bluuebunny/crossref_metadata_2025 huggingface dataset:
Cavitation in soft matter
Authors: Barney Christopher W. , Dougan Carey E. , McLeod Kelly R. , Kazemi-Moridani Amir , Zheng Yue , Ye Ziyu , Tiwari Sacchita , Sacligil Ipek , Riggleman Robert A. , Cai Shengqiang , Lee Jae-Hwang , Peyton Shelly R. , Tew Gregory N. , Crosby Alfred J.
Published: April 2020

Cavitation is the sudden, unstable expansion of a void or bubble within a liquid or solid subjected to a negative hydrostatic stress. Cavitation rheology is a field emerging from the development of a suite of materials characterization, damage quantification, and therapeutic techniques that exploit the physical principles of cavitation. Cavitation rheology is inherently complex and broad in scope with wide-ranging applications in the biology, chemistry, materials, and mechanics communities. This perspective aims to drive collaboration among these communities and guide discussion by defining a common core of high-priority goals while highlighting emerging opportunities in the field of cavitation rheology. A brief overview of the mechanics and dynamics of cavitation in soft matter is presented. This overview is followed by a discussion of the overarching goals of cavitation rheology and an overview of common experimental techniques. The larger unmet needs and challenges of cavitation in soft matter are then presented alongside specific opportunities for researchers from different disciplines to contribute to the field.
Molecular and isotopic evidence for milk, meat, and plants in prehistoric eastern African herder food systems
Authors: Grillo Katherine M. , Dunne Julie , Marshall Fiona , Prendergast Mary E. , Casanova Emmanuelle , Gidna Agness O. , Janzen Anneke , Karega-Munene  , Keute Jennifer , Mabulla Audax Z. P. , Robertshaw Peter , Gillard Toby , Walton-Doyle Caitlin , Whelton Helen L. , Ryan Kathleen , Evershed Richard P.
Published: April 2020

Significance

Lipid residue analysis of archaeological ceramics provides the earliest direct chemical evidence for milk, meat, and plant consumption by pastoralist societies in eastern Africa. Data for milk in specialized pastoral systems (c. 5000 to 1200 BP) reveal changing selective pressures for lactase persistence and provide support for models of gene–culture coevolution among pastoral populations.
Pathogen manipulation of chloroplast function triggers a light-dependent immune recognition
Authors: Gao Chuyun , Xu Huawei , Huang Jie , Sun Biying , Zhang Fan , Savage Zachary , Duggan Cian , Yan Tingxiu , Wu Chih-hang , Wang Yuanchao , Vleeshouwers Vivianne G. A. A. , Kamoun Sophien , Bozkurt Tolga O. , Dong Suomeng
Published: April 2020

In plants and animals, nucleotide-binding leucine-rich repeat (NLR) proteins are intracellular immune sensors that recognize and eliminate a wide range of invading pathogens. NLR-mediated immunity is known to be modulated by environmental factors. However, how pathogen recognition by NLRs is influenced by environmental factors such as light remains unclear. Here, we show that the agronomically important NLR Rpi-vnt1.1 requires light to confer disease resistance against races of the Irish potato famine pathogen
Phytophthora infestans
that secrete the effector protein AVRvnt1. The activation of Rpi-vnt1.1 requires a nuclear-encoded chloroplast protein, glycerate 3-kinase (GLYK), implicated in energy production. The pathogen effector AVRvnt1 binds the full-length chloroplast-targeted GLYK isoform leading to activation of Rpi-vnt1.1. In the dark, Rpi-vnt1.1–mediated resistance is compromised because plants produce a shorter GLYK—lacking the intact chloroplast transit peptide—that is not bound by AVRvnt1. The transition between full-length and shorter plant GLYK transcripts is controlled by a light-dependent alternative promoter selection mechanism. In plants that lack Rpi-vnt1.1, the presence of AVRvnt1 reduces GLYK accumulation in chloroplasts counteracting GLYK contribution to basal immunity. Our findings revealed that pathogen manipulation of chloroplast functions has resulted in a light-dependent immune response.
SLA developmental stages in the CEFR-related learner corpus MERLIN
Authors: Wisniewski Katrin
Published: April 2020

Little is known about the link between Second Language Acquisition (SLA) developmental stages (Pienemann 1998) and the Common European Framework of Reference (CEFR) proficiency levels.
Therefore, this study examines the inversion (INV) and verb-end (VEND) stages in L2 German MERLIN texts rated B1
(N = 104) or A2 (N = 32). Two acquisition criteria are applied to individual texts
(emergence, Pienemann 1998; 75%-correct, Ellis
1989) and combined with analyses of texts grouped at CEFR levels. Results suggest links between developmental stages
and CEFR levels: VEND was emerged in 44% of B1 texts, while most A2 texts did not contain VEND. Many B1 texts (61.5%), but only
37.5% of A2 texts showed emergence of INV. However, analyses also revealed persisting problems with INV accuracy at B1. More
generally, the study points out shared challenges for Learner Corpus Research, SLA, and proficiency/assessment research related to
the availability of linguistic evidence in learner texts.
Hippo/Mst signaling coordinates cellular quiescence with terminal maturation in iNKT cell development and fate decisions
Authors: Raynor Jana L. , Liu Chaohong , Dhungana Yogesh , Guy Cliff , Chapman Nicole M. , Shi Hao , Neale Geoffrey , Sesaki Hiromi , Chi Hongbo
Published: April 2020

