bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular Dynamics Simulation reveals the mechanism by which the Influenza Cap-dependent Endonuclease acquires resistance against Baloxavir marboxil
Authors: Yoshino Ryunosuke , Yasuo Nobuaki , Sekijima Masakazu 
Published: November 2019

AbstractBaloxavir marboxil (BXM), an antiviral drug for influenza virus, inhibits RNA replication by binding to RNA replication cap-dependent endonuclease (CEN) of influenza A and B viruses. Although this drug was only approved by the FDA in October 2018, drug resistant viruses have already been detected from clinical trials owing to an I38 mutation of CEN. To investigate the reduction of drug sensitivity by the I38 mutant variants, we performed a molecular dynamics (MD) simulation on the CEN-BXM complex structure to analyze variations in the mode of interaction. Our simulation results suggest that the side chain methyl group of I38 in CEN engages in a CH-pi interaction with the aromatic ring of BXM. This interaction is abolished in various I38 mutant variants. Moreover, MD simulation on various mutation models and binding free energy prediction by MM/GBSA method suggest that the I38 mutation precludes any interaction with the aromatic ring of BXA and thereby reduces BXA sensitivity.
Identification of exosomal miR-455-5p and miR-1255a as therapeutic targets for breast cancer
Authors: Xin Ying , Wang Xueqiang , Meng Kexin , Ni Chao , Lv Zhenye , Guan Dandan 
Published: November 2019

Abstract
Accumulated evidence has demonstrated exosomes of cancer cells carry microRNAs (miRNAs) to non-malignant cells to induce metastasis. The present study aimed to identify crucial exosomal miRNAs for breast cancer (BC) using microarray data (GSE83669 and GSE50429) from Gene Expression Omnibus database, including exosomal samples from human BC cells (MCF7, MDA-MB-231) and normal mammary epithelial cell line (MCF10, MCF-10A), as well as original cell samples. Differentially expressed miRNAs (DEMs) were identified using EdgeR package, and mRNA targets were predicted using miRWalk2 database. The target genes were overlapped with BC genes from Comparative Toxicogenomics Database (CTD) to construct BC-related interaction network. Potential functions were analyzed by DAVID. The expression of crucial miRNAs and target genes were confirmed in other microarray datasets or TCGA sequencing data. Their associations with survival and other clinical characteristics were validated by Kaplan–Meier plotter and LinkedOmics database. As a result, 9 and 8 DEMs were identified to be shared in two datasets for exosomal and original cells, respectively. Further comparison showed that miR-455-5p was specifically differentially expressed in exosomes, and miR-1255a was commonly expressed in exosomal and original cells samples. miR-455-5p could interact with CDKN1B to influence cell cycle process and miR-1255a could regulate SMAD4 to participate in TGF-β signaling pathway. High expressed miR-455-5p (basal-like) and miR-1255a (overall) were associated with poor overall survival, while the high expression of their target genes was associated with excellent overall, recurrence-free or distant metastasis-free survival. In conclusion, the present study preliminarily indicates that exosomal miR-455-5p and miR-1255a may be novel therapeutic targets for BC.
Gastric mucosal devitalization (GMD): translation to a novel endoscopic metabolic therapy
Authors: Fayad Lea , Oberbach Andreas , Schweitzer Michael , Askin Frederic , Voltaggio Lysandra , Larman Tatianna , Enderle Markus , Hahn Hartmut , Khashab Mouen A. , Kalloo Anthony N. , Kumbhari Vivek 
Published: November 2019

