bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical significance of the bronchodilator response in children with severe asthma
Authors: Coverstone Andrea M. , Bacharier Leonard B. , Wilson Bradley S. , Fitzpatrick Anne M. , Teague William Gerald , Phipatanakul Wanda , Wenzel Sally E. , Gaston Benjamin M. , Bleecker Eugene R. , Moore Wendy C. , Ramratnam Sima , Jarjour Nizar N. , Ly Ngoc P. , Fahy John V. , Mauger David T. , Schechtman Kenneth B. , Yin‐DeClue Huiqing , Boomer Jonathan S. , Castro Mario
Published: August 2019

Background

Our objective was to determine those characteristics associated with reversibility of airflow obstruction and response to maximal bronchodilation in children with severe asthma through the Severe Asthma Research Program (SARP).

Methods

We performed a cross‐sectional analysis evaluating children ages 6 to 17 years with nonsevere asthma (NSA) and severe asthma (SA). Participants underwent spirometry before and after 180 µg of albuterol to determine reversibility (≥12% increase in FEV1). Participants were then given escalating doses up to 720 µg of albuterol to determine their maximum reversibility.

Results

We evaluated 230 children (n = 129 SA, n = 101 NSA) from five centers across the United States in the SARP I and II cohorts. SA (odds ratio [OR], 2.08, 95% confidence interval [CI], 1.05‐4.13), second‐hand smoke exposure (OR, 2.81, 95%CI, 1.23‐6.43), and fractional exhaled nitric oxide (FeNO; OR, 1.97, 95%CI, 1.35‐2.87) were associated with increased odds of airway reversibility after maximal bronchodilation, while higher prebronchodilator (BD) FEV1% predicted (OR, 0.91, 95%CI, 0.88‐0.94) was associated with decreased odds. In an analysis using the SARP III cohort (n = 186), blood neutrophils, immunoglobulin E (IgE), and FEV1% predicted were significantly associated with BD reversibility. In addition, children with BD response have greater healthcare utilization. BD reversibility was associated with reduced lung function at enrollment and 1‐year follow‐up though less decline in lung function over 1 year compared to those without reversibility.

Conclusions

Lung function, that is FEV1% predicted, is a predictor of BD response in children with asthma. Additionally, smoke exposure, higher FeNO or IgE level, and low peripheral blood neutrophils are associated with a greater likelihood of BD reversibility. BD response can identify a phenotype of pediatric asthma associated with low lung function and poor asthma control.
Management of Tamm–Horsfall Protein for Reliable Urinary Analytics
Authors: Xu Xiaomeng , Barreiro Karina , Musante Luca , Kretz Oliver , Lin Hanfei , Zou Hequn , Huber Tobias B. , Holthofer Harry
Published: August 2019

Purpose

Urinary extracellular vesicles (uEVs) are a novel source of biomarkers. However, urinary Tamm–Horsfall Protein (THP; uromodulin) interferes with all vesicle isolation attempts, precipitates with normal urinary proteins, thus, representing an unwanted “contaminant” in urinary assays. Thus, the aim is to develop a simple method to manage THP efficiently.

Experimental design

The uEVs are isolated by hydrostatic filtration dialysis (HFD) and treated with a defined solution of urea to optimize release of uEVs from sample. Presence of uEVs is confirmed by transmission electron microscopy, Western blotting, and proteomic profiling in MS.

Results

Using HFD with urea treatment for uEV isolation reduces sample complexity to a great extent. The novel simplified uEV isolation protocol allows comprehensive vesicle proteomics analysis and should be part of any urine analytics to release all sample constituents from THP trap.

Conclusions and clinical relevance

The method brings a quick and easy protocol for THP management during uEV isolation, providing major benefits for comprehensive sample analytics.
VHH characterization. Comparison of recombinant with chemically synthesized anti‐HER2 VHH
Authors: Hartmann Lucie , Botzanowski Thomas , Galibert Mathieu , Jullian Magali , Chabrol Eric , Zeder‐Lutz Gabrielle , Kugler Valérie , Stojko Johann , Strub Jean‐Marc , Ferry Gilles , Frankiewicz Lukasz , Puget Karine , Wagner Renaud , Cianférani Sarah , Boutin Jean A.
Published: August 2019

In the continuous exploration of the VHH chemistry, biochemistry and therapeutic future use, we investigated two different production strategies of this small antibody‐like protein, using an anti‐HER2 VHH as a model. The total chemical synthesis of the 125 amino‐acid peptide was performed with reasonable yield, even if optimization will be necessary to upgrade this kind of production. In parallel, we expressed the same sequence in two different hosts: Escherichia coli and Pichia pastoris. Both productions were successful and led to a fair amount of VHHs. The integrity and conformation of the VHH were characterized by complementary mass spectrometry approaches, while surface plasmon resonance experiments were used to assess the VHH recognition capacity and affinity toward its “antigen.” Using this combination of orthogonal techniques, it was possible to show that the three VHHs—whether synthetic or recombinant ones—were properly and similarly folded and recognized the “antigen” HER2 with similar affinities, in the nanomolar range. This opens a route toward further exploration of modified VHH with unnatural amino acids and subsequently, VHH‐drug conjugates.
Corn silk decoction for blood lipid in patients with angina pectoris: A systematic review and meta‐analysis
Authors: Shi Shihua , Yu Baili , Li Weihao , Shan Jiayue , Ma Tianhong
Published: August 2019

