bluuebunny/crossref_metadata_2025 huggingface dataset:
The Early Cambrian Mianyang-Changning Intracratonic Sag and Its Control on Petroleum Accumulation in the Sichuan Basin, China
Authors: Liu Shugen , Deng Bin , Jansa Luba , Zhong Yong , Sun Wei , Song Jinmin , Wang Guozhi , Wu Juan , Li Zhiwu , Tian Yanhong
Published: August 2017

The older and deeper hydrocarbon accumulations receive increasing attention across the world, providing more technical and commercial challenges to hydrocarbon exploration. We present a study of an asymmetrical, N-S striking intracratonic sag which developed across the Sichuan basin, south China, from Late Ediacaran to Early Cambrian times. The Mianyang-Changning intracratonic sag is ~50 km wide, with its steepest part in the basin center. In particular the eastern margin shows its greatest steepness. Five episodes in the evolutions of the sag can be recognized. It begins in the Late Ediacaran with an uplift and erosion correlated to Tongwan movement. Initial extension occurred during the Early Cambrian Maidiping period, when more strata of the Maidiping Formation were deposited across the sag. Subsequently, maximum extension occurred during the Early Cambrian Qiongzhusi period that resulted in 450–1700 m thick Maidiping-Canglangpu Formations being deposited in the sag. Then, the sag disappeared at the Longwangmiao period, as it was infilled by the sediments. The intracratonic sag has significant influence on the development of high-quality reservoirs in the Dengying and Longwangmiao Formations and source-rock of the Niutitang Formation. It thus indicates that a high probability for oil/gas accumulation exists along the intracratonic sag, across the central Sichuan basin.
Selective ATP-Binding Cassette Subfamily C Gene Expression and Proinflammatory Mediators Released by BEAS-2B after PM2.5, Budesonide, and Cotreated Exposures
Authors: Encarnación-Medina Jarline , Rodríguez-Cotto Rosa I. , Bloom-Oquendo Joseph , Ortiz-Martínez Mario G. , Duconge Jorge , Jiménez-Vélez Braulio
Published: August 2017

ATP-binding cassette subfamily C (ABCC) genes code for phase III metabolism proteins that translocate xenobiotic (e.g., particulate matter 2.5 (PM2.5)) and drug metabolites outside the cells. IL-6 secretion is related with the activation of the ABCC transporters. This study assesses ABCC1–4 gene expression changes and proinflammatory cytokine (IL-6, IL-8) release in human bronchial epithelial cells (BEAS-2B) exposed to PM2.5 organic extract, budesonide (BUD, used to control inflammation in asthmatic patients), and a cotreatment (Co-T: PM2.5 and BUD). A real-time PCR assay shows that ABCC1 was upregulated in BEAS-2B exposed after 6 and 7 hr to PM2.5 extract or BUD but downregulated after 6 hr of the Co-T. ABCC3 was downregulated after 6 hr of BUD and upregulated after 6 hr of the Co-T exposures. ABCC4 was upregulated after 5 hr of PM2.5 extract, BUD, and the Co-T exposures. The cytokine assay revealed an increase in IL-6 release by BEAS-2B exposed after 5 hr to PM2.5 extract, BUD, and the Co-T. At 7 hr, the Co-T decreases IL-6 release and IL-8 at 6 hr. In conclusion, the cotreatment showed an opposite effect on exposed BEAS-2B as compared with BUD. The results suggest an interference of the BUD therapeutic potential by PM2.5.
Ultrasound Mediated Microbubbles Destruction Augmented Sonolysis: An In Vitro and In Vivo Study
Authors: Cui Hai , Zhu Qiong , Gao Yunhua , Xia Hongmei , Tan Kaibin , He Ying , Liu Zheng , Xu Yali
Published: August 2017

Objective. This study was aimed at exploring ultrasound mediated microbubbles destruction (UMMD) assisted sonolysis in both the in vitro and in vivo clots. Methods. Therapeutic ultrasound (TUS) and lipid microbubbles (MBs) were used in whole blood clots and divided into the control, TUS group, and TUS + MB group. Thrombolytic rates and microscopy were performed. Color Doppler flow imaging (CDFI) and angiography were performed to evaluate the recanalization rates and flow scores in femoral arterial thrombus (FAT) in rabbits. FAT were dyed with H&E. Results. The average thrombolytic ratios of TUS + MB group were significantly higher than those of TUS group and the control group (both P<0.05). Clots had different pathological changes. Recanalization rates and flow scores in TUS + MB group were significantly higher than the control and TUS group. Flow scores and recanalization ratios were grade 0 in 0% of the control group, grade I in 25% of TUS group, and grade II or higher in 87.5% of TUS + MB group after 30 min sonolysis. Conclusions. Both the in vitro and in vivo sonolysis can be significantly augmented by the introduction of MBs without thrombolytic agents, which might be induced by the enhanced cavitation via UMMD.
Direct Assessment of Wall Shear Stress by Signal Intensity Gradient from Time-of-Flight Magnetic Resonance Angiography
Authors: Han Kap-Soo , Lee Sang Hyuk , Ryu Han Uk , Park Se-Hyoung , Chung Gyung-Ho , Cho Young I. , Jeong Seul-Ki
Published: August 2017

