bluuebunny/crossref_metadata_2025_split huggingface dataset:
How do we increase uptake of tamoxifen and other anti-estrogens for breast cancer prevention?
Authors: Crew Katherine D. , Albain Kathy S. , Hershman Dawn L. , Unger Joseph M. , Lo Shelly S. 
Published: May 2017

AbstractSeveral randomized controlled trials of anti-estrogens, such as tamoxifen and aromatase inhibitors, have demonstrated up to a 50–65% decrease in breast cancerincidence among high-risk women. Approximately 15% of women, age 35–79 years, in the U.S. meet criteria for breast cancer preventive therapies, but uptake of these medications remain low. Explanations for this low uptake includelack of awareness of breast cancer risk status, insufficient knowledge about breast cancer preventive therapies among patients and physicians, and toxicity concerns. Increasing acceptance of pharmacologic breast cancer prevention will require effective communication of breast cancer risk, accurate representation about the potential benefits and side effects of anti-estrogens, targeting-specific high-risk populations most likely to benefit from preventive therapy, and minimizing the side effects of current anti-estrogens with novel administration and dosing options. One strategy to improve the uptake of chemoprevention strategies is to consider lessons learned from the use of drugs to prevent other chronic conditions, such as cardiovascular disease. Enhancing uptake and adherence to anti-estrogens for primary prevention holds promise for significantly reducing breast cancer incidence, however, this will require a significant change in our current clinical practice and stronger advocacy and awareness at the national level.
A malaria vaccine protects Aotus monkeys against virulent Plasmodium falciparum infection
Authors: Srinivasan Prakash , Baldeviano G. Christian , Miura Kazutoyo , Diouf Ababacar , Ventocilla Julio A. , Leiva Karina P. , Lugo-Roman Luis , Lucas Carmen , Orr-Gonzalez Sachy , Zhu Daming , Villasante Eileen , Soisson Lorraine , Narum David L. , Pierce Susan K. , Long Carole A. , Diggs Carter , Duffy Patrick E. , Lescano Andres G. , Miller Louis H. 
Published: May 2017

AbstractThe Plasmodium falciparum protein, apical membrane antigen 1 forms a complex with another parasite protein, rhoptry neck protein 2, to initiate junction formation with the erythrocyte and is essential for merozoite invasion during the blood stage of infection. Consequently, apical membrane antigen 1 has been a target of vaccine development but vaccination with apical membrane antigen 1 alone in controlled human malaria infections failed to protect and showed limited efficacy in field trials. Here we show that vaccination with AMA1–RON2L complex in Freund’s adjuvant protects Aotus monkeys against a virulent Plasmodium falciparum infection. Vaccination with AMA1 alone gave only partial protection, delaying infection in one of eight animals. However, the AMA1–RON2L complex vaccine completely protected four of eight monkeys and substantially delayed infection (>25 days) in three of the other four animals. Interestingly, antibodies from monkeys vaccinated with the AMA1–RON2L complex had significantly higher neutralizing activity than antibodies from monkeys vaccinated with AMA1 alone. Importantly, we show that antibodies from animals vaccinated with the complex have significantly higher neutralization activity against non-vaccine type parasites. We suggest that vaccination with the AMA1–RON2L complex induces functional antibodies that better recognize AMA1 as it appears complexed with RON2 during merozoite invasion. These data justify progression of this next generation AMA1 vaccine towards human trials.
Activated hepatic stellate cells secrete periostin to induce stem cell-like phenotype of residual hepatocellular carcinoma cells after heat treatment
Authors: Zhang Rui , Yao Rong-Rong , Li Jing-Huan , Dong Gang , Ma Min , Zheng Qiong-Dan , Gao Dong-Mei , Cui Jie-Feng , Ren Zheng-Gang , Chen Rong-Xin 
Published: May 2017

