bluuebunny/crossref_metadata_2025 huggingface dataset:
Acquiring spatially varying appearance of printed holographic surfaces
Authors: Toisoul Antoine , Dhillon Daljit Singh , Ghosh Abhijeet
Published: November 2018

We present two novel and complimentary approaches to measure diffraction effects in commonly found planar spatially varying holographic surfaces. Such surfaces are increasingly found in various decorative materials such as gift bags, holographic papers, clothing and security holograms, and produce impressive visual effects that have not been previously acquired for realistic rendering. Such holographic surfaces are usually manufactured with one dimensional diffraction gratings that are varying in periodicity and orientation over an entire sample in order to produce a wide range of diffraction effects such as gradients and kinematic (rotational) effects. Our proposed methods estimate these two parameters and allow an accurate reproduction of these effects in real-time. The first method simply uses a point light source to recover both the grating periodicity and orientation in the case of regular and stochastic textures. Under the assumption that the sample is made of the same repeated diffractive tile, good results can be obtained using just one to five photographs on a wide range of samples. The second method is based on polarization imaging and enables an independent high resolution measurement of the grating orientation and relative periodicity at each surface point. The method requires a minimum of four photographs for accurate results, does not assume repetition of an exemplar tile, and can even reveal minor fabrication defects. We present point light source renderings with both approaches that qualitatively match photographs, as well as real-time renderings under complex environmental illumination.
Shading atlas streaming
Authors: Mueller Joerg H. , Voglreiter Philip , Dokter Mark , Neff Thomas , Makar Mina , Steinberger Markus , Schmalstieg Dieter
Published: November 2018

Streaming high quality rendering for virtual reality applications requires minimizing perceived latency. We introduce Shading Atlas Streaming (SAS), a novel object-space rendering framework suitable for streaming virtual reality content. SAS decouples server-side shading from client-side rendering, allowing the client to perform framerate upsampling and latency compensation autonomously for short periods of time. The shading information created by the server in object space is temporally coherent and can be efficiently compressed using standard MPEG encoding. Our results show that SAS compares favorably to previous methods for remote image-based rendering in terms of image quality and network bandwidth efficiency. SAS allows highly efficient parallel allocation in a virtualized-texture-like memory hierarchy, solving a common efficiency problem of object-space shading. With SAS, untethered virtual reality headsets can benefit from high quality rendering without paying in increased latency.
Hybrid grains
Authors: Yue Yonghao , Smith Breannan , Chen Peter Yichen , Chantharayukhonthorn Maytee , Kamrin Ken , Grinspun Eitan
Published: November 2018

We propose a technique to simulate granular materials that exploits the dual strengths of discrete and continuum treatments. Discrete element simulations provide unmatched levels of detail and generality, but prove excessively costly when applied to large scale systems. Continuum approaches are computationally tractable, but limited in applicability due to built-in modeling assumptions; e.g., models suitable for granular flows typically fail to capture clogging, bouncing and ballistic motion. In our hybrid approach, an oracle dynamically partitions the domain into continuum regions where safe, and discrete regions where necessary. The domains overlap along transition zones, where a Lagrangian dynamics mass-splitting coupling principle enforces agreement between the two simulation states. Enrichment and homogenization operations allow the partitions to evolve over time. This approach accurately and efficiently simulates scenarios that previously required an entirely discrete treatment.
Deep inertial poser
Authors: Huang Yinghao , Kaufmann Manuel , Aksan Emre , Black Michael J. , Hilliges Otmar , Pons-Moll Gerard
Published: November 2018

We demonstrate a novel deep neural network capable of reconstructing human full body pose in real-time from 6 Inertial Measurement Units (IMUs) worn on the user's body. In doing so, we address several difficult challenges. First, the problem is severely under-constrained as multiple pose parameters produce the same IMU orientations. Second, capturing IMU data in conjunction with ground-truth poses is expensive and difficult to do in many target application scenarios (e.g., outdoors). Third, modeling temporal dependencies through non-linear optimization has proven effective in prior work but makes real-time prediction infeasible. To address this important limitation, we learn the temporal pose priors using deep learning. To learn from sufficient data, we synthesize IMU data from motion capture datasets. A bi-directional RNN architecture leverages past and future information that is available at training time. At test time, we deploy the network in a sliding window fashion, retaining real time capabilities. To evaluate our method, we recorded DIP-IMU, a dataset consisting of 10 subjects wearing 17 IMUs for validation in 64 sequences with 330 000 time instants; this constitutes the largest IMU dataset publicly available. We quantitatively evaluate our approach on multiple datasets and show results from a real-time implementation. DIP-IMU and the code are available for research purposes.
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Targeting Cancer at the Intersection of Signaling and Epigenetics
Authors: Guerra Stephanie , Cichowski Karen
Published: November 2018

While mutations resulting in the chronic activation of signaling pathways drive human cancer, the epigenetic state of a cell ultimately dictates the biological response to any given oncogenic signal. Moreover, large-scale genomic sequencing efforts have now identified a plethora of mutations in chromatin regulatory genes in human tumors, which can amplify, modify, or complement traditional oncogenic events. Nevertheless, the co-occurrence of oncogenic and epigenetic defects appears to create novel therapeutic vulnerabilities, which can be targeted by specific drug combinations. Here we discuss general mechanisms by which oncogenic and epigenetic alterations cooperate in human cancer and synthesize the field's early efforts in developing promising therapeutic combinations. Collectively, these studies reveal common themes underlying potential chemical synthetic lethal interactions and support both the expansion and refinement of this type of therapeutic approach.
Cell Death in the Lung: The Apoptosis–Necroptosis Axis
Authors: Sauler Maor , Bazan Isabel S. , Lee Patty J.
Published: November 2018

