bluuebunny/crossref_metadata_2025 huggingface dataset:
A Cross-Over Trial Comparing Conventional to Compression-Adjusted Ventilations with Metronome-Guided Compressions
Authors: Nikolla Dhimitri A. , Kramer Brandon J. , Carlson Jestin N.
Published: April 2019

Introduction:

Hyperventilation during cardiopulmonary resuscitation (CPR) negatively affects cardiopulmonary physiology. Compression-adjusted ventilations (CAVs) may allow providers to deliver ventilation rates more consistently than conventional ventilations (CVs). This study sought to compare ventilation rates between these two methods during simulated cardiac arrest.

Null Hypothesis:

That CAV will not result in different rates than CV in simulated CPR with metronome-guided compressions.

Methods:

Volunteer Basic Life Support (BLS)-trained providers delivered bag-valve-mask (BVM) ventilations during simulated CPR with metronome-guided compressions at 100 beats/minute. For the first 4-minute interval, volunteers delivered CV. Volunteers were then instructed on how to perform CAV by delivering one breath, counting 12 compressions, and then delivering a subsequent breath. They then performed CAV for the second 4-minute interval. Ventilation rates were manually recorded. Minute-by-minute ventilation rates were compared between the techniques.

Results:

A total of 23 volunteers were enrolled with a median age of 36 years old and with a median of 14 years of experience. Median ventilation rates were consistently higher in the CV group versus the CAV group across all 1-minute segments: 13 vs 9, 12 vs 8, 12 vs 8, and 12 vs 8 for minutes one through four, respectively (P <.01, all). Hyperventilation (>10 breaths per minute) occurred 64% of the time intervals with CV versus one percent with CAV (P <.01). The proportion of time which hyperventilation occurred was also consistently higher in the CV group versus the CAV group across all 1-minute segments: 78% vs 4%, 61% vs 0%, 57% vs 0%, and 61% vs 0% for minutes one through four, respectively (P <.01, all).

Conclusions:

In this simulated model of cardiac arrest, CAV had more accurate ventilation rates and fewer episodes of hyperventilation compared with CV.

Nikolla DA, Kramer BJ, Carlson JN. A cross-over trial comparing conventional to compression-adjusted ventilations with metronome-guided compressions. Prehosp Disaster Med. 2019;34(2):220–223
Teaching Computerized Content Analysis for Undergraduate Research Papers
Authors: Wilson Steven L. , Herrera Yoshiko M.
Published: April 2019

Content analysis is the process of turning text into data, with either automated or manual techniques, and it provides a feasible and attractive option for undergraduate students to develop and utilize original data. This article presents a cohesive framework for teaching computerized content analysis in undergraduate political science courses. The article discusses examples of how we have taught the techniques in our own classrooms and provides a framework for a content-analysis research assignment. We describe coding, sources of text data available to students, software recommendations appropriate for students, and write-up issues. In the process, we also discuss various learning opportunities that arise from both the strengths and weaknesses of computerized content analysis as a methodological strategy.
(Trans-)planetary sustainability once more – a reply to Losch
Authors: Beisbart Claus
Published: April 2019

In this reply to Losch (2019), I show that, Losch's own judgement notwithstanding, his plea for a concept of (trans-)planetary sustainability does propose conceptual change. I further argue that he has not provided convincing reasons to think that the label ‘planetary’ is superior to ‘trans-planetary’. I summarize my concerns about the plea for introducing the notion of (trans-)planetary sustainability and a related ethics.
A compact quad-band bandpass filter with mixed electric and magnetic coupling
Authors: Zhou Jie , Wang Litian , Wang Zhipeng , Zhang Shengfang , He Ming
Published: April 2019

In this paper, based on a novel multimode stub-loaded resonator, a second-order quad-band bandpass filter (BPF) with mixed electric and magnetic coupling is presented. The electric coupling and magnetic coupling are realized by arranging the parallel coupled lines and the grounded stub, respectively. Eight controllable resonant modes can be simultaneously excited and easily tuned. Eight transmission zeros are created, enhancing the passband selectivity. In addition, the bandwidths can be controlled independently by adjusting the coupling strength. A quad-band BPF centering at 0.67, 1.51, 2.84, 3.58 GHz with respective 3 dB fractional bandwidths of 13.4, 15.6, 9.2, 11.5% is designed, fabricated, and measured. The filter is compact with overall size 0.058λg × 0.13λg. The measured results show a good consistence with the simulated ones.
Placental imprinted gene expression mediates the effects of maternal psychosocial stress during pregnancy on fetal growth
Authors: Lambertini L. , Li Q. , Ma Y. , Zhang W. , Hao K. , Marsit C. , Chen J. , Nomura Y.
Published: April 2019

