bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamics of an Anisotropic Metaphosphate LiNaKCsPO3Glass by Inelastic X‐Ray Scattering
Authors: Hosokawa Shinya , Inaba Seiji , Uchiyama Hiroshi , Tsutsui Satoshi
Published: June 2020

To clarify the mechanism of the entropic shrinkage of a metaphosphate LiNaKCsPO3glass, high‐resolution inelastic X‐ray scattering is carried out in the momentum transfer (Q) range from 1.6 to 15.9 nm−1by changing the stretched sample rod directions perpendicular and parallel to the X‐ray scattering plane. Phonon excitations are found only in a lowQrange below about 3 nm−1, and the so‐called Boson peaks are observed in theQregion beyond 5.6 nm−1. These excitations exhibit mostly no differences in the rod direction. A spectral enhancement at the prepeak position in the total X‐ray scattering spectrum is due to the quasielastic contributions. The direction difference in the width of the quasielastic peak becomes largely broadened near the prepeak region, which may be owing to a low excitation energy of the phosphate chains across the chain direction.
Effects of a Rhodiola rosea extract on mental resource allocation and attention: An event‐related potential dual task study
Authors: Koop Tina , Dienel Angelika , Heldmann Marcus , Münte Thomas F.
Published: June 2020

Rhodiola rosea extract is widely used to alleviate stress and improve cognition and mental resources. A total of 50 adult participants were treated with 2 × 200 mg R. rosea extract (Rosalin®, WS® 1,375) for 12 weeks and were subjected to a neuropsychological test battery as well as an event‐related brain potential measurement in a dual task paradigm prior to administration, after 6 weeks and after 12 weeks. The study followed a single‐arm open‐label design. Reaction times improved for the attention network task (ANT), the Go/Nogo task, and the divided attention task. Moreover, the orienting effect and the executive effect in the ANT showed an improvement. The P3 component in a dual task paradigm was increased in amplitude. The results of this pilot study show an improvement of mental speed and moreover, suggest improved mental resources. As the current study is single‐armed these findings need to be replicated in a double‐blind placebo controlled study.
Improving convergence of experimental and computed vertical ionization energies using the ionization potential equation‐of‐motion coupled‐cluster with singles and doubles method
Authors: Buzzanca Marissa , Brummeyer Brandon , Gutow Jonathan H.
Published: June 2020

Comparison of statistically evaluated experimental vertical ionization energies (IEs) for 53 medium‐sized molecules (6‐34 atoms) with ionization potential equation‐of‐motion coupled‐cluster with singles and doubles (IP‐EOMCCSD) computations shows that discrepancies between computed and experimental results can be accounted for with a combination of experimental and theoretical contributions. Discrepancies can be minimized by extrapolating computations to the complete basis set limit and correcting for vibrational zero‐point energy (ZPE) while comparing with experimental IEs calculated as the intensity‐weighted mean band position to account for band asymmetries. This procedure reduced the average discrepancy for ethylene, (E)‐2‐butene, 2,5‐dihydrofuran, and pyrrole from 0.25 to 0.05 eV. Agreement between reported vertical IEs and computations without either making adjustments as described in this paper or using complete simulation of the ionization spectrum should be considered fortuitous. The comparisons made in this work show that estimates of vertical and adiabatic IE made using IP‐EOMCCSD extrapolated to the complete basis set limit and corrected for vibrational ZPE can be used with reasonable confidence when experimental values are not available.
The conformational space of a flexible amino acid at metallic surfaces
Authors: Maksimov Dmitrii , Baldauf Carsten , Rossi Mariana
Published: June 2020

In interfaces between inorganic and biological materials relevant for technological applications, the general challenge of structure determination is exacerbated by the high flexibility of bioorganic components, chemical bonding, and charge rearrangement at the interface. In this paper, we investigate a chemically complex building block, namely, the arginine (Arg) amino acid interfaced with Cu, Ag, and Au (111) surfaces. We investigate how the environment changes the accessible conformational space of this amino acid by building and analyzing a database of thousands of structures optimized with the Perdew‐Burke‐Ernzerhof (PBE) functional, including screened pairwise van der Waals interactions. When in contact with metallic surfaces, the accessible space for Arg is dramatically reduced, while the one for Arg‐H+ is instead increased if compared to the gas phase. This is explained by the formation of strong bonds between Arg and the surfaces and by their absence and charge screening on Arg‐H+ upon adsorption. We also observe protonation‐dependent stereoselective binding of the amino acid to the metal surfaces: Arg adsorbs with its chiral CαH center pointing H away from the surfaces, while Arg‐H+ adsorbs with H pointing toward the surface.
Local decoding and testing of polynomials over grids
Authors: Bafna Mitali , Srinivasan Srikanth , Sudan Madhu
Published: June 2020

We study the local decodability and (tolerant) local testability of low‐degree n‐variate polynomials over arbitrary fields, evaluated over the domain {0,1}n. We show that for every field there is a tolerant local test whose query complexity depends only on the degree. In contrast we show that decodability is possible over fields of positive characteristic, but not over the reals.
A new test specimen for the determination of the field of view of small‐area X‐ray photoelectron spectrometers
Authors: Stockmann Jörg M. , Radnik Jörg , Bütefisch Sebastian , Busch Ingo , Weimann Thomas , Passiu Cristiana , Rossi Antonella , Unger Wolfgang E.S.
Published: June 2020

