bluuebunny/crossref_metadata_2025_split huggingface dataset:
FGF5 methylation is a sensitivity marker of esophageal squamous cell carcinoma to definitive chemoradiotherapy
Authors: Iwabu Jun , Yamashita Satoshi , Takeshima Hideyuki , Kishino Takayoshi , Takahashi Takamasa , Oda Ichiro , Koyanagi Kazuo , Igaki Hiroyasu , Tachimori Yuji , Daiko Hiroyuki , Nakazato Hidetsugu , Nishiyama Kazuhiro , Lee Yi-Chia , Hanazaki Kazuhiro , Ushijima Toshikazu 
Published: September 2019

AbstractDefinitive chemoradiotherapy (dCRT) is the major treatment for esophageal squamous cell carcinoma (ESCC), and prediction of the response to dCRT is important so as not to miss an opportunity to cure an ESCC. Nevertheless, few validated markers are available. Here, we aimed to identify a highly reproducible marker using multi-layer omics analysis. 117 ESCC samples from 67 responders and 50 non-responders were divided into screening, validation, and re-validation sets. In the screening cohort (n = 41), somatic mutations in 114 genes showed no association with dCRT response. Genome-wide DNA methylation analysis using Infinium HumanMethylation450 BeadChip array identified four genic regions significantly associated with dCRT response. Among them, FGF5 methylation was validated to be associated with dCRT response (n = 34; P = 0.001), and further re-validated (n = 42; P = 0.020) by bisulfite-pyrosequencing. The sensitivity and specificity in the combined validation and re-validation sets (n = 76) were 45% and 90%, respectively, by using the cut-off value established in the screening set, and FGF5 methylation had predictive power independent from clinicopathological parameters. In ESCC cell lines, FGF5 promoter methylation repressed its expression. FGF5 expression was induced by cisplatin (CDDP) treatment in three unmethylated cell lines, but not in two methylated cell lines. Exogenous FGF5 overexpression in a cell line with its methylation conferred resistance to CDDP. In non-cancerous esophageal tissues, FGF5 was not expressed, and its methylation was present in a small fraction of cells. These results showed that FGF5 methylation is a validated marker for ESCC sensitivity to dCRT.
Prediction of MAYV peptide antigens for immunodiagnostic tests by immunoinformatics and molecular dynamics simulations
Authors: Rodrigues Roger Luiz , Menezes Gabriela De Lima , Saivish Marielena Vogel , Costa Vivaldo Gomes Da , Pereira Maristela , Moreli Marcos Lázaro , Silva Roosevelt Alves Da 
Published: September 2019

AbstractThe Mayaro virus is endemic to South America, and the possible involvement of Aedes spp. mosquitoes in its transmission is a risk factor for outbreaks of greater proportions. The virus causes a potentially disabling illness known as Mayaro fever, which is similar to that caused by the chikungunya virus. The cocirculation of both viruses, with their clinical and structural similarities, and the absence of prophylactic and therapeutic measures highlight the need for studies that seek to understand the Mayaro virus. Using approaches in silico, we identified an antigenic and specific epitope (p_MAYV4) in domain A of the E2 glycoprotein of the Mayaro virus. This epitope was theoretically predicted to be stable and exposed on the surface of the protein, where it showed key properties that enable its interaction with neutralizing antibodies. These characteristics make it an interesting target for the development of immunodiagnostic platforms. Molecular dynamics simulation-based structural analysis showed that the PHE95 residue in the E1 fusion loop region is conserved among Alphavirus family members. PHE95 interacts with the hydrophobic residues of the E2 glycoprotein to form a cage-shaped structure that is critical to assemble and stabilize the E1/E2 heterodimer. These results provide important insights useful for the advancement of diagnostic platforms and the study of therapeutic alternatives.
Tunable subwavelength ultrasound focusing in mesoscale spherical lenses using liquid mixtures
Authors: Pérez-López Sergio , Fuster José Miguel , Minin Igor V. , Minin Oleg V. , Candelas Pilar 
Published: September 2019