Imprinted genes uniquely drive and support fetoplacental growth by controlling the allocation of maternal resources to the fetus and affecting the newborn’s growth. We previously showed that alterations of the placental imprinted gene expression are associated with suboptimal perinatal growth and respond to environmental stimuli including socio-economic determinants. At the same time, maternal psychosocial stress during pregnancy (MPSP) has been shown to affect fetal growth. Here, we set out to test the hypothesis that placental imprinted gene expression mediates the effects of MPSP on fetal growth in a well-characterized birth cohort, the Stress in Pregnancy (SIP) Study. We observed that mothers experiencing high MPSP deliver infants with lower birthweight (P=0.047). Among the 109 imprinted genes tested, we detected panels of placental imprinted gene expression of 23 imprinted genes associated with MPSP and 26 with birthweight. Among these genes, five imprinted genes (CPXM2, glucosidase alpha acid (GAA),GPR1, SH3 and multiple ankyrin repeat domains 2 (SHANK2)andTHSD7A) were common to the two panels. In multivariate analyses, controlling for maternal age and education and gestational age at birth and infant gender, two genes,GAAandSHANK2, each showed a 22% mediation of MPSP on fetal growth. These data provide new insights into the role that imprinted genes play in translating the maternal stress message into a fetoplacental growth pattern.
Predictors and moderators of burden of care and emotional distress in first-episode psychosis caregivers: results from the GET UP pragmatic cluster randomised controlled trial
Authors: Onwumere J. , Bonetto C. , Lasalvia A. , Miglietta E. , Veronese A. , Bellini F. , Imbesi M. , Bebbington P. , Kuipers E , Ruggeri M. ,   The GET UP Group
Published: April 2019

Aims

First-episode psychosis (FEP) is a major life event and can have an adverse impact on the diagnosed individual and their families. The importance of intervening early and providing optimal treatments is widely acknowledged. In comparison to patient groups, literature is scarce on identifying treatment predictors and moderators of caregiver outcomes. This study aimed to identify pre-treatment characteristics predicting and/or moderating carer outcomes, based on data from a multi-element psychosocial intervention to FEP patients and carers (GET-UP PIANO trial).

Methods

Carer demography, type of family relationship, patient contact hours, pre-treatment carer burden, patient perceptions of parental caregiving and expressed emotion (EE) were selected, a priori, as potential predictors/moderators of carer burden and emotional distress at 9 months post treatment. Outcomes were analysed separately in mixed-effects random regression models.

Results

Analyses were performed on 260 carers. Only patient perceptions of early maternal criticism predicted reports of lower carer burden at follow-up. However, multiple imputation analysis failed to confirm this result. For treatment moderators: higher levels of carer burden at baseline yielded greater reductions in carer emotional distress at follow-up in the experimental group compared with treatment as usual (TAU). Higher levels of perceived EE moderated greater reductions in carer reports of tension in experimental group, compared with TAU, at follow-up. In younger caregivers (<51 years old), there were greater reductions in levels of worry during the baseline to follow-up period, within the experimental group compared with TAU.

Conclusion

The study failed to identify significant treatment predictors of FEP carer outcomes. However, our preliminary findings suggest that optimal treatment outcomes for carers at first episode might be moderated by younger carer age, and carers reporting higher baseline levels of burden, and where patients perceive higher levels of negative effect from caregivers.
Cell therapy of critical limb ischemia-problems and	prospects
Authors: Osipova Olesia , Saaya Shoraan , Karpenko Andrei , Zakian Suren , Aboian Edouard
Published: April 2019

Summary. Cell therapy is proposed for indirect revascularization for the patient’s incurable by endovascular or surgical revascularization. The therapy with stem cells (SCs) or progenitor cells is assumed to be more efficient as compared with protein or gene therapy not only because of their direct vasculogenic properties, but also thanks to their paracrine effect via secretion of manifold biologically active substances. This review gives an overview of the potential of SC-based therapy for critical limb ischemia (CLI), putative mechanism underlying cell therapy, and comparison of cell therapy to angiogenesis gene therapy in CLI treatment. Human trial data and meta-analysis, as well as some problems of clinical trials and considerations for future SC-based therapy in CLI are also discussed.
Ultrasound assisted endovascular treatment of acute venous	thromboses
Authors: Heckmann Markus B. , Wangler Susanne , Katus Hugo A. , Erbel Christian
Published: April 2019

Summary. Deep vein thromboses lead to post thrombotic syndrome in up to 50% of patients, which entails significant morbidity and socioeconomic costs. Endovascular treatment of iliofemoral deep vein thrombosis aims to reduce the development and the severity of post thrombotic syndrome. This case series of four cases demonstrates that acute and chronic thrombotic stenoses or occlusions can be safely managed by ultrasound guided endovascular treatment minimizing the number of interventions, bleeding risk and radiation exposure.
Induced Seismicity Driven by Fluid Diffusion Revealed by a Near‐Field Hydraulic Stimulation Monitoring Array in the Montney Basin, British Columbia
Authors: Yu H. , Harrington R. M. , Liu Y. , Wang B.
Published: April 2019

This study presents observations using new data from a deployment of eight broadband seismometers surrounding a horizontal well pad at distances of ~1–3 km for the period before, during, and after a hydraulic fracturing treatment in the Montney Basin, British Columbia, Canada. We use a multistation‐matched filter detection and double‐difference earthquake relocation to develop a catalog of 350 events associated with hydraulic fracturing stimulation, with magnitudes ranging from −2.8 to 1.8 and estimated catalog completeness of approximately −0.2. The seismicity distribution suggests a statistically significant association with injection, and event migration can be described by a hydraulic diffusivity of ~0.2 m2/s. A comparison between daily seismicity rate and analytical stress evolution inferred from daily injection volumes implies that pore pressure diffusion largely controls earthquake nucleation at distances less than 1 km, whereas poroelastic stress transfer likely dominates at intermediate distances of ~1–4 km at time scales shorter than diffusion. Both mechanisms likely have a limited effect on stress perturbation at distances over 5 km.
Increased Dust Deposition in New Zealand Related to Twentieth Century Australian Land Use
Authors: Brahney Janice , Ballantyne Ashley P. , Vandergoes Marcus , Baisden Troy , Neff Jason C.
Published: April 2019