Invariant natural killer T (iNKT) cells acquire effector functions during development by mechanisms that remain poorly understood. Here, we show that the Hippo kinases Mst1 and Mst2 act as molecular rheostats for the terminal maturation and effector differentiation programs of iNKT cells. Loss of Mst1 alone or together with Mst2 impedes iNKT cell development, associated with defective IL-15–dependent cell survival. Mechanistically, Mst1 enforces iNKT cellular and transcriptional quiescence associated with maturation and commitment to iNKT1 cells by suppressing proliferation and Opa1-related mitochondrial metabolism that are dynamically regulated during iNKT cell development. Furthermore, Mst1 shapes the reciprocal fate decisions between iNKT1 and iNKT17 effector cells, which respectively depend upon mitochondrial dynamics and ICOS–mTORC2 signaling. Collectively, these findings establish Mst1 as a crucial regulator of mitochondrial homeostasis and quiescence in iNKT cell development and effector lineage differentiation and highlight that establishment of quiescence programs underlies iNKT cell development and effector maturation.
Endothelial mTOR maintains hematopoiesis during aging
Authors: Ramalingam Pradeep , Poulos Michael G. , Gutkin Michael C. , Katsnelson Lizabeth , Freire Ana G. , Lazzari Elisa , Butler Jason M.
Published: April 2020

Aging leads to a decline in hematopoietic stem and progenitor cell (HSPC) function. We recently discovered that aging of bone marrow endothelial cells (BMECs) leads to an altered crosstalk between the BMEC niche and HSPCs, which instructs young HSPCs to behave as aged HSPCs. Here, we demonstrate aging leads to a decrease in mTOR signaling within BMECs that potentially underlies the age-related impairment of their niche activity. Our findings reveal that pharmacological inhibition of mTOR using Rapamycin has deleterious effects on hematopoiesis. To formally determine whether endothelial-specific inhibition of mTOR can influence hematopoietic aging, we conditionally deleted mTOR in ECs (mTOR(ECKO)) of young mice and observed that their HSPCs displayed attributes of an aged hematopoietic system. Transcriptional profiling of HSPCs from mTOR(ECKO) mice revealed that their transcriptome resembled aged HSPCs. Notably, during serial transplantations, exposure of wild-type HSPCs to an mTOR(ECKO) microenvironment was sufficient to recapitulate aging-associated phenotypes, confirming the instructive role of EC-derived signals in governing HSPC aging.
Targeting potential drivers of COVID-19: Neutrophil extracellular traps
Authors: Barnes Betsy J. , Adrover Jose M. , Baxter-Stoltzfus Amelia , Borczuk Alain , Cools-Lartigue Jonathan , Crawford James M. , Daßler-Plenker Juliane , Guerci Philippe , Huynh Caroline , Knight Jason S. , Loda Massimo , Looney Mark R. , McAllister Florencia , Rayes Roni , Renaud Stephane , Rousseau Simon , Salvatore Steven , Schwartz Robert E. , Spicer Jonathan D. , Yost Christian C. , Weber Andrew , Zuo Yu , Egeblad Mikala
Published: April 2020

Coronavirus disease 2019 (COVID-19) is a novel, viral-induced respiratory disease that in ∼10–15% of patients progresses to acute respiratory distress syndrome (ARDS) triggered by a cytokine storm. In this Perspective, autopsy results and literature are presented supporting the hypothesis that a little known yet powerful function of neutrophils—the ability to form neutrophil extracellular traps (NETs)—may contribute to organ damage and mortality in COVID-19. We show lung infiltration of neutrophils in an autopsy specimen from a patient who succumbed to COVID-19. We discuss prior reports linking aberrant NET formation to pulmonary diseases, thrombosis, mucous secretions in the airways, and cytokine production. If our hypothesis is correct, targeting NETs directly and/or indirectly with existing drugs may reduce the clinical severity of COVID-19.
A search for neutron magicity in the isotopic series of Z = 122, 128 superheavy nuclei
Authors: Siddiqui Tasleem Ahmad , Quddus Abdul , Ahmad Shakeb , Patra S K
Published: April 2020

The superheavy nuclei have been examined systematically in the region 158 ⩽ N ⩽ 218, 162 ⩽ N ⩽ 212 for Z = 122 and 128, respectively. The explicit density-dependent meson-exchange (DD-ME) and point-coupling (DD-PC) models within the framework of covariant density functional theory (CDFT) have been used to study the structural and decay properties of the isotopic series which includes the separable form of a finite range of pairing interaction. From the potential energy curves, the ground state properties of nuclei are predicted. Due to the importance of the shell effect in the superheavy region, the Strutinsky shell correction method has been employed for a better understanding of the extra stability of nuclei. The results from neutron pairing energy, two-neutron separation energy (S
2n
), single-particle energy levels, and total shell-correction energy strongly support N = 168, 174, and 178 as deformed neutron-magic numbers from both the force parameter, in both the isotopic series. N = 172 and 184 are predicted as spherical magic with DD-ME2 interaction in the Z = 122 isotopic series. Using three different semi-empirical approaches named UNIV2, SemFIS2, and ImSahu, the α-decay properties are studied and compared with available experimental data, FRDM2012 and the WS4 mass model. The stability of synthesized superheavy nuclei can be determined by comparing spontaneous fission half-lives with α-decay half-lives.
Optimization of compliant adaptive structures in the design of a morphing droop nose
Authors: Cavalieri Vittorio , De Gaspari Alessandro , Ricci Sergio
Published: April 2020

