E. , Rolain J. M.
Published: August 2018

This study presents antimicrobial properties of Uvaria chamae roots, commonly used for the treatment of various infections in south Benin. Their constituents were extracted and then fractionated in order to isolate the active ingredients. Antimicrobial susceptibility tests were performed against several multidrug-resistant bacteria using the Mueller Hilton well agar diffusion method. Results showed that ethanol extracts were highly active against Gram-positive cocci. This activity was more extensive than that measured from conventional broad-spectrum antibiotics. Indeed, vancomycin-resistant enterococcus (VRE) and methicillin-resistant Staphylococcus aureus (MRSA) strains were all sensitive to this root extract. The aim of this study was to link the antimicrobial activity of the root to chemical structures. The ion mobility mass spectrometry analysis revealed for the first time the presence of ten chalcone and dihydrochalcone structures responsible for the antimicrobial activity of Uvaria chamae ethanol extracts. Two structures were described here for the first time in these roots. These findings confirm and justify the medical properties of these roots used as a traditional medicine.
Clinical Utility of Rapid Pathogen Identification for Detecting the Causative Organisms in Sepsis: A Single-Center Study in Korea
Authors: Kim Won-Young , Jeong Eun Suk , Kim Insu , Lee Kwangha
Published: August 2018

Purpose. The aim of this pre- and postintervention cohort study was evaluating how effectively rapid pathogen identification with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) detected the causative organisms in sepsis.Methods. All consecutive adult patients who had bacteremia within 72 h of intensive care unit admission and met ≥2 quick Sequential Organ Failure Assessment criteria at intensive care unit admission were analyzed. The patients whose microorganisms were identified via MALDI-TOF MS between March 2014 and February 2016 formed the postintervention group. The patients whose microorganisms were identified by using conventional methods between March 2011 and February 2013 formed the preintervention group.Results. The postintervention group (n=58) had a shorter mean time from blood draw to receiving the antimicrobial susceptibility results than the preintervention group (n=40) (90.2 ± 32.1 vs. 108.7 ± 43.1 h;p=0.02). The postintervention group was also more likely to have received active antimicrobial therapy by the time the susceptibility report became available (77% vs. 47%;p=0.005). Its 28-day mortality was also lower (40% vs. 70%;p=0.003). Univariate analysis showed that identification via MALDI-TOF MS (odds ratio, 0.28; 95% confidence interval, 0.12–0.66;p=0.004) and active therapy (odds ratio, 0.38; 95% confidence interval, 0.16–0.95;p=0.04) were associated with lower 28-day mortality.Conclusion. Rapid microorganism identification via MALDI-TOF MS followed by appropriate antimicrobial therapy may improve the clinical outcomes of patients with sepsis.
Superior Mesenteric Artery Syndrome: Clinical, Endoscopic, and Radiological Findings
Authors: Sinagra Emanuele , Raimondo Dario , Albano Domenico , Guarnotta Valentina , Blasco Melania , Testai Sergio , Marasà Marta , Mastrella Vincenzo , Alaimo Valerio , Bova Valentina , Albano Giovanni , Sorrentino Dario , Tomasello Giovanni , Cappello Francesco , Leone Angelo , Rossi Francesca , Galia Massimo , Lagalla Roberto , Midiri Federico , Morreale Gaetano Cristian , Amvrosiadis Georgios , Martorana Guido , Spampinato Marcello Giuseppe , Virgilio Vittorio , Midiri Massimo
Published: August 2018

