bluuebunny/crossref_metadata_2025 huggingface dataset:
Endoscopic ultrasonography in pancreatic diseases: advances in tissue acquisition
Authors: Mitselos Ioannis V. , Karoumpalis Ioannis , Theopistos Vasileios I. , Tzilves Dimitrios , Christodoulou Dimitrios K.
Published: July 2019

Background and study aims Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) improved the diagnostic performance and upgraded the role of endoscopic ultrasonography (EUS) into an interventional modality, able to guide patient management and treatment.This review aimed to highlight the advances, emerging practices, procedural techniques and technological innovations in EUS tissue acquisition in pancreatic diseases.

Methods A thorough review of the literature was performed using PubMed to identify articles that describe techniques, advances, and practices in EUS tissue acquisition in gastrointestinal diseases.

Conclusion Since the first EUS-FNA procedure, EUS guided-tissue acquisition has been evolving continuously. Development of needles with innovative tip design enabled procurement of larger samples with preserved histological architecture. Moreover, sampling techniques and complementary methods, such as contrast harmonic imaging and EUS-elastography, have been introduced in an effort to improve diagnostic performance and sample adequacy.
Effect and Complications of Everolimus Use for Giant Cardiac Rhabdomyomas with Neonatal Tuberous Sclerosis
Authors: Shibata Yuka , Maruyama Hidehiko , Hayashi Taiyu , Ono Hiroshi , Wada Yuka , Fujinaga Hideshi , Fujino Shuhei , Nagasawa Junko , Amari Shoichiro , Tsukamoto Keiko , Ito Yushi
Published: July 2019

Most cardiac rhabdomyomas with tuberous sclerosis (TS) are asymptomatic and spontaneously regress. However, some cases require surgical intervention due to arrhythmia and severe obstruction of cardiac inflow or outflow. We report herein a neonatal case of giant cardiac rhabdomyomas with TS and insufficient pulmonary blood flow from the right ventricle. Lipoprostaglandin E1 was necessary to maintain patency of the ductus arteriosus. We used everolimus, a mammalian target of rapamycin inhibitor, to diminish the cardiac rhabdomyomas. After treatment, the rhabdomyomas shrank rapidly, but the serum concentration of everolimus increased sharply (maximum serum trough level: 76.1 ng/mL) and induced complications including pulmonary hemorrhage, liver dysfunction, and acne. After the everolimus level decreased, the complications resolved. Everolimus may be a viable treatment option for rhabdomyomas, but its concentration requires close monitoring to circumvent complications associated with its use.
Metaphyseal Core Decompression and Anterograde Fixation for Scaphoid Proximal Pole Fracture Nonunion without Avascular Necrosis
Authors: Rellan Ignacio , Gallucci Gerardo Luis , Boretto Jorge Guillermo , Donndorff Agustin Guillermo , Zaidenberg Ezequiel Ernesto , De Carli Pablo
Published: July 2019

Objective To report the consolidation rate and the results of a series of 22 patients with metaphyseal core decompression of the distal radius and an antegrade compression screw.

Methods We present a prospective series of patients with scaphoid proximal pole nonunion in whom the presence of intraoperative bleeding was confirmed in both fragments. Patients with displacement, degenerative changes, fragmentation of the proximal pole, cavitation of the focus, loss of height, and necrosis, as well as those with carpal instability, were excluded. The patients were evaluated with X-rays and computed tomography to evaluate their consolidation; their mobility and fist strength were recorded and an analog visual scale (VAS) of pain at rest, pain in activity, subjective functional status, and DASH questionnaire were completed.

Results Of the 23 patients, 21 accomplished union. The average follow-up was 19 months and the average final range of motion was flexion 86%, extension 85%, radial deviation 79%, ulnar deviation 84%, and grip strength 84%. The average VAS for pain at rest was 1 point, the average VAS for activity pain was 2 points, the average VAS for function was 9 points, and the average DASH score was 8.

Conclusions Using this simple and reliable technique, we obtained 91% union and very good functional results. Metaphyseal core decompression of the distal radius associated with an antegrade scaphoid screw is a reasonable and effective option for the treatment of proximal pole scaphoid nonunions without avascular necrosis in carefully selected patients.

Level of Evidence This is Level IV study.
Building an artificial neural network with neurons
Authors: Rigby M. , Anthonisen M. , Chua X. Y. , Kaplan A. , Fournier A. E. , Grütter P.
Published: July 2019

