bluuebunny/crossref_metadata_2025_split huggingface dataset:
A biophysical model explains the spontaneous bursting behavior in the developing retina
Authors: Matzakos-Karvouniari Dora , Gil Lionel , Orendorff Elaine , Marre Olivier , Picaud Serge , Cessac Bruno 
Published: February 2019

AbstractDuring early development, waves of activity propagate across the retina and play a key role in the proper wiring of the early visual system. During a particular phase of the retina development (stage II) these waves are triggered by a transient network of neurons, called Starburst Amacrine Cells (SACs), showing a bursting activity which disappears upon further maturation. The underlying mechanisms of the spontaneous bursting and the transient excitability of immature SACs are not completely clear yet. While several models have attempted to reproduce retinal waves, none of them is able to mimic the rhythmic autonomous bursting of individual SACs and reveal how these cells change their intrinsic properties during development. Here, we introduce a mathematical model, grounded on biophysics, which enables us to reproduce the bursting activity of SACs and to propose a plausible, generic and robust, mechanism that generates it. The core parameters controlling repetitive firing are fast depolarizing V-gated calcium channels and hyperpolarizing V-gated potassium channels. The quiescent phase of bursting is controlled by a slow after hyperpolarization (sAHP), mediated by calcium-dependent potassium channels. Based on a bifurcation analysis we show how biophysical parameters, regulating calcium and potassium activity, control the spontaneously occurring fast oscillatory activity followed by long refractory periods in individual SACs. We make a testable experimental prediction on the role of voltage-dependent potassium channels on the excitability properties of SACs and on the evolution of this excitability along development. We also propose an explanation on how SACs can exhibit a large variability in their bursting periods, as observed experimentally within a SACs network as well as across different species, yet based on a simple, unique, mechanism. As we discuss, these observations at the cellular level have a deep impact on the retinal waves description.
Inflammatory and anti-inflammatory markers in plasma: from late pregnancy to early postpartum
Authors: Bränn Emma , Edvinsson Åsa , Rostedt Punga Anna , Sundström-Poromaa Inger , Skalkidou Alkistis 
Published: February 2019

AbstractDuring pregnancy, the woman’s body undergoes tremendous changes in immune system adaptation. The immunological shifts that occur in pregnancy can partially be explained by alterations in hormonal levels. Furthermore, during pregnancy, many autoimmune diseases go into remission, only to flare again in the early postpartum period. Given these important changes in the clinical course of a number of autoimmune disorders, surprisingly little has been done to investigate the inflammatory profile changes across pregnancy and the postpartum period. Thus, the aim of this study was to describe how inflammatory and anti-inflammatory markers change from late pregnancy to the early postpartum period, using a multiplexed assay consisting of both well-known as well as exploratory proteins. Two-hundred-and-ninety women were included in this study and donated a total of 312 blood samples; 198 in late pregnancy (~gw38) and 114 in the postpartum period (~w8). The plasma blood samples were analyzed for 92 immune system related protein markers using Proseek Multiplex Inflammation I panel, a high-sensitivity assay based on proximity extension assay technology. Fifty-six inflammatory and anti-inflammatory markers were significantly different between pregnancy and the postpartum, of which 50 survived corrections for multiple comparisons. Out of these 50 markers, 41 decreased from pregnancy to postpartum, while the remaining 9 increased in the postpartum period. The top five markers with the greatest decrease in the postpartum period were Leukemia inhibitory factor receptor (LIF-R), Latency-associated peptide Transforming growth factor beta-1 (LAP TGF-beta-1), C-C motif chemokine 28 (CCL28), Oncostatin M (OSM) and Fibroblast growth factor 21 (FGF21). Top three markers that increased in the postpartum period were Tumor necrosis factor ligand superfamily member 11 (TRANCE), Tumor necrosis factor ligand superfamily member 12 (TWEAK), and C-C motif chemokine/Eotaxin (CCL11). This study revealed that the majority of the markers decreased from pregnancy to postpartum, and only a few increased. Several of the top proteins that were higher in pregnancy than postpartum have anti-inflammatory and immune modulatory properties promoting pregnancy progress. These results clearly reflect the tremendous change in the immune system in the pregnancy to postpartum transition.
PRSS3/Mesotrypsin and kallikrein-related peptidase 5 are associated with poor prognosis and contribute to tumor cell invasion and growth in lung adenocarcinoma
Authors: Ma Honghai , Hockla Alexandra , Mehner Christine , Coban Matt , Papo Niv , Radisky Derek C. , Radisky Evette S. 
Published: February 2019

