bluuebunny/crossref_metadata_2025 huggingface dataset:
Stabilizing Large Financial Institutions with Contingent Capital Certificates
Authors: Flannery Mark J.
Published: November 2015

The 2008–2009 financial crisis clearly indicated that government regulators are reluctant to let a large financial institution fail. In order to minimize the transfer of future losses to taxpayers or to solvent banks, we need a system for assuring that large institutions continuously maintain sufficient capital. For a variety of reasons, supervisors find it difficult to require institutions to sell new shares after they have suffered losses. This paper describes and evaluates a proposed security that converts from debt to equity automatically when the issuer’s equity ratio falls too low. “Contingent capital certificates” (CCCs) can greatly reduce the probability that a large financial firm will suffer losses in excess of its common equity, and will provide market discipline by forcing shareholders to internalize more of their assets’ poor outcomes. The proposed reliance on equity’s market value to trigger conversion creates some problems, which must be compared to the shortcomings of our current application of capital adequacy standards.
Patterns of gene expression among murine models of hemorrhagic shock/trauma and sepsis
Authors: Mira Juan C. , Szpila Benjamin E. , Nacionales Dina C. , Lopez Maria-Cecilia , Gentile Lori F. , Mathias Brittany J. , Vanzant Erin L. , Ungaro Ricardo , Holden David , Rosenthal Martin D. , Rincon Jaimar , Verdugo Patrick T. , Larson Shawn D. , Moore Frederick A. , Brakenridge Scott C. , Mohr Alicia M. , Baker Henry V. , Moldawer Lyle L. , Efron Philip A.
Published: November 2015

Controversy remains whether the leukocyte genomic response to trauma or sepsis is dependent upon the initiating stimulus. Previous work illustrated poor correlations between historical models of murine trauma and sepsis (i.e., trauma-hemorrhage and lipopolysaccharide injection, respectively). The aim of this study is to examine the early genomic response in improved murine models of sepsis [cecal ligation and puncture (CLP)] and trauma [polytrauma (PT)] with and without pneumonia (PT+Pp). Groups of naïve, CLP, PT, and PT+Pp mice were killed at 2 h, 1 or 3 days. Total leukocytes were isolated for genome-wide expression analysis, and genes that were found to differ from control (false discovery rate adjusted P < 0.001) were assessed for fold-change differences. Spearman correlations were also performed. For all time points combined (CLP, PT, PT+Pp), there were 10,426 total genes that were found to significantly differ from naïve controls. At 2 h, the transcriptomic changes between CLP and PT showed a positive correlation ( r s) of 0.446 ( P < 0.0001) but were less positive thereafter. Correlations were significantly improved when we limited the analysis to common genes whose expression differed by a 1.5 fold-change. Both pathway and upstream analyses revealed the activation of genes known to be associated with pathogen-associated and damage-associated molecular pattern signaling, and early activation patterns of expression were very similar between polytrauma and sepsis at the earliest time points. This study demonstrates that the early leukocyte genomic response to sepsis and trauma are very similar in mice.
An Improved EMD and Its Applications to Find the Basis Functions of EMI Signals
Authors: Li Hongyi , Wang Chaojie , Zhao Di
Published: November 2015

A B-spline empirical mode decomposition (BEMD) method is proposed to improve the celebrated empirical mode decomposition (EMD) method. The improvement of BEMD on EMD mainly concentrates on the sifting process. First, instead of the curve that resulted from computing the average of upper and lower envelopes, the curve interpolated by the midpoints of local maximal and minimal points is used as the mean curve, which can reduce the cost of computation. Second, the cubic spline interpolation is replaced with cubic B-spline interpolation on account of the advantages of B-spline over polynomial spline. The effectiveness of BEMD compared with EMD is validated by numerical simulations and an application to find the basis functions of EMI signals.
The Use of High-Density SNP Array to Map Homozygosity in Consanguineous Families to Efficiently Identify Candidate Genes: Application to Woodhouse-Sakati Syndrome
Authors: Sheridan Molly B. , Wohler Elizabeth , Batista Denise A. S. , Applegate Carolyn , Hoover-Fong Julie
Published: November 2015

Two consanguineous Qatari siblings presented for evaluation: a 17-4/12-year-old male with hypogonadotropic hypogonadism, alopecia, intellectual disability, and microcephaly and his 19-year-old sister with primary amenorrhea, alopecia, and normal cognition. Both required hormone treatment to produce secondary sex characteristics and pubertal development beyond Tanner 1. SNP array analysis of both probands was performed to detect shared regions of homozygosity which may harbor homozygous mutations in a gene causing their common features of abnormal pubertal development, alopecia, and variable cognitive delay. Our patients shared multiple homozygous genomic regions; ten shared regions were >1 Mb in length and constituted 0.99% of the genome.DCAF17, encoding a transmembrane nuclear protein of uncertain function, was the only gene identified in a homozygous region known to cause hypogonadotropic hypogonadism.DCAF17mutations are associated with Woodhouse-Sakati syndrome, a rare disorder characterized by alopecia, hypogonadotropic hypogonadism, sensorineural hearing loss, diabetes mellitus, and extrapyramidal movements. Sequencing of the coding exons and flanking intronic regions ofDCAF17in the proband revealed homozygosity for a previously described founder mutation (c.436delC). TargetedDCAF17sequencing of his affected sibling revealed the same homozygous mutation. This family illustrates the utility of SNP array testing in consanguineous families to efficiently and inexpensively identify regions of genomic homozygosity in which genetic candidates for recessive conditions can be identified.
An Automatic Traffic Sign Detection and Recognition System Based on Colour Segmentation, Shape Matching, and SVM
Authors: Wali Safat B. , Hannan Mahammad A. , Hussain Aini , Samad Salina A.
Published: November 2015