Artificial neural networks are based on mathematical models of biological networks, but it is not clear how similar these two networks are. We have recently demonstrated that we can mechanically manipulate single neurons and create functioning synapses. Here, we build on this discovery and investigate the feasibility and time scales to build an artificial neural network with biological neurons. To achieve this, we characterized the dynamics and forces when pulling functional axonal neurites using a micromanipulation technique with maximum speeds about 300 times faster than the average natural growth rate of 0.0017μm/s. We find that the maximum force required to initiate and extend the neurites is about 1nN. The dynamics of the mechanical extension of the neurite is well described by many elastic springs and viscous dashpots in series. Interestingly, we find that the transport networks, specifically the actin network, lags behind the mechanically pulled structure. These insights could potentially open a new avenue to facilitate and encourage neuronal regrowth not relying on chemical queues. The extracted mechanical parameters and timescales characterize the neurite growth. We predict that it should be possible to use a magnetic trap to wire an artificial network such as a multi-layer perceptron in 17 hours. Once wired, we believe the biological neural network could be trained to process a hand-written digit using artificial neural network concepts applied to biological systems. We show how one could test the stability and robustness of this network by axotomizing (i.e. cutting) specific axons and reconnecting them using mechanical manipulation.
FARO: A new type of neutron spectrometer with flux and resolution optimized
Authors: Bewley R.
Published: July 2019

A new type of high intensity and high resolution time-of-flight near backscattering neutron spectrometer is presented which is capable of an energy resolution of 4.0 μeV with a data collection rate an order of magnitude larger than current near backscattering spectrometers capable of this resolution. This design challenges two accepted norms of high resolution indirect neutron spectrometers: it uses large mosaic pyrolytic graphite (002) crystals instead of nearly perfect silicon (111) crystals to select the final neutron energy, and it operates well away from the normal backscattering condition 2φ ≈ 180° instead using 2φ = 160°. This paper describes the methodology behind this spectrometer along with ray-tracing simulations of the instrument using the McStas program.
Circularly polarized dust Alfvén solitary waves in magnetized gravitative-radiative quantum dusty plasma
Authors: Khattak S. A. , Mushtaq A. , Jan Qasim
Published: July 2019

An effective single fluid quantum magnetohydrodynamic model is used for multicomponent dusty plasma composed of degenerate electrons, ions, and nondegenerate dust species for the investigation of nonlinear circularly polarized dust Alfvén waves in the presence of quantum corrected terms like Fermi and radiation pressures of electrons and ions as well as Jeans term that originates in a self-gravitating, dusty plasma. A set of Zakharovlike equations are derived and are used independently for soliton solutions, incorporating quantum terms and the Jeans term. Using the Sagdeev potential approach, it is observed that ordinary solitons may result in the absence of the Jeans term, whereas cusp solitons are obtained in the presence of the Jeans term. The variation of Sagdeev potential and its associated solitary structure for different parameters are discussed for both right and left handed circularly polarized dust Alfvén waves. It is also observed that increasing the values of the magnetic field and decreasing the dust mass enhance the width of the cusp soliton, while the amplitude remains the same. The modulational instability of the system in view of both quantum and Jeans terms is also looked into, and different conditions of stability and instability for both right and left handed circularly polarized quantum dust Alfvén waves are discussed.
Interlayer impacts to deep-coupling dynamical networks: A snapshot of equilibrium stability
Authors: Wu Jiening , Li Xiang
Published: July 2019

This paper defines deep-coupling networks with two categories of interlayer structures and investigates the equilibrium stability, when every node in the network is governed by a differential dynamical system. Several stability criteria of the equilibrium of deep-coupling networks are arrived at when the equilibrium of each node system is stable or unstable in two categories of interlayer couplings, which clarify interlayer impacts with the dependence of network topology and intralayer intensity as well. Several two-layer and three-layer numerical examples are provided to verify the analytical results.
Differential chopping controller with high-resolution and accuracy using digital signal processor
Authors: Flaxer Eli , Fleischer Sharly
Published: July 2019

This work presents a digital mixer that receives two signals at different frequencies and produces their difference or their sum. Unlike analog circuits that are limited in their ability to separate between close frequencies and require an additional filtering step, we present a digital signal processor-based circuit with excellent frequency separation capabilities. Since software is used to calculate the output function, the obtained output signal is practically unlimited.
Simple multi-sections unit-cell model for sound absorption characteristics of lotus-type porous metals
Authors: Ning Jingfeng , Li Yueming , Zhao Guiping
Published: July 2019

This paper presents a simple multisection unit-cell model (UCM) with which to investigate the sound absorption characteristics of lotus-type porous metals (LTPMs). This model is inspired by analyzing micrographs of the LTPMs and by considering the relationship between the average pore diameter and the porosity. The multisection UCM is used to establish the analytical relationships between the basic nonacoustic parameters (namely, flow resistivity, tortuosity, and porosity) and the sound absorption characteristics of the LTPMs. The analytical predictions are compared with existing experimental data and with analytical results from a uniform UCM. Good agreement is found between the multisections UCM and the existing experimental results. The comparative relationships of the sound absorption coefficients of the LTPMs and uniform and graded open-cell foam aluminum are plotted as well.
Three stable phases and thermodynamic anomaly in a binary mixture of hard particles
Authors: Rodrigues Nathann T. , Oliveira Tiago J.
Published: July 2019