Background. The superior mesenteric artery (SMA) syndrome is a rare entity presenting with upper gastrointestinal tract obstruction and weight loss. Studies to determine the optimal methods of diagnosis and treatment are required. Aims and Methods. This study aims at analyzing the clinical presentation, diagnosis, and management of SMA syndrome. Ten cases of SMA syndrome out of 2074 esophagogastroduodenoscopies were suspected. A contrast-enhanced computed tomography (CECT) scan was performed to confirm the diagnosis. After, a gastroenterologist and a nutritionist personalized the therapy. Furthermore, we compared the demographical, clinical, endoscopic, and radiological parameters of these cases with a control group consisting of 10 cases out of 2380 EGDS of initially suspected (but not radiologically confirmed) SMA over a follow-up 2-year period (2015-2016). Results. The prevalence of SMA syndrome was 0.005%. Median age and body mass index were 23.5 years and 21.5 kg/m2, respectively. Symptoms developed between 6 and 24 months. Median aortomesenteric angle and aorta-SMA distance were 22 and 6 mm, respectively. All patients improved on conservative treatment. In our series, a marked (>5 kg) weight loss (p=0.006) and a long-standing presentation (more than six months in 80% of patients) (p=0.002) are significantly related to a diagnosis of confirmed SMA syndrome at CECT after an endoscopic suspicion. A “resembling postprandial distress syndrome dyspepsia” presentation may be helpful to the endoscopist in suspecting a latent SMA syndrome (p=0.02). The narrowing of both the aortomesenteric angle (p=0.001) and the aortomesenteric distance (p<0.001) was significantly associated with the diagnosis of SMA after an endoscopic suspicion; however, the narrowing of the aortomesenteric distance seemed to be more accurate, rather than the narrowing of the aortomesenteric angle. Conclusion. SMA syndrome represents a diagnostic and therapeutic challenge. Our results show the following findings: the importance of the endoscopic suspicion of SMA syndrome; the preponderance of a long-standing and chronic onset; a female preponderance; the importance of the nutritional counseling for the treatment; no need of surgical intervention; and better diagnostic accuracy of the narrowing of the aorta-SMA distance. Larger prospective studies are needed to clarify the best diagnosis and management of the SMA syndrome.
Targeted Optical Imaging Agents in Cancer: Focus on Clinical Applications
Authors: Joshi Bishnu P. , Wang Thomas D.
Published: August 2018

Molecular imaging is an emerging strategy for in vivo visualization of cancer over time based on biological mechanisms of disease activity. Optical imaging methods offer a number of advantages for real-time cancer detection, particularly in the epithelium of hollow organs and ducts, by using a broad spectral range of light that spans from visible to near-infrared. Targeted ligands are being developed for improved molecular specificity. These platforms include small molecule, peptide, affibody, activatable probes, lectin, and antibody. Fluorescence labeling is used to provide high image contrast. This emerging methodology is clinically useful for early cancer detection by identifying and localizing suspicious lesions that may not otherwise be seen and serves as a guide for tissue biopsy and surgical resection. Visualizing molecular expression patterns may also be useful to determine the best choice of therapy and to monitor efficacy. A number of these imaging agents are overcoming key challenges for clinical translation and are being validated in vivo for a wide range of human cancers.
Interplay between Body Size Measures and Thyroid Cancer Aggressiveness: A Retrospective Analysis
Authors: de Melo Thaís Gomes , da Assumpção Ligia Vera Montali , Zantut-Wittmann Denise Engelbrecht
Published: August 2018

Considering controversial data about the relationship between body size and prognosis of differentiated thyroid cancer (DTC), the current study aimed to assess the influence of body weight, body mass index (BMI), and body surface area (BSA) on DTC. We conducted a retrospective analysis of patients’ records from the Thyroid Cancer Unit, assessing body size measures, clinical and laboratory prognostic factors, and disease evolution. 337 patients, aged 45.95 ± 13.04 years old, with BMI of 27.87 ± 5.13 kg/m2 and BSA of 1.74 ± 0.18 m2 were enrolled. After 9.5 ± 6.9 years of follow-up, 87.29% of patients were disease-free and 12.71% had persistent disease; no patient had deceased. Patients aged <45 years old with extrathyroidal invasion tumor had greater baseline body weight and BSA than those without extrathyroidal invasion (median 79.5 kg versus 67 kg and 1.85 m2 versus 1.74 m2). Women with poorly differentiated tumor and patients aged ≥45 years old with distant metastasis presented greater weight loss during follow-up compared to patients without such characteristics (median −2 kg versus +1.5 kg and −3 kg versus +1 kg, respectively). The relationship between body size and DTC evolution was not observed. In conclusion, higher weight and BSA were associated with a greater chance of extrathyroidal tumor invasion in younger patients. Specific subgroups of patients with aggressive disease presented higher weight loss. Young patients with higher BSA should be carefully treated due to possible worse prognosis related to increased incidence of extrathyroid invasion. Findings related to tumor aggressiveness and weight loss in specific groups deserve further mechanistic studies.
Meningococcal Pneumonia in a Young Healthy Male
Authors: Al Alawi Abdullah M.
Published: August 2018