Mineral aerosols (dust) generated in the dryland regions of Australia have the potential to reach New Zealand through atmospheric transport. Although a large portion of dust in New Zealand originates in Australia, little is known about how dust deposition has varied over time in New Zealand or what may have caused this variation. We used geochemical dust proxies to examine the recent history of dust deposition to two alpine lakes in Kahurangi National Park, South Island, New Zealand. Geochemical indicators suggest that dust deposition began to increase around 1900, with the greatest deposition rates occurring from ~1920 to ~1990. In subsequent decades, dust deposition rates to New Zealand lakes appear to have declined. This rise and fall of dust deposition recorded in New Zealand lakes is consistent with dust records from the Antarctic Ice Sheet, Eastern Australia, and incidents of low visibility due to dust events recorded at Australian climate stations. The dust deposition rate over time also follows the temporal pattern of land use in south and central Australia over the time scale of the twentieth century suggesting a causal linkage. It is possible, and perhaps likely, that drought cycles also affected both emissions and transport pathways but over shorter time periods this was difficult to discern at the temporal resolution of these lake sediment cores. The increase in dust deposition to the high‐elevation regions of New Zealand likely has implications for the biogeochemistry of alpine lakes in the Tasman Mountains.
A New Way to Analyze Evidence of Martian Oceans
Authors: Thompson Elizabeth
Published: April 2019

Mars’s aqueous past holds the answers to many questions about the Red Planet. A new study provides a tool for scouring planetary surfaces for ancient shorelines.
Did Global Glaciation Cause the Great Unconformity?
Authors: Chakravorty Adityarup
Published: April 2019

In a new study, researchers make the case that large-scale glaciation during parts of the Neoproterozoic era led to extensive erosion of Earth’s crust.
Secrets from the New Madrid Seismic Zone’s Quaking Past
Authors: Crowell Rachel
Published: April 2019

High-resolution lidar topography reveals a long history of ancient earthquakes.
A stochastic view on surface inhomogeneity of nanoparticles
Authors: Post R. A. J. , van der Zwaag D. , Bet G. , Wijnands S. P. W. , Albertazzi L. , Meijer E. W. , van der Hofstad R. W.
Published: April 2019

The interactions between and with nanostructures can only be fully understood when the functional group distribution on their surfaces can be quantified accurately. Here we apply a combination of direct stochastic optical reconstruction microscopy (dSTORM) imaging and probabilistic modelling to analyse molecular distributions on spherical nanoparticles. The properties of individual fluorophores are assessed and incorporated into a model for the dSTORM imaging process. Using this tailored model, overcounting artefacts are greatly reduced and the locations of dye labels can be accurately estimated, revealing their spatial distribution. We show that standard chemical protocols for dye attachment lead to inhomogeneous functionalization in the case of ubiquitous polystyrene nanoparticles. Moreover, we demonstrate that stochastic fluctuations result in large variability of the local group density between particles. These results cast doubt on the uniform surface coverage commonly assumed in the creation of amorphous functional nanoparticles and expose a striking difference between the average population and individual nanoparticle coverage.
The simplest construction of single-site catalysts by the synergism of micropore trapping and nitrogen anchoring
Authors: Zhang Zhiqi , Chen Yugang , Zhou Liqi , Chen Chi , Han Zhen , Zhang Bingsen , Wu Qiang , Yang Lijun , Du Lingyu , Bu Yongfeng , Wang Peng , Wang Xizhang , Yang Hui , Hu Zheng
Published: April 2019

Single-site catalysts feature high catalytic activity but their facile construction and durable utilization are highly challenging. Herein, we report a simple impregnation-adsorption method to construct platinum single-site catalysts by synergic micropore trapping and nitrogen anchoring on hierarchical nitrogen-doped carbon nanocages. The optimal catalyst exhibits a record-high electrocatalytic hydrogen evolution performance with low overpotential, high mass activity and long stability, much superior to the platinum-based catalysts to date. Theoretical simulations and experiments reveal that the micropores with edge-nitrogen-dopants favor the formation of isolated platinum atoms by the micropore trapping and nitrogen anchoring of [PtCl6]2-, followed by the spontaneous dechlorination. The platinum-nitrogen bonds are more stable than the platinum-carbon ones in the presence of adsorbed hydrogen atoms, leading to the superior hydrogen evolution stability of platinum single-atoms on nitrogen-doped carbon. This method has been successfully applied to construct the single-site catalysts of other precious metals such as palladium, gold and iridium.
Piezoresponse force microscopy and nanoferroic phenomena
Authors: Gruverman Alexei , Alexe Marin , Meier Dennis
Published: April 2019

Since its inception more than 25 years ago, Piezoresponse Force Microscopy (PFM) has become one of the mainstream techniques in the field of nanoferroic materials. This review describes the evolution of PFM from an imaging technique to a set of advanced methods, which have played a critical role in launching new areas of ferroic research, such as multiferroic devices and domain wall nanoelectronics. The paper reviews the impact of advanced PFM modes concerning the discovery and scientific understanding of novel nanoferroic phenomena and discusses challenges associated with the correct interpretation of PFM data. In conclusion, it offers an outlook for future trends and developments in PFM.
Perovskite nickelates as bio-electronic interfaces
Authors: Zhang Hai-Tian , Zuo Fan , Li Feiran , Chan Henry , Wu Qiuyu , Zhang Zhan , Narayanan Badri , Ramadoss Koushik , Chakraborty Indranil , Saha Gobinda , Kamath Ganesh , Roy Kaushik , Zhou Hua , Chubykin Alexander A. , Sankaranarayanan Subramanian K. R. S. , Choi Jong Hyun , Ramanathan Shriram
Published: April 2019

