bluuebunny/crossref_metadata_2025 huggingface dataset:
Rolling Element Bearing Performance Degradation Assessment Using Variational Mode Decomposition and Gath-Geva Clustering Time Series Segmentation
Authors: Li Yaolong , Li Hongru , Wang Bing , Gu Hongqiang
Published: October 2017

By focusing on the issue of rolling element bearing (REB) performance degradation assessment (PDA), a solution based on variational mode decomposition (VMD) and Gath-Geva clustering time series segmentation (GGCTSS) has been proposed. VMD is a new decomposition method. Since it is different from the recursive decomposition method, for example, empirical mode decomposition (EMD), local mean decomposition (LMD), and local characteristic-scale decomposition (LCD), VMD needs a priori parameters. In this paper, we will propose a method to optimize the parameters in VMD, namely, the number of decomposition modes and moderate bandwidth constraint, based on genetic algorithm. Executing VMD with the acquired parameters, the BLIMFs are obtained. By taking the envelope of the BLIMFs, the sensitive BLIMFs are selected. And then we take the amplitude of the defect frequency (ADF) as a degradative feature. To get the performance degradation assessment, we are going to use the method called Gath-Geva clustering time series segmentation. Afterwards, the method is carried out by two pieces of run-to-failure data. The results indicate that the extracted feature could depict the process of degradation precisely.
Human ADMC-Derived Adipocyte Thermogenic Capacity Is Regulated by IL-4 Receptor
Authors: Lizcano Fernando , Vargas Diana , Gómez Ángela , Torrado Astrid
Published: October 2017

Type two innate immune system is anti-inflammatory and may play an important role as the means whereby “browning” is induced in subcutaneous adipocytes. It was shown that IL-4 may influence the fate of adipose cell precursors by promoting differentiation towards more thermogenic adipocytes in mice. Here, we investigated the influence of IL-4 and IL-4 receptor, a type two immune cytokine pathway, on the metabolic activity and thermogenic potential of human adipocytes differentiated from adipose-derived mesenchymal stem cells (ADMSCs) obtained from subcutaneous samples of healthy women undergoing abdominoplasty. Western blot analysis, qPCR, and biochemical analyses were performed 10 days after ADMSC differentiation into mature adipocytes was induced. IL-4 receptor was expressed in both precursor and differentiated adipocytes, and IL-4 treatment increased phosphorylation Y641 of signal transducer and activator of transcription 6 (STAT6) in both cell types. IL-4 treatment also increased expression of thermogenic proteins PGC-1α, UCP-1, and CITED1. In addition, IL-4 increased the secretion of adiponectin, leptin, and FGF21 and promoted lipolysis in differentiated adipocytes. In conclusion, IL-4 may directly modulate differentiation of human adipocytes towards a beige phenotype acting through IL-4 receptors on both adipose precursors and differentiated human adipocytes, metabolic effect that must be considered in some antiallergic drugs.
Design, Modeling, and CFD Analysis of a Micro Hydro Pelton Turbine Runner: For the Case of Selected Site in Ethiopia
Authors: Nigussie Tilahun , Engeda Abraham , Dribssa Edessa
Published: October 2017

This paper addresses the design, modeling, and performance analysis of a Pelton turbine using CFD for one of the selected micro hydro potential sites in Ethiopia to meet the requirements of the energy demands. The site has a net head of 47.5 m and flow rate of 0.14 m3/s. The design process starts with the design of initial dimensions for the runner based on different literatures and directed towards the modeling of bucket using CATIA V5. The performance of the runner has been analyzed in ANSYS CFX (CFD) under given loading conditions of the turbine. Consequently, the present study has also the ambition to reduce the size of the runner to have a cost effective runner design. The case study described in this paper provides an example of how the size of turbine can affect the efficiency of the turbine. These were discussed in detail which helps in understanding of the underlying fluid dynamic design problem as an aid for improving the efficiency and lowering the manufacturing cost for future study. The result showed that the model is highly dependent on the size and this was verified and discussed properly using flow visualization of the computed flow field and published result.
Numerical Analysis on Chaotic Vibration of Drive System for a Movable Tooth Piezoelectric Motor
Authors: Li Chong , Xing Jichun , Fang Jiwen , Zhao Zhong
Published: October 2017

The nonlinear dynamic equations of the drive system for movable tooth piezoelectric motor are established. Using these equations, the chaotic vibrations of the system are investigated. The results show that chaotic vibrations occur in the movable tooth drive system under some parameters. The average mesh stiffness, theoretical radius, and wave generator offset significantly influence the nonlinear chaotic vibrations of the drive system of the movable tooth piezoelectric motor. The ranges for the system parameters that lead to a motor with bad dynamics are shown. The results can be used to predict the dynamic load and optimize power density of the proposed piezoelectric motor.
Evaluation of Deformable Image Registration for Three-Dimensional Temporal Subtraction of Chest Computed Tomography Images
Authors: Yan Ping , Kodera Yoshie , Shimamoto Kazuhiro
Published: October 2017