Regulated cell death is a major mechanism to eliminate damaged, infected, or superfluous cells. Previously, apoptosis was thought to be the only regulated cell death mechanism; however, new modalities of caspase-independent regulated cell death have been identified, including necroptosis, pyroptosis, and autophagic cell death. As an understanding of the cellular mechanisms that mediate regulated cell death continues to grow, there is increasing evidence that these pathways are implicated in the pathogenesis of many pulmonary disorders. This review summarizes our understanding of regulated cell death as it pertains to the pathogenesis of chronic obstructive pulmonary disease, asthma, idiopathic pulmonary fibrosis, acute respiratory distress syndrome, and pulmonary arterial hypertension.
Blocking the REDD1/TXNIP axis ameliorates LPS-induced vascular endothelial cell injury through repressing oxidative stress and apoptosis
Authors: Hou Xuhui , Yang Songbai , Yin Jian
Published: November 2018

The aim of the present study was to investigate the potential role of regulated in development and DNA damage response 1 (REDD1) in LPS-induced vascular endothelial injury by using human umbilical vein endothelial cells (HUVECs). We observed that REDD1 expression was apparently elevated in HUVECs after exposure to LPS. Additionally, elimination of REDD1 strikingly attenuated the secretion of the proinflammatory cytokines TNF-α, IL-6, IL-1β, and monocyte chemotactic protein-1 and the endothelial cell adhesion markers ICAM-1 and VCAM-1 that was induced by LPS stimulation. Subsequently, knockdown of REDD1 augmented cell viability but ameliorated lactate dehydrogenase release in HUVECs stimulated with LPS. Meanwhile, depletion of REDD1 effectively restricted LPS-induced HUVEC apoptosis, as exemplified by reduced DNA fragmentation, and it also elevated antiapoptotic Bcl-2 protein, concomitant with reduced levels of proapoptotic proteins Bax and cleaved caspase-3. Furthermore, repression of REDD1 remarkably alleviated LPS-triggered intracellular reactive oxygen species generation accompanied by decreased malondialdehyde content and increased the activity of the endogenous antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase. Most important, depletion of REDD1 protected HUVECs against inflammation-mediated apoptosis and oxidative damage partly through thioredoxin-interacting protein (TXNIP). Collectively, these findings indicate that blocking the REDD1/TXNIP axis repressed the inflammation-mediated vascular injury process, which may be closely related to oxidative stress and apoptosis in HUVECs, implying that the REDD1/TXNIP axis may be a new target for preventing the endothelial cell injury process.
TRPA1: a molecular view
Authors: Meents Jannis E. , Ciotu Cosmin I. , Fischer Michael J. M.
Published: November 2018

The transient receptor potential ankyrin 1 (TRPA1) ion channel is expressed in pain-sensing neurons and other tissues and has become a major target in the development of novel pharmaceuticals. A remarkable feature of the channel is its long list of activators, many of which we are exposed to in daily life. Many of these agonists induce pain and inflammation, making TRPA1 a major target for anti-inflammatory and analgesic therapies. Studies in human patients and in experimental animals have confirmed an important role for TRPA1 in a number of pain conditions. Over the recent years, much progress has been made in elucidating the molecular structure of TRPA1 and in discovering binding sites and modulatory sites of the channel. Because the list of published mutations and important molecular sites is steadily growing and because it has become difficult to see the forest for the trees, this review aims at summarizing the current knowledge about TRPA1, with a special focus on the molecular structure and the known binding or gating sites of the channel.
Evaluation of Antifingerprint Properties of Plastic Surfaces Used in Automotive Components
Authors: Luda M. P. , Li Pira N. , Trevisan D. , Pau V.
Published: November 2018

The antifingerprint properties of a range of surfaces produced with different technologies (in-mould decoration, in-mould labeling, and painted) were objectively evaluated by depositing on them in standard conditions an artificial fingerprint for direct determination of its visibility. The artificial fingerprint behaves similarly to the real human fingerprints. A classification method is then proposed to classify surfaces on the base of antifingerprint properties by measuring the roughness profile (Ra) and calculating the % variation of gloss (GU 20 and 60°), haze, luminance (L), and diffuse reflectance (R) values after fingerprint deposition. This approach provides an objective and quantitative test method to determine visual antifingerprint properties of coated surfaces, instead of the “easy-to-clean” properties commonly evaluated. The data acquired provides a design guideline for fabricating visually fingerprint-free surfaces by controlling roughness, texture, color, and transparency of surfaces, with the aim of optically masking fingerprints.
Characterization of Flow Interactions in a One-Stage Shrouded Axial Turbine
Authors: Ghenaiet Adel
Published: November 2018