A design procedure for the synthesis of active camber morphing wing devices is proposed. A topology optimization initially defines the internal structure that is further enhanced by structural size and shape optimizations, and these optimizations are based on the distributed compliance concept. The size optimization enables the adaption of the topology solution to other materials and geometries while refining the topology solution to improve the shape quality of the skin deformation. Then, the structural shape optimization enables the reduction of the stress peaks inside the compliant structure and the finalization of the details to obtain a solution that is closer to the manufacturing process stage. The proposed methodology is used in the design of an adaptive droop nose to be installed on a reference regional aircraft, and two different design applications are considered. The first application is the validation of the procedure at the full–scale level using a superelastic material for the internal structure. The second application is the design of a corresponding 3D–printed prototype, in which both geometry and material changes are considered, for experimental validation. The results show satisfactory shape quality and the achievement of structural feasibility. The experimental functional test of the scaled prototype demonstrates the effectiveness of the adopted morphing solution.
Scaling theory for Mott–Hubbard transitions-II: quantum criticality of the doped Mott insulator
Authors: Mukherjee Anirban , Lal Siddhartha
Published: April 2020

We present a T = 0 K renormalization group (RG) phase diagram for the hole-doped 2D Hubbard model on the square lattice. The RG method employed is nonperturbative in treating quantum fluctuations of the single-particle occupation number via the unitarily decoupling of one electronic state at every RG step. As a result, the RG phase diagram possesses the quantum fluctuation energy scale (ω) as one of its axes. Using effective Hamiltonians and wavefunctions for the low-energy many-body eigenstates for the doped Mott liquid obtained from the stable fixed point of the RG flows, we demonstrate the collapse of the pseudogap for charge excitations (Mottness) at a quantum critical point (QCP) possessing a nodal non-Fermi liquid with superconducting fluctuations, and spin-pseudogapping near the antinodes. The QCP is characterised using both thermodynamic and quantum information-theoretic measures. d-wave superconducting order is shown to arise from this quantum critical state of matter. The pseudogap phase possesses a variety of fluctuations that lead to several symmetry-broken phases at low-energies. Benchmarking of the ground state energy per particle and the double-occupancy fraction obtained from a finite-size scaling analysis against existing numerical results yields excellent agreement. We present detailed insight into the T = 0 origin of several experimentally observed findings in the cuprates, including Homes law and Planckian dissipation. We also establish that the heirarchy of temperature scales for the pseudogap (T
PG), onset temperature for pairing (T
ons), formation of the Mott liquid (T
ML) and superconductivity (T
C) obtained from our analysis is quantitatively consistent with that observed experimentally for some members of the cuprates. Our results offer insight on the ubiquitous origin of superconductivity in doped Mott insulating states, and pave the way towards a systematic search for higher superconducting transition temperatures in such systems.
Influence of model resolution on bomb cyclones revealed by HighResMIP-PRIMAVERA simulations
Authors: Jiaxiang Gao , Shoshiro Minobe , Roberts Malcolm J , Haarsma Rein , Putrasahan Dian , Roberts Christopher D , Scoccimarro Enrico , Terray Laurent , Vannière Benoît , Vidale Pier Luigi
Published: April 2020

Bomb cyclones are explosively intensifying extratropical cyclones that can cause severe damage to life and property. However, the poor ability of coarse-resolution climate models to simulate bomb cyclones, including underestimation of the frequency of bomb cyclones, remains a problem. In this study, the dependence of bomb cyclone characteristics on horizontal resolution from 135 to 18 km is investigated by analyzing the outputs of HighResMIP historical simulations of atmospheric general circulation models and four reanalysis datasets. Robust resolution dependence of bomb cyclone characteristics is identified for both the models and the reanalyses. Finer horizontal resolution significantly increases the frequency of bomb cyclones and reduces their average horizontal size. A regression analysis indicates that bomb cyclone frequency is roughly doubled from 140 km to 25 km resolution. The overall increase in bomb cyclone number is associated with a large increase in small bomb cyclones and a moderate decrease in large ones. Bomb cyclones in higher-resolution models are also accompanied by a higher maximum wind speed and more extreme wind events, which is probably related to the increased pressure gradients due to the smaller size of the bomb cyclones. These results imply that high-resolution models should be used for evaluating the impacts of bomb cyclones.
Quantifying uncertainty in groundwater depth from sparse well data in the California Central Valley
Authors: Quay Amanda N. , Hering Amanda S. , Mauter Meagan S.
Published: April 2020

Groundwater is a critical freshwater resource for irrigation in the California Central Valley, particularly in times of drought. Groundwater depth has dropped rapidly in California’s overdrafted basins, but irregular monitoring across space and time limits the accuracy of the groundwater depth projections in the Groundwater Sustainability Plans required by the California Sustainable Groundwater Management Act (SGMA). This work constructs a Bayesian hierarchical model for predicting groundwater depth from sparse monitoring data in three Central Valley counties. We apply this model to generate 300 m resolution monthly groundwater depth estimates for drought years 2013–2015, and compare our smoothed groundwater depth map to smoothed rasterized maps published by the CA Department of Water Resources. Finally, we quantify uncertainty in groundwater depth predictions that are made by imputing missing well data and interpolating predictions across the study domain, which is helpful in directing future sampling efforts towards areas with high uncertainty. The BHM model accurately captures the spatiotemporal pattern in groundwater depth, as evidenced by 94.54% of withheld test samples’ true depth being covered by the 95% prediction interval drawn from the BHM posterior distribution. The model converged despite a very sparse dataset, demonstrating broad applicability for evaluating changes in regional groundwater depth as required by SGMA. Depth prediction intervals can also help prioritize future groundwater depth sampling activity and increase the utility of groundwater depth maps in total storage predictions by enabling sensitivity analysis.
Toda lattice hierarchy and soliton equations on square lattice
Authors: Kakei Saburo
Published: April 2020