Purpose. To perform lung image registration for reducing misregistration artifacts on three-dimensional (3D) temporal subtraction of chest computed tomography (CT) images, in order to enhance temporal changes in lung lesions and evaluate these changes after deformable image registration (DIR). Methods. In 10 cases, mutual information (MI) lung mask affine mapping combined with cross-correlation (CC) lung diffeomorphic mapping was used to implement lung volume registration. With advanced normalization tools (ANTs), we used greedy symmetric normalization (greedy SyN) as a transformation model, which involved MI-CC-SyN implementation. The resulting displacement fields were applied to warp the previous (moving) image, which was subsequently subtracted from the current (fixed) image to obtain the lung subtraction image. Results. The average minimum and maximum log-Jacobians were 0.31 and 3.74, respectively. When considering 3D landmark distance, the root-mean-square error changed from an average of 20.82 mm for Pfixed to Pmoving to 0.5 mm for Pwarped to Pfixed. Clear shadows were observed as enhanced lung nodules and lesions in subtraction images. The lesion shadows showed lesion shrinkage changes over time. Lesion tissue morphology was maintained after DIR. Conclusions. DIR (greedy SyN) effectively and accurately enhanced temporal changes in chest CT images and decreased misregistration artifacts in temporal subtraction images.
Effect of Acupotomy on FAK‐PI3K Signaling Pathways in KOA Rabbit Articular Cartilages
Authors: Ma Shi-Ning , Xie Zhan-guo , Guo Yan , Yu Jia-Ni , Lu Juan , Zhang Wei , Wang Li-Juan , Xu Jing , Zhao Rui-Li , Zhou Shuai , Guo Chang-Qing
Published: October 2017

Objective. By observing the needle‐knife of KOA rabbit morphology, knee joint cartilage p‐FAK, p‐PI3K, Aggrecan gene, and protein expression, to study the effect of needle‐knife to promote cartilage cell synthesis metabolism mechanism. Method. 49 male New Zealand rabbits, randomly divided into normal group (Z), model group (M), model‐inhibitors (MP), needle‐knife group (D), needle‐knife inhibitors group (DP), electroacupuncture group (E), and electroacupuncture inhibitors (EP). RT‐PCR and Western Blot were used to test each animal cartilage p‐FAK, p‐PI3K, and Aggrecan gene and protein expression level. Results. Compared with N group, p‐FAK and p‐PI3K protein and mRNA expression of M group, D group, and E group increased (P < 0.05), while the protein and mRNA expression of Aggrecan reduced (P < 0.05). Compared with M group, p‐FAK, p‐PI3K, Aggrecan protein, and mRNA of E and D group increased (P < 0.05). Compared with E group, p‐FAK, p‐PI3K, Aggrecan protein, and mRNA expression of D group increased (P < 0.05); after adding inhibitors, p‐FAK, p‐PI3K, Aggrecan protein, and mRNA expression reduced (P < 0.05). Conclusion. Needle‐knife therapy can promote the repairment of cartilage cells by activating FAK‐PI3K signaling pathways, promoting the synthesis of cartilage cell metabolism.
Qingchang Wenzhong Decoction Attenuates DSS‐Induced Colitis in Rats by Reducing Inflammation and Improving Intestinal Barrier Function via Upregulating the MSP/RON Signalling Pathway
Authors: Mao Tangyou , Li Junxiang , Liu Lijuan , Zhao Weihan , Liu Yuyue , Gao Kangli , Guo Yi , Xie Tianhong , Li Ningfei , Shi Rui
Published: October 2017

Ulcerative colitis (UC) is a chronic, nonspecific, inflammatory disease for which an effective treatment is lacking. Our previous study found that Qingchang Wenzhong Decoction (QCWZD) can significantly improve the clinical symptoms of UC and ameliorate dextran sulphate sodium‐ (DSS‐) induced ulcerative colitis in rats by downregulating the IP10/CXCR3 axis–mediated inflammatory response. The purpose of the present study was to further explore the mechanism of QCWZD for UC in rats models, which were established by 7‐day administration of 4.5% dextran sulphate sodium solution. QCWZD was administered daily for 7 days; then we determined the serum macrophage‐stimulating protein concentration (MSP) and recepteur d’origine nantais (RON) expression and its downstream proteins (protein kinase B [Akt], phosphorylated [p] Akt, occludin, zona occluden‐ [ZO‐] 1, and claudin‐2) in colon tissue using Western blotting and quantitative polymerase chain reaction. In DSS‐induced UC, QCWZD significantly alleviated colitis‐associated inflammation, upregulated serum MSP expression and RON expression in the colon, reduced the pAkt levels, promoted colonic occluding and ZO‐1 expression, and depressed claudin‐2 expression. In conclusion, the MSP/RON signalling pathway plays an important role in the pathogenesis of UC by involving the inflammatory response and improving intestinal barrier function. QCWZD appears to attenuate DSS‐induced UC in rats by upregulating the MSP/RON signalling pathway.
Convergence Analysis of ParallelS-Iteration Process for System of Generalized Variational Inequalities
Authors: Sahu D. R. , Kang Shin Min , Kumar Ajeet
Published: October 2017

We consider a new system of generalized variational inequalities (SGVI) defined on two closed convex subsets of a real Hilbert space. To find the solution of considered SGVI, a parallel Mann iteration process and a parallelS-iteration process have been proposed and the strong convergence of the sequences generated by these parallel iteration processes is discussed. Numerical example illustrates that the proposed parallelS-iteration process has an advantage over parallel Mann iteration process in computing altering points of some mappings.
Uncertainty Instability Risk Analysis of High Concrete Arch Dam Abutments
Authors: Cao Xin , Gu Chongshi , Zhao Erfeng
Published: October 2017

The uncertainties associated with concrete arch dams rise with the increased height of dams. Given the uncertainties associated with influencing factors, the stability of high arch dam abutments as a fuzzy random event was studied. In addition, given the randomness and fuzziness of calculation parameters as well as the failure criterion, hazard point and hazard surface uncertainty instability risk ratio models were proposed for high arch dam abutments on the basis of credibility theory. The uncertainty instability failure criterion was derived through the analysis of the progressive instability failure process on the basis of Shannon’s entropy theory. The uncertainties associated with influencing factors were quantized by probability or possibility distribution assignments. Gaussian random theory was used to generate random realizations for influence factors with spatial variability. The uncertainty stability analysis method was proposed by combining the finite element analysis and the limit equilibrium method. The instability risk ratio was calculated using the Monte Carlo simulation method and fuzzy random postprocessing. Results corroborate that the modeling approach is sound and that the calculation method is feasible.
A Hybrid Service Recommendation Prototype Adapted for the UCWW: A Smart-City Orientation
Authors: Zhang Haiyang , Ganchev Ivan , Nikolov Nikola S. , Ji Zhanlin , O’Droma Máirtín
Published: October 2017

