bluuebunny/crossref_metadata_2025 huggingface dataset:
Herbal Medicine for Hot Flushes Induced by Endocrine Therapy in Women with Breast Cancer: A Systematic Review and Meta‐Analysis
Authors: Li Yuanqing , Zhu Xiaoshu , Bensussan Alan , Li Pingping , Moylan Eugene , Delaney Geoff , McPherson Luke
Published: June 2016

Objective. This systematic review was conducted to evaluate the clinical effectiveness and safety of herbal medicine (HM) as an alternative management for hot flushes induced by endocrine therapy in breast cancer patients. Methods. Key English and Chinese language databases were searched from inception to July 2015. Randomized Controlled Trials (RCTs) evaluating the effects of HM on hot flushes induced by endocrine therapy in women with breast cancer were retrieved. We conducted data collection and analysis in accordance with the Cochrane Handbook for Systematic Reviews of Interventions. Statistical analysis was performed with the software (Review Manager 5.3). Results. 19 articles were selected from the articles retrieved, and 5 articles met the inclusion criteria for analysis. Some included individual studies showed that HM can relieve hot flushes as well as other menopausal symptoms induced by endocrine therapy among women with breast cancer and improve the quality of life. There are minor side effects related to HM which are well tolerated. Conclusion. Given the small number of included studies and relatively poor methodological quality, there is insufficient evidence to draw positive conclusions regarding the objective benefit of HM. Additional high quality studies are needed with more rigorous methodological approach to answer this question.
Cancer Stem Cell Quiescence and Plasticity as Major Challenges in Cancer Therapy
Authors: Chen Wanyin , Dong Jihu , Haiech Jacques , Kilhoffer Marie-Claude , Zeniou Maria
Published: June 2016

Cells with stem‐like properties, tumorigenic potential, and treatment‐resistant phenotypes have been identified in many human malignancies. Based on the properties they share with nonneoplastic stem cells or their ability to initiate and propagate tumors in vivo, such cells were designated as cancer stem (stem‐like) or tumor initiating/propagating cells. Owing to their implication in treatment resistance, cancer stem cells (CSCs) have been the subject of intense investigation in past years. Comprehension of CSCs’ intrinsic properties and mechanisms they develop to survive and even enhance their aggressive phenotype within the hostile conditions of the tumor microenvironment has reoriented therapeutic strategies to fight cancer. This report provides selected examples of malignancies in which the presence of CSCs has been evidenced and briefly discusses methods to identify, isolate, and functionally characterize the CSC subpopulation of cancer cells. Relevant biological targets in CSCs, their link to treatment resistance, proposed targeting strategies, and limitations of these approaches are presented. Two major aspects of CSC physiopathology, namely, relative in vivo quiescence and plasticity in response to microenvironmental cues or treatment, are highlighted. Implications of these findings in the context of the development of new therapies are discussed.
Outcome of Home-Based Early Intervention for Autism in Sri Lanka: Follow-Up of a Cohort and Comparison with a Nonintervention Group
Authors: Perera Hemamali , Jeewandara Kamal Chandima , Seneviratne Sudarshi , Guruge Chandima
Published: June 2016

This paper presents the outcome of a home-based autism intervention program (HBAIP) in 18- to 40-month-old children newly diagnosed and treatment naïve. Intervention was exclusively implemented at home. Outcome was measured at 3 months and 6 months after intervention and compared with a group of newly diagnosed children with autism who were >40 months at intake but had not received any autism specific clinical management. Aim was also to estimate whether natural development would contribute to gain in skills and compare with the effect of intervention. Five selected parameters of behavior representing social interaction and social communication were used to assess outcome. Results showed a statistically significant improvement between preintervention and postintervention in all the measured parameters. The effect size was large when compared to preintervention and gains were indicated by changes in mean scores andpvalues within a narrow confidence interval. Highest gains were in first 3 months of postintervention which continued up to 6 months. Although the comparison group was more advanced in the measured skills at intake, they were significantly below the level reached by experimental group at 3 months and 6 months after intervention. This study was registered in the Sri Lanka Clinical Trials Registry (SLCTR/2009/011).
Numerical Implementation of Spatial Elastoplastic Damage Model of Concrete in the Framework of Isogeometric Analysis Approach
Authors: Ma Cheng , Chen Wei-zhen , Sun Jian-yuan
Published: June 2016

This paper is a study of the numerical implementation of the spatial elastoplastic damage model of concrete by isogeometric analysis (IGA) method from three perspectives: the geometric modeling and the numerical formulation via IGA method, the constitutive model of concrete, and the solution algorithms for the local and global problems. The plasticity of concrete is considered on the basis of a nonassociated flow rule, where a three-parameter Barcelona yield surface and a modified Drucker-Prager plastic potential are used. The damage evolution of concrete driven by the internal variables is expressed by a piecewise function. In the study, the return-mapping algorithm and the substepping strategy are used for stress updating, and a new dissipation-based arc-length method with constraint path that considers the combined contribution of plasticity and damage to the energy dissipation is employed to trace the equilibrium path. After comparisons between simulation results and experimental data, the use of the elastoplastic damage model in the framework of IGA approach is proven to be practical in reflecting material properties of concrete.
Ameliorative Effect of Chronic Supplementation of Protocatechuic Acid Alone and in Combination with Ascorbic Acid in Aniline Hydrochloride Induced Spleen Toxicity in Rats
Authors: Khairnar Upasana , Upaganlawar Aman , Upasani Chandrashekhar
Published: June 2016

