bluuebunny/crossref_metadata_2025_split huggingface dataset:
Large marine protected areas represent biodiversity now and under climate change
Authors: Davies T. E. , Maxwell S. M. , Kaschner K. , Garilao C. , Ban N. C. 
Published: August 2017

AbstractLarge marine protected areas (>30,000 km2) have a high profile in marine conservation, yet their contribution to conservation is contested. Assessing the overlap of large marine protected areas with 14,172 species, we found large marine protected areas cover 4.4% of the ocean and at least some portion of the range of 83.3% of the species assessed. Of all species within large marine protected areas, 26.9% had at least 10% of their range represented, and this was projected to increase to 40.1% in 2100. Cumulative impacts were significantly higher within large marine protected areas than outside, refuting the critique that they only occur in pristine areas. We recommend future large marine protected areas be sited based on systematic conservation planning practices where possible and include areas beyond national jurisdiction, and provide five key recommendations to improve the long-term representation of all species to meet critical global policy goals (e.g., Convention on Biological Diversity’s Aichi Targets).
Functionalized Non-vascular Nitinol Stent via Electropolymerized Polydopamine Thin Film Coating Loaded with Bortezomib Adjunct to Hyperthermia Therapy
Authors: Aguilar Ludwig Erik , Tumurbaatar Batgerel , Ghavaminejad Amin , Park Chan Hee , Kim Cheol Sang 
Published: August 2017

AbstractGastrointestinal malignancies have been a tremendous problem in the medical field and cover a wide variety of parts of the system, (i.e. esophagus, duodenum, intestines, and rectum). Usually, these malignancies are treated with palliation with the use of non-vascular nitinol stents. However, stenting is not a perfect solution for these problems. While it can enhance the quality of life of the patient, in time the device will encounter problems such as re-occlusion due to the rapid growth of the tumor. In this study, we propose a functionalization technique using electropolymerization of polydopamine directly onto the nitinol stent struts for the combined application of hyperthermia and chemotherapy. The coating was characterized using FESEM, XPS, and FT-IR. Drug release studies show that facile release of the anticancer drug BTZ from the surface of the polydopamine-coated stent could be achieved by the dissociation between catechol groups of polydopamine and the boronic acid functionality of BTZ in a pH-dependent manner. The anti-cancer property was also evaluated, and cytotoxicity on ESO26 and SNU-5 cancer cell lines were observed. Our results suggest that the introduced approach can be considered as a potential method for therapeutic stent application.
Giant magnetoresistance in lateral metallic nanostructures for spintronic applications
Authors: Zahnd G. , Vila L. , Pham V. T. , Marty A. , Beigné C. , Vergnaud C. , Attané J. P. 
Published: August 2017

AbstractIn this letter, we discuss the shift observed in spintronics from the current-perpendicular-to-plane geometry towards lateral geometries, illustrating the new opportunities offered by this configuration. Using CoFe-based all-metallic LSVs, we show that giant magnetoresistance variations of more than 10% can be obtained, competitive with the current-perpendicular-to-plane giant magnetoresistance. We then focus on the interest of being able to tailor freely the geometries. On the one hand, by tailoring the non-magnetic parts, we show that it is possible to enhance the spin signal of giant magnetoresistance structures. On the other hand, we show that tailoring the geometry of lateral structures allows creating a multilevel memory with high spin signals, by controlling the coercivity and shape anisotropy of the magnetic parts. Furthermore, we study a new device in which the magnetization direction of a nanodisk can be detected. We thus show that the ability to control the magnetic properties can be used to take advantage of all the spin degrees of freedom, which are usually occulted in current-perpendicular-to-plane devices. This flexibility of lateral structures relatively to current-perpendicular-to-plane structures is thus found to offer a new playground for the development of spintronic applications.
Treatment patterns, efficacy and toxicity of regorafenib in gastrointestinal stromal tumour patients
Authors: Schvartsman Gustavo , Wagner Michael J. , Amini Behrang , Zobniw Chrystia M. , Trinh Van Anh , Barbo Andrea G. , Lin Heather Y. , Wang Wei-Lien , Conley Anthony Paul , Ravi Vinod , Araujo Dejka M. , Zarzour Maria Alejandra , Benjamin Robert S. , Patel Shreyaskumar , Somaiah Neeta 
Published: August 2017

