bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic signatures of local adaptation to the degree of environmental predictability in rotifers
Authors: Franch-Gras Lluis , Hahn Christoph , García-Roger Eduardo M. , Carmona María José , Serra Manuel , Gómez Africa 
Published: October 2018

AbstractEnvironmental fluctuations are ubiquitous and thus essential for the study of adaptation. Despite this, genome evolution in response to environmental fluctuations —and more specifically to the degree of environmental predictability– is still unknown. Saline lakes in the Mediterranean region are remarkably diverse in their ecological conditions, which can lead to divergent local adaptation patterns in the inhabiting aquatic organisms. The facultatively sexual rotifer Brachionus plicatilis shows diverging local adaptation in its life-history traits in relation to estimated environmental predictability in its habitats. Here, we used an integrative approach —combining environmental, phenotypic and genomic data for the same populations– to understand the genomic basis of this diverging adaptation. Firstly, a novel draft genome for B. plicatilis was assembled. Then, genome-wide polymorphisms were studied using genotyping by sequencing on 270 clones from nine populations in eastern Spain. As a result, 4,543 high-quality SNPs were identified and genotyped. More than 90 SNPs were found to be putatively under selection with signatures of diversifying and balancing selection. Over 140 SNPs were correlated with environmental or phenotypic variables revealing signatures of local adaptation, including environmental predictability. Putative functions were associated to most of these SNPs, since they were located within annotated genes. Our results reveal associations between genomic variation and the degree of environmental predictability, providing genomic evidence of adaptation to local conditions in natural rotifer populations.
Radiogenomics Profiling for Glioblastoma-related Immune Cells Reveals CD49d Expression Correlation with MRI parameters and Prognosis
Authors: Cho Hye Rim , Jeon Hyejin , Park Chul-Kee , Park Sung-Hye , Choi Seung Hong 
Published: October 2018

AbstractAlthough there have been a plethora of radiogenomics studies related to glioblastoma (GBM), most of them only used genomic information from tumor cells. In this study, we used radiogenomics profiling to identify MRI-associated immune cell markers in GBM, which was also correlated with prognosis. Expression levels of immune cell markers were correlated with quantitative MRI parameters in a total of 60 GBM patients. Fourteen immune cell markers (i.e., CD11b, CD68, CSF1R, CD163, CD33, CD123, CD83, CD63, CD49d and CD117 for myeloid cells, and CD4, CD3e, CD25 and CD8 for lymphoid cells) were selected for RNA-level analysis using quantitative RT-PCR. For MRI analysis, quantitative MRI parameters from FLAIR, contrast-enhanced (CE) T1WI, dynamic susceptibility contrast perfusion MRI and diffusion-weighted images were used. In addition, PFS associated with interesting mRNA data was performed by Kaplan-Meier survival analysis. CD163, which marks tumor associated microglia/macrophages (TAMs), showed the highest expression level in GBM patients. CD68 (TAMs), CSF1R (TAMs), CD33 (myeloid-derived suppressor cell) and CD4 (helper T cell, regulatory T cell) levels were highly positively correlated with nCBV values, while CD3e (helper T cell, cytotoxic T cell) and CD49d showed a significantly negative correlation with apparent diffusion coefficient (ADC) values. Moreover, regardless of any other molecular characteristics, CD49d was revealed as one independent factor for PFS of GBM patients by Cox proportional-hazards regression analysis (P = 0.0002). CD49d expression level CD49d correlated with ADC can be considered as a candidate biomarker to predict progression of GBM patients.
Prognostic Influence of Preoperative Mammographic Breast Density in Operable Invasive Female Breast Cancer
Authors: Hwang Ki-Tae , Chu A. Jung , Kim Jongjin , Lee Jong Yoon , Chang Ji Hyun , Oh Sohee , Kim Young A. , Jung Jiwoong , Oh Bumjo 
Published: October 2018

