bluuebunny/crossref_metadata_2025 huggingface dataset:
VSC HVDC active damping for the Sylwin 1 offshore wind power plants
Authors: Hernandez Manchola Alvaro , Priebe Torsten , Hölzer Michael , Dommaschk Mike
Published: May 2019

SylWin1 is a VSC HVDC link connecting 864 MW offshore wind power generation to Germany's high voltage network. This paper presents a harmonic performance analysis of the offshore network carried out during the design and commissioning phase with a focus on the distortions at the 155 kV and 33 kV offshore networks caused by the amplification of harmonics generated by the HVDC and wind turbine converters. Low frequency harmonic amplification problems are mitigated by introducing active damping in the HVDC converter controls in order to achieve a cost effective solution with the aim of reducing offshore harmonic current and voltage distortions. The analysis was carried out with the help of detailed frequency domain model offline simulations of the offshore network and on‐site measurements.
First resolved observations of a highly asymmetric debris disc around HD 160305 with VLT/SPHERE
Authors: Perrot Clément , Thebault Philippe , Lagrange Anne-Marie , Boccaletti Anthony , Vigan Arthur , Desidera Silvano , Augereau Jean-Charles , Bonnefoy Mickael , Choquet Élodie , Kral Quentin , Loh Alan , Maire Anne-Lise , Ménard François , Messina Sergio , Olofsson Johan , Gratton Raffaele , Biller Beth , Brandner Wolfgang , Buenzli Esther , Chauvin Gaël , Cheetham Anthony , Daemgen Sebastien , Delorme Philippe , Feldt Markus , Lagadec Eric , Langlois Maud , Lannier Justine , Mesa Dino , Mouillet David , Peretti Sébastien , Janin-Potiron Pierre , Salter Graeme , Sissa Elena , Roux Alain , Llored Marc , Buey Jean-Tristan , Pavlov Alexei , Weber Luc , Petit Cyril
Published: May 2019

Context. Direct imaging of debris discs gives important information about their nature, their global morphology, and allows us to identify specific structures possibly in connection with the presence of gravitational perturbers. It is the most straightforward technique to observe planetary systems as a whole.

Aims. We present the first resolved images of the debris disc around the young F-type star HD 160305, detected in scattered light using the VLT/SPHERE instrument in the near infrared.

Methods. We used a post-processing method based on angular differential imaging and synthetic images of debris discs produced with a disc modelling code (GRaTer) to constrain the main characteristics of the disc around HD 160305. All of the point sources in the field of the IRDIS camera were analysed with an astrometric tool to determine whether they are bound objects or background stars.

Results. We detect a very inclined (~82°) ring-like debris disc located at a stellocentric distance of about 86 au (deprojected width ~27 au). The disc displays a brightness asymmetry between the two sides of the major axis, as can be expected from scattering properties of dust grains. We derive an anisotropic scattering factor g > 0.5. A second right-left asymmetry is also observed with respect to the minor axis. We measure a surface brightness ratio of 0.73 ± 0.18 between the bright and the faint sides. Because of the low signal-to-noise ratio (S/N) of the images we cannot easily discriminate between several possible explanations for this left-right asymmetry, such as perturbations by an unseen planet, the aftermath of the breakup of a massive planetesimal, or the pericenter glow effect due to an eccentric ring. Two epochs of observations allow us to reject the companionship hypothesis for the 15 point sources present in the field.
Pituitary Disease in Pregnancy: Special Aspects of Diagnosis and Treatment?
Authors: Petersenn Stephan , Christ-Crain Mirjam , Droste Michael , Finke Reinhard , Flitsch Jörg , Kreitschmann-Andermahr Ilonka , Luger Anton , Schopohl Jochen , Stalla Günter
Published: May 2019

The diagnosis and treatment of pituitary disease in pregnancy represents a special clinical challenge. Not least because there is very little data on the treatment of pregnant patients with pituitary disorders. A selective search of the literature was carried out with the aim of compiling evidence about the diagnosis and treatment of pituitary disease in pregnancy. The search covered the databases PubMed/MEDLINE including PubMed Central and also used the Livivo (ZB MED) search engine. Recent studies were evaluated for recommendations about the care of pregnant patients with hormone-inactive and hormone-active pituitary adenomas (prolactinoma, acromegaly and Cushingʼs disease), pituitary insufficiency, pituitary apoplexy and hypophysitis. The most well-established forms of treatment are for prolactinoma, due to the incidence of this disease and its impact on fertility. When pregnancy has been confirmed, prolactinoma treatment with dopamine agonists should be paused. Although microprolactinomas rarely increase significantly in size after the administration of dopamine agonists is discontinued, symptomatic tumor growth of macroprolactinomas can occur. In such cases, treatment with dopamine agonists can be resumed. If the primary tumor is large and the risk that it will continue to grow is high, it may be necessary to continue medical treatment from the start of pregnancy. If one of the partners has a pituitary disorder, it is often still possible for many couples to achieve their wish of having children if they receive medical support to plan and the pregnancy is carefully monitored. Given the complexity of pituitary disease, pregnant patients with pituitary disorders should be cared for and treated by a multidisciplinary team in centers specializing in the diagnosis and treatment of pituitary disease.
Die Verordnungen bei Asthma und COPD in Deutschland für die Jahre 2007, 2010, 2013, 2015 – 2017
Authors: Hausen T.
Published: May 2019

Aus den Verordnungszahlen einer statistisch relevanten Zahl von Hausärzten, Internisten und Pneumologen wurden die Zahlen der wichtigsten Substanzen/Substanzkombinationen für die Therapie bei Asthma und COPD extrahiert und analysiert.