While the realistic modeling of the thermodynamic behavior of fluids usually demands elaborated atomistic models, much has been learned from simplified ones. Here, we investigate a model where pointlike particles (with activity z0) are mixed with molecules that exclude their first and second neighbors (i.e., cubes of lateral size λ=3a, with activity z2), both placed on the sites of a simple cubic lattice with parameter a. Only hard-core interactions exist among the particles so that the model is athermal. Despite its simplicity, the grand-canonical solution of this model on a Husimi lattice built with cubes revels a fluid-fluid demixing, yielding a phase diagram with two fluid phases (one of them dominated by small particles—F0) and a solidlike phase coexisting at a triple-point. Moreover, the fluid-fluid coexistence line ends at a critical point. An anomaly in the total density (ρT) of particles is also found, which is hallmarked by minima in the isobaric curves of ρT vs z0 (or z2). Interestingly, the line of minimum density crosses the phase diagram starting inside the region where both fluid phases are stable, passing through the F0 one and ending deep inside its metastable region, in a point where the spinodals of both fluid phases cross each other.
Integrating fertility preservation and cryo-banking into the conservation of rare and endangered deer species
Authors: Comizzoli P.
Published: July 2019

More than 50 deer species live in diverse ecosystems around the world. Unfortunately, most of them are threatened or endangered because of over-hunting, poaching or habitat destruction. Protection of wild populations (in situ) and management of animal collections in zoos and breeding centres (ex situ) are complementary conservation efforts relying on multidisciplinary approaches. Reproductive biology of deer species is one of the critical areas that still needs to be thoroughly studied to ensure the success of in situ or ex situ programs. Interestingly, there is a vast diversity in reproductive traits within the deer family (from anatomy to breeding-season patterns). On the basis of this fundamental knowledge, adapted reproductive biotechnologies have been developed to enhance reproduction and preserve fertility of individuals. Early works on artificial insemination (AI), in vitro fertilisation (IVF), and germplasm freezing in the more common red deer, sika deer and white-tailed deer have been highly inspiring to projects aiming at saving endangered deer species. A few fawn births following AI or IVF using frozen semen have been reported in wild species (e.g. Eld’s deer, Rucervus eldii thamin); however, assisted reproductive techniques and cryo-banking are currently not integrated into the management of rare and endangered populations. Knowing that many deer populations are rapidly declining in situ and ex situ, there is now an urgent need for better strategies and more fertility preservation options. The objectives of the present article are to review (1) existing reproductive biotechnologies to preserve fertility of different deer species and (2) how to integrate these approaches into the management of rare and endangered populations to address conservation issues.
Corrigendum to: Lothar Becker’s contributions to anthropology
Authors: Howes Hilary
Published: July 2019

WarningReaders of this article are warned that it may contain terms, descriptions and opinions that are culturally sensitive and/or offensive to Aboriginal and Torres Strait Islanders.
Silesian traveller-naturalist Lothar Becker's two visits to Victoria in 1849–52 and 1855–65 brought him into contact with Aboriginal people living in Western Victoria, Melbourne, the Murray River at Albury, and Gippsland. His travels took him to areas now recognised as the traditional lands of the Gunaikurnai, Wathaurung, Wiradjuri and Wurundjeri peoples. Becker's publications include scattered observations on Aboriginal appearance, lifeways, diet, skills, and beliefs. Although these observations were limited by his inability to speak any Aboriginal languages and coloured by his assumptions about the inferiority of Aboriginal culture, they nevertheless document small but significant fragments of what has recently been termed ‘Aboriginal Biocultural Knowledge'.
New treatment options for Neisseria gonorrhoeae in the era of emerging antimicrobial resistance
Authors: Lewis David A.
Published: July 2019

Neisseria gonorrhoeae, the causative agent of gonorrhoea, has rapidly evolved from an exquisitely susceptible pathogen into a ‘superbug’ with the capacity to exhibit an extensively drug resistant (XDR) phenotype. The threat of untreatable gonorrhoea now looms on the horizon while the arsenal of effective antimicrobial agents diminishes with time. Ceftriaxone remains the mainstay of first-line therapy as a single agent or as the backbone of a dual therapy regimen. The implementation of new assays to facilitate ‘precision’ treatment, based on the prediction of N. gonorrhoeae susceptibility to old anti-gonococcal drugs, may enable sparing use of ceftriaxone in those countries that can afford this technology. A few existing drugs, such as ertapenem, can be repositioned to help manage multi-drug resistant and XDR gonorrhoea. Recent clinical trials involving solithromycin and delafloxacin have generated disappointing results in that both agents failed to show non-inferiority to conventional ceftriaxone-based regimens. At present, zoliflodacin and gepotidacin appear to be the most promising antimicrobial agents in clinical development. Both drugs performed well in eradicating urogenital gonorrhoea in recent Phase 2 trials; however, treatment failures were reported at the oropharyngeal site, which is an important site of infection in men who have sex with men and sex workers. Given this observation, it is unlikely that either of these new agents could be promoted for monotherapy of gonorrhoea. The pre-clinical pipeline remains relatively empty of agents likely to progress to clinical development for gonorrhoea treatment and increased investment into gonorrhoea-specific drug discovery is recommended.
Towards a framework for collective behavior in growth-driven systems, based on plant-inspired allotropic pairwise interactions
Authors: Bastien Renaud , Porat Amir , Meroz Yasmine
Published: July 2019