Lattice soliton equations of KdV-family and Boussinesq-family are investigated from the viewpoint of the Toda lattice hierarchy. As a consequence, special solutions such as soliton solutions and algebro-geometric solutions are constructed in a unified manner.
The influence of deposition gases on the material properties of Y2SiO5: Ce3+ thin films deposited by pulsed laser deposition (PLD) method
Authors: Haile H T , Dejene F B
Published: April 2020

The material properties of Y2SiO5: Ce3+ thin films have been investigated. The X-ray powder diffraction (XRD) analysis shows that the films are structurally monoclinic with the most prominent diffraction peak of 15.7 °. The maximum crystallize size was obtained for samples deposited under oxygen deposition. The PL emission peaks are observed at 423 nm when probed at 370 nm, which can be ascribed to the transition of the electrons from the excited state of 5d to the ground state of 4f. Due to the spin–orbit interactions, the 4f ground state splits into 2f5/2 and 2f7/2 energy sub-levels. The scanning electron microscopy (SEM) measurement shows a rough and uniform distribution of grains with small agglomerated topographic areas. The energy dispersive spectroscopy (EDS) measurements shows the presence of all elements (Y, Si, O, and Ce). The maximum and minimum absorbance of the visible ultraviolet (UV–vis) spectrum was observed for the thin films deposited under the Argon and vacuum atmospheres with small shifts from Argon to the other depositions. The energy bandgap varies between 3.14 and 4.33 eV. The CIE measurement gives the blue emission band at an emission wavelength of 423 nm. The activation energy was obtained in the range of 0.1733 and 0.1938 eV. The maximum activation energy was obtained under the argon gas deposition.
Room temperature chiral smectic C liquid crystal bearing para-phenylchclohexyl mesogenic core
Authors: Kim Doo Hun , Goh Munju
Published: April 2020

Novel calamitic chiral liquid crystal (LC) was synthesized by introducing chiral butanol moiety into the para-phenylcyclohexyl mesogenic core. We confirmed the liquid crystallinity of chiral LC using DSC, POM and XRD measurements. The chiral LC shows a stable enantiomeric LC phase both cooling and heating procedure. It was found that the chiral LC exhibits a stable LC phase at room temperature. In addition, the chiral LC was assigned as chiral smectic C (Sc*) phase with a tilted angle of 22.7°.
Thermochemical method of synthesizing stemmed nanoflower TiO2/eC3N4 heterojunction structures with enhanced solar water splitting
Authors: Tejasvi Ravi , Basu Suddhasatwa
Published: April 2020

TiO2 nanoflower array linking to stem on a Ti foil is synthesized by thermochemical digestion of titanium at 80 °C by hydrogen peroxide and hydrofluoric acid solution. TiO2 nanoflower comprised of the anatase TiO2 which encased Ti metal core as seen by transmission electron microscopy (TEM), x-ray Photoelectron Spectroscopy based depth profiling, x-ray diffraction (XRD) analysis, and energy dispersive x-ray based elemental mapping. The TEM, selected area electron diffraction, and XRD analysis of air annealed TiO2 nanoflower show presence of anatase (101) and anatase (200) crystals of about 35 nm size. The Photoelectrochemical activity in water splitting is assessed for heterojunction formed by the TiO2 nanoflower with exfoliated carbon nitride (eC3N4), and the same is compared with heterojunction of TiO2 nanotubular array and eC3N4. It was found from linear sweep voltammetry and electrochemical impedance spectroscopy that the synthesized stemmed-nanoflower TiO2 offers superior PEC activity towards water splitting when used in heterojunction with eC3N4 as compared to that of TiO2 nanotube with eC3N4.
Voxelotor Treatment Interferes With Quantitative and Qualitative Hemoglobin Variant Analysis in Multiple Sickle Cell Disease Genotypes
Authors: Rutherford-Parker Nicola J , Campbell Sean T , Colby Jennifer M , Shajani-Yi Zahra
Published: April 2020

Objectives

Voxelotor was recently approved for use in the United States as a treatment for sickle cell disease (SCD) and has been shown to interfere with the quantitation of hemoglobin (Hb) S percentage. This study aimed to determine the effect of voxelotor on the quantitation of hemoglobin variant levels in patients with multiple SCD genotypes.

Methods

In vitro experiments were performed to assess the impact of voxelotor treatment on hemoglobin variant testing. Whole blood samples were incubated with voxelotor and then analyzed by routinely used quantitative and qualitative clinical laboratory methods (high-performance liquid chromatography [HPLC], capillary zone electrophoresis [CZE], and acid and alkaline electrophoresis).

Results

Voxelotor modified the α-globin chain of multiple hemoglobins, including HbA, HbS, HbC, HbD-Punjab, HbE, HbA2, and HbF. These voxelotor-hemoglobin complexes prevented accurate quantitation of multiple hemoglobin species, including HbS, by HPLC and CZE.