With the development of ubiquitous computing, recommendation systems have become essential tools in assisting users in discovering services they would find interesting. This process is highly dynamic with an increasing number of services, distributed over networks, bringing the problems of cold start and sparsity for service recommendation to a new level. To alleviate these problems, this paper proposes a hybrid service recommendation prototype utilizing user and item side information, which naturally constitute a heterogeneous information network (HIN) for use in the emerging ubiquitous consumer wireless world (UCWW) wireless communication environment that offers a consumer-centric and network-independent service operation model and allows the accomplishment of a broad range of smart-city scenarios, aiming at providing consumers with the “best” service instances that match their dynamic, contextualized, and personalized requirements and expectations. A layered architecture for the proposed prototype is described. Two recommendation models defined at both global and personalized level are proposed, with model learning based on the Bayesian Personalized Ranking (BPR). A subset of the Yelp dataset is utilized to simulate UCWW data and evaluate the proposed models. Empirical studies show that the proposed recommendation models outperform several widely deployed recommendation approaches.
Effects of Variety and Postharvest Handling Practices on Microbial Population at Different Stages of the Value Chain of Fresh Tomato(Solanum lycopersicum)in Western Terai of Nepal
Authors: Khadka Ram B. , Marasini Madan , Rawal Ranjana , Gautam Durga M. , Acedo Antonio L.
Published: October 2017

Background. Fresh vegetables such as tomato should have low microbial population for safe consumption and long storage life. The aerobic bacterial count (ABC) and coliform bacterial count (CBC), yeast, and mold population are the most widely used microbial indicators in fresh vegetables which should be lower than 4 log CFU g−1for safe consumption. The stages of the supply chain, postharvest handling methods, and crop varieties had significant effects on microbial population. ABC, CBC, yeast, and mold population were significantly highest (P<0.05) at retail market (5.59, 4.38, 2.60, and 3.14 log CFU g−1, resp.), followed by wholesale market (4.72, 4.71, 2.43, and 2.44 log CFU g−1, resp.), and were least at farm gate (3.89, 3.63, 2.38, and 2.03 log CFU g−1, resp.). Improved postharvest practices (washing in clean water and grading and packaging in clean plastic crate) helped to reduce ABC, CBC, and mold population by 2.51, 32.70, and 29.86 percentage as compared to the conventional method (no washing and no grading and packaging in mud plastered bamboo baskets). Among varieties, Pusa ruby had the lowest microbial load of 2.58, 4.53, 0.96, and 1.77 log CFU g−1for ABC, CBC, yeast, and mold count, respectively. Significantly negative correlation (P<0.05) was observed between fruit pH & ABC and pH & mold count. Although the microbial quality of fresh tomato is safe in the local market of western Terai of Nepal both in conventional and in improved practices however still it is essential to follow improved postharvest handling practices in production and marketing of newly introduced tomato cultivars (high-pH cultivars) for ensuring the safe availability of fresh tomato in the market.
Ectopic Breast Tissue of the Vulva in a Postmenopausal Woman
Authors: Mikhael Sasha , Nilsson Wesley , Patel Kruti , Graf Sherri
Published: October 2017

Ectopic breast tissue is a rare condition caused by remnants of the mammary ridges that fail to involute during embryologic development. To date, only 39 cases have been reported in the literature worldwide. Here, we report the 40th case of a 69-year-old G3P2 postmenopausal Caucasian woman who presented with complaint of vulvar swelling. Biopsy of the mass revealed the presence of a benign mammary gland-like adenoma which was completely excised shortly thereafter. Clinical presentation of vulvar breast tissue is highly variable depending on the amount of breast tissue developed and its functionality. Diagnosis is ultimately made by tissue biopsy and histopathologic examination. Due to the scarce evidence that exists pertaining to supernumerary breast tissue located on the vulva, specific management guidelines are lacking. Since this ectopic tissue serves no function, but rather may provide a source for future malignancy, surgical excision is recommended.
Ethanol Extract of Root of Prunus persica Inhibited the Growth of Liver Cancer Cell HepG2 by Inducing Cell Cycle Arrest and Migration Suppression
Authors: Shen Hongchun , Wang Honglian , Wang Li , Wang Lu , Zhu Menglian , Ming Yao , Zhao Sha , Fan Junming , Lai En Yin
Published: October 2017

Liver cancer is the second most lethal cancer and hepatocellular carcinoma (HCC) is the primary cancer subgroup. However, the current chemotherapy agents remain ineffective and present wide side effects for advanced HCC patient. In this study, we investigated the antitumor role of ethanol extract of root of peach tree (Prunus persica (L.) Batsch and hereafter designated as TSG in short of its Chinese name), which is an important ingredient in Chinese medicine prescription, in liver cancer cell HepG2. By cell viability assay, we showed that addition of TSG in the culture medium inhibited the cell growth of HepG2 cells in a dose and time‐dependent way. Cell cycle analysis indicated that TSG caused sustained M/G2 phase arrest. The expression of mitosis‐related protein Cdc25c was impaired upon TSG treatment. Furthermore, wound healing assay demonstrated that TSG treatment notably suppressed the migration of HepG2 cells and the expression of extracellular matrix metalloprotease, MMP3 and MMP9. Most significantly, administration of TSG inhibited in vivo tumor growth in nude mice. Our findings suggested that TSG may serve as a source to isolate anti‐HCC therapeutic ingredients.
Hypoxemic Respiratory Failure from Acute Respiratory Distress Syndrome Secondary to Leptospirosis
Authors: Fernando Shannon M. , Cardinal Pierre , Brindley Peter G.
Published: October 2017