A 23-year-old male presented to the emergency department with one-day history of right-sided pleuritic chest pain, haemoptysis, and fever. In the emergency department, the blood pressure was 140/60 mmHg, heart rate 89/min, body temperature 40°C, respiratory rates 20 breaths/min, and oxygen saturation 98% in room air. Physical examination revealed rales and bronchial breathing in the right infrascapular region. Laboratory analysis showed raised white blood cell counts and elevated inflammation markers. Chest X-ray showed right lower lobe consolidation. Intravenous(IV) ceftriaxone and doxycycline were started for the management of community-acquired pneumonia as per the local guideline. Later, on admission, blood culture was positive for Neisseria meningitidis (N. meningitidis). Ceftriaxone was continued for 4 days, and the patient was discharged while being on oral amoxicillin (1 gm TDS) for another 3 days. He remained well during the outpatient follow-up.
An Investigation on the Therapeutic Effect of Thymosinβ4 and Its Expression Levels in Streptozotocin-Induced Diabetic Mice
Authors: Cho Kyung Sook , Kim Dong-Jin , Shim Bomee , Kim Jung Yeon , Kang Jun Mo , Park Seon Hwa , Lee Sang-Ho , Yang Hyung-In , Kim Kyoung Soo
Published: August 2018

Thymosinβ4 (Tβ4) treatment was known to show the potential therapeutic effects on diabetic complications. This study was performed to determine if Tβ4 expression is changed in both serum and tissues under diabetic conditions and can be a serum biomarker. Type 1 diabetic mice were induced in C57/BL6J mice by intraperitoneal injection of streptozotocin (STZ) at a dose of 50 mg/kg body weight. The mice were sacrificed at 16 weeks after STZ injection. Tissues and plasmas were obtained to determine the expression levels of Tβ4 using ELISA, real time RT-PCR, and immunohistochemistry. The average serum glucose level was increased to approximately 400 mg/dL beginning 2 weeks after the five injections of STZ and lasting for at least 13 weeks until sacrifice. The plasma and tissue levels of Tβ4 in the age-matched control mice were not significantly different from those of the diabetic mice. In conclusion, the Tβ4 expression level in the plasmas and tissues of diabetic mice was not affected by diabetic conditions. It indirectly suggests that the therapeutic effect of Tβ4 on diabetic complications is due to its regenerative effects on damaged tissue but not to the changed expression level of Tβ4 in plasma and tissues of diabetes.
LA-GRU: Building Combined Intrusion Detection Model Based on Imbalanced Learning and Gated Recurrent Unit Neural Network
Authors: Yan Binghao , Han Guodong
Published: August 2018

The intrusion detection models (IDMs) based on machine learning play a vital role in the security protection of the network environment, and, by learning the characteristics of the network traffic, these IDMs can divide the network traffic into normal behavior or attack behavior automatically. However, existing IDMs cannot solve the imbalance of traffic distribution, while ignoring the temporal relationship within traffic, which result in the reduction of the detection performance of the IDM and increase the false alarm rate, especially for low-frequency attacks. So, in this paper, we propose a new combined IDM called LA-GRU based on a novel imbalanced learning method and gated recurrent unit (GRU) neural network. In the proposed model, a modified local adaptive synthetic minority oversampling technique (LA-SMOTE) algorithm is provided to handle imbalanced traffic, and then the GRU neural network based on deep learning theory is used to implement the anomaly detection of traffic. The experimental results evaluated on the NSL-KDD dataset confirm that, compared with the existing state-of-the-art IDMs, the proposed model not only obtains excellent overall detection performance with a low false alarm rate but also more effectively solves the learning problem of imbalanced traffic distribution.
Medical Image Retrieval Approach by Texture Features Fusion Based on Hausdorff Distance
Authors: Xiaoming Sun , Ning Zhang , Haibin Wu , Xiaoyang Yu , Xue Wu , Shuang Yu
Published: August 2018