The aim of this paper is to characterize the steady and unsteady flow interactions through a one-stage high-pressure (hp) shrouded axial turbine with a tip cavity. The vane and blade passages were reduced based on the scaling technique, and the domains of compromise were identified and used in the flow computations. The flow structures are mainly in the form of vanes’ wakes and vortices inducing circumferential distortions and interacting with the rotor blades. Fast Fourier transform (FFT) of the static pressure fluctuations recorded at the selected points and lines through the turbine stage revealed high unsteadiness characterized by a space-time periodic behavior, and described by the double Fourier decomposition. The vane-rotor interactions (VRI) appeared in the form of a potential flow field about the blades extending both upstream and downstream and correlated with the rotational speed. The other sources of unsteadiness are induced in the rotor blades by the vanes’ wakes and referred to as the wake interaction, in addition to the secondary flows and vortices in endwall regions.
Improvement of Solar Cell Characteristics Using PbS Quantum Dot Superlattice Prepared by Sedimentation
Authors: Mukai Kohki , Ishida Yoshikazu
Published: November 2018

We report the characteristics of organic solar cells on Si substrates using quantum dot superlattices (QDSLs) prepared by sedimentation. When colloidal quantum dots (QDs) are deposited on a substrate in a solvent, they are closely packed and form multiple grains in a film. We found that the PbS QD grains grew into a large superlattice when the deposition proceeded for a long period of time. A solar cell was fabricated using the QD superlattice film as an absorbing layer. When the deposition was slow, the short-circuit current density of the solar cell doubled compared with that of the rapid deposition case. Simulations based on the superposition model suggest that the superlattice formation process is responsible for the observed change in the cell characteristics.
Novel Curcumin C66 That Protects Diabetes‐Induced Aortic Damage Was Associated with Suppressing JNK2 and Upregulating Nrf2 Expression and Function
Authors: Li Cheng , Miao Xiao , Wang Shudong , Adhikari Binay Kumar , Wang Xin , Sun Jian , Liu Quan , Tong Qian , Wang Yonggang
Published: November 2018

Diabetes‐related cardiovascular diseases are leading causes of the mortality worldwide. Our previous study has explored the protective effect of curcumin analogue C66 on diabetes‐induced pathogenic changes of the aorta. In the present study, we sought to reveal the underlying protective mechanisms of C66. Diabetes was induced in male WT and JNK2−/− mice with a single intraperitoneal injection of streptozotocin. Diabetic mice and age‐matched nondiabetic mice were randomly treated with either vehicle (WT, WT DM, JNK2−/−, and JNK2−/−DM) or C66 (WT + C66, WT DM + C66, JNK2−/− + C66, and JNK2−/−DM + C66) for three months. Aortic oxidative stress, cell apoptosis, inflammatory changes, fibrosis, and Nrf2 expression and function were assessed by immunohistochemical staining for the protein level and real‐time PCR method for mRNA level. The results suggested that either C66 treatment or JNK2 deletion can reverse diabetes‐induced aortic oxidative stress, cell apoptosis, inflammation, and fibrosis. Nrf2 was also found to be activated either by C66 or JNK2 deletion. However, C66 had no extra effect on diabetic aortic damage or Nrf2 activation without JNK2. These results suggest that diabetes‐induced pathological changes in the aorta can be protected by C66 mainly via inhibition of JNK2 and accompanied by the upregulation of Nrf2 expression and function.
A Case Report of High-Grade Endometrial Stromal Sarcoma: A Rare Cause of Abnormal Uterine Bleeding in a Young Woman
Authors: Eamudomkarn Nuntasiri , Itarat Yuwadee , Kleebkaow Pilaiwan , Kietpeerakool Chumnan
Published: November 2018

High-grade endometrial stromal sarcoma (HG-ESS) is a rare clinical entity, particularly among young women, and only few cases have been reported in the literature. Herein, we describe the case of a 21-year-old woman who presented with a four-month history of excessive bleeding per vagina. Endometrial curettage and cervical biopsy revealed a malignant round cell tumor suggestive of metastatic sarcoma of uterine origin. Computed tomography of the abdominopelvic region showed an enlarged uterus with diffused thickening throughout the entire endometrial cavity. Intraabdominal lymphadenopathy and ascites in the pelvic cavity were noted. The patient underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, resections of the enlarged pelvic nodes, omentectomy, and biopsy of the peritoneal nodules in the cul-de-sac. Histological examination revealed a tumor with a permeative growth pattern composed of uniformly high-grade round cells with brisk mitotic activity and extensive lymphovascular space invasion. Sections of the pelvic lymph nodes on both sides and the peritoneal nodule revealed multiple metastatic foci. Immunohistochemical studies showed positive diffuse staining for vimentin, CD 10, and cyclin D1. The pathological diagnosis was HG-ESS stage IIIC. The patient experienced rapid progression of the disease while receiving adjuvant treatment and succumbed eight months after the operation. HG-ESS is a rare cause of AUB in adolescents and young women but should be considered in the differential diagnosis.
Guanylate-Binding Protein 1 Promotes Migration and Invasion of Human Periodontal Ligament Stem Cells
Authors: Bai Shi , Chen Tao , Deng Xia
Published: November 2018