Acute respiratory distress syndrome (ARDS), characterized by hypoxemic respiratory failure, is associated with a mortality of 30–50% and is precipitated by both direct and indirect pulmonary insults. Treatment is largely supportive, consisting of lung protective ventilation and thereby necessitating Intensive Care Unit (ICU) admission. The most common precipitant is community-acquired bacterial pneumonia, but other putative pathogens include viruses and fungi. On rare occasions, ARDS can be secondary to tropical disease. Accordingly, a history should include travel to endemic regions. Leptospirosis is a zoonotic disease most common in the tropics and typically associated with mild pulmonary complications. We describe a case of a 25-year-old male with undiagnosed leptospirosis, presenting with fever and severe hypoxemic respiratory failure, returning from a Costa Rican holiday. There was no other organ failure. He was intubated and received lung protective ventilation. His condition improved after ampicillin and penicillin G were added empirically. This case illustrates the rare complication of ARDS from leptospirosis, the importance of taking a travel history, and the need for empiric therapy because of diagnostic delay.
Living Conditions and Helicobacter pylori in Adults
Authors: Amaral Odete , Fernandes Isabel , Veiga Nélio , Pereira Carlos , Chaves Claudia , Nelas Paula , Silva Daniel
Published: October 2017

Introduction. Infection by the bacterium Helicobacter pylori (H. pylori) is transmissible and is considered a public health issue which affects people of all ages. The objective of this study was to identify factors (lifestyles, dietary factors, and hygiene conditions) related to the prevalence of H. pylori infection. Methods. We carried out an observational cross-sectional study with a community sample of adults from the municipalities of Viseu and Sátão, Portugal. The final sample resulted in 166 adults. The data were collected through a self-administered questionnaire with questions regarding sociodemographic aspects and lifestyles. H. pylori infection was identified using the 13C-urea breath test. Results. No association was found between the prevalence of H. pylori infection and the use of tobacco, alcohol, or coffee or dietary factors. The prevalence of H. pylori infection was higher in adults who reported higher consumption of fried food and lower consumption of vegetables and fruit. H. pylori infection was significant for the variables of lower frequency of handwashing before going to the bathroom (p=0.02) and well water consumption (p=0.05). Conclusion. A significant association was found for H. pylori infection with the lower frequency of handwashing before going to the bathroom and the consumption of well water.
A Psychological Perspective on Preterm Children: The Influence of Contextual Factors on Quality of Family Interactions
Authors: Gatta Michela , Miscioscia Marina , Svanellini Lorenza , Peraro Chiara , Simonelli Alessandra
Published: October 2017

Preterm birth has a critical influence on interactive, communicative, and expressive child behaviour, particularly during the first years of life. Few studies have stressed the assessment of mother-father-child interaction in families with preterm children, generating contradictory results. The present study wished to develop these fields: (i) comparing the quality of family interactions between families with preterm children and families with children born at full term; (ii) observing the development of family interactions after six months in the families with children born preterm; (iii) assessing family and contextual factors, as parental stress and social support, in parents of preterm children in order to observe their influence on the quality of family interactions. 78 families are recruited: 39 families with preterm children (M= 19,8 months, SD = 11,05) and 39 families with full-term children (M= 19,66 months; SD = 13,10). Results show that families with preterm children display a low quality of mother-father-child interactions. After six months, family interactions result is generally stable, except for some LTP-scales reflecting a hard adjustment of parenting style to the evolution of the child. In families with preterm children, the parenting stress seemed to be correlated with the quality of mother-father-child interactions.
Patients Affected by Unmethylated O(6)-Methylguanine-DNA Methyltransferase Glioblastoma Undergoing Radiochemotherapy May Benefit from Moderately Dose-Escalated Radiotherapy
Authors: Tini Paolo , Nardone Valerio , Pastina Pierpaolo , Battaglia Giuseppe , Miracco Clelia , Sebaste Lucio , Rubino Giovanni , Cerase Alfonso , Pirtoli Luigi
Published: October 2017

Purpose. To compare the therapeutic results of two radiotherapy (RT) dose schedules in combined temozolomide- (TMZ-) RT treatment in newly diagnosed glioblastoma (GB), according to the O(6)-methylguanine-DNA methyltransferase (MGMT) methylation status.Material and Method. Patients received either standard (60 Gy) or moderately escalated dose (70 Gy) radiotherapy (RT) with concomitant and adjuvant TMZ between June 2006 and October 2013. We retrospectively evaluated the therapeutic effectiveness of RT schedules in terms of Overall Survival (OS) and Progression-Disease Free Survival (PDFS) analyzing the MGMT methylation status.Results. One hundred and seventeen patients were selected for the present analysis. Seventy-two out of the selected cases received the standard RT-TMZ course (SDRT-TMZ) whereas the remaining 45 underwent the escalated schedule (HDRT-TMZ). The analysis according to the MGMT promoter methylation status showed that, in unmethylated-MGMT GB patients, HDRT-TMZ and SDRT-TMZ groups had different median OS (p=0,01) and PDFS (p=0,007), that is, 8 months and 5 months for the SDRT-TMZ group and 14 months and 9 months for the HDRT-TMZ group, respectively. No difference in survival outcomes was found in methylated MGMT patients according to the two RT schedules (p=0,12).Conclusions. In our experience, unmethylated-MGMT GB patients benefited from a moderately escalated dose of RT plus TMZ.
Design and Testing of an Experimental Steam-Induced Burn Model in Rats
Authors: Porumb Vlad , Trandabăț Alexandru Florentin , Terinte Cristina , Căruntu Irina Draga , Porumb-Andrese Elena , Dimofte Mihail Gabriel , Pieptu Dragoş
Published: October 2017