Background. Present study was designed to evaluate the protective effects of protocatechuic acid alone and in combination with ascorbic acid in aniline hydrochloride induced spleen toxicity in rats.Materials and Methods. Male Wistar rats of either sex (200–250 g) were used and divided into different groups. Spleen toxicity was induced by aniline hydrochloride (100 ppm) in drinking water for a period of 28 days. Treatment group received protocatechuic acid (40 mg/kg/day, p.o.), ascorbic acid (40 mg/kg/day, p.o.), and combination of protocatechuic acid (20 mg/kg/day, p.o.) and ascorbic acid (20 mg/kg/day, p.o.) followed by aniline hydrochloride. At the end of treatment period serum and tissue parameters were evaluated.Result. Rats supplemented with aniline hydrochloride showed a significant alteration in body weight, spleen weight, feed consumption, water intake, hematological parameters (haemoglobin content, red blood cells, white blood cells, and total iron content), tissue parameters (lipid peroxidation, reduced glutathione, and nitric oxide content), and membrane bound phosphatase (ATPase) compared to control group. Histopathology of aniline hydrochloride induced spleen showed significant damage compared to control rats. Treatment with protocatechuic acid along with ascorbic acid showed better protection as compared to protocatechuic acid or ascorbic acid alone in aniline hydrochloride induced spleen toxicity.Conclusion. Treatment with protocatechuic acid and ascorbic acid in combination showed significant protection in aniline hydrochloride induced splenic toxicity in rats.
FusariumEndophthalmitis following Cataract Surgery: Successful Treatment with Intravitreal and Systemic Voriconazole
Authors: Alves da Costa Pertuiset Paulo A. , Logroño Juan F. Batlle
Published: June 2016

Purpose. To report a case of postoperative endophthalmitis caused byFusariumspecies successfully treated with intravitreal and systemic voriconazole after treatment failure with amphotericin B.Methods. Clinical case report of a 60-year-old immunocompetent woman who presents with endophthalmitis of unknown origin 4 weeks after uneventful cataract extraction and IOL implantation surgery. IOL explantation, vitrectomy with capsular bag removal, vitreous aspiration for culture, and intravitreal injection of amphotericin B (5 μg/0.1 mL) were performed. Diagnosis was established by culturing the vitreous aspirate on a Sabouraud agar medium and staining with lactophenol blue solution. Five days later, there was no clinical response. The decision was made to administer a single dose of intravitreal voriconazole (2.5 μg/0.1 mL) and oral voriconazole (200 mg BID) for 30 days.Results.Fusariumsp. grew on culture. Treatment with local and systemic voriconazole was started after no improvement with vitrectomy, IOL explantation, and intravitreal amphotericin B. After 1 month of treatment, the infection resolved and best-corrected visual acuity was 20/25.Conclusion. In patients with endophthalmitis caused byFusariumsp., topical and systemic voriconazole treatment should be considered in cases resistant to intravitreal amphotericin B.
Assessment of Left Ventricular Structural Remodelling in Patients with Diabetic Cardiomyopathy by Cardiovascular Magnetic Resonance
Authors: Shang Yongning , Zhang Xiaochun , Chen Liu , Leng Weiling , Lei Xiaotian , Yang Qi , Liang Ziwen , Wang Jian
Published: June 2016

Background. Diabetic cardiomyopathy (DCM) is always accompanied with alteration of left ventricular structure and function. The aims of this study were to assess the structural remodelling in patients with DCM by cardiovascular magnetic resonance (CMR) and correlation of structural remodelling with severity of DCM.Methods. Twenty-five patients (53.8±8.8years, 52.0% males) with DCM and thirty-one normal healthy controls (51.9±13.6years, 45.2% males) were scanned by CMR cine to assess function and structure of left ventricular. Length of diabetic history and results of cardiac echocardiography (E′, A′, and E′/A′) were also measured.Results. Compared with normal controls group, DCM group was associated with significantly increased ratio of left ventricular mass at end diastole to end-diastolic volume (MVR) (P<0.05) and no significant difference was in mass at end diastole (P>0.05). The ratio correlated with both length of diabetic history and echocardiographic Doppler tissue imaging E′ (allP<0.05).Conclusions. CMR can be a powerful technique to assess LV remodelling, and MVR may be considered as an imaging marker to evaluate the severity of LV remodelling in patients with DCM.
Reversible Akinetic Mutism after Aneurysmal Subarachnoid Haemorrhage in the Territory of the Anterior Cerebral Artery without Permanent Ischaemic Damage to Anterior Cingulate Gyri
Authors: Sibille François-Xavier , Hantson Philippe , Duprez Thierry , van Pesch Vincent , Giglioli Simone
Published: June 2016

We report on two cases of transient akinetic mutism after massive subarachnoid haemorrhage due to the rupture of an intracranial aneurysm of the anterior cerebral artery (ACA). In the two cases, vasospasm could not be demonstrated by imaging studies throughout the clinical course. Both patients shared common radiological features: a hydrocephalus due to haemorrhagic contamination of the ventricular system and a mass effect of a subpial hematoma on the borders of the corpus callosum. Patients were also investigated using auditory event-related evoked potentials at acute stage. In contrast to previous observations of akinetic mutism, P300 wave could not be recorded. Both patients had good recovery and we hypothesized that this unexpectedly favourable outcome was due to the absence of permanent structural damage to the ACA territory, with only transient dysfunction due to a reversible mass effect on cingulate gyri.
Transformation Mechanism of Fluormica to Fluoramphibole in Fluoramphibole Glass Ceramics
Authors: Si Wei , Xu Hua-Shen , Sun Ming , Ding Chao , Zhang Wei-Yi
Published: June 2016