Abstract
Background and study aims The metabolic effects of bariatric surgery may partially result from removal of the gastric mucosa, an often underappreciated endocrine organ. Using argon plasma coagulation (APC), we may be able to selectively devitalize (ablate) the mucosa. The aim of this study was to identify the optimal tissue color that would correspond to selective gastric mucosal devitalization (GMD) using ex-vivo human stomach specimens.
Patients and methods Stomach specimens were obtained at sleeve gastrectomy. Prior to APC application, a submucosal fluid cushion was created. APC was then applied over a 2 × 2-cm area to the fundus and body, aiming for the three indicator colors (white, golden, brown). Pathological analysis was then performed independently and in a blinded fashion by two pathologists to determine the depth of mucosal and submucosal percent thermal injury and mucosal percent cell death.
Results Six patients were enrolled. There was a significant correlation between tissue color and mucosal percent thermal injury. The highest percent mucosal thermal injury was seen with brown (99.6 %, 95 % CI: 98.7, 100), followed by golden (92.5 %, 95 % CI: 85.5, 99.5), and then white (75.2 %, 95 % CI: 58.3, 92.1, P < 0.01). Submucosal thermal injury was seen in 88.9 % of the slides. Greater than minimal submucosal injury (> 10 % depth) was found significantly more with brown tissue color (91.6 %) than golden (75 %) or white (33.3 %, P < 0.05). However, 91.7 % of the entire sample set < 50 % injury.
Conclusion GMD is achievable using APC without thermal injury to muscularis propria. A golden color results in sufficient mucosal injury with only superficial injury to the submucosa.
Comparison of colon adenoma detection rates using cap-assisted and Endocuff-assisted colonoscopy: a randomized controlled trial
Authors: Marsano Joseph , Johnson Sheeva , Yan Stephanie , Alli-Akintade Latifat , Wilson Machelle , Al-Juburi Amar , Stondell Jesse , Tejaswi Sooraj 
Published: November 2019

Abstract
Objectives and study aim Colonoscopy prevents colorectal cancer by removing adenomatous polyps, but missed adenomas lead to interval cancers. Different devices have been used to increase adenoma detection rates (ADR). Two such devices of interest are the transparent cap (Olympus) and Endocuff (ARC Medical). Our study aimed to compare differences in ADR between Endocuff-assisted colonoscopy (EAC), cap-assisted colonoscopy (CAC) and standard colonoscopy (SC).
Patients and methods A sample size of 126 subjects was calculated to determine an effect size of 30 %. Patients undergoing screening or surveillance colonoscopy between March 2016 and January 2017 were randomized to SC, CAC or EAC groups. Three experienced endoscopists performed all colonoscopies. Patient demographics, procedure indication, Boston Bowel Prep Score (BBPS), withdrawal time, polyp size, location, histopathology, were analyzed.
Results There was no difference in ADR (52 %, 40 % and 54 %) in the SC, CAC and EAC groups respectively (P = 0.4). Similar findings were also observed for proximal ADR (45 %, 35 %, and 50 %, P = 0.4) and SSA detection rate (16 %, 14 %, and 23 %, P = 0.5). EAC detected higher mean ADR per colonoscopy compared to CAC (1.70 vs 0.76, P = 0.01). However, there was no significant difference in mean ADR per positive colonoscopy (2.08, 1.63, and 2.59, P = 0.21).
Conclusion In a randomized controlled trial comparing AC to CAC and SC, neither device conferred additional benefits in ADR among high detectors. When comparing each device, EAC may be better than CAC at detecting more total adenomas.
International multicenter expert survey on endoscopic treatment of upper gastrointestinal anastomotic leaks
Authors: Rodrigues-Pinto Eduardo , Repici Alessandro , Donatelli Gianfranco , Macedo Guilherme , Devière Jacques , van Hooft Jeanin E. , Campos Josemberg M. , Galvao Neto Manoel , Silva Marco , Eisendrath Pierre , Kumbhari Vivek , Khashab Mouen A. 
Published: November 2019