Medical images play an important role in the hospital diagnosis and treatment, which include a lot of valuable medical information. Manually annotated viewing is obviously not effective in managing large amounts of medical imaging data. Hence it is an important task to establish an efficient and accurate medical image retrieval system. In this paper, a medical image retrieval approach based on Hausdorff distance combining Tamura texture features and wavelet transform algorithm is proposed. The combination of Tamura texture features and wavelet transform features can extract the texture features of medical images more effectively, and Hausdorff distance can reflect the overall similarity of medical image feature set. In this paper, 6 group experiments of brain MRI database and the lung CT database were conducted separately. Experiments show that the proposed approach has higher accuracy than a single feature texture algorithm and is also higher than the approach of Tamura texture features and wavelet transform features combined with Euclidean distance.
Calculation and Analysis of Microstate Related to Variation in Executed and Imagined Movement of Force of Hand Clenching
Authors: Fu Yunfa , Chen Jian , Xiong Xin
Published: August 2018

Objective. In order to investigate electroencephalogram (EEG) instantaneous activity states related to executed and imagined movement of force of hand clenching (grip force: 4 kg, 10 kg, and 16 kg), we utilized a microstate analysis in which the spatial topographic map of EEG behaves in a certain number of discrete and stable global brain states. Approach. Twenty subjects participated in EEG collection; the global field power of EEG and its local maximum were calculated and then clustered using cross validation and statistics; the 4 parameters of each microstate (duration, occurrence, time coverage, and amplitude) were calculated from the clustering results and statistically analyzed by analysis of variance (ANOVA); finally, the relationship between the microstate and frequency band was analyzed. Main Results. The experimental results showed that all microstates related to executed and imagined grip force tasks were clustered into 3 microstate classes (A, B, and C); these microstates generally transitioned from A to B and then from B to C. With the increase of the target value of executed and imagined grip force, the duration and time coverage of microstate B gradually decreased, while these parameters of microstate C gradually increased. The occurrence times of microstate B and C related to executed grip force were significantly more than those related to imagined grip force; furthermore, the amplitudes of these 3 microstates related to executed grip force were significantly greater than those related to imagined grip force. The correlation coefficients between the microstates and the frequency bands indicated that the microstates were correlated to mu rhythm and beta frequency bands, which are consistent with event-related desynchronization/synchronization (ERD/ERS) phenomena of sensorimotor rhythm. Significance. It is expected that this microstate analysis may be used as a new method for observing EEG instantaneous activity patterns related to variation in executed and imagined grip force and also for extracting EEG features related to these tasks. This study may lay a foundation for the application of executed and imagined grip force training for rehabilitation of hand movement disorders in patients with stroke in the future.
Amplification of Glyceronephosphate O-Acyltransferase and Recruitment of USP30 Stabilize DRP1 to Promote Hepatocarcinogenesis
Authors: Gu Li , Zhu Yahui , Lin Xi , Li Yajun , Cui Kaisa , Prochownik Edward V. , Li Youjun
Published: August 2018

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide, and the underlying pathophysiology of HCC is highly complex. In this study, we report that, in a bioinformatic screen of 2,783 genes encoding metabolic enzymes, GNPAT, which encodes the enzyme glyceronephosphate O-acyltransferase, is amplified, upregulated, and highly correlated with poor clinical outcome in human patients with HCC. High GNPAT expression in HCC was due to its amplification and transcriptional activation by the c-Myc/KDM1A complex. GNPAT compensated the oncogenic phenotypes in c-Myc–depleted HCC cells. Mechanistically, GNPAT recruited the enzyme USP30, which deubiquitylated and stabilized dynamin-related protein 1 (DRP1), thereby facilitating regulation of mitochondrial morphology, lipid metabolism, and hepatocarcinogenesis. Inhibition of GNPAT and DRP1 dramatically attenuated lipid metabolism and hepatocarcinogenesis. Furthermore, DRP1 mediated the oncogenic phenotypes driven by GNPAT. Taken together, these results indicate that GNPAT and USP30-mediated stabilization of DRP1 play a critical role in the development of HCC.