The aim of the study was to calculate the arterial wall signal intensity gradient (SIG) from time-of-flight MR angiography (TOF-MRA) and represent arterial wall shear stress. We developed a new algorithm that uses signal intensity (SI) of a TOF-MRA to directly calculate the signal intensity gradient (SIG). The results from our phantom study showed that the TOF-MRA SIG could be used to distinguish the magnitude of blood flow rate as high (mean SIG ± SD, 2.2 ± 0.4 SI/mm for 12.5 ± 2.3 L/min) and low (0.9 ± 0.3 SI/mm for 8.5 ± 2.6 L/min) in vessels (p<0.001). Additionally, we found that the TOF-MRA SIG values were highly correlated with various flow rates (β=0.96, p<0.001). Remarkably, the correlation coefficient between the WSS obtained from the computational fluid dynamics (CFD) analysis and the TOF-MRA SIG was greater than 0.8 in each section at the carotid artery (p<0.001 for all β values). This new technique using TOF-MRA could enable the rapid calculation of the TOF-MRA SIG and thereby the WSS. Thus, the TOF-MRA SIG can provide clinicians with an accurate and efficient screening method for making rapid decisions on the risk of vascular disease for a patient in clinical practice.
Comparison of the Therapeutic Effects of Acupuncture at PC6 and ST36 for Chronic Myocardial Ischemia
Authors: Shi Li , Fang Jiliang , Zhao Jiping , Liu Guiyong , Zhao Qing , Zhang Jinling , Zhang Jinzhao , Zhu Bing , Liang Fanrong , Rong Peijing
Published: August 2017

We aimed to compare the differences of the effects on chronic myocardial ischemia (MI) of acupuncture at PC6 and ST36. The chronic MI model of minipigs was created by implanting an Ameroid constrictor on the left anterior descending coronary artery (LAD) and then two weeks’ acupuncture was stimulated at PC6 or ST36, respectively. The results showed that both acupoints’ stimulation decreased the serous cardiac troponin T (cTnT) and ischemia modified albumin (IMA) significantly and improved the ischemic ECG changes. The amplitude of pathological Q wave in the PC6 group decreased more significantly than that of the ST36 group. The cardiovascular magnetic resonance imaging (cMRI) results showed that the decreased left ventricular ejection fraction (LVEF) was not improved obviously in both groups. The left ventricular end‐diastolic volume (LVEDV) and left ventricular end‐systolic volume (LVESV) enlarged progressively even after acupuncture. The left ventricular wall mass (LVWM) in the ST36 group increased more obviously than that of the PC6 group, which paralleled the decreasing angiotensin II (Ang II) concentration in the plasma. These results suggested that acupuncture at PC6 or ST36 was effective for protecting the myocardium from chronic ischemic injury, and the effect of PC6 seemed to be better.
Analysis of Pressure Pulsation Induced by Rotor-Stator Interaction in Nuclear Reactor Coolant Pump
Authors: Zhang Xu , Wang Pengfei , Ruan Xiaodong , Xu Zhongbin , Fu Xin
Published: August 2017

The internal flow of reactor coolant pump (RCP) is much more complex than the flow of a general mixed-flow pump due to high temperature, high pressure, and large flow rate. The pressure pulsation that is induced by rotor-stator interaction (RSI) has significant effects on the performance of pump; therefore, it is necessary to figure out the distribution and propagation characteristics of pressure pulsation in the pump. The study uses CFD method to calculate the behavior of the flow. Results show that the amplitudes of pressure pulsation get the maximum between the rotor and stator, and the dissipation rate of pressure pulsation in impellers passage is larger than that in guide vanes passage. The behavior is associated with the frequency of pressure wave in different regions. The flow rate distribution is influenced by the operating conditions. The study finds that, at nominal flow, the flow rate distribution in guide vanes is relatively uniform and the pressure pulsation amplitude is the smallest. Besides, the vortex shedding or backflow from the impeller blade exit has the same frequency as pressure pulsation but there are phase differences, and it has been confirmed that the absolute value of phase differences reflects the vorticity intensity.
Pesticide Residues in Honey from the Major Honey Producing Forest Belts in Ghana
Authors: Darko Godfred , Addai Tabi Jonah , Adjaloo Michael Kodwo , Borquaye Lawrence Sheringham
Published: August 2017

Concentrations of pesticides residues in honey sampled from the major honey producing forest belts in Ghana were determined. Samples were purposively collected and extracted using the QuEChERS (Quick, Easy, Cheap, Effective, Rugged, and Safe) method and analysed for synthetic pyrethroids, organochlorine, and organophosphate pesticide residues. Aldrin, γ-HCH, β-HCH, ∑endosulfan, cyfluthrin, cypermethrin, deltamethrin, permethrin methoxychlor, ∑DDT, chlorpyrifos, fenvalerate, malathion, dimethoate, and diazinon were all detected at the concentration of 0.01 mg/kg, while cyfluthrin and permethrin were detected at mean concentrations of 0.02 and 0.04 mg/kg, respectively. All the pesticide residues detected were very low and below their respective maximum residue limits set by the European Union. Hence, pesticide residues in honey samples analyzed do not pose any health risk to consumers.
Outcomes of Laparoscopic Gastric Greater Curvature Plication in Morbidly Obese Patients
Authors: Khidir N. , Al Dhaheri M. , El Ansari W. , Al Kuwari M. , Sargsyan D. , Bashah M.
Published: August 2017

Background. Laparoscopic gastric greater curvature plication (LGGCP) is a restrictive bariatric procedure without gastrectomy. However, limited literature on effectiveness of gastric plication exists. Objectives. We assessed LGGCP’s efficacy, effects on associated comorbidities, safety and the rate of complications, and patient satisfaction with LGGCP’s outcomes among morbidly obese patients. Method. Analysis of retrospectively data collected from medical records of 26 patients who had undergone LGGCP at Hamad General Hospital, Qatar, during 2011-2012. Results. Most patients (92%) were Qatari nationals. The sample’s mean age was 35.1 years. Mean duration of hospital stay was 3.9±1.2 days. Mean preoperative BMI was 40.7 kg/m2 that decreased at 2 years to 34.6 kg/m2. LGGCP’s effects on comorbidities were such that 7.6% of patients experienced resolutions of their comorbidities. There were no mortality or postoperative complications that required reoperation. Six patients (23%) were satisfied with the LGGCP’s outcomes while 10 patients (38.5%) underwent sleeve gastrectomy subsequently. Conclusion. LGGCP had acceptable short term weight loss results, exhibited almost no postoperative complications, and improved patients’ comorbidities. Despite the durability of the gastric fold, some patients regained weight. Future research may assess the possibility of an increase in the gastric pouch size postplication associated with weight regain.
Gene Expression Profiling Identifies Downregulation of the Neurotrophin-MAPK Signaling Pathway in Female Diabetic Peripheral Neuropathy Patients
Authors: Luo Lin , Zhou Wen-Hua , Cai Jiang-Jia , Feng Mei , Zhou Mi , Hu Su-Pei , Xu Jin , Ji Lin-Dan
Published: August 2017