AbstractIn this work, we present a configurable spherical lens for underwater focusing applications, which consists on a hollow ABS container filled with a liquid mixture. Two miscible liquids with different sound speeds are required to implement this novel configurable lens. We show that by adjusting the mixing ratio between the volumes of both liquids, the sound speed of the liquid mixture can be accurately selected. This results in a modification of the acoustic jet properties and a continuous tuning on the lens focal length. This procedure can be fully automatized providing a dynamic control mechanism that can shift the lens focal length to any desired value inside a continuous range in both directions. Depending on the acoustic properties of the selected liquids, subwavelength resolution or even beyond the diffraction limit resolution can be achieved. We provide experimental measurements for ethanol-water mixtures achieving subwavelength resolution for a certain focal length ranging between 34.6 and 42.8 mm.
On–off switching of cell cycle and melanogenesis regulation of melanocytes by non-thermal atmospheric pressure plasma-activated medium
Authors: Lee Jin-Woo , Han Se Jik , Kang Hye Young , Wi Sung-Suk , Jung Min-Hyung , Kim Kyung Sook 
Published: September 2019

AbstractNon-thermal atmospheric pressure (NAP) plasma has demonstrated potential in biomedical applications, such as cancer treatment, bactericidal sterilization, and cell growth promotion or inhibition. In this study, for the first time, we demonstrated on–off switching of cell cycle progression and regulated melanogenesis in normal human skin melanocytes by NAP plasma-activated medium (PAM). The melanocytes were exposed to NAP plasma at durations varying from 0 to 20 min, and the effects of PAM on cell proliferation, cell cycle progression, and melanogenesis were investigated. Although PAM showed no cytotoxicity, the proliferation of melanocytes was inhibited. The melanocyte cell cycle was arrested by PAM for a relatively short period (48 h), after which it recovered slowly. PAM promoted melanogenesis through the activation of the enzymes tyrosinase, tyrosinase-related protein-1, and tyrosinase-related protein-2. These effects seem to be related to reactive oxygen species induced by PAM. Our finding that PAM modulates the cell cycle may provide insight into the recurrence of cancer. The regulation of the melanogenesis of melanocytes may facilitate the control of skin tone without incurring negative side effects.
Transgenerational inheritance of shuffled symbiont communities in the coral Montipora digitata
Authors: Quigley Kate M. , Willis Bette L. , Kenkel Carly D. 
Published: September 2019

AbstractAdult organisms may “prime” their offspring for environmental change through a number of genetic and non-genetic mechanisms, termed parental effects. Some coral species may shuffle the proportions of Symbiodiniaceae within their endosymbiotic communities, subsequently altering their thermal tolerance, but it is unclear if shuffled communities are transferred to offspring. We evaluated Symbiodiniaceae community composition in tagged colonies of Montipora digitata over two successive annual spawning seasons and the 2016 bleaching event on the Great Barrier Reef. ITS2 amplicon sequencing was applied to four families (four maternal colonies and 10–12 eggs per family) previously sampled and sequenced the year before to characterize shuffling potential in these M. digitata colonies and determine if shuffled abundances were preserved in gametes. Symbiont densities and photochemical efficiencies differed significantly among adults in 2016, suggesting differential responses to increased temperatures. Low-abundance (“background”) sequence variants differed more among years than between maternal colonies and offspring. Results indicate that shuffling can occur in a canonically ‘stable’ symbiosis, and that the shuffled community is heritable. Hence, acclimatory changes like shuffling of the Symbiodiniaceae community are not limited to the lifetime of an adult coral and that shuffled communities are inherited across generations in a species with vertical symbiont transmission. Although previously hypothesized, to our knowledge, this is the first evidence that shuffled Symbiodiniaceae communities (at both the inter- and intra- genera level) can be inherited by offspring and supports the hypothesis that shuffling in microbial communities may serve as a mechanism of rapid coral acclimation to changing environmental conditions.
Autoregulation assessment by direct visualisation of pial arterial blood flow in the piglet brain
Authors: Klein S. P. , De Sloovere V. , Meyfroidt G. , Depreitere B. 
Published: September 2019

AbstractImpairment of cerebrovascular autoregulation (CAR) is common after brain injury, although the pathophysiology remains elusive. The mechanisms of vascular dysregulation, their impact on brain function, and potential therapeutic implications are still incompletely understood. Clinical assessment of CAR remains challenging. Observational studies suggest that CAR impairment is associated with worse outcomes, and that optimization of cerebral blood flow (CBF) by individual arterial blood pressure (ABP) targets could potentially improve outcome. We present a porcine closed cranial window model that measures the hemodynamic response of pial arterioles, the main site of CBF control, based on changes in their diameter and red blood cell velocity. This quantitative direct CAR assessment is compared to laser Doppler flow (LDF). CAR breakpoints are determined by segmented regression analysis and validated using LDF and brain tissue oxygen pressure. Using a standardized cortical impact, CAR impairment in traumatic brain injury can be studied using our method of combining pial arteriolar diameter and RBC velocity to quantify RBC flux in a large animal model. The model has numerous potential applications to investigate CAR physiology and pathophysiology of CAR impairment after brain injury, the impact of therapeutic interventions, drugs, and other confounders, or to develop personalized ABP management strategies.
ECM alterations in Fndc3a (Fibronectin Domain Containing Protein 3A) deficient zebrafish cause temporal fin development and regeneration defects
Authors: Liedtke Daniel , Orth Melanie , Meissler Michelle , Geuer Sinje , Knaup Sabine , Köblitz Isabell , Klopocki Eva 
Published: September 2019

