bluuebunny/crossref_metadata_2025 huggingface dataset:
Transition‐Metal Complexes of Bidentate Schiff‐Base Ligands: In Vitro and In Silico Evaluation as Non‐Classical Carbonic Anhydrase and Potential Acetylcholinesterase Inhibitors
Authors: Yaşar Ümit , Gönül İlyas , Türkeş Cüneyt , Demir Yeliz , Beydemir Şükrü
Published: August 2021

Schiff bases display superior features for many areas, such as significant intermediates in industrial biological, pharmacological, catalytic and optical properties, organic synthesis, and coordination chemistry. The pre‐synthesized two Schiff base ligands (HL1andHL2) and their bidentate metal complexes (Co(L1)2,Cu(L1)2,Ni(L1)2,Co(L2)2,Cu(L2)2, andNi(L2)2) were tested for their inhibition activities on acetylcholinesterase (AChE) and human carbonic anhydrase (hCA I andhCA II) isoforms. The transition metal complexes of bidentate Schiff base ligands displayed the potent inhibition effect withKIconstants ranging from 16.39±0.15 to 88.63±0.27 nM and 9.32±0.13 to 33.66±0.57 nM forhCA isoenzymes and AChE, respectively. The compoundCu(L1)2forhCA I andNi(L2)2for AChE andhCA II had the highest inhibitory effect. Besides, the molecular docking analyses of the most active complexes (Cu(L1)2andNi(L2)2) were performed to understand the binding interactions on the enzymes’ binding sites. According to both in vitro and in silico analysis results, all the compounds were potential inhibitors of AChE andhCA I, II isoenzymes.
Green Carbon Dots (GCDs) for Photocatalytic Hydrogen Evolution and Antibacterial Applications
Authors: Genc Munevver Tuna , Yanalak Gizem , Aksoy Ilknur , Aslan Emre , Patır Imren Hatay
Published: August 2021

Microwave technique was used to synthesize Green Carbon Dots (GCDs) from Aloe vera leaves because of easy to apply, accessible, time‐saving, cheap, safe and environmental‐friendly way. The prepared GCDs/TiO2 composite was obtained via sensitization of TiO2 with the help of GCDs. The characterization of the GCDs/TiO2 was made optically, structurally and morphologically. The photocatalytic hydrogen activity of GCDs/TiO2 was investigated under visible light (λ>420 nm) irradiation in the aqueous solution using triethanolamine (TEOA) sacrificial electron donor. When Pt was used, GCDs/TiO2/Pt showed advanced hydrogen evolution production (1294 μmol g−1 h−1) approximately two‐fold compared to GCDs/TiO2 (718 μmol g−1 h−1). In addition, NIR light‐triggered antibacterial activity of GCDs on Gram‐negative Escherichia coli (E. coli) and Gram‐positive Staphylococcus aureus (S. aureus) were investigated by studying bacterial growth curve and abiotic GSH oxidation assay. GSH oxidation ability of GCDs was increased through NIR light irradiation. According to the bacterial growth curve test, E. coli was found to be more susceptible to our GCDs than S. aureus.
Polymer‐Based Anti‐Solvent Engineering to Fabricate Stable and Efficient Triple‐Cation Perovskite Solar Cells
Authors: Naji Amel Muhson , Nief Olfat A. , Kareem Sahira Hassan , Mohammed Mustafa K. A.
Published: August 2021