Abstract
Background and study aims A variety of endoscopic techniques are currently available for treatment of upper gastrointestinal (UGI) anastomotic leaks; however, no definite consensus exists on the most appropriate therapeutic approach. Our aim was to explore current management of UGI anastomotic leaks.
Methods A survey questionnaire was distributed among international expert therapeutic endoscopists regarding management of UGI anastomotic leaks.
Results A total of 44 % of 163 surveys were returned; 69 % were from gastroenterologists and 56 % had > 10 years of experience. A third of respondents treat between 10 and 19 patients annually. Fifty-six percent use fully-covered self-expandable metal stents as their usual first option; 80% use techniques to minimize migration; 4 weeks was the most common reported stent dwell time. Sixty percent perform epithelial ablation prior to over-the-scope-clip placement or suturing. Regarding endoscopic vacuum therapy (EVT), 56 % perform balloon dilation and intracavitary EVT in patients with large cavities but small leak defects. Regarding endoscopic septotomy, 56 % consider a minimal interval of 4 weeks from surgery and 90 % consider the need to perform further sessions. Regarding endoscopic internal drainage (EID), placement of two stents and shorter stents is preferred. Persistent inflammation with clinical sepsis was the definition most commonly reported for endoscopic failure. EVT/stent placement and EVT/EID were the therapeutic options most often chosen in patients with previous oncologic surgery and previous bariatric surgery, respectively.
Conclusions There is a wide variation in the management of patients with UGI anastomotic leaks. Future prospective studies are needed to move from an expert- to evidence- and personalization-based care.
Effect of Variable Injection Sites for Indocyanine Green Dye on the Success of Lymphaticovenular Anastomosis
Authors: Nuri Takashi , Iwanaga Hiroyuki , Otsuki Yuki , Ueda Koichi 
Published: November 2019

Abstract
Background Indocyanine green lymphography (ICGL) allows more accurate visualization for lymphaticovenular anastomosis (LVA). However, the protocol for ICGL has not been established yet. We investigated how injection sites of ICG affect lymphography results by comparing ICGL images based on different injection sites on the same patients.
Methods Our hospital followed two ICGL protocols over time: ICG was injected into patients' 1st to 4th toe web spaces during 2013 to 2017 (Protocol 1), but into their lateral and medial ankles and 1st and 4th toe web spaces starting in 2018 (Protocol 2). Ten patients with secondary lymphedema who underwent LVA twice, using each protocol, were included in this study. We compared their results in detail and evaluated the effects of variable ICG injection sites.
Results The average period between patients' first and second LVAs was 506 days. In six patients, Protocol 2 detected new and additional linear findings that had not been detected by Protocol 1. Average reduction of lower limb circumferences after second LVAs (using Protocol 2) was 2.73 cm in patients who showed new linear findings, whereas those with no new findings showed little reduction.
Conclusion LVA based on ICG injections only into the dorsum of the foot can miss valuable findings. Variable ICG injection sites may improve detection of lymphatic flow and LVA efficacy.
Misunderstanding the Universal Audience
Authors: Gross Alan G. 
Published: November 2019

ABSTRACT
A major contribution to rhetorical theory and an important tool of rhetorical criticism, Perelman’s distinction between particular audiences and the universal audience has been misconstrued by his critics and even by Perelman himself. Properly construed, the universal audience is focused on facts and truths and consists of all human beings in so far as they are rational; consequently, discourse addressed to it eschews proofs from character and emotion. In contrast, addresses to particular audiences focus on values; they embrace not only proofs reason, but also those from character and emotion.
Poor man’s scaling and Lie algebras
Authors: Kogan Eugene 
Published: November 2019

Abstract
We consider a general model, describing a quantum impurity with degenerate energy levels, interacting with a gas of itinerant electrons, derive general scaling equation for the model, and analyse the connection between its particular forms and the symmetry of interaction. On the basis of this analysis we write down scaling equations for the Hamiltonians which are the direct products of su(3) Lie algebras and have either SU(2) × U(1) or SU(2) symmetry. We also put into a new context anisotropic Coqblin—Schrieffer models proposed by us earlier.
Ferroelectricity and stability measurements in perovskite solar cells
Authors: Colsmann Alexander , Röhm Holger 
Published: November 2019