The main objective of this study is to develop an efficient TSDR system which contains an enriched dataset of Malaysian traffic signs. The developed technique is invariant in variable lighting, rotation, translation, and viewing angle and has a low computational time with low false positive rate. The development of the system has three working stages: image preprocessing, detection, and recognition. The system demonstration using a RGB colour segmentation and shape matching followed by support vector machine (SVM) classifier led to promising results with respect to the accuracy of 95.71%, false positive rate (0.9%), and processing time (0.43 s). The area under the receiver operating characteristic (ROC) curves was introduced to statistically evaluate the recognition performance. The accuracy of the developed system is relatively high and the computational time is relatively low which will be helpful for classifying traffic signs especially on high ways around Malaysia. The low false positive rate will increase the system stability and reliability on real-time application.
Inhibitory Effect of a French Maritime Pine Bark Extract-Based Nutritional Supplement on TNF-α-Induced Inflammation and Oxidative Stress in Human Coronary Artery Endothelial Cells
Authors: McGrath Kristine C. Y. , Li Xiao-Hong , McRobb Lucinda S. , Heather Alison K.
Published: November 2015

Oxidative stress and inflammation, leading to endothelial dysfunction, contribute to the pathogenesis of atherosclerosis. The popularity of natural product supplements has increased in recent years, especially those with purported anti-inflammatory and/or antioxidant effects. The efficacy and mechanism of many of these products are not yet well understood. In this study, we tested the antioxidant and anti-inflammatory effects of a supplement, HIPER Health Supplement (HIPER), on cytokine-induced inflammation and oxidative stress in human coronary artery endothelial cells (HCAECs). HIPER is a mixture of French maritime pine bark extract (PBE), honey, aloe vera, and papaya extract. Treatment for 24 hours with HIPER reduced TNF-α-induced reactive oxygen species (ROS) generation that was associated with decreased NADPH oxidase 4 and increased superoxide dismutase-1 expression. HIPER inhibited TNF-αinduced monocyte adhesion to HCAECs that was in keeping with decreased expression of vascular cell adhesion molecule-1 and intercellular cell adhesion molecule-1 and decreased nuclear factor-kappa B (NF-κB) activation. Further investigation of mechanism showed HIPER reduced TNF-αinduced IκBαand p38 and MEK1/2 MAP kinases phosphorylation. Our findings show that HIPER has potent inhibitory effects on HCAECs inflammatory and oxidative stress responses that may protect against endothelial dysfunction that underlies early atherosclerotic lesion formation.
A Rare Case of Tumoral Calcium Pyrophosphate Dihydrate Crystal Deposition Disease of the Wrist Joint
Authors: Nakamura Osamu , Kaji Yoshio , Yamagami Yoshiki , Yamaguchi Kounosuke , Nishimura Hideki , Fukuoka Natsuko , Yamamoto Tetsuji
Published: November 2015

Introduction. Tumoral calcium pyrophosphate dihydrate (CPPD) crystal deposition disease (CPPDCD), also known as tophaceous calcium pyrophosphate deposition disease (CPDD), is a tumorlike lesion, and it should be distinguished from usual CPDD that causes severe joint inflammation and arthralgia. A case of tumoral CPPDCD of the wrist joint that required differentiation from synovial osteochondromatosis is described.Case Presentation. The patient was a 78-year-old woman with a 5-year history of nodular lesions at the right wrist that had gradually increased in size. An excisional biopsy and a histological examination of the excised nodular lesions by hematoxylin and eosin (H&E) staining were performed, demonstrating numerous polarizable, rhabdoid, and rectangular crystals, surrounded by fibroblasts, macrophages, and foreign body-type giant cells, consistent with tumoral CPPDCD.Conclusion. Tumoral CPPDCD, especially at the wrist joint, is rare, and, to the best of our knowledge, only 2 articles have been published. This case seems to need further follow-up for recurrence, because tumoral CPPDCD may recur after complete or incomplete surgical excision.
Germination Ecology of Arundinaria alpina (K. Schum.) and Oxytenanthera abyssinica (A. Rich.) Munro Seeds: Indigenous Bamboo Species in Ethiopia
Authors: Bahru Tinsae , Mulatu Yigardu , Kidane Berhane
Published: November 2015

Highland bamboo (Arundinaria alpina) and lowland bamboo (Oxytenanthera abyssinica) are indigenous to Ethiopia and endemic to Africa. Seeds of A. alpina were collected from Dawa Wereda (District), while O. abyssinica seeds were collected from Pawe and Sherkole Weredas. In this study, seed presowing treatments, effects of dry heat, moist heat, and light/dark treatments on the germination of seeds were tested. The averages were of 59,416 and 8,393 seeds contained within 1 kg of A. alpina and O. abyssinica seeds within 86 and 91% pure seeds, respectively. From 1 kg of pure seeds 37,301 and 7,168 seedlings are raised in the laboratory in their respective orders. The result revealed that control seeds of A. alpina and O. abyssinica showed the best germination of 73 and 98%. Germination of both dry and moist heat treatments of O. abyssinica seeds was significantly improved at 60 and 80°C. Unlike A. alpina seeds, seeds of O. abyssinica had better germination for light treatment compared to dark. For effective large scale plantation and raising of A. alpina and O. abyssinica seedlings from its seeds for laboratory, control seeds supply to necessary light source (for O. abyssinica seeds) is recommended.
The Effects of High-Frequency Transcutaneous Electrical Nerve Stimulation for Dental Professionals with Work-Related Musculoskeletal Disorders: A Single-Blind Randomized Placebo-Controlled Trial
Authors: Suh Hye Rim , Kim Tae Hoon , Han Gyeong-Soon
Published: November 2015