AbstractSerine proteases have been implicated as key drivers and facilitators of lung cancer malignancy, and while these proteins represent straightforward targets for therapeutic inhibitors, identification of optimal points for intervention has been complicated by the complex networks in which these enzymes function. Here we implicate a signaling pathway consisting of PRSS3/mesotrypsin and kallikrein-related peptidase 5 (KLK5) in lung adenocarcinoma malignancy. We show that elevated PRSS3/mesotrypsin expression is prognostic for poor outcome for patients with lung adenocarcinoma, and that genetic or pharmacologic targeting of PRSS3/mesotrypsin reduces lung adenocarcinoma cell invasiveness and proliferation. We further show that genetic targeting of KLK5, a known target of PRSS3/mesotrypsin, phenocopies the effect of PRSS3/mesotrypsin knockdown, and also that elevated expression of KLK5 is similarly prognostic for outcome in lung adenocarcinoma. Finally, we use transcriptional profiling experiments to show that PRSS3/mesotrypsin and KLK5 control a common malignancy-promoting pathway. These experiments implicate a potential PRSS3/mesotrypsin-KLK5 signaling module in lung adenocarcinoma and reveal the potential therapeutic benefit of selectively targeting these pathways.
Evolution of Superconductivity with Sr-Deficiency in Antiperovskite Oxide Sr3−xSnO
Authors: Oudah Mohamed , Hausmann Jan Niklas , Kitao Shinji , Ikeda Atsutoshi , Yonezawa Shingo , Seto Makoto , Maeno Yoshiteru 
Published: February 2019

AbstractBulk superconductivity was recently reported in the antiperovskite oxide Sr3−xSnO, with a possibility of hosting topological superconductivity. We investigated the evolution of superconducting properties such as the transition temperature Tc and the size of the diamagnetic signal, as well as normal-state electronic and crystalline properties, with varying the nominal Sr deficiency x0. Polycrystalline Sr3−xSnO was obtained up to x0 = 0:6 with a small amount of SrO impurities. The amount of impurities increases for x0 > 0.6, suggesting phase instability for high deficiency. Mössbauer spectroscopy reveals an unusual Sn4− ionic state in both stoichiometric and deficient samples. By objectively analyzing superconducting diamagnetism data obtained from a large number of samples, we conclude that the optimal x0 lies in the range 0.5 < x0 < 0.6. In all superconducting samples, two superconducting phases appear concurrently that originate from Sr3−xSnO but with varying intensities. These results clarify the Sr deficiency dependence of the normal and superconducting properties of the antiperovskite oxide Sr3−xSnO will ignite future work on this class of materials.
Elastic net-based prediction of IFN-β treatment response of patients with multiple sclerosis using time series microarray gene expression profiles
Authors: Fukushima Arika , Sugimoto Masahiro , Hiwa Satoru , Hiroyasu Tomoyuki 
Published: February 2019

AbstractINF-β has been widely used to treat patients with multiple sclerosis (MS) in relapse. Accurate prediction of treatment response is important for effective personalization of treatment. Microarray data have been frequently used to discover new genes and to predict treatment responses. However, conventional analytical methods suffer from three difficulties: high-dimensionality of datasets; high degree of multi-collinearity; and achieving gene identification in time-course data. The use of Elastic net, a sparse modelling method, would decrease the first two issues; however, Elastic net is currently unable to solve these three issues simultaneously. Here, we improved Elastic net to accommodate time-course data analyses. Numerical experiments were conducted using two time-course microarray datasets derived from peripheral blood mononuclear cells collected from patients with MS. The proposed methods successfully identified genes showing a high predictive ability for INF-β treatment response. Bootstrap sampling resulted in an 81% and 78% accuracy for each dataset, which was significantly higher than the 71% and 73% accuracy obtained using conventional methods. Our methods selected genes showing consistent differentiation throughout all time-courses. These genes are expected to provide new predictive biomarkers that can influence INF-β treatment for MS patients.
Metabotyping as a Stopover in Genome-to-Phenome Mapping
Authors: Handakumbura Pubudu P. , Stanfill Bryan , Rivas-Ubach Albert , Fortin Dan , Vogel John P. , Jansson Christer 
Published: February 2019