Conclusions

Technical limitations in quantifying HbS percentage may preclude the use of HPLC or CZE for monitoring patients treated with voxelotor. Furthermore, it is unclear whether HbS-voxelotor complexes are clinically equivalent to HbS. Consensus guidelines for reporting hemoglobin variant percentages for patients taking voxelotor are needed, as these values are necessary for determining the number of RBC units to exchange in acute situations.
ShallowHRD: detection of homologous recombination deficiency from shallow whole genome sequencing
Authors: Eeckhoutte Alexandre , Houy Alexandre , Manié Elodie , Reverdy Manon , Bièche Ivan , Marangoni Elisabetta , Goundiam Oumou , Vincent-Salomon Anne , Stoppa-Lyonnet Dominique , Bidard François-Clément , Stern Marc-Henri , Popova Tatiana
Published: April 2020

We introduce shallowHRD, a software tool to evaluate tumor homologous recombination deficiency (HRD) based on whole genome sequencing (WGS) at low coverage (shallow WGS or sWGS; ∼1X coverage). The tool, based on mining copy number alterations profile, implements a fast and straightforward procedure that shows 87.5% sensitivity and 90.5% specificity for HRD detection. shallowHRD could be instrumental in predicting response to poly(ADP-ribose) polymerase inhibitors, to which HRD tumors are selectively sensitive. shallowHRD displays efficiency comparable to most state-of-art approaches, is cost-effective, generates low-storable outputs and is also suitable for fixed-formalin paraffin embedded tissues.

Availability and implementation

shallowHRD R script and documentation are available at https://github.com/aeeckhou/shallowHRD.

Supplementary information

Supplementary data are available at Bioinformatics online.
Making Sense of Social Work’s Troubled Past: Professional Identity, Collective Memory and the Quest for Historical Justice
Authors: Ioakimidis Vasilios , Trimikliniotis Nicos
Published: April 2020

Social work historiography has neglected to engage meaningfully with the most troubling aspects of the profession’s past: the histories of complicity, or at least acquiescence, in acts of state violence and institutionalised oppression. Through the exploration of historical case studies, this article provides a tentative typology of social work’s ‘horrible histories’ focusing on the project of engineering the ideal-type family, in colonial and oppressive socio-political contexts. The authors argue that practices of oppression and complicity can neither be reduced to the ‘few bad apples’ approach nor judged through the individualising prism of moralism, prevalent in Kantian Ethics. Instead, they propose an ethics of transformative reconciliation which is based on the principles of apology, respect for victims and collective action for—professional and social—change.
Bisphenol S is a haemodialysis-associated xenobiotic that is less toxic than bisphenol A
Authors: Mas Sebastian , Ruiz-Priego Alberto , Abaigar Pedro , Santos Javier , Camarero Vanesa , Egido Jesús , Ortiz Alberto , Gonzalez-Parra Emilio
Published: April 2020

Background

Bisphenol S (BPS) is a structural analogue of bisphenol A (BPA) that is found in the environment. BPS may accumulate in anuric patients due to decreased urinary excretion. The toxicity and health effects of BPS are poorly characterized.

Methods

A cross-over study was performed using polynephron (PN) or polysulphone (PS) dialysers for a short (1 week each, 14 patients) or long (3 months each, 20 patients) period on each dialyser. Plasma BPA, BPS and hippuric acid were assessed by SRM mass spectrometry (SRM-MS). The biological significance of the BPS concentrations found was explored in cultured kidney tubular cells.

Results

In haemodiafiltration (HDF) patients, plasma BPS was 10-fold higher than in healthy subjects (0.53 ± 0.52 versus 0.05 ± 0.01 ng/mL; P = 0.0015), while BPA levels were 35-fold higher (13.23 ± 14.65 versus 0.37 ± 0.12 ng/mL; P = 0.007). Plasma hippuric acid decreased after an HDF session, while BPS and BPA did not. After 3 months of HDF with the same membranes, the BPS concentration was 1.01 ± 0.87 ng/mL for PN users and 0.62 ± 0.21 ng/mL for PS users (P non-statistically significant). In vitro, BPS and BPA leaked from dialysers containing them. In cultured tubular cells, no biological impact (cytotoxicity, inflammatory and oxidative stress gene expression) was observed for BPS up to 200 µM, while BPA was toxic at concentrations ≥100 µM.

Conclusions

BPS may be released from dialysis membranes, and dialysis patients display high BPS concentrations. However, BPS concentrations are lower than BPA concentrations and no BPS toxicity was observed at concentrations found in patient plasma.
Negative Voters? Electoral Competition with Loss-Aversion
Authors: Lockwood Ben , Rockey James
Published: April 2020

This paper studies the effect of voter loss aversion in preferences over both candidate policy platforms and candidate valence on electoral competition. Loss-aversion over platforms leads to both platform rigidity and reduced platform polarisation, whereas loss-aversion over valence results in increased polarisation and the possibility of asymmetric equilibria with a self-fulfilling (dis)-advantage for the incumbent. The results are robust to a stochastic link between platforms and outcomes; they hold approximately for a small amount of noise. A testable implication of loss-aversion over platforms is that incumbents adjust less than challengers to shifts in voter preferences. We find some empirical support for this using data for elections to the US House of Representatives.
Long Live Keju! The Persistent Effects of China’s Civil Examination System
Authors: Chen Ting , Kung James Kai-sing , Ma Chicheng
Published: April 2020

China's civil examination system (keju), an incredibly long-lived institution, has a persistent impact on human capital outcomes today. Using the variation in the density of jinshi—the highest qualification—across 278 Chinese prefectures in the Ming-Qing period (c. 1368–1905) to proxy for this effect, we find that a doubling of jinshi per 10,000 population leads to an 8.5% increase in years of schooling in 2010. The persistent effect of keju can be attributed to a multitude of channels including cultural transmission, educational infrastructure, social capital and, to a lesser extent, political elites.
The impact of obesity on orthodontic treatment outcome in adolescents: a prospective clinical cohort study
Authors: Saloom Hayder F , Boustan Roshanak , Seehra Jadbinder , Papageorgiou Spyridon N , Carpenter Guy H , Cobourne Martyn T
Published: April 2020

Introduction

This prospective clinical cohort study investigated the potential influence of obesity on orthodontic treatment outcome.