AbstractRegorafenib was approved as third-line therapy for advanced Gastrointestinal Stromal Tumour (GIST) at a starting dose of 160 mg daily 3 weeks on, 1 week off, based on improvement in progression free survival over placebo (4.8 vs. 0.9 months), but the response rate was low at 4.5%. Given the high toxicity rate in GIST patients, there is variability in the post-marketing dosing of regorafenib. We aimed to summarize our experience regarding prescribing patterns, efficacy and toxicity of regorafenib and determine the role of response assessment by Choi criteria in GIST patients. We included 28 patients who received regorafenib from our pharmacy. Baseline patient characteristics and treatment outcomes were recorded and an independent radiologist assessed response using Choi and RECIST. Seventy-nine percent of patients started at a 120 mg continuous daily dosing schedule, different from the standard intermittent dosing schedule. Grade 3/4 adverse events were experienced by 43% of patients. Median progression-free survival was 8.7 months. Continuous dosing with regorafenib at 120 mg daily is the preferred prescribing pattern and appears to be better tolerated and with comparable efficacy to the current standard dose. Similar to imatinib, the partial response rate for regorafenib by Choi (29%) was higher compared to RECIST (4%).
Cyclooxygenase-2 contributes to oxidopamine-mediated neuronal inflammation and injury via the prostaglandin E2 receptor EP2 subtype
Authors: Kang Xu , Qiu Jiange , Li Qianqian , Bell Katherine A. , Du Yifeng , Jung Da Woon , Lee Jae Yeol , Hao Jiukuan , Jiang Jianxiong 
Published: August 2017

AbstractCyclooxygenase-2 (COX-2) triggers pro-inflammatory processes that can aggravate neuronal degeneration and functional impairments in many neurological conditions, mainly via producing prostaglandin E2 (PGE2) that activates four membrane receptors, EP1-EP4. However, which EP receptor is the culprit of COX-2/PGE2-mediated neuronal inflammation and degeneration remains largely unclear and presumably depends on the insult types and responding components. Herein, we demonstrated that COX-2 was induced and showed nuclear translocation in two neuronal cell lines – mouse Neuro-2a and human SH-SY5Y – after treatment with neurotoxin 6-hydroxydopamine (6-OHDA), leading to the biosynthesis of PGE2 and upregulation of pro-inflammatory cytokine interleukin-1β. Inhibiting COX-2 or microsomal prostaglandin E synthase-1 suppressed the 6-OHDA-triggered PGE2 production in these cells. Treatment with PGE2 or EP2 selective agonist butaprost, but not EP4 agonist CAY10598, increased cAMP response in both cell lines. PGE2-initiated cAMP production in these cells was blocked by our recently developed novel selective EP2 antagonists – TG4-155 and TG6-10-1, but not by EP4 selective antagonist GW627368X. The 6-OHDA-promoted cytotoxicity was largely blocked by TG4-155, TG6-10-1 or COX-2 selective inhibitor celecoxib, but not by GW627368X. Our results suggest that PGE2 receptor EP2 is a key mediator of COX-2 activity-initiated cAMP signaling in Neuro-2a and SH-SY5Y cells following 6-OHDA treatment, and contributes to oxidopamine-mediated neurotoxicity.
Spatially resolved investigation of all optical magnetization switching in TbFe alloys
Authors: Arora Ashima , Mawass Mohamad-Assaad , Sandig Oliver , Luo Chen , Ünal Ahmet A. , Radu Florin , Valencia Sergio , Kronast Florian 
Published: August 2017

AbstractOptical control of magnetization using femtosecond laser without applying any external magnetic field offers the advantage of switching magnetic states at ultrashort time scales. Recently, all-optical helicity-dependent switching (AO-HDS) has drawn a significant attention for potential information and data storage device applications. In this work, we employ element and magnetization sensitive photoemission electron microscopy (PEEM) to investigate the role of heating in AO-HDS for thin films of the rare-earth transition-metal alloy TbFe. Spatially resolved measurements in a 3–5 μm sized stationary laser spot demonstrate that AO-HDS is a local phenomenon in the vicinity of thermal demagnetization in a ‘ring’ shaped region. The efficiency of AO-HDS further depends on a local temperature profile around the demagnetized region and thermally activated domain wall motion. We also demonstrate that the thickness of the film determines the preferential switching direction for a particular helicity.
Time-of-Flight Three Dimensional Neutron Diffraction in Transmission Mode for Mapping Crystal Grain Structures
Authors: Cereser Alberto , Strobl Markus , Hall Stephen A. , Steuwer Axel , Kiyanagi Ryoji , Tremsin Anton S. , Knudsen Erik B. , Shinohara Takenao , Willendrup Peter K. , da Silva Fanta Alice Bastos , Iyengar Srinivasan , Larsen Peter M. , Hanashima Takayasu , Moyoshi Taketo , Kadletz Peter M. , Krooß Philipp , Niendorf Thomas , Sales Morten , Schmahl Wolfgang W. , Schmidt Søren 
Published: August 2017