AbstractSome evidences show that residual tumor after thermal ablation will progress rapidly. However, its mechanisms remain unclear. Here, we assessed whether activated HSCs could regulate stem cell-like property of residual tumor after incomplete thermal ablation to promote tumor progression. Human HCC cell lines were exposed to sublethal heat treatment to simulate the peripheral zone of thermal ablation. After residual HCC cells were cultured with conditional medium (CM) from activated HSCs, parameters of the stem cell-like phenotypes were analyzed. Nude mice bearing heat-exposed residual HCC cells and HSCs were subjected to metformin treatment to thwarter tumor progression. CM from activated primary HSCs or LX-2 cells significantly induced the stem cell-like phenotypes of residual HCC cells after heat treatment. These effects were significantly abrogated by neutralizing periostin (POSTN) in the CM. POSTN regulated the stemness of heat-exposed residual HCC cells via activation of integrin β1/AKT/GSK-3β/β-catenin/TCF4/Nanog signaling pathway. Metformin significantly inhibited in vivo progression of heat-exposed residual HCC via suppressing POSTN secretion and decreasing cancer stem cell marker expression. Our data propose a new mechanism of activated HSCs promoting the stemness traits of residual HCC cells after incomplete thermal ablation and suggest metformin as a potential drug to reverse this process.
Room-temperature Magnetism in Carbon Dots and Enhanced Ferromagnetism in Carbon Dots-Polyaniline Nanocomposite
Authors: Liu Jian , Bi Hong , Cesar Morais Paulo , Zhang Xiang , Zhang Fapei , Hu Lin 
Published: May 2017

AbstractRoom temperature magnetic ordering is reported for very small carbon dots (CDs), mat-like polyaniline nanofibers (Mat-PANI) and a composite of CDs@Mat-PANI containing 0.315 wt% CDs. We have found saturation magnetization (M
S
) of CDs, Mat-PANI and CDs@Mat-PANI at 5 (20/300) K equals to 0.0079 (0.0048/0.0019), 0.0116 (0.0065/0.0055) and 0.0349 (0.0085/0.0077) emu/g, respectively. The M
S
enhancement in CDs@Mat-PANI (200% and 40% at 5 K and 300 K, respectively) is attributed to electron transfer from Mat-PANI imine N-atoms to the encapsulated CDs. Changes in M
S
values reveal that 0.81 (0.08) electron/CD is transferred at 5 (300) K, which is supported by observation of CDs photoluminescence (PL) redshift while in CDs@Mat-PANI. Band-bending and bandgap-renormalization calculations are used to predict a redshift of 117 meV at 300 K as a result of the electron transfer, in excellent agreement with the PL data (110 meV). Raman, X-ray diffraction and X-ray photoelectron spectroscopy data are used to confirm the electron transfer process as well as the strong interaction of CDs with PANI within CDs@Mat-PANI, which increases the crystalline domain size of Mat-PANI from about 4.8 nm to 9.2 nm while reducing the tensile strain from about 6.2% to 1.8%.
Musashi-1 promotes a cancer stem cell lineage and chemoresistance in colorectal cancer cells
Authors: Chiou Guang-Yuh , Yang Tzu-Wei , Huang Chi-Chou , Tang Chia-Ying , Yen Jung-Yi , Tsai Ming-Chang , Chen Hsuan-Yi , Fadhilah Nurul , Lin Chun-Che , Jong Yuh-Jyh 
Published: May 2017

AbstractColorectal cancers (CRCs) are a critical health issue worldwide. Cancer stem cell (CSC) lineages are associated with tumour transformation, progression, and malignant transformation. However, how lineages are transformed and how chemoresistance is acquired by CRCs remain largely unknown. In this report, we demonstrated that the RNA-binding protein Musashi-1 enhanced the development of CD44+ colorectal CSCs and triggered the formation of anti-apoptotic stress granules (SGs). Our results indicated that CD44+ CSC lineage-specific induction of tumour malignancies was controlled by Musashi-1. In addition, Musashi-1 formed SGs when CRC cell lines were treated with 5-fluorouracil. The C-terminal domain of Musashi-1 was critical for recruitment of Musashi-1 into SGs. Intracellular Musashi-1 SGs enhanced the chemoresistance of CRCs. Analysis of clinical CRC samples indicated that Musashi-1 expression was prominent in CRC stage IIA and IIB. In summary, we demonstrated that Musashi-1, a stemness gene, is a critical modulator that promotes the development of CD44+ colorectal CSCs and also enhances CRC chemoresistance via formation of SGs. Our findings elucidated a novel mechanism of CRC chemoresistance through increased anti-apoptotic effects via Musashi-1-associated SGs.
Combined use of metformin and atorvastatin attenuates atherosclerosis in rabbits fed a high-cholesterol diet
Authors: Luo Fei , Guo Yuan , Ruan Gui-yun , Long Jun-ke , Zheng Xi-long , Xia Qin , Zhao Shui-ping , Peng Dao-quan , Fang Zhen-fei , Li Xiang-ping 
Published: May 2017