Significance: This study identifies and establishes the role of the enzyme GNPAT in liver cancer progression, which may serve as a potential therapeutic target for liver cancer. Cancer Res; 78(20); 5808–19. ©2018 AACR.
CSTF2-Induced Shortening of the RAC1 3′UTR Promotes the Pathogenesis of Urothelial Carcinoma of the Bladder
Authors: Chen Xin , Zhang Jia-Xing , Luo Jun-Hang , Wu Song , Yuan Gang-Jun , Ma Ning-Fang , Feng Yong , Cai Mu-Yan , Chen Ri-Xin , Lu Jun , Jiang Li-Juan , Chen Jie-Wei , Jin Xiao-Han , Liu Hai-Liang , Chen Wei , Guan Xin-Yuan , Kang Tie-Bang , Zhou Fang-Jian , Xie Dan
Published: August 2018

Shortening of the 3′ untranslated regions (3′UTR) of mRNA is an important mechanism for oncogene activation. However, 3′UTR alteration events, their pathologic functions, and underlying mechanisms in human urothelial carcinoma of the bladder (UCB) are not clear. Here, we combine RNA sequencing, bioinformatics, and clinical studies in two independent cohorts of patients with UCB to identify a novel RAC1 shorter 3′UTR isoform that is frequently expressed in UCB and is critical in the tumorigenesis and acquisition of a poor prognostic phenotype in patients. Short 3′UTR isoform of RAC1 substantially upregulated RAC1 expression by escaping from miRNA-targeted repression and played an essential oncogenic role in UCB pathogenesis. An important cleavage/polyadenylation factor, cleavage stimulation factor 2 (CSTF2), induced 3′UTR shortening of RAC1 in UCB by mediating slow transcriptional elongation at RAC1. Cotranscriptional recruitment of CSTF2 on the GUAAU motif at proximal polyadenylation site of RAC1 attenuated the recruitment of two transcription factors AFF1 and AFF4, causing the defects in elongation. CSTF2 regulated the tumorigenic functions of the shorter RAC1 isoform in UCB cells, enhancing cell proliferation, migration, and invasion. The combination of high expression of CSTF2 and high usage of RAC1 short-3′UTR isoform may be used as a powerful biomarker to predict poor prognosis in UCB. Our findings also suggest a CSTF2-regulated RAC1-3′UTR shortening program as an exploitable therapeutic strategy for patients with UCB.

Significance: These findings demonstrate that the short isoform of RAC1 is critical in UCB tumorigenesis and may have implications for developing new therapeutic strategies to treat this disease. Cancer Res; 78(20); 5848–62. ©2018 AACR.
Restoration of Endogenous Retrovirus Infectivity Impacts Mouse Cancer Models
Authors: Ottina Eleonora , Levy Prisca , Eksmond Urszula , Merkenschlager Julia , Young George R. , Roels Juliette , Stoye Jonathan P. , Tüting Thomas , Calado Dinis P. , Kassiotis George
Published: August 2018

Mouse models have been instrumental in establishing fundamental principles of cancer initiation and progression and continue to be invaluable in the discovery and further development of cancer therapies. Nevertheless, important aspects of human disease are imperfectly approximated in mouse models, notably the involvement of endogenous retroviruses (ERVs). Replication-defective ERVs, present in both humans and mice, may affect tumor development and antitumor immunity through mechanisms not involving infection. Here, we revealed an adverse effect of murine ERVs with restored infectivity on the behavior of mouse cancer models. In contrast to human cancer, where infectious ERVs have never been detected, we found that ERV infectivity was frequently restored in transplantable, as well as genetic, mouse cancer models. Such replication-competent, ERV-derived retroviruses were responsible for unusually high expression of retroviral nucleic acids and proteins in mouse cancers. Infectious ERV-derived retroviruses produced by mouse cancer cells could directly infect tumor-infiltrating host immune cells and fundamentally modified the host's immune defenses to cancer, as well as the outcome of immunotherapy. Therefore, infectious retroviruses, variably arising in mouse cancer models, but not in human cancer, have the potential to confound many immunologic studies and should be considered as a variable, if not altogether avoided. Cancer Immunol Res; 6(11); 1292–300. ©2018 AACR.
Rezidivierendes diabetisches Makulaödem: Was tun?
Authors: Santos Gonçalves Rita , Teixeira Carla , Coelho Pedro
Published: August 2018