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes mellitus (DM). It is not diagnosed or managed properly in the majority of patients because its pathogenesis remains controversial. In this study, human whole genome microarrays identified 2898 and 4493 differentially expressed genes (DEGs) in DM and DPN patients, respectively. A further KEGG pathway analysis indicated that DPN and DM share four pathways, including apoptosis, B cell receptor signaling pathway, endocytosis, and Toll-like receptor signaling pathway. The DEGs identified through comparison of DPN and DM were significantly enriched in MAPK signaling pathway, NOD-like receptor signaling pathway, and neurotrophin signaling pathway, while the “neurotrophin-MAPK signaling pathway” was notably downregulated. Seven DEGs from the neurotrophin-MAPK signaling pathway were validated in additional 78 samples, and the results confirmed the initial microarray findings. These findings demonstrated that downregulation of the neurotrophin-MAPK signaling pathway may be the major mechanism of DPN pathogenesis, thus providing a potential approach for DPN treatment.
In Vivo Articular Cartilage Regeneration Using Human Dental Pulp Stem Cells Cultured in an Alginate Scaffold: A Preliminary Study
Authors: Mata Manuel , Milian Lara , Oliver Maria , Zurriaga Javier , Sancho-Tello Maria , Llano Jose Javier Martin de , Carda Carmen
Published: August 2017

Osteoarthritis is an inflammatory disease in which all joint-related elements, articular cartilage in particular, are affected. The poor regeneration capacity of this tissue together with the lack of pharmacological treatment has led to the development of regenerative medicine methodologies including microfracture and autologous chondrocyte implantation (ACI). The effectiveness of ACI has been shown in vitro and in vivo, but the use of other cell types, including bone marrow and adipose-derived mesenchymal stem cells, is necessary because of the poor proliferation rate of isolated articular chondrocytes. In this investigation, we assessed the chondrogenic ability of human dental pulp stem cells (hDPSCs) to regenerate cartilage in vitro and in vivo. hDPSCs and primary isolated rabbit chondrocytes were cultured in chondrogenic culture medium and found to express collagen II and aggrecan. Both cell types were cultured in 3% alginate hydrogels and implanted in a rabbit model of cartilage damage. Three months after surgery, significant cartilage regeneration was observed, particularly in the animals implanted with hDPSCs. Although the results presented here are preliminary, they suggest that hDPSCs may be useful for regeneration of articular cartilage.
Synergistic Antioxidant and Anti‐Inflammatory Effects between Modified Citrus Pectin and Honokiol
Authors: Ramachandran Cheppail , Wilk Barry , Melnick Steven J. , Eliaz Isaac
Published: August 2017

Inflammation is a normal physiological process; however, dysregulation of this process may contribute to inflammatory‐based chronic disorders and diseases in animals and humans. Therefore, the antioxidant and anti‐inflammatory properties of natural products, often recognized in traditional medicine systems, represent therapeutic modalities to reduce or prevent uncontrolled inflammatory processes which in turn potentially ameliorate or prevent sequelae of inflammatory‐based symptoms of chronic diseases. We have investigated the antioxidant and anti‐inflammatory effects of honokiol (HNK) and modified citrus pectin (MCP) in vitro and examined whether the MCP : HNK combination has synergistic effects on antioxidant and anti‐inflammatory properties. Although both HNK and MCP induced a dose‐dependent increase in antioxidant activity, the latter has a consistently higher antioxidant effect. The MCP : HNK (9 : 1) combination induced a synergistic effect on antioxidant activity suggesting that the combination is significantly more efficacious than individual compounds. In mouse monocytes, the lipopolysaccharide‐ (LPS‐) induced tumor necrosis‐α (TNF‐α) synthesis was significantly inhibited by HNK and the MCP : HNK combination in a dose‐dependent manner and synergistic effects were clearly demonstrated with the combination on TNF‐α inhibition. This combination effect was also evident on inhibition of nuclear factor‐kappa B activity, cyclooxygenase‐II activity, and lipid peroxidation in mouse monocytes. Further research into the combination is warranted.
Predictors of Hypertension among Nonpregnant Females Attending Health Promotion Clinic with Special Emphasis on Smokeless Tobacco: A Cross-Sectional Study
Authors: Bhatt Devika , Sharma Shashi , Gupta Ruchika , Sinha Dhirendra N. , Mehrotra Ravi
Published: August 2017