During isothermal sintering at 820°C, the transformation mechanism of fluormica to fluoramphibole in powder compacts of fluormica and soda-lime glass was investigated using differential thermal analysis, infrared reflection spectrometry, X-ray diffraction, scanning electron microscopy, and so forth. Results show that an interaction between fluormica and glass occurred during isothermal heating; O2−, Na+, and Ca2+ions were diffused from glass to fluormica. This diffusion facilitates the transformation of the sheet structures of fluormica crystals to double-chain structures by the breakage of bridge oxygen bonds in the sheet. Subsequently, the broken two parallel double chains were rearranged by relative displacement along thec-axis direction of the fluormica crystal and were linked by Na+and Ca2+ions to form fluoramphibole. A crystallography model of fluormica-fluoramphibole transformation was established in this study.
Review on Optical and Electrical Properties of Conducting Polymers
Authors: Bajpai Manisha , Srivastava Ritu , Dhar Ravindra , Tiwari R. S.
Published: June 2016

We reviewed optical and electrical properties of conjugated polymers. The charge transport models to describe the hole and electron transport mechanism are also included in the electrical properties of conjugated polymers. The effect of optical and electrical properties after doping is also indexed in this paper.
Comparative Efficacy of the Air-Q Intubating Laryngeal Airway during General Anesthesia in Pediatric Patients: A Systematic Review and Meta-Analysis
Authors: Ahn Eun Jin , Choi Geun Joo , Kang Hyun , Baek Chong Wha , Jung Yong Hun , Woo Young Cheol , Bang Si Ra
Published: June 2016

Air-Q® (air-Q) is a supraglottic airway device which can be used as a guidance of intubation in pediatric as well as in adult patients. We evaluated the efficacy and safety of air-Q compared to other airway devices during general anesthesia in pediatric patients by conducting a systematic review and meta-analysis. A total of 10 studies including 789 patients were included in the final analysis. Compared with other supraglottic airway devices, air-Q showed no evidence for a difference in leakage pressure and insertion time. The ease of insertion was significantly lower than other supraglottic airway devices. The success rate of intubation was significantly lower than other airway devices. However, fiberoptic view was better through the air-Q than other supraglottic airway devices. Therefore, air-Q could be a safe substitute for other airway devices and may provide better fiberoptic bronchoscopic view.
A BTT-Based Colorimetric Dual Sensor for Hg(II) and Selected Anions with Molecular Logic Operations
Authors: Uahengo Veikko , Cai Ping , Daniel Likius S.
Published: June 2016

A benzotrithiophenes (BTT) based colorimetric sensor (2) was synthesized via a simple one-step reaction process, and its recognition properties towards several biologically important anions and cations were investigated by naked eye observation and spectroscopic methods of UV-vis and 1H NMR analysis in DMSO. The molar addition of anions such as F−, AcO−, and H2PO4- induced a marked red shift of the charge transfer band (Δλ=94 nm, from 440 nm to 534 nm) concomitant with a clearly visible “naked eye” detectable colorimetric activities (from orange to pink). However, the molar addition of H2PO4- did not induce significant spectral changes, compared to F− and AcO−. Furthermore, the molar addition of Hg2+ to 2 resulted in hypochromic shift at 440 nm and the eventual disappearance of a low energy band at 534 nm, concomitant with the colorimetric activities (from orange to yellow). Moreover, both spectral and color changes induced by the addition of anions (F− and AcO−) were all reversible by the molar addition of metal cations of 3d5–10. The reversibility properties triggered the logic operation studies, and, subsequently, the complementary IMP/INH logic functions based on color and spectral switching (ON/OFF) were confirmed. Conclusively, 2 can thus be utilized as a colorimetric molecular switch modulated by AcO−/MII.
Importance of Molds for Nanoimprint Lithography: Hard, Soft, and Hybrid Molds
Authors: Kwon B. , Kim Jong H.
Published: June 2016

Nanoimprint lithography has attracted considerable attention in academic and industrial fields as one of the most prominent lithographic techniques for the fabrication of the nanoscale devices. Effectively controllable shapes of fabricated elements, extremely high resolution, and cost-effectiveness of this especial lithographic system have shown unlimited potential to be utilized for practical applications. In the past decade, many different lithographic techniques have been developed such as electron beam lithography, photolithography, and nanoimprint lithography. Among them, nanoimprint lithography has proven to have not only various advantages that other lithographic techniques have but also potential to minimize the limitations of current lithographic techniques. In this review, we summarize current lithography techniques and, furthermore, investigate the nanoimprint lithography in detail in particular focusing on the types of molds. Nanoimprint lithography can be categorized into three different techniques (hard-mold, soft-mold, and hybrid nanoimprint) depending upon the molds for imprint with different advantages and disadvantages. With numerous studies and improvements, nanoimprint lithography has shown great potential which maximizes its effectiveness in patterning by minimizing its limitations. This technique will surely be the next generation lithographic technique which will open the new paradigm for the patterning and fabrication in nanoscale devices in industry.
Coherent RAKE Receiver for CPM-Based Direct Sequence Spread Spectrum
Authors: Zhou Ke , Wang Shilian , Zhang Eryang
Published: June 2016