Work-related musculoskeletal symptom disorders (WMSDs) have a significant issue for dental professionals. This study investigated the effects of high-frequency transcutaneous electrical nerve stimulation (TENS) on work-related pain, fatigue, and the active range of motion in dental professionals. Among recruited 47 dental professionals with WMSDs, 24 subjects received high-frequency TENS (the TENS group), while 23 subjects received placebo stimulation (the placebo group). TENS was applied to the muscle trigger points of the levator scapulae and upper trapezius, while placebo-TENS was administered without electrical stimulation during 60 min. Pain and fatigue at rest and during movement were assessed using the visual analog scale (VAS), pain pressure threshold (PPT), and active range of motion (AROM) of horizontal head rotation at six time points: prelabor, postlabor, post-TENS, and at 1 h, 3 h, and 1 day after TENS application. Both groups showed significantly increased pain and fatigue and decreased PPT and AROM after completing a work task. The TENS group showed significantly greater improvements in VAS score, fatigue, PPT, and AROM at post-TENS and at 1 h and 3 h after application (allP< 0.05) as compared to the placebo group. A single session high-frequency TENS may immediately reduce symptoms related to WMSDs in dental professionals.
Double Bolus Thrombolysis for Suspected Massive Pulmonary Embolism during Cardiac Arrest
Authors: O’Connor Gerard , Fitzpatrick Gareth , El-Gammal Ayman , Gilligan Peadar
Published: November 2015

More than 70% of cardiac arrest cases are caused by acute myocardial infarction (AMI) or pulmonary embolism (PE). Although thrombolytic therapy is a recognised therapy for both AMI and PE, its indiscriminate use is not routinely recommended during cardiopulmonary resuscitation (CPR). We present a case describing the successful use of double dose thrombolysis during cardiac arrest caused by pulmonary embolism. Notwithstanding the relative lack of high-level evidence, this case suggests a scenario in which recombinant tissue Plasminogen Activator (rtPA) may be beneficial in cardiac arrest. In addition to the strong clinical suspicion of pulmonary embolism as the causative agent of the patient’s cardiac arrest, the extremely low end-tidal CO2suggested a massive PE. The absence of dilatation of the right heart on subxiphoid ultrasound argued against the diagnosis of PE, but not conclusively so. In the context of the circulatory collapse induced by cardiac arrest, this aspect was relegated in terms of importance. The second dose of rtPA utilised in this case resulted in return of spontaneous circulation (ROSC) and did not result in haemorrhage or an adverse effect.
Contribution of River Mouth Reach to Sediment Load of the Yangtze River
Authors: Wang C. , Dai S. B. , Ran L. S. , Jiang L. , Li W. T.
Published: November 2015

This paper examined the sediment gain and loss in the river mouth reach of the Yangtze River by considering sediment load from the local tributaries, erosion/accretion of the river course, impacts of sand mining, and water extraction. A quantitative estimation of the contribution of the river mouth reach to the sediment load of the Yangtze River was conducted before and after impoundment of the Three Gorges Dam (TGD) in 2003. The results showed that a net sediment load loss of 1.78 million ton/yr (Mt/yr) occurred from 1965 to 2002 in the study area. The contribution of this reach to the sediment discharge into the sea is not as high as what was expected before the TGD. With impoundment of the TGD, channel deposition (29.90 Mt/yr) and a net sediment loss of 30.89 Mt/yr occurred in the river mouth reach from 2003 to 2012. The river mouth reach has acted as a sink but not a source of sediment since impoundment of the TGD, which has exacerbated the decrease in sediment load. Technologies should be advanced to measure changes in river channel morphology, as well as in water and sediment discharges at the river mouth reach.
Improved Photocatalytic Performance of a Novel Fe3O4@SiO2/Bi2SiO5Hierarchical Nanostructure with Magnetic Recoverability
Authors: Zhang Xinxin , Dong Xiaoli , Leng Baiyu , Ma Hongchao , Zhang Xiufang
Published: November 2015

Magnetic Fe3O4@SiO2/Bi2SiO5composites with a novel hierarchical nanostructure were synthesized by sol-gel and hydrothermal methods and were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), and UV-visible diffuse reflectance spectroscopy (UV-vis DRS). It was found that the introduction of Fe3O4@SiO2could turn the morphology of Bi2SiO5from close-grained slab to hollow hierarchical architecture with fabric-structure. The Fe3O4@SiO2/Bi2SiO5composite showed enhanced photodegradation efficiency for the degradation of reactive brilliant red dye (X-3B) in aqueous solution under simulated sunlight irradiation, as compared with that of commercial P25. In addition, the Fe3O4@SiO2/Bi2SiO5composite exhibited good magnetic recoverability and excellent photocatalytic stability (no obvious activity loss after recycling tests).
Dynamics of Uncertain Discrete-Time Neural Network with Delay and Impulses
Authors: Mei Xuehui , Zhang Liwei , Jiang Haijun , Yu Zhiyong
Published: November 2015