Aim. To determine the predictors of hypertension among nonpregnant females attending a health promotion clinic. Design and Setting. A cross-sectional study was conducted during March to June 2016, at the National Institute of Cancer Prevention and Research, India. Methods. The study included 319 nonpregnant females of age 20–70 years. Demographics such as age, literacy, and income were noted. History regarding use, frequency, and quantity of smokeless tobacco was taken. Height, weight, and blood pressure were measured and body mass index was calculated. Statistical Analysis. Pearson’s product-moment correlation coefficient was calculated between each of the variables of age, smokeless tobacco consumption, and body mass index versus systolic and diastolic blood pressure, respectively. The linear as well as multiple linear regression analysis was employed to identify the risk factors for hypertension. Results. A univariate linear regression analysis showed that age, smokeless tobacco consumption, and body mass index were associated with systolic blood pressure (P value < 0.001 for each). For diastolic blood pressure, high body mass index was a predictor. Multiple linear regression analysis showed that both systolic and diastolic hypertension were associated with high body mass index and low level of education. Moreover, the systolic hypertension was associated with higher age and smokeless tobacco use. Conclusion. Health promotion requires control of body mass index and smokeless tobacco cessation for preventing hypertension and its complications.
Influencing Factors of Knowledge, Attitude, and Practice regarding Medical Nutrition Therapy in Patients with Diabetes: A National Cross-Sectional Study in Urban China
Authors: Li Zijian , Jin Haimin , Chen Wei , Sun Zilin , Jing Lulu , Zhao Xiaohui , Zhu Sainan , Guo Xiaohui , Study Group China NEEDs
Published: August 2017

To investigate the knowledge-attitude-practice (KAP) score in diabetes patients living in urban China regarding Medical Nutrition Therapy (MNT) and explore the influencing factors, this national survey recruited diabetes and prediabetes patients in 40 hospitals across 26 provinces in China. A self-designed questionnaire was used to collect the data and assess the knowledge, attitude, and practice regarding MNT. Logistic regression was used to explore the factor influencing KAP scores. A total of 6441 diabetes patients (mean age: 60.02±13.14 years) completed this survey. The mean glycosylated hemoglobin (HbA1c) level was 8.12±2.12%, and the control rate of HbA1c (HbA1c < 7.0%) was 38.92%. Of the total, 53.56% had received MNT education. Over half of the patients had a poor total KAP score as well as poor K, A, and P scores. Patients with higher KAP scores had higher control rate of HbA1c (P<0.05) but lower levels of fasting plasma glucose (FPG) and 2-hour postprandial blood glucose (2h-PG). Gender, occupation, residence, education level, and MNT education could influence the KAP scores (P<0.05). This study showed that diabetes patients in urban China generally had poor understandings and practices related to MNT. Patients with higher KAP scores exhibited better control of blood glucose.
Earlier Intervention with Deep Brain Stimulation for Parkinson’s Disease
Authors: Suarez-Cedeno Gerson , Suescun Jessika , Schiess Mya C.
Published: August 2017

Neuromodulation of subcortical areas of the brain as therapy to reduce Parkinsonian motor symptoms was developed in the mid-twentieth century and went through many technical and scientific advances that established specific targets and stimulation parameters. Deep Brain Stimulation (DBS) was approved by the FDA in 2002 as neuromodulation therapy for advanced Parkinson’s disease, prompting several randomized controlled trials that confirmed its safety and effectiveness. The implantation of tens of thousands of patients in North America and Europe ignited research into its potential role in early disease stages and the therapeutic benefit of DBS compared to best medical therapy. In 2013 the EARLY-STIM trial provided Class I evidence for the use of DBS earlier in Parkinson’s disease. This finding led to the most recent FDA approval in patients with at least 4 years of disease duration and 4 months of motor complications as an adjunct therapy for patients not adequately controlled with medications. This following review highlights the historical development and advances made overtime in DBS implantation, the current application, and the challenges that come with it.
Consensus of Fractional-Order Multiagent Systems with Double Integrator under Switching Topologies
Authors: Shen Shiyun , Li Wenjing , Zhu Wei
Published: August 2017

Due to the complexity of the practical environments, many systems can only be described with the fractional-order dynamics. In this paper, the consensus of fractional-order multiagent systems with double integrator under switching topologies is investigated. By applying Mittag-Leffler function, Laplace transform, and dwell time technique, a sufficient condition on consensus is obtained. Finally, a numerical simulation is presented to illustrate the effectiveness of the theoretical result.
Chinese Herbal Formula, Modified Danggui Buxue Tang, Attenuates Apoptosis of Hematopoietic Stem Cells in Immune-Mediated Aplastic Anemia Mouse Model
Authors: Zhou Jingwei , Li Xue , Deng Peiying , Wei Yi , Liu Juan , Chen Meng , Xu Yamei , Zhang Dongmei , Zhu Lingqun , Lou Lixia , Dong Bin , Jin Qiushuo , Chai Limin
Published: August 2017

A derivative formula, DGBX, which is composed of three herbs (Radix astragali,Radix Angelicae sinensis, andCoptis chinensisFranch), is derived from a famous Chinese herbal formula, Danggui Buxue Tang (DBT) (Radix astragaliandRadix Angelicae sinensis). We aimed to investigate the effects of DGBX on the regulation of the balance between proliferation and apoptosis of hematopoietic stem cells (HSCs) due to the aberrant immune response in a mouse model of aplastic anemia (AA). Cyclosporine (CsA), an immunosuppressor, was used as the positive control. Our results indicated that DGBX could downregulate the production of IFNγin bone marrow cells by interfering with the binding between SLAM and SAP and the expressions of Fyn and T-bet. This herbal formula can also inhibit the activation of Fas-mediated apoptosis, interferon regulatory factor-1-induced JAK/Stat, and eukaryotic initiation factor 2 signaling pathways and thereby induce proliferation and attenuate apoptosis of HSCs. In conclusion, DGBX can relieve the immune-mediated destruction of HSCs, repair hematopoietic failure, and recover the hematopoietic function of HSCs in hematogenesis. Therefore, DGBX can be used in traditional medicine against AA as a complementary and alternative immunosuppressive therapeutic formula.
Epithelial-to-Mesenchymal and Mesenchymal-to-Epithelial Transition in Mesenchymal Tumors: A Paradox in Sarcomas?
Authors: Sannino Giuseppina , Marchetto Aruna , Kirchner Thomas , Grünewald Thomas G.P.
Published: August 2017