Background. Most of the current models for experimental burns pose difficulties in ensuring consistency and standardization.Aim of Study. We aimed to develop an automated, reproducible technique for experimental burns using steam-based heat transfer.Methods. The system developed for steam exposure was based on a novel, integrated, computer-controlled design. Three groups of rats were exposed to steam for 1, 3, and 7 seconds. The lesions were evaluated after 20 minutes, 48 hours, and 72 hours after burn induction.Results. One-second steam application produced a superficial second-degree burn; three-second application induced deep second-degree burn; and seven-second application led to a third-degree burn.Conclusion. The high level of automation of our integrated, computer-controlled system makes the difference between our system and other models, by ensuring the control of the duration of exposure, temperature, and pressure and eliminating as many potential human generated errors as possible. The automated system can accurately reproduce specific types of burns, according to histological assessment. This model could generate the reproducible data needed in the study of burn pathology and in order to assess new treatments.
Metabolite Profiling Reveals the Glutathione Biosynthetic Pathway as a Therapeutic Target in Triple-Negative Breast Cancer
Authors: Beatty Alexander , Fink Lauren S. , Singh Tanu , Strigun Alexander , Peter Erik , Ferrer Christina M. , Nicolas Emmanuelle , Cai Kathy Q. , Moran Timothy P. , Reginato Mauricio J. , Rennefahrt Ulrike , Peterson Jeffrey R.
Published: October 2017

Cancer cells can exhibit altered dependency on specific metabolic pathways and targeting these dependencies is a promising therapeutic strategy. Triple-negative breast cancer (TNBC) is an aggressive and genomically heterogeneous subset of breast cancer that is resistant to existing targeted therapies. To identify metabolic pathway dependencies in TNBC, we first conducted mass spectrometry–based metabolomics of TNBC and control cells. Relative levels of intracellular metabolites distinguished TNBC from nontransformed breast epithelia and revealed two metabolic subtypes within TNBC that correlate with markers of basal-like versus non-basal–like status. Among the distinguishing metabolites, levels of the cellular redox buffer glutathione were lower in TNBC cell lines compared to controls and markedly lower in non-basal–like TNBC. Significantly, these cell lines showed enhanced sensitivity to pharmacologic inhibition of glutathione biosynthesis that was rescued by N-acetylcysteine, demonstrating a dependence on glutathione production to suppress ROS and support tumor cell survival. Consistent with this, patients whose tumors express elevated levels of γ-glutamylcysteine ligase, the rate-limiting enzyme in glutathione biosynthesis, had significantly poorer survival. We find, further, that agents that limit the availability of glutathione precursors enhance both glutathione depletion and TNBC cell killing by γ-glutamylcysteine ligase inhibitors in vitro. Importantly, we demonstrate the ability to this approach to suppress glutathione levels and TNBC xenograft growth in vivo. Overall, these findings support the potential of targeting the glutathione biosynthetic pathway as a therapeutic strategy in TNBC and identify the non-basal-like subset as most likely to respond. Mol Cancer Ther; 17(1); 264–75. ©2017 AACR.
Ovarian Cancer: A Heterogeneous Disease
Authors: Kossaï Myriam , Leary Alexandra , Scoazec Jean-Yves , Genestie Catherine
Published: October 2017

Ovarian cancer encompasses a collection of neoplasms with distinct clinicopathological and molecular features and prognosis. Despite there being a variety of ovarian cancer subtypes, these are treated as a single disease. Tremendous efforts have been made to characterize these subtypes and identify tumoral pathways and potential biomarkers for therapeutic strategies. As in other cancer types, tumor heterogeneity appears to be very high across subtypes and within a single tumor, representing a major cause of treatment failure. We describe the morphological and molecular heterogeneity among ovarian cancers and discuss recent advances in our understanding of intratumor heterogeneity.
Mechanism of Action of TiF4 on Dental Enamel Surface: SEM/EDX, KOH-Soluble F, and X-Ray Diffraction Analysis
Authors: Comar Lívia P. , Souza Beatriz M. , Al-Ahj Luana P. , Martins Jessica , Grizzo Larissa T. , Piasentim Isabelle S. , Rios Daniela , Buzalaf Marília Afonso Rabelo , Magalhães Ana Carolina
Published: October 2017

This in vitro study aimed to evaluate the action of TiF4 on sound and carious bovine and human enamel. Sound (S) and pre-demineralised (DE) bovine and human (primary and permanent) enamel samples were treated with TiF4 (pH 1.0) or NaF varnishes (pH 5.0), containing 0.95, 1.95, or 2.45% F for 12 h. The enamel surfaces were analysed using SEM-EDX (scanning electron microscopy/energy-dispersive X-ray spectroscopy) (n = 10, 5 S and 5 DE) and KOH-soluble fluoride was quantified (n = 20, 10 S and 10 DE). Hydroxyapatite powder produced by precipitation method was treated with the corresponding fluoride solutions for 1 min (n = 2). The formed compounds were detected using X-ray diffraction (XRD). All TiF4 varnishes produced a coating layer rich in Ti and F on all types of enamel surface, with micro-cracks in its extension. TiF4 (1.95 and 2.45% F) provided higher fluoride deposition than NaF, especially for bovine enamel (p < 0.0001). It also induced a higher fluoride deposition on DE samples compared to S samples (p < 0.0001), except for primary enamel. The Ti content was higher for bovine and human primary enamel than human permanent enamel, with some differences between S and DE. The XRD analysis showed that TiF4 induced the formation of new compounds such as CaF2, TiO2, and Ti(HPO4)2·H2O. In conclusion, TiF4 (>0.95% F) interacts better, when compared to NaF, with bovine and human primary enamel than with human permanent enamel. TiF4 provoked higher F deposition compared to NaF. Carious enamel showed higher F uptake than sound enamel by TiF4 application, while Ti uptake was dependent on the enamel condition and origin.
Identifying a Potential Summary Measure for Overall Caries Level in Children Examined with the International Caries Detection and Assessment System
Authors: ElSalhy Mohamed , Alsumait Aishah , Lai Hollis , Almerich-Silla José Manuel , Piovesan Chaiana , Flores-Mir Carlos , Amin Maryam
Published: October 2017