AbstractPredicting phenotypic expression from genomic and environmental information is arguably the greatest challenge in today’s biology. Being able to survey genomic content, e.g., as single-nucleotide polymorphism data, within a diverse population and predict the phenotypes of external traits, represents the holy grail across genome-informed disciplines, from personal medicine and nutrition to plant breeding. In the present study, we propose a two-step procedure in bridging the genome to phenome gap where external phenotypes are viewed as emergent properties of internal phenotypes, such as molecular profiles, in interaction with the environment. Using biomass accumulation and shoot-root allometry as external traits in diverse genotypes of the model grass Brachypodium distachyon, we established correlative models between genotypes and metabolite profiles (metabotypes) as internal phenotypes, and between metabotypes and external phenotypes under two contrasting watering regimes. Our results demonstrate the potential for employing metabotypes as an integrator in predicting external phenotypes from genomic information.
Impact of post-hatching maturation on the pharmacokinetics of paracetamol in zebrafish larvae
Authors: van Wijk Rob C. , Krekels Elke H. J. , Kantae Vasudev , Harms Amy C. , Hankemeier Thomas , van der Graaf Piet H. , Spaink Herman P. 
Published: February 2019

AbstractZebrafish larvae are increasingly used in pharmacological and toxicological studies, but it is often overlooked that internal exposure to exogenous compounds, rather than the incubation medium concentration, is driving observed effects. Moreover, as the zebrafish larva is a developing organism, continuous physiological changes impact pharmacokinetic or toxicokinetic processes like the absorption and elimination of exogenous compounds, influencing the interpretation of observations and conclusions drawn from experiments at different larval ages. Here, using paracetamol as paradigm compound, mathematical modelling is used to quantify absorption and elimination rates from internal exposure over time profiles after waterborne treatment, as well as changes in these parameters in post-hatching larvae of 3, 4, and 5 days post fertilisation (dpf). An increase of 106% in absorption rate was observed between 3 and 4 dpf, but no further increase at 5 dpf, and an increase of 17.5% in elimination rate for each dpf. Paracetamol clearance, determined from elimination rate constants and reported total larval volumes of 253, 263, and 300 nL at 3, 4, and 5 dpf respectively, correlates best with higher vertebrates at 5 dpf. This suggests that when studying direct effects of exogenous compounds, experiments with zebrafish larvae are best performed at 5 dpf.
Ocean variability and air-sea fluxes produced by atmospheric rivers
Authors: Shinoda Toshiaki , Zamudio Luis , Guo Yanjuan , Metzger E. Joseph , Fairall Chris W. 
Published: February 2019

AbstractAtmospheric rivers (ARs) cause heavy precipitation and flooding in the coastal areas of many mid-latitude continents, and thus the atmospheric processes associated with the AR have been intensively studied in recent years. However, AR-associated ocean variability and air-sea fluxes have received little attention because of the lack of high-resolution ocean data until recently. Here we demonstrate that typical ARs can generate strong upper ocean response and substantial air-sea fluxes using a high-resolution (1/12°) ocean reanalysis. AR events observed during the CalWater 2015 field campaign generate large-scale on-shore currents that hit the coast, generating strong narrow northward jets along the west coast of North America, in association with a substantial rise of sea level at the coast. In the open ocean, the AR generates prominent changes of mixed layer depth, especially south of 30°N due to the strong surface winds and air-sea heat fluxes. The prominent cooling of SST is observed only in the vicinity of AR upstream areas primarily due to the large latent heat flux. Using a long-term AR dataset, composite structure and variations of upper ocean and air-sea fluxes are presented, which are consistent with those found in the events during CalWater 2015.
Three Dimensional Glomerular Reconstruction: A Novel Approach to Evaluate Renal Microanatomy in Diabetic Kidney Disease
Authors: Torkamani Niloufar , Jerums George , Crammer Paul , Skene Alison , Power David A. , Panagiotopoulos Sianna , Clarke Michele , MacIsaac Richard J. , Ekinci Elif I. 
Published: February 2019

AbstractMesangial metrics reflect glomerular filtration surface area in diabetes. The point-sampled intercept (PSI) method is the conventional method to calculate these parameters. However, this is time consuming and subject to underestimation. We introduce a novel three-dimensional (3D) reconstruction method applicable to light microscopy to measure mesangial metrics. Transmission electron microscopy (TEM), PSI and our new 3D imaging methods were used to quantify mesangial metrics from 22 patients with type 2 diabetes, normo-, micro- and macroalbuminuria and an estimated glomerular filtration rate of <60 mL/min/1.73 m2. Repeated-measures ANOVA test was used to test the equality of the measurement means from the three methods and the degree of inter method variability. Repeated-measures and post-estimation ANOVA tests together with correlation coefficient measurements were used to compare the methods with TEM as reference. There was a statistically significant difference in mesangial volume measurements (F(2, 16) = 15.53, p = 0.0002). The PSI method underestimated measurements compared to TEM and 3D methods by 30% (p = 0.001) and 15%, respectively (p < 0.001). 3D and TEM measurements did not differ significantly. 3D reconstruction is a reliable and time efficient method for calculating mesangial metrics. It may prove to be a useful tool in clinical and experimental diabetic kidney disease.
Multicentre MDR Elizabethkingia anophelis isolates: Novel random amplified polymorphic DNA with capillary electrophoresis systems to rapid molecular typing compared to genomic epidemiology analysis
Authors: Jian Ming-Jr , Perng Cherng-Lih , Sun Jun-Ren , Cheng Yun-Hsiang , Chung Hsing-Yi , Cheng Yu-Hsuan , Lee Shih-Yi , Kuo Shu-Chen , Shang Hung-Sheng 
Published: February 2019