Perovskite materials, due to their excellent photovoltaic features, have aroused the researchers′ admiration as a photon‐absorption film for the next‐generation photovoltaics. The interface tailoring of perovskites and hole‐transport layer (HTL) is one of the critical approaches to achieve effective and stabilized perovskite solar cell (PSC). Hence, poly[4,8‐bis[(2‐ethylhexyl)oxy]benzo[1,2‐b:4,5‐b′]dithiophene‐2,6‐diyl][3‐fluoro‐2‐[(2 ethylhexyl)carbonyl]thieno[3,4‐b]‐thiophenediyl] (PTB7) as a polymeric organic semiconductors was employed for doping of anti‐solvent solution to modify the perovskite film. Results showed with PTB7 dopant; grain boundaries (GBs) of the perovskites are reduced. It suppressed carriers′ trap centers in the perovskite film and decreased recombination processes within perovskite layers. Besides, the high intrinsic conductivity of PTB7 material assisted charge injection at the perovskites/HTL interfaces and hindered carrier's accumulation. The device with PTB7 showed a more matched energy level and a higher prevention for recombination than the device without PTB7 dopant, which are reasons for the considerable boost in the open‐circuit voltage (VOC) and fill‐factor (FF), giving rise a power conversion efficiency (PCE) of 19.18 % for the champion performing PVs. Most important, the hydrophobic origin of PTB7 leads to superb humidity stability in the device with PTB7 dopant with 85 % of the original performance remaining after more than 800 h storing in air with ∼40 % RH.
Carbon Quantum Dots Based on Carbohydrates as Nano Sensors for Food Quality and Safety
Authors: Arias Velasco Valentina , Caicedo Chacón Wilson D. , Carvajal Soto Angélica M. , Ayala Valencia Germán , Granada Echeverri Juan C. , Agudelo Henao Ana C.
Published: August 2021

Carbon quantum dots (CQDs) are a special type of nanostructure characterized for their low toxicity, environmentally friendliness, and ease of manufacture from varied carbon sources like carbohydrates. This carbon source is abundant in natural products and organic wastes, and it is suitable to be used in food applications like nano sensors for food quality and safety. Indeed, CQDs are foreseen as a potential new type of practical and unexpensive sensor to detect harmful substances commonly found in food. Limits of detection (LOD) of CQDs nano sensors have reached concentration level standards established by European Food Safety Authority for additives and heavy metals; nevertheless, for pathogens, safe limits of LOD are still not achieved. This study aims to carry out a review of CQDs obtained from carbohydrates of natural products and organic wastes as well as to describe their performance as sensors of additives, pathogens, and heavy metals in food quality and safety.
Modifying effects of menthol against benzo(a)pyrene‐induced forestomach carcinogenesis in female Swiss mice
Authors: Santo Sara Gomes Espírito , Romualdo Guilherme Ribeiro , Santos Leandro Alves dos , Grassi Tony Fernando , Barbisan Luís Fernando
Published: July 2021

Benzo(a)pyrene (BaP) is a polycyclic aromatic hydrocarbon widespread in the environment and closely associated to tobacco use, which is an important risk factor for highly incident stomach cancer. Menthol, a monoterpene extracted from Mentha genus species, has multiple biological properties, including anti‐inflammatory and gastroprotective properties, but its effects on carcinogenesis are still to be fully understood. Thus, we evaluated the modifying effects of Ment against BaP‐induced forestomach carcinogenesis. Female Swiss mice received BaP by intragastrical (i.g.) administration (50 mg/kg of body weight [b wt], 2×/week), from weeks 1–5 weeks. Concomitantly, mice received Menthol at 25 (Ment25) or 50 (Ment50) mg/kg b wt (i.g, 3×/week). Animals were euthanized at weeks 5 (n = 5 mice/group) or 30 (n = 10 mice/group). At week 5, both Ment doses reduced peripheral leukocyte blood genotoxicity 4 h after the last BaP administration, but only Ment50 attenuated this biomarker 8 h after the last BaP administration. In accordance to these findings, both Ment interventions attenuated BaP‐induced increase in the percentage of H2A.X‐positive forestomach epithelial cells. Moreover, Ment50 reduced cell proliferation and apoptosis (i.e., Ki‐67 and caspase‐3, respectively) in forestomach epithelium but exerted no significant effects on NFκB, and Nrf2 protein levels. At week 30, Ment50 reduced by ~55% the incidence of BaP‐induced forestomach diffuse hyperplasia and multiplicity of forestomach tumors (squamous cell papillomas and carcinomas). Our findings indicate that Ment50, administered during initiation phase, attenuates forestomach carcinogenesis by reducing early genotoxicity, cell proliferation, and apoptosis induced by BaP.
COD fractionation and solubility assessment of sonicated waste‐activated sludge
Authors: Al‐Hoqani Manal , Zafar Mohd. , Al Musharafi Salma K. , Mahanty Biswanath , Behera Shishir Kumar
Published: July 2021