The stability of discrete-time impulsive delay neural networks with and without uncertainty is investigated. First, by using Razumikhin-type theorem, a new less conservative condition for the exponential stability of discrete-time neural network with delay and impulse is proposed. Moreover, some new sufficient conditions are derived to guarantee the stability of uncertain discrete-time neural network with delay and impulse by using Lyapunov function and linear matrix inequality (LMI). Finally, several examples with numerical simulation are presented to demonstrate the effectiveness of the obtained results.
Potential of Neural Stem Cell-Based Therapy for Parkinson’s Disease
Authors: Chou Chung-Hsing , Fan Hueng-Chuen , Hueng Dueng-Yuan
Published: November 2015

Neural stem cell (NSC) transplantation is an emerging strategy for restoring neuronal function in neurological disorders, such as Parkinson’s disease (PD), which is characterized by a profound and selective loss of nigrostriatal dopaminergic (DA) neurons. Adult neurogenesis generates newborn neurons that can be observed at specialized niches where endothelial cells (ECs) play a significant role in regulating the behavior of NSCs, including self-renewal and differentiating into all neural lineage cells. In this minireview, we highlight the importance of establishing an appropriate microenvironment at the target site of NSC transplantation, where grafted cells integrate into the surroundings in order to enhance DA neurotransmission. Using a novel model of NSC-EC coculture, it is possible to combine ECs with NSCs, to generate such a neurovascular microenvironment. With appropriate NSCs selected, the composition of the transplant can be investigated through paracrine and juxtacrine signaling within the neurovascular unit (NVU). With target site cellular and acellular compartments of the microenvironment recognized, guided DA differentiation of NSCs can be achieved. As differentiated DA neurons integrate into the existing nigrostriatal DA pathway, the symptoms of PD can potentially be alleviated by reversing characteristic neurodegeneration.
Extensive Subcutaneous Emphysema as a Presentation of Ischemic Colitis
Authors: Carvalho Ana Franky , Branco Claudio , Leão Pedro , Antunes Conceição
Published: November 2015

Introduction. Subcutaneous emphysema is usually benign and self-limited; however, it may be associated with a life-threating situation.Case Report. An elderly woman with progressive malaise with extensive subcutaneous emphysema (cervical to abdominal wall) was observed at the emergency department. Colonic perforation was diagnosed and the patient underwent surgery. Intraoperatively, necrosis and perforation of the sigmoid colon into the retroperitoneum were found and a Hartmann procedure was performed.Conclusion. Cervical and thoracic subcutaneous emphysema may be the first sign of intra-abdominal lesion.
Neurosupportive Role of Vanillin, a Natural Phenolic Compound, on Rotenone Induced Neurotoxicity in SH-SY5Y Neuroblastoma Cells
Authors: Dhanalakshmi Chinnasamy , Manivasagam Thamilarasan , Nataraj Jagatheesan , Justin Thenmozhi Arokiasamy , Essa Musthafa Mohamed
Published: November 2015

Vanillin, a phenolic compound, has been reported to offer neuroprotection against experimental Huntington’s disease and global ischemia by virtue of its antioxidant, anti-inflammatory, and antiapoptotic properties. The present study aims to elucidate the underlying neuroprotective mechanism of vanillin in rotenone induced neurotoxicity. Cell viability was assessed by exposing SH-SY5Y cells to various concentrations of rotenone (5–200 nM) for 24 h. The therapeutic effectiveness of vanillin against rotenone was measured by pretreatment of vanillin at various concentrations (5–200 nM) and then incubation with rotenone (100 nM). Using effective dose of vanillin (100 nM), mitochondrial membrane potential, levels of reactive oxygen species (ROS), and expression patterns of apoptotic markers were assessed. Toxicity of rotenone was accompanied by the loss of mitochondrial membrane potential, increased ROS generation, release of cyt-c, and enhanced expressions of proapoptotic and downregulation of antiapoptotic indices via the upregulation of p38 and JNK-MAPK pathway proteins. Our results indicated that the pretreatment of vanillin attenuated rotenone induced mitochondrial dysfunction, oxidative stress, and apoptosis. Thus, vanillin may serve as a potent therapeutic agent in the future by virtue of its multiple pharmacological properties in the treatment of neurodegenerative diseases including PD.
Smart One-Channel Sensor Node for Ambient Vibration Test with Applications to Structural Health Monitoring of Large Civil Infrastructures
Authors: Park Young-Soo , Kim Sehoon , Sim Sung-Han , Koo Ki-Young , Lee Wontae , Lee Jong-Jae
Published: November 2015

Dynamic characteristics of structures have been monitored for safe operation and efficient maintenance of large civil infrastructures. For vibration data measurement, the conventional system uses cables, which cause very expensive costs and inconvenient installation. Therefore, various wireless sensor nodes have been developed to replace the conventional wired system. However, there still remain lots of issues to be resolved such as time synchronization between sensor nodes, data loss, data security, and power supply. In this study, Smart One-Channel Sensor Node (SOSN) was developed to measure vibration data, which can practically solve the issues on installation, time synchronization, and data storage. It is designed for temporal measurement with a limited capacity to operate for several hours using embedded batteries. Laboratory tests were carried out to verify the performance of the developed SOSN compared with conventional wired system. Its practical advantages were investigated through three full-scale tests on large civil infrastructures. Three field applications revealed that SOSN is a very practical tool for short-term monitoring of large civil infrastructures with respect to traffic control, installation time and convenience, secure data gathering, and so forth.
A Comparison of Endothelial Cell Loss in Combined Cataract and MIGS (Hydrus) Procedure to Phacoemulsification Alone: 6-Month Results
Authors: Fea Antonio M. , Consolandi Giulia , Pignata Giulia , Cannizzo Paola Maria Loredana , Lavia Carlo , Billia Filippo , Rolle Teresa , Grignolo Federico M.
Published: November 2015