AbstractStatins are widely used to reduce cardiovascular risk. Unfortunately, some patients still experience cardiovascular events though prescribed with high-intensity statins. Metformin, an anti-diabetic drug, was reported to possess anti-atherosclerotic effects. Therefore, the experiments were designed to evaluate whether combined use of metformin and atorvastatin can achieve additional benefits. In rabbits fed a high-cholesterol diet, we evaluated the effects of the combination therapy on atherosclerotic plaques, lipid profiles, blood glucose levels, liver and kidney functions. Effects of combination therapy on cholesterol efflux and the expression of related transporters were studied in vitro. Our results showed that the combination therapy induced a more significant decrease in atherosclerotic lesion area than atorvastatin without additional lipid-lowering effect. The combination therapy significantly increased the percentage of large high-density lipoprotein subfraction. The intravenous glucose tolerance test showed that atorvastatin-treated rabbits had an increased area under the curve for time-dependent glucose levels after a bolus injection of glucose, which was completely reversed by metformin treatment. In cultured macrophages, co-treatment with metformin and atorvastatin promoted cholesterol efflux and up-regulated expression of ATP-binding cassette transporters A1 and G1. Taken together, our results suggest that atorvastatin/metformin combination therapy may achieve additional anti-atherosclerotic benefits likely through increasing cholesterol efflux in macrophages.
The Transcription Factor IRF6 Co-Represses PPARγ-Mediated Cytoprotection in Ischemic Cerebrovascular Endothelial Cells
Authors: Huang Rongzhong , Hu Zicheng , Feng Yuxing , Yu Lehua , Li Xingsheng 
Published: May 2017

AbstractActivation of peroxisome proliferator-activated receptor gamma (PPARγ) in the cerebrovascular endothelium is a key suppressor of post-stroke brain damage. However, the role of PPARγ’s co-regulators during cerebral ischemia remains largely unknown. Here, we show that the transcription factor IRF6 is a novel PPARγ co-regulator that directly binds to and suppresses PPARγ activity in murine cerebrovascular endothelial cells. Moreover, IRF6 was also revealed to be a transcriptional target of PPARγ suppression, with PPARγ silencing significantly promoting IRF6 expression in cerebrovascular endothelial cells. In addition, IRF6 silencing significantly promoted pioglitazone’s cytoprotective effects in ischemic murine cerebrovascular endothelial cells. Mechanistically, IRF6 significantly suppressed PPARγ’s transcriptional inhibition of the ischemia-induced, pro-apoptotic microRNA miR-106a. In conclusion, we identified IRF6 as a novel PPARγ co-suppressor that serves a key role in suppressing PPARγ-mediated cerebrovascular endothelial cytoprotection following ischemia. Further investigation into IRF6 and other PPARγ co-regulators should provide additional insights into PPARγ’s cytoprotective role in the cerebrovascular endothelium following stroke.
Aberrant functional connectivity in depression as an index of state and trait rumination
Authors: Rosenbaum David , Haipt Alina , Fuhr Kristina , Haeussinger Florian B. , Metzger Florian G. , Nuerk Hans-Christoph , Fallgatter Andreas J. , Batra Anil , Ehlis Ann-Christine 
Published: May 2017

AbstractDepression has been shown to be related to a variety of aberrant brain functions and structures. Particularly the investigation of alterations in functional connectivity (FC) in major depressive disorder (MDD) has been a promising endeavor, since a better understanding of pathological brain networks may foster our understanding of the disease. However, the underling mechanisms of aberrant FC in MDD are largely unclear. Using functional near-infrared spectroscopy (fNIRS) we investigated FC in the cortical parts of the default mode network (DMN) during resting-state in patients with current MDD. Additionally, we used qualitative and quantitative measures of psychological processes (e.g., state/trait rumination, mind-wandering) to investigate their contribution to differences in FC between depressed and non-depressed subjects. Our results indicate that 40% of the patients report spontaneous rumination during resting-state. Depressed subjects showed reduced FC in parts of the DMN compared to healthy controls. This finding was linked to the process of state/trait rumination. While rumination was negatively correlated with FC in the cortical parts of the DMN, mind-wandering showed positive associations.
Influence of soil moisture on codenitrification fluxes from a urea-affected pasture soil
Authors: Clough Timothy J. , Lanigan Gary J. , de Klein Cecile A. M. , Samad Md. Sainur , Morales Sergio E. , Rex David , Bakken Lars R. , Johns Charlotte , Condron Leo M. , Grant Jim , Richards Karl G. 
Published: May 2017