Das diabetische Makulaödem (DMÖ) ist die häufigste Erblindungsursache bei Menschen im erwerbsfähigen Alter. In der vorliegenden Arbeit berichten wir über eine Patientin mit einem seit etwa 6 Jahren rezidivierenden DMÖ trotz verschiedener medizinischer und chirurgischer Therapien, das mit einer einzelnen intravitrealen Implantation eines lang wirksamen Fluocinolonacetonid-Implantats im rechten Auge erfolgreich behandelt wurde. Die Sehschärfe des betroffenen Auges betrug vor der Injektion 2/10 und die zentrale Makuladicke lag bei 488 µm. Nach der Behandlung mit dem intravitrealen Fluocinolonacetonid-haltigen Implantat zeigte sich am rechten Auge der Patientin eine Verbesserung der bestkorrigierten Sehschärfe auf 6/10 und ein Rückgang der zentralen Makuladicke auf 198 µm. Diese funktionellen und anatomischen Ergebnisse hatten über einen Nachbeobachtungszeitraum von mehr als 12 Monaten Bestand und es war ein akzeptables und beherrschbares Sicherheitsprofil zu beobachten. Die Ergebnisse zeigen, dass die intravitreale Implantation eines Fluocinolonacetonid-Implantats eine wirksame therapeutische Option bei DMÖ darstellt und bei der DMÖ-Behandlung in Erwägung gezogen werden sollte. Übersetzung aus Case Rep Ophthalmol 2017;8:465-474
Immunological and Quality-of-Life Profiles in Women with Breast Cancer: Complementary versus Conventional Care
Authors: Hamrin Elisabeth , Ernerudh Jan , Rosén Anders
Published: August 2018

Background: Previous studies showed that women with breast cancer treated in anthroposophic clinic versus conventional care had increased quality of life (QoL) parameters, fighting spirit, and anxiety coping. We have now analyzed immune and QoL factors in these 2 groups for possible differences during the first 6 months after admission, prompted by anthroposophic studies, including mistletoe extracts, showing beneficial immune system effects. Patients and Methods: Fourteen immunological variables, including leukocyte count, lymphocyte count, activated T cells (CD4+ and CD8+), NK cells, B cells, IL1β, IL6, IL10, and oxytocin, were longitudinally analyzed in both groups (n = 2 × 26). A panel of QoL parameters were analyzed using 3 different instruments. Statistical evaluation included that each patient was its own control. Results: Cytotoxic CD8+ T cell frequency (percent of lymphocytes analyzed by flow-cytometry) significantly decreased over time in the anthroposophic group versus the conventional group (repeated measures ANOVA, p = 0.05). No major differences were observed in other immunological parameters, whereas QoL variables, anxiety decreased and physical symptoms increased/improved significantly in the anthroposophic group (p = 0.04 and p = 0.05, respectively). Conclusion: Overall, women with breast cancer in anthroposophic or conventional therapy did not differ in their immune profiles over time, with exception of decreased cytotoxic T cells in the anthroposophic group. Improvement in physical symptoms along with less anxiety in this group may have influenced the brain-immune axis resulting in lower frequency of CD8+ T cells, a feature associated with less aggressive cancer stages. To evaluate whether this observation is associated with good or bad prognosis, further detailed analyses of memory and naïve CD8+ T cells at tumor site and in blood circulation are essential.
Spectral-Domain Optische Kohärenztomographie- Angiographie in der Diagnostik und Beurteilung von polypoidaler choroidaler Vaskulopathie
Authors: Treder Maximilian
Published: August 2018

Purpose: To compare the diagnostic ability of optical coher- ence tomography angiography (OCTA) with indocyanine green angiography (ICGA) in polypoidal choroidal vasculopathy (PCV). Methods: Retrospective review of 47 eyes with PCV imaged with ICGA and OCTA. For each eye, it was determined which imaging modality better delineated the PCV complex. The presence of a branching vascular network (BVN) and polyp(s) were noted. Results: PCV was better visualized with ICGA in 21 eyes (44.7%) and with OCTA in 9 eyes (19.2%). The results were comparable in 17 eyes (36.2%). Of the 44 eyes with BVN on ICGA, 41 eyes (93.2%) also showed BVN on OCTA. Of the 28 eyes with polyp(s) on ICGA, 22 eyes (78.6%) also showed polyp(s) on OCTA. Polyps were highflow lesions or faint low-flow dilations on OCTA. Conclusion: OCTA readily detects BVNs and can detect most polyps, but in many cases ICGA is better able to detect the PCV complex.
EGFR T790M Mutation in TKI-Naïve Clinical Samples: Frequency, Tissue Mosaicism, Predictive Value and Awareness on Artifacts
Authors: Lavdovskaia Elena D. , Iyevleva Aglaya G. , Sokolenko Anna P. , Mitiushkina Natalia V. , Preobrazhenskaya Elena V. , Tiurin Vladislav I. , Ivantsov Alexandr O. , Bizin Ilya V. , Stelmakh Liliya V. , Moiseyenko Fedor V. , Karaseva Nina A. , Orlov Sergey V. , Moiseyenko Vladimir M. , Korzhenevskaya Marina A. , Zaitsev Ivan A. , Kozak Andrey R. , Chistyakov Ivan V. , Akopov Andrey L. , Volkov Nikita M. , Togo Alexandr V. , Imyanitov Evgeny N.
Published: August 2018