Functional interfaces between electronics and biological matter are essential to diverse fields including health sciences and bio-engineering. Here, we report the discovery of spontaneous (no external energy input) hydrogen transfer from biological glucose reactions into SmNiO3, an archetypal perovskite quantum material. The enzymatic oxidation of glucose is monitored down to ~5 × 10−16 M concentration via hydrogen transfer to the nickelate lattice. The hydrogen atoms donate electrons to the Ni d orbital and induce electron localization through strong electron correlations. By enzyme specific modification, spontaneous transfer of hydrogen from the neurotransmitter dopamine can be monitored in physiological media. We then directly interface an acute mouse brain slice onto the nickelate devices and demonstrate measurement of neurotransmitter release upon electrical stimulation of the striatum region. These results open up avenues for use of emergent physics present in quantum materials in trace detection and conveyance of bio-matter, bio-chemical sciences, and brain-machine interfaces.
Mechanisms of redundancy and specificity of the Aspergillus fumigatus Crh transglycosylases
Authors: Fang Wenxia , Sanz Ana Belén , Bartual Sergio Galan , Wang Bin , Ferenbach Andrew T. , Farkaš Vladimír , Hurtado-Guerrero Ramon , Arroyo Javier , van Aalten Daan M. F.
Published: April 2019

Fungal cell wall synthesis is achieved by a balance of glycosyltransferase, hydrolase and transglycosylase activities. Transglycosylases strengthen the cell wall by forming a rigid network of crosslinks through mechanisms that remain to be explored. Here we study the function of the Aspergillus fumigatus family of five Crh transglycosylases. Although crh genes are dispensable for cell viability, simultaneous deletion of all genes renders cells sensitive to cell wall interfering compounds. In vitro biochemical assays and localisation studies demonstrate that this family of enzymes functions redundantly as transglycosylases for both chitin-glucan and chitin-chitin cell wall crosslinks. To understand the molecular basis of this acceptor promiscuity, we solved the crystal structure of A. fumigatus Crh5 (AfCrh5) in complex with a chitooligosaccharide at the resolution of 2.8 Å, revealing an extensive elongated binding cleft for the donor (−4 to −1) substrate and a short acceptor (+1 to +2) binding site. Together with mutagenesis, the structure suggests a “hydrolysis product assisted” molecular mechanism favouring transglycosylation over hydrolysis.
Lineage-specific RUNX2 super-enhancer activates MYC and promotes the development of blastic plasmacytoid dendritic cell neoplasm
Authors: Kubota Sho , Tokunaga Kenji , Umezu Tomohiro , Yokomizo-Nakano Takako , Sun Yuqi , Oshima Motohiko , Tan Kar Tong , Yang Henry , Kanai Akinori , Iwanaga Eisaku , Asou Norio , Maeda Takahiro , Nakagata Naomi , Iwama Atsushi , Ohyashiki Kazuma , Osato Motomi , Sashida Goro
Published: April 2019

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive subtype of acute leukemia, the cell of origin of which is considered to be precursors of plasmacytoid dendritic cells (pDCs). Since translocation (6;8)(p21;q24) is a recurrent anomaly for BPDCN, we demonstrate that a pDC-specific super-enhancer of RUNX2 is associated with the MYC promoter due to t(6;8). RUNX2 ensures the expression of pDC-signature genes in leukemic cells, but also confers survival and proliferative properties in BPDCN cells. Furthermore, the pDC-specific RUNX2 super-enhancer is hijacked to activate MYC in addition to RUNX2 expression, thereby promoting the proliferation of BPDCN. We also demonstrate that the transduction of MYC and RUNX2 is sufficient to initiate the transformation of BPDCN in mice lacking Tet2 and Tp53, providing a model that accurately recapitulates the aggressive human disease and gives an insight into the molecular mechanisms underlying the pathogenesis of BPDCN.
Multimodal interference-based imaging of nanoscale structure and macromolecular motion uncovers UV induced cellular paroxysm
Authors: Gladstein Scott , Almassalha Luay M. , Cherkezyan Lusik , Chandler John E. , Eshein Adam , Eid Aya , Zhang Di , Wu Wenli , Bauer Greta M. , Stephens Andrew D. , Morochnik Simona , Subramanian Hariharan , Marko John F. , Ameer Guillermo A. , Szleifer Igal , Backman Vadim
Published: April 2019

Understanding the relationship between intracellular motion and macromolecular structure remains a challenge in biology. Macromolecular structures are assembled from numerous molecules, some of which cannot be labeled. Most techniques to study motion require potentially cytotoxic dyes or transfection, which can alter cellular behavior and are susceptible to photobleaching. Here we present a multimodal label-free imaging platform for measuring intracellular structure and macromolecular dynamics in living cells with a sensitivity to macromolecular structure as small as 20 nm and millisecond temporal resolution. We develop and validate a theory for temporal measurements of light interference. In vitro, we study how higher-order chromatin structure and dynamics change during cell differentiation and ultraviolet (UV) light irradiation. Finally, we discover cellular paroxysms, a near-instantaneous burst of macromolecular motion that occurs during UV induced cell death. With nanoscale sensitive, millisecond resolved capabilities, this platform could address critical questions about macromolecular behavior in live cells.
Orbitally driven giant thermal conductance associated with abnormal strain dependence in hydrogenated graphene-like borophene
Authors: He Jia , Li Dengfeng , Ying Yan , Feng Chunbao , He Junjie , Zhong Chengyong , Zhou Hangbo , Zhou Ping , Zhang Gang
Published: April 2019