AbstractFin development and regeneration are complex biological processes that are highly relevant in teleost fish. They share genetic factors, signaling pathways and cellular properties to coordinate formation of regularly shaped extremities. Especially correct tissue structure defined by extracellular matrix (ECM) formation is essential. Gene expression and protein localization studies demonstrated expression of fndc3a (fibronectin domain containing protein3a) in both developing and regenerating caudal fins of zebrafish (Danio rerio). We established a hypomorphic fndc3a mutant line (fndc3awue1/wue1) via CRISPR/Cas9, exhibiting phenotypic malformations and changed gene expression patterns during early stages of median fin fold development. These developmental effects are mostly temporary, but result in a fraction of adults with permanent tail fin deformations. In addition, caudal fin regeneration in adult fndc3awue1/wue1 mutants is hampered by interference with actinotrichia formation and epidermal cell organization. Investigation of the ECM implies that loss of epidermal tissue structure is a common cause for both of the observed defects. Our results thereby provide a molecular link between these developmental processes and foreshadow Fndc3a as a novel temporal regulator of epidermal cell properties during extremity development and regeneration in zebrafish.
18F-FDG uptake in PET/CT is a potential predictive biomarker of response to anti-PD-1 antibody therapy in non-small cell lung cancer
Authors: Takada Kazuki , Toyokawa Gouji , Yoneshima Yasuto , Tanaka Kentaro , Okamoto Isamu , Shimokawa Mototsugu , Wakasu Sho , Haro Akira , Osoegawa Atsushi , Tagawa Tetsuzo , Oda Yoshinao , Nakanishi Yoichi , Mori Masaki 
Published: September 2019

AbstractTo examine the association between 18F-fluorodeoxyglucose (18F-FDG) uptake in positron emission tomography/computed tomography (PET/CT) and the response to anti-programmed cell death-1 (PD-1) monoclonal antibody therapy in non-small cell lung cancer (NSCLC) patients, 89 patients with advanced or recurrent NSCLC were retrospectively analysed. Maximum standardized uptake value (SUVmax) in 18F-FDG PET/CT and the response to anti-PD-1 antibodies were recorded. A cut-off value of SUVmax was determined by receiver operating characteristic curve analysis for patient stratification. Among the 89 patients evaluated, 24 were classified as responders (all partial response), and 65 as non-responders. The average SUVmax of the responders was 15.60 (range, 6.44–51.10), which was significantly higher than that of the non-responders (11.61; range, 2.13–32.75; P = 0.0168, Student’s t-test). The cut-off SUVmax value selected for stratification was 11.16 (sensitivity and specificity, 0.792 and 0.585, respectively). The response rate of patients with SUVmax value ≥ 11.16 (41.3% [19/46]) was significantly higher than that of patients with SUVmax < 11.16 (11.6% [5/43], P = 0.0012, Chi-squared test). The SUVmax in 18F-FDG PET/CT is a potential predictive marker of response to anti-PD-1 antibody therapy in NSCLC patients. Further prospective studies of large populations are necessary to validate these results.
Ultimate Photo-Thermo-Acoustic Efficiency of Graphene Aerogels
Authors: Nicola Francesco De , Tenuzzo Lorenzo Donato , Viola Ilenia , Zhang Rujing , Zhu Hongwei , Marcelli Augusto , Lupi Stefano 
Published: September 2019