A variety of biological systems are not motile, but sessile in nature, relying on growth as the main driver of their movement. Groups of such growing organisms can form complex structures, such as the functional architecture of growing axons, or the adaptive structure of plant root systems. These processes are not yet understood, however the decentralized growth dynamics bear similarities to the collective behavior observed in groups of motile organisms, such as flocks of birds or schools of fish. Equivalent growth mechanisms make these systems amenable to a theoretical framework inspired by tropic responses of plants, where growth is considered implicitly as the driver of the observed bending towards a stimulus. We introduce two new concepts related to plant tropisms: point tropism, the response of a plant to a nearby point signal source, and allotropism, the growth-driven response of plant organs to neighboring plants. We first analytically and numerically investigate the 2D dynamics of single organs responding to point signals fixed in space. Building on this we study pairs of organs interacting via allotropism, i.e. each organ senses signals emitted at the tip of their neighbor and responds accordingly. In the case of local sensing we find a rich state-space. We describe the different states, as well as the sharp transitions between them. We also find that the form of the state-space depends on initial conditions. This work sets the stage towards a theoretical framework for the investigation and understanding of systems of interacting growth-driven individuals.
Sediment accumulation expectations for growing desert cities: a realistic desired outcome to be used in constructing appropriately sized sediment storage of flood control structures
Authors: Jeong Ara
Published: July 2019

Many rapidly urbanizing desert cities (RUDC) around the globe experience an acute risk of flooding. To reduce this risk, properly engineered flood control structures (FCS) must account for sediment accumulation as well as flood waters. While the Phoenix area, USA, uses regional data from non-urban, non-desert watersheds to generate sediment yield rates, the proposed desired outcome for RUDCs is to base FCS on data related to urbanization. Wolman (1967 Geogr. Ann. A 49 385–95) recognized that sediment yields spike during a relatively short period of bare-ground exposure associated with urban growth, followed by surface sealing resulting in a great reduction in sediment yield. This research presents a new analysis of empirical data where two regression models provide estimates of a more realistic sediment accumulation for arid regions and also urbanization of a desert cities: (i) linear regression between drainage area and sediment yield based on a compilation of more than 150 global sediment yield data for warm desert (BWh Köppen‐Geiger) climate; and (ii) linear regression relating percent urban growth with sediment yield using available data on urbanization-generated sediment associated with growth of a desert city. The new model can be used to predict the realistic sediment accumulation for helping provide data where few data exists in urbanizing parts of arid Africa, southwest Asia, and India.
Riverine plastic emission from Jakarta into the ocean
Authors: van Emmerik Tim , Loozen Michelle , van Oeveren Kees , Buschman Frans , Prinsen Geert
Published: July 2019

Plastic pollution in aquatic environments is an increasing global risk. In recent years, marine plastic pollution has been studied to a great extent, and it has been hypothesized that land-based plastics are its main source. Global modeling efforts have suggested that rivers in South East Asia are in fact the main contributors to plastic transport from land to the oceans. However, due to a lack of plastic transport observations, the origin and fate of riverine plastic waste is yet unclear. Here, we present results from a first assessment of riverine macroplastic emission from rivers and canals that run through a densely populated coastal urban city. Using a combination of field measurements, empirical relations and hydraulic modeling, we provide an estimate of total riverine plastic export originating from Jakarta, Indonesia, into the ocean. Furthermore, we provide insights in its composition, and variation in time and space. We found that most macroplastics in Jakarta consists of films and foils. We estimate that 2.1 × 103 tonnes of plastic waste, is transported from land to sea annually, equaling 3% of the total annual unsoundly disposed plastic waste in the Jakarta area.
Molecular signal communication during arbuscular mycorrhizal formation induces significant transcriptional reprogramming of wheat (Triticum aestivum) roots
Authors: Tian Hui , Wang Runze , Li Mengjiao , Dang Haiyan , Solaiman Zakaria M
Published: July 2019

Background and Aims

Arbuscular mycorrhizal (AM) symbiosis begins with molecular signal communication (MSC) between AM fungi and the roots of the host plant. We aimed to test the hypothesis that the transcriptional profiles of wheat roots can be changed significantly by AM symbiotic signals, without direct contact.

Methods

Non-mycorrhizal (NM) and MSC treatments involved burying filter membrane bags containing sterilized and un-sterilized inoculum of the AM fungus Rhizophagus irregularis, respectively. The bags physically separated roots and AM structures but allowed molecular signals to pass through. Extracted RNA from wheat roots was sequenced by high-throughput sequencing.

Results

Shoot total nitrogen and phosphorus content of wheat plants was decreased by the MSC treatment. A total of 2360 differentially expressed genes (DEGs), including 1888 up-regulated DEGs and 472 down-regulated DEGs, were found dominantly distributed on chromosomes 2A, 2B, 2D, 3B, 5B and 5D. The expression of 59 and 121 genes was greatly up- and down-regulated, respectively. Only a portion of DEGs could be enriched into known terms during gene ontology analysis, and were mostly annotated to ‘catalytic activity’, ‘protein metabolic process’ and ‘membrane’ in the molecular function, biological process and cellular component ontology categories, respectively. More than 120 genes that may be involved in key processes during AM symbiosis development were regulated at the pre-physical contact stages.