Mesenchymal stem/stromal cells (MSCs) are capable of migrating to sites of injury and inflammation in response to various cytokines to improve tissue repair. Previous studies have shown interferon-gamma (IFN-γ) promoted migration of the V54/2 cell line and dental pulp stem cells (DPSCs), but the underlying mechanisms remain largely unknown. In this study, we found IFN-γinduced migration and invasion of periodontal ligament stem cells (PDLSCs) in a dose-dependent mannerin vitro. While knockdown of guanylate-binding protein 1 (GBP1) suppressed IFN-γ-induced migration and invasion, ectopic expression of GBP1 potentiated IFN-γ-induced migration and invasion of PDLSCs. Furthermore, we demonstrated GBP1 was required for IFN-γ-induced processing of matrix metallopeptidase 2 (MMP2) in PDLSCs. Our findings indicate that GBP1 promotes IFN-γ-induced migration and invasion of PDLSCs by MMP2, and GBP1 may serve as a new target to facilitate MSC homing and migration.
Recurrent Desmoid Tumor of the Neck: A Case Report of a Benign Disease with Aggressive Behavior
Authors: Klonaris Dionisios A. , Karatzanis Alexander D. , Velegrakis Stylianos G. , Lagoudakis Eleni D. , Prokopakis Emmanuel P. , Velegrakis George A.
Published: November 2018

We present a case of a desmoid tumor recurrence in a patient with a history of a resected desmoid tumor of the right neck area with free surgical margins six months earlier. The neoplasm was found to invade the parapharyngeal space, and wide excision was performed including most of the sternocleidomastoid muscle (SCM), the thrombosed internal jugular vein (IJV), and the infiltrated spinal accessory nerve (SAN). The histopathologic findings displayed free microscopic margins, with close margins at the site of the parapharyngeal space extension. After 3 months, there was no sign of tumor recurrence. After 6 months, local tumor recurrence was identified on clinical examination and imaging. The decision of the Oncology Board was further treatment with radiotherapy (RT). Response to treatment was satisfactory, and the patient was on close follow-up for twelve months. Desmoid tumors are very rare benign neoplasms of mesenchymal origin with negligible mortality but high morbidity, due to their high recurrence rates, local tissue infiltration, and unpredictable disease course and response to treatment. No universally acceptable treatment protocols have been introduced to date. Appropriate patient counseling and close follow-up are warranted in all cases.
Height-Diameter Modeling ofCinnamomum tamalaGrown in Natural Forest in Mid-Hill of Nepal
Authors: Subedi Mukti Ram , Oli Bishwa Nath , Shrestha Surendra , Chhin Sophan
Published: November 2018

Tree height (H) and diameter at breast height (D) are key variables to calculate tree volume and biomass. We developed a height-diameter (H-D) model forCinnamomum tamalaby evaluating 18 nonlinear models. Akaike Information Criterion (AIC), Bayesian Information Criterion (BIC), Root Mean Square Error (RMSE), mean bias, Mean Absolute Error (MAE), graphical appearance, and biological logic were the criteria used to evaluate the predictive performance of the models. Gompertz model (M14) performed the best for predicting the total height ofC. tamalatrees with the least RMSE (1.742 m), mean bias (0.012 m), and MAE (1.342 m) and satisfied model assumptions and biological logic. Validation data ranked the Gompertz model as the best model with RMSE (1.546 m), mean bias (-0.106 m), and MAE (1.149 m). Despite the consistent performance of the Gompertz model, it tended to underestimate the height prediction for taller (dominant crown class) and larger trees. Further work on refitting and validation of the proposed model with data from a larger geographic area, wider-ranging sites, and stand conditions is recommended.
Some Similarity Measures of Neutrosophic Sets Based on the Euclidean Distance and Their Application in Medical Diagnosis
Authors: Liu Donghai , Liu Guangyan , Liu Zaiming
Published: November 2018

Similarity measure is an important tool in multiple criteria decision-making problems, which can be used to measure the difference between the alternatives. In this paper, some new similarity measures of single-valued neutrosophic sets (SVNSs) and interval-valued neutrosophic sets (IVNSs) are defined based on the Euclidean distance measure, respectively, and the proposed similarity measures satisfy the axiom of the similarity measure. Furthermore, we apply the proposed similarity measures to medical diagnosis decision problem; the numerical example is used to illustrate the feasibility and effectiveness of the proposed similarity measures of SVNSs and IVNSs, which are then compared to other existing similarity measures.
Working Mechanism of Nonresonance Friction in Driving Linear Piezoelectric Motors with Rigid Shaking Beam
Authors: Chen Xifu , Lu Qian , Huang Weiqing , Wang Yin
Published: November 2018

A kind of nonresonance shaking beam motors is proposed with the advantages of simple structure, easy processing, and low cost due to its wide application prospects in precision positioning technology and precision instruments. The normal vibration model between the stator and slider is divided into contact and noncontact types to investigate the nonresonance friction drive principle for this motor. The microscopic kinematics model for stator protruding section and the interface friction model for motor systems during both operating stages are established. Accordingly, the trajectory of the stator protruding section consists of two different elliptical motions, which differ from those of resonance-type motors. The output characteristic of the nonresonance shaking beam motor is proposed under steady working conditions with reference to the research method of standing-wave-type ultrasonic motors. Numerical analysis is used to simulate the normal vibration and mechanical output characteristics of the motor. Experimental and theoretical data fitting validates the numerical analysis results and allows the future optimization of nonresonance-type motors.
Enhancement of the Thermomechanical Properties of a Fly Ash- and Carbon Black-Filled Polyvinyl Chloride Composite by Using Epoxidized Soybean Oil as a Secondary Bioplasticizer
Authors: Nguyen Toan Duy , Nguyen Chinh Thuy , Tran Van Thanh Thi , Nguyen Giang Vu , Le Hai Viet , Tran Lam Dai , Bach Giang Long , Thai Hoang
Published: November 2018