AbstractThe ability to generate, amplify, mix, and modulate sound with no harmonic distortion in a passive opto-acoustic device would revolutionize the field of acoustics. The photo-thermo-acoustic (PTA) effect allows to transduce light into sound without any bulk electro-mechanically moving parts and electrical connections, as for conventional loudspeakers. Also, PTA devices can be integrated with standard silicon complementary metal-oxide semiconductor (CMOS) fabrication techniques. Here, we demonstrate that the ultimate PTA efficiency of graphene aerogels, depending on their particular thermal and optical properties, can be experimentally achieved by reducing their mass density. Furthermore, we illustrate that the aerogels behave as an omnidirectional pointsource throughout the audible range with no harmonic distortion. This research represents a breakthrough for audio-visual consumer technologies and it could pave the way to novel opto-acoustic sensing devices.
Lactulose drives a reversible reduction and qualitative modulation of the faecal microbiota diversity in healthy dogs
Authors: Ferreira Marisa da Fonseca , Salavati Schmitz Silke , Schoenebeck Jeffrey Joseph , Clements Dylan Neil , Campbell Susan Mary , Gaylor Donna Elaine , Mellanby Richard J. , Gow Adam George , Salavati Mazdak 
Published: September 2019

AbstractHepatic encephalopathy is a frequent and debilitating complication of liver disorders. Lactulose is an established and reasonably effective treatment, yet with incompletely understood mechanisms of action. The aims of this study were to examine how the faecal microbiota composition changed before, during and after lactulose treatment in a large animal model. Healthy, privately owned dogs (n = 18) completed a prospective cohort study. Faecal samples were collected weekly, while the subjects were either on their usual diet (week 1), or a standardised diet (weeks 2–9), with added oral lactulose in weeks 6–7. DNA extraction and 16S rRNA gene sequencing were undertaken. Faecal samples from week 7 had a significantly lower microbiota richness/diversity, based on observed operational taxonomic units, Shannon/Chao1 indexes and Pielou’s Evenness. Beta diversity based on UniFrac distances was significantly different in week 7 compared to weeks 1, 5 and 9. At the phylum level, week 7 was associated with a significant increase of Firmicutes and Actinobacteria, and a decrease of Bacteroidetes and Fusobacteria, when compared to weeks 5 and 9. In summary, we have shown that lactulose induces a reversible qualitative and quantitative change of the faecal microbiota, which may explain its clinical efficacy in the management of hepatic encephalopathy.
Total ankle arthroplasty and ankle arthrodesis affect the biomechanics of the inner foot differently
Authors: Wang Yan , Wong Duo Wai-chi , Tan Qitao , Li Zengyong , Zhang Ming 
Published: September 2019

AbstractAnkle arthrodesis and total ankle arthroplasty are the two primary surgeries for treatment of end-stage degenerative ankle arthritis. The biomechanical effects of them on the inner foot are insufficient to identify which is superior. This study compared biomechanical parameters among a foot treated by ankle arthrodesis, a foot treated by total ankle arthroplasty, and an intact foot using computational analysis. Validated finite element models of the three feet were developed and used to simulate the stance phase of gait. The results showed total ankle arthroplasty provides a more stable plantar pressure distribution than ankle arthrodesis. The highest contact pressure, 3.17 MPa, occurred in the medial cuneonavicular joint in the total ankle arthroplasty foot. Neither of the surgeries resulted in contact pressure increase in the subtalar joint. The peak stress in the metatarsal bones was increased in both surgical models, especially the second and third metatarsals. This study enables us to get visual to the biomechanics inside of an intact foot, and feet treated by total ankle arthroplasty and ankle arthrodesis during walking.
Distinct gene expression profiles between primary breast cancers and brain metastases from pair-matched samples
Authors: Iwamoto Takayuki , Niikura Naoki , Ogiya Rin , Yasojima Hiroyuki , Watanabe Ken-ichi , Kanbayashi Chizuko , Tsuneizumi Michiko , Matsui Akira , Fujisawa Tomomi , Iwasa Tsutomu , Shien Tadahiko , Saji Shigehira , Masuda Norikazu , Iwata Hiroji 
Published: September 2019

AbstractOur objectives were to determine whether clinic-pathological markers and immune-related gene signatures in breast cancer exhibit any change upon brain metastasis and whether previously reported genes significantly associated with brain metastases and the epithelial-mesenchymal transition (EMT) were reproducible and consistent in our dataset. Sixteen pair-matched samples from primary breast cancers and brain metastases diagnosed were collected from the Japan Clinical Oncology Group Breast Cancer Study Group. Gene expression profiles for immune-, brain metastases-, and EMT-related genes were compared between primary breast cancers and brain metastases. Potential therapeutic target genes of 41 FDA-approved or under-investigation agents for brain metastases were explored. Immune-related signatures exhibited significantly lower gene expression in brain metastases than in primary breast cancers. No significant differences were detected for the majority of genes associated with brain metastases and EMT in the two groups. Among 41 therapeutic target candidates, VEGFA and DNMT3A demonstrated significantly higher gene expression in brain metastases. We found that distinct patterns of gene expression exist between primary breast cancers and brain metastases. Further studies are needed to explore whether these distinct expression profiles derive from or underlie disease status and compare these features between metastases to the brain and other sites.
Berberine inhibits adipocyte differentiation, proliferation and adiposity through down-regulating galectin-3
Authors: Wang Can , Wang Yan , Ma Shu-Rong , Zuo Zeng-Yan , Wu Yan-Bin , Kong Wei-Jia , Wang Ai-Ping , Jiang Jian-Dong 
Published: September 2019