The aims of this study were to evaluate the efficacy of corn silk decoction on lipid profile in patients with angina pectoris. PubMed, Cochrane, Embase, Google Scholar, Chongqing VIP Chinese Science and Technology Periodical Database, China National Knowledge Infrastructure, and Wanfang database were searched up to January 2019 for randomized controlled trials that assessed the impact of corn silk decoction on total cholesterol, triglycerides, low‐density lipoprotein cholesterol, and high‐density lipoprotein cholesterol in patients with angina pectoris. Study evaluation and synthesis methods were in accordance with the Cochrane Handbook, and data were analyzed using Review Manager (version 5.3) software. Random effects model was applied in this systematic review and meta‐analysis to compensate for potential heterogeneity among the included studies. A total of four randomized controlled trials were eligible for meta‐analysis. Pooled results of these studies indicated that corn silk decoction might improve high‐density lipoprotein cholesterol and reduce total cholesterol, triglycerides, and low‐density lipoprotein cholesterol in patients with angina pectoris. Subgroup analyses showed that corn silk decoction or modified corn silk decoction plus conventional pharmaceutical treatment could have favorable effects on blood lipids. However, the lack of blinding in most studies may have led to overestimation of these effects. Further studies with better design are needed to confirm these findings.
Visible LED‐Assisted Effective Charge Separation in Ruthenium‐Doped ZnS System for Efficient Photodegradation of Organic Dye
Authors: Mandal Sujoy K. , Karmakar Devdas , Ghosal Supriya , Paul Sumana , Jana Debnarayan
Published: August 2019

Harvesting solar light efficiently and effective photo‐induced charge separated photocatalysts becoming an immense demand for environment salvation. Herein, the one‐step solvothermal method has been employed to synthesize Zn1–xRuxS nanoparticles (NPs). A systematic study for the photocatalytic degradation of Methylene blue (MB) for the first time in Ru doped ZnS system has been carried out with visible light (LED) irradiation. Density functional theory has been employed to study the structural, electronic properties and charge transfer mechanism throughout the Ru doped ZnS system. Theoretical results and UV‐Vis spectra suggest a reduction of bandgap as a function of Ru concentration. Bader charge analysis for both the structures as well as photoluminescence quenching has shown Ru acts as a charge center in the charge transfer process. The optimum photodegradation efficiency is achieved in case of 1% Ru doped ZnS NPs. Thus Ru doping in ZnS NPs has a significant role in showing effective photocatalytic behaviour.
Recent Advances and Prospects in the Chemistry of o‐Benzoquinones
Authors: Radhika Sankaran , Saranya Salim , Harry Nissy Ann , Anilkumar Gopinathan
Published: August 2019

Ortho‐benzoquinones play a vital role as reactive intermediate having high electrophilic character. Sterically crowded 1,2‐benzoquinones and their derivatives exhibiting divergent functionality have marked attraction in organic synthesis. Their intermolecular Diels‐Alder reactions reflect wide versatile applications. They act as a powerful tool towards the synthesis of biologically active complex heterocyclic ligands. This review focuses on the various novel advancements in the synthesis, reactions and applications of 1,2‐benzoquinones that have been achieved recently.
Multifunctional Nanoengineered Hydrogels Consisting of Black Phosphorus Nanosheets Upregulate Bone Formation
Authors: Wang Zhenming , Zhao Jin , Tang Wanze , Hu Liqiu , Chen Xin , Su Yiping , Zou Chang , Wang Jianhong , Lu William W. , Zhen Wanxin , Zhang Ronghua , Yang Dazhi , Peng Songlin
Published: August 2019

Tissue‐engineered hydrogels have received extensive attention as their mechanical properties, chemical compositions, and biological signals can be dynamically modified for mimicking extracellular matrices (ECM). Herein, the synthesis of novel double network (DN) hydrogels with tunable mechanical properties using combinatorial screening methods is reported. Furthermore, nanoengineered (NE) hydrogels are constructed by addition of ultrathin 2D black phosphorus (BP) nanosheets to the DN hydrogels with multiple functions for mimicking the ECM microenvironment to induce tissue regeneration. Notably, it is found that the BP nanosheets exhibit intrinsic properties for induced CaP crystal particle formation and therefore improve the mineralization ability of NE hydrogels. Finally, in vitro and in vivo data demonstrate that the BP nanosheets, mineralized CaP crystal nanoparticles, and excellent mechanical properties provide a favorable ECM microenvironment to mediate greater osteogenic cell differentiation and bone regeneration. Consequently, the combination of bioactive chemical materials and excellent mechanical stimuli of NE hydrogels inspire novel engineering strategies for bone‐tissue regeneration.
Watch out for this commit! A study of influential software changes
Authors: Li Daoyuan , Li Li , Kim Dongsun , Bissyandé Tegawendé F. , Lo David , Le Traon Yves
Published: August 2019

One single code change can significantly influence a wide range of software systems and their users. For example, (a) adding a new feature can spread defects in several modules, while (b) changing an API method can improve the performance of all client programs. Unfortunately, developers often may not clearly know whether code changes are influential at commit time. This paper investigates influential software changes and proposes an approach to identify them immediately when they are applied. Our goals are to (a) identify existing influential changes (ICs) in software projects, (b) understand their characteristics, and (c) build a classification model of ICs to help developers find and address them early. We first conduct a post‐mortem analysis to discover existing influential changes by using intuitions (eg, changes referred by other changes). Then, we re‐categorize all identified changes through an open‐card sorting process. Subsequently, we conduct a survey with about 100 developers to finalize a taxonomy. Finally, from our ground truth, we extract features, including metrics such as the complexity of changes and file centrality in co‐change graphs to build machine learning classifiers. The experiment results show that our classification model with random samples achieves 86.8% precision, 74% recall, and 80.4% F‐measure, respectively.
The Effects of Differential Income Replacement and Mortality on U.S. Social Security Redistribution
Authors: Tan Li , Koedel Cory
Published: August 2019