Purpose. To compare the corneal endothelial cell loss after phacoemulsification, alone or combined with microinvasive glaucoma surgery (MIGS), in nonglaucomatous versus primary open angle glaucoma (POAG) eyes affected by age-related cataract.Methods. 62 eyes of 62 patients were divided into group 1 (n=25, affected by age-related cataract) and group 2 (n=37, affected by age-related cataract and POAG). All patients underwent cataract surgery. Group 2 was divided into subgroups A (n=19, cataract surgery alone) and B (n=18, cataract surgery and MIGS). Prior to and 6 months after surgery the patients’ endothelium was studied. Main outcomes were CD (cell density), SD (standard deviation), CV (coefficient of variation), and 6A (hexagonality coefficient) variations after surgeries.Results. There were no significant differences among the groups concerning preoperative endothelial parameters. The differences in CD before and after surgery were significant in all groups: 9.1% in group 1, 17.24% in group 2A, and 11.71% in group 2B. All endothelial parameters did not significantly change after surgery.Conclusions. Phacoemulsification determined a loss of endothelial cells in all groups. After surgery the change in endothelial parameters after MIGS was comparable to the ones of patients who underwent cataract surgery alone.
A Nonmonotone Weighting Self-Adaptive Trust Region Algorithm for Unconstrained Nonconvex Optimization
Authors: Lu Yunlong , Yang Weiwei , Li Wenyu , Jiang Xiaowei , Yang Yueting
Published: November 2015

A new trust region method is presented, which combines nonmonotone line search technique, a self-adaptive update rule for the trust region radius, and the weighting technique for the ratio between the actual reduction and the predicted reduction. Under reasonable assumptions, the global convergence of the method is established for unconstrained nonconvex optimization. Numerical results show that the new method is efficient and robust for solving unconstrained optimization problems.
Identification and Endodontic Management of Middle Mesial Canal in Mandibular Second Molar Using Cone Beam Computed Tomography
Authors: Paul Bonny , Dube Kavita
Published: November 2015

Endodontic treatments are routinely done with the help of radiographs. However, radiographs represent only a two-dimensional image of an object. Failure to identify aberrant anatomy can lead to endodontic failure. This case report presents the use of three-dimensional imaging with cone beam computed tomography (CBCT) as an adjunct to digital radiography in identification and management of mandibular second molar with three mesial canals.
Free Space Optics: Current Applications and Future Challenges
Authors: Malik Aditi , Singh Preeti
Published: November 2015

FSO is a communication system where free space acts as medium between transceivers and they should be in LOS for successful transmission of optical signal. Medium can be air, outer space, or vacuum. This system can be used for communication purpose in hours and in lesser economy. There are many advantages of FSO like high bandwidth and no spectrum license. The transmission in FSO is dependent on the medium because the presence of foreign elements like rain, fog, and haze, physical obstruction, scattering, and atmospheric turbulence are some of these factors. Different studies on weather conditions and techniques employed to mitigate their effect are discussed in this paper.
The Effect of Lycopene Preexposure on UV‐B‐Irradiated Human Keratinocytes
Authors: Ascenso Andreia , Pedrosa Tiago , Pinho Sónia , Pinho Francisco , Oliveira José Miguel P. Ferreira de , Cabral Marques Helena , Oliveira Helena , Simões Sandra , Santos Conceição
Published: November 2015

Lycopene has been reported as the antioxidant most quickly depleted in skin upon UV irradiation, and thus it might play a protective role. Our goal was to investigate the effects of preexposure to lycopene on UV‐B‐irradiated skin cells. Cells were exposed for 24 h to 10 M lycopene, and subsequently irradiated and left to recover for another 24 h period. Thereafter, several parameters were analyzed by FCM and RT‐PCR: genotoxicity/clastogenicity by assessing the cell cycle distribution; apoptosis by performing the Annexin‐V assay and analyzing gene expression of apoptosis biomarkers; and oxidative stress by ROS quantification. Lycopene did not significantly affect the profile of apoptotic, necrotic and viable cells in nonirradiated cells neither showed cytostatic effects. However, irradiated cells previously treated with lycopene showed an increase in both dead and viable subpopulations compared to nonexposed irradiated cells. In irradiated cells, lycopene preexposure resulted in overexpression of BAX gene compared to nonexposed irradiated cells. This was accompanied by a cell cycle delay at S‐phase transition and consequent decrease of cells in G0/G1 phase. Thus, lycopene seems to play a corrective role in irradiated cells depending on the level of photodamage. Thus, our findings may have implications for the management of skin cancer.
Checkpoint Kinase 2 Negatively Regulates Androgen Sensitivity and Prostate Cancer Cell Growth
Authors: Ta Huy Q. , Ivey Melissa L. , Frierson Henry F. , Conaway Mark R. , Dziegielewski Jaroslaw , Larner James M. , Gioeli Daniel
Published: November 2015