AbstractThis study is designed to investigate the effects of berberine (BBR) on galectin-3 (Gal-3) and the relationships to its suppressive activities on adipocyte differentiation, proliferation and adiposity. Our results showed that BBR greatly suppressed the differentiation and proliferation of mouse primary preadipocytes isolated from epididymal white adipose tissue (eWAT), during which the expression level of Gal-3 was down-regulated significantly. Overexpression of Gal-3 totally abolished the suppressive activities of BBR on Gal-3 expression, preadipocyte differentiation and proliferation. BBR reduced Gal-3 promoter activity, destabilized its mRNA and inhibited firefly luciferase activity of a recombinant plasmid containing the Gal-3 3′ untranslated region (UTR). Furthermore, BBR up-regulated microRNA (miRNA) let-7d expression and the suppressive activity on Gal-3 3′UTR was abolished by point mutation on the let-7d binding site. In mice fed a high-fat diet (HFD), BBR up-regulated let-7d and down-regulated Gal-3 expression in eWAT; it also suppressed adipocyte differentiation and proliferation and reduced adiposity greatly. In summary, our study proves that BBR inhibits the differentiation and proliferation of adipocytes through down-regulating Gal-3, which is closely associated with its anti-obesity effect. Our results may support the future clinical application of BBR for the treatment of obesity or related diseases.
Solute-solvent electronic interaction is responsible for initial charge separation in ruthenium complexes [Ru(bpy)3]2+ and [Ru(phen)3]2+
Authors: Stark Charles W. , Trummal Aleksander , Uudsemaa Merle , Pahapill Juri , Rammo Matt , Petritsenko Katrin , Sildoja Meelis-Mait , Rebane Aleksander 
Published: September 2019

AbstractOrigin of the initial charge separation in optically-excited Ruthenium(II) tris(bidentate) complexes of intrinsic D3 symmetry has remained a disputed issue for decades. Here we measure the femtosecond two-photon absorption (2PA) cross section spectra of [Ru(2,2′-bipyridine)3]2 and [Ru(1,10-phenanthroline)3]2 in a series of solvents with varying polarity and show that for vertical transitions to the lower-energy 1MLCT excited state, the permanent electric dipole moment change is nearly solvent-independent, Δμ = 5.1–6.3 D and 5.3–5.9 D, respectively. Comparison of experimental results with quantum-chemical calculations of complexes in the gas phase, in a polarizable dielectric continuum and in solute-solvent clusters containing up to 18 explicit solvent molecules indicate that the non-vanishing permanent dipole moment change in the nominally double-degenerate E-symmetry state is caused by the solute-solvent interaction twisting the two constituent dipoles out of their original opposite orientation, with average angles matching the experimental two-photon polarization ratio.
Unique acrylic resins with aromatic side chains by homopolymerization of cinnamic monomers
Authors: Imada Motosuke , Takenaka Yasumasa , Hatanaka Hidehito , Tsuge Takeharu , Abe Hideki 
Published: September 2019

AbstractCinnamic monomers, which are useful chemicals derived from biomass, contain α,β-unsaturated carbonyl groups with an aromatic ring at the β-position. Homopolymers synthesized by addition polymerization of these compounds are expected to be innovative bio-based polymer materials, as they have both polystyrene and polyacrylate structures. However, polymerization of these compounds by many methods is challenging, including by radical methods, owing to steric hindrance of the substituents and delocalization of electrons throughout the molecule via unsaturated π-bonding. Herein we report that homopolymers of these compounds with molecular weights (Mn) of ~18,100 g mol−1 and controlled polymer backbones can be synthesized by the group-transfer polymerization technique using organic acid catalysts. Additionally, these homopolymers are shown to have high heat resistance comparable to that of engineering plastics. Overall, these findings may open up possibilities for the convenient homopolymerization of cinnamic monomers to produce high-performance polymer materials.