Direct sequence spread spectrum (DSSS) using continuous phase modulation (CPM) inherits the techniques’ benefits, constant envelope, anti-interference, and spectral efficiency. To get diversity gains over a Rayleigh-fading multipath channel as in conventional direct sequence spread-spectrum binary phase shift keying (DSSS-BPSK) system, a new class of coherent RAKE receivers is proposed in this work. By introducing chip branch metric to the receiver scheme, despreading and data detection can be done meanwhile based on Maximum Likelihood Sequence Detection (MLSD). Compared to the conventional RAKE receiver which sums decision metrics symbol-by-symbol, the proposed DSSS-CPM RAKE receiver accumulates symbol branch metric increments over every phase state of multiple paths after chip phase synchronization. Numerical results show that DSSS-CPM using the synchronous despreading and demodulation algorithm has no performance loss compared to CPM system that employs MLSD algorithm under the same test conditions. Moreover, the proposed RAKE receiver outperforms conventional RAKE receiver and achieves a remarkable diversity gain of bit error rate (BER) under the Rayleigh-fading multipath channel.
Seismic Performance Evaluations of Mega-Sub Isolation System
Authors: Li Xiangxiu , Tan Ping , Li Xiaojun , Liu Aiwen
Published: June 2016

This paper presents mega-sub isolation system. Shaking table test of the mega-sub isolation system is carried out in this paper. Three test models have been developed. One is called aseismic model, in which all the substructures are fixedly connected with the megastructures. The second one is known as isolated model, where the substructures are connected with the megastructures with isolators, and the last one is called the lower substructure consolidated (LSC) model, in which all the substructures except for the substructures at the lowest level, in other words, substructures at the second mega floor, are isolated from the megastructures. Nonlinear dynamic time analysis of the test models is conducted by SAP2000. Acceleration responses of the megastructure, story drift responses of the megastructure and the substructure, and the deformations of the isolation layer are compared between experimental and numerical simulation results. The results show that the experimental results and numerical simulation results agree well with each other, and the isolated model and LSC model perform better than the counterpart aseismic model. The structures with isolation devices can reduce the structural responses effectively and are much safer than the structure without isolation devices.
Sagnac Interferometer Based Generation of Controllable Cylindrical Vector Beams
Authors: Acevedo Cristian , Guzmán Angela , Torres Moreno Yezid , Dogariu Aristide
Published: June 2016

We report on a novel experimental geometry to generate cylindrical vector beams in a very robust manner. Continuous control of beams’ properties is obtained using an optically addressable spatial light modulator incorporated into a Sagnac interferometer. Forked computer-generated holograms allow introducing different topological charges while orthogonally polarized beams within the interferometer permit encoding the spatial distribution of polarization. We also demonstrate the generation of complex waveforms obtained by combining two orthogonal beams having both radial modulations and azimuthal dislocations.
How Do Patients with Chronic Neck Pain Experience the Effects of Qigong and Exercise Therapy? A Qualitative Interview Study
Authors: Holmberg Christine , Farahani Zubin , Witt Claudia M.
Published: June 2016

Background. The high prevalence of chronic neck pain in high income countries impacts quality of life and the social and work‐related activities of those afflicted. We aimed to understand how mind‐body therapies and exercise therapy may influence the experience of pain among patients with chronic neck pain. Methods. This qualitative interview study investigated how patients with chronic neck pain experienced the effects of exercise or qigong therapy at two time points: during an intervention at three months and after the intervention at six months. Interviews were analysed thematically across interviews and within person‐cases. Based on other qualitative studies, a sample size of 20 participants was deemed appropriate. Results. The sample (n = 20) consisted of 16 women and four men (age range: 29 to 59). Patients’ experiences differed according to the therapies’ philosophies. Exercise therapy group interviewees described a focus on correct posture and muscle tension release. Qigong group interviewees discussed calming and relaxing effects. Maintaining regular exercise was easier to achieve with exercise therapy. Conclusions. The findings of this study may help health care providers when counselling chronic pain patients on self‐help interventions by informing them of different bodily and emotional experiences of mind‐body interventions compared to exercise therapy.
The Feasibility of a Land Ferry System to Reduce Highway Maintenance Cost and Associated Externalities
Authors: Merrill Steve J. , Paz Alexander , Molano Victor , Shrestha Pramen P. , Maheshwari Pankaj , Stephen Haroon , de la Fuente-Mella Hanns
Published: June 2016

This study provides an economic evaluation for a Land Ferry, which is a rail system capable of carrying trucks and all other types of vehicles, passengers, and cargo. The Land Ferry system involves a sliding loading system to roll heavy loads onto a flatbed; as a result, loading and unloading of all vehicles and cargo could be accomplished simultaneously. The evaluation for this system included (1) the design of a new track alignment over which the Land Ferry system would run, (2) evaluation of various sources of power, (3) estimation of how many local jobs the Land Ferry would generate, and (4) a benefit-cost analysis. It was estimated that the Land Ferry would create over 45,788 temporary jobs in Nevada during the three-year construction period and 318 permanent jobs during operation. The majority of the benefits were attributed to savings in travel time ($356.4 M), vehicle operating costs ($1000.4 M), reduction of accidents ($544.6 M), and pavement maintenance ($503.2 M). These benefits would be a consequence of the shift of trucks from the highway, thus resulting in higher speeds, decrease fuel consumption, and decrease vehicle maintenance costs. The overall benefit-cost ratio of 1.7 implies a cost-effective project.
Total Laparoscopic Hysterectomy in Patients with Large Uteri: Comparison of Uterine Removal by Transvaginal and Uterine Morcellation Approaches
Authors: Wang Haibo , Li Ping , Li Xiujuan , Gao Licai , Lu Caihong , Zhao Jinrong , Zhou Ai-ling
Published: June 2016