Small‐area/spot photoelectron spectroscopy (SAXPS) is a powerful tool for the investigation of small surface features like microstructures of electronic devices, sensors or other functional surfaces, and so forth. For evaluating the quality of such microstructures, it is often crucial to know whether a small signal in a spectrum is an unwanted contamination of the field of view (FoV), defined by the instrument settings, or it originated from outside. To address this issue, the d80/20 parameter of a line scan across a chemical edge is often used. However, the typical d80/20 parameter does not give information on contributions from the long tails of the X‐ray beam intensity distribution or the electron‐optical system as defined by apertures. In the VAMAS TWA2 A22 project “Applying planar, patterned, multi‐metallic samples to assess the impact of analysis area in surface‐chemical analysis,” new test specimen was developed and tested. The here presented testing material consists of a silicon wafer substrate with an Au‐film and embedded Cr circular and square spots with decreasing dimensions from 200 μm down to 5 μm. The spot sizes are traceable to the length unit due to size measurements with a metrological SEM. For the evaluation of the FoV, we determined the Au4f intensities measured with the center of the FoV aligned with the center of the spot and normalized to the Au4f intensity determined on the Au‐film. With this test specimen, it was possible to characterize, as an example, the FoV of a Kratos AXIS Ultra DLD XPS instrument.
XPS study of a laser‐nitrided iron surface using a focused pulsed Nd:YAG laser under various conditions
Authors: Takiguchi Kodai , Miura Koyo , Ohtsu Naofumi
Published: June 2020

Laser nitridation of a pure iron (Fe) surface was conducted using a focused pulsed Nd:YAG laser under a nitrogen atmosphere, and the effects of nitrogen gas pressure, laser power, and repetition number of laser shots on the surface characteristics were analyzed using XPS. The laser‐irradiated surface consisted of the topmost surface layer of Fe oxynitride (FeOxNy) and the underlayer beneath, which mainly comprised Fe nitride (Fe4N). The topmost surface layer is a post‐formed layer due to the oxidation of the nitride layer. The thickness of the underlayer corresponding to the original nitride layer drastically increased under nitrogen gas at atmospheric pressure. Increasing the repetition number of laser shots enhanced layer thickness up to 5 shots, after which no change was observed. Moreover, the layer thickness increased monotonically with increasing laser power. Nitridation through pulsed laser irradiation was likely predominated by the melting and resolidification of a specific surface area, as well as the convection of nitrogen therein. Thickness variation under various conditions can be explained appropriately using this assumption.
In‐depth analysis of InAlN/GaN HEMT heterostructure after annealing using angle‐resolved X‐ray photoelectron spectroscopy
Authors: Bourlier Yoan , Bouttemy Muriel , Fregnaux Mathieu , Patard Olivier , Gamarra Piero , Piotrowicz Stephane , Delage Sylvain , Etcheberry Arnaud
Published: June 2020

During high‐electron‐mobility transistor elaboration process, a thermal treatment of In0.2Al0.8N (InAlN) barrier layer is performed in order to improve electrical performances. We showed previously that In0.2Al0.8N/GaN heterostructures, annealed at 850°C under O2 partial pressure, present a specific in‐depth organization. Angle‐resolved X‐ray photoelectron spectroscopy is a powerful tool to precisely determine the spatial localization and relative position of the different interfaces, from InAlN until buried GaN layer. The proposed in‐depth model of the stack evidences (1) an Al‐rich surface oxide with embedded N2 molecules, (2) an interlayer of InAlN<1 governed by nitrogen lattice defects, (3) a stable In0.2Al0.8N matrix, and finally (4) the GaN buffer layer underneath.
Synthesis, Solution and Solid‐State Fluorescence of 2‐(N‐cycloamino)cinchomeronic Dinitrile Derivatives
Authors: Ershova Anastasia I. , Ievlev Mikhail Yu. , Maksimova Veronika N. , Belikov Mikhail Yu. , Ershov Oleg V.
Published: June 2020

A facile approach to the synthesis of novel 2‐(N‐cycloamino)cinchomeronic dinitriles showing intense photoluminescence both in solution and solid state was developed. Absorption, fluorescence and solvatochromic properties were investigated. It was found that the 2‐(N‐cycloamino)cinchomeronic dinitrile derivatives containing conjugated aryl moiety show intense emission in nonpolar solvents with fluorescence quantum yield up to 0.8.
Chemoselective Hydrogenation of Functionalized Nitroarenes into Anilines by Supported Molybdenum Catalysts
Authors: Yan Shasha , Guo Yanzhu , Xiao Ling‐Ping , Chen Xiaohong , Sun Run‐Cang
Published: June 2020

Anilines are the most important fine chemicals that have been widely used as the intermediates of industrial products. Herein, a new series of nanostructured Mo‐based catalysts were reported, such as MoOx/ZSM‐5(25), MoOx/ZSM‐5(50) and MoOx/SBA‐15, which can serve as efficient catalysts in the hydrogenation of nitroarenes by using hydrogen as the reducing reagent to afford functionalized anilines. Those catalysts showed both excellent activity and high chemoselectivity of the nitro group even though other reducible groups (C−X, C=C, C=O and C≡N) were exiting. This protocol constitutes an economically responsible pathway for the synthesis of anilines in high yields, good functional group compatibility and high chemselectivity.
High Throughput Screening of Cell Mechanical Response Using a Stretchable 3D Cellular Microarray Platform
Authors: Sakthivel Kabilan , Kumar Hitendra , Mohamed Mohamed G. A. , Talebjedi Bahram , Shim Justin , Najjaran Homayoun , Hoorfar Mina , Kim Keekyoung
Published: June 2020