We study redistribution via the U.S. Social Security retirement system for cohorts of men born during the second half of the 20th century. Our focus is on redistribution across race and education groups. The cohorts we study are younger than cohorts studied in previous, similar research and thus more exposed to recent increases in earnings inequality. All else equal, this should increase the degree of progressivity of Social Security redistribution due to the structure of the benefit formula. However, we find that redistribution is only modestly progressive for individuals born as late as 1980. Differential mortality rates across race and education groups are the primary explanation. While Black–White mortality gaps have narrowed some in recent years, they remain large and dull progressivity. Mortality gaps by education level are also large and unlike the gaps by race, they are widening, which puts additional regressive pressure on Social Security redistribution.
Energy dissipation and self‐centering capacities of posttensioning precast segmental ultra‐high performance concrete bridge columns
Authors: Wang Zhen , Wang Jingquan , Zhu Junzheng , Zhao Guotang , Zhang Jian
Published: August 2019

The research aims to better balance energy dissipation (ED) and self‐centering capacities of posttensioning (PT) precast segmental ultra‐high performance concrete bridge columns by adjusting common design parameters. A numerical model is established based on the equivalent plastic hinge model and validated by the cyclic loading test. The validated model is used to conduct a parametric study to investigate the effects of seven common design parameters on ED and self‐centering capacities. The results show the proposed numerical model can accurately predict ED and self‐centering capacities of the proposed bridge columns. The effect of the strength‐yield ratio can be neglected when it is more than 1.2. The lower aspect ratio can first weaken and then improve the equivalent viscous damping ratio with drift ratio up, while the lower aspect ratio can reduce the residual drift ratio. With larger ED bar ratio, smaller unbonded length of ED bars and lower PT tendon ratio, the equivalent viscous damping ratio, and the residual drift ratio are significantly increased. It is not a perfect way to improve ED capacity by increasing the ED bar ratio, which can significantly magnify the residual drift ratio and limitedly enhance the equivalent viscous damping ratio, besides economical considering. Improving the gravity loading ratio and the initial PT stress are deemed to be effective ways to reduce the residual drift ratio because they not only have little influence on the equivalent viscous damping ratio but also result in no more costs.
Electrochemically Induced Diels‐Alder Reaction: An Overview
Authors: Heravi Majid M. , Zadsirjan Vahideh , Kouhestanian Elham , AlimadadiJani Behnoush
Published: August 2019

One of the most important name reactions in organic chemistry, is the Diels‐Alder cycloaddition reaction. It is a chemical reaction between a conjugated diene and a substituted alkene, commonly termed the dienophile to construct a substituted cyclohexene derivative. It is the stereotypical example of a pericyclic reaction with a concerted mechanism. In synthesis, the use of electricity instead of stoichiometric amounts of oxidant or reducing agents is definitely appealing for economic, ecological and selective, reasons. In this review, we try to underscore the combination of the electrosynthesis with Diels‐Alder cycloaddition reaction to establish of a powerful synthetic tool which may encourage synthetic organic chemists to use it in the future.
Cytotoxic potentials of S. cumini methanolic seed kernel extract in human hepatoma HepG2 cells
Authors: Solai Prakash Ashwin Kumar , Devaraj Ezhilarasan
Published: August 2019

Syzygium cumini (Myrtaceae) is commonly called as Jamun or Jambolan. It has antidiabetic, anti‐inflammatory, antipyretic, and antioxidant activities. Hepatocellular carcinoma is the most frequent and deadliest cancers worldwide. We investigated the cytotoxic potentials of S. cumini methanolic seed kernel extract against human hepatoma HepG2 cells. HepG2 cells were treated with 10, 20, and 40 μg/mL of seed kernel extract for 24 hours and cytotoxic analysis was performed by MTT assay. S. cumini induced apoptosis related morphological changes in HepG2 cells were analyzed by annexin V and propidium iodide double staining. Nuclear fragmentation and chromatin condensation were analyzed by Hoechst nuclear staining. Mitochondrial membrane potential (MMP) was investigated by 5,5′,6,6′‐tetrachloro‐1,1′,3,3′‐tetraethylbenzimidazolyl‐carbocyanine iodide (JC‐1) staining. Protein expressions of hepatocyte nuclear factor‐1α (HFN‐1α) was performed using western blotting. S. cumini treatments caused a significant and a concentration‐dependent increase in the cytotoxicity of HepG2 cells. S. cumini treatments increased the percentage of cells in an early and late apoptosis stage. This treatment also caused chromatin condensation and nuclear fragmentation. Further, S. cumini treatments decreased MMP and also caused a significant downregulation of HFN‐1α protein expression. The present study demonstrated that S. cumini seed extract induced apoptosis in HepG2 cells through decrease in MMP and downregulation of HFN‐1α.
Preparation and application of bagasse‐based adsorbent for highly efficient removal of mercury ions
Authors: Ma Nianfang , Li Jinrong , Zeng Jian , Liang Lei , Zhang Jiayong
Published: August 2019

A high‐performance bagasse‐based adsorbent was prepared from agricultural waste bagasse by grafting of acrylamide and aminating with diethylenetriamine. Effects of catalyst dosage, acrylamide concentration, reaction temperature, and bath ratio on the grafting yield were investigated. The adsorption performances for mercury ions were evaluated by batch adsorption experiments and kinetic experiments. The results show that the adsorbent has high adsorption capacity for mercury in a wide range of pH values. The adsorption capacity could be as high as 813.0 mg/g, and the removal percentage for mercury ions can reach 99.9%. The kinetic adsorption experiments show it can achieve adsorption equilibrium rapidly, which implies that the adsorbent has a strong ability to capture mercury ions. Besides, the bagasse‐based adsorbent showed promising regeneration performance, and its adsorption amount of regenerated adsorbent only slightly decreased after five recycling.