Methods

A prospective cohort of adolescent patients undergoing routine fixed appliance treatment were recruited into normal-weight or obese groups based upon body mass index (BMI) centile and followed up until the completion of treatment. Primary outcome was treatment duration, and secondary outcomes included treatment outcome (occlusal change measured using peer assessment rating [PAR]), appointment characteristics, and compliance measures.

Results

A total of 45 patients mean age 14.8 (1.6) years were included in the final analysis. The normal-weight group included 23 patients with mean BMI 19.4 (2.4) kg/m2 and the obese group 22 patients with mean BMI 30.5 (3.8) kg/m2. There were no significant differences in baseline demographics between groups, except for BMI and pre-treatment PAR. The normal-weight group had a mean pre-treatment PAR of 25.6 (8.3) and the obese 33.3 (11.8) giving the obese group a more severe pre-treatment malocclusion (P = 0.02). There were no significant differences in treatment duration between groups (P = 0.36), but obese patients needed less time per each additional baseline PAR point compared to normal weight (P = 0.02). Obese patients also needed less appointments compared to normal-weight patients (P = 0.02). There were no significant differences between groups for appointment characteristics or compliance. Finally, obese patients were more likely to experience a great PAR reduction than normal-weight patients (relative risk = 2.6; 95% confidence interval = 1.2–4.2; P = 0.02).

Conclusions

There were no significant differences in treatment duration between obese and normal-weight patients. Obesity does not appear to be a risk factor for negative orthodontic treatment outcome with fixed appliances.
Ser and Thr acceptor preferences of the GalNAc-Ts vary among isoenzymes to modulate mucin-type O-glycosylation
Authors: Daniel Earnest James Paul , las Rivas Matilde , Lira-Navarrete Erandi , García-García Ana , Hurtado-Guerrero Ramon , Clausen Henrik , Gerken Thomas A
Published: April 2020

A family of polypeptide GalNAc-transferases (GalNAc-Ts) initiates mucin-type O-glycosylation, transferring GalNAc onto hydroxyl groups of Ser and Thr residues of target substrates. The 20 GalNAc-T isoenzymes in humans are classified into nine subfamilies according to sequence similarity. GalNAc-Ts select their sites of glycosylation based on weak and overlapping peptide sequence motifs, as well prior substrate O-GalNAc glycosylation at sites both remote (long-range) and neighboring (short-range) the acceptor. Together, these preferences vary among GalNAc-Ts imparting each isoenzyme with its own unique specificity. Studies on the first identified GalNAc-Ts showed Thr acceptors were preferred over Ser acceptors; however studies comparing Thr vs. Ser glycosylation across the GalNAc-T family are lacking. Using a series of identical random peptide substrates, with single Thr or Ser acceptor sites, we determined the rate differences (Thr/Ser rate ratio) between Thr and Ser substrate glycosylation for 12 isoenzymes (representing 7 GalNAc-T subfamilies). These Thr/Ser rate ratios varied across subfamilies, ranging from ~2 to ~18 (for GalNAc-T4/GalNAc-T12 and GalNAc-T3/GalNAc-T6, respectively), while nearly identical Thr/Ser rate ratios were observed for isoenzymes within subfamilies. Furthermore, the Thr/Ser rate ratios did not appreciably vary over a series of fixed sequence substrates of different relative activities, suggesting the ratio is a constant for each isoenzyme against single acceptor substrates. Finally, based on GalNAc-T structures, the different Thr/Ser rate ratios likely reflect differences in the strengths of the Thr acceptor methyl group binding to the active site pocket. With this work, another activity that further differentiates substrate specificity among the GalNAc-Ts has been identified.
Unresolved Heterogeneity in Meta-Analysis: Combined Construct Invalidity, Confounding, and Other Challenges to Understanding Mean Effect Sizes
Authors: Levine Timothy R , Weber René
Published: April 2020

We examined the interplay between how communication researchers use meta-analyses to make claims and the prevalence, causes, and implications of unresolved heterogeneous findings. Heterogeneous findings can result from substantive moderators, methodological artifacts, and combined construct invalidity. An informal content analysis of meta-analyses published in four elite communication journals revealed that unresolved between-study effect heterogeneity was ubiquitous. Communication researchers mainly focus on computing mean effect sizes, to the exclusion of how effect sizes in primary studies are distributed and of what might be driving effect size distributions. We offer four recommendations for future meta-analyses. Researchers are advised to be more diligent and sophisticated in testing for heterogeneity. We encourage greater description of how effects are distributed, coupled with greater reliance on graphical displays. We council greater recognition of combined construct invalidity and advocate for content expertise. Finally, we endorse greater awareness and improved tests for publication bias and questionable research practices.
Economic analysis of the adoption of capsule endoscopy within the British NHS
Authors: Lobo Alan , Torrejon Torres Rafael , McAlindon Mark , Panter Simon , Leonard Catherine , van Lent Nancy , Saunders Rhodri
Published: April 2020

Objective

Identification of a cost-effective treatment strategy is an unmet need in Crohn’s disease (CD). Here we consider the patient outcomes and cost impact of pan-intestinal video capsule endoscopy (PVCE) in the English National Health Service (NHS).