Cells in vivo are constantly subjected to multiple microenvironmental mechanical stimuli that regulate cell function. Although 2D cell responses to the mechanical stimulation have been established, these methods lack relevance as physiological cell microenvironments are in 3D. Moreover, the existing platforms developed for studying the cell responses to mechanical cues in 3D either offer low‐throughput, involve complex fabrication, or do not allow combinatorial analysis of multiple cues. Considering this, a stretchable high‐throughput (HT) 3D cell microarray platform is presented that can apply dynamic mechanical strain to cells encapsulated in arrayed 3D microgels. The platform uses inkjet‐bioprinting technique for printing cell‐laden gelatin methacrylate (GelMA) microgel array on an elastic composite substrate that is periodically stretched. The developed platform is highly biocompatible and transfers the applied strain from the stretched substrate to the cells. The HT analysis is conducted to analyze cell mechano‐responses throughout the printed microgel array. Also, the combinatorial analysis of distinct cell behaviors is conducted for different GelMA microenvironmental stiffnesses in addition to the dynamic stretch. Considering its throughput and flexibility, the developed platform can readily be scaled up to introduce a wide range of microenvironmental cues and to screen the cell responses in a HT way.
Computational Fluid Dynamics Simulation of Iron Ore Reduction in Industrial‐Scale Fluidized Beds
Authors: Schneiderbauer Simon , Kinaci Mustafa Efe , Hauzenberger Franz
Published: June 2020

Detailed simulations of industrial‐scale fluidized beds such as the FINEX process are still unfeasible due to the wide range of spatial scales. Due to the computational limitations it is common to apply coarse grids, which do not resolve all relevant structures. In our previous study (Schneiderbauer, AIChE J. 2017, 63, 3562), we have presented subgrid models, which enable the coarse grid simulation of dense large‐scale gas–solid flows. Herein, these corrections are applied to a parcel‐based the dense discrete phase model (DDPM), allowing to study the hydrodynamics of the FINEX process. Furthermore, the parcel approach is augmented by an unreacted shrinking core model (USCM) to account for the direct reduction of the iron ore particles by the reducing agents of H2 and CO. This DDPM model is tested first for a cold pilot‐scale fluidized bed, and second, the USCM approach is validated for the direct reduction in a lab‐scale fluidized bed. Finally, the model is applied to the FINEX process. The results show fairly good agreement with measurements of the average bed voidage and with experimentally determined particle size distributions. The results further indicate that fines are immediately reduced, whereas the reduction of the largest ore grains takes considerably longer.
Effect of Work‐Hardening Mechanisms in Asymmetrically Cyclic‐Loaded Austenitic Stainless Steels on Low‐Cycle and High‐Cycle Fatigue Behavior
Authors: Moshtaghi Masoud , Safyari Mahdieh
Published: June 2020

Dislocation characteristics and deformation‐induced martensite (DIM) transformation in an asymmetrically cyclic‐loaded metastable type 304 stainless steel (SS) are investigated compared with a stable type 316SS using EBSD and X‐ray diffraction line‐profile analysis. In low‐cycle fatigue (LCF) regime, differences between dislocation densities of type 304SS and type 316SS are increased with decreasing fatigue life, and contribution of α′‐martensite to work hardening of cyclically loaded type 304SS increased with decreasing fatigue life. However, the contribution of austenite slightly changed. Higher work hardening via DIM transformation improves the fatigue life of type 304SS than that of type 316SS in LCF regime in the same fatigue stress amplitude. Thus, the contribution of α′‐martensite to work hardening is a determinant parameter, affecting the fatigue behavior of type 304SS. In HCF regime when the α′‐martensite had a small contribution to the work hardening, the fatigue life of type 304SS is slightly higher than that of type 316SS.
A systematic approach to estimating traffic load effects on bridges using weigh‐in‐motion data
Authors: Sjaarda Matthew , Meystre Thierry , Nussbaumer Alain , Hirt Manfred A.
Published: June 2020

In contrast to the Swiss load model used for new bridge structures (SIA 261), which has roots in a Europe‐wide weigh‐in‐motion (WIM) study and considers the full design life of new structures, the model for existing structures (SIA 269) from 2005 is derived from load effects produced by traffic measured by country‐specific WIM observations and considers a reduced return period.

With growing concerns regarding the scarcity of resources, efforts should be made to ensure safety by increasing the knowledge of loads and load‐carrying mechanisms, rather than through overdesign. This paper presents the methodology employed to use WIM data for generating maximum expected load effects on bridges and thus give engineers a tool with which bridge load effects can be accurately derived from real traffic. A re‐evaluation using the methodology outlined here began this year. It is planned to use the results of this for the next revision of the Swiss National Annexes to the Eurocodes and SIA 269.
Faculty Mentorship of Health Professions Students in Academic Difficulty
Authors: Bulloch Marilyn N. , Giovane Richard
Published: June 2020

Mentorship has existed in the health professions disciplines for centuries. This chapter discusses the challenges of mentorship specifically tailored to students in academic difficulty.
The Community Engaged Physician: Teaching Social Accountability Through Interprofessional Teamwork and Service‐Learning
Authors: Whisenant Ebony B. , Garba Nana Aisha , Schneider Gregory W. , Camps‐Romero Eduardo , Lage Onelia G. , Pedoussaut Maryse , Brown David R. , Greer Pedro J.
Published: June 2020