AbstractElizabethkingia species are ubiquitous bacteria that uncommonly cause human infection. Elizabethkingia anophelis was first identified in 2011 from the mosquito Anopheles gambiae. The currently available bacterial typing systems vary greatly with respect to labour, cost, reliability, and ability to discriminate among bacterial strains. Polymerase chain reaction (PCR)-based fingerprinting using random amplified polymorphic DNA (RAPD) is commonly used to identify genetic markers. To our knowledge, no system coupling RAPD-PCR and capillary gel electrophoresis (CGE) has been utilized for the epidemiological typing of E. anophelis. Thus, the aim of the present study was to establish a reliable and reproducible molecular typing technique for E. anophelis isolates based on a multi-centre assessment of bacteraemia patients. Here, we used a rapid CGE-light-emitting diode-induced fluorescence (LEDIF)-based method in conjunction with RAPD-PCR to genotype E. anophelis with a high level of discrimination. All clinical isolates of E. anophelis were found to be typeable, and isolates from two hospitals formed two distinct clusters. The results demonstrated the potential of coupling RAPD and CGE as a rapid and efficient molecular typing tool, providing a reliable method for surveillance and epidemiological investigations of bacterial infections. The proposed method shows promise as a novel, cost-effective, high-throughput, first-pass typing method.
Solar wind charge exchange in cometary atmospheres
Authors: Simon Wedlund Cyril , Behar Etienne , Nilsson Hans , Alho Markku , Kallio Esa , Gunell Herbert , Bodewits Dennis , Heritier Kevin , Galand Marina , Beth Arnaud , Rubin Martin , Altwegg Kathrin , Volwerk Martin , Gronoff Guillaume , Hoekstra Ronnie 
Published: February 2019

Context. Solar wind charge-changing reactions are of paramount importance to the physico-chemistry of the atmosphere of a comet. The ESA/Rosetta mission to comet 67P/Churyumov-Gerasimenko (67P) provides a unique opportunity to study charge-changing processes in situ.
Aims. To understand the role of these reactions in the evolution of the solar wind plasma and interpret the complex in situ measurements made by Rosetta, numerical or analytical models are necessary.
Methods. We used an extended analytical formalism describing solar wind charge-changing processes at comets along solar wind streamlines. The model is driven by solar wind ion measurements from the Rosetta Plasma Consortium-Ion Composition Analyser (RPC-ICA) and neutral density observations from the Rosetta Spectrometer for Ion and Neutral Analysis-Comet Pressure Sensor (ROSINA-COPS), as well as by charge-changing cross sections of hydrogen and helium particles in a water gas.
Results. A mission-wide overview of charge-changing efficiencies at comet 67P is presented. Electron capture cross sections dominate and favor the production of He and H energetic neutral atoms (ENAs), with fluxes expected to rival those of H+ and He2+ ions.
Conclusions. Neutral outgassing rates are retrieved from local RPC-ICA flux measurements and match ROSINA estimates very well throughout the mission. From the model, we find that solar wind charge exchange is unable to fully explain the magnitude of the sharp drop in solar wind ion fluxes observed by Rosetta for heliocentric distances below 2.5 AU. This is likely because the model does not take the relative ion dynamics into account and to a lesser extent because it ignores the formation of bow-shock-like structures upstream of the nucleus. This work also shows that the ionization by solar extreme-ultraviolet radiation and energetic electrons dominates the source of cometary ions, although solar wind contributions may be significant during isolated events.
Lungensonografie für Anästhesie, Intensiv- und Notfallmedizin
Authors: Armbruster Wolf , Eichholz Rüdiger , Notheisen Thomas 
Published: February 2019