Die Verordnungszahlen über 10 Jahre belegen eine Zunahme von Präparaten mit inhalativer Applikationsform und eine Abnahme oral zu applizierender Präparate bei der Therapie von Asthma und COPD.

Beim Asthma ist eine deutliche Zunahme antientzündlicher Pharmaka bei gleichzeitiger Abnahme von kurzwirksamen Beta-Agonisten zu beobachten. Die Verordnungen von kurzwirksamen Beta-Agonisten nehmen im Verhältnis zu und die von kurzwirksamen Muscarin-Antagonisten und kurzwirksamen Beta-Agonisten/kurzwirksamen Muscarin-Antagonisten ab.

Bei der COPD belegen die Verordnungszahlen eine deutliche Zunahme für langwirksame Bronchodilatatoren und eine leichte Tendenz zur Abnahme von ICS-haltigen Präparaten. Letztere fällt aber so gering aus, dass unverändert eine erhebliche Übertherapie mit ICS bei der COPD zu befürchten ist. Die Verordnungen von kurzwirksamen Bronchodilatatoren steigen leicht an zu Ungunsten von kurzwirksamen Beta-Agonisten, und es gibt einen Rückgang von Verordnungen von kurzwirksamen Muscarin-Antagonisten und kurzwirksamen Beta-Agonisten/kurzwirksamen Muscarin-Antagonisten.
Epidemiologie, Klinik, Diagnostik und Therapie von Infektionen durch Mycobacterium chimaera
Authors: Becker S. L. , Schlotthauer U. , Schäfers H.-J. , Bals R. , Trudzinski F. C.
Published: May 2019

Die Erkennung, Diagnosestellung und Behandlung von Infektionen durch atypische Mykobakterien stellen eine besondere klinische Herausforderung dar. Über invasive Erkrankungen durch das zum Mycobacterium avium-intracellulare complex gehörige Mycobacterium chimaera wurde in den letzten Jahren vermehrt berichtet, insbesondere bei Patienten nach kardiochirurgischen Operationen mit Thorakotomie. Es konnte nachgewiesen werden, dass diese Infektionen durch eine intraoperative, Aerosol-gebundene Übertragung des Pathogens über kontaminierte Hypothermiegeräte (Heater-Cooler-Units), die zum Betrieb von Herz-Lungen-Maschinen eingesetzt werden, zu erklären waren. Es handelt sich dabei um ein weltweites Ausbruchsgeschehen mit bisher etwa 120 diagnostizierten Fällen, wobei die Latenz zwischen Exposition und dem Auftreten erster Symptome häufig mehrere Jahre beträgt. Das klinische Bild einer M. chimaera-Infektion ist mannigfaltig und kann neben Endokarditis oder Implantat-assoziierten Prozessen auch mit nicht kardialer Manifestation (z. B. Sarkoidose-ähnliches Krankheitsbild, Spondylodiscitis, Chorioretinitis) einhergehen. Die Diagnosestellung erfolgt über den Erregernachweis aus speziellen Blutkulturen oder intraoperativen Gewebeproben, insofern eine spezifische mikrobiologische Testung auf Mykobakterien angefordert wird. Ein noninvasives Testverfahren steht nicht zur Verfügung, sodass bei entsprechender Exposition bei Patienten mit passender Klinik aktiv an diese Erkrankung gedacht werden sollte. Die Behandlung von M. chimaera-Infektionen erfordert neben der Entfernung infizierter Implantate eine prolongierte antimykobakterielle Kombinationstherapie. Dieser Übersichtsartikel stellt die aktuelle Bedeutung, Epidemiologie, klinische Symptomatik, Diagnostik und Therapie von M. chimaera-Infektionen für Pneumologen zusammenfassend dar.
Optical edge detection based on high-efficiency dielectric metasurface
Authors: Zhou Junxiao , Qian Haoliang , Chen Ching-Fu , Zhao Junxiang , Li Guangru , Wu Qianyi , Luo Hailu , Wen Shuangchun , Liu Zhaowei
Published: May 2019

Significance

Edge detection is a fundamental tool in image processing, computing, and machine vision. Compared with digital processes, optical analog approaches show enormous advantages owing to its intrinsic parallel nature for high-speed operation. Recently, optical metamaterials and metasurfaces have performed edge detection via analog spatial differentiation, which shows superior integration capability compared with the traditional bulky system. Unfortunately, experimental realization of optical-edge detection with metamaterials and metasurfaces remains challenging based on previous theoretical proposals. Here, we demonstrated a mechanism to realize an optical spatial differentiator consisting of a designed metasurface sandwiched by two orthogonally aligned linear polarizers. This approach relies on spin-orbit interaction of light and the metasurface, showing versatile edge-detection capability with exceptional quality.
Microsecond and millisecond dynamics in the photosynthetic protein LHCSR1 observed by single-molecule correlation spectroscopy
Authors: Kondo Toru , Gordon Jesse B. , Pinnola Alberta , Dall’Osto Luca , Bassi Roberto , Schlau-Cohen Gabriela S.
Published: May 2019