This chapter describes the goals and structure of a service‐learning experience integrated into a medical education curriculum. The curricular innovation fosters student understanding of social accountability, interprofessional teamwork as well as social determinants of health and can serve as an educational model for training future providers.
Redesigning Classroom and Experiential Teaching Peer Evaluation Tools to Strengthen the Peer Review Process
Authors: Eiland Lea S. , Helmer Allison M. , Kelley Kristi W. , Hester E. Kelly
Published: June 2020

This chapter describes the process of redesigning classroom and clinical experiential teaching peer evaluation tools to enhance formative peer review. The peer‐evaluation process is a commitment to improve teaching in all types of settings. Periodic peer evaluation is essential to ensure quality student education and growth of teachers.
Transitioning to a Competency‐Driven Curriculum
Authors: Hornsby Lori , Wright Bradley M.
Published: June 2020

The role of the pharmacist is evolving with pharmacists’ taking more direct responsibility for patient outcomes. As a result, pharmacy education must be designed to ensure graduates are competent and prepared to function within a complex healthcare system. Transitioning to a competency‐driven curriculum, can ultimately place the focus of the learner and faculty on outcomes specific to the skills and abilities needed for graduates to provide desired levels of care.
Challenges to Health Professions Education and Strategies for Moving Forward
Authors: Ford Channing R. , Moseley Lindsey
Published: June 2020

As the final chapter of this special issue, we recognize there are multiple challenges to working in the health professions that impact health professions educators’ abilities to teach and support learners. We provide a broad overview of the next generation of learners, in addition to exploring teaching and learning approaches for this population. Strategies include emerging best practices, learner expectations regarding technology, and mechanisms for supporting faculty as they transition to teaching Generation Z students.
Caustics bounding entanglement wedges
Authors: De Clerck Marine , Rabideau Charles , Tanger Niklas
Published: June 2020

Abstract

We study the caustics on the boundaries of entanglement wedges in the context of holography in asymptotically AdS3 spacetimes. These entanglement wedges play an important role in our understanding of the emergence of bulk locality. A procedure was proposed by Sanches and Weinberg for identifying boundary operators which are local in the bulk, which also applies to certain regions that lie beyond the reach of HRT surfaces by taking advantage of the lightsheets which bound entanglement wedges. We identify the caustics which terminate these lightsheets in conical deficit and BTZ black hole spacetimes and find that in some examples these caustics lead to a sharp corner in the entanglement wedge. The unexpected shape of these entanglement wedges leads, in those cases, to a breakdown of this procedure. Many of the properties of the rich variety of caustics possible in higher dimensions remains to be explored which, as this work demonstrates, could lead to more unexpected features in the shapes of entanglement wedges.
Dark Matter in scalar Sp($$ \mathcal{N} $$) gauge dynamics
Authors: Landini Giacomo , Wang Jin-Wei
Published: June 2020

Abstract

We consider a model with Sp dark gauge group and a scalar field in the fundamental representation, which leads to two co-stable DM candidates at the perturbative level thanks to a global U(1) accidental symmetry. After gauge confinement at low energy scale, only one of the two candidates is still stable. We compute the DM relic abundance by solving the Boltzmann equations numerically. The presence of light dark glueballs gives extra cosmological effects and can affect Higgs physics. We study the DM phenomenology, providing the predictions for direct and indirect detection (including the Sommerfeld enhancement). We show that the model predicts a slightly suppressed indirect detection cross section in comparison to the usual WIMPs paradigm.
Cylinder partition function of the 6-vertex model from algebraic geometry
Authors: Bajnok Zoltan , Jacobsen Jesper Lykke , Jiang Yunfeng , Nepomechie Rafael I. , Zhang Yang
Published: June 2020

Abstract

We compute the exact partition function of the isotropic 6-vertex model on a cylinder geometry with free boundary conditions, for lattices of intermediate size, using Bethe ansatz and algebraic geometry. We perform the computations in both the open and closed channels. We also consider the partial thermodynamic limits, whereby in the open (closed) channel, the open (closed) direction is kept small while the other direction becomes large. We compute the zeros of the partition function in the two partial thermodynamic limits, and compare with the condensation curves.
Geometry on the lines of polar spine spaces
Authors: Petelczyc Krzysztof , Prażmowski Krzysztof , Żynel Mariusz
Published: June 2020

The concept of spine geometry over a polar Grassmann space is introduced. We determine conditions under which the structure of lines together with a binary coplanarity relation is a sufficient system of primitive notions for polar spine spaces. These assumptions also allow to characterize polar spine spaces in terms of the binary relation of being in one pencil of lines.
Cellular and molecular effects of hyperglycemia on ion channels in vascular smooth muscle
Authors: Nieves-Cintrón Madeline , Flores-Tamez Víctor A. , Le Thanhmai , Baudel Miguel Martín-Aragón , Navedo Manuel F.
Published: June 2020