AbstractWe aimed to investigate the potential of preoperative mammographic breast density (MBD) as a prognostic factor in breast cancer. Data of 969 patients with primary breast cancer were analyzed. We defined low MBD as fatty or fibroglandular breast, and high MBD as heterogeneously dense or extremely dense breast, respectively. The high MBD group demonstrated a superior overall survival rate compared to the low MBD group (p < 0.001). Favorable prognostic effects of high MBD were observed in subgroups aged >50 years (p < 0.001) and with positive hormone receptor (HRc) and negative human epidermal growth factor receptor 2 (HER2) (p < 0.001). The high MBD group had a higher proportion of patients aged ≤50 years (p < 0.001) and patients with body mass index (BMI) ≤25 kg/m2 (p < 0.001), and a higher proportion of patients who received chemotherapy (p < 0.001). MBD was a significant independent prognostic factor by multivariable analysis (hazard ratio, 0.382; 95% confidence interval, 0.206–0.708). The high MBD group was associated with superior overall survival rates. Preoperative MBD was a strong independent prognostic factor in operable primary invasive female breast cancer, especially in patients with age >50 years and the HRc(+)/HER2(−) subtype. Favorable clinicopathologic features, active treatments, and other factors could contribute to this causality.
Dynamic interaction of multiple shear bands
Authors: Giarola Diana , Capuani Domenico , Bigoni Davide 
Published: October 2018

AbstractA mechanical model for waves impinging different configurations of multiple shear bands already formed in a ductile material, allows to analyze the ways in which dynamic interactions promote failure. It is shown that the presence of more than one shear band may lead to resonance and correspondent growth of a shear band or, conversely, to its annihilation. At the same time, multiple scattering may bring about focusing or, conversely, shielding from waves. The proposed mechanical modelling, represents the only way to analyze the fine micromechanisms governing material collapse, and discloses the complex interplay between dynamics and shear band growth or arrest.
DNA damage interactions on both nanometer and micrometer scale determine overall cellular damage
Authors: Friedrich Thomas , Ilicic Katarina , Greubel Christoph , Girst Stefanie , Reindl Judith , Sammer Matthias , Schwarz Benjamin , Siebenwirth Christian , Walsh Dietrich W. M. , Schmid Thomas E. , Scholz Michael , Dollinger Günther 
Published: October 2018

AbstractDNA double strand breaks (DSB) play a pivotal role for cellular damage, which is a hazard encountered in toxicology and radiation protection, but also exploited e.g. in eradicating tumors in radiation therapy. It is still debated whether and in how far clustering of such DNA lesions leads to an enhanced severity of induced damage. Here we investigate - using focused spots of ionizing radiation as damaging agent - the spatial extension of DNA lesion patterns causing cell inactivation. We find that clustering of DNA damage on both the nm and µm scale leads to enhanced inactivation compared to more homogeneous lesion distributions. A biophysical model interprets these observations in terms of enhanced DSB production and DSB interaction, respectively. We decompose the overall effects quantitatively into contributions from these lesion formation processes, concluding that both processes coexist and need to be considered for determining the resulting damage on the cellular level.
Goats worm burden variability also results from non-homogeneous larval intake
Authors: Bonneau Mathieu , Bambou Jean-Christophe , Mandonnet Nathalie , Arquet Rémy , Mahieu Maurice 
Published: October 2018

AbstractFor small ruminants, Gastrointestinal Nematodes (GINs) are responsible for severe economic losses and they are also an animal welfare problem. GIN use their host to reproduce and disperse eggs on the pasture, from where they can re-infect another animal. The high density of hosts on the pasture and the extreme tolerance of GIN to environmental constraints make GIN eradication almost impossible. In addition, significant resistance to anthelmintic treatment requires sustainable and integrated management to maintain the health and financial well-being of livestock farming. In this context, models of the complex interactions between host, GIN and environment can help us to design long term optimal management strategies. To build such models, quantitative information is needed but are generally very challenging to collect. In this article, we focus on the number of ingested larvae per animal, which we propose to characterise by using a simulation framework based on the estimation of the spatial distribution of the host over time. Our framework allows us to show that worm burden individual variation is not only explained by the host’s genetics, as is often the case, but is also a result of the grazing spatial process.
Direct imaging of Indium-rich triangular nanoprisms self-organized formed at the edges of InGaN/GaN core-shell nanorods
Authors: Schmidt Gordon , Müller Marcus , Veit Peter , Metzner Sebastian , Bertram Frank , Hartmann Jana , Zhou Hao , Wehmann Hergo-Heinrich , Waag Andreas , Christen Jürgen 
Published: October 2018