Objective: To identify a potential summative summary measure that reflects a patient's overall caries level in children examined with the International Caries Detection and Assessment System (ICDAS). Subjects and Methods: Participants were 1- to 15-year-old children from Kuwait, Brazil, and Spain. Children's teeth were examined using the ICDAS. Multiple measures of central tendency and dentition-specific indices were considered as potential summative measures. The relationship between the summative measures and number of caries lesions was evaluated considering degrees of caries severity using Spearman's correlation analysis. The results were generated using the Kuwaiti sample and were cross-validated using the Brazilian and Spanish samples. Results: A total of 2,808 children participated in the present study. Total ICDAS score and mean ICDAS score showed a strong correlation with the number of caries lesions at different caries severity levels in primary, mixed, and permanent dentitions. The total ICDAS score of 51 buccal (B), 61B, 54 occlusal (O), 55O, 64O, 65O, 74O, 75O, 84O, and 85O surfaces in primary dentition and the total ICDAS score of 14O, 16 lingual (L), 16O, 24O, 26L, 26O, 36B, 36O, 37O, 46O, 46B, and 47O surfaces in permanent dentition or mixed dentition (if present) showed strong correlations with the number of caries lesions at different caries severity levels. Conclusions: Total ICDAS and mean ICDAS scores were the best summary measures of overall caries level at different dental stages. Total ICDAS scores of selectively examined 10 surfaces in primary dentition and 12 surfaces in permanent dentition can give an excellent summary measure for a patient's overall caries level with high diagnostic accuracy.
Impact of Typhoon Haiyan on a Philippine Tarsier Population
Authors: Gursky Sharon , Salibay Cristina , Grow Nanda , Fields Lori
Published: October 2017

Over the last 2 decades the Philippine tarsier (Carlito syrichta aka Tarsius syrichta) has had its conservation status revised from Endangered to Data Deficient to Near Threatened. The last status change was based on a study of the species' population density, which suggested that a single natural catastrophe could potentially wipe out the Philippine tarsier. In 2013 typhoon Haiyan hit Bohol, one of the island strongholds for this species. In this study we compare the density of the Bohol tarsier population within the Philippine Tarsier and Wildlife Sanctuary before and after the typhoon. We demonstrate that the typhoon significantly affected the density of the Philippine tarsier in the sanctuary. Before the typhoon, tarsier density was approximately 157 individuals/km2 whereas after the typhoon the density was a mere 36 individuals/km2. Prior to the typhoon, more Philippine tarsiers were found in older secondary forest than in younger secondary forest, whereas after the typhoon all observed individuals were found in relatively younger secondary forest. Vegetation plots where we observed Philippine tarsiers prior to the typhoon contained a mean of 33 trees/m2, with a mean diameter at breast height (DBH) of 24 cm, and a mean height of 4 m. After the typhoon vegetation plots contained an average of 156 trees, had a mean DBH of 6 cm, and a mean height of 2 m. Based on the IUCN Red List criteria, the reduction and fluctuation in the density of this species suggests that the conservation status of the Philippine tarsier should be changed to Vulnerable. This study indicates natural disasters can have a significant effect on the extinction risk of primates, with implications for future effects of anthropogenic climate change.
Ein scharfer Blick hinter getrübte Kulissen: Alexithymie bei Psoriasis
Authors: Gieler Uwe
Published: October 2017

Hintergrund/Ziele: Psoriasis als dermatologische Erkrankung hat komplexe Auswirkungen auch auf die psychische Gesundheit und die seelische Verfassung des Patienten. Viele Autoren vertreten die Auffassung, dass es für die Beurteilung der Schwere einer Psoriasiserkrankung sinnvoller ist, die Auswirkungen der Psoriasis auf das Leben des Patienten zu betrachten als eine Körperoberflächenmessung durchzuführen. Alexithymie ist eine Persönlichkeitsdimension, die durch Schwierigkeiten bei der Benennung von Empfindungen und Beschreibung von Gefühlen sowie bei einer auf das Äußere ausgerichteten Denkweise gekennzeichnet ist und bei vielen klinischen Krankheitsbildern vorkommt, insbesondere bei psychosomatischen Störungen. Das Ziel der vorliegenden Studie war der Vergleich der Alexithymie-Prävalenz bei Patienten mit Plaque-Psoriasis und bei Gesunden, unter Berücksichtigung demographischer und klinischer Variablen. Methoden: 250 Patienten mit chronischer Plaque-Psoriasis ohne systemische Vorbehandlung und 215 gesunde Personen wurden in die Studie eingeschlossen. Zur Beurteilung der Alexithymie wurde die Toronto-Alexithymie-Skala mit 20 Items (TAS-20) angewendet. Die erhobenen Daten wurden analysiert. Ergebnisse: Der mittlere TAS-Score betrug 53,5 (±15,3) in der Gruppe der Psoriasis-Patienten und 45,1 (±10,8) in der Kontrollgruppe (p < 0,0001). Die Psoriasis-Patienten zeigten im Vergleich zu den Kontrollpersonen signifikante Anzeichen von Alexithymie (32,4 vs. 9,3%); hierbei bestand kein signifikanter Unterschied zwischen den Patienten mit hohem oder niedrigem Schweregrad der Erkrankung. Ein signifikanter Zusammenhang bestand zwischen Alexithymie und weiblichem Geschlecht sowie Beteiligung sensibler Körperregionen, z.B. Gesicht, Hände und Genitalbereich. Schlussfolgerung: Diese Studie legt nahe, dass die Untersuchung auf Alexithymie Bestandteil der umfassenden Versorgung von Patienten mit mittel- bis hochgradiger Schuppenflechte werden sollte. Der TAS-20-Fragebogen ist hierfür ein sinnvolles und einfach anzuwendendes Instrument für die tägliche Praxis.
Antidiabetika in der Psoriasis-Therapie
Authors: Hedtrich Sarah
Published: October 2017