Diabetes affects millions of people worldwide. This devastating disease dramatically increases the risk of developing cardiovascular disorders. A hallmark metabolic abnormality in diabetes is hyperglycemia, which contributes to the pathogenesis of cardiovascular complications. These cardiovascular complications are, at least in part, related to hyperglycemia-induced molecular and cellular changes in the cells making up blood vessels. Whereas the mechanisms mediating endothelial dysfunction during hyperglycemia have been extensively examined, much less is known about how hyperglycemia impacts vascular smooth muscle function. Vascular smooth muscle function is exquisitely regulated by many ion channels, including several members of the potassium (K+) channel superfamily and voltage-gated L-type Ca2+channels. Modulation of vascular smooth muscle ion channels function by hyperglycemia is emerging as a key contributor to vascular dysfunction in diabetes. In this review, we summarize the current understanding of how diabetic hyperglycemia modulates the activity of these ion channels in vascular smooth muscle. We examine underlying mechanisms, general properties, and physiological relevance in the context of myogenic tone and vascular reactivity.
Correction to: On the equivalence of spherical splines with least-squares collocation and Stokes’s formula for regional geoid computation
Authors: Ophaug Vegard , Gerlach Christian
Published: June 2020

The authors would like to apologize to the editor and readers for a bug in the numerical implementation of the formula for the initial guess on the regularization parameter 2013, as given in the second paragraph on page 1370, and repeated here for convenience.
Chemical carcinogen safety testing: OECD expert group international consensus on the development of an integrated approach for the testing and assessment of chemical non-genotoxic carcinogens
Authors: Jacobs Miriam N. , Colacci Annamaria , Corvi Raffaella , Vaccari Monica , Aguila M. Cecilia , Corvaro Marco , Delrue Nathalie , Desaulniers Daniel , Ertych Norman , Jacobs Abigail , Luijten Mirjam , Madia Federica , Nishikawa Akiyoshi , Ogawa Kumiko , Ohmori Kiyomi , Paparella Martin , Sharma Anoop Kumar , Vasseur Paule
Published: June 2020

While regulatory requirements for carcinogenicity testing of chemicals vary according to product sector and regulatory jurisdiction, the standard approach starts with a battery of genotoxicity tests (which include mutagenicity assays). If any of the in vivo genotoxicity tests are positive, a lifetime rodent cancer bioassay may be requested, but under most chemical regulations (except plant protection, biocides, pharmaceuticals), this is rare. The decision to conduct further testing based on genotoxicity test outcomes creates a regulatory gap for the identification of non-genotoxic carcinogens (NGTxC). With the objective of addressing this gap, in 2016, the Organization of Economic Cooperation and Development (OECD) established an expert group to develop an integrated approach to the testing and assessment (IATA) of NGTxC. Through that work, a definition of NGTxC in a regulatory context was agreed. Using the adverse outcome pathway (AOP) concept, various cancer models were developed, and overarching mechanisms and modes of action were identified. After further refining and structuring with respect to the common hallmarks of cancer and knowing that NGTxC act through a large variety of specific mechanisms, with cell proliferation commonly being a unifying element, it became evident that a panel of tests covering multiple biological traits will be needed to populate the IATA. Consequently, in addition to literature and database investigation, the OECD opened a call for relevant assays in 2018 to receive suggestions. Here, we report on the definition of NGTxC, on the development of the overarching NGTxC IATA, and on the development of ranking parameters to evaluate the assays. Ultimately the intent is to select the best scoring assays for integration in an NGTxC IATA to better identify carcinogens and reduce public health hazards.
Dopamine boosts intention and action awareness in Parkinson’s disease
Authors: Di Costa Steven , Barow Ewgenia , Hidding Ute , Mainka Tina , Pötter-Nerger Monika , Buhmann Carsten , Moll Christian K. E. , Haggard Patrick , Ganos Christos
Published: June 2020

Dopaminergic deficiency in Parkinson’s disease (PD) has been associated with underactivation of the supplementary motor area and a reduction of voluntary actions. In these patients, awareness of intention to act has been shown to be delayed. However, delayed awareness of intention to act has also been shown in patients with hyperdopaminergic states and an excess of unwilled movements, as in Tourette’s, and in patients with functional movement disorders. Hence, the role of dopamine in the awareness of intention and action remains unclear. 36 PD patients were tested ON and OFF dopaminergic medication and compared with 35 healthy age-matched controls. In addition, 17 PD patients with subthalamic deep brain stimulation (DBS) were tested ON medication and ON and OFF stimulation. Participants judged either the moment a self-generated action was performed, or the moment the urge to perform the action was felt, using the “Libet method”. Temporal judgments of intention and action awareness were comparable between unmedicated PD patients and controls. Dopaminergic medication boosted anticipatory awareness of both intentions and actions in PD patients, relative to an unmedicated condition. The difference between ON/OFF DBS was not statistically reliable. Functional improvement of motor ability in PD through dopaminergic supplementation leads to earlier awareness of both intention, and of voluntary action.
The value of 18F-FDG PET/CT for the diagnosis of device-related infections in patients with a left ventricular assist device: a systematic review and meta-analysis
Authors: ten Hove D. , Treglia G. , Slart R. H. J. A. , Damman K. , Wouthuyzen-Bakker M. , Postma D. F. , Gheysens O. , Borra R. J. H. , Mecozzi G. , van Geel P. P. , Sinha B. , Glaudemans A. W. J. M.
Published: June 2020

Background

Left ventricular assist devices (LVADs) are increasingly used for the treatment of advanced heart failure. LVADs improve quality of life and decrease mortality, but the driveline carries substantial risk for major infections. These device-related LVAD and driveline infections are difficult to diagnose with conventional imaging. We reviewed and analysed the current literature on the additive value of 18F-fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG-PET/CT) imaging for the diagnosis of LVAD-related infections.”