Plasticized polyvinyl chloride (PVC) was fabricated using epoxidized soybean oil (ESBO) as a secondary bioplasticizer with dioctyl phthalate (DOP). The PVC/MFA/CB composites were prepared by melt mixing of the plasticized PVC with modified fly ash (MFA), carbon black N330 (CB), and polychloroprene (CR) in a Haake Rheomix mixer using a rotation speed of 50 rpm at 175°C for 6 min and then compressed by Toyoseiki pressure machine under 15 MPa. The effect of ESBO content on morphology, melt viscosity, tensile properties, and flame retardancy of PVC/MFA/CB composites was investigated. The obtained results showed that the incorporation of ESBO has significantly enhanced the processing ability, Young’s modulus, tensile strength, and elongation at break of the PVC/MFA/CB composites. The torque of PVC/MFA/CB composites was increased to approximately 12% when 50 wt% of DOP was replaced by ESBO. When ESBO was 20 wt% in comparison with DOP weight, the elongation at break, tensile strength, and Young’s modulus of the composites were increased to 48%, 24%, and 4.5%, respectively. Correspondingly, thermogravimetric analysis results confirmed that ESBO had improved the thermostability of the PVC composites. The ESBO have potential as a secondary bioplasticizer replacement material for DOP owing to their better thermomechanical stability.
Methods for Extraction of Muscle Proteins from Meat and Fish Using Denaturing and Nondenaturing Solutions
Authors: Malva Antonella della , Albenzio Marzia , Santillo Antonella , Russo Donatella , Figliola Lucia , Caroprese Mariangela , Marino Rosaria
Published: November 2018

The objective of the present study was to test two extraction methods including solutions with different ionic strengths on the extraction and separation of the myofibrillar proteins from meat and fish muscles of different species. Meat samples from longissimus thoracis muscle of beef and lamb, pectoralis major muscle of chicken, and dorsal white muscle of fish from sole (Solea solea), European hake (Merluccius merluccius), and sea bass (Dicentrarchus labrax) were analyzed. The extraction method using nondenaturing solution led to a major extraction of high molecular-weight proteins as myosin heavy chain, α-actinin, and desmin; on the contrary, the denaturing method provided a good protein extractability of proteins and fragments with low molecular-weight as actin, troponin-T, tropomyosin, and myosin light chain 1 and 2 proteins for the most meat and fish samples. The nondenaturing extraction method showed several advantages resulting in time and labour saving and in minimizing the use of toxic and polluting agents.
Force Analysis and Evaluation of a Pelvic Support Walking Robot with Joint Compliance
Authors: Ji Jiancheng , Guo Shuai , Xi Fengfeng (Jeff)
Published: November 2018

The force analysis of a pelvic support walking robot with joint compliance is discussed in this paper. During gait training, pelvic motions of hemiplegic patients may be excessively large or out of control; however, restriction of pelvic motions is not likely to facilitate successful rehabilitation. A robot-assisted pelvic balance trainer (RAPBT) is proposed to help patients control the range of motion via force field, and force analysis is necessary for the control of the compliant joints. Thus, kinematic model and static model are developed to derive the Jacobian and the relation between the interaction forces and the pelvic movements, respectively. Since the joint compliance is realized through a nontorsional spring, a conventional (linear) Jacobian method and a piecewise linear method are derived to relate the interaction forces with the pelvis movements. Three preliminary experiments are carried out to evaluate the effectiveness of the proposed methods and the feasibility of the RAPBT. The experiment results indicate that the piecewise linear method is effective in the calculation of the interaction forces. Gait with pelvic brace strongly resembles free overground walking and partly decreases motion range via force field. The findings of this research demonstrate that the pelvic brace with joint compliance may provide effective interventions.
Racial Disparities in the Receipt of Guideline Care and Cancer Deaths for Women with Ovarian Cancer
Authors: Cronin Kathleen A. , Howlader Nadia , Stevens Jennifer L. , Trimble Edward L. , Harlan Linda C. , Warren Joan L.
Published: November 2018

Background:

Black women with ovarian cancer experience worse survival than white women. Receipt of guideline care improves survival, yet care may vary by race. We assessed rates of guideline care and role of guideline treatment on survival disparities.

Methods:

This retrospective cohort analysis used the NCI's Patterns of Care data for women diagnosed with ovarian cancer, 2002 and 2011 (weighted n = 3,999), with follow-up through December 12, 2014. Logistic regression included patient characteristics, insurance, and gynecologic oncologist (GO) consultation to produce adjusted standardized percentages of women receiving guideline treatment by race. Cox proportional hazards analysis assessed risk of ovarian cancer death.

Results:

Guideline care was significantly lower for black women compared with white women (adjusted 27.5% vs. 34.1%). Increased receipt of guideline care was associated with GO consultation, younger ages, stage, and insurance. Rates of GO consultation were comparable for black and white women, approximately 60%. Black women were more likely to receive no surgery or no chemotherapy if they did not consult a GO. The unadjusted death risk was significantly higher in black women (HR = 1.33). After adjusting for receipt of guideline care and other factors, black and white women had similar risk of death (HR = 1.05).