Practitioner points

An amino‐rich adsorbent was prepared from bagasse.

The adsorbent possesses high adsorption capacity and high removal efficiency for mercury.

The aminated bagasse adsorbs mercury rapidly.

The adsorbent functionalized with amino possesses strong affinity toward mercury.
HTX-011 reduced pain intensity and opioid consumption versus bupivacaine HCl in herniorrhaphy: results from the phase 3 EPOCH 2 study
Authors: Viscusi E. , Minkowitz H. , Winkle P. , Ramamoorthy S. , Hu J. , Singla N.
Published: August 2019

Purpose

Currently available local anesthetics have not demonstrated sufficient analgesia beyond 12–24 h postoperatively. The purpose of the study was to assess the safety and efficacy of HTX-011 (bupivacaine and meloxicam in Biochronomer® polymer technology), a long-acting investigational anesthetic, in reducing both postoperative pain over 72 h and postoperative opioid use compared to bupivacaine hydrochloride (HCl).

Methods

A phase 3, randomized, double-blind, active-controlled multi-center study (EPOCH 2; NCT03237481) in subjects undergoing unilateral open inguinal herniorrhaphy with mesh placement was performed. Subjects randomly received a single intraoperative dose of HTX-011, immediate-release bupivacaine HCl, or saline placebo prior to closure.

Results

The study evaluated 418 subjects, and the primary and all key secondary efficacy endpoints were in favor of HTX-011. HTX-011 reduced mean pain intensity by 23% versus placebo (primary endpoint; p < 0.001) and by 21% versus bupivacaine HCl (p < 0.001) with significant reductions in the number of patients experiencing severe pain. Opioid consumption over 72 h was reduced by 38% versus placebo (p < 0.001) and 25% versus bupivacaine HCl (p = 0.024). Overall, 51% of HTX-011 subjects were opioid-free through 72 h (versus 22% for placebo [p < 0.001] and 40% for bupivacaine HCl [p = 0.049]). HTX-011 was generally well-tolerated with fewer opioid-related adverse events reported compared to the bupivacaine HCl and placebo and no evidence of local anesthetic systemic toxicity.

Conclusions

HTX-011 demonstrated significant improvement in postoperative pain control and a clinically meaningful reduction in opioid consumption when compared to the most widely used local anesthetic, bupivacaine HCl.
The development of entrustable professional activities reference cards to support the implementation of Competence by Design in emergency medicine
Authors: Stoneham Emily J. , Witt Lara , Paterson Quinten S. , Martin Lynsey J. , Thoma Brent
Published: August 2019

We designed two practical, user-friendly, low-cost, aesthetically pleasing resources, with the goal of introducing residents and observers to a new Competence by Design assessment system based on entrustable professional activities. They included a set of rotation- and stage-specific entrustable professional activities reference cards for bedside use by residents and observers and a curriculum board to organize the entrustable professional activities reference cards by stages of training based on our program's curriculum map. A survey of 14 emergency medicine residents evaluated the utilization and helpfulness of these resources. They had a positive impact on our program's transition to Competence by Design and could be successfully incorporated into other residency programs to support the introduction of entrustable professional activities-based Competence by Design assessment systems.
General public perceptions and motivations to adopt children from out-of-home care in New South Wales, Australia
Authors: Luu Betty , Wright Amy Conley , Randle Melanie
Published: August 2019

Recent reforms in New South Wales (NSW), Australia, prioritise adoption over long-term foster care. While previous research has examined motivation to foster, less is known about the interest by the general public in adoption from out-of-home care. A general sample of the NSW public (N = 1030) completed an online survey about adoption practices and their willingness to consider adopting from out-of-home care, with background questions on perceived social support and life satisfaction. Barriers to pursuing adoption were identified, including concerns about the characteristics of the child related to their experiences of care and personal impacts including financial costs. Availability of post-adoption supports was viewed positively as increasing interest in adoption. General Linear Model univariate analyses identified that likelihood of considering adoption was primarily predicted by younger age, knowing someone who had been adopted as a child, actively practicing religion, living in the city rather than a regional area and higher life satisfaction. Customised marketing campaigns can target people more likely to consider adoption, with messages that resonate with their social and psychological characteristics. There is also a need for policy changes to ensure adequate provision of post-adoption support.
Changes in Psychiatric Emergency Room Visits Following the Boston Marathon Bombing
Authors: Frank Amber , Noy Gaddy , Chow Clifton , Leff H. Stephen
Published: August 2019

Objective:

This study reviews patient encounters at a Boston-area community hospital Psychiatric Emergency Services (PES) following the Boston Marathon bombings, with the goal of describing the impact of terrorist attacks on PES encounters.

Methods:

All PES encounters for 2 months preceding and 2 months following the bombing were identified in the electronic medical record. Demographics, current and past psychiatric problems, and trauma history were assessed for all records. Encounters seen post-bombing were compared with those before the bombing.