Materials/methods

We performed a systematic literature review using several databases from their inception until the 31st of December, 2019. Studies investigating the diagnostic performance of FDG-PET/CT in patients with suspected LVAD infection were retrieved. After a bias risk assessment using QUADAS-2, a study-aggregate meta-analysis was performed on a per examination-based analysis.

Results

A total of 10 studies were included in the systematic review, eight of which were also eligible for study-aggregate meta-analysis. For the meta-analysis, a total of 256 FDG-PET/CT scans, examining pump/pocket and/or driveline infection, were acquired in 230 patients. Pooled sensitivity of FDG-PET/CT was 0.95 (95% confidence interval (CI) 0.89–0.97) and pooled specificity was 0.91 (95% CI 0.54–0.99) for the diagnosis of device-related infection. For pump/pocket infection, sensitivity and specificity of FDG-PET/CT were 0.97 (95%CI 0.69–1.00) and 0.93 (95%CI 0.64–0.99), respectively. For driveline infection, sensitivity and specificity were 0.96 (95%CI 0.88–0.99) and 0.99 (95%CI 0.13–1.00) respectively. Significant heterogeneity existed across studies for specificity, mostly caused by differences in scan procedures. Predefined criteria for suspicion of LVAD and/or driveline infection were lacking in all included studies.

Conclusions

FDG-PET/CT is a valuable tool for assessment of device-related infection in LVAD patients, with high sensitivity and high, albeit variable, specificity. Standardization of FDG-PET/CT procedures and criteria for suspected device-related LVAD infections are needed for consistent reporting of FDG-PET/CT scans.
Exploration of Concerns about the Evidence-Based Guideline Approach in Conservation Management: Hints from Medical Practice
Authors: Gutzat Fabian , Dormann Carsten F.
Published: June 2020

The importance of using evidence in decision-making is frequently highlighted in policy reports and scientific papers. However, subjective judgments of the reliability of environmental evidence vary widely, and large-scale systematic searches for evidence are only common for climate-related topics. In the medical field, evidence-based guidelines are routinely used to guide treatments. In the management of multiple-use landscapes similar guidelines could substantially narrow the science-practice gap but are largely absent. The challenges potential guidelines face are therefore unknown. For the case of forest conservation, we conducted 14 semistructured interviews with mainly forest practitioners and presented them an example medical guideline together with evidence-based statements on forest conservation (hereinafter: statement paper). We identified 28 concerns related to potential evidence-based guidelines in forest conservation. The interviews yielded approximately three major findings. First, recommendations on forest conservation are better accepted if they include clear instructions and are formulated for a specific context. Fragmentary conservation evidence complicates the formulation of specific recommendations. Second, the level of evidence framework, which indicates the strength of the available evidence, is perceived as too complex. Third, neglecting forest multifunctionality in a potential guideline hampers its application but, if addressed, potentially weakens its ecological relevance. We show that major concerns about potential evidence-based conservation guidelines are similar to the challenges experienced by medical guidelines. We also identify concerns unique to forestry.
Wide variation in tissue, systemic, and drain fluid exposure after oxaliplatin-based HIPEC: results of the GUTOX study
Authors: de Jong Loek A. W. , Elekonawo Fortuné M. K. , Lambert Marie , de Gooyer Jan Marie , Verheul Henk M. W. , Burger David M. , de Wilt Johannes H. W. , Chatelut Etienne , ter Heine Rob , de Reuver Philip R. , Bremers Andre J. A. , van Erp Nielka P.
Published: June 2020

Purpose

In this exploratory study, the effect of postprocedural flushing with crystalloids after oxaliplatin-based hyperthermic intraperitoneal chemotherapy (HIPEC) on platinum concentrations in peritoneal tissue, blood, and drain fluid was studied. Interpatient variability in oxaliplatin pharmacokinetics and the relation between platinum concentration in peritoneal fluid and platinum exposure in tissue and blood was explored.

Methods

Ten patients with peritoneal carcinomatosis of colorectal origin were treated with HIPEC including postprocedural flushing, followed by ten patients without flushing afterwards. Tissue, peritoneal fluid, blood, and drain fluid samples were collected for measurement of total and ultrafiltered platinum concentrations.

Results

Peritoneal tissue concentration and systemic ultrafiltered platinum exposure showed large inter individual variability, ranging from 65 to 1640 µg/g dry weight and 10.5 to 28.0 µg*h/ml, respectively. No effect of flushing was found on geometric mean platinum concentration in peritoneal tissue (348 vs. 356 µg/g dry weight), blood (14.8 vs. 18.1 µg*h/ml), or drain fluid (day 1: 7.6 vs. 7.7 µg/ml; day 2: 1.7 vs. 1.9 µg/ml). The platinum concentration in peritoneal fluid at the start of HIPEC differed twofold between patients and was positively correlated with systemic exposure (p = .04) and peak plasma concentration (p = .04).

Conclusion

In this exploratory study, no effect was found for postprocedural flushing on platinum concentrations in peritoneal tissue, blood, or drain fluid. BSA-based HIPEC procedure leads to large interpatient variability in platinum exposure in all compartments.

The study was registered at ClinicalTrials.gov on 7 December 2017 under registration number NCT03364907.
Clinically significant prostate cancer detection and segmentation in low-risk patients using a convolutional neural network on multi-parametric MRI
Authors: Arif Muhammad , Schoots Ivo G. , Castillo Tovar Jose , Bangma Chris H. , Krestin Gabriel P. , Roobol Monique J. , Niessen Wiro , Veenland Jifke F.
Published: June 2020

Objectives

To develop an automatic method for identification and segmentation of clinically significant prostate cancer in low-risk patients and to evaluate the performance in a routine clinical setting.