Conclusions

The transcriptional profiles of wheat roots can be changed dramatically by MSC. Much of the information provided by our study is of great importance for understanding the mechanisms underlying the development of AM symbiosis.
A comprehensive review and evaluation of computational methods for identifying protein complexes from protein–protein interaction networks
Authors: Wu Zhourun , Liao Qing , Liu Bin
Published: July 2019

Protein complexes are the fundamental units for many cellular processes. Identifying protein complexes accurately is critical for understanding the functions and organizations of cells. With the increment of genome-scale protein–protein interaction (PPI) data for different species, various computational methods focus on identifying protein complexes from PPI networks. In this article, we give a comprehensive and updated review on the state-of-the-art computational methods in the field of protein complex identification, especially focusing on the newly developed approaches. The computational methods are organized into three categories, including cluster-quality-based methods, node-affinity-based methods and ensemble clustering methods. Furthermore, the advantages and disadvantages of different methods are discussed, and then, the performance of 17 state-of-the-art methods is evaluated on two widely used benchmark data sets. Finally, the bottleneck problems and their potential solutions in this important field are discussed.
Computational approaches to therapeutic antibody design: established methods and emerging trends
Authors: Norman Richard A , Ambrosetti Francesco , Bonvin Alexandre M J J , Colwell Lucy J , Kelm Sebastian , Kumar Sandeep , Krawczyk Konrad
Published: July 2019

Antibodies are proteins that recognize the molecular surfaces of potentially noxious molecules to mount an adaptive immune response or, in the case of autoimmune diseases, molecules that are part of healthy cells and tissues. Due to their binding versatility, antibodies are currently the largest class of biotherapeutics, with five monoclonal antibodies ranked in the top 10 blockbuster drugs. Computational advances in protein modelling and design can have a tangible impact on antibody-based therapeutic development. Antibody-specific computational protocols currently benefit from an increasing volume of data provided by next generation sequencing and application to related drug modalities based on traditional antibodies, such as nanobodies. Here we present a structured overview of available databases, methods and emerging trends in computational antibody analysis and contextualize them towards the engineering of candidate antibody therapeutics.
DeePaC: predicting pathogenic potential of novel DNA with reverse-complement neural networks
Authors: Bartoszewicz Jakub M , Seidel Anja , Rentzsch Robert , Renard Bernhard Y
Published: July 2019

Motivation

We expect novel pathogens to arise due to their fast-paced evolution, and new species to be discovered thanks to advances in DNA sequencing and metagenomics. Moreover, recent developments in synthetic biology raise concerns that some strains of bacteria could be modified for malicious purposes. Traditional approaches to open-view pathogen detection depend on databases of known organisms, which limits their performance on unknown, unrecognized and unmapped sequences. In contrast, machine learning methods can infer pathogenic phenotypes from single NGS reads, even though the biological context is unavailable.

Results

We present DeePaC, a Deep Learning Approach to Pathogenicity Classification. It includes a flexible framework allowing easy evaluation of neural architectures with reverse-complement parameter sharing. We show that convolutional neural networks and LSTMs outperform the state-of-the-art based on both sequence homology and machine learning. Combining a deep learning approach with integrating the predictions for both mates in a read pair results in cutting the error rate almost in half in comparison to the previous state-of-the-art.

Availability and implementation

The code and the models are available at: https://gitlab.com/rki_bioinformatics/DeePaC.

Supplementary information

Supplementary data are available at Bioinformatics online.
In vitro reconstitution of germ cell development†
Authors: Hayashi Katsuhiko
Published: July 2019

Germ cell development is a series of highly specialized processes through which diploid pluripotent cells differentiate into haploid gametes. The processes include biologically important events such as epigenetic reprogramming, sex determination, and meiosis. The mechanisms underlying these events are key issues in reproductive and developmental biology, yet they still remain elusive. As a tool to elucidate these mechanisms, in vitro gametogenesis, which reproduces germ cell development in culture, has long been sought for decades. Recently, methods of in vitro gametogenesis have undergone rapid development in association with stem cell biology, opening many possibilities in this field. This new technology is considered an alternative source of gametes for the reproduction of animals and perhaps humans. This review summarizes current advances and problems in in vitro gametogenesis.
Aminophylline and progesterone prevent inflammation-induced preterm parturition in the mouse†
Authors: Herbert Bronwen R , Markovic Danijela , Georgiou Ektoras , Lai Pei F , Singh Natasha , Yulia Angela , Johnson Mark R
Published: July 2019