Conclusions:

Race was not associated with risk of death when guideline care was included in multivariate survival models. However, black patients received less guideline care. GO consultation significantly increased receipt of guideline care.

Impact:

Research is needed to understand treatment perspectives for black patients and their providers to increase the receipt of guideline care and reduce survival disparities.
Evaluation of Emergent Mutations in Circulating Cell-Free DNA and Clinical Outcomes in Patients with Metastatic Colorectal Cancer Treated with Panitumumab in the ASPECCT Study
Authors: Peeters Marc , Price Timothy , Boedigheimer Michael , Kim Tae Won , Ruff Paul , Gibbs Peter , Thomas Anne , Demonty Gaston , Hool Kristina , Ang Agnes
Published: November 2018

Purpose:

Mutations in EGFR pathway genes are poor prognostic indicators in patients with metastatic colorectal cancer. Plasma analysis of cell-free DNA is a minimally invasive and highly sensitive method to detect somatic mutations in tumors.

Experimental Design:

Plasma samples collected from panitumumab-treated patients in the ASPECCT study at baseline and safety follow-up (SFU) were analyzed by a next-generation sequencing–based approach for extended RAS mutant allele frequency as a continuous variable and their association with clinical outcomes and the mutational prevalence of 63 cancer-related genes. The correlation between patient outcome and baseline mutational status of EGFR pathway genes was also examined.

Results:

Overall, 261 patients in the panitumumab arm had evaluable plasma samples. Patients with a higher RAS mutant allele frequency at baseline had worse clinical outcomes than those with a lower frequency (P < 0.001, Cox PH model); however, RAS mutations did not necessarily preclude patients from deriving benefits. The objective response rate (complete or partial response) was 10.8% for patients with baseline RAS mutations and 21.7% for those with BRAF mutations. The 63-gene panel analysis revealed an increase in tumor mutational burden from baseline to SFU (P < 0.001, Wilcoxon signed rank test). Baseline mutations in EGFR pathway genes, when analyzed both categorically and continuously, were associated with shorter survival.

Conclusions:

When mutations in EGFR pathway genes were analyzed continuously, higher mutant allele frequency correlated with poorer outcomes. However, extended RAS mutation, by itself, did not preclude clinical responses to panitumumab in a monotherapy setting.
On the Enigma of the Human Neurenteric Canal
Authors: Rulle Alexander , Tsikolia Nikoloz , de Bakker Bernadette , Drummer Charis , Behr Rüdiger , Viebahn Christoph
Published: November 2018

Existence and biomedical relevance of the neurenteric canal, a transient midline structure during early neurulation in the human embryo, have been controversially discussed for more than a century by embryologists and clinicians alike. In this study, the authors address the long-standing enigma by high-resolution histology and three-dimensional reconstruction using new and historic histological sections of 5 human 17- to 21-day-old embryos and of 2 marmoset monkey embryos of the species Callithrix jacchus at corresponding stages. The neurenteric canal presents itself as the classical vertical connection between the amniotic cavity and the yolk sac cavity and is lined (a) craniolaterally by a horseshoe-shaped “hinge of involuting notochordal cells” within Hensen’s node and (b) caudally by the receding primitive streak epiblast dorsally and by notochordal plate epithelium ventrally, the latter of which covered the (longitudinal) notochordal canal on its ventral side at the preceding stage. Furthermore, asymmetric parachordal nodal expression in Callithrix and morphological asymmetries within the nodes of the other specimens suggest an early non-cilium-dependent left-right symmetry breaking mode previously postulated for other mammals. We conclude that structure and position of the mammalian neurenteric canal support the notion of its homology with the reptilian blastopore as a whole and with a dorsal segment of the blastopore in amphibia. These new features of the neurenteric canal may further clarify the aetiology of foetal malformations such as junctional neurulation defects, neuroendodermal cysts, and the split notochord syndrome.
Establishment of a Nomogram by Integrating Molecular Markers and Tumor-Node-Metastasis Staging System for Predicting the Prognosis of Hepatocellular Carcinoma
Authors: Huang Xi-Tai , Chen Liu-Hua , Huang Chen-Song , Li Jian-Hui , Cai Jian-Peng , Chen Wei , Yin Xiao-Yu
Published: November 2018

Aims: This study aimed to develop a valuable nomogram by integrating molecular markers and tumor-node-metastasis (TNM) staging system for predicting the long-term outcome of patients with hepatocellular carcinoma (HCC). Methods: The gene expression profiles of HCC patients undergoing liver resection were obtained from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. One hundred and ninety-nine patients from TCGA and 94 patients from GEO were selected to be part of the training cohort and validation cohort respectively. Univariate and multivariate cox analyses were performed to identify genes with independent prognostic values for overall survival (OS) of HCC patients in training cohort. Risk score was calculated based on the coefficients and Z-score of 3 genes for each patient. The nomogram was developed based on the risk score and TNM staging system. Discrimination and predictive accuracy of the nomogram were measured by using the concordance index (C-index) and calibration curve. The efficacy of the nomogram was tested in the external validation cohort. Results: Univariate and multivariate cox analyses revealed that EXT2 (p = 0.035, hazard ratio 13.412), ETV5 (p = 0.010, hazard ratio 4.325), and CHODL (p < 0.001, hazard ratio 6.286) were independent prognostic factors and chosen for further nomogram establishment. The C-index of the nomogram for predicting the OS in the training cohort was superior to that of the TNM staging system (0.77 vs. 0.64, p < 0.01). The calibration curve of predicted 1-, 3-, and 5-year OS showed satisfactory accuracy. The external validation cohort showed good performance of comprehensive nomogram as well. Conclusion: The novel nomogram by integrating the molecular markers and TNM staging system has better performance in predicting long-term prognosis in HCC patients than the TNM staging system alone.
Multisegmental Lumbar Corporectomy and Transcorporal Fixation for Correction of Extreme Thoracolumbar Kyphosis in Myelomeningocele with Chronic Decubitus
Authors: Kiepe Felix , Hermann Elvis Josef , Heissler Hans E. , Henseler Helga , Vogt Peter M. , Krauss Joachim K.
Published: November 2018