Abstract
With the ferroelectric nature of modern perovskite solar cells being more and more accepted by the community, new questions arise. How do the microscopic electric fields within the polar domains affect the device performance, and how must measurement routines be adapted to account for the ferroelectric effect within the light-harvesting layer? This becomes particularly important, if devices are measured constantly for a long time as commonly performed in solar cell ageing tests. In this perspective article, we discuss which effects may arise from creeping poling even under low driving voltages or under illumination, as well as effects from phase transitions when crossing the Curie temperature for accelerated ageing at elevated temperatures. We elucidate why ferroelectric effects must be carefully considered when assessing the lifetime of perovskite solar cells and where comparability comes to its limits.
Seed release by a serotinous pine in the absence of fire: implications for invasion into temperate regions
Authors: Wyse Sarah V , Brown Jerusha E , Hulme Philip E 
Published: November 2019

AbstractIn pines, the release of seeds from serotinous cones is primarily considered a response to the high temperatures of a fire. However, the naturalization of serotinous pines in regions where fires are rare highlights the need to quantify environmental conditions that determine seed release to allow accurate prediction of dispersal and spread risk. We investigated the conditions that break cone serotiny in Pinus radiata, a widely planted forestry species that has naturalized in temperate regions worldwide. We quantified the cone temperatures at which cones open in this species, while also assessing potential confounding effects of cone moisture and age on these temperature requirements. We compared our laboratory results with cone opening behaviour under typical field conditions during summer in Canterbury, New Zealand. Cones opened at a mean temperature of 45 °C, much higher than maximum ambient air temperatures recorded in New Zealand. We found no influence of cone age or moisture content on opening temperature. Under field conditions, cones opened upon reaching similar temperatures to those determined in the laboratory; however, passive solar heating caused cones to reach temperatures up to 15 °C higher than ambient conditions. This resulted in 50 % of cones opening in field conditions where maximum air temperatures never exceeded 30 °C. Our results highlight the need for complementary laboratory and field experiments for understanding seed release from serotinous cones. Our findings have important implications for weed risk assessments, showing that serotinous pines can release seed in temperate climates without fire.
Sustained involuntary muscle activity in cerebral palsy and stroke: same symptom, diverse mechanisms
Authors: Forman Christian Riis , Svane Christian , Kruuse Christina , Gracies Jean-Michel , Nielsen Jens Bo , Lorentzen Jakob 
Published: November 2019

Abstract
Individuals with lesions of central motor pathways frequently suffer from sustained involuntary muscle activity. This symptom shares clinical characteristics with dystonia but is observable in individuals classified as spastic. The term spastic dystonia has been introduced, although the underlying mechanisms of involuntary activity are not clarified and vary between individuals depending on the disorder. This study aimed to investigate the nature and pathophysiology of sustained involuntary muscle activity in adults with cerebral palsy and stroke. Seventeen adults with cerebral palsy (Gross Motor Function Classification System I–V), 8 adults with chronic stroke and 14 control individuals participated in the study. All individuals with cerebral palsy or stroke showed increased resistance to passive movement with Modified Ashworth Scale &gt;1. Two-minute surface EMG recordings were obtained from the biceps muscle during attempted rest in three positions of the elbow joint; a maximally flexed position, a 90-degree position and a maximally extended position. Cross-correlation analysis of sustained involuntary muscle activity from individuals with cerebral palsy and stroke, and recordings of voluntary isometric contractions from control individuals were performed to examine common synaptic drive. In total, 13 out of 17 individuals with cerebral palsy and all 8 individuals with stroke contained sustained involuntary muscle activity. In individuals with cerebral palsy, the level of muscle activity was not affected by the joint position. In individuals with stroke, the level of muscle activity significantly (P &lt; 0.05) increased from the flexed position to the 90 degree and extended position. Cumulant density function indicated significant short-term synchronization of motor unit activities in all recordings. All groups exhibited significant coherence in the alpha (6–15 Hz), beta (16–35 Hz) and early gamma band (36–60 Hz). The cerebral palsy group had lower alpha band coherence estimates, but higher gamma band coherence estimates compared with the stroke group. Individuals with increased resistance to passive movement due to cerebral palsy or stroke frequently suffer sustained involuntary muscle activity, which cannot exclusively be described by spasticity. The sustained involuntary muscle activity in both groups originated from a common synaptic input to the motor neuron pool, but the generating mechanisms could differ between groups. In cerebral palsy it seemed to originate more from central mechanisms, whereas peripheral mechanisms likely play a larger role in stroke. The sustained involuntary muscle activity should not be treated simply like the spinal stretch reflex mediated symptom of spasticity and should not either be treated identically in both groups.
A comparative life-cycle analysis of tall onshore steel wind-turbine towers
Authors: Stavridou N , Koltsakis E , Baniotopoulos C C 
Published: November 2019