Heat energy in solids is carried by phonons and electrons. However, in most two-dimensional (2D) materials, the contribution from electrons to total thermal conduction is much lower than that for phonons. In this work, through first-principles calculations combined with non-equilibrium Green’s function theory, we studied electron and phonon thermal conductance in recently synthesized 2D hydrogen boride. The hexagonal boron network with bridging hydrogen atoms is suggested to exhibit comparable lattice thermal conductance (4.07 nWK−1 nm−2) as graphene (4.1 nWK−1 nm−2), and similar electron thermal conductance (3.6 nWK−1 nm−2), which is almost ten times that of graphene. As a result, total thermal conductance of 2D hydrogen boride is about two-fold of graphene, being the highest value in all known 2D materials. Moreover, tensile strain along the armchair direction leads to an increase in carrier density, significantly increasing electron thermal conductance. The increase in electron thermal conductance offsets the reduction in phonon thermal conductance, contributing to an abnormal increase in thermal conductance. We demonstrate that the high electron density governs extraordinarily high thermal conductance in 2D hydrogen boride, distinctive among 2D materials.
A data citation roadmap for scholarly data repositories
Authors: Fenner Martin , Crosas Mercè , Grethe Jeffrey S. , Kennedy David , Hermjakob Henning , Rocca-Serra Phillippe , Durand Gustavo , Berjon Robin , Karcher Sebastian , Martone Maryann , Clark Tim
Published: April 2019

This article presents a practical roadmap for scholarly data repositories to implement data citation in accordance with the Joint Declaration of Data Citation Principles, a synopsis and harmonization of the recommendations of major science policy bodies. The roadmap was developed by the Repositories Expert Group, as part of the Data Citation Implementation Pilot (DCIP) project, an initiative of FORCE11.org and the NIH-funded BioCADDIE (https://biocaddie.org) project. The roadmap makes 11 specific recommendations, grouped into three phases of implementation: a) required steps needed to support the Joint Declaration of Data Citation Principles, b) recommended steps that facilitate article/data publication workflows, and c) optional steps that further improve data citation support provided by data repositories. We describe the early adoption of these recommendations 18 months after they have first been published, looking specifically at implementations of machine-readable metadata on dataset landing pages.
A Multi-Trait Approach Identified Genetic Variants Including a Rare Mutation in RGS3 with Impact on Abnormalities of Cardiac Structure/Function
Authors: Yazdani Akram , Yazdani Azam , Méndez Giráldez Raúl , Aguilar David , Sartore Luca
Published: April 2019

Heart failure is a major cause for premature death. Given the heterogeneity of the heart failure syndrome, identifying genetic determinants of cardiac function and structure may provide greater insights into heart failure. Despite progress in understanding the genetic basis of heart failure through genome wide association studies, the heritability of heart failure is not well understood. Gaining further insights into mechanisms that contribute to heart failure requires systematic approaches that go beyond single trait analysis. We integrated a Bayesian multi-trait approach and a Bayesian networks for the analysis of 10 correlated traits of cardiac structure and function measured across 3387 individuals with whole exome sequence data. While using single-trait based approaches did not find any significant genetic variant, applying the integrative Bayesian multi-trait approach, we identified 3 novel variants located in genes, RGS3, CHD3, and MRPL38 with significant impact on the cardiac traits such as left ventricular volume index, parasternal long axis interventricular septum thickness, and mean left ventricular wall thickness. Among these, the rare variant NC_000009.11:g.116346115C > A (rs144636307) in RGS3 showed pleiotropic effect on left ventricular mass index, left ventricular volume index and maximal left atrial anterior-posterior diameter while RGS3 can inhibit TGF-beta signaling associated with left ventricle dilation and systolic dysfunction.
Publisher Correction: Grassland dynamics in response to climate change and human activities in Xinjiang from 2000 to 2014
Authors: Zhang Renping , Liang Tiangang , Guo Jing , Xie Hongjie , Feng Qisheng , Aimaiti Yusupujiang
Published: April 2019

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
Plastic waste interferes with chemical communication in aquatic ecosystems
Authors: Trotter B. , Ramsperger A. F. R. M. , Raab P. , Haberstroh J. , Laforsch C.
Published: April 2019

Environmental pollution with plastic waste has gained increasing attention, as the contamination of aquatic habitats poses a challenge to these ecosystems. Plastic waste has direct negative effects on animals such as reduced growth rate, fecundity or life span. However, the indirect effects of plastic waste, which has the ability to sorb chemicals from the surrounding media, on chemical communication have yet to be investigated. Chemical communication is crucial for aquatic organisms, e.g., to avoid predation. The planktonic water flea Daphnia (Crustacea), an important link between trophic levels, relies on info-chemicals (kairomones) to assess its current predation risk and to form inducible defences. We show that plastic waste, composed of high-density polyethylene (HDPE) and polyethylene terephthalate (PET) interferes with the formation of inducible defences in Daphnia longicephala when exposed to a combination of kairomones of Notonecta glauca and plastic waste. D. longicephala shows a reduction in all defensive traits, including body length, crest width and time until primiparity, compared to exposure to solely kairomone conditioned media. Plastic waste in the absence of kairomones had no effect on defensive traits. Since it is vital to adjust these defences to the current predation risk, any misperception can have far-reaching ecological consequences. Therefore, plastic waste can have indirect effects on organisms, which may manifest at the community level.
Metal resistant PGPR lowered Cd uptake and expression of metal transporter genes with improved growth and photosynthetic pigments in Lycopersicon esculentum under metal toxicity
Authors: Khanna Kanika , Jamwal Vijay Lakshmi , Gandhi Sumit G. , Ohri Puja , Bhardwaj Renu
Published: April 2019