Methods

A consecutive cohort (n = 292) from a prospective database of low-risk patients eligible for the active surveillance was selected. A 3-T multi-parametric MRI at 3 months after inclusion was performed. Histopathology from biopsies was used as reference standard. MRI positivity was defined as PI-RADS score ≥ 3, histopathology positivity was defined as ISUP grade ≥ 2. The selected cohort contained four patient groups: (1) MRI-positive targeted biopsy-positive (n = 116), (2) MRI-negative systematic biopsy-negative (n = 55), (3) MRI-positive targeted biopsy-negative (n = 113), (4) MRI-negative systematic biopsy-positive (n = 8). Group 1 was further divided into three sets and a 3D convolutional neural network was trained using different combinations of these sets. Two MRI sequences (T2w, b = 800 DWI) and the ADC map were used as separate input channels for the model. After training, the model was evaluated on the remaining group 1 patients together with the patients of groups 2 and 3 to identify and segment clinically significant prostate cancer.

Results

The average sensitivity achieved was 82–92% at an average specificity of 43–76% with an area under the curve (AUC) of 0.65 to 0.89 for different lesion volumes ranging from > 0.03 to > 0.5 cc.

Conclusions

The proposed deep learning computer-aided method yields promising results in identification and segmentation of clinically significant prostate cancer and in confirming low-risk cancer (ISUP grade ≤ 1) in patients on active surveillance.

Key Points

• Clinically significant prostate cancer identification and segmentation on multi-parametric MRI is feasible in low-risk patients using a deep neural network.

• The deep neural network for significant prostate cancer localization performs better for lesions with larger volumes sizes (> 0.5 cc) as compared to small lesions (> 0.03 cc).

• For the evaluation of automatic prostate cancer segmentation methods in the active surveillance cohort, the large discordance group (MRI positive, targeted biopsy negative) should be included.
Experimental investigation of the effect of transpiration cooling on second mode instabilities in a hypersonic boundary layer
Authors: Camillo Giannino Ponchio , Wagner Alexander , Dittert Christian , Benjamin Leroy , Wartemann Viola , Neumann Jens , Hink Rüdiger
Published: June 2020

The influence of localized nitrogen transpiration on second mode instabilities in a hypersonic boundary layer is experimentally investigated. The study is conducted using a $$7^\circ$$

7
∘

half-angle cone with a length of 1100 mm and small nose bluntness at $$0^\circ$$

0
∘

angle-of-attack. Transpiration is realized through a porous Carbon/Carbon patch of $$44 \times 82$$

44
×
82

mm located near the expected boundary layer transition onset location. Transpiration mass flow rates in the range of 0.05–1% of the equivalent boundary layer edge mass flow rate were used. Experiments were conducted in the High Enthalpy Shock Tunnel Göttingen (HEG) at total enthalpies around 3 MJ/kg and unit Reynolds numbers in the range of $$1.4 \cdot 10^6 \,$$

1.4
·

10
6

to $$6.4 \cdot 10^6 \, {\text {m}}^{-1}$$

6.4
·

10
6

m

-
1

. Measurements were conducted by means of coaxial thermocouples, Atomic Layer Thermopiles (ALTP), pressure transducers and high-speed schlieren. The present study shows that the most amplified second mode frequencies were shifted to lower values as nitrogen is transpired into the boundary layer. In some cases the instability amplitudes were found to be significantly reduced. The observed frequency reduction was verified to correlate with the change of the relative sonic line height in the boundary layer. The amplitude damping was observed to occur only until the most amplified frequencies were reduced to around 50% of their undisturbed values. When transpiration within this limit was performed shortly upstream of the natural boundary layer transition onset, a transition delay of approximately 17% could be observed.

Graphic abstract
Nuclear ErbB2 expression in hepatocytes in liver disease
Authors: Döring Paula , Calvisi Diego F. , Dombrowski Frank
Published: June 2020

ErbB2 is a prominent representative of the epidermal growth factor receptors that mainly attract attention as oncogenic drivers and therapeutic targets in cancer. Besides transmembrane signaling, ErbB2 may also translocate into the nucleus and mediate distinct nuclear signaling effects including DNA repair and cell cycle arrest. Unexpectedly, we found nuclear ErbB2 expression in human hepatocytes in various liver diseases so we aimed to investigate the characteristics of liver disease leading to nuclear ErbB2 translocation. The immunohistochemical pattern of ErbB2 staining was analyzed in 1125 liver biopsy samples from patients with hepatic dysfunction. Further signaling and metabolic markers were analyzed by immunohistochemistry in selected liver biopsy samples. We found a cytoplasmic and nuclear ErbB2 expression in hepatocytes from different disease conditions with the strongest expression detected in alcoholic steatohepatitis. Nuclear ErbB2 positivity significantly correlated with histologic parameters of hepatocellular damage including inflammatory activity in steatohepatitis, hepatocellular ballooning, and cholestasis. ErbB2 overexpressing hepatocytes revealed an increase of phospho-STAT3, a downstream effector of nuclear ErbB2 signaling. Notably, we observed in nuclear ErbB2-positive hepatocytes a downregulation of estrogen receptor expression. In alcoholic steatohepatitis and other toxic liver diseases, hepatocytes revealed a nuclear ErbB2 expression implying a so far unknown mechanism in hepatocytes upon cellular stress that might lead to resistance to cell death. Nuclear ErbB2-positive hepatocytes showed downregulation of estrogen receptor expression and increased levels of pSTAT3, which are signs of functionality of nuclear ErbB2 signaling. Furthermore, analysis of hepatocellular ErbB2 expression could serve as helpful tool for diagnosis of liver disease.
Creatine, guanidinoacetate and homoarginine in statin-induced myopathy
Authors: Neu Axel , Hornig Sönke , Sasani Ali , Isbrandt Dirk , Gerloff Christian , Tsikas Dimitris , Schwedhelm Edzard , Choe Chi-un
Published: June 2020