The aim of this study was to compare the clinical results of total laparoscopic hysterectomy (TLH) for large uterus with uterus size of 12 gestational weeks (g.w.) or greater through transvaginal or uterine morcellation approaches. We retrospectively collected the clinical data of those undergoing total laparoscopic hysterectomies between January 2004 and June 2012. Intraoperative and postoperative outcomes were compared between patients whose large uterus was removed through transvaginal or morcellation approaches. The morcellation group has significantly shorter mean operation time and uterus removal time and smaller incidence of intraoperative complications than the transvaginal group (allP<0.05). No statistical significant difference regarding the mean blood loss, uterine weight, and length of hospital stay was noted in the morcellation and transvaginal groups (allP>0.05). In two groups, there was one patient in each group who underwent conversion to laparotomy due to huge uterus size. With regard to postoperative complications, there was no statistical significant difference regarding the frequencies of pelvic hematoma, vaginal stump infection, and lower limb venous thrombosis in two groups (allP>0.05). TLH through uterine morcellation can reduce the operation time, uterus removal time, and the intraoperative complications and provide comparable postoperative outcomes compared to that through the transvaginal approaches.
Immunogenicity Assessment of Lipegfilgrastim in Patients with Breast Cancer Receiving Chemotherapy
Authors: Zou Linglong , Buchner Anton , Roberge Martin , Liu Patrick M.
Published: June 2016

Lipegfilgrastim is a long-acting, once-per-cycle, glycopegylated recombinant granulocyte colony-stimulating factor (G-CSF) used to prevent neutropenia in patients receiving myelosuppressive chemotherapy. This integrated analysis examined the immunogenicity of lipegfilgrastim and its potential clinical impact in two double-blind randomized studies (phases II and III) of patients with breast cancer receiving chemotherapy. Serum samples were analyzed using sequential assays for screening, confirmation, antibody titer, and characterization of antidrug antibodies (ADA). Neutropenia-related efficacy measures were reviewed for each ADA-positive patient. Among 255 patients receiving lipegfilgrastim (154 in phase II, 101 in phase III) and 155 patients receiving pegfilgrastim (54 in phase II, 101 in phase III), the incidence of treatment-emergent ADA was low and similar between the lipegfilgrastim (phase II: 1.3%; phase III: 1.0%) and pegfilgrastim (phase II: 1.9%; phase III: 1.0%) arms. None of the treatment-emergent ADA-positive samples exhibited neutralizing activity against lipegfilgrastim, pegfilgrastim, or glycosylated G-CSF in a cell-based neutralizing antibody assay. No changes were observed in neutropenia-related efficacy measures among ADA-positive patients, and no treatment-related hypersensitivity or anaphylaxis occurred. These results indicate that there is no apparent impact of ADA on lipegfilgrastim efficacy and safety.
Predictive Modeling of a Two-Stage Gearbox towards Fault Detection
Authors: Diehl Edward J. , Tang J.
Published: June 2016

This paper presents a systematic approach to the modeling and analysis of a benchmark two-stage gearbox test bed to characterize gear fault signatures when processed with harmonic wavelet transform (HWT) analysis. The eventual goal of condition monitoring is to be able to interpret vibration signals from nonstationary machinery in order to identify the type and severity of gear damage. To advance towards this goal, a lumped-parameter model that can be analyzed efficiently is developed which characterizes the gearbox vibratory response at the system level. The model parameters are identified through correlated numerical and experimental investigations. The model fidelity is validated first by spectrum analysis, using constant speed experimental data, and secondly by HWT analysis, using nonstationary experimental data. Model prediction and experimental data are compared for healthy gear operation and a seeded fault gear with a missing tooth. The comparison confirms that both the frequency content and the predicted, relative response magnitudes match with physical measurements. The research demonstrates that the modeling method in combination with the HWT data analysis has the potential for facilitating successful fault detection and diagnosis for gearbox systems.
TMEM2 Is a SOX4-Regulated Gene That Mediates Metastatic Migration and Invasion in Breast Cancer
Authors: Lee Hyeseung , Goodarzi Hani , Tavazoie Sohail F. , Alarcón Claudio R.
Published: June 2016

The developmental transcription factor SOX4 contributes to the metastatic spread of multiple solid cancer types, but its direct target genes that mediate cancer progression are not well defined. Using a systematic molecular and genomic approach, we identified the TMEM2 transmembrane protein gene as a direct transcriptional target of SOX4. TMEM2 was transcriptionally activated by SOX4 in breast cancer cells where, like SOX4, TMEM2 was found to mediate proinvasive and promigratory effects. Similarly, TMEM2 was sufficient to promote metastatic colonization of breast cancer cells and its expression in primary breast tumors associated with a higher likelihood of metastatic relapse. Given earlier evidence that genetic inactivation of SOX4 or TMEM2 yield similar defects in cardiac development, our findings lead us to propose that TMEM2 may not only mediate the pathologic effects of SOX4 on cancer progression but also potentially its contributions to embryonic development. Cancer Res; 76(17); 4994–5005. ©2016 AACR.
Differential Effects of IL6 and Activin A in the Development of Cancer-Associated Cachexia
Authors: Chen Justin L. , Walton Kelly L. , Qian Hongwei , Colgan Timothy D. , Hagg Adam , Watt Matthew J. , Harrison Craig A. , Gregorevic Paul
Published: June 2016