Design

An analysis of a protocolized CD care pathway, informed by guidelines and expert consensus, was performed in Microsoft Excel. Population, efficacy and safety data of treatments and monitoring modalities were identified using a structured PubMed review with English data prioritized. Costs were taken from the NHS and Payer Provided Services (PSS) 2016–17 tariffs for England and otherwise literature. Analysis was via a discrete-individual simulation with discounting at 3.5% per annum.

Setting

NHS provider and PSS perspective

Participants

4000 simulated CD patients

Interventions

PVCE versus colonoscopy ± magnetic resonance enterography (MRE)

Main outcome measures

Costs in 2017 GBP and quality-adjusted life years (QALY)

Results

The mean, total 20-year cost per patient was £42 266 with colonoscopy ± MRE and £38 043 with PVCE. PVCE incurred higher costs during the first 2 years due to higher treatment uptake. From year 3 onwards, costs were reduced due to fewer surgeries. Patients accrued 10.67 QALY with colonoscopy ± MRE and 10.96 with PVCE. PVCE dominated (less cost and higher QALY) colonoscopy ± MRE and was likely (>74%) to be considered cost-effective by the NHS. Results were similar if a lifetime time horizon was used.

Conclusions

PVCE is likely to be a cost-effective alternative to colonoscopy ± MRE for CD surveillance. Switching to PVCE resulted in lower treatment costs and gave patients better quality of life.
Physician-to-Physician Electronic Consultation: A Tool for the Pediatric Infectious Diseases Specialist to Document Encounters and Quantify Effort
Authors: Gonzalez Blanca E , Sabella Camille , Esper Frank P , Daniels Heather L , Saracusa Carla , Boutros Jasmine , Foster Charles B
Published: April 2020

E-consults replace “curbside” interactions, facilitate provider–specialist communication, document within the medical record, and track relative value units (RVUs). Pediatric infectious diseases (PID) E-consults commonly relate to vaccines, exposures, diagnoses, and treatments. The documented RVU effort of 197 consecutive PID E-consults was equivalent to 70 level 4 new outpatient consults.
Community universal face mask use during the COVID 19 pandemic—from households to travellers and public spaces
Authors: Raina MacIntyre C , Jay Hasanain S
Published: April 2020

As the COVID-19 pandemic grows globally, universal face mask use (UFMU) has become a topic of discussion, with a recommendation made from the US Centers for Disease Control (CDC) for cloth mask use by community members. Other countries and the World Health Organization advise against UFMU. We outline the rationale and evidence supporting UFMU in households, during travel and in crowded public spaces in high transmission community settings.
In vitro anti-Pythium insidiosum activity of amorolfine hydrochloride and azithromycin, alone and in combination
Authors: Ianiski Lara Baccarin , Stibbe Paula Cristina , Denardi Laura Bedin , Weiblen Carla , Soares Mauro Pereira , Valente Julia de Souza Silveira , Sangioni Luís Antônio , Pereira Daniela Isabel Brayer , Santurio Janio Morais , Botton Sônia de Avila
Published: April 2020

Pythium insidiosum infections have been widely studied in an attempt to develop an effective therapeutic protocol for the treatment of human and animal pythiosis. Several antifungal agents are still prescribed against this oomycete, although they present contradictory results. To evaluate the susceptibility profile and to verify the morphological alterations in P. insidiosum isolates treated with amorolfine hydrochloride and azithromycin, alone or in combination. Susceptibility tests for P. insidiosum isolates (n = 20) against amorolfine hydrochloride (AMR) and azithromycin (AZM) were performed according to Clinical and Laboratory Standards Institutes (CLSI) protocol M38-A2. Combinations of both drugs were evaluated using the checkerboard microdilution method. Additionally, transmission and scanning electron microscopy were performed in order to verify the morphological alterations in P. insidiosum isolates in response to these drugs. All P. insidiosum isolates had a minimum inhibitory concentration (MIC) ranging from 16 to 64 mg/l and 8 to 64 mg/l for amorolfine hydrochloride and azithromycin, respectively. Synergistic interactions between the drugs were not observed, with antagonism in 59.8% of isolates, and indifferent interactions in 36.2%. Electron microscopy showed changes in the surface of P. insidiosum hyphae, disorganization of intracellular organelles, and changes in the plasma membrane and cell wall of oomycetes treated with the drugs. This is the first study to demonstrate in vitro anti-P. insidiosum effect of amorolfine hydrochloride. These results indicate the therapeutic potential of this drug against cutaneous and subcutaneous forms of pythiosis, but further studies are necessary to confirm this potential.
Encounters of merger and accretion shocks in galaxy clusters and their effects on intracluster medium
Authors: Zhang Congyao , Churazov Eugene , Dolag Klaus , Forman William R , Zhuravleva Irina
Published: April 2020