Results:

Demographics, current and past psychiatric problems, and trauma history were not significantly different before versus after the bombing; 36 of 440 (8.2%) post-bombing encounters directly mentioned the bombings. New-onset posttraumatic stress disorder (PTSD) symptoms caused by the bombing occurred in only 4 encounters (0.9%).

Conclusions:

PES encounters after a terrorist event are likely to mirror those seen before a terrorist event, with only a minority of encounters presenting for new PTSD or acute stress disorder.
Turbulent shear-layer mixing: initial conditions, and direct-numerical and large-eddy simulations
Authors: Sharan Nek , Matheou Georgios , Dimotakis Paul E.
Published: August 2019

Aspects of turbulent shear-layer mixing are investigated over a range of shear-layer Reynolds numbers, $Re_{\unicode[STIX]{x1D6FF}}=\unicode[STIX]{x0394}U\unicode[STIX]{x1D6FF}/\unicode[STIX]{x1D708}$, based on the shear-layer free-stream velocity difference, $\unicode[STIX]{x0394}U$, and mixing-zone thickness, $\unicode[STIX]{x1D6FF}$, to probe the role of initial conditions in mixing stages and the evolution of the scalar-field probability density function (p.d.f.) and variance. Scalar transport is calculated for unity Schmidt numbers, approximating gas-phase diffusion. The study is based on direct-numerical simulation (DNS) and large-eddy simulation (LES), comparing different subgrid-scale (SGS) models for incompressible, uniform-density, temporally evolving forced shear-layer flows. Moderate-Reynolds-number DNS results help assess and validate LES SGS models in terms of scalar-spectrum and mixing estimates, as well as other metrics, to $Re_{\unicode[STIX]{x1D6FF}}\lesssim 3.3\times 10^{4}$. High-Reynolds-number LES investigations to $Re_{\unicode[STIX]{x1D6FF}}\lesssim 5\times 10^{5}$ help identify flow parameters and conditions that influence the evolution of scalar variance and p.d.f., e.g. marching versus non-marching. Initial conditions that generate shear flows with different mixing behaviour elucidate flow characteristics in each flow regime and identify elements that induce p.d.f. transition and scalar-variance behaviour. P.d.f. transition is found to be largely insensitive to local flow parameters, such as $Re_{\unicode[STIX]{x1D6FF}}$, or a previously proposed vortex-pairing parameter based on downstream distance, or other equivalent criteria. The present study also allows a quantitative comparison of LES SGS models in moderate- and high-$Re_{\unicode[STIX]{x1D6FF}}$ forced shear-layer flows.
Bronze Age Beginnings – a Scalar View from the Global Outskirts
Authors: Vandkilde Helle
Published: August 2019

This article tracks the formation of the rich and socially complex Nordic Bronze Age (NBA),c.2000–1500bc, by applying a scalar methodology and using theentrepôtand early metalworking site of Pile in Scania as its point of departure. By regarding the Bronze Age as an ancient example of globalisation, Island Melanesia at the outskirts of contemporary globalisation is first examined to provide an analogue to the Nordic entrepreneurial and maritime culture into which metallurgy was first adopted. How did this northern margin become ‘Bronze Age’, and what impact did its inclusion have? Various scales, from local to Bronze-Age-global were found to intersect in the Pile hoard, and in similar sites near and far. Byc.2000bc, metals and other commodities travelled along well-established local, regional, and super-regional networks, which even incorporated the British Isles and Únětician hubs at the Middle Elbe–Saale. Back in Scandinavia, metal and metal-related culture provided a comparative advantage when navigating local competition for influence and leadership. The transculturally global was strategically appropriated locally, using the reinvention of tradition as a principal strategy. The first metal boom caused friction and slow social change, rather than a social revolution. The real tipping point came in 1600–1500bc, when the nearly full-blown NBA emerged, through engagement with a considerably expanded world. By this time, large amounts of metal were in circulation. Seen from the non-urban north, this unprecedented expansion of their world brought new opportunities but likely also deep social tensions. Thus, the effects of adopting metallurgy permeated society and connectivity at every level, even at the outskirts of the Bronze Age world.
Equality case for an elliptic area condenser inequality and a related Schwarz type lemma
Authors: Kelgiannis Georgios
Published: August 2019

We give an equality condition for a symmetrization inequality for condensers proved by F.W. Gehring regarding elliptic areas. We then use this to obtain a monotonicity result involving the elliptic area of the image of a holomorphic function f.
Pseudocoordination with posture verbs in Mainland Scandinavian: A grammaticalized progressive construction?
Authors: Lødrup Helge
Published: August 2019

Pseudocoordination with posture verbs in Mainland Scandinavian (e.g. the NorwegianHan sitter og arbeider‘he sits and works’) is traditionally considered a grammaticalized progressive construction. The posture verb is said to have a bleached meaning, and to have the grammatical status of an auxiliary or a light verb. In recent years, some researchers have expressed doubt about this view. In this article, I argue that the traditional arguments for grammaticalization do not hold. However, I also give new evidence for early grammaticalization. Posture verbs can to some extent be used as light verbs in sentences such asKebab må sittes og nytes‘kebab must sit.passand enjoy.pass’, which have never been discussed in connection with grammaticalization. Finally, I argue that pseudocoordination with posture verbs should not be seen as progressive, but rather as a locational (or situative) construction.
I am a total failure: associations between beliefs and anxiety and depression in patients with inflammatory bowel disease with poor mental quality of life
Authors: Bennebroek Evertsz’ Floor , Sprangers Mirjam A.G. , de Vries Laura M. , Sanderman Robbert , Stokkers Pieter C.F. , Verdam Mathilde G.E. , Burger Huibert , Bockting Claudi L.H.
Published: August 2019

Background:

According to cognitive behavioural theory, cognitive factors (i.e. underlying general dysfunctional beliefs and (situation) specific illness beliefs) are theorized to lead to outcomes like anxiety and depression. In clinical practice, general dysfunctional beliefs are generally not tackled directly in short-term-therapy.