Although progesterone (P4) supplementation is the most widely used therapy for the prevention of preterm labor (PTL), reports of its clinical efficacy have been conflicting. We have previously shown that the anti-inflammatory effects of P4 can be enhanced by increasing intracellular cyclic adenosine monophosphate (cAMP) levels in primary human myometrial cells. Here, we have examined whether adding aminophylline (Am), a non-specific phosphodiesterase inhibitor that increases intracellular cAMP levels, to P4 might improve its efficacy using in vivo and in vitro models of PTL. In a mouse model of lipopolysaccharide (LPS)-induced PTL, we found that the combination of P4 and Am delayed the onset of LPS-induced PTL, while the same dose of P4 and Am alone had no effect. Pup survival was not improved by either agent alone or in combination. Myometrial prolabor and inflammatory cytokine gene expression was reduced, but the reduction was similar in P4 and P4/Am treated mice. There was no effect of the combination of P4 and Am on an ex vivo assessment of myometrial contractility. In human myometrial cells and myometrial tissue explants, we found that the combination had marked anti-inflammatory effects, reducing cytokine and COX-2 mRNA and protein levels to a greater extent than either agent alone. These data suggest that the combination of P4 and Am has a more potent anti-inflammatory effect than either agent alone and may be an effective combination in women at high-risk of PTL.
Oxidative stress-induced downregulation of glycogen synthase kinase 3 beta in fetal membranes promotes cellular senescence†
Authors: Lavu Narmada , Richardson Lauren , Radnaa Enkhtuya , Kechichian Talar , Urrabaz-Garza Rheanna , Sheller-Miller Samantha , Bonney Elizabeth , Menon Ramkumar
Published: July 2019

Objective

Oxidative stress (OS)-induced stress signaler p38 mitogen-activated protein kinase (p38MAPK) activation and fetal membrane senescence are associated with parturition. This study determined changes in glycogen synthase kinase 3 beta (GSK3β) and its regulation by p38MAPK in effecting senescence to further delineate the molecular mechanism involved in senescence.

Methods

Primary human amnion epithelial cells and amnion mesenchymal cells were treated with cigarette smoke extract (CSE, OS inducer). Expression of total and phosphorylated GSK3β and p38MAPK, and that of GSK3β’s downstream targets: beta-catenin (β-Cat) and nuclear factor erythroid 2-related factor 2 (Nrf2) (western blot analysis), cell cycle regulation and senescence (flow cytometry) were determined. The specificity of GSK3β and p38MAPK’s mechanistic role was tested by co-treating cells with their respective inhibitors, CHIR99021 and SB203580. Exosomal secretion of β-Cat from OS-induced cells was confirmed by immunofluorescence confocal microscopy and western blot.

Results

OS induced by CSE resulted in phosphorylation of GSK3β (inactivation) and p38MAPK (activation) that was associated with cell cycle arrest and senescence. Inhibitors to GSK3β and p38MAPK verified their roles. Glycogen synthase kinase 3 beta inactivation was associated with nuclear translocation of antioxidant Nrf2 and exosomal secretion of β-Cat.

Conclusions

OS-induced P-p38MAPK activation is associated with functional downregulation of GSK3β and arrest of cell cycle progression and senescence of amnion cells. Lack of nuclear translocation of β-Cat and its excretion via exosomes further supports the postulation that GSK3β down-regulation by p38MAPK may stop cell proliferation preceding cell senescence. A better understanding of molecular mechanisms of senescence will help develop therapeutic strategies to prevent preterm birth.
Sustainability of Handshake Stewardship: Extending a Hand Is Effective Years Later
Authors: MacBrayne Christine E , Williams Manon C , Levek Claire , Child Jason , Pearce Kelly , Birkholz Meghan , Todd James K , Hurst Amanda L , Parker Sarah K
Published: July 2019

Background

Children’s Hospital Colorado created a unique method of antimicrobial stewardship, called handshake stewardship, that effectively decreased hospital anti-infective use and costs in its pilot year (2013). Handshake stewardship is distinguished by: (1) the lack of prior authorization; (2) a review of all prescribed anti-infectives; (3) a shared review by the physician and the pharmacist; and (4) a daily, rounding-based, in-person approach to supporting providers. We sought to reevaluate the outcomes of the program after 5 years of experience, totaling 8 years of data.

Methods

We retrospectively measured anti-infective (antibiotic, antiviral, antifungal) use hospital-wide by unit and by drug for an 8-year period spanning October 2010 to October 2018. Aggregated monthly use was measured in days of therapy per thousand patient days (DOT/1000 PD). The percentage of children admitted ever receiving an anti-infective was also measured, as well as severity-adjusted mortality, readmissions, and lengths of stay.

Results

Hospital-wide mean anti-infective use significantly decreased, from 891 (95% confidence interval [CI] 859–923) in the pre-implementation phase to 655 (95% CI 637–694) DOT/1000 PD in post-implementation Year 5; in a segmented regression time series analysis, this was a rate of -2.6 DOT/1000 PD (95% CI -4.8 to -0.4). This is largely attributable to decreased antibacterial use, from 704 (95% CI 686–722) to 544 (95% CI 525 –562) DOT/1000 PD. The percentage of children ever receiving an anti-infective during admission likewise declined, from 65% to 52% (95% CI 49–54). There were no detrimental effects on severity adjusted mortality, readmissions, or lengths of stay.