Significance

Protein flexibility is essential for the robustness of biological systems, yet the dynamics underlying this flexibility are difficult to observe, because they are small, fast, and stochastic. Photoprotection in plants is critical for robust growth under highly variable sunlight, but the complexity of photosynthetic proteins means that identifying conformational states and dynamics responsible is challenging. Here, we develop a method using the correlation function of the fluorescence lifetime to characterize multiple dynamical processes in single proteins. By applying this method to the protein Light-Harvesting Complex Stress Related 1 (LHCSR1), we identify two local protein motions that control quenching of excess sunlight, which is a photoprotective effect. Our analytical approach enables a structure-based understanding of the photoprotective mechanisms in green plants.
Stabilizing the metastable superhard material wurtzite boron nitride by three-dimensional networks of planar defects
Authors: Chen Chunlin , Yin Deqiang , Kato Takeharu , Taniguchi Takashi , Watanabe Kenji , Ma Xiuliang , Ye Hengqiang , Ikuhara Yuichi
Published: May 2019

Significance

Metastable high-pressure materials often possess outstanding properties. However, the stabilization of metastable high-pressure materials usually is challenging due to the very low kinetic barrier for the transformation back to ambient phases. Wurtzite boron nitride (w-BN) is a metastable high-pressure polymorph of BN, which can only be fabricated as micrometer-size powders by the shock compression of hexagonal BN. Here, we fabricate millimeter-size w-BN bulk crystals and reveal an unprecedented stabilization mechanism for w-BN. We find that the metastable high-pressure phase can be stabilized by 3D networks of planar defects. Our findings unambiguously demonstrate the retarding effect of crystal defects on the phase transformations of metastable materials.
Concepts and tools for mechanism and selectivity analysis in synthetic organic electrochemistry
Authors: Costentin Cyrille , Savéant Jean-Michel
Published: May 2019

Significance

It seems opportune to accompany the present revival of synthetic organic electrochemistry by drawing attention of synthetic chemists to the heterogeneous nature of electrochemical reactions. Quantitative analysis of the successive layers in between working electrode and solution––electrical double layer, forced convection–diffusion layer, and reaction–diffusion layers––allows the mastering of the relationships between mechanism and product selectivity. The multiple connections between catalysis and electrochemical reactions are emphasized and illustrated by typical examples. Advantage is taken of the recent advances in activation of small molecules in response to modern energy and environment challenges with extension to synthetic organic electrochemical reactions.
Chaperone-mediated reflux of secretory proteins to the cytosol during endoplasmic reticulum stress
Authors: Igbaria Aeid , Merksamer Philip I. , Trusina Ala , Tilahun Firehiwot , Johnson Jeffrey R. , Brandman Onn , Krogan Nevan J. , Weissman Jonathan S. , Papa Feroz R.
Published: May 2019

Significance

Approximately one-third of eukaryotic proteins are synthesized on ribosomes attached to the endoplasmic reticulum (ER) membrane. Many of these polypeptides co- or posttranslationally translocate into the ER, wherein they fold and mature. An ER quality control system proofreads these proteins by facilitating their folding and modification, while eliminating misfolded proteins through ER-associated degradation (ERAD). Yet the fate of many secretory proteins during ER stress is not completely understood. Here, we uncovered an ER stress-induced “protein reflux” system that delivers intact, folded ER luminal proteins back to the cytosol without degrading them. We found that ER protein reflux works in parallel with ERAD and requires distinct ER-resident and cytosolic chaperones and cochaperones.
Are You Estimating the Right Thing? An Editor Reflects
Authors: Gibson John
Published: May 2019

A key aspect of applied economics over the last decade has been the status accorded to research designs that may credibly identify causal effects. Without such designs, one may not estimate the right thing and publishing options may be limited. Yet situations where reported results are not for parameters that researchers think they have identified are potentially more widespread than what is usually considered in discussion of research designs or identification strategies. I give five examples of applied practice where what is estimated may not identify what is wanted. Each practice came up in submissions I handled as co‐editor of an agricultural economics journal, and these issues seem common in applied work. A narrow focus on identification strategies may lead to the neglect of these examples, and of other productive ways to improve the credibility and usefulness of applied economics research.
Steps in the Tumen River
Authors: Song Nianshen
Published: May 2019

This article records my field experiences with the Tumen River, which forms the boundary between China and Korea. Based on my field notes at three different locations—the river mouth, where territories belonging to China, North Korea, and Russia adjoin; a small town midway along the river where pioneer Korean immigrants risked their lives to cross the border; and the “source” of the contemporary border in a dense mountain forest—my narrative links historical memories of the Tumen border from the seventeenth century to the present. The trips, which were taken over the course of thirteen years, urged me to inquire about and rethink the meaning of state borders from the perspective of local residents, trespassers, and the environment. The article questions the popular notion that boundaries are naturally formed, static, and always clearly defined. On the contrary, they are arbitrarily made, fluid, and often ambiguous. As my physical and intellectual journey along this river revealed the humanistic aspect of boundaries, I myself completed a transformation from journalist to historian.
Experimental ‘morphogenesis in miniature’ illuminates the evolution and development of pollen wall patterns. A commentary on: ‘Mimicking pollen and spore walls: self-assembly in action’
Authors: Blackmore Stephen
Published: May 2019

This article comments on:

Nina I. Gabarayeva, Valentina V. Grigorjeva and Alexey L. Shavarda. 2019. Mimicking pollen and spore walls: self-assembly in action. Annals of Botany 123(7): 1205–1218.
The effects of microhabitat specialization on mating communication in a wolf spider
Authors: Rosenthal Malcolm F , Hebets Eileen A , Kessler Benji , McGinley Rowan , Elias Damian O
Published: May 2019