AbstractIntensively managed agricultural pastures contribute to N2O and N2 fluxes resulting in detrimental environmental outcomes and poor N use efficiency, respectively. Besides nitrification, nitrifier-denitrification and heterotrophic denitrification, alternative pathways such as codenitrification also contribute to emissions under ruminant urine-affected soil. However, information on codenitrification is sparse. The objectives of this experiment were to assess the effects of soil moisture and soil inorganic-N dynamics on the relative contributions of codenitrification and denitrification (heterotrophic denitrification) to the N2O and N2 fluxes under a simulated ruminant urine event. Repacked soil cores were treated with 15N enriched urea and maintained at near saturation (−1 kPa) or field capacity (−10 kPa). Soil inorganic-N, pH, dissolved organic carbon, N2O and N2 fluxes were measured over 63 days. Fluxes of N2, attributable to codenitrification, were at a maximum when soil nitrite (NO2−) concentrations were elevated. Cumulative codenitrification was higher (P = 0.043) at −1 kPa. However, the ratio of codenitrification to denitrification did not differ significantly with soil moisture, 25.5 ± 15.8 and 12.9 ± 4.8% (stdev) at −1 and −10 kPa, respectively. Elevated soil NO2− concentrations are shown to contribute to codenitrification, particularly at −1 kPa.
Essential hypertension: A filtered serum based metabolomics study
Authors: Ameta Keerti , Gupta Ashish , Kumar Sudeep , Sethi Rishi , Kumar Deepak , Mahdi Abbas Ali 
Published: May 2017

AbstractDespite the easy and reliable methods of blood pressure measurement, the screening of essential hypertension (EH) is usually ignored due to delayed onset of symptoms. A probe into the biochemical changes in hypertension would serve as a welcome asset to provide insight into the mechanistic aspects of EH. Filtered serum samples from 64 EH patients and 59 healthy controls (HC) were analysed using 800 MHz nuclear magnetic resonance (NMR) spectroscopy. Application of principal component analysis (PCA) and orthogonal partial least-squares discriminant analysis (OPLS-DA) following receiver operating characteristic (ROC) curve of NMR data reveals significantly perturbed metabolites: alanine, arginine, methionine, pyruvate, adenine, and uracil. This set of metabolites correctly classified 99% of cases from HC and also showed excellent correlation in both isolated elevated diastolic blood pressure (DBP) cases and combined elevated systolic-diastolic blood pressure cases. Proton NMR metabolomics of EH may prove helpful in defining associated biomarkers and serve as an alternate diagnostic tool with judicious clinical assessment.
A broad-spectrum bactericidal lipopeptide with anti-biofilm properties
Authors: Meir Ohad , Zaknoon Fadia , Cogan Uri , Mor Amram 
Published: May 2017

AbstractPrevious studies of the oligoacyllysyl (OAK) series acyl-lysyl-lysyl-aminoacyl-lysine-amide, suggested their utility towards generating robust linear lipopeptide-like alternatives to antibiotics, although to date, none exhibited potent broad-spectrum bactericidal activity. To follow up on this premise, we produced a new analog (C14KKc12K) and investigated its properties in various media. Mechanistic studies suggest that C14KKc12K uses a non-specific membrane-disruptive mode of action for rapidly reducing viability of Gram-negative bacteria (GNB) similarly to polymyxin B (PMB), a cyclic lipopeptide used as last resort antibiotic. Indeed, C14KKc12K displayed similar affinity for lipopolysaccharides and induced cell permeabilization associated with rapid massive membrane depolarization. Unlike PMB however, C14KKc12K was also bactericidal to Gram-positive bacteria (GPB) at or near the minimal inhibitory concentration (MIC), as assessed against a multispecies panel of >50 strains, displaying MIC50 at 3 and 6 µM, respectively for GPB and GNB. C14KKc12K retained activity in human saliva, reducing the viability of cultivable oral microflora by >99% within two minutes of exposure, albeit at higher concentrations, which, nonetheless, were similar to the commercial gold standard, chlorhexidine. This equipotent bactericidal activity was also observed in pre-formed biofilms of Streptococcus mutans, a major periodontal pathogen. Such compounds therefore, may be useful for eradication of challenging poly-microbial infections.
Inductive flash-annealing of bulk metallic glasses
Authors: Kosiba K. , Pauly S. 
Published: May 2017