AbstractThe physical properties of polycrystalline materials depend on their microstructure, which is the nano- to centimeter scale arrangement of phases and defects in their interior. Such microstructure depends on the shape, crystallographic phase and orientation, and interfacing of the grains constituting the material. This article presents a new non-destructive 3D technique to study centimeter-sized bulk samples with a spatial resolution of hundred micrometers: time-of-flight three-dimensional neutron diffraction (ToF 3DND). Compared to existing analogous X-ray diffraction techniques, ToF 3DND enables studies of samples that can be both larger in size and made of heavier elements. Moreover, ToF 3DND facilitates the use of complicated sample environments. The basic ToF 3DND setup, utilizing an imaging detector with high spatial and temporal resolution, can easily be implemented at a time-of-flight neutron beamline. The technique was developed and tested with data collected at the Materials and Life Science Experimental Facility of the Japan Proton Accelerator Complex (J-PARC) for an iron sample. We successfully reconstructed the shape of 108 grains and developed an indexing procedure. The reconstruction algorithms have been validated by reconstructing two stacked Co-Ni-Ga single crystals, and by comparison with a grain map obtained by post-mortem electron backscatter diffraction (EBSD).
Deep Brain Stimulation of the subthalamic nucleus does not negatively affect social cognitive abilities of patients with Parkinson’s disease
Authors: Enrici Ivan , Mitkova Antonia , Castelli Lorys , Lanotte Michele , Lopiano Leonardo , Adenzato Mauro 
Published: August 2017

AbstractBilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a treatment option for patients with advanced idiopathic PD successful at alleviating disabling motor symptoms. Nevertheless, the effects of STN-DBS on cognitive functions remain controversial and few studies have investigated modification of social cognitive abilities in patients with PD treated with STN-DBS. Here we expanded the typically-investigated spectrum of these abilities by simultaneously examining emotion recognition, and both affective and cognitive Theory of Mind (ToM). By means of a cross-sectional study, 20 patients with PD under dopaminergic replacement therapy, 18 patients with PD treated with STN-DBS, and 20 healthy controls performed the Ekman 60-Faces test, the full version of the Reading the Mind in the Eyes test, and the Protocol for the Attribution of Communicative Intentions. There were no differences between the PD groups (treated and not treated with STN-DBS) on any of the social cognitive tests. Our results suggest that patients with PD who are treated with STN-DBS do not experience detrimental effects on their social cognitive abilities. The present study, the first one examining a wide spectrum of social cognitive abilities after DBS of the STN, suggests that this surgical procedure can be considered safe from this standpoint.
Rational identification of aggregation hotspots based on secondary structure and amino acid hydrophobicity
Authors: Matsui Daisuke , Nakano Shogo , Dadashipour Mohammad , Asano Yasuhisa 
Published: August 2017

AbstractInsolubility of proteins expressed in the Escherichia coli expression system hinders the progress of both basic and applied research. Insoluble proteins contain residues that decrease their solubility (aggregation hotspots). Mutating these hotspots to optimal amino acids is expected to improve protein solubility. To date, however, the identification of these hotspots has proven difficult. In this study, using a combination of approaches involving directed evolution and primary sequence analysis, we found two rules to help inductively identify hotspots: the α-helix rule, which focuses on the hydrophobicity of amino acids in the α-helix structure, and the hydropathy contradiction rule, which focuses on the difference in hydrophobicity relative to the corresponding amino acid in the consensus protein. By properly applying these two rules, we succeeded in improving the probability that expressed proteins would be soluble. Our methods should facilitate research on various insoluble proteins that were previously difficult to study due to their low solubility.
DDX3 localizes to the centrosome and prevents multipolar mitosis by epigenetically and translationally modulating p53 expression
Authors: Chen Wei-Ju , Wang Wei-Ting , Tsai Tsung-Yuan , Li Hao-Kang , Lee Yan-Hwa Wu 
Published: August 2017