ZusammenfassungDie Lungensonografie ist in der Intensiv- und Notfallmedizin ein unterschätztes Werkzeug: Bei bestimmten klinischen Fragestellungen ist ihre Sensitivität drastisch höher als die der Röntgen-Thoraxuntersuchung 1. Ein standardisierter Untersuchungsgang verbessert dabei die Untersuchungsqualität 2. Dieser Artikel vermittelt Grundlagenwissen der Lungensonografie und stellt die Überlegenheit des Ultraschalls gegenüber Röntgenverfahren heraus.
Influence of 18F-FDG-PET/CT on staging of
cervical cancer
Authors: Cegla Paulina , Urbanski Bartosz , Burchardt Ewa , Roszak Andrzej , Cholewinski Witold 
Published: February 2019

Abstract
Aim Cervical cancer is one of the most common cancers of the female
reproductive system. The aim of the study was to assess the usefulness of the
18F-FDG-PET/CT study in staging of cervical cancer, with focus on
the primary tumor parameters.
Material & Methods 105 patients (mean age 56 ± 11y) with newly
diagnosed cervical cancer underwent PET/CT examination which was performed
60 min after IV injection of 18F-FDG with a mean activity of
364 ± 75MBq. 68 patients were diagnosed with stage IIIA/IIIB, 19 patients with
IIB, 10 patients with IB, 8 patients with stage IVA/IVB. Wilcoxon-Mann-Whitney
test and ROC curves were used for statistical analysis.
Results In 35 cases 18F-FDG-PET/CT did not show active
proliferative process outside the cervix. In 38 cases metastases were found in
iliac lymph nodes and in 32 patients scans showed metastases above the aortic
bifurcation including lymph nodes and other organs. The largest volumes of
primary tumor occurred in patients with distant metastases, while the lowest in
patients with disease limited only to cervix. In 63 % of the patients PET/CT
result was compatible with FIGO classification, in 20 % patients PET/CT result
showed less advanced disease and in 17 % of the patients PET/CT results were
higher than FIGO classification.
Conclusion PET/CT using 18F-FDG has an important impact on the
assessment of the stage of cervical cancer. In over 30 % of patients, this study
resulted in a radical change in the treatment plan.
Response of locally advanced rectal cancer (LARC) to
radiochemotherapy: DW-MRI and multiparametric PET/CT in correlation with
histopathology
Authors: Cerny Milena , Dunet Vincent , Rebecchini Caterina , Hahnloser Dieter , Prior John , Sempoux Christine , Schmidt Sabine 
Published: February 2019

Abstract
Aim To prospectively evaluate histological significance and predictive
value of changes in apparent diffusion coefficient (ADC) and 18F-FDG
PET/CT parameters in locally advanced rectal cancer (LARC) after neoadjuvant
radiochemotherapy (RCT).
Methods Twenty-one patients with untreated LARC underwent pre-RCT and
post-RCT 18F-FDG PET/CT and diffusion-weighted magnetic resonance
imaging (DW-MRI), followed by surgery. For both datasets, two readers measured
the tumor SUVmax, SUVmean, MTV, TLG, ADCmin, ADCmean, and respective differences
(∆SUVmax, ∆SUVmean, ∆MTV, ∆TLG, ∆ADCmin, ∆ADCmean) for the whole tumor. Tumor
regression grade according to Mandard (TRGm), percentage of residual tumor cells
and fibrosis were estimated by two pathologists in consensus. Relationship
between parameters was assessed on stepwise multivariate regression analysis and
ROC curve analysis to evaluate their performance and predict the treatment
response.
Results Eighteen LARCs were analyzed. SUVmax and SUVmean decreased from
21.3 ± 8.9 to 9.3 ± 5.5 g/mL, (p = 0.0002) and 12.3 ± 5.1 to 5.4 ± 3.1 g/mL,
(p = 0.0002), respectively, after RCT, whereas ADCmin and ADCmean increased from
396 ± 269 to 573 ± 313×10–6 mm2/s (p = 0.014) and
1159 ± 212 to 1355 ± 194×10–6 mm2/s (p = 0.0008),
respectively. TRGm and percentage of residual tumor cells independently
correlated with post-RCT SUVmean (β = 0.73 and β = 0.76, p < 0.001) and
post-RCT SUVmax (β = 0.72 and β = 0.78, p < 0.001), whereas percentage of
fibrosis independently correlated with ∆ADCmean (β = 0.38, p = 0.008). Post-RCT,
SUVmax and SUVmean performed well in predicting TRGm < 3 and residual tumor
cells ≤ 20 %. ΔADCmean predicted fibrosis > 70 % well.
Conclusion Post-RCT SUVmean, SUVmax and ∆ADCmean are complementary
parameters for respectively evaluating residual tumor burden and amount of
fibrosis in LARC. However, only SUV independently correlated with TRGm.