Animal signals experience selection for detectability, which is determined in large part by the signal transmission properties of the habitat. Understanding the ecological context in which communication takes place is therefore critical to understanding selection on the form of communication signals. In order to determine the influence of environmental heterogeneity on signal transmission, we focus on a wolf spider species native to central Florida, Schizocosa floridana, in which males court females using a substrate-borne vibratory song. We test the hypothesis that S. floridana is a substrate specialist by 1) assessing substrate use by females and males in the field, 2) quantifying substrate-specific vibratory signal transmission in the laboratory, and 3) determining substrate-specific mating success in the laboratory. We predict a priori that 1) S. floridana restricts its signaling to oak litter, 2) oak litter best transmits their vibratory signal, and 3) S. floridana mates most readily on oak litter. We find that S. floridana is almost exclusively found on oak litter, which was found to attenuate vibratory courtship signals the least. Spiders mated with equal frequency on oak and pine, but did not mate at all on sand. Additionally, we describe how S. floridana song contains a novel component, chirps, which attenuate more strongly than its other display components on pine and sand, but not on oak, suggesting that the ways in which the environment relaxes restrictions on signal form may be as important as the ways in which it imposes them.
Consistency and overfitting of multi-omics methods on experimental data
Authors: McCabe Sean D , Lin Dan-Yu , Love Michael I
Published: May 2019

Knowledge on the relationship between different biological modalities (RNA, chromatin, etc.) can help further our understanding of the processes through which biological components interact. The ready availability of multi-omics datasets has led to the development of numerous methods for identifying sources of common variation across biological modalities. However, evaluation of the performance of these methods, in terms of consistency, has been difficult because most methods are unsupervised. We present a comparison of sparse multiple canonical correlation analysis (Sparse mCCA), angle-based joint and individual variation explained (AJIVE) and multi-omics factor analysis (MOFA) using a cross-validation approach to assess overfitting and consistency. Both large and small-sample datasets were used to evaluate performance, and a permuted null dataset was used to identify overfitting through the application of our framework and approach. In the large-sample setting, we found that all methods demonstrated consistency and lack of overfitting; however, in the small-sample size setting, AJIVE provided the most stable results. We provide an R package so that our framework and approach can be applied to evaluate other methods and datasets.
Statistical test of structured continuous trees based on discordance matrix
Authors: Bai Xiangqi , Ma Liang , Wan Lin
Published: May 2019

Motivation

Cell fate determination is a continuous process in which one cell type diversifies to other cell types following a hierarchical path. Advancements in single-cell technologies provide the opportunity to reveal the continuum of cell progression which forms a structured continuous tree (SCTree). Computational algorithms, which are usually based on a priori assumptions on the hidden structures, have previously been proposed as a means of recovering pseudo trajectory along cell differentiation process. However, there still lack of statistical framework on the assessments of intrinsic structure embedded in high-dimensional gene expression profile. Inherit noise and cell-to-cell variation underlie the single-cell data, however, pose grand challenges to testing even basic structures, such as linear versus bifurcation.

Results

In this study, we propose an adaptive statistical framework, termed SCTree, to test the intrinsic structure of a high-dimensional single-cell dataset. SCTree test is conducted based on the tools derived from metric geometry and random matrix theory. In brief, by extending the Gromov–Farris transform and utilizing semicircular law, we formulate the continuous tree structure testing problem into a signal matrix detection problem. We show that the SCTree test is most powerful when the signal-to-noise ratio exceeds a moderate value. We also demonstrate that SCTree is able to robustly detect linear, single and multiple branching events with simulated datasets and real scRNA-seq datasets. Overall, the SCTree test provides a unified statistical assessment of the significance of the hidden structure of single-cell data.

Availability and implementation

SCTree software is available at https://github.com/XQBai/SCTree-test.

Supplementary information

Supplementary data are available at Bioinformatics online.
Teleonomy and the proximate–ultimate distinction revisited
Authors: Corning Peter A
Published: May 2019

It is now widely accepted that living systems exhibit an internal teleology (or teleonomy), but there are conflicting views about how this should be interpreted. Colin Pittendrigh and others have defined teleonomy broadly. It encompasses all ‘proximate’ (functional) biological phenomena. In contrast, Ernst Mayr and others would limit teleonomy to an a priori ‘program’ (the genome) and exclude proximate phenomena. I argue that living systems exhibit an ex post facto, means–ends teleonomy. Purposiveness is also a property of proximate functional phenomena. Mayr’s definition would also discount the causal role of teleonomy in shaping differential survival, i.e. natural selection and evolution. Proximate and ‘ultimate’ (evolutionary) causes are deeply interpenetrated. Going forward, we must integrate the various domains of causation better.
Raising awareness of unspecified living kidney donation: an ELPAT* view
Authors: Burnapp Lisa , Van Assche Kristof , Lennerling Annette , Slaats Dorthe , Van Dellen David , Mamode Nizam , Citterio Franco , Zuidema Willij , Weimar Willem , Dor Frank J M F
Published: May 2019

Background

Living donor kidney transplantation (LDKT) is the preferred treatment for patients with end-stage renal disease and unspecified living kidney donation is morally justified. Despite the excellent outcomes of LDKT, unspecified kidney donation (UKD) is limited to a minority of European countries due to legal constraints and moral objections. Consequently, there are significant variations in practice and approach between countries and the contribution of UKD is undervalued. Where UKD is accepted as routine, an increasing number of patients in the kidney exchange programme are successfully transplanted when a ‘chain’ of transplants is triggered by a single unspecified donor. By expanding the shared living donor pool, the benefit of LDKT is extended to patients who do not have their own living donor because a recipient on the national transplant list always completes the chain. Is there a moral imperative to increase the scope of UKD and how could this be achieved?