AbstractThe DEAD-box RNA helicase DDX3 plays divergent roles in tumorigenesis, however, its function in mitosis is unclear. Immunofluorescence indicated that DDX3 localized to centrosome throughout the cell cycle and colocalized with centrosome-associated p53 during mitosis in HCT116 and U2OS cells. DDX3 depletion promoted chromosome misalignment, segregation defects and multipolar mitosis, eventually leading to G2/M delay and cell death. DDX3 prevented multipolar mitosis by inactivation and coalescence of supernumerary centrosomes. DDX3 silencing suppressed Ser15phosphorylation of p53 which is required for p53 centrosomal localization. Additionally, knockout of p53 dramatically diminished the association of DDX3 with centrosome, which was rescued by overexpression of the centrosomal targeting-defective p53 S15A mutant, indicating that centrosomal localization of DDX3 is p53 dependent but not through centrosomal location of p53. Furthermore, DDX3 knockdown suppressedp53transcription through activation of DNA methyltransferases (DNMTs) along with hypermethylation ofp53promoter and promoting the binding of repressive histone marks top53promoter. Moreover, DDX3 modulatedp53mRNA translation. Taken together, our study suggests that DDX3 regulates epigenetic transcriptional and translational activation of p53 and colocalizes with p53 at centrosome during mitosis to ensure proper mitotic progression and genome stability, which supports the tumor-suppressive role of DDX3.
Pepcan-12 (RVD-hemopressin) is a CB2 receptor positive allosteric modulator constitutively secreted by adrenals and in liver upon tissue damage
Authors: Petrucci Vanessa , Chicca Andrea , Glasmacher Sandra , Paloczi Janos , Cao Zongxian , Pacher Pal , Gertsch Jürg 
Published: August 2017

AbstractPepcan-12 (RVD-hemopressin; RVDPVNFKLLSH) is the major peptide of a family of endogenous peptide endocannabinoids (pepcans) shown to act as negative allosteric modulators (NAM) of cannabinoid CB1 receptors. Noradrenergic neurons have been identified to be a specific site of pepcan production. However, it remains unknown whether pepcans occur in the periphery and interact with peripheral CB2 cannabinoid receptors. Here, it is shown that pepcan-12 acts as a potent (K
i
value ~50 nM) hCB2 receptor positive allosteric modulator (PAM). It significantly potentiated the effects of CB2 receptor agonists, including the endocannabinoid 2-arachidonoyl glycerol (2-AG), for [35S]GTPγS binding and cAMP inhibition (5–10 fold). In mice, the putative precursor pepcan-23 (SALSDLHAHKLRVDPVNFKLLSH) was identified with pepcan-12 in brain, liver and kidney. Pepcan-12 was increased upon endotoxemia and ischemia reperfusion damage where CB2 receptors play a protective role. The adrenals are a major endocrine site of production/secretion of constitutive pepcan-12, as shown by its marked loss after adrenalectomy. However, upon I/R damage pepcan-12 was strongly increased in the liver (from ~100 pmol/g to ~500 pmol/g) independent of adrenals. The wide occurrence of this endogenous hormone-like CB2 receptor PAM, with unforeseen opposite allosteric effects on cannabinoid receptors, suggests its potential role in peripheral pathophysiological processes.
Evidence-based tailoring of bioinformatics approaches to optimize methods that predict the effects of nonsynonymous amino acid substitutions in glucokinase
Authors: Šimčíková Daniela , Kocková Lucie , Vackářová Kateřina , Těšínský Miroslav , Heneberg Petr 
Published: August 2017

AbstractComputational methods that allow predicting the effects of nonsynonymous substitutions are an integral part of exome studies. Here, we validated and improved their specificity by performing a comprehensive bioinformatics analysis combined with experimental and clinical data on a model of glucokinase (GCK): 8835 putative variations, including 515 disease-associated variations from 1596 families with diagnoses of monogenic diabetes (GCK-MODY) or persistent hyperinsulinemic hypoglycemia of infancy (PHHI), and 126 variations with available or newly reported (19 variations) data on enzyme kinetics. We also proved that high frequency of disease-associated variations found in patients is closely related to their evolutionary conservation. The default set prediction methods predicted correctly the effects of only a part of theGCK-MODY-associated variations and completely failed to predict the normoglycemic or PHHI-associated variations. Therefore, we calculated evidence-based thresholds that improved significantly the specificity of predictions (≤75%). The combined prediction analysis even allowed to distinguish activating from inactivating variations and identified a group of putatively highly pathogenic variations (EVmutation score <−7.5 and SNAP2 score >70), which were surprisingly underrepresented among MODY patients and thus under negative selection during molecular evolution. We suggested and validated the first robust evidence-based thresholds, which allow improved, highly specific predictions of disease-associated GCK variations.
The validity and reliability of remote diabetic foot ulcer assessment using mobile phone images
Authors: van Netten Jaap J. , Clark Damien , Lazzarini Peter A. , Janda Monika , Reed Lloyd F. 
Published: August 2017