Aims:

The goal of the present study was to investigate the associations of general versus specific illness beliefs on anxiety and depressive symptoms and psychiatric disorders among a subgroup of patients with inflammatory bowel disease (IBD) with poor mental quality of life (QoL).

Method:

This study concerns cross-sectional data, collected at baseline from a randomized clinical trial. One hundred and eighteen patients, recruited at four Dutch hospitals, with poor QoL (score ≤23 on the mental health subscale of the Short-Form 36-item Health-Survey; SF-36) were included. General dysfunctional beliefs were measured by the Dysfunctional Attitude Scale (DAS), specific illness beliefs by the Illness Perceptions Questionnaire-Revised (IPQ-R), anxiety and depressive symptoms by the Hospital Anxiety and Depression Scale (HADS), and psychiatric disorders by the Structured Clinical Interview for DSM-IV Axis-I Disorders (SCID-I).

Results:

Univariate analyses showed associations between the level of anxiety and/or depression and general dysfunctional beliefs and four specific illness beliefs (consequences, personal control, emotional representations and treatment control). Among patients with IBD with psychiatric disorders, only the DAS was significantly associated with anxiety and depression (DAS added to IPQ-R and IPQ-R added to DAS).

Conclusions:

Psychological interventions may have to target general dysfunctional beliefs of patients with IBD with co-morbid psychiatric disorders to be effective. These patients with IBD are especially in need of psychological treatment.
Aromatherapy improves nausea, pain, and mood for patients receiving pediatric palliative care symptom-based consults: A pilot design trial
Authors: Weaver Meaghann S. , Robinson Jacob , Wichman Christopher
Published: August 2019

Objective

The role of aromatherapy in supportive symptom management for pediatric patients receiving palliative care has been underexplored. This pilot study aimed to measure the impact of aromatherapy using validated child-reported nausea, pain, and mood scales 5 minutes and 60 minutes after aromatherapy exposure.

Methods

The 3 intervention arms included use of a symptom-specific aromatherapy sachet scent involving deep breathing. The parallel default control arm (for those children with medical exclusion criteria to aromatherapy) included use of a visual imagery picture envelope and deep breathing. Symptom burden was sequentially assessed at 5 and 60 minutes using the Baxter Retching Faces scale for nausea, the Wong-Baker FACES scale for pain, and the Children's Anxiety and Pain Scale (CAPS) for anxious mood. Ninety children or adolescents (mean age 9.4 years) at a free-standing children's hospital in the United States were included in each arm (total n = 180).

Results

At 5 minutes, there was a mean improvement of 3/10 (standard deviation [SD] 2.21) on the nausea scale; 2.6/10 (SD 1.83) on the pain scale; and 1.6/5 (SD 0.93) on the mood scale for the aromatherapy cohort (p< 0.0001). Symptom burden remained improved at 60 minutes post-intervention (<0.0001). Visual imagery with deep breathing improved self-reports of symptoms but was not as consistently sustained at 60 minutes.

Significance of results

Aromatherapy represents an implementable supportive care intervention for pediatric patients receiving palliative care consults for symptom burden. The high number of children disqualified from the aromatherapy arm because of pulmonary or allergy indications warrants further attention to outcomes for additional breathing-based integrative modalities.
Improving Medium‐Range Forecasts of Rain‐on‐Snow Events in Prealpine Areas
Authors: Fehlmann Michael , Gascón Estíbaliz , Rohrer Mario , Schwarb Manfred , Stoffel Markus
Published: August 2019

Rain‐on‐snow (RoS) events have caused severe floods in mountainous catchments in the recent past. Challenges in forecasting such events are uncertainties in meteorological input variables, the accurate estimation of snow cover and deficits in process understanding during runoff formation. Here, we evaluate the potential of the European Centre for Medium‐Range Weather Forecasts Integrated Forecasting System (ECMWF IFS) to forecast RoS disposition (i.e., minimum rainfall amounts, initial snow cover, and meltwater contribution) several days ahead. We thereby evaluate forecasts of rain and snowfall with disdrometer observations and show that ensemble‐based forecasts have larger potential than the high‐resolution forecast of ECMWF IFS. Then, we use ECMWF IFS weather forecasts as input to a conceptual hydrological model, which is calibrated using estimates of snow‐covered area (SCA), snow water equivalent (SWE), and discharge observations. We show that the forecast skill of this model chain is reasonably high with respect to SCA and SWE, even several days ahead. However, a number of RoS events are missed in the forecast, mainly due to an underestimation of rainfall amounts. These misses can be reduced by lowering the rainfall amount threshold for the forecast as compared to the analysis, being accompanied by only a moderate increase in false alarm rates. In contrast, the forecast of RoS disposition is found to be less sensitive to thresholds of initial snow cover and meltwater contribution. We conclude that valuable disposition warnings for RoS events can be issued several days ahead, and we illustrate this idea with a case study.
A Geophysical Model Function for S‐Band Reflectometry of Ocean Surface Winds in Tropical Cyclones
Authors: Zhang Han , Garrison James L. , Wijekularatne Rozaine , Warnecke James
Published: August 2019