Background: This study evaluated the distribution of epidermal growth factor receptor (EGFR) T790M mutations in treatment-naïve tumor and normal samples obtained from cancer patients. Methods: We utilized allele-specific PCR (AS-PCR), digital droplet PCR (ddPCR) and next generation sequencing (NGS) to detect EGFR T790M allele in several collections of tumor and normal human tissues. Results: AS-PCR analysis of treatment-naïve tumor samples revealed somatic T790M mutation in 3/394 (1%) non-small cell lung carcinomas (NSCLC) carrying the tyrosine kinase inhibitor (TKI)-sensitizing EGFR mutation, but in none of 334 NSCLC lacking EGFR exon 19 deletions (ex19del) or L858R substitutions and in none of 235 non-lung tumors. Use of highly sensitive and quantitative assays, such as ddPCR and NGS, produced a high number of T790M-specific signals even in presumably T790M-negative DNA specimens. This background noise was evidently higher in degraded DNA isolated from formalin-fixed paraffin-embedded tissues as compared to high molecular weight DNA. A combination of AS-PCR, ddPCR and NGS revealed mosaic EGFR T790M allele in 2/68 (3%) NSCLC treated with the first-generation TKI. Both these tumors produced evident and durable response to gefitinib. Conclusion: Detection of mosaic EGFR T790M mutation in treatment-naïve samples may be compromised by yet unresolved technical issues and may have limited clinical value.
A Patient with Third Corpus Cavernosum, Severe Penile Ventral Deviation and Partial Peno-scrotal Transposition: First Worldwide Report
Authors: Hosseini Jalil , Rahavian Amirhossein , Soleimanzadeh Farzen
Published: August 2018

Chordee – a variety of penile deviations with or without hypospadias – is a relatively prevalent condition. This is quite a unique kind of chordee and peno-scrotal transposition with a considerable tension effect on the ventral side of the penis due to an additional corpus cavernosum, and this condition is confirmed by histopathologic evaluation. We treated the patient by wide resection of the third corpus cavernosum with scrotoplasty and postponed the urethroplasty for a second stage repair. It was interesting that we did not come across a similar report as a result of our deep literature search.
Psychometric Validation of the Czech Version of the Quality of Life – Alzheimer’s Disease Scale in Patients with Early-Stage Dementia
Authors: Kisvetrová Helena , Školoudík David , Herzig Roman , Vališ Martin , Jurašková Božena , Krulová Petra , Langová Kateřina , Bermellová Jana , Yamada Yukari
Published: August 2018

Background/Aims: The aim of this study was to perform a psychometric validation of the Czech version of the Quality of Life – Alzheimer’s Disease scale (QoL-AD) for patients with early-stage dementia. Methods: The sample included 212 patient-proxy pairs. For convergent validity, the Czech version of the Bristol Activities of Daily Living Scale (BADLS-CZ), the Short Physical Performance Battery (SPPB), and the Geriatric Depression Scale (GDS) were used. Results: The reliability of the QoL-AD for patients and caregivers was good (Cronbach’s α = 0.85, ICC = 0.25–0.54). A positive correlation existed between the QoL-AD and the SPPB, and negative correlations existed between the QoL-AD and the BADLS-CZ as well as between the QoL-AD and the GDS. Factor analysis resulted in a three-factor solution (physical and mental health, family life, and social security). Conclusion: The Czech version of the QoL-AD has good psychometric properties in compliance with international recommendations.