AbstractHigher indium incorporation in self-organized triangular nanoprisms at the edges of InGaN/GaN core-shell nanorods is directly evidenced by spectral cathodoluminescence microscopy in a scanning transmission electron microscope. The nanoprisms are terminated by three 46 nm wide a-plane nanofacets with sharp interfaces forming a well-defined equilateral triangular base in the basal plane. Redshifted InGaN luminescence and brighter Z-contrast are resolved for these structures compared to the InGaN layers on the nanorod sidewalls, which is attributed to at least 4 % higher indium content. Detailed analysis of the inner optical and structural properties reveals luminescence contributions from 417 nm up to 500 nm peak wavelength proving the increasing indium concentration inside the nanoprism towards the nanorod surface.
Effects of wettability on droplet movement in a V-shaped groove
Authors: Han Taeyang , Noh Hyunwoo , Park Hyun Sun , Kim Moo Hwan 
Published: October 2018

AbstractAs basic research to understand the behavior of droplets on structured surfaces, we investigated droplet movement in a V-shaped groove while the volume of the droplet changes. We developed a model to explain the mechanism of the droplet movement and the effects of the wettability of the inner walls of the groove on the droplet movement. Furthermore, the model predicted new phenomena and explains the effect of the nonhomogeneous wettability on droplet movement. The predictions of the model match the experimental results well. This research can provide the basic knowledge for manipulating droplets with structured surfaces for various applications.
In vivo two-photon imaging of the embryonic cortex reveals spontaneous ketamine-sensitive calcium activity
Authors: Yuryev Mikhail , Andriichuk Liliia , Leiwe Marcus , Jokinen Ville , Carabalona Aurelie , Rivera Claudio 
Published: October 2018

AbstractPrior to sensory experience spontaneous activity appears to play a fundamental role in the correct formation of prominent functional features of different cortical regions. The use of anaesthesia during pregnancy such as ketamine is largely considered to negatively affect neuronal development by interfering with synaptic transmission. Interestingly, the characteristics of spontaneous activity as well as the acute functional effects of maternal anaesthesia remain largely untested in the embryonic cortex in vivo. In the present work, we performed in vivo imaging of spontaneous calcium activity and cell motility in the marginal zone of the cortex of E14-15 embryos connected to the mother. We made use of a preparation where the blood circulation from the mother through the umbilical cord is preserved and fluctuations in intracellular calcium in the embryonic frontal cortex are acquired using two-photon imaging. We found that spontaneous transients were either sporadic or correlated in clusters of neuronal ensembles at this age. These events were not sensitive to maternal isoflurane anaesthesia but were strongly inhibited by acute in situ or maternal application of low concentration of the anaesthetic ketamine (a non-competitive antagonist of NMDA receptors). Moreover, simultaneous imaging of cell motility revealed a correlated strong sensitivity to ketamine. These results show that anaesthetic compounds can differ significantly in their impact on spontaneous early cortical activity as well as motility of cells in the marginal zone. The effects found in this study may be relevant in the etiology of heightened vulnerability to cerebral dysfunction associated with the use of ketamine during pregnancy.
Acid bone lysate activates TGFβ signalling in human oral fibroblasts
Authors: Strauss Franz Josef , Stähli Alexandra , Beer Lucian , Mitulović Goran , Gilmozzi Valentina , Haspel Nina , Schwab Gerhild , Gruber Reinhard 
Published: October 2018

AbstractDemineralized bone matrix is a widely used allograft from which not only the inorganic mineral but also embedded growth factors are removed by hydrochloric acid (HCl). The cellular response to the growth factors released during the preparation of demineralized bone matrix, however, has not been studied. Here we investigated thein vitroimpact of acid bone lysate (ABL) prepared from porcine cortical bone chips on oral fibroblasts. Proteomic analysis of ABL revealed a large spectrum of bone-derived proteins including TGF-β1. Whole genome microarrays and RT-PCR together with the pharmacologic blocking of TGF-β receptor type I kinase with SB431542 showed that ABL activates the TGF-β target genes interleukin 11, proteoglycan 4, and NADPH oxidase 4. Interleukin 11 expression was confirmed at the protein level by ELISA. Immunofluorescence and Western blot showed the nuclear localization of Smad2/3 and increased phosphorylation of Smad3 with ABL, respectively. This effect was independent of whether ABL was prepared from mandible, calvaria or tibia. These results demonstrate that TGF-β is a major growth factor that is removed upon the preparation of demineralized bone matrix.
Molecular weight of surface immobilized hyaluronic acid influences CD44-mediated binding of gastric cancer cells
Authors: Amorim Sara , da Costa Diana Soares , Freitas Daniela , Reis Celso A. , Reis Rui L. , Pashkuleva Iva , Pires Ricardo A. 
Published: October 2018