Ocean surface wind remote sensing using reflectometry measurements from S‐band (2.3 GHz) digital communication satellite transmissions is demonstrated in tropical cyclones. Twelve days of airborne data were collected during the 2014 Atlantic hurricane season. An empirical model function, relating the sensed ocean surface mean square slope to wind speed, was first developed by fitting mean square slope estimates to comparison wind speed data from the Stepped Frequency Microwave Radiometer on the same aircraft and wind direction data from the Hurricane Weather Research and Forecasting model. This model function was then applied for wind speed retrievals using an independent set of reflectometry measurements and validated against four data sources: Stepped Frequency Microwave Radiometer, the Hurricane Weather Research and Forecasting model, dropsondes, and flight‐level winds. Good agreement between these retrievals and comparison data was found, with a root‐mean square error between 4.9 and 6.6 m/s and a bias between −1.4 and −0.2 m/s for wind speeds up to 50 m/s.
Observation of Rapid Seabed Erosion Near Closure Depth During a Storm Period at Hujeong Beach, South Korea
Authors: Do Jong Dae , Jin Jae‐Youll , Jeong Weon Mu , Chang Yeon S.
Published: August 2019

We report extraordinary seabed erosion that occurred at a depth of ~8.3 m at Hujeong Beach, South Korea. The seabed was eroded for 0.7 m during a ~2.3‐day period under storm conditions. The maximum significant wave height was ~3.8 m, which was unexpected considering the traditional closure depth concept. Four storm events were recorded within 36 day of the experimental period, but the severe erosion only occurred during the first storm. The erosion started when the nearbed flow velocity rapidly increased to reach its maximum at 0.27 m/s, and it continued until this velocity remained at its maximum. Additional factors responsible for the unanticipated erosion process were the current and wave skewness. The erosion was facilitated when the current direction was actively changing and the magnitude of positive skewness increased during the storm period. These factors are likely to have intensified the nearbed flow turbulence and bed shear stress.
Four‐Spacecraft Measurements of the Shape and Dimensionality of Magnetic Structures in the Near‐Earth Plasma Environment
Authors: Fadanelli S. , Lavraud B. , Califano F. , Jacquey C. , Vernisse Y. , Kacem I. , Penou E. , Gershman D. J. , Dorelli J. , Pollock C. , Giles B. L. , Avanov L. A. , Burch J. , Chandler M. O. , Coffey V. N. , Eastwood J. P. , Ergun R. , Farrugia C. J. , Fuselier S. A. , Genot V. N. , Grigorenko E. , Hasegawa H. , Khotyaintsev Y. , Le Contel O. , Marchaudon A. , Moore T. E. , Nakamura R. , Paterson W. R. , Phan T. , Rager A. C. , Russell C. T. , Saito Y. , Sauvaud J.‐A. , Schiff C. , Smith S. E. , Toledo Redondo S. , Torbert R. B. , Wang S. , Yokota S.
Published: August 2019

We present a new method for determining the main relevant features of the local magnetic field configuration, based entirely on the knowledge of the magnetic field gradient four‐spacecraft measurements. The method, named “magnetic configuration analysis” (MCA), estimates the spatial scales on which the magnetic field varies locally. While it directly derives from the well‐known magnetic directional derivative and magnetic rotational analysis procedures (Shi et al., 2005, htpps://doi.org/10.1029/2005GL022454; Shen et al., 2007, https://doi.org/10.1029/2005JA011584), MCA was specifically designed to address the actual magnetic field geometry. By applying MCA to multispacecraft data from the Magnetospheric Multiscale (MMS) satellites, we perform both case and statistical analyses of local magnetic field shape and dimensionality at very high cadence and small scales. We apply this technique to different near‐Earth environments and define a classification scheme for the type of configuration observed. While our case studies allow us to benchmark the method with those used in past works, our statistical analysis unveils the typical shape of magnetic configurations and their statistical distributions. We show that small‐scale magnetic configurations are generally elongated, displaying forms of cigar and blade shapes, but occasionally being planar in shape like thin pancakes (mostly inside current sheets). Magnetic configurations, however, rarely show isotropy in their magnetic variance. The planar nature of magnetic configurations and, most importantly, their scale lengths strongly depend on the plasma β parameter. Finally, the most invariant direction is statistically aligned with the electric current, reminiscent of the importance of electromagnetic forces in shaping the local magnetic configuration.
Deletion of OSBPL2 in auditory cells increases cholesterol biosynthesis and drives reactive oxygen species production by inhibiting AMPK activity
Authors: Wang Hongshun , Lin Changsong , Yao Jun , Shi Hairong , Zhang Cui , Wei Qinjun , Lu Yajie , Chen Zhibin , Xing Guangqian , Cao Xin
Published: August 2019