Several types/classes of shocks naturally arise during formation and evolution of galaxy clusters. One such class is represented by accretion shocks, associated with deceleration of infalling baryons. Such shocks, characterized by a very high Mach number, are present even in 1D models of cluster evolution. Another class is composed of ‘runaway merger shocks’, which appear when a merger shock, driven by a sufficiently massive infalling subcluster, propagates away from the main-cluster centre. We argue that, when the merger shock overtakes the accretion shock, a new long-living shock is formed that propagates to large distances from the main cluster (well beyond its virial radius), affecting the cold gas around the cluster. We refer to these structures as Merger-accelerated Accretion shocks (MA-shocks) in this paper. We show examples of such MA-shocks in one-dimensioanal (1D) and three-dimensional (3D) simulations and discuss their characteristic properties. In particular, (1) MA-shocks shape the boundary separating the hot intracluster medium (ICM) from the unshocked gas, giving this boundary a ‘flower-like’ morphology. In 3D, MA-shocks occupy space between the dense accreting filaments. (2) Evolution of MA-shocks highly depends on the Mach number of the runaway merger shock and the mass accretion rate parameter of the cluster. (3) MA-shocks may lead to the misalignment of the ICM boundary and the splashback radius.
Detection of weak magnetic fields in two HgMn stars
Authors: Hubrig S , Järvinen S P , Korhonen H , Ilyin I , Schöller M , Niemczura E , Chojnowski S D
Published: April 2020

The main-sequence mercury–manganese (HgMn) stars are known to exhibit large overabundances of exotic elements and, similar to magnetic Ap/Bp stars, are spectrum variables, implying the presence of an inhomogeneous element distribution over the stellar surface. A number of magnetic field studies have been attempted in the last decades, indicating that magnetic fields in HgMn stars, if they exist, should be rather weak. The presence of tangled magnetic fields was suggested by several authors who detected quadratic magnetic fields using the moment technique. We employ the least-squares deconvolution technique to carry out a sensitive search for weak magnetic fields in spectropolarimetric observations of three HgMn stars, HD 221507, HD 65949, and HD 101189, which have different fundamental parameters and spectral characteristics. A definite weak longitudinal field is discovered in HD 221507 and HD 65949 on single epochs, while only marginal field detections were achieved for HD 101189. The new measurements indicate that the structure of the magnetic fields is probably rather complex: our analysis reveals the presence of reversed Stokes V profiles at the same observational epoch if individual elements are used in the measurements. This is the first observational evidence that individual elements sample distinct local magnetic fields of different polarity across the stellar surface.
Modeling glioblastoma invasion using human brain organoids and single-cell transcriptomics
Authors: Krieger Teresa G , Tirier Stephan M , Park Jeongbin , Jechow Katharina , Eisemann Tanja , Peterziel Heike , Angel Peter , Eils Roland , Conrad Christian
Published: April 2020

Background

Glioblastoma (GBM) consists of devastating neoplasms with high invasive capacity, which have been difficult to study in vitro in a human-derived model system. Therapeutic progress is also limited by cellular heterogeneity within and between tumors, among other factors such as therapy resistance. To address these challenges, we present an experimental model using human cerebral organoids as a scaffold for patient-derived GBM cell invasion.

Methods

This study combined tissue clearing and confocal microscopy with single-cell RNA sequencing of GBM cells before and after co-culture with organoid cells.

Results

We show that tumor cells within organoids extend a network of long microtubes, recapitulating the in vivo behavior of GBM. Transcriptional changes implicated in the invasion process are coherent across patient samples, indicating that GBM cells reactively upregulate genes required for their dispersion. Potential interactions between GBM and organoid cells identified by an in silico receptor–ligand pairing screen suggest functional therapeutic targets.

Conclusions

Taken together, our model has proven useful for studying GBM invasion and transcriptional heterogeneity in vitro, with applications for both pharmacological screens and patient-specific treatment selection on a time scale amenable to clinical practice.
A combined approach of convection-enhanced delivery of peptide nanofiber reservoir to prolong local DM1 retention for diffuse intrinsic pontine glioma treatment
Authors: Bellat Vanessa , Alcaina Yago , Tung Ching-Hsuan , Ting Richard , Michel Adam O , Souweidane Mark , Law Benedict
Published: April 2020

Background

Diffuse intrinsic pontine glioma (DIPG) is a highly lethal malignancy that occurs predominantly in children. DIPG is inoperable and post-diagnosis survival is less than 1 year, as conventional chemotherapy is ineffective. The intact blood–brain barrier (BBB) blocks drugs from entering the brain. Convection-enhanced delivery (CED) is a direct infusion technique delivering drugs to the brain, but it suffers from rapid drug clearance. Our goal is to overcome the delivery barrier via CED and maintain a therapeutic concentration at the glioma site with a payload-adjustable peptide nanofiber precursor (NFP) that displays a prolonged retention property as a drug carrier.

Methods

The post-CED retention of 89Zr-NFP was determined in real time using PET/CT imaging. Emtansine (DM1), a microtubule inhibitor, was conjugated to NFP. The cytotoxicity of the resulting DM1-NFP was tested against patient-derived DIPG cell lines. The therapeutic efficacy was evaluated in animals bearing orthotopic DIPG, according to glioma growth (measured using bioluminescence imaging) and the long-term survival.

Results

DM1-NFP demonstrated potency against multiple glioma cell lines. The half-maximal inhibitory concentration values were in the nanomolar range. NFP remained at the infusion site (pons) for weeks, with a clearance half-life of 60 days. DM1-NFP inhibited glioma progression in animals, and offered a survival benefit (median survival of 62 days) compared with the untreated controls (28 days) and DM1-treated animal group (26 days).

Conclusions

CED, in combination with DM1-NFP, complementarily functions to bypass the BBB, prolong drug retention at the fusion site, and maintain an effective therapeutic effect against DIPG to improve treatment outcome.