Methods

An examination of the literature and individual country practices was performed to identify the limitations on UKD in Europe and recommend strategies to increase transplant opportunities.

Results

Primary limitations to UKD, key players and their roles and responsibilities were identified.

Conclusions

Raising awareness to encourage the public to volunteer to donate is appropriate and desirable to increase UKD. Recommendations are made to provide a framework for increasing awareness and engagement in UKD. The public, healthcare professionals, policy makers and society and religious leaders have a role to play in creating an environment for change.
Mechanical circulatory support with the Impella 5.0 and the Impella Left Direct pumps for postcardiotomy cardiogenic shock at La Pitié-Salpêtrière Hospital
Authors: David Charles-Henri , Quessard Astrid , Mastroianni Ciro , Hekimian Guillaume , Amour Julien , Leprince Pascal , Lebreton Guillaume
Published: May 2019

OBJECTIVES

Postcardiotomy cardiogenic shock (PCCS) is associated with high mortality rates of 50–80%. Although veno-arterial extracorporeal membrane oxygenation has been used as mechanical circulatory support in patients with PCCS, it is associated with a high rate of complications and poor quality of life. The Impella 5.0 and Impella Left Direct (LD) (Impella 5.0/LD) are minimally invasive left ventricular assist devices that provide effective haemodynamic support resulting in left ventricular unloading and systemic perfusion. Our goal was to describe the outcome of patients with PCCS supported with the Impella 5.0/LD at La Pitié-Salpêtrière Hospital.

METHODS

We retrospectively reviewed consecutive patients supported with the Impella 5.0/LD for PCCS between December 2010 and June 2015. Survival outcome and in-hospital complications were assessed.

RESULTS

A total of 29 patients (63 ± 14 years, 17% women) with PCCS were supported with the Impella 5.0/LD. At baseline, 69% experienced chronic heart failure, 66% had dilated cardiomyopathy and 57% had valvular disease. The mean EuroSCORE II was 22 ± 17 and the ejection fraction was 28 ± 11%. Most of the patients underwent isolated valve surgery (45%) or isolated coronary artery bypass grafting (38%). The mean duration of Impella support was 9 ± 7 days. Weaning from the Impella was successful in 72.4%, and 58.6% survived to discharge. Recovery of native heart function was observed in 100% of discharged patients. Survival to 30 days and to 1 year from Impella implant was 58.6% and 51.7%, respectively.

CONCLUSIONS

The Impella 5.0 and the Impella LD represent an excellent treatment option for critically ill patients with PCCS and are associated with favourable survival outcome and native heart recovery.
The Association of a Single-Nucleotide Polymorphism in the Nuclear Factor (Erythroid-Derived 2)-Like 2 Gene With Adverse Drug Reactions, Multimorbidity, and Frailty in Older People
Authors: Scutt Greg , Overall Andrew , Bakrania Prijay , Krasteva Eliseveta , Parekh Nikesh , Ali Khalid , Davies J Graham , Rajkumar Chakravarthi
Published: May 2019

Susceptibility to adverse drug reactions (ADRs), multimorbidity, and frailty are associated with human aging, yet there is wide variation in the severity and age at which individuals are afflicted. Identifying genetic markers of increased risk of this phenotype would help stratify individuals to specialist interventions. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) regulates a cell’s response to stressors, including the expression of enzymes involved in drug metabolism. Its expression has been shown to decline in animal aging models. In this study, we tested the hypothesis that Nrf2 gene (NFE2L2) transcription/translation decline in human aging and that single-nucleotide polymorphisms (SNPs) in the NFE2L2 gene are associated with increased ADR risk, multimorbidity, and frailty in older people. Gene expression and protein levels were measured in peripheral blood mononuclear cells donated from healthy patients aged 18–80 years old. NFE2L2 genotypes were determined at three loci in a subpopulation of patients recruited to the PRIME study (a multicenter prospective cohort study that followed older adults for 8 weeks post-discharge to determine ADR). Both NFE2L2 gene and Nrf2 protein expression declined significantly with age in human peripheral blood mononuclear cells. In the PRIME substudy population, the rs35652124 NFE2L2 SNP was associated with increased ADR risk and decreased frailty and multimorbidity scores.
P-Glycoprotein–Mediated Efflux Reduces the In Vivo Efficacy of a Therapeutic Targeting the Gastrointestinal Parasite Cryptosporidium
Authors: Arnold Samuel L M , Choi Ryan , Hulverson Matthew A , Whitman Grant R , Mccloskey Molly C , Dorr Carlie S , Vidadala Rama S R , Khatod Mansi , Morada Mary , Barrett Lynn K , Maly Dustin J , Yarlett Nigel , Van Voorhis Wesley C
Published: May 2019