Oxysterol-binding protein like 2 (OSBPL2) was identified as a novel causal gene for autosomal dominant nonsyndromic hearing loss. However, the pathogenesis of OSBPL2 deficits in ADNSHL was still unclear. The function of OSBPL2 as a lipid-sensing regulator in multiple cellular processes suggested that OSBPL2 might play an important role in the regulation of cholesterol-homeostasis, which was essential for inner ear. In this study the potential roles of OSBPL2 in cholesterol biosynthesis and ROS production were investigated in Osbpl2-KO OC1 cells and osbpl2b-KO zebrafish. RNA-seq-based analysis suggested that OSBPL2 was implicated in cholesterol biosynthesis and AMPK signaling pathway. Furthermore, Osbpl2/osbpl2b-KO resulted in a reduction of AMPK activity and up-regulation of Srebp2/srebp2, Hmgcr/hmgcr and Hmgcs1/hmgcs1, key genes in the sterol biosynthetic pathway and associated with AMPK signaling. In addition, OSBPL2 was also found to interact with ATIC, key activator of AMPK. The levels of total cholesterol and ROS in OC1 cells or zebrafish inner ear were both increased in Osbpl2/osbpl2b-KO mutants and the mitochondrial damage was detected in Osbpl2-KO OC1 cells. This study uncovered the regulatory roles of OSBPL2 in cellular cholesterol biosynthesis and ROS production. These founds might contribute to the deep understanding of the pathogenesis of OSBPL2 mutation in ADNSHL.
Genome-wide systematic identification of methyltransferase recognition and modification patterns
Authors: Jensen Torbjørn Ølshøj , Tellgren-Roth Christian , Redl Stephanie , Maury Jérôme , Jacobsen Simo Abdessamad Baallal , Pedersen Lasse Ebdrup , Nielsen Alex Toftgaard
Published: August 2019

Genome-wide analysis of DNA methylation patterns using single molecule real-time DNA sequencing has boosted the number of publicly available methylomes. However, there is a lack of tools coupling methylation patterns and the corresponding methyltransferase genes. Here we demonstrate a high-throughput method for coupling methyltransferases with their respective motifs, using automated cloning and analysing the methyltransferases in vectors carrying a strain-specific cassette containing all potential target sites. To validate the method, we analyse the genomes of the thermophile Moorella thermoacetica and the mesophile Acetobacterium woodii, two acetogenic bacteria having substantially modified genomes with 12 methylation motifs and a total of 23 methyltransferase genes. Using our method, we characterize the 23 methyltransferases, assign motifs to the respective enzymes and verify activity for 11 of the 12 motifs.
Mitogenic and progenitor gene programmes in single pilocytic astrocytoma cells
Authors: Reitman Zachary J. , Paolella Brenton R. , Bergthold Guillaume , Pelton Kristine , Becker Sarah , Jones Robert , Sinai Claire E. , Malkin Hayley , Huang Ying , Grimmet Leslie , Herbert Zachary T. , Sun Yu , Weatherbee Jessica L. , Alberta John A. , Daley John F. , Rozenblatt-Rosen Orit , Condurat Alexandra L. , Qian Kenin , Khadka Prasidda , Segal Rosalind A. , Haas-Kogan Daphne , Filbin Mariella G. , Suva Mario L. , Regev Aviv , Stiles Charles D. , Kieran Mark W. , Goumnerova Liliana , Ligon Keith L. , Shalek Alex K. , Bandopadhayay Pratiti , Beroukhim Rameen
Published: August 2019

Pilocytic astrocytoma (PA), the most common childhood brain tumor, is a low-grade glioma with a single driver BRAF rearrangement. Here, we perform scRNAseq in six PAs using methods that enabled detection of the rearrangement. When compared to higher-grade gliomas, a strikingly higher proportion of the PA cancer cells exhibit a differentiated, astrocyte-like phenotype. A smaller proportion of cells exhibit a progenitor-like phenotype with evidence of proliferation. These express a mitogen-activated protein kinase (MAPK) programme that was absent from higher-grade gliomas. Immune cells, especially microglia, comprise 40% of all cells in the PAs and account for differences in bulk expression profiles between tumor locations and subtypes. These data indicate that MAPK signaling is restricted to relatively undifferentiated cancer cells in PA, with implications for investigational therapies directed at this pathway.
Directly transforming copper (I) oxide bulk into isolated single-atom copper sites catalyst through gas-transport approach
Authors: Yang Zhengkun , Chen Bingxu , Chen Wenxing , Qu Yunteng , Zhou Fangyao , Zhao Changming , Xu Qian , Zhang Qinghua , Duan Xuezhi , Wu Yuen
Published: August 2019

Single-atom metal catalysts have sparked tremendous attention, but direct transformation of cheap and easily obtainable bulk metal oxide into single atoms is still a great challenge. Here we report a facile and versatile gas-transport strategy to synthesize isolated single-atom copper sites (Cu ISAS/NC) catalyst at gram levels. Commercial copper (I) oxide powder is sublimated as mobile vapor at nearly melting temperature (1500 K) and subsequently can be trapped and reduced by the defect-rich nitrogen-doped carbon (NC), forming the isolated copper sites catalyst. Strikingly, this thermally stable Cu ISAS/NC, which is obtained above 1270 K, delivers excellent oxygen reduction performance possessing a recorded half-wave potential of 0.92 V vs RHE among other Cu-based electrocatalysts. By varying metal oxide precursors, we demonstrate the universal synthesis of different metal single atoms anchored on NC materials (M ISAS/NC, where M refers to Mo and Sn). This strategy is readily scalable and the as-prepared sintering-resistant M ISAS/NC catalysts hold great potential in high-temperature applications.
Author Correction: SREBP1 drives keratin-80-dependent cytoskeletal changes and invasive behavior in endocrine-resistant ERα breast cancer
Authors: Perone Ylenia , Farrugia Aaron J. , Rodríguez-Meira Alba , Győrffy Balázs , Ion Charlotte , Uggetti Andrea , Chronopoulos Antonios , Marrazzo Pasquale , Faronato Monica , Shousha Sami , Davies Claire , Steel Jennifer H. , Patel Naina , del Rio Hernandez Armando , Coombes Charles , Pruneri Giancarlo , Lim Adrian , Calvo Fernando , Magnani Luca
Published: August 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.