Our study evaluated the effect of creatine and homoarginine in AGAT- and GAMT-deficient mice after simvastatin exposure. Balestrino and Adriano suggest that guanidinoacetate might explain the difference between AGAT- and GAMT-deficient mice in simvastatin-induced myopathy. We agree with Balestrino and Adriano that our data shows that (1) creatine possesses a protective potential to ameliorate statin-induced myopathy in humans and mice and (2) homoarginine did not reveal a beneficial effect in statin-induced myopathy. Third, we agree that guanidinoacetate can be phosphorylated and partially compensate for phosphocreatine. In our study, simvastatin-induced damage showed a trend to be less pronounced in GAMT-deficient mice compared with wildtype mice. Therefore, (phospo) guanidinoacetate cannot completely explain the milder phenotype of GAMT-deficient mice, but we agree that it might contribute to ameliorate statin-induced myopathy in GAMT-deficient mice compared with AGAT-deficient mice. Finally, we agree with Balestino and Adriano that AGAT metabolites should further be evaluated as potential treatments in statin-induced myopathy.
A Mathematical Model of HIF-1 Regulated Cellular Energy Metabolism
Authors: Bocharov Gennady , Jäger Willi , Knoch Jonas , Neuss-Radu Maria , Thiel Manfred
Published: June 2020

In this study, we formulated a mathematical model of hypoxia-inducible factor 1 (HIF-1) mediated regulation of cellular energy metabolism describing the reprogramming of cell metabolic processes from oxidative phosphorylation to glycolysis under reduced oxygen levels. The model considers the dynamics of fifteen biochemical species and the proton concentration with the underlying reaction processes localized in three intracellular compartments, i.e. the cytoplasm, mitochondrion and nucleus. More than sixty parameters of the model were calibrated using both the published data and the system steady-state based identification procedure. The model was validated by generating predictions which could be compared to empirical observations. The model behaviors representing the cell metabolism switching over in response to transitioning from a normoxic to hypoxic environment are consistent with the current views of the role of HIF-1 in hypoxia.
Response to commentary ‘towards more meaningful scenarios of biodiversity responses to land-use change in Central Asia
Authors: Nunez Sarahi , Alkemade Rob , Kok Kasper , Leemans Rik
Published: June 2020

With this letter, we respond to the commentary by Kamp et al. on our paper (Nunez et al. in Reg Environ Chang 20:39, 2020) that reports on potential biodiversity change in Central Asian grasslands using climate and land-use change scenarios. In their commentary, Kamp et al. criticize data and methods employed and discuss several shortfalls of our approach. In this response, we argue that in our paper projections of future biodiversity already acknowledge the issues indicated by Kamp et al. We elaborate on the reasons why. We maintain our main finding that, based on a number of contrasting scenarios (shared socioeconomic pathways and representative concentration pathways combinations), biodiversity in grasslands in Central Asia will potentially decline under each scenario. We conclude that while our data and methods conservatively estimate potential biodiversity changes in the Central Asian grasslands, they could be enriched with more elements. The results, however, are likely to confirm the vulnerability of these grasslands and the possible decline in their biodiversity.
Dealing with Moral Challenges in Treatment of Transgender Children and Adolescents: Evaluating the Role of Moral Case Deliberation
Authors: Vrouenraets Lieke Josephina Jeanne Johanna , Hartman Laura A. , Hein Irma M. , de Vries Annelou L. C. , de Vries Martine C. , Molewijk Bert A. C.
Published: June 2020

Treatment teams providing affirmative medical transgender care to young people frequently face moral challenges arising from the care they provide. An adolescent’s capacity to consent, for example, could raise several issues and challenges. To deal with these challenges more effectively, several Dutch treatment teams started using a relatively well-established form of clinical ethics support (CES) called Moral Case Deliberation (MCD). MCD is a facilitator-led, collective moral inquiry based on a real case. This study’s purpose is to describe the teams’ perceived value and effectiveness of MCD. We conducted a mixed methods evaluation study using MCD session reports, individual interviews, focus groups, and MCD evaluation questionnaires. Our results show that Dutch transgender care providers rated MCD as highly valuable in situations where participants were confronted with moral challenges. The health care providers reported that MCD increased mutual understanding and open communication among team members and strengthened their ability to make decisions and take action when managing ethically difficult circumstances. However, the health care providers also expressed criticisms of MCD: some felt that the amount of time spent discussing individual cases was excessive, that MCD should lead to more practical and concrete results, and that MCD needed better integration and follow-up in the regular work process. We recommend future research on three matters: studying how MCD contributes to the quality of care, involvement of transgender people themselves in MCD, and integration of CES into daily work processes.