Recent studies have illustrated the burden Cryptosporidium infection places on the lives of malnourished children and immunocompromised individuals. Treatment options remain limited, and efforts to develop a new therapeutic are currently underway. However, there are unresolved questions about the ideal pharmacokinetic characteristics of new anti-Cryptosporidium therapeutics. Specifically, should drug developers optimize therapeutics and formulations to increase drug exposure in the gastrointestinal lumen, enterocytes, or systemic circulation? Furthermore, how should researchers interpret data suggesting their therapeutic is a drug efflux transporter substrate? In vivo drug transporter–mediated alterations in efficacy are well recognized in multiple disease areas, but the impact of intestinal transporters on therapeutic efficacy against enteric diseases has not been established. Using multiple in vitro models and a mouse model of Cryptosporidium infection, we characterized the effect of P-glycoprotein efflux on bumped kinase inhibitor pharmacokinetics and efficacy. Our results demonstrated P-glycoprotein decreases bumped kinase inhibitor enterocyte exposure, resulting in reduced in vivo efficacy against Cryptosporidium. Furthermore, a hollow fiber model of Cryptosporidium infection replicated the in vivo impact of P-glycoprotein on anti-Cryptosporidium efficacy. In conclusion, when optimizing drug candidates targeting the gastrointestinal epithelium or gastrointestinal epithelial infections, drug developers should consider the adverse impact of active efflux transporters on efficacy.
Usefulness of a Novel System for Feedback of Patient-Reported Outcome Measures in Children Recovering From Burns
Authors: Riobueno-Naylor Alexa , Romo Stephanie , Kazis Lewis , Wang Shirley , Lydon Martha , Nelson Judith , Fowler Laura , Drexler Alana , Kogosov Ann , Haile Haregnesh , Ryan Colleen M , Chang Philip , Warner Petra , Palmieri Tina L , Lee Austin F , Stoddard Frederick , Murphy J Michael , Sheridan Robert L
Published: May 2019

The Burn Outcomes Questionnaire for children ages 5–18 years (BOQ5–18) is a widely used, reliable, and valid parent-reported outcome measure designed to assess children’s recovery from burn injuries in 12 physical and psychosocial domains. This study evaluated the feasibility, acceptability, and usefulness of a feedback system that delivered BOQ and Pediatric Symptom Checklist (PSC-17; a widely used measure of psychosocial functioning) results to burn care clinicians prior to an outpatient appointment or a postoperative surgical encounter. The BOQ and the PSC-17 were administered to the parents of 147 children receiving outpatient or surgical care in two pediatric burn hospitals. Clinician and parent perceptions of the feedback system were evaluated using debriefing questionnaires. Over half of all patients were at-risk on at least one BOQ subscale, and risk on three or more BOQ domains was significantly associated with a higher likelihood of poor psychological scores on the PSC-17 (P < .001). Significant differences in BOQ scores were found between the two hospital sites on four BOQ subscales, three related to physical ability and one to psychosocial well-being. Parent ratings of the feedback system were positive, with 90% of parents in both settings agreeing that the BOQ tablet experience was easy and helpful. Clinician attitudes differed across the two settings with more positive clinician ratings of the system in the outpatient setting (P < .001). Clinician interviews revealed that the data was especially useful in bringing to light psychosocial aspects of functioning relevant to long-term recovery from burn injuries.
Molecular Characterization of Primary Juvenile Hormone Responders Methoprene-Tolerant (Met) and Krüppel Homolog 1 (Kr-h1) in Grapholita molesta (Lepidoptera: Tortricidae) with Clarification of Their Roles in Metamorphosis and Reproduction
Authors: Zhang Jing , Liu Xiaoxia , Liu Yichen , An Yueqing , Fang Haibo , Michaud J P , Zhang Huaijiang , Li Yisong , Zhang Qingwen , Li Zhen
Published: May 2019

Methoprene-tolerant (Met) is a putative JH intracellular receptor that transduces JH signal by activation of the inducible Krüppel homolog 1 (Kr-h1). We analyzed the gene sequences of Met and Kr-h1 and their patterns of expression in Grapholita molesta (Busck) immature and adult stages in order to better understand the roles of these primary JH responders in regulating the metamorphosis and reproduction of this global pest of fruit crops. The deduced amino acid sequences of both GmMet and GmKr-h1 were highly homologous to those of other Lepidoptera, especially the cotton bollworm, Helicoverpa armigera (Hubner) (Lepidoptera: Noctuidae). Peak expression of GmMet occurred during the last 3 to 5 d of the final instar, followed by that of GmKr-h1, in the last 3 d of final instar. Similar patterns of GmMet and GmKr-h1 expression were detected across various tissue types in the fifth-instar larvae, with the highest expression observed in the head, followed by the epidermis, and the fat body. When expression of GmMet and GmKr-h1 was knocked down via dsRNA injection in the fifth instar, the results were increased larval mortality, abnormal pupation, delayed pupal duration, reduced adult emergence, extended preoviposition period, and reduced fecundity. We infer that both GmMet and GmKr-h1 participated in regulation of metamorphosis and reproduction in G. molesta, the former acting upstream of the latter, and could present biorational targets for novel pest control compounds.
Decaying Organic Matter Does Not Remove Sublethal Effects of Imidacloprid on Mating in Spalangia endius (Hymenoptera: Pteromalidae), a Parasitoid of Filth Flies
Authors: Kremer A N , King B H
Published: May 2019

Both the parasitoid wasp Spalangia endius Walker and the insecticide imidacloprid are used to control house flies. A recent study found that negative sublethal effects of imidacloprid on killing flies and on offspring production by this parasitoid wasp are eliminated when females have the opportunity to crawl through decaying matter. An enzyme-linked immunosorbent assay showed that the presence of decaying matter reduces the amount of pesticide on their bodies. This study examined whether this was also true for sublethal effects on mating. S. endius were exposed to a realistic concentration of imidacloprid that induces very low mortality. Then, individual parasitoids were allowed to burrow through decaying organic matter or not, followed by mating tests in the absence of decaying matter. Even after 24 h with the decaying matter, copulation for both males and females that had previously been exposed to imidacloprid was delayed compared with no-pesticide controls. Furthermore, for pesticide-exposed males, subsequently burrowing through media made copulation even more delayed than if they were not exposed to media. For pesticide-exposed females, subsequently burrowing through media neither increased or decreased the negative effect of the pesticide exposure. Together with other studies, these results reinforce that use of S. endius and use of imidacloprid are incompatible, even at much lower than recommended concentration, unless application is sufficiently separated in place and time.
Inferring Biological Control Potential of Adult Predatory Coccinellids Using Life History Traits and Putative Habitat Preference
Authors: Jalali M Amin , Mehrnejad M Reza , Ellsworth Peter C
Published: May 2019