Cachexia is a life-threatening wasting syndrome lacking effective treatment, which arises in many cancer patients. Although ostensibly induced by multiple tumor-produced cytokines (tumorkines), their functional contribution to initiation and progression of this syndrome has proven difficult to determine. In this study, we used adeno-associated viral vectors to elevate circulating levels of the tumorkines IL6 and/or activin A in animals in the absence of tumors as a tactic to evaluate hypothesized roles in cachexia development. Mice with elevated levels of IL6 exhibited 8.1% weight loss after 9 weeks, whereas mice with elevated levels of activin A lost 11% of their body weight. Co-elevation of both tumorkines to levels approximating those observed in cancer cachexia models induced a more rapid and profound body weight loss of 15.4%. Analysis of body composition revealed that activin A primarily triggered loss of lean mass, whereas IL6 was a major mediator of fat loss. Histologic and transcriptional analysis of affected organs/tissues (skeletal muscle, fat, and liver) identified interactions between the activin A and IL6 signaling pathways. For example, IL6 exacerbated the detrimental effects of activin A in skeletal muscle, whereas activin A curbed the IL6-induced acute-phase response in liver. This study presents a useful model to deconstruct cachexia, opening a pathway to determining which tumorkines are best targeted to slow/reverse this devastating condition in cancer patients. Cancer Res; 76(18); 5372–82. ©2016 AACR.
Mutation Analysis of Cell-Free DNA and Single Circulating Tumor Cells in Metastatic Breast Cancer Patients with High Circulating Tumor Cell Counts
Authors: Shaw Jacqueline A. , Guttery David S. , Hills Allison , Fernandez-Garcia Daniel , Page Karen , Rosales Brenda M. , Goddard Kate S. , Hastings Robert K. , Luo Jinli , Ogle Olivia , Woodley Laura , Ali Simak , Stebbing Justin , Coombes R. Charles
Published: June 2016

Purpose: The purpose of this study was to directly compare mutation profiles in multiple single circulating tumor cells (CTC) and cell-free DNA (cfDNA) isolated from the same blood samples taken from patients with metastatic breast cancer (MBC). We aimed to determine whether cfDNA would reflect the heterogeneity observed in 40 single CTCs.

Experimental Design: CTCs were enumerated by CELLSEARCH. CTC count was compared with the quantity of matched cfDNA and serum CA15-3 and alkaline phosphatase (ALP) in 112 patients with MBC. In 5 patients with ≥100 CTCs, multiple individual EpCAM-positive CTCs were isolated by DEPArray and compared with matched cfDNA and primary tumor tissue by targeted next-generation sequencing (NGS) of about 2,200 mutations in 50 cancer genes.

Results: In the whole cohort, total cfDNA levels and cell counts (≥5 CTCs) were both significantly associated with overall survival, unlike CA15-3 and ALP. NGS analysis of 40 individual EpCAM-positive CTCs from 5 patients with MBC revealed mutational heterogeneity in PIK3CA, TP53, ESR1, and KRAS genes between individual CTCs. In all 5 patients, cfDNA profiles provided an accurate reflection of mutations seen in individual CTCs. ESR1 and KRAS gene mutations were absent from primary tumor tissue and therefore likely either reflect a minor subclonal mutation or were acquired with disease progression.

Conclusions: Our results demonstrate that cfDNA reflects persisting EpCAM-positive CTCs in patients with high CTC counts and therefore may enable monitoring of the metastatic burden for clinical decision-making. Clin Cancer Res; 23(1); 88–96. ©2016 AACR.
Immunotherapy of Cancer Visualized by Live Microscopy: Seeing Is Believing
Authors: Teijeira Alvaro , Etxeberria Iñaki , Ponz-Sarvise Mariano , Melero Ignacio
Published: June 2016

The success of immunotherapy of cancer depends on several cellular events in the tumors that can be visualized by live microscopy strategies in experimental models. Taking advantage of advanced microscopy techniques, Lehmann and colleagues explore in this issue of CCR the mechanism of action of a novel bispecific mAb (TCB-CEA) that targets membrane-bound CEA and CD3ϵ. Clin Cancer Res; 22(17); 4277–9. ©2016 AACR.

See related article by Lehmann et al., p. 4417
Effect of Resveratrol on the Prevention of Intra-Abdominal Adhesion Formation in a Rat Model
Authors: Wei Guangbing , Chen Xin , Wang Guanghui , Fan Lin , Wang Kang , Li Xuqi
Published: June 2016