The epithelial-to-mesenchymal transition (EMT) is a reversible process comprised of various subprograms via which epithelial cells reduce their intercellular adhesions and proliferative capacity while gaining a mesenchymal phenotype with increased migratory and invasive properties. This process has been well described in several carcinomas, which are cancers of epithelial origin, and is crucial to metastatic tumor cell dissemination and drug resistance. In contrast, the precise role of EMT-related processes in tumors originating from mesenchymal tissues, such as bone and soft-tissues sarcomas, is still largely unclear. In fact, although the existence of the EMT in sarcomas appears paradoxical because these cancers are, by definition, mesenchymal ab initio, accumulating evidence suggests that many sarcomas can undergo EMT-related processes, which may be associated with aggressive clinical behavior. These processes may be especially operative in certain sarcoma subtypes, such as carcinosarcomas displaying a biphenotypic morphology with characteristics of both mesenchymal and epithelial tumors. In this review, we discuss findings regarding the potential existence of EMT-related processes in sarcomas and propose that sarcomas can reside in a metastable state, enabling them to become either more mesenchymal or epithelial under specific conditions, which likely has important clinical implications. Cancer Res; 77(17); 4556–61. ©2017 AACR.
PPARγ Ligand–induced Annexin A1 Expression Determines Chemotherapy Response via Deubiquitination of Death Domain Kinase RIP in Triple-negative Breast Cancers
Authors: Chen Luxi , Yuan Yi , Kar Shreya , Kanchi Madhu M. , Arora Suruchi , Kim Ji E. , Koh Pei F. , Yousef Einas , Samy Ramar P. , Shanmugam Muthu K. , Tan Tuan Z. , Shin Sung W. , Arfuso Frank , Shen Han M. , Yang Henry , Goh Boon C. , Park Joo I. , Gaboury Louis , Lobie Peter E. , Sethi Gautam , Lim Lina H.K. , Kumar Alan P.
Published: August 2017

Metastatic breast cancer is still incurable so far; new specifically targeted and more effective therapies for triple-negative breast cancer (TNBC) are required in the clinic. In this study, our clinical data have established that basal and claudin-low subtypes of breast cancer (TNBC types) express significantly higher levels of Annexin A1 (ANXA1) with poor survival outcomes. Using human cancer cell lines that model the TNBC subtype, we observed a strong positive correlation between expression of ANXA1 and PPARγ. A similar correlation between these two markers was also established in our clinical breast cancer patients' specimens. To establish a link between these two markers in TNBC, we show de novo expression of ANXA1 is induced by activation of PPARγ both in vitro and in vivo and it has a predictive value in determining chemosensitivity to PPARγ ligands. Mechanistically, we show for the first time PPARγ-induced ANXA1 protein directly interacts with receptor interacting protein-1 (RIP1), promoting its deubiquitination and thereby activating the caspase-8–dependent death pathway. We further identified this underlying mechanism also involved a PPARγ-induced ANXA1-dependent autoubiquitination of cIAP1, the direct E3 ligase of RIP1, shifting cIAP1 toward proteosomal degradation. Collectively, our study provides first insight for the suitability of using drug-induced expression of ANXA1 as a new player in RIP1-induced death machinery in TNBCs, presenting itself both as an inclusion criterion for patient selection and surrogate marker for drug response in future PPARγ chemotherapy trials. Mol Cancer Ther; 16(11); 2528–42. ©2017 AACR.
Targeting AR Variant–Coactivator Interactions to Exploit Prostate Cancer Vulnerabilities
Authors: Magani Fiorella , Peacock Stephanie O. , Rice Meghan A. , Martinez Maria J. , Greene Ann M. , Magani Pablo S. , Lyles Rolando , Weitz Jonathan R. , Burnstein Kerry L.
Published: August 2017

Castration-resistant prostate cancer (CRPC) progresses rapidly and is incurable. Constitutively active androgen receptor splice variants (AR-Vs) represent a well-established mechanism of therapeutic resistance and disease progression. These variants lack the AR ligand-binding domain and, as such, are not inhibited by androgen deprivation therapy (ADT), which is the standard systemic approach for advanced prostate cancer. Signaling by AR-Vs, including the clinically relevant AR-V7, is augmented by Vav3, an established AR coactivator in CRPC. Using mutational and biochemical studies, we demonstrated that the Vav3 Diffuse B-cell lymphoma homology (DH) domain interacted with the N-terminal region of AR-V7 (and full length AR). Expression of the Vav3 DH domain disrupted Vav3 interaction with and enhancement of AR-V7 activity. The Vav3 DH domain also disrupted AR-V7 interaction with other AR coactivators: Src1 and Vav2, which are overexpressed in PC. This Vav3 domain was used in proof-of-concept studies to evaluate the effects of disrupting the interaction between AR-V7 and its coactivators on CRPC cells. This disruption decreased CRPC cell proliferation and anchorage-independent growth, caused increased apoptosis, decreased migration, and resulted in the acquisition of morphological changes associated with a less aggressive phenotype. While disrupting the interaction between FL-AR and its coactivators decreased N-C terminal interaction, disrupting the interaction of AR-V7 with its coactivators decreased AR-V7 nuclear levels.