AbstractDespite their potential for telemedicine in diabetic foot ulcer treatment, diagnostic accuracy of assessment of diabetic foot ulcers using mobile phone images is unknown. Our aim was to determine the validity and reliability of remote diabetic foot ulcer assessment using mobile phone images. Fifty diabetic foot ulcers were assessed live and photographed. Five independent observers remotely assessed the mobile phone images twice for presence of nine clinical characteristics and three treatment decisions. Positive likelihood (LLR+) and negative likelihood (LLR−) ratios were calculated for validity. Multirater Randolph’s and bi-rater Bennet kappa values were calculated for reliability. LLR+ ranged from 1.3–4.2; LLR− ranged from 0.13–0.88; the treatment decision ‘peri-wound debridement’ was the only item with ‘strong diagnostic evidence’. Inter-observer reliability kappa ranged from 0.09–0.71; test-retest reliability from 0.45–0.86; the treatment decision ‘peri-wound debridement’ was the only item with ‘adequate agreement’. In conclusion, mobile phone images had low validity and reliability for remote assessment of diabetic foot ulcers and should not be used as a stand-alone diagnostic instrument. Clinicians who use mobile phone images in clinical practice should obtain as much additional information as possible when making treatment decisions based on these images, and be cautious of the low diagnostic accuracy.
Prevalence and risk factors associated with stroke in middle-aged and older Chinese: A community-based cross-sectional study
Authors: Gan Yong , Wu Jiang , Zhang Shengchao , Li Liqing , Yin Xiaoxv , Gong Yanhong , Herath Chulani , Mkandawire Naomie , Zhou Yanfeng , Song Xingyue , Zeng Xiaozhou , Li Wenzhen , Liu Qiaoyan , Shu Chang , Wang Zhihong , Lu Zuxun 
Published: August 2017

AbstractAlthough the prevalence of stroke and its risk factors has been widely reported in some Western countries, information on essential stroke parameters is lacking in China, the most populous nation. A community-based cross-sectional study with 8,018 Chinese adults aged ≥40 years was used to determine the prevalence of stroke and associated risk factors. Within the screened population, the prevalence of stroke was 2.21% for both sexes, 1.60% for females, and 3.18% for males. Prevalence increased with age in both sexes (P < 0.0001). In a multivariable model, factors significantly associated with stroke were increasing age (odds ratio [OR] = 1.87, 95% CI: 1.58–2.24), male gender (OR = 2.03, 95% CI: 1.42–2.90), family history of stroke (OR = 4.33, 95% CI: 2.89–6.49), history of hyperlipidemia (OR = 1.87, 95% CI 1.31–2.68), history of hypertension (OR = 1.47, 95% CI 1.02–2.12), and physical inactivity (OR = 1.74, 95% CI: 1.16–2.59). The findings indicate that stroke prevalence in middle-aged and older Chinese adults is higher in males than in females, and increases with age in both sexes. Population-based public health intervention programs and policies targeting hyperlipidemia and hypertension control and encouragement of physical activity should be highly prioritized for middle-aged and older adults in Shenzhen, China.
Spatial multi-scale relationships of ecosystem services: A case study using a geostatistical methodology
Authors: Liu Yang , Bi Jun , Lv Jianshu , Ma Zongwei , Wang Ce 
Published: August 2017

AbstractAdequately understanding the spatial multi-scale relationships of ecosystem services (ES) is an important step for environmental management decision-making. Here, we used spatially explicit methods to estimate five critical ES (nitrogen and phosphorous purifications, crop production, water supply and soil retention) related to non-point source (NPS) pollution in the Taihu Basin region of eastern China. Then a factorial kriging analysis and stepwise multiple regression were performed to identify the spatial multi-scale relationships of ES and their dominant factors at each scale. The spatial variations in ES were characterized at the 12 km and 83 km scales and the result indicated that the relationships of these services were scale dependent. It was inferred that at the 12 km scale, ES were controlled by anthropogenic activities and their relationships were dependent on socio-economic factors. At the 83 km scale, we suggested that ES were primarily dominated by the physical environment. Moreover, the policy implications of ES relationships and their dominant factors were discussed for the multi-level governance of NPS pollution. Overall, this study presents an optimized approach to identifying ES relationships at multiple spatial scales and illustrates how appropriate information can help guide water management.