Conclusions

The handshake method is an effective and sustainable approach to stewardship.
Anemia and iron deficiency among chronic kidney disease Stages 3–5ND patients in the Chronic Kidney Disease Outcomes and Practice Patterns Study: often unmeasured, variably treated
Authors: Wong Michelle M Y , Tu Charlotte , Li Yun , Perlman Rachel L , Pecoits-Filho Roberto , Lopes Antonio A , Narita Ichiei , Reichel Helmut , Port Friedrich K , Sukul Nidhi , Stengel Benedicte , Robinson Bruce M , Massy Ziad A , Pisoni Ronald L ,   the CKDopps Investigators, Combe Christian , Jacquelinet Christian , Ayav Carole , Briançon Serge , Fouque Denis , Frimat Luc , Laville Maurice , Pascal Christophe , Herpe Yves-Edouard , Lange Céline , Legrans Karine , Liabeuf Sophie , Metzger Marie , Speyer Elodie , Combe Christian , Jacquelinet Christian , Ayav Carole , Briançon Serge , Fouque Denis , Frimat Luc , Laville Maurice , Pascal Christophe , Herpe Yves-Edouard , Lange Céline , Legrans Karine , Liabeuf Sophie , Metzger Marie , Speyer Elodie
Published: July 2019

Background

International variation in anemia assessment and management practices in chronic kidney disease (CKD) is poorly understood.

Methods

We performed a cross-sectional analysis of anemia laboratory monitoring, prevalence and management in the prospective Chronic Kidney Disease Outcomes and Practice Patterns Study (CKDopps). A total of 6766 participants with CKD Stages 3a–5ND from nephrology clinics in Brazil, France, Germany and the USA were included.

Results

Among patients with anemia (hemoglobin <12 g/dL), 36–58% in Brazil, the USA and Germany had repeat hemoglobin measured and 40–61% had iron indices measured within 3 months of the index hemoglobin measurement. Anemia was more common in the USA and Brazil than in France and Germany across CKD stages. Higher ferritin and lower iron saturation (TSAT) levels were observed with lower hemoglobin levels, and higher ferritin with more advanced CKD. The proportion of anemic patients with ferritin <100 ng/mL or TSAT <20% ranged from 42% in Brazil to 53% in France and Germany, and of these patients, over 40% in Brazil, Germany and the USA, compared with 27% in France, were treated with oral or intravenous iron within 3 months after hemoglobin measurement. The proportion of patients with hemoglobin <10 g/dL treated with erythropoiesis-stimulating agents ranged from 28% in the USA to 57% in Germany.

Conclusions

Hemoglobin and iron stores are measured less frequently than per guidelines. Among all regions, there was a substantial proportion of anemic patients with iron deficiency who were not treated with iron, highlighting an area for practice improvement in CKD care.
Podocyte and tubular involvement in AngioJet-induced kidney injury
Authors: Esteras Raquel , Cannata-Ortiz Pablo , Palacio-Tamarit Marta del , Guerrero-Hue Melania , García-Caballero Cristina , Egido Jesús , Gimeno Javier , Ortiz Alberto , Gracia-Iguacel Carolina , Moreno Juan Antonio
Published: July 2019

The AngioJet technique combines localized thrombolysis and percutaneous mechanical thrombectomy (PMT). However, PMT may cause acute kidney injury (AKI), which has been ascribed to severe mechanical haemolysis, although no renal biopsies have been reported. We now report the first renal biopsy in a patient with AKI following PMT. There is histological evidence of haemoglobin (Hb)-induced tubular injury and podocyte stress characterized by intracellular Hb and staining for ferritin and hemo-oxygenase-1, suggestive of an adaptive response to oxidative stress. This confirms that Hb is involved in kidney cell injury and supports the existence of several different kidney cellular targets.
The age of randomized clinical trials: three important aspects of randomized clinical trials in cardiovascular pharmacotherapy with examples from lipid and diabetes trials
Authors: Drexel Heinz , Rosano Giuseppe M C , Lewis Basil S , Huber Kurt , Vonbank Alexander , Dopheide Jörn F , Mader Arthur , Niessner Alexander , Savarese Gianluigi , Wassmann Sven , Agewall Stefan
Published: July 2019

Randomized clinical trials (RCTs) are important and the Gold Standard for drugs in modern cardiovascular (CV) therapy. The cornerstone of RCTs is the recording of hard clinical endpoints instead of surrogates. It is important to select an appropriate endpoint. Efficacy endpoints must be clinically relevant and can be hierarchically divided. A very interesting innovation in endpoint acquisition is the total event paradigm.
Autism and psychosis as diametrical disorders of embodiment
Authors: Crespi Bernard , Dinsdale Natalie
Published: July 2019