Implications: This study demonstrates the potential therapeutic utility of inhibiting constitutively active AR-V signaling by disrupting coactivator binding. Such an approach is significant, as AR-Vs are emerging as important drivers of CRPC that are particularly recalcitrant to current therapies. Mol Cancer Res; 15(11); 1469–80. ©2017 AACR.
Primary Tumors Limit Metastasis Formation through Induction of IL15-Mediated Cross-Talk between Patrolling Monocytes and NK Cells
Authors: Kubo Hiroshi , Mensurado Sofia , Gonçalves-Sousa Natacha , Serre Karine , Silva-Santos Bruno
Published: August 2017

Metastases are responsible for the vast majority of cancer-related deaths. Although tumor cells can become invasive early during cancer progression, metastases formation typically occurs as a late event. How the immune response to primary tumors may dictate this outcome remains poorly understood, which hampers our capacity to manipulate it therapeutically. Here, we used a two-step experimental model, based on the highly aggressive B16F10 melanoma, that temporally segregates the establishment of primary tumors (subcutaneously) and the formation of lung metastases (from intravenous injection). This allowed us to identify a protective innate immune response induced by primary tumors that inhibits experimental metastasis. We found that in the presence of primary tumors, increased numbers of natural killer (NK) cells with enhanced IFNγ, granzyme B, and perforin production were recruited to the lung upon metastasis induction. These changes were mirrored by a local accumulation of patrolling monocytes and macrophages with high expression of MHC class II and NOS2. Critically, the protective effect on metastasis was lost upon patrolling monocyte or NK cell depletion, IL15 neutralization, or IFNγ ablation. The combined analysis of these approaches allowed us to establish a hierarchy in which patrolling monocytes, making IL15 in response to primary tumors, activate NK cells and IFNγ production that then inhibit lung metastasis formation. This work identifies an innate cell network and the molecular determinants responsible for “metastasis immunosurveillance,” providing support for using the key molecular mediator, IL15, to improve immunotherapeutic outcomes. Cancer Immunol Res; 5(9); 812–20. ©2017 AACR.
Uterine Cervical Length Measurement to Reduce Length of Stay in Patients Admitted for Threatened Preterm Labor: A Randomized Trial
Authors: Palacio Montse , Caradeux Javier , Sánchez Miriam , Cobo Teresa , Figueras Francesc , Coll Oriol , Gratacós Eduard , Cararach Vicenç
Published: August 2017

Objective: To study whether knowledge of cervical length (CL) is useful in reducing the length of hospital stay in women admitted because of threatened preterm labor. Methods: We performed a single-center, parallel, randomized trial at the Hospital Clínic of Barcelona. Inclusion criteria were single pregnancy, gestational age (GA) between 24+0 and 35+6 weeks, Bishop score <6, no parturition within 24-48 h after admission, and no clinical signs of chorioamnionitis, vaginal bleeding, or nonreassuring fetal status. CL measurement was performed 24-48 h after admission. In the control group, the patient and the physician in charge were blinded. In the study group, this information was given; if CL was >25 mm, early discharge within 12-24 h from randomization was recommended. Length of hospital stay was the main outcome. Results: After randomization, 149 patients had complete follow-up (control group, n = 74; study group, n = 75). The mean (SD) length of stay was significantly shorter - 3.0 (2.2) vs. 4.0 (2.0) days (p = 0.004) - in the study group, with a higher proportion of women remaining hospitalized ≤3 days (relative risk [95% confidence interval] 0.43 [0.26-0.70]), with no differences in GA at delivery or preterm birth rate. Conclusions: Knowledge of CL in women admitted because of threatened preterm labor is useful in reducing length of stay, with no impact on GA at delivery or preterm birth rate.
Tocolysis for in utero Surgery: Atosiban Performs Distinctly Better than Magnesium Sulfate
Authors: Ochsenbein-Kölble Nicole , Krähenmann Franziska , Hüsler Margret , Meuli Martin , Moehrlen Ueli , Mazzone Lucca , Biro Peter , Zimmermann Roland
Published: August 2017

Introduction: To compare tocolysis with magnesium sulfate versus atosiban regarding the occurrence of short-term preterm labor and maternal side effects during and after open fetal myelomeningocele (MMC) repair. Material and Methods: A prospective nonrandomized cohort study was performed including 30 fetal MMC cases. The first 15 cases (group 1) received magnesium sulfate according to the MOMS protocol. In the following 15 cases (group 2), magnesium sulfate was substituted by atosiban. Chorioamniotic membrane separation (CMS), premature prelabor rupture of the fetal membranes (PPROM), preterm delivery <3 weeks after fetal MMC repair, and maternal complications due to the tocolytic medication were the major endpoints. Results: In both groups, one CMS but no PPROM was diagnosed <3 weeks after fetal MMC repair. One patient of group 2 delivered <3 weeks after fetal MMC repair because of an intraoperative placental abruption at 25 weeks. All women of group 1 showed an electrolyte imbalance during magnesium sulfate administration. One woman of group 1 developed several episodes of a third-degree atrioventricular block within the first 3 days after fetal surgery. Lethargy was found in all women during magnesium sulfate therapy. No maternal side effects were found under atosiban. Discussion: The use of atosiban resulted in an almost identical short-term uterine outcome without any serious maternal complications as seen when magnesium sulfate was given. Thus, the authors suggest using atosiban instead of magnesium sulfate in the context of open fetal surgery.
Exploring the Use of a Participative Design in the Early Development of a Predictive Test: The Importance of Physician Involvement
Authors: Veilleux Sophie , Villeneuve Maude , Lachapelle Nathalie , Kohen Rita , Vachon Luc , White Guay Brian , Rioux John D. , Bitton Alain ,   for the IBD Genomic Medicine Consortium (iGenoMed)
Published: August 2017