Aspects of the nutritional ecology and life histories of five predatory coccinellids (Coleoptera: Coccinellidae)—two arboreal predator species, Oenopia conglobata contaminata (Menetries) and Adalia bipunctata (Linnaeus), and three herbaceous dwelling predator species, Coccinella undecimpunctata aegyptica (Reiche), Exochomus nigripennis (Erichson), and Hippodamia variegata (Goeze) (Coleoptera: Coccinellidae)—were compared when fed either Agonoscena pistaciae Burckhardt and Lauterer (Hemiptera: Aphalaridae), the key psylla pest of pistachio trees, or Aphis gossypii Glover (Hemiptera: Aphididae), a common aphid on herbaceous plants in pistachio orchards. The putative habitat preferences of four of the five coccinellids studied were consistent with their performance on the major herbivore present in those two habitats in terms of net reproductive rate. Oenopia conglobata contaminata and Ad. bipunctata showed higher net reproductive rates when fed on pistachio psylla prey, whereas C. undecimpunctata aegyptiaca and E. nigripennis had better reproductive output on aphid prey. Moreover, E. nigripennis was the most specialized of these generalist predators, eating more and reproducing better when fed aphids. Hippodamia variegata was relatively unaffected by the diet offered, suggesting greater ability to switch among herbivore prey and perhaps better potential as a biocontrol agent with abilities to exploit Ag. pistaciae without large life history tradeoffs.
Governance of the Global Financial System: The Legitimacy of the BCBS 10 years after the 2008 Crisis
Authors: Prieto Muñoz Jose Gustavo
Published: May 2019

This article explores the question of legitimacy that underpins Basel III. First, I present a general framework for assessing how legitimacy operates within the global financial system through an analysis of the internal and external dimensions. I next address the internal dimension, exploring the legitimacy of the Basel Committee on Banking Supervision (BCBS) as a body that exercises a type of public authority through the generation of norms/standards. I then analyse how the public law standards of transparency and accountability are currently being implemented within the BCBS system. Finally, I examine the external dimension, considering how the legitimacy of the BCBS is related to the international system. In particular, it is argued that because of the direct link between bailouts and human rights violations, the legitimacy of the BCBS is also tied to its role in promoting financial stability in the post-crisis architecture by protecting social rights within states.
Generic Ledipasvir-Sofosbuvir Treatment for Adolescents With Chronic Hepatitis C Virus Infection
Authors: Fouad Hanan M , Sabry Magda A , Ahmed Amal , Hassany Mohamed , Al Soda Mohamed F , Abdel Aziz Hossam
Published: May 2019

We assessed the safety and efficacy of a generic form of ledipasvir-sofosbuvir for the treatment of hepatitis C virus infection in Egyptian adolescents and compared the results with those of treatment with the brand-named form. The generic form resulted in a high response rate, significant improvement in liver function, and mild adverse effects. These results are comparable with those of the brand form at a reduced price.
Investigation of JAK2V617F Mutation Prevalence in Patients with Beta Thalassemia Major
Authors: Tahannejad Asadi Zari , Yarahmadi Reza , Saki Najmaldin , Jalali Mohammad Taha , Amin Asnafi Ali , Tangestani Raheleh
Published: May 2019

Background

Beta (β)–thalassemia major is a genetic disorder with anemia and an increased level of erythropoietin by Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathway. JAK plays an important role in cell signaling, and the common mutation in the JAK2 gene in myeloid disorders is called JAK2V617F.

Methods

A total of 75 patients with beta (β)-thalassemia major patients, including 34 males (45%) and 41 females (55%), were enrolled in this study. The presence of the JAK2V617F mutation was assessed using the amplification-refractory mutation–polymerase chain reaction (ARMS-PCR) technique.

Results

Among the 75 patients, 14 patients (19%) tested positive and 61 patients (81%) tested negative for JAK2V617F mutation. We observed no statistically significant difference in sex, age, genotype, and JAK2V617F mutation among patients (P> .05). However, a significant difference between blood-transfusion frequency and JAK2V617F mutation was observed (P <.05).

Conclusion

Due to the low prevalence of JAK2V617F mutation in thalassemia, using a larger population of the patients to investigate this mutation in ineffective erythropoiesis can be useful.
Optical photometric variable stars towards Cygnus OB7
Authors: Dutta Somnath , Mondal Soumen , Joshi Santosh , Das Ramkrishna
Published: May 2019