Humans have evolved an elaborate system of self-consciousness, self-identity, self-agency, and self-embodiment that is grounded in specific neurological structures including an expanded insula. Instantiation of the bodily self has been most-extensively studied via the ‘rubber hand illusion’, whereby parallel stimulation of a hidden true hand, and a viewed false hand, leads to the felt belief that the false hand is one’s own. Autism and schizophrenia have both long been regarded as conditions centrally involving altered development of the self, but they have yet to be compared directly with regard to the self and embodiment. Here we synthesize the embodied cognition literature for these and related conditions, and describe evidence that these two sets of disorders exhibit opposite susceptibilities from typical individuals to the rubber hand illusion: reduced on the autism spectrum and increased in schizophrenia and other psychotic-affective conditions. Moreover, the opposite illusion effects are mediated by a consilient set of associated phenomena, including empathy, interoception, anorexia risk and phenotypes, and patterns of genetic correlation. Taken together, these findings: (1) support the diametric model of autism and psychotic-affective disorders, (2) implicate the adaptive human system of self-embodiment, and its neural bases, in neurodevelopmental disorders, and suggest new therapies, and (3) experimentally-ground bayesian predictive coding models with regard to autism compared to psychosis.
Microbial communities in a dynamic in vitro model for the human ileum resemble the human ileal microbiota
Authors: Stolaki Maria , Minekus Mans , Venema Koen , Lahti Leo , Smid Eddy J , Kleerebezem Michiel , Zoetendal Erwin G
Published: July 2019

The important role for the human small intestinal microbiota in health and disease has been widely acknowledged. However, the difficulties encountered in accessing the small intestine in a non-invasive way in healthy subjects have limited the possibilities to study its microbiota. In this study, a dynamic in vitro model that simulates the human ileum was developed, including its microbiota. Ileostomy effluent and fecal inocula were employed to cultivate microbial communities within the in vitro model. Microbial stability was repetitively achieved after 10 days of model operation with bacterial concentrations reaching on average 107 to 108 16S rRNA copy numbers/ml. High diversities similar to those observed in in vivo ileum samples were achieved at steady state using both fecal and ileostomy effluent inocula. Functional stability based on Short Chain Fatty Acid concentrations was reached after 10 days of operation using fecal inocula, but was not reached with ileostomy effluent as inoculum. Principal Components and cluster analysis of the phylogenetic profiles revealed that in vitro samples at steady state clustered closest to two samples obtained from the terminal ileum of healthy individuals, independent of the inoculum used, demonstrating that the in vitro microbiota at steady state resembles that of the human ileum.
The Power of Mantis Shrimp Strikes: Interdisciplinary Impacts of an Extreme Cascade of Energy Release
Authors: Patek S N
Published: July 2019

In the course of a single raptorial strike by a mantis shrimp (Stomatopoda), the stages of energy release span six to seven orders of magnitude of duration. To achieve their mechanical feats of striking at the outer limits of speeds, accelerations, and impacts among organisms, they use a mechanism that exemplifies a cascade of energy release—beginning with a slow and forceful, spring-loading muscle contraction that lasts for hundreds of milliseconds and ending with implosions of cavitation bubbles that occur in nanoseconds. Mantis shrimp use an elastic mechanism built of exoskeleton and controlled with a latching mechanism. Inspired by both their mechanical capabilities and evolutionary diversity, research on mantis shrimp strikes has provided interdisciplinary and fundamental insights to the fields of elastic mechanisms, fluid dynamics, evolutionary dynamics, contest dynamics, the physics of fast, small systems, and the rapidly-expanding field of bioinspired materials science. Even with these myriad connections, numerous discoveries await, especially in the arena of energy flow through materials actuating and controlling fast, impact fracture resistant systems.
Using a two-sample Mendelian randomization design to investigate a possible causal effect of maternal lipid concentrations on offspring birth weight
Authors: Hwang Liang-Dar , Lawlor Deborah A , Freathy Rachel M , Evans David M , Warrington Nicole M
Published: July 2019

Background

The intrauterine environment is critical for fetal growth and development. However, observational associations between maternal gestational lipid concentrations and offspring birth weight (BW) have been inconsistent and ascertaining causality is challenging.

Methods

We used a novel two-sample Mendelian randomization (MR) approach to estimate the causal effect of maternal gestational high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglyceride concentrations on offspring BW. Single nucleotide polymorphisms (SNPs) associated with serum HDL-C, LDL-C and triglyceride concentrations identified in the Global Lipids Genetics Consortium genome-wide association study meta-analysis (n = 188 577 European-ancestry individuals; sample 1) were selected as instrumental variables. The effects of these SNPs on offspring BW were estimated using a structural equation model in the UK Biobank and Early Growth Genetics consortium (n = 230 069 European-ancestry individuals; sample 2) that enabled partitioning of the genetic associations into maternal- (intrauterine) and fetal-specific effects.

Results

We found no evidence for a causal effect of maternal gestational HDL-C, LDL-C or triglyceride concentrations on offspring BW [standard deviation change in BW per standard deviation higher in HDL-C = −0.005 (95% confidence interval: −0.039, 0.029), LDL-C = 0.014 (−0.017, 0.045), and triglycerides = 0.014 (−0.025, 0.052)].

Conclusions

Our findings suggest that maternal gestational HDL-C, LDL-C and triglyceride concentrations play a limited role in determining offspring BW. However, we cannot comment on the impact of these and other lipid fractions on fetal development more generally. Our study illustrates the power and flexibility of two-sample MR in assessing the causal effect of maternal environmental exposures on offspring outcomes.