AbstractThe physiological importance of the interactions between hyaluronic acid (HA) and its main membrane receptor, CD44, in pathological processes, e.g. cancer, is well recognized. However, these interactions are mainly studied in solution, whereas HA in the extracellular matrix (ECM) is partially immobilized via its interactions with other ECM components. We therefore, developed substrates in which HA is presented in an ECM-relevant manner. We immobilized HA with different molecular weights (Mw) in a Layer-by-Layer (LbL) fashion and studied the interactions of the substrates with CD44 and two human gastric cancer cell lines that overexpress this receptor, namely AGS and MKN45. We demonstrate that MKN45 cells are more sensitive to the LbL substrates as compared with AGS. This difference is due to different CD44 expression: while CD44 is detected mainly in the cytoplasm of AGS, MKN45 express CD44 predominantly at the cell membrane where it is involved in the recognition and binding of HA. The invasiveness of the studied cell lines was also evaluated as a function of HA Mw. Invasive profile characterized by low cell adhesion, high cell motility, high expression of cortactin, formation of invadopodia and cell clusters was observed for MKN45 cells when they are in contact with substrates presenting HA of high Mw.
The impact of Arctic warming on increased rainfall
Authors: Bintanja R. 
Published: October 2018

AbstractThe Arctic region is warming two to three times faster than the global mean, intensifying the hydrological cycle in the high north. Both enhanced regional evaporation and poleward moisture transport contribute to a 50–60% increase in Arctic precipitation over the 21st century. The additional precipitation is diagnosed to fall primarily as rain, but the physical and dynamical constraints governing the transition to a rain-dominated Arctic are unknown. Here we use actual precipitation, snowfall, rainfall output of 37 global climate models in standardised 21st-century simulations to demonstrate that, on average, the main contributor to additional Arctic (70–90°N) rainfall is local warming (~70%), whereas non-local (thermo)dynamical processes associated with precipitation changes contribute only 30%. Surprisingly, the effect of local warming peaks in the frigid high Arctic, where modest summer temperature changes exert a much larger effect on rainfall changes than strong wintertime warming. This counterintuitive seasonality exhibits steep geographical gradients, however, governed by non-linear changes in the temperature-dependent snowfall fraction, thereby obscuring regional-scale attribution of enhanced Arctic rainfall to climate warming. Detailed knowledge of the underlying causes behind Arctic snow/rainfall changes will contribute to more accurate assessments of the (possibly irreversible) impacts on hydrology/run-off, permafrost thawing, ecosystems, sea ice retreat, and glacier melt.
Utility of Oblique Sagittal Reformatted and Three-dimensional Surface Reconstruction Computed Tomography in Foraminal Stenosis Decompression
Authors: Oshina Masahito , Oshima Yasushi , Tanaka Sakae , Tan Lee A. , Li Xudong Josh , Tuchman Alexander , Riew K. Daniel 
Published: October 2018

AbstractDetermining the responsible level of cervical radiculopathy can be difficult. Because asymptomatic findings are common in cervical radiculopathy, diagnoses based on imaging studies can be inaccurate. Therefore, we investigated whether the application of oblique sagittal reformatted computed tomography (oblique sagittal CT) and three-dimensional surface reconstruction CT (3DCT) affects surgical plans for patients with cervical foraminal stenosis and whether it assists diagnosis of foraminal stenosis. Accordingly, four reviewers, with office notes, observed the CT and magnetic resonance imaging (MRI) images of 18 patients undergoing surgical treatment for cervical radiculopathy. After reviewing the MRI and sagittal, coronal, and axial CT images, the reviewers recorded the operation to be performed; they examined oblique sagittal CT and 3DCT images of the same patients and noted any differences from their surgical plans. Consequently, we analyzed these changes in the decompressed foramina in the surgical plan; mean percent change in the plan was 18.1%. Inter-rater reliability improved from κ - 0.194 to κ - 0.240. Therefore, the addition of oblique and 3DCT images improves inter-rater reliability owing to changes in a part of decompressed foramina. The addition of oblique sagittal CT and 3DCT is helpful in evaluating the foramen and planning surgical treatment of cervical radiculopathy.
Identification and antitumor activity of a novel inhibitor of the NIMA-related kinase NEK6
Authors: De Donato Marta , Righino Benedetta , Filippetti Flavia , Battaglia Alessandra , Petrillo Marco , Pirolli Davide , Scambia Giovanni , De Rosa Maria Cristina , Gallo Daniela 
Published: October 2018