Psoriasis ist eine verbreitete chronisch-entzündliche Hauterkrankung, die sich mit schuppig-erythematösen Plaques infolge der Proliferation von Keratinozyten und Entzündungsreaktionen manifestiert. Psoriasis tritt häufig im Zusammenhang mit Komorbiditäten wie Diabetes, Adipositas oder dem metabolischen Syndrom auf. Für die Therapie der Psoriasis stehen zwar zahlreiche effektive Therapieoptionen zur Verfügung, jedoch weisen diese klare Limitierungen auf, wie beispielsweise hinsichtlich der Bioverfügbarkeit, Toxizität (z.B. Immunsuppression) oder hohen Kosten. Mehrere Studien konnten nun positive Effekte verschiedener blutzuckersenkender Wirkstoffe (z.B. Agonisten des Glucagon-like-Peptid-1-Rezeptors (GLP-1), Dipeptidylpeptidase-4-Hemmer (DPP-4-Hemmer), Thiazolidine oder Biguanide) nachweisen, die sich positiv auf die Symptomatik der Psoriasis auswirken. In dieser Übersichtsarbeit wird die Evidenz für die therapeutische Rolle hypoglykämischer Wirkstoffe bei Psoriasis zusammengefasst und die potenziell zugrunde liegenden Mechanismen diskutiert. Wir gelangen zu dem Schluss, dass Dermatologen den Einsatz hypoglykämischer Wirkstoffe bei Psoriasis in Betracht ziehen sollten, insbesondere in Fällen mit koexistierendem Diabetes oder wenn eine Immunsuppression kontraindiziert ist. Eine frühzeitige Konsultation von Endokrinologen könnte angezeigt sein.
Acupuncture May Improve Quality of Life in Menopausal Women: A Meta-Analysis of Randomized Controlled Trials
Authors: Li Weihan , Luo Yunyun , Fu Wenbin , Lei Rui
Published: October 2017

Objective: This analysis aims to identify, on the basis of the results of randomized controlled trials (RCTs), whether acupuncture therapy can alleviate menopausal symptoms and promote health-related quality of life. Methods: We included RCTs that directly compared any type of acupuncture with sham acupuncture in treating menopause-related symptoms and which were published from January 1, 2010 to December 31, 2016 in 6 electronic databases. Two authors performed this work independently; ‘risk-of-bias' assessment and data extraction were also independently performed by these 2 review authors. The outcomes are presented as scores of the menopause rating scale (MRS), which represents the self-assessment of patients. Results: Six studies were included. Our analysis found that acupuncture can reduce the MRS score in menopausal women by the end of the treating period (2-3 months, on average) and even in the follow-up period (1-3 months), not only in the total score but also in each subscale score. But the grade of evidence is very low. Conclusions: Both the total score and the subgroup analysis strongly indicated that acupuncture can alleviate menopause-related symptoms. However, the evidence is not very strong. Thus, further studies about the efficiency of acupuncture on menopausal symptoms based on well-designed trials are needed.
Bipolar Disorder and/or Creative Bipolarity: Robert Schumann's Exemplary Psychopathology - Combining Symptomatological and Psychosocial Perspectives with Creativity Research
Authors: Holm-Hadulla Rainer Matthias , Koutsoukou-Argyraki Asimina
Published: October 2017

The psychopathological condition of Robert Schumann has been a prominent object of study in psychiatry since his hospitalization in 1854. Renowned psychiatrists have diagnosed Schumann with syphilis, schizophrenia, and bipolar and personality disorders. Until today, these analyses of his symptomatology have led to contradictory results. Recent discussion has suggested that his hospitalization was due to professional failure and separation wishes on the part of his wife, her family, and her friends. In line with this hypothesis is the opinion that the separation insisted upon by Clara Schumann was reinforced by the economic interests of the psychiatrist who kept Schumann in custody for 2 years until his death in 1856. In this article, we trace the complex interaction of bipolar vulnerability and pathogenic life events with hypersensitive talent and “creative bipolarity,” defined as the capacity, motivation, and resilience to transform emotional stress and cognitive inconsistency into coherent artistic products. Finally, we present our conclusions about comprehensive psychiatric and psychotherapeutic treatment with respect to “creative bipolarity.”
Effect of Concurrent Src Kinase Inhibition with Short-Duration Hypothermia on Ca2+/Calmodulin Kinase IV Activity and Neuropathology after Hypoxia-Ischemia in the Newborn Swine Brain
Authors: Kratimenos Panagiotis , Koutroulis Ioannis , Jain Amit , Malaeb Shadi , Delivoria-Papadopoulos Maria
Published: October 2017