In this study, we contribute to the personalized medicine and health care management literature by developing and testing a new participative design approach. We propose that involving gastroenterologists in the development of a predictive test to assist them in their clinical decision-making process for the treatment of inflammatory bowel diseases will increase the likelihood of their acceptance of the innovation. Based on data obtained from 6 focus groups across Canada from a total of 28 physicians, analyses reveal that current tools do not enable discriminating between treatment options to find the best fit for each patient. Physicians expect a new predictive tool to have the capability of showing clear reliability and significant benefits for the patient, while being accessible in a timely manner that facilitates clinical decisions. Physicians also insist on their key role in the implementation process, hence confirming the relevance and importance of participative designs in personalized medicine.
Subjects at Risk for Genetic Late-Onset Neurological Diseases: Objective Knowledge
Authors: Leite Ângela , Leite Fernanda , Dinis Maria Alzira P.
Published: August 2017

Background/Aims: This study addresses the objective knowledge about the disease of subjects at risk for 3 genetic late-onset neurological diseases (LOND): familial amyloid polyneuropathy (FAP) TTR V30M, Huntington disease (HD), and Machado-Joseph disease (MJD). Methods: Subjects at risk for FAP, HD, and MJD submitted to genetic counseling to know their status (carrier or non-carrier) and subjects at risk for hereditary hemochromatosis (HH), the control group, completed a sociodemographic questionnaire and answered the open-ended question: “What do you know about this disease?.” Results: From 10 categories of answers, references to the disease, quantitative answers, references to the family, and metaphors stood out. References to the disease, references to the family, and metaphors were mentioned more often by subjects at risk for LOND than by subjects at risk for HH (control group). Conclusion: The disease itself and its meaning as well as sick relatives play a key role in the objective knowledge about LOND. Thus, genetic counseling protocols of subjects at risk for LOND should include questions concerning family knowledge and disease experience.
Subacute Cerebellar Degeneration due to a Paraneoplastic Phenomenon Associated with Metastatic Merkel Cell Carcinoma: A Case Report
Authors: Sharobeam Angelos , Ray Jason , Dong Juliana , Chong Victor
Published: August 2017

Purpose: The aim of this article is to illustrate the diagnostic challenges and management of paraneoplastic neurological syndromes in Merkel cell carcinoma. Materials and Methods: We describe a previously functionally independent 85-year-old woman who presented with subacute onset of dizziness and gait ataxia in the setting of metastatic Merkel cell carcinoma. Results: Diagnosis was made on biopsy after positron emission tomography imaging revealed increased metabolic activity in 2 left inguinofemoral lymph nodes. Cerebrospinal fluid analysis was positive for anti-Hu on subsequent admission. Her functional status improved with methylprednisolone treatment and radiotherapy. Conclusion: The case highlights the challenge of the evaluation of patients who present with progressive cerebellar signs and the need to consider a paraneoplastic syndrome, especially in the setting of previous malignancy.
The Lncrna-TUG1/EZH2 Axis Promotes Pancreatic Cancer Cell Proliferation, Migration and EMT Phenotype Formation Through Sponging Mir-382
Authors: Zhao Liang , Sun Hongwei , Kong Hongru , Chen Zongjing , Chen Bicheng , Zhou Mengtao
Published: August 2017

Background/Aims: Pancreatic carcinoma (PC) is the one of the most common and malignant cancers worldwide. LncRNA taurine upregulated gene 1 (TUG1) was initially identified as a transcript upregulated by taurine, and the abnormal expression of TUG1 has been reported in many cancers. However, the biological role and molecular mechanism of TUG1 in PC still needs further investigation. Methods: Quantitative real-time PCR (qRT-PCR) was performed to measure the expression of TUG1 in PC cell lines and tissues. MTT and colony formation assays were used to measure the effect of TUG1 on cell proliferation. A wound healing assay, transwell assay and western blot assay were employed to determine the effect of TUG1 on cell migration and the epithelial mesenchymal transition (EMT) phenotype. RNA-binding protein immunoprecipitation (RIP) and a biotin-avidin pulldown system were performed to confirm the interaction between miR-328 and TUG1. A gene expression array analysis using clinical samples and RT-qPCR suggested that enhancer of zeste homolog 2 (EZH2) was a target of miR-382 in PC. Results: In this study, we reported that TUG1 was overexpressed in PC tissues and cell lines, and high expression of TUG1 predicted poor prognosis. Further experiments revealed that overexpressed TUG1 promoted cell proliferation, migration and contributed to EMT formation, whereas silenced TUG1 led to opposing results. Additionally, luciferase reporter assays, an RIP assay and an RNA-pulldown assay demonstrated that TUG1 could competitively sponge miR-382 and thereby regulate EZH2. Conclusion: Collectively, these findings revealed that TUG1 functions as an oncogenic lncRNA that promotes tumor progression, at least partially, by functioning as an endogenous ‘sponge’ and competing for miR-382 binding to the miRNA target EZH2.
P38 Kinase, SGK1 and NF-κB Dependent Up-Regulation of Na+/Ca2+ Exchanger Expression and Activity Following TGFß1 Treatment of Megakaryocytes
Authors: Al-Maghout Tamer , Pelzl Lisann , Sahu Itishri , Sukkar Basma , Hosseinzadeh Zohreh , Gutti Ravi , Laufer Stefan , Voelkl Jakob , Pieske Burkert , Gawaz Meinrad , Lang Florian
Published: August 2017