We introduce a novel technique for the treatment of severe kyphosis in myelomeningocele. A 5-year-old paraplegic boy with myelomeningocele presented with severe thoracolumbar kyphosis and a chronic ulcus at the site of the gibbus. The myelomeningocele had been treated during his first week of life, and an accompanying Chiari type II malformation had been treated by ventriculoperitoneal shunting. He subsequently developed a rapidly progressive thoracolumbar kyphosis with an angle of 180° between T10 and L5. He also suffered from a chronic superinfected skin ulcus at the site of the gibbus. Since the skin ulcus required plastic surgery reconstruction, we deemed classical posterior fixation after kyphectomy unfeasible. The subsequent operative steps of our novel surgical approach were performed in a single-stage surgery. First, a three-level lumbar corporectomy from L1 to L3 was performed. Subsequently, the body of the removed L2 vertebra was isolated and configured as an autologous graft to bridge the gap between the thoracic and the caudal lumbar spine. The graft was fixed via a transcorporal interbody fusion technique with titanium screws, and chopped autologous bone was added for fusion. The skin was closed using rotation flaps. At the 3-year follow-up, the patient and his family reported marked improvement of quality of life, imaging showed solid fusion and the wound was unremarkable. Our novel technique with transcorporal fixation provides new perspectives in the treatment of severe kyphosis and skin ulceration in myelomeningocele.
Nalmefene, Given as Needed, in the Routine Treatment of Patients with Alcohol Dependence: An Interventional, Open-Label Study in Primary Care
Authors: Castera Philippe , Stewart Edmund , Großkopf Josef , Brotons Carlos , Brix Schou Maiken , Zhang Doris , Steiniger Brach Björn , Meulien Didier ,   on behalf of the PICASO Study Investigators
Published: November 2018

Aims: This 12-week, open-label, primary care study (NCT02195817) evaluated the efficacy and safety of nalmefene, taken as needed, to reduce alcohol consumption in adults with a diagnosis of alcohol dependence and drinking at least at high drinking risk levels (DRL, > 60 g/day for men, > 40 g/day for women). Methods: Following the Screening Visit, patients recorded their daily alcohol consumption for 2 weeks. Patients were then categorised by their self-reported drinking levels; those who maintained at least a high DRL in the 2-week period were included in Cohort-A, and those who reduced their alcohol consumption below high DRL were included in Cohort-B. Cohort-A received simple psychosocial interventions and were supplied with nalmefene 18 mg to be taken on days when they perceived a risk of drinking alcohol. Patients in Cohort-B received a simple psychosocial intervention and were treated per normal practice. Results: Of the 378 enrolled patients, 330 were included in Cohort-A and 48 in Cohort-B. For patients in Cohort-A, the mean change from screening to Week-12 in the number of heavy drinking days/month was –13.1 days/month (95% CI –14.4 to –11.9, p < 0.0001). Overall, 55% of patients reduced their DRL by ≥2 risk levels and 44% of patients reduced to a low DRL. The most common adverse events were nausea (18.3%) and dizziness (17.7%). Patients in Cohort-B maintained their lower level alcohol consumption at the 12-week follow-up. Conclusions: Patients with alcohol dependence treated in primary care with nalmefene, taken as needed, in conjunction with simple psychosocial support, significantly reduced their alcohol consumption. Treatment was well tolerated.
Whole Genome Sequencing Analysis of a Stage IV Colon Cancer Patient with a 10-Year Disease-Free Survival following Systemic Chemotherapy/Bevacizumab
Authors: Yeatman Timothy J. , Yang Mingli , Coppola Domenico
Published: November 2018

It is rare that stage IV colon cancer is cured with chemotherapy. Here we report the long-term survival of a patient who presented with highly advanced disease characterized by a papillary architecture as well as porta hepatis lymph nodes but responded extremely well to FOLFIRI/bevacizumab. His original tumor underwent comprehensive genomic testing that included whole genome DNA sequencing, targeted sequencing, and RNA sequencing. These genetic results suggest the patient’s tumor harbored mutations in APC, KRAS, and TP53 as well as in PIK3CB. Moreover, the RNA-seq data suggested that the tumor belonged to the consensus molecular subtype 4, the “inflamed, immune phenotype,” with increased angiogenesis. Deep sequencing of highly responsive cancers may yield molecular insights into mechanisms underpinning a remarkable response.
Successful Endoscopic Closure Using Polyglycolic Acid Sheets with Fibrin Glue for Nonhealing Duodenal Ulcer with Perforation after Proton Beam Therapy of Liver Tumor
Authors: Watanabe Ko , Hikichi Takuto , Nakamura Jun , Hashimoto Minami , Takagi Tadayuki , Suzuki Rei , Sugimoto Mitsuru , Konno Naoki , Takasumi Mika , Sato Yuki , Irie Hiroki , Kimura Takashi , Kenjo Akira , Marubashi Shigeru , Obara Katsutoshi , Ohira Hiromasa
Published: November 2018