We present optical I-band light curves of the stars towards a star-forming region Cygnus OB7 from 17-night photometric observations. The light curves are generated from a total of 381 image frames with very good photometric precision. From the light curves of 1900 stars and their periodogram analyses, we detect 31 candidate variables including five previously identified. 14 out of 31 objects are periodic and exhibit the rotation rates in the range of 0.15–11.60 d. We characterize those candidate variables using optical/infrared colour–colour diagram and colour–magnitude diagram (CMD). From spectral indices of the candidate variables, it turns out that four are probably Classical T-Tauri stars (CTTSs), rest remain unclassified from present data, they are possibly field stars or discless pre-main-sequence stars towards the region. Based on their location on the various CMDs, the ages of two T Tauri Stars were estimated to be ∼5 Myr. The light curves indicate at least five of the periodic variables are eclipsing systems. The spatial distribution of young variable candidates on Planck 857 GHz (350 $\mu$m) and 2MASS (Two Micron All Sky Survey) Ks images suggest that at least two of the CTTSs are part of the active star-forming cloud Lynds 1003.
Pseudouridines on Trypanosoma brucei spliceosomal small nuclear RNAs and their implication for RNA and protein interactions
Authors: Rajan K Shanmugha , Doniger Tirza , Cohen-Chalamish Smadar , Chen Dana , Semo Oz , Aryal Saurav , Glick Saar Efrat , Chikne Vaibhav , Gerber Doron , Unger Ron , Tschudi Christian , Michaeli Shulamit
Published: May 2019

The parasite Trypanosoma brucei, the causative agent of sleeping sickness, cycles between an insect and a mammalian host. Here, we investigated the presence of pseudouridines (Ψs) on the spliceosomal small nuclear RNAs (snRNAs), which may enable growth at the very different temperatures characterizing the two hosts. To this end, we performed the first high-throughput mapping of spliceosomal snRNA Ψs by small RNA Ψ-seq. The analysis revealed 42 Ψs on T. brucei snRNAs, which is the highest number reported so far. We show that a trypanosome protein analogous to human protein WDR79, is essential for guiding Ψ on snRNAs but not on rRNAs. snoRNA species implicated in snRNA pseudouridylation were identified by a genome-wide approach based on ligation of RNAs following in vivo UV cross-linking. snRNA Ψs are guided by single hairpin snoRNAs, also implicated in rRNA modification. Depletion of such guiding snoRNA by RNAi compromised the guided modification on snRNA and reduced parasite growth at elevated temperatures. We further demonstrate that Ψ strengthens U4/U6 RNA–RNA and U2B"/U2A’ proteins-U2 snRNA interaction at elevated temperatures. The existence of single hairpin RNAs that modify both the spliceosome and ribosome RNAs is unique for these parasites, and may be related to their ability to cycle between their two hosts that differ in temperature.
Proteomics and metabolomics studies exploring the pathophysiology of renal dysfunction in autosomal dominant polycystic kidney disease and other ciliopathies
Authors: Zacchia Miriam , Marchese Emanuela , Trani Elena Martina , Caterino Marianna , Capolongo Giovanna , Perna Alessandra , Ruoppolo Margherita , Capasso Giovambattista
Published: May 2019

The primary cilium (PC) was considered as a vestigial organelle with no significant physiological importance, until the discovery that PC perturbation disturbs several signalling pathways and results in the dysfunction of a variety of organs. Genetic studies have demonstrated that mutations affecting PC proteins or its anchoring structure, the basal body, underlie a class of human disorders (known as ciliopathies) characterized by a constellation of clinical signs. Further investigations have demonstrated that the PC is involved in a broad range of biological processes, in both developing and mature tissues. Kidney disease is a common clinical feature of cilia disorders, supporting the hypothesis of a crucial role of the PC in kidney homoeostasis. Clinical proteomics and metabolomics are an expanding research area. Interestingly, the application of these methodologies to the analysis of urine, a biological sample that can be collected in a non-invasive fashion and possibly in large amounts, makes these studies feasible also in patients. The present article describes the most recent proteomic and metabolomic studies exploring kidney dysfunction in the setting of ciliopathies, showing the potential of these methodologies in the elucidation of disease pathophysiology and in the discovery of biomarkers.
Sex is an important prognostic factor for glioblastoma but not for nonglioblastoma
Authors: Gittleman Haley , Ostrom Quinn T , Stetson L C , Waite Kristin , Hodges Tiffany R , Wright Christina H , Wright James , Rubin Joshua B , Berens Michael E , Lathia Justin , Connor James R , Kruchko Carol , Sloan Andrew E , Barnholtz-Sloan Jill S
Published: May 2019

Background

Glioblastoma (GBM) is the most common and most malignant glioma. Nonglioblastoma (non-GBM) gliomas (WHO Grades II and III) are invasive and also often fatal. The goal of this study is to determine whether sex differences exist in glioma survival.

Methods

Data were obtained from the National Cancer Database (NCDB) for years 2010 to 2014. GBM (WHO Grade IV; N = 2073) and non-GBM (WHO Grades II and III; N = 2963) were defined using the histology grouping of the Central Brain Tumor Registry of the United States. Non-GBM was divided into oligodendrogliomas/mixed gliomas and astrocytomas. Sex differences in survival were analyzed using Kaplan–Meier and multivariable Cox proportional hazards models adjusted for known prognostic variables.

Results

There was a female survival advantage in patients with GBM both in the unadjusted (P = .048) and adjusted (P = .003) models. Unadjusted, median survival was 20.1 months (95% CI: 18.7-21.3 months) for women and 17.8 months (95% CI: 16.9-18.7 months) for men. Adjusted, median survival was 20.4 months (95% CI: 18.9-21.6 months) for women and 17.5 months (95% CI: 16.7-18.3 months) for men. When stratifying by age group (18-55 vs 56+ years at diagnosis), this female survival advantage appeared only in the older group, adjusting for covariates (P = .017). Women (44.1%) had a higher proportion of methylated MGMT (O6-methylguanine-DNA methyltransferase) than men (38.4%). No sex differences were found for non-GBM.

Conclusions

Using the NCDB data, there was a statistically significant female survival advantage in GBM, but not in non-GBM.