Plant growth promoting rhizobacteria (PGPRs) are very effective in immobilization of heavy metals and reducing their translocation in plants via precipitation, complex formation and adsorption. The present study was therefore designed to understand the role of Pseudomonas aeruginosa and Burkholderia gladioli in mitigation of Cd stress (0.4 mM) in 10-days old L. esculentum seedlings. The present work investigated growth characteristics, photosynthetic pigments, metal tolerance index, metal uptake and the contents of metal chelating compounds (protein bound and non-protein bound thiols, total thiols) in microbes inoculated Cd treated L. esculentum seedlings. The gene expression profiling of different metal transporters was conducted in order to investigate the quantitative analysis. Our results revealed Cd generated toxicity in seedlings in terms of reduced growth (root length, shoot length and fresh weight) and photosynthetic pigments (chlorophyll, carotenoid and xanthophyll) which enhanced upon inoculations of P. aeruginosa and B. gladioli. Further, the metal uptake along with levels of protein and non-protein bound thiols was also enhanced in Cd-treated seedlings. Gene expression studies suggested enhanced expression in the metal transporter genes which were further declined in the microbe supplemented seedlings. Therefore, micro-organisms possess growth promoting traits that enable them to reduce metal toxicity in plants.
Roles of cellular heterogeneity, intrinsic and extrinsic noise in variability of p53 oscillation
Authors: Wang Dao-Guang , Wang Shaobing , Huang Bo , Liu Feng
Published: April 2019

The p53 protein is a key mediator of the cellular response to various stress signals. In response to DNA damage, the concentration of p53 can temporally oscillate with fluctuations in both the amplitude and period. The underlying mechanism for p53 variability is not fully understood. Here, we construct a core regulatory network of p53 dynamics comprising the ATM-p53-Wip1 and p53-Mdm2 negative feedback loops. We dissect the contributions of cellular heterogeneity, intrinsic noise, and multiple forms of extrinsic noise to p53 variability in terms of the coefficients of variation of four quantities. Cellular heterogeneity greatly determines the fraction of oscillating cells among a population of isogenic cells. Intrinsic noise—fluctuation in biochemical reactions–has little impact on p53 variability given large amounts of molecules, whereas extrinsic colored noise with proper strength and correlation time contributes much to oscillatory variability in individual cells. With the three sources of noise combined, our results reproduce the experimental observations, suggesting that the long correlation time of colored noise is essential to p53 variability. Compared with previous studies, the current work reveals both the individual and integrated effects of distinct noise sources on p53 variability. This study provides a framework for exploring the variability in oscillations in cellular signaling pathways.
Improved predictions of time-dependent drug-drug interactions by determination of cytosolic drug concentrations
Authors: Filppula Anne M. , Parvizi Rezvan , Mateus André , Baranczewski Pawel , Artursson Per
Published: April 2019

The clinical impact of drug-drug interactions based on time-dependent inhibition of cytochrome P450 (CYP) 3A4 has often been overpredicted, likely due to use of improper inhibitor concentration estimates at the enzyme. Here, we investigated if use of cytosolic unbound inhibitor concentrations could improve predictions of time-dependent drug-drug interactions. First, we assessed the inhibitory effects of ten time-dependent CYP3A inhibitors on midazolam 1′-hydroxylation in human liver microsomes. Then, using a novel method, we determined the cytosolic bioavailability of the inhibitors in human hepatocytes, and used the obtained values to calculate their concentrations at the active site of the enzyme, i.e. the cytosolic unbound concentrations. Finally, we combined the data in mechanistic static predictions, by considering different combinations of inhibitor concentrations in intestine and liver, including hepatic concentrations corrected for cytosolic bioavailability. The results were then compared to clinical data. Compared to no correction, correction for cytosolic bioavailability resulted in higher accuracy and precision, generally in line with those obtained by more demanding modelling. The best predictions were obtained when the inhibition of hepatic CYP3A was based on unbound maximal inhibitor concentrations corrected for cytosolic bioavailability. Our findings suggest that cytosolic unbound inhibitor concentrations improves predictions of time-dependent drug-drug interactions for CYP3A.
Comparison of a personalized breast dosimetry method with standard dosimetry protocols
Authors: Salomon Elisabeth , Homolka Peter , Semturs Friedrich , Figl Michael , Gruber Michael , Hummel Johann
Published: April 2019