We describe the first case of a nonhealing duodenal ulcer with perforation after proton beam therapy (PBT) of a liver tumor that was successfully treated endoscopically using polyglycolic acid (PGA) sheets with fibrin glue. A 69-year-old man received PBT for a liver tumor. Esophagogastroduodenoscopy (EGD) 3 months after PBT revealed a duodenal ulcer. A proton pump inhibitor was administered for 7 weeks, and the ulcer healed. Six months after the EGD, recurrence of the duodenal ulcer with perforation occurred. An emergency open surgery with placement of the omental patch was performed. However, 5 days after the surgery, because the EGD revealed a perforation site in the duodenal ulcer that was not closed, the conservative treatment was continued. Twenty-eight days after the surgery, EGD revealed that the perforation size had increased. Therefore, we conducted endoscopic closure therapy using PGA sheets with fibrin glue. Eleven days after the closure procedure, the EGD showed that the perforation site was filled with granulation tissue and was closed. Forty-nine days after the procedure, EGD revealed that the ulcer had healed. This endoscopic closure treatment was effective for a nonhealing duodenal ulcer with perforation after PBT of a liver tumor.
L-Carnitine Supplementation Increases Trimethylamine-N-Oxide but not Markers of Atherosclerosis in Healthy Aged Women
Authors: Samulak Joanna J. , Sawicka Angelika K. , Hartmane Dace , Grinberga Solveiga , Pugovics Osvalds , Lysiak-Szydlowska Wieslawa , Olek Robert A.
Published: November 2018

Background: L-carnitine can be metabolized to trimethylamine N-oxide (TMAO), a molecule that promotes atherogenesis through its interaction with macrophages and lipid metabolism. Objective: The aim of the present study was to assess whether L-carnitine supplementation may promote changes in selected serum biomarkers of atherosclerosis. Methods: Before the start, in the mid-point and after completing the 24-weeks supplementation protocol, fasting blood samples were taken from the antecubital vein. Plasma free L-carnitine and TMAO were determined by the UPLC/MS/MS method. Serum proteins were determined by the enzyme immunoassay method using commercially available kits. Total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, and triglycerides have been determined using standard automatic analyzer. Results: L-carnitine supplementation elevated fasting plasma carnitine in the mid-point of our study and it remained increased until the end of supplementation period. Moreover, it induced tenfold increase in plasma TMAO concentration but did not affect serum C-reactive protein, interleukin-6, tumour necrosis factor-α, L-selectin, P-selectin, vascular cell adhesion molecule-1, intercellular adhesion molecule-1 or lipid profile markers. Conclusion: We demonstrated that ­although oral L-carnitine supplementation significantly ­increased plasma TMAO concentration, no lipid profile changes or other markers of adverse cardiovascular events were detected in healthy aged women over the period of 24 weeks.
Prediction of Complications in Radical Prostatectomy Prostate Cancer Patients: Simulated Annealing versus Co-Morbidity Indexes
Authors: Leyh-Bannurah Sami-Ramzi , Zaffuto Emanuele , Dell’Oglio Paolo , Tian Zhe , Moschini Marco , Capitanio Umberto , Briganti Alberto , Montorsi Francesco , Fisch Margit , Chun Felix , Kachanov Mykyta , Budäus Lars , Graefen Markus , Huland Hartwig , Karakiewicz Pierre I.
Published: November 2018

Background: The Deyo/Charlson co-morbidity index (CCI) and Klabunde co-morbidity index (KCI) co-morbidity indexes represent outdated indexes when the endpoint of complications after radical prostatectomy (RP) is considered. A novel group of co-morbidities derived from International Classification of Diseases-9 diagnostic codes in a contemporary RP database could provide better accuracy. Research Design, Subjects and Measures: We relied on 20,484 patients with clinically localized non-metastatic prostate cancer treated with RP between 2000 and 2009 in the Surveillance, Epidemiology, and End Results-Medicare linked database. We examined 2 endpoints, namely, 90-day medical complication rate and 90-day surgical complication rate after RP. Simulated annealing (SA) was used to develop a novel co-morbidity index. Finally, the newly identified groups of co-morbid conditions were compared with the CCI and Klabunde indexes. Results: Our SA identified 10 and 7 individual co-morbid conditions able to predict 90-day medical and surgical complications respectively. This novel model showed improved predictive accuracy over CCI and KCI for the 2 endpoints considered (respectively: 59.4 vs. 58.1 and 58.0% for medical complications, 58.0 vs. 56.8 and 56.7% for surgical complications). Conclusions: The newly defined groupings of co-morbid conditions resulted in better ability to predict the 2 endpoints of interest compared to CCI and KCI. However, the gain was marginal. This implies that better tools should be defined to more accurately predict these outcomes.