Background: Intra-abdominal adhesions are a very common complication following abdominal surgery. Our previous studies have demonstrated that the inhibition of inflammation at the sites of peritoneal injury can prevent the formation of intra-abdominal adhesions. Resveratrol is a natural extract with a broad range of anti-inflammatory effects. Therefore, we propose that resveratrol can reduce the formation of intra-abdominal adhesions after surgery. The aim of this study was to investigate the effect of resveratrol on intra-abdominal adhesion prevention in a rat model with surgery-induced peritoneal adhesions. Materials and Methods: The cecum wall and its opposite parietal peritoneum were abraded following laparotomy to induce intra-abdominal adhesion formation. Varying doses of resveratrol were administered to the animals. On the eighth day after surgery, the adhesion score was assessed using a visual scoring system. Picrosirius red staining and a hydroxyproline assay were used to assess the amount of collagen deposition in the adhesion tissues. The levels of serum interleukin-6 (IL-6), tumor necrosis factor (TNF-α), and transforming growth factor beta-1 (TGF-β1) were determined by an enzyme-linked immunosorbent assay (ELISA). Western blotting was performed to determine the protein expression of TGF-β1, fibrinogen, and α-smooth muscle actin (α-SMA) in rat peritoneal adhesion tissue. Real-time RT-PCR was performed to quantify the mRNA expression of TGF-β1, fibrinogen, and α-SMA. Results: Resveratrol significantly reduced intra-abdominal adhesion formation and fibrin deposition in the rat model. Furthermore, resveratrol significantly reduced the serum levels of IL-6, TNF-α, and TGF-β1. The protein and mRNA expression of TGF-β1, fibrinogen, and α-SMA in the rat peritoneum and adhesion tissues were also down-regulated due to resveratrol intervention. Conclusion: Resveratrol can effectively prevent the formation of postoperative intra-abdominal adhesions in a rat model. This effect may be related to the suppression of inflammatory cytokine expression in the injured peritoneum by resveratrol. This study suggests that resveratrol may be a new and effective anti-adhesive agent that is worthy of further study and has potential application value.
Deoxygenation Affects Composition of Membrane-Bound Proteins in Human Erythrocytes
Authors: Luneva Oksana G. , Sidorenko Svetlana V. , Ponomarchuk Olga O. , Tverskoy Artem M. , Cherkashin Aleksander A. , Rodnenkov Oleg V. , Alekseeva Natalia V. , Deev Leonid I. , Maksimov Georgy V. , Grygorczyk Ryszard , Orlov Sergei N.
Published: June 2016

Background/Aims: ATP release from erythrocyte plays a key role in hypoxia-induced elevation of blood flow in systematic circulation. We have previously shown that hemolysis contributes to erythrocyte ATP release triggered by several stimuli, including hypoxia, but the molecular mechanisms of hypoxia-increased membrane fragility remain unknown. Methods: In this study, we compared the action of hypoxia on hemolysis, ATP release and the composition of membrane-bound proteins in human erythrocytes. Results: Twenty minutes incubation of human erythrocytes in the oxygen-free environment increased the content of extracellular hemoglobin by ∼1.5 fold. Paired measurements of hemoglobin and ATP content in the same samples, showed a positive correlation between hemolysis and ATP release. Comparative analysis of SDS-PAGE electrophoresis of erythrocyte ghosts obtained under control and deoxygenated conditions revealed a ∼2-fold elevation of the content of membrane-bound protein with Mr of ∼60 kDa. Conclusion: Deoxygenation of human erythrocytes affects composition of membrane-bound proteins. Additional experiments should be performed to identify the molecular origin of 60 kDa protein and its role in the attenuation of erythrocyte integrity and ATP release in hypoxic conditions.
Protective Effect of Morocco Carob Honey Against Lead-Induced Anemia and Hepato-Renal Toxicity
Authors: Fihri Aicha Fassi , Al-Waili Noori S. , El-Haskoury Redouan , Bakour Meryem , Amarti Afaf , Ansari Mohammad J. , Lyoussi Badiaa
Published: June 2016

Background/Aims: Natural honey has many biological activities including protective effect against toxic materials. The aim of this study was to evaluate the protective effect of carob honey against lead-induced hepato-renal toxicity and lead-induced anemia in rabbits. Methods: Twenty four male rabbits were allocated into four groups six rabbits each; group 1: control group, received distilled water (0.1 ml / kg.b.wt /daily); group 2: received oral lead acetate (2 g/kg.b.wt/daily); group 3: treated with oral honey (1g /kg.b.wt/daily) and oral lead (2 g/kg.b.wt/daily), and group 4: received oral honey (1 g/kg.b.wt/daily). Honey and lead were given daily during 24 days of experimentation. Laboratory tests and histopathological evaluations of kidneys were done. Results: Oral administration of lead induced hepatic and kidney injury and caused anemia during three weeks of the exposure. Treatment with honey prevented hepato-renal lead toxicity and ameliorated lead-induced anemia when honey was given to animals during lead exposure. Conclusion: It might be concluded that honey has a protective effect against lead-induced blood, hepatic and renal toxic effects.
Autoimmunity and Inflammation in Myelodysplastic Syndromes
Authors: Wolach Ofir , Stone Richard
Published: June 2016

Autoimmune and inflammatory conditions (AICs) are encountered in up to 25% of patients with myelodysplastic syndromes (MDS). A wide range of AICs have been reported in association with MDS and can range from limited clinical manifestations to systemic diseases affecting multiple organs. Vasculitides, connective tissue diseases, and inflammatory arthritis are frequently reported in different studies; noninfectious fever and constitutional symptoms at presentation are common. Associations between AICs and specific MDS characteristics vary by study, but the available data suggest that AICs cluster more often in younger patients with higher-risk MDS. In general, AICs do not seem to confer worse survival, although certain AICs may be associated with adverse outcome (e.g. vasculitis) or progression of MDS (Sweet's syndrome). Nonetheless, these complications may have a significant impact on quality of life and affect the timing and type of MDS-directed therapy. The mainstay of management of these complications in the short term relies on immunosuppressive drugs. Increasing evidence suggests that hypomethylating agents may be effective in treating these complications and reduce steroid dependence. While the pathogenesis of AICs is incompletely understood, growing appreciation of cellular immune deregulation, cytokine hypersecretion, and the genetic heterogeneity underlying MDS may improve our understanding of common pathways linking MDS, inflammation, and autoimmunity.
Preventive Ceftriaxone in Patients with Stroke Treated with Intravenous Thrombolysis: Post Hoc Analysis of the Preventive Antibiotics in Stroke Study
Authors: Vermeij Jan-Dirk , Westendorp Willeke F. , Roos Yvo B. , Brouwer Matthijs C. , van de Beek Diederik , Nederkoorn Paul J. ,   for the PASS Investigators
Published: June 2016