Average glandular dose (AGD) in digital mammography crucially depends on the estimation of breast glandularity. In this study we compared three different methods of estimating glandularities according to Wu, Dance and Volpara with respect to resulting AGDs. Exposure data from 3050 patient images, acquired with a GE Senographe Essential constituted the study population of this work. We compared AGD (1) according to Dance et al. applying custom g, c, and s factors using HVL, breast thickness, patient age and incident air kerma (IAK) from the DICOM headers; (2) according to Wu et al. as determined by the GE system; and (3) AGD derived with the Dance model with personalized c factors using glandularity determined with the Volpara (Volpara Solutions, Wellington, New Zealand) software (Volpare AGD). The ratios of the resulting AGDs were analysed versus parameters influencing dose. The highest deviation between the resulting AGDs was found in the ratio of GE AGD to Volpara AGD for breast thicknesses between 20 and 40 mm (ratio: 0.80). For thicker breasts this ratio is close to one (1 ± 0.02 for breast thicknesses >60 mm). The Dance to Volpara ratio was between 0.86 (breast thickness 20–40 mm) and 0.99 (>80 mm), and Dance/GE AGD was between 1.07 (breast thickness 20–40 mm) and 0.98 (41–60, and >80 mm). Glandularities by Volpara were generally smaller than the one calculated with the Dance method. This effect is most pronounced for small breast thickness and older ages. Taking the considerable divergences between the AGDs from different methods into account, the selection of the method should by done carefully. As the Volpara method provides an analysis of the individual breast tissue, while the Wu and the Dance methods use look up tables and custom parameter sets, the Volpara method might be more appropriate if individual ADG values are sought. For regulatory purposes and comparison with diagnostic reference values, the method to be used needs to be defined exactly and clearly be stated. However, it should be accepted that dose values calculated with standardized models, like AGD and also effective dose, are afflicted with a considerable uncertainty budgets that need to be accounted for in the interpretation of these values.
First Trimester Circulating MicroRNA Biomarkers Predictive of Subsequent Preterm Delivery and Cervical Shortening
Authors: Cook Joanna , Bennett Phillip R. , Kim Sung Hye , Teoh Tiong Ghee , Sykes Lynne , Kindinger Lindsay M. , Garrett Alice , Binkhamis Reem , MacIntyre David A. , Terzidou Vasso
Published: April 2019

Preterm birth (PTB) is the leading cause of infant death and disability worldwide. The onset of preterm uterine contractions is preceded by asymptomatic cervical remodelling and ripening, which can be seen on trans-vaginal ultrasound as cervical shortening. This study aimed to identify plasma miRNA biomarkers that predict preterm birth and/or cervical shortening. We collected serial plasma samples from pregnant women prospectively from 12 to 22 weeks gestation. The nCounter miRNA assay was used to identify differentially expressed miRNAs associated with spontaneous PTB and/or cervical shortening (n = 16 term no short, n = 13 preterm, n = 24 short). Predictive values of the miRNA biomarkers were confirmed in an independent validation cohort consisting of 96 women who delivered at term, 14 preterm and 21 early cervical shortening at <20 weeks gestation. Nine miRNAs (hsa-let-7a-5p, hsa-miR-374a-5p, hsa-miR-15b-5p, hsa-miR-19b-3p, hsa-miR-23a-3p, hsa-miR-93-5p, hsa-miR-150-5p, hsa-miR-185-5p and hsa-miR-191-5p) were differentially expressed (P < 0.001) in women subsequently experiencing PTB or cervical shortening. Hsa-miR-150-5p had the strongest ability to predict PTB (AUC = 0.8725) and cervical shortening (AUC = 0.8514). Plasma miRNAs in the first trimester can predict PTB and cervical shortening in women at risk of preterm delivery. This is a key period in pregnancy when early identification of PTB risk allows time to deliver outcome-modifying interventions.
Histological Chorioamnionitis Induces Differential Gene Expression in Human Cord Blood Mononuclear Leukocytes from Term Neonates
Authors: Gayen nee’ Betal Suhita , Murthy Swati , Favara Michael , Fong Gina , Chan Joanna S. Y. , Addya Sankar , Shaffer Thomas H. , Greenspan Jay , Bhandari Vineet , Rahman Irfan , Aghai Zubair H.
Published: April 2019

Histological chorioamnionitis (HCA) is an infection of fetal membranes and complicates 5.2% to 28.5% of all live births. HCA is associated with increased mortality and morbidity in both premature and term neonates. Exposure to HCA may have long-term consequences, including an increased risk for allergic disorders and asthma later in childhood, the mechanism(s) of which are still not yet well understood. The objective of this study was to determine the mRNA transcriptome of cord blood mononuclear leukocytes from term neonates to identify key genes and pathways involved in HCA. We found 366 differentially expressed probe IDs with exposure to HCA (198 upregulated, 168 downregulated). These transcriptomes included novel genes and pathways associated with exposure to HCA. The differential gene expression included key genes regulating inflammatory, immune, respiratory and neurological pathways, which may contribute to disorders in those pathways in neonates exposed to HCA. Our data may lead to understanding of the role of key genes and pathways identified on the long-term sequelae related to exposure to HCA, as well as to identifying potential markers and therapies to prevent HCA-associated complications.
Collagen XXV promotes myoblast fusion during myogenic differentiation and muscle formation
Authors: Gonçalves Tristan J. M. , Boutillon Florence , Lefebvre Suzie , Goffin Vincent , Iwatsubo Takeshi , Wakabayashi Tomoko , Oury Franck , Armand Anne-Sophie
Published: April 2019