Prostate cancer is the second leading cause of cancer death in American men, and curing metastatic disease remains a significant challenge. Nearly all patients with disseminated prostate cancer initially respond to androgen deprivation therapy (ADT), but virtually all patients will relapse and develop incurable castration-resistant prostate cancer (CRPC). A high-throughput RNAi screen to identify signaling pathways regulating prostate cancer cell growth led to our discovery that checkpoint kinase 2 (CHK2) knockdown dramatically increased prostate cancer growth and hypersensitized cells to low androgen levels. Mechanistic investigations revealed that the effects of CHK2 were dependent on the downstream signaling proteins CDC25C and CDK1. Moreover, CHK2 depletion increased androgen receptor (AR) transcriptional activity on androgen-regulated genes, substantiating the finding that CHK2 affects prostate cancer proliferation, partly, through the AR. Remarkably, we further show that CHK2 is a novel AR-repressed gene, suggestive of a negative feedback loop between CHK2 and AR. In addition, we provide evidence that CHK2 physically associates with the AR and that cell-cycle inhibition increased this association. Finally, IHC analysis of CHK2 in prostate cancer patient samples demonstrated a decrease in CHK2 expression in high-grade tumors. In conclusion, we propose that CHK2 is a negative regulator of androgen sensitivity and prostate cancer growth, and that CHK2 signaling is lost during prostate cancer progression to castration resistance. Thus, perturbing CHK2 signaling may offer a new therapeutic approach for sensitizing CRPC to ADT and radiation. Cancer Res; 75(23); 5093–105. ©2015 AACR.
p53: Protection against Tumor Growth beyond Effects on Cell Cycle and Apoptosis
Authors: Wang Xuyi , Simpson Evan R. , Brown Kristy A.
Published: November 2015

The tumor suppressor p53 has established functions in cancer. Specifically, it has been shown to cause cell-cycle arrest and apoptosis in response to DNA damage. It is also one of the most commonly mutated or silenced genes in cancer and for this reason has been extensively studied. Recently, the role of p53 has been shown to go beyond its effects on cell cycle and apoptosis, with effects on metabolism emerging as a key contributor to cancer growth in situations where p53 is lost. Beyond this, the role of p53 in the tumor microenvironment is poorly understood. The publication by Wang and colleagues demonstrates for the first time that p53 is a key negative regulator of aromatase and, hence, estrogen production in the breast tumor microenvironment. It goes further by demonstrating that an important regulator of aromatase, the obesity-associated and tumor-derived factor prostaglandin E2, inhibits p53 in the breast adipose stroma. This review presents these findings in the context of established and emerging roles of p53 and discusses possible implications for the treatment of breast cancer. Cancer Res; 75(23); 5001–7. ©2015 AACR.
The Immune Checkpoint Regulator PD-L1 Is Highly Expressed in Aggressive Primary Prostate Cancer
Authors: Gevensleben Heidrun , Dietrich Dimo , Golletz Carsten , Steiner Susanne , Jung Maria , Thiesler Thore , Majores Michael , Stein Johannes , Uhl Barbara , Müller Stefan , Ellinger Jörg , Stephan Carsten , Jung Klaus , Brossart Peter , Kristiansen Glen
Published: November 2015

Purpose: Therapies targeting the programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) pathway promote anti-tumor immunity and have shown promising results in various tumors. Preliminary data further indicate that immunohistochemically detected PD-L1 may be predictive for anti-PD-1 therapy. So far, no data are available on PD-L1 expression in primary prostate cancer.

Experimental Design: Following validation of a monoclonal antibody, immunohistochemical analysis of PD-L1 expression was performed in two independent, well-characterized cohorts of primary prostate cancer patients following radical prostatectomy (RP), and resulting data were correlated to clinicopathological parameters and outcome.

Results: In the training cohort (n = 209), 52.2% of cases expressed moderate to high PD-L1 levels, which positively correlated with proliferation (Ki-67, P < 0.001), Gleason score (P = 0.004), and androgen receptor (AR) expression (P < 0.001). Furthermore, PD-L1 positivity was prognostic for biochemical recurrence [BCR; P = 0.004; HR, 2.37; 95% confidence interval (CI), 1.32–4.25]. In the test cohort (n = 611), moderate to high PD-L1 expression was detected in 61.7% and remained prognostic for BCR in univariate Cox analysis (P = 0.011; HR, 1.49; 95% CI, 1.10–2.02). The correlation of Ki-67 and AR with PD-L1 expression was confirmed in the test cohort (P < 0.001). In multivariate Cox analysis of all patients, PD-L1 was corroborated as independently prognostic for BCR (P = 0.007; HR, 1.46; 95% CI, 1.11–1.92).

Conclusions: We provide first evidence that expression of the therapy target PD-L1 is not only highly prevalent in primary prostate cancer cells but is also an independent indicator of BCR, suggesting a biologic relevance in primary tumors. Further studies need to ascertain if PD-1/PD-L1–targeted therapy might be a treatment option for hormone-naïve prostate cancers. Clin Cancer Res; 22(8); 1969–77. ©2015 AACR.
Cepstral, Spectral and Time-Based Analysis of Voices of Esophageal Speakers
Authors: Shim Hee-Jeong , Jang Hyo Ryung , Shin Hee Baek , Ko Do-Heung
Published: November 2015