Abstract
Earth has lately been suffering from unforeseen catastrophic phenomena related to the consequences of the greenhouse effect. It is therefore essential not only that sustainability criteria be incorporated into the everyday lifestyle, but also that energy-saving procedures be enhanced. According to the number of wind farms installed annually, wind energy is among the most promising sustainable-energy sources. Taking into account the last statement for energy-saving methods, it is essential to value the contribution of wind energy not only in eliminating CO2 emissions when producing electricity from wind, but also in assessing the total environmental impact associated with the entire lifetime of all the processes related with this energy-production chain. In order to quantify such environmental impacts, life-cycle analysis (LCA) is performed. As a matter of fact, there are a very limited number of studies devoted to LCA of onshore wind-energy-converter supporting towers—a fact that constitutes a first-class opportunity to perform high-end research. In the present work, the life-cycle performance of two types of tall onshore wind-turbine towers has been investigated: a lattice tower and a tubular one. For comparison reasons, both tower configurations have been designed to sustain the same loads, although they have been manufactured by different production methods, different amounts of material were used and different mounting procedures have been applied; all the aforementioned items diversify in their overall life-cycle performance as well as their performance in all LCA phases examined separately. The life-cycle performance of the two different wind-turbine-tower systems is calculated with the use of efficient open LCA software and valuable conclusions have been drawn when combining structural and LCA results in terms of comparing alternative configurations of the supporting systems for wind-energy converters.
Melatonin inhibits inflammasome-associated activation of endothelium and macrophages attenuating pulmonary arterial hypertension
Authors: Zhang Jingyuan , Lu Xiaohui , Liu Mei , Fan Hanlu , Zheng Han , Zhang Shanshan , Rahman Nafis , Wołczyński Sławomir , Kretowski Adam , Li Xiangdong 
Published: November 2019

Abstract

Aims
Pulmonary arterial hypertension (PAH) is a pathophysiological syndrome associated with pulmonary/systemic inflammation. Melatonin relieves PAH, but the molecular mode of action remains unclear. Here, we investigated the role of melatonin in normalizing vascular homeostasis.

Methods and results
Light-time mean serum melatonin concentration was lower in patients with PAH than in normal controls [11.06 ± 3.44 (7.13–15.6) vs. 14.55 ± 1.28 (8.0–19.4) pg/mL], which was negatively correlated with increased serum levels of interleukin-1β (IL-1β) in patients with PAH. We showed that inflammasomes were activated in the PAH mice model and that melatonin attenuated IL-1β secretion. On one hand, melatonin reduced the number of macrophages in lung by inhibiting the endothelial chemokines and adhesion factors. Moreover, use of Il1r−/− mice, Caspase1/11−/− mice, and melatonin-treated mice revealed that melatonin reduced hypoxia-induced vascular endothelial leakage in the lung. On the other hand, we verified that melatonin reduced the formation of inflammasome multiprotein complexes by modulating calcium ions in macrophages using a live cell station, and melatonin decreased inositol triphosphate and increased cAMP. Furthermore, knockdown of melatonin membrane receptors blocked melatonin function, and a melatonin membrane receptors agonist inactivated inflammasomes in macrophages.

Conclusion
Melatonin attenuated inflammasome-associated vascular disorders by directly improving endothelial leakage and decreasing the formation of inflammasome multiprotein complexes in macrophages. Taken together, our data provide a theoretical basis for applying melatonin clinically, and inflammasomes may be a possible target of PAH treatment.