Background: Hypoxia-ischemia (HI) results in increased activation of Ca2+/calmodulin kinase IV (CaM kinase IV) mediated by Src kinase. Therapeutic hypothermia ameliorates neuronal injury in the newborn. Hypothesis: Inhibition of Src kinase concurrently with hypothermia further attenuates the hypoxia-induced increased activation of CaM kinase IV compared with hypothermia alone. Design/Methods: Ventilated piglets were exposed to HI, received saline or a selective Src kinase inhibitor (PP2), and were cooled to 33°C. Neuropathology, adenosine triphosphate (ATP) and phosphocreatine (PCr) concentrations, and CaM kinase IV activity were determined. Results: The neuropathology mean score (mean ± SD) was 0.4 ± 0.43 in normoxia-normothermia (p < 0.05 vs. hypoxia-normothermia), 3.5 ± 0.89 in hypoxia-normothermia (p < 0.05 vs. normoxia-normothermia), 0.7 ± 0.73 in hypoxia-hypothermia (p < 0.05 vs. normoxia-normothermia), and 0.5 ± 0.70 in normoxia-hypothermia (p < 0.05 vs. hypoxia-normothermia). The CaM kinase IV activity in cerebral tissue (pmol Pi/mg protein/min; mean ± SD) was 2,002 ± 729 in normoxia-normothermia, 1,704 ± 18 in normoxia-hypothermia, 6,017 ± 2,510 in hypoxia-normothermia, 4,104 ± 542 in hypoxia-hypothermia (p < 0.05 vs. normoxia-hypothermia), and 2,165 ± 415 in hypoxia-hypothermia with PP2 (p < 0.05 vs. hypoxia-hypothermia). The hypoxic groups with and without hypothermia or Src kinase inhibitor were comparable in the levels of ATP and PCr, indicating that they were similar in their degree of energy failure prior to treatments. Hypothermia or Src kinase inhibitor (PP2) did not restore the ATP and PCr levels. Conclusions: Hypothermia and Src kinase inhibition attenuated apoptotic cell death and improved neuropathology after hypoxia. The combination of short-duration hypothermia with Src kinase inhibition following hypoxia further attenuates the increased activation of CaM kinase IV compared to hypothermia alone in the newborn swine brain.
Kognitive Verhaltenstherapie bei komplizierter Trauer
Authors: Doering Bettina K. , Kühl Kerstin , Hofmann Mareike
Published: October 2017

Akute Trauer als normale Reaktion auf den Verlust einer nahestehenden Person wird in der Regel schmerzhaft erlebt. Dennoch bewältigen die meisten Betroffenen ihre Trauer ohne professionelle Hilfe. Eine Minderheit erlebt anhaltende und schwerwiegende Trauersymptome, die das Bild einer komplizierten Trauerstörung erfüllen können. Die Aufmerksamkeit für komplizierte Trauer als eigenständiges Störungsbild nimmt zu, auch bedingt durch die Berücksichtigung in den Neuauflagen der Klassifikationssysteme «International Statistical Classification of Diseases and Related Health Problems» (ICD-11) und «Diagnostisches und Statistisches Manual Psychischer Störungen» (DSM-5). Die Diagnostik muss allerdings die Gefahr einer Pathologisierung normaler Trauerreaktionen sowie Fehlklassifikationen berücksichtigen. Interventionen, die sich an alle Trauernden richten (universelle Prävention), zeigen nur minimale Effekte. Die Möglichkeit der Prävention komplizierter Trauer in Risikogruppen oder bei hochbelasteten Akuttrauernden wird kritisch diskutiert. Aktuelle randomisiert-kontrollierte Studien belegten aber die Überlegenheit störungsspezifischer gegenüber anderen Behandlungsansätzen (interpersonelle Psychotherapie) bei komplizierter Trauer. Bezüglich kognitiv-verhaltenstherapeutischer Interventionen sind die Exposition gegenüber trauer- oder verlustassoziierten Stimuli sowie die kognitive Umstrukturierung trauerspezifischer dysfunktionaler Gedanken hochgradig evidenzbasiert. Ein weiteres Behandlungselement ist die Etablierung neuer Ziele für ein Leben ohne die verstorbene Person. Auch die Verhaltensaktivierung zeigte erste positive Effekte. Neben der klassischen Face-to-Face-Psychotherapie sind dabei auch Internet-basierte Behandlungsangebote vielversprechend. Dennoch besteht weiterer Forschungsbedarf, beispielsweise hinsichtlich der differenziellen Effektivität einzelner Behandlungskomponenten.
Hopes and Difficulties for Blastocyst Complementation
Authors: Freedman Benjamin S.
Published: October 2017

Context: The clinical need for organ replacement therapies has inspired the idea of growing human organs in animal hosts. The injection of human pluripotent stem cells into animal blastocysts provides a possible strategy to accomplish this goal. Subject of Review: A recent study [Wu et al. Cell 2017;168:473-486.e415] tests the feasibility of this approach by creating chimeric embryos between humans and large domestic animals, including pigs and cattle. The study further examines the potential of combining CRISPR-Cas9 gene editing with blastocyst complementation to grow fully foreign organs in chimeric hosts. Second Opinion: Here, we consider what this report and related studies reveal about the likelihood of human-animal chimeras reaching the clinic and translating into therapies. A careful look suggests hope for eventual success in this area but also underscores important challenges that will require dedicated effort to resolve.
Acinar Cell Cystadenoma - a Rarity in Advanced von Hippel-Lindau Disease: A Case Report
Authors: Fahlbusch Tim , Tannapfel Andrea , Uhl Waldemar , Braumann Chris
Published: October 2017

Background: Von Hippel-Lindau (VHL) disease may occur at various localisations which can be both intra- and extrapancreatic as well as challenging to diagnose by medical imaging. Case Report: A positron emission tomography/magnetic resonance imaging in a 40-year-old woman was performed to monitor a haemangioblastoma. Additionally, it showed findings which were considered to be a pancreatic neuroendocrine tumour (pNET) and retroumbilical metastasis. The suspected metastasis was laparoscopically resected; however, pathological evaluation did not lead to a clear categorisation. Consequently, the pancreatic head was resected in which a pNET and various acinar cell cystadenomas were found. Conclusion: Diagnostic and therapy of advanced VHL disease can be difficult; if in doubt, a surgical approach may establish clarity.