Objective: To evaluate esophageal speech quality in patients after total laryngectomy using cepstral, spectral and time-based measures. Patients and Methods: The subjects were all males and included 20 total laryngectomy patients and 20 age-matched normal controls. The sustained vowel /a/ was measured using the tools of MDVP (Multi-Dimensional Voice Program) and ADSV (Analysis of Dysphonia in Speech and Voice). Results: Compared to normal controls, esophageal speakers showed significantly lower values for cepstral peak prominence (CPP) and a low- to high-frequency spectral energy (L/H) ratio, but their mean CPP fundamental frequency (CPP F0) was higher. Highly negative correlations were found between CPP and jitter (percent jitter), shimmer (percent shimmer) and noise-to-harmonics ratio (NHR). Positive correlations were also found between L/H ratio and CPP. CPP F0 showed a positive correlation with F0, shimmer and NHR. In addition, CPP and L/H ratio parameters indicated an area under the curve of 0.93 or higher compared to that for time-based measures. Conclusion: This study showed that cepstral and spectral analyses are more effective than time-based analysis in examining the voice quality of alaryngeal speakers. The present findings are expected to contribute to establishing the baseline for voice quality characteristics in total laryngectomy patients.
Osseous Metaplasia and Subsequent Spontaneous Pregnancy Chance: A Case Report and Review of the Literature
Authors: Bozdag Gurkan , Mumusoglu Sezcan , Dogan Selen , Esinler Ibrahim , Gunalp Serdar
Published: November 2015

Backgrounds: What is not clear as yet is not only the etiology, but also the management of osseous metaplasia. We describe an infertile patient with osseous metaplasia and subsequent pregnancy after treatment and review the literature from infertility perspective. Method: We presented a 30-year-old woman with 8 years of secondary infertility who conceived spontaneously after removal of osseous tissue by operative hysteroscopy (HS) following one failed in vitro fertilization cycle. The current literature regarding the osseous metaplasia and fertility potential after removal of osseous tissue was also systematically reviewed in which 21 reports (n = 64 women) were eligible. Results: The available data suggest that restoration of endometrial cavity with HS or curettage provides a spontaneous pregnancy rate of 54.2% within 12 months. Conclusion: According to the available data, irrespective from the duration of subfertility, spontaneous pregnancy should be expected for at least 1 year following the ‘complete' restoration of endometrial cavity. In that context, further infertility treatments such as assisted reproduction cycles should be postponed, unless there is another reason for infertility.
Quality of Preoperative Biopsy Is a Risk Factor for Positive Surgical Margins in Organ-Confined Prostate Cancer Treated with Nerve-Sparing Robot-Assisted Radical Prostatectomy
Authors: Bütow Zentia , Schunk Stefan , Janssen Martin , Gräber Stefan , Saar Matthias , Kamradt Jörn , Siemer Stefan , Stöckle Michael , Ohlmann Carsten-Henning
Published: November 2015

Purpose: Positive surgical margins (PSM) during robot-assisted radical prostatectomy (RARP) negatively influence patients' prognosis. The aim of our study was to identify risk factors for PSM in patients with organ-confined prostate cancer (PCa). Methods: A clinical database of all patients that underwent a RARP at our institution was used. Uni- and multivariable logistic regression analyses were conducted on the PSM rates for all patients with organ-confined PCa. Results: Altogether, 1,600 patients were identified, including 1,085 organ-confined PCa with a PSM rate of 7.8%. On multivariable analysis, bilateral nerve-sparing (OR 3.025, 95% CI 1.587-5.765), surgeon volume <200 cases (OR 1.881, 95% CI 1.120-3.159) and a preoperative PSA >10 ng/ml (OR 3.674, 95% CI 1.379-9.796) remained independent prognostic factors. In a subgroup of patients undergoing a nerve-sparing RARP, the quality of the prostate biopsy (OR 2.398, 95% CI 1.325-4.341) was the sole independent risk factor for a PSM. Conclusion: An elevated preoperative PSA, surgical experience and a nerve-sparing procedure are all significantly associated with a higher risk for a PSM after RARP. For those undergoing a nerve sparing RARP, an accurate preoperative biopsy with detailed information on the location of positive cores is essential to prevent PSMs.
Alopecic and Aseptic Nodules of the Scalp/Pseudocyst of the Scalp: Clinicopathological and Therapeutic Analyses in 11 Korean Patients
Authors: Seol Jung Eun , Park In Ho , Kim Do Hyeong , Park So Hee , Kang Jeong Nan , Kim Hyojin , Seo Jong Keun
Published: November 2015

Background: Alopecic and aseptic nodule of the scalp (AANS) is a rare disease entity first reported in 1992 as pseudocyst of the scalp (PCS). Controversy exists regarding the histopathology and etiology of reported cases. Objective: We performed this study to analyze the clinical and histopathologic features of AANS/PCS in Korean patients. Methods: A retrospective review of medical records from 2008 to 2013 at Inje University Busan Paik Hospital was performed. Results: Eleven patients were enrolled. All patients were male, and their mean age was 21.6 years. Most patients had a solitary nodule (10/11) located predominantly on the vertex. The mean nodule size was 20 mm. Inflammatory cell infiltration in the deep dermis was a histologic feature of AANS/PCS. Eight patients showed granulomatous infiltration. All patients were treated with short-term antibiotics and intralesional steroid injection. Conclusion: Our results suggest that dermatologists should consider AANS when diagnosing an alopecic nodule on the scalp.
Anti-Coagulation and Deep Brain Stimulation: Never the Twain Shall Meet?
Authors: Ashkan Keyoumars , Alamri Alexander , Ughratdar Ismail
Published: November 2015