Background: The Preventive Antibiotics in Stroke Study (PASS), a randomized open-label masked endpoint trial, showed that preventive ceftriaxone did not improve functional outcome at 3 months in patients with acute stroke (adjusted common OR 0.95; 95% CI 0.82-1.09). Post-hoc analyses showed that among patients who received intravenous thrombolysis (IVT), patients who received ceftriaxone had a significantly better outcome as compared with the control group. This study aimed to gain more insight into the characteristics of these patients. Methods: In PASS, 2,550 patients were randomly assigned to preventive antibiotic treatment with ceftriaxone or standard care. In current post-hoc analysis, 836 patients who received IVT were included. Primary outcome included functional status on the modified Rankin Scale, analyzed with adjusted ordinal regression. Secondary outcomes included infection rate and symptomatic intracerebral hemorrhage (sICH) rate. Results: For all patients in PASS, the p value for the interaction between IVT and preventive ceftriaxone regarding functional outcome was 0.03. Of the 836 IVT-treated patients, 437 were administered ceftriaxone and 399 were allocated to the control group. Baseline characteristics were similar. In the IVT subgroup, preventive ceftriaxone was associated with a significant reduction in unfavorable outcome (adjusted common OR 0.77; 95% CI 0.61-0.99; p = 0.04). Mortality at 3 months was similar (OR 0.75; 95% CI 0.48-1.18). Preventive ceftriaxone was associated with a reduction in infections (OR 0.43; 95% CI 0.28-0.66), and a trend towards an increased risk for sICH (OR 3.09; 95% CI 0.85-11.31). Timing of ceftriaxone administration did not influence the outcome (aOR 1.00; 95% CI 0.98-1.03; p = 0.85). Conclusions: According to the post-hoc analysis of PASS, preventive ceftriaxone may improve the functional outcome in IVT-treated patients with acute stroke, despite a trend towards an increased rate of post-IVT-sICH.
A Novel Phytase Derived from an Acidic Peat-Soil Microbiome Showing High Stability under Acidic Plus Pepsin Conditions
Authors: Tan Hao , Wu Xiang , Xie Liyuan , Huang Zhongqian , Peng Weihong , Gan Bingcheng
Published: June 2016

Four novel phytases of the histidine acid phosphatase family were identified in two publicly available metagenomic datasets of an acidic peat-soil microbiome in northeastern Bavaria, Germany. These enzymes have low similarity to all the reported phytases. They were overexpressed in Escherichia coli and purified. Catalytic efficacy in simulated gastric fluid was measured and compared among the four candidates. The phytase named rPhyPt4 was selected for its high activity. It is the first phytase identified from unculturable Acidobacteria. The phytase showed a longer half-life than all the gastric-stable phytases that have been reported to date, suggesting a strong resistance to low pH and pepsin. A wide pH profile was observed between pH 1.5 and 5.0. At the optimum pH (2.5) the activity was 2,790 μmol/min/mg at the physiological temperature of 37°C and 3,989 μmol/min/mg at the optimum temperature of 60°C. Due to the competent activity level as well as the high gastric stability, the phytase could be a potential candidate for practical use in livestock and poultry feeding
The Planar Cell Polarity Transmembrane Protein Vangl2 Promotes Dendrite, Spine and Glutamatergic Synapse Formation in the Mammalian Forebrain
Authors: Okerlund Nathan D. , Stanley Robert E. , Cheyette Benjamin N.R.
Published: June 2016

The transmembrane protein Vangl2, a key regulator of the Wnt/planar cell polarity (PCP) pathway, is involved in dendrite arbor elaboration, dendritic spine formation and glutamatergic synapse formation in mammalian central nervous system neurons. Cultured forebrain neurons from Vangl2 knockout mice have simpler dendrite arbors, fewer total spines, less mature spines and fewer glutamatergic synapse inputs on their dendrites than control neurons. Neurons from mice heterozygous for a semidominant Vangl2 mutation have similar but not identical phenotypes, and these phenotypes are also observed in Golgi-stained brain tissue from adult mutant mice. Given increasing evidence linking psychiatric pathophysiology to these subneuronal sites and structures, our findings underscore the relevance of core PCP proteins including Vangl2 to the underlying biology of major mental illnesses and their treatment.
Cystic Fibrosis Lung Immunity: The Role of the Macrophage
Authors: Bruscia Emanuela M. , Bonfield Tracey L.
Published: June 2016

Cystic fibrosis (CF) pathophysiology is hallmarked by excessive inflammation and the inability to efficiently resolve lung infections, contributing to major morbidity and eventually the mortality of patients with this disease. Macrophages (MΦs) are major players in lung homeostasis through their diverse contributions to both the innate and adaptive immune networks. The setting of MΦ function and activity in CF is multifaceted, encompassing the response to the unique environmental cues in the CF lung as well as the intrinsic changes resulting from CFTR dysfunction. The complexity is further enhanced with the identification of modifier genes, which modulate the CFTR contribution to disease, resulting in epigenetic and transcriptional shifts in MΦ phenotype. This review focuses on the contribution of MΦ to lung homeostasis, providing an overview of the diverse literature and various perspectives on the role of these immune guardians in CF.