Fusion of myoblasts into multinucleated myofibers is crucial for skeletal muscle development and regeneration. However, the mechanisms controlling this process remain to be determined. Here we identified the involvement of a new extracellular matrix protein in myoblast fusion. Collagen XXV is a transmembrane-type collagen highly transcribed during early myogenesis when primary myofibers form. Limb muscles of E12.5 and E14.5 Col25a1−/− embryos show a clear defect in the formation of multinucleated myofibers. In cell culture, the cleaved soluble extracellular domain of the collagen XXV is sufficient to promote the formation of highly multinucleated myofibers. Col25a1 is transiently expressed during myogenic differentiation and Col25a1 transcripts are down-regulated in multinucleated myofibers by a muscle-specific microRNA, miR-499. Altogether, these findings indicate that collagen XXV is required in vivo and in vitro for the fusion of myoblasts into myofibers and give further evidence that microRNAs participate to the regulation of this process.
Novel chemical route for CeO2/MWCNTs composite towards highly bendable solid-state supercapacitor device
Authors: Pandit Bidhan , Sankapal Babasaheb R. , Koinkar Pankaj M.
Published: April 2019

Electrode materials having high capacitance with outstanding stability are the critical issues for the development of flexible supercapacitors (SCs), which have recently received increasing attention. To meet these demands, coating of CeO2 nanoparticles have been performed onto MWCNTs by using facile chemical bath deposition (CBD) method. The formed CeO2/MWCNTs nanocomposite exhibits excellent electrochemical specific capacitance of 1215.7 F/g with 92.3% remarkable cyclic stability at 10000 cycles. Light-weight flexible symmetric solid-state supercapacitor (FSSC) device have been engineered by sandwiching PVA-LiClO4 gel between two CeO2/MWCNTs electrodes which exhibit an excellent supercapacitive performance owing to the integration of pseudocapacitive CeO2 nanoparticles onto electrochemical double layer capacitance (EDLC) behaved MWCNTs complex web-like structure. Remarkable specific capacitance of 486.5 F/g with much higher energy density of 85.7 Wh/kg shows the inherent potential of the fabricated device. Moreover, the low internal resistance adds exceptional stability along with unperturbed behavior even under high mechanical stress which can explore its applicability towards high-performance flexible supercapacitor for advanced portable electronic devices.
Bacterial disease induced changes in fungal communities of olive tree twigs depend on host genotype
Authors: Gomes Teresa , Pereira José Alberto , Lino-Neto Teresa , Bennett Alison E. , Baptista Paula
Published: April 2019

In nature, pathogens live and interact with other microorganisms on plant tissues. Yet, the research area exploring interactions between bacteria-fungi and microbiota-plants, within the context of a pathobiome, is still scarce. In this study, the impact of olive knot (OK) disease caused by the bacteriaPseudomonas savastanoipv.savastanoi(Psv) on the epiphytic and endophytic fungal communities of olive tree twigs from three different cultivars, was investigated in field conditions. The ITS-DNA sequencing of cultivable fungi, showed that OK disease disturbs the resident fungal communities, which may reflect changes in the habitat caused by Psv. In particular, a reduction on epiphyte abundance and diversity, and changes on their composition were observed. Compared to epiphytes, endophytes were less sensitive to OK, but their abundance, in particular of potential pathogens, was increased in plants with OK disease. Host genotype, at cultivar level, contributed to plant fungal assembly particularly upon disease establishment. Therefore, besides fungi - Psv interactions, the combination of cultivar - Psv also appeared to be critical for the composition of fungal communities in olive knots. Specific fungal OTUs were associated to the presence and absence of disease, and their role in the promotion or suppression of OK disease should be studied in the future.
Deep learning versus human graders for classifying diabetic retinopathy severity in a nationwide screening program
Authors: Ruamviboonsuk Paisan , Krause Jonathan , Chotcomwongse Peranut , Sayres Rory , Raman Rajiv , Widner Kasumi , Campana Bilson J. L. , Phene Sonia , Hemarat Kornwipa , Tadarati Mongkol , Silpa-Archa Sukhum , Limwattanayingyong Jirawut , Rao Chetan , Kuruvilla Oscar , Jung Jesse , Tan Jeffrey , Orprayoon Surapong , Kangwanwongpaisan Chawawat , Sukumalpaiboon Ramase , Luengchaichawang Chainarong , Fuangkaew Jitumporn , Kongsap Pipat , Chualinpha Lamyong , Saree Sarawuth , Kawinpanitan Srirut , Mitvongsa Korntip , Lawanasakol Siriporn , Thepchatri Chaiyasit , Wongpichedchai Lalita , Corrado Greg S. , Peng Lily , Webster Dale R.
Published: April 2019

Deep learning algorithms have been used to detect diabetic retinopathy (DR) with specialist-level accuracy. This study aims to validate one such algorithm on a large-scale clinical population, and compare the algorithm performance with that of human graders. A total of 25,326 gradable retinal images of patients with diabetes from the community-based, nationwide screening program of DR in Thailand were analyzed for DR severity and referable diabetic macular edema (DME). Grades adjudicated by a panel of international retinal specialists served as the reference standard. Relative to human graders, for detecting referable DR (moderate NPDR or worse), the deep learning algorithm had significantly higher sensitivity (0.97 vs. 0.74, p < 0.001), and a slightly lower specificity (0.96 vs. 0.98, p < 0.001). Higher sensitivity of the algorithm was also observed for each of the categories of severe or worse NPDR, PDR, and DME (p < 0.001 for all comparisons). The quadratic-weighted kappa for determination of DR severity levels by the algorithm and human graders was 0.85 and 0.78 respectively (p < 0.001 for the difference). Across different severity levels of DR for determining referable disease, deep learning significantly reduced the false negative rate (by 23%) at the cost of slightly higher false positive rates (2%). Deep learning algorithms may serve as a valuable tool for DR screening.