AbstractThe NIMA (never in mitosis, gene A)-related kinase-6 (NEK6), which is implicated in cell cycle control and plays significant roles in tumorigenesis, is an attractive target for the development of novel anti-cancer drugs. Here we describe the discovery of a potent ATP site-directed inhibitor of NEK6 identified by virtual screening, adopting both structure- and ligand-based techniques. Using a homology-built model of NEK6 as well as the pharmacophoric features of known NEK6 inhibitors we identified novel binding scaffolds. Twenty-five compounds from the top ranking hits were subjected to in vitro kinase assays. The best compound, i.e. compound 8 ((5Z)-2-hydroxy-4-methyl-6-oxo-5-[(5-phenylfuran-2-yl)methylidene]-5,6-dihydropyridine-3-carbonitrile), was able to inhibit NEK6 with low micromolar IC50 value, also displaying antiproliferative activity against a panel of human cancer cell lines. Our results suggest that the identified inhibitor can be used as lead candidate for the development of novel anti-cancer agents, thus opening the possibility of new therapeutic strategies.
A new cerebral vessel benchmark dataset (CAPUT) for validation of image-based aneurysm deformation estimation algorithms
Authors: Schetelig Daniel , Frölich Andreas , Knopp Tobias , Werner René 
Published: October 2018

AbstractHemodynamic properties and deformation of vessel structures are assumed to be correlated to the initiation, development, and rupture of cerebral aneurysms. Therefore, precise quantification of wall motion is essential. However, using standard-of-care imaging data, approaches for patient-specific estimation of pulsatile deformation are prone to uncertainties due to, e.g., contrast agent inflow-related intensity changes and small deformation compared to the image resolution. A ground truth dataset that allows evaluating and finetuning algorithms for deformation estimation is lacking. We designed a flow phantom with deformable structures that resemble cerebral vessels and exhibit physiologically plausible deformation. The deformation was simultaneously recorded using a flat panel CT and a video camera, yielding video data with higher resolution and SNR, which was used to compute ‘ground truth’ structure deformation measures. The dataset was further applied to evaluate registration-based deformation estimation. The results illustrate that registration approaches can be used to estimate deformation with adequate precision. Yet, the accuracy depended on the registration parameters, illustrating the need to evaluate and finetune deformation estimation approaches by ground truth data. To fill the existing gap, the acquired benchmark dataset is provided freely available as the CAPUT (Cerebral Aneurysm PUlsation Testing) dataset, accessible at https://www.github.com/IPMI-ICNS-UKE/CAPUT.
Neuromodulation treats Chikungunya arthralgia: a randomized controlled trial
Authors: Silva-Filho Edson , Okano Alexandre H. , Morya Edgard , Albuquerque Jessica , Cacho Enio , Unal Gozde , Bikson Marom , Pegado Rodrigo 
Published: October 2018

AbstractThe Chikungunya (CHIK) virus is epidemic in Brazil, with 170,000 cases in the first half of 2016. More than 60% of patients present relapsing and remitting chronic arthralgia with debilitating pain lasting years. There are no specific therapeutic agents to treat and rehabilitee infected persons with CHIK. Persistent pain can lead to incapacitation, requiring long-term pharmacological treatment. Advances in non-pharmacological treatments are necessary to promote pain relief without side effects and to restore functionality. Clinical trials indicate transcranial direct current stimulation (tDCS) can treat a broad range of chronic pain disorders, including diffuse neuromuscular pain and arthralgia. Here, we demonstrate that the tDCS across the primary motor cortex significantly reduces pain in the chronic phase of CHIK. High-resolution computational model was created to analyze the cortical electric field generated during tDCS and a diffuse and clustered brain current flow including M1 ipsilateral and contralateral, left DLPFC, nucleus accumbens, and cingulate was found. Our findings suggest tDCS could be an effective, inexpensive and deployable therapy to areas lacking resources with a significant number of patients with chronic CHIK persistent pain.