Deep brain stimulation (DBS) for movement disorders is usually performed in older patients who may be prone to vascular co-morbidities such as atrial fibrillation or valvular disease that may require anti-coagulation. This potentially increases the risk of peri-operative intra-cranial haemorrhage and thus anti-coagulation therapy is generally considered a contraindication for DBS implantation. Cessation of anti-coagulants has to be balanced with the risk of thrombosis or ischaemic complications and, to compound issues, there is a paucity of guidelines and consensus on the management of anti-coagulation in patients undergoing DBS. To date, we have performed DBS successfully in 4 patients on lifelong anti-coagulation, having carefully managed their anti-coagulation in the peri-operative period. One patient developed a moderate haematoma around the implantable pulse generator 2 days post-operatively that was treated conservatively. Otherwise no other adverse effects or haemorrhagic complications occurred. We therefore propose that DBS implantation in this group of patients is safe, provided strict observation of protocols and careful management of the anti-coagulation therapy are undertaken. We describe the indications for anti-coagulation and provide a guideline for therapy in such patients according to our experience.
Abnormal Middle Cerebral Artery Doppler Associates with Spontaneous Preterm Birth in Normally Grown Fetuses
Authors: Morales-Roselló José , Khalil Asma , Salvi Sylvia , Townsend Rosemary , Premakumar Yaami , Perales-Marín Alfredo
Published: November 2015

Objective: Our aim was to evaluate whether Doppler changes in the fetal middle cerebral (MCA) and umbilical arteries (UA) suggesting fetal hypoxemia precede the onset of spontaneous preterm birth (PTB). Methods: We studied 2,340 appropriate-for-gestational-age singleton pregnancies that had MCA and UA pulsatility indices (PI) recorded at 28-32 weeks. Values including the cerebroplacental ratio (CPR) were converted into multiples of the median and evaluated according to both gestational age at the onset of labor and the interval between ultrasound and labor. ROC analysis was used to calculate the ability in the prediction of spontaneous PTB before 32, 34 and 37 weeks' gestation. Results: While no correlations were observed for the UA PI and CPR, lower MCA PI values were associated with an earlier onset of labor (p < 0.001) and a shorter ultrasound-labor interval (p = 0.028). The ROC analysis at different gestational ages and intervals to labor indicated that MCA PI values were poorly predictive of spontaneous PTB (all areas under the curve <0.7). Conclusions: Low MCA PI values at 28-32 weeks are associated with subsequent spontaneous PTB, indicating that fetal hypoxemia unrelated with placental disease might be implicated in the onset of labor. This association, however, is unlikely to be useful in the prediction of PTB.
Enalapril Associated with Furosemide Induced Acute Kidney Injury in an Infant with Heart Failure. A Case Report, a Revision of the Literature and a Pharmacovigilance Database Analysis
Authors: Fabiano Valentina , Carnovale Carla , Gentili Marta , Radice Sonia , Zuccotti Gian Vincenzo , Clementi Emilio , Perrotta Cristiana , Mameli Chiara
Published: November 2015

The use of angiotensin converting enzyme (ACE) inhibitors in combination with diuretics is a common strategy used for the treatment of patients affected by heart failure. An infant affected by initial congestive cardiac failure, after starting the treatment with enalapril in association with furosemide, developed acute kidney injury (AKI). No underlying renal disease or renal artery stenosis was found. He recovered from kidney injury after the therapy was suspended, thus suggesting that the drug combination is responsible for the onset of the adverse reaction. The present case report, the appraisal of the current knowledge on the onset of AKI and the analysis of available pharmacovigilance databases indicate that particular caution should be exercised when infants affected by heart failure are treated with the enalapril and furosemide combination therapy. Moreover, we strongly suggest an up-to-date revision of the ACE-inhibitor dosing guidelines in pediatric patients to define unambiguously the safe upper limits of this class of drugs.
Gender, Race, and Age at Diagnosis as Risk Factors for Metastasis or Recurrence among 1,657 Thyroid Cancer Patients Treated with Radioiodine across 40 Years in Singapore
Authors: Kao Yung Hsiang , Gan Hui Kong , Zaheer Sumbul , Lam Winnie W. C. , Loke Kelvin S. H. , Wong Wai Yin , Ng David C. E. , Goh Anthony S. W.
Published: November 2015

Background: To obtain descriptive data on Singaporean thyroid cancer patients treated with radioiodine and to assess gender, race, and age at diagnosis as risk factors for metastasis or recurrence. Methods: This is a retrospective study of all thyroid cancer patients treated with radioiodine of any prescribed activity at our institution. Data collected included: age at diagnosis, gender, race, histopathological type, duration of follow-up, and metastasis at diagnosis (locoregional or distant) or recurrence at any time. Gender, race, and age at diagnosis were analyzed for possible associations with metastasis or recurrence. Results: A total of 1,657 thyroid cancer patients were treated with radioiodine across a 40-year period; mean follow-up 6.4 ± 6.9 years (median 4.2 years). 656 (39.6%) patients had metastasis or recurrence over the duration of their follow-up. Male gender (odds ratio (OR) 1.38; p = 0.006), Malay race (OR 1.71; p < 0.0001), and age at diagnosis of > 46 years (OR 1.31; p = 0.007) were significantly associated with metastasis or recurrence. Conclusion: Male gender, Malay race, and age at diagnosis of > 46 years were significant risk factors for metastasis or recurrence in Singaporean thyroid cancer patients treated with radioiodine.
Towards Health for All: WHO and IMIA Intensify Collaboration
Authors: Geissbuhler A. , Haux R. , Kwankam S. Y.
Published: November 2015

Objective:
To intensify the collaboration between WHO, the World Health Organization, and IMIA, the International Medical Informatics Association.

Methods:
Identifying key areas of collaboration and publishing a joint communiqué during Medinfo 2007 in Brisbane, Australia.

Results and Conclusions:
WHO and IMIA have identified three keyareas of joint work for the next three years: the Global Observatory for eHealth, the use of I CT for the development of the health and health care workforce, and sharing eHealth products and services related to intellectual property for development.