Background: TGFβ1, a decisive regulator of megakaryocyte maturation and platelet formation, has previously been shown to up-regulate both, store operated Ca2+ entry (SOCE) and Ca2+ extrusion by Na+/Ca2+ exchange. The growth factor thus augments the increase of cytosolic Ca2+ activity ([Ca2+]i) following release of Ca2+ from intracellular stores and accelerates the subsequent decline of [Ca2+]i. The effect on SOCE is dependent on a signaling cascade including p38 kinase, serum & glucocorticoid inducible kinase SGK1, and nuclear factor NFκB. The specific Na+/Ca2+ exchanger isoforms involved and the signalling regulating the Na+/Ca2+ exchangers remained, however elusive. The present study explored, whether TGFβ1 influences the expression and function of K+ insensitive (NCX) and K+ sensitive (NCKX) Na+/Ca2+ exchangers, and aimed to shed light on the signalling involved. Methods: In human megakaryocytic cells (MEG01) RT-PCR was performed to quantify NCX/NCKX isoform transcript levels, [Ca2+]i was determined by Fura-2 fluorescence, and Na+/Ca2+ exchanger activity was estimated from the increase of [Ca2+]i following switch from an extracellular solution with 130 or 90 mM Na+ and 0 mM Ca2+ to an extracellular solution with 0 Na+ and 2 mM Ca2+. K+ concentration was 0 mM for analysis of NCX and 40 mM for analysis of NCKX. Results: TGFβ1 (60 ng/ml, 24 h) significantly increased the transcript levels of NCX1, NCKX1, NCKX2 and NCKX5. Moreover, TGFβ1 (60 ng/ml, 24 h) significantly increased the activity of both, NCX and NCKX. The effect of TGFβ1 on NCX and NCKX transcript levels and activity was significantly blunted by p38 kinase inhibitor Skepinone-L (1 µM), the effect on NCX and NCKX activity further by SGK1 inhibitor GSK-650394 (10 µM) and NFκB inhibitor Wogonin (100 µM). Conclusions: TGFβ1 markedly up-regulates transcription of NCX1, NCKX1, NCKX2, and NCKX5 and thus Na+/Ca2+ exchanger activity, an effect requiring p38 kinase, SGK1 and NFκB.
Natural History of Localized and Locally Advanced Atypical Lung Carcinoids after Complete Resection: A Joined French-Italian Retrospective Multicenter Study
Authors: Marciello Francesca , Mercier Olaf , Ferolla Piero , Scoazec Jean-Yves , Filosso Pier Luigi , Chapelier Alain , Guggino Gianluca , Monaco Roberto , Grimaldi Franco , Pizzolitto Stefano , Guigay Joël , de Latour Bertrand Richard , Giuffrida Dario , Longchampt Elisabeth , de Montpreville Vincent Thomas , Fadel Elie , Colao Annamaria , Planchard David , Papotti Mauro , Faggiano Antongiulio , Baudin Eric
Published: August 2017

Background: The natural history and the best modality of follow-up of atypical lung carcinoids (AC) remain ill defined. The aim of this study was to analyze recurrence-free survival (RFS) after complete resection (R0) of stage I-III pulmonary AC. Secondary objectives were prognostic parameters, the location of recurrences, and the modality of follow-up. Methods: A retrospective review of 540 charts of AC patients treated between 1998 and 2008 at 10 French and Italian centers with experience in lung neuroendocrine tumor management was undertaken. The exclusion criteria were MEN1-related tumor, history of another cancer, referral after tumor relapse, and being lost to follow-up. A central pathological review was performed in each country. Results: Sixty-two patients were included. After a median follow-up time of 91 months (mean 85, range 6-165), 35% of the patients experienced recurrence: 16% were regional recurrences and 19% were distant metastases. Median RFS was not reached. The 1-, 3-, and 5-year RFS rate was 90, 79, and 68%, respectively. In univariate analysis, lymph node involvement (p = 0.0001), stage (p = 0.0001), mitotic count (p = 0.004), and type of surgery (p = 0.043) were significantly associated with RFS. In multivariate analysis, lymph node involvement was significantly associated with RFS (HR 95% CI: 0.000-0.151; p = 0.004). During follow-up, somatostatin receptor scintigraphy, fibroscopy, and abdominal examination results were available for 22, 12, and 25 patients, respectively. The median time interval for imaging follow-up was 10 months. Conclusions: After complete resection of AC, recurrences were observed mostly within the first 5 years of follow-up, within bronchi, mediastinal nodes, the liver, and bones. In R0 patients, lymph node involvement could help to stratify follow-up intervals. Suboptimal imaging is evidenced.
Philatelic Propaganda: U.S. Postage Stamps during the Cold War
Authors: Modarressi Matin
Published: August 2017

Throughout the Cold War, the leading powers used postage stamps to promote their foreign policy goals. This brief research note cites illustrative examples of U.S. and Cuban postage stamps and discusses how and why they were produced.
Alejandra Pizarnik and the Poetics of Radical Incarnation
Authors: Glover Adam
Published: August 2017

Generally appreciated as one of the most original and creative voices in twentieth-century Latin American poetry, Alejandra Pizarnik (Argentina, 1936–1972) has not been regarded as a religious poet. Yet despite her explicit disavowal of all forms of religious commitment, Pizarnik’s work is nonetheless animated by fundamentally theological concerns. This article examines in detail the theological motif of “incarnation” in Pizarnik’s verse. It argues that, despite her avowed secularism, Pizarnik frames her own poetic project in explicitly incarnational language and that this theologically inflected vision underwrites her conception of poetic meaning-making.
Emotional Forecasting of Happiness
Authors: Ringnes Hege Kristin , Stålsett Gry , Hegstad Harald , Danbolt Lars Johan
Published: August 2017

The aim of this study was to explore which group-based emotion regulation goals and strategies are offered in the group culture of Jehovah's Witnesses (JWS). Based on interviews with 29 group-active JWS in Norway, a thematic analysis was conducted in which an overall pattern of cognition taking precedence over emotions was found. Due to endtime expectations and a long-term goal of eternal life in Paradise, future emotions were prioritized. The emotion regulation strategies identified among JWS were social sharing and the interconnected cognitive reappraisal. A new concept, emotional forecasting, was introduced, describing a reappraisal tactic of regulation using prospects of future emotions to regulate the here and now. It was concluded that the prospection of the future is a strong regulator of emotions of the here and now and should be included in psychological models of emotion regulation.