AbstractWe developed a temperature-controlled inductive flash-annealing device, which heats bulk metallic glasses (BMGs) at defined rates of up to 200 K/s to a given temperature. Subsequent instantaneous quenching in water allows preserving the microstructures obtained at various stages of crystallization. One Zr-based and two CuZr-based BMGs were flash-annealed at the onset of crystallization with different heating rates in order to prepare advanced BMG-matrix composites. The highly reproducible composite microstructures contain uniformly dispersed crystals and a narrow crystal size distribution. In order to assess the limitations of the present process, which mainly originate from non-uniform inductive heating, the skin depth was calculated. It is determined to be about 2.3 mm, which enables flash-annealing of rather bulky samples. The cooling rate was estimated from the interlamellar spacing of eutectic Al-Cu alloys to be on the order of 103 K/s. This ensures that decomposition of the microstructure during quenching is prevented. The present flash-annealing procedure is applicable to a wide variety of glass-forming liquids and has a large potential for tailoring the microstructure and, consequently, the mechanical properties of BMG-matrix composites.
Computationally-driven engineering of sublattice ordering in a hexagonal AlHfScTiZr high entropy alloy
Authors: Rogal Lukasz , Bobrowski Piotr , Körmann Fritz , Divinski Sergiy , Stein Frank , Grabowski Blazej 
Published: May 2017

AbstractMulti-principle element alloys have enormous potential, but their exploration suffers from the tremendously large range of configurations. In the last decade such alloys have been designed with a focus on random solid solutions. Here we apply an experimentally verified, combined thermodynamic and first-principles design strategy to reverse the traditional approach and to generate a new type of hcp Al-Hf-Sc-Ti-Zr high entropy alloy with a hitherto unique structure. A phase diagram analysis narrows down the large compositional space to a well-defined set of candidates. First-principles calculations demonstrate the energetic preference of an ordered superstructure over the competing disordered solid solutions. The chief ingredient is the Al concentration, which can be tuned to achieve a D019 ordering on the hexagonal lattice. The computationally designed D019 superstructure is experimentally confirmed by transmission electron microscopy and X-ray studies. Our scheme enables the exploration of a new class of high entropy alloys.
Large field of view, fast and low dose multimodal phase-contrast imaging at high x-ray energy
Authors: Astolfo Alberto , Endrizzi Marco , Vittoria Fabio A. , Diemoz Paul C. , Price Benjamin , Haig Ian , Olivo Alessandro 
Published: May 2017

AbstractX-ray phase contrast imaging (XPCI) is an innovative imaging technique which extends the contrast capabilities of ‘conventional’ absorption based x-ray systems. However, so far all XPCI implementations have suffered from one or more of the following limitations: low x-ray energies, small field of view (FOV) and long acquisition times. Those limitations relegated XPCI to a ‘research-only’ technique with an uncertain future in terms of large scale, high impact applications. We recently succeeded in designing, realizing and testing an XPCI system, which achieves significant steps toward simultaneously overcoming these limitations. Our system combines, for the first time, large FOV, high energy and fast scanning. Importantly, it is capable of providing high image quality at low x-ray doses, compatible with or even below those currently used in medical imaging. This extends the use of XPCI to areas which were unpractical or even inaccessible to previous XPCI solutions. We expect this will enable a long overdue translation into application fields such as security screening, industrial inspections and large FOV medical radiography – all with the inherent advantages of the XPCI multimodality.
Grassland restoration reduces water yield in the headstream region of Yangtze River
Authors: Li Jia , Liu Dan , Wang Tao , Li Yingnian , Wang Shiping , Yang Yuting , Wang Xiaoyi , Guo Hui , Peng Shushi , Ding Jinzhi , Shen Miaogen , Wang Lei 
Published: May 2017

AbstractLarge–scale ecological restoration programs are considered as one of the key strategies to enhance ecosystem services. The Headstream region of Yangtze River (HYZR), which is claimed to be China’s Water Tower but witnessed the rapid grassland deterioration during 1970s–2000, has seen a series of grassland restoration programs since 2000. But few studies have thoroughly estimated the hydrological effect of this recent grassland restoration. Here we show that restoration significantly reduces growing-season water yield coefficient (WYC) from 0.37 ± 0.07 during 1982–1999 to 0.24 ± 0.07 during 2000–2012. Increased evapotranspiration (ET) is identified as the main driver for the observed decline in WYC. After factoring out climate change effects, vegetation restoration reduces streamflow by 9.75 ± 0.48 mm from the period 1982–1999 to the period 2000–2012, amounting to 16.4 ± 0. 80% of climatological growing-season streamflow. In contrary to water yield, restoration is conducive to soil water retention – an argument that is supported by long-term in-situ grazing exclusion experiment. Grassland restoration therefore improves local soil water conditions but undercuts gain in downstream water resources associated with precipitation increases.