Ultrasonic treatment is adopted as one of the important strategies to accelerate the hydrolysis of waste‐activated sludge (WAS). This study intends to optimize amplitude and time for ultrasonic treatment of WAS using statistically designed experiments that would render a better degree of disintegration, measured in terms of chemical oxygen demand (COD) solubilization. The main and interaction effects of nonlinear regression analysis revealed a significant interaction between amplitude and time over the degree of sludge disintegration. The ultrasonic density of 0.45 W/mL for 30 min favored a 153.84% increase in COD solubilization with a 27.65% degree of sludge disintegration. This condition also favored the minimum specific energy input of 801.58 kJ/g total suspended solids compared to other sonication conditions. Besides, the sludge volume index was reduced by 45% and 26% at the ultrasonic density of 0.45 W/mL for 60 and 30 min, respectively. Microscopic examination of WAS revealed disintegration of bacterial flocs during the ultrasonication process releasing filamentous bacteria with smaller floc sizes. The results from this study indicate that higher ultrasonic density for short time could improve the sludge disintegration with minimum specific energy input.
Simultaneous removal of Cd (II), Ni (II), and Pb (II) from water by a submerged macrophyte pondweed (Potamogeton malaianus)
Authors: Lyu Rongtao , Gu Bowen , Zhang Ting , Yang Zhaoguang
Published: July 2021

The current work investigated the potential of submerged macrophyte pondweed (Potamogeton malaianus) in treating cadmium, nickel, and lead‐contaminated water through phytoremediation. The adsorption for the three metal ions occurred rapidly within 2 h and attained dynamic equilibrium in no more than 72 h. The removal efficiencies of Cd (II), Ni (II), and Pb (II) were high, passing 94% in both single‐ and multi‐metal systems. The kinetic adsorption curves of Cd (II), Ni (II), and Pb (II) were fitted well by both pseudo‐first‐order and pseudo‐second‐order kinetics (R2 = 0.9875–0.9995). The equilibrium adsorption capacities of Cd (II), Ni (II), and Pb (II) for P. malaianus were 6.29–6.97 mg kg−1. In plants, the higher concentration of each metal ions was accumulated in leaves (12.44–38.15 mg kg−1) than in roots (10.32–26.10 mg kg−1). The chlorophyll contents increased from 0.69 to 0.89–1.00 mg g−1 under the treatment of Cd (II), Ni (II), and Pb (II), whereas the chlorophyll a/b ratio was kept constant. There was no significant difference between single‐ and multi‐metal systems. FT‐IR spectra showed that COH and C═N might be involved in the adsorption of Cd (II), Ni (II), and Pb (II). This study demonstrated that P. malaianus could be a suitable submerged macrophyte for the simultaneous removal of Cd (II), Ni (II), and Pb (II) from water.
Established Urban Research Traditions and the Platform for Space Syntax
Authors: van Nes Akkelies , Yamu Claudia
Published: July 2021

This chapter provides an overview of established researchtraditions in the analysis of physical elements of the built environment. Herein, we address the morphological, place phenomenological, andurban network traditions. Following this, a synopsis about spatial elements applied to these traditions, including space syntax, is given. Furthermore, in this chapter, we explain the differences between extrinsic and intrinsic properties of space and clarify the typology concepts of the built form. Finally, we introduce the basic spatial elements used in space syntax and the simplest spatialstructures that cities can have. Exercises are provided at the end of this chapter.
Empirical Data Collection and Analysis, and Connecting Data with Space Syntax
Authors: van Nes Akkelies , Yamu Claudia
Published: July 2021

Inprevious chapters, we demonstrated various analytic techniques focusing on the spatial aspects of the built environment. In this chapter, we discuss various methods and techniques for collecting qualitative andquantitative data dealing with human behaviour and how to connect such data to the results from various space syntax analyses. This chapter provides a brief introduction to these methods to stimulate ideas for connecting an array of spatial and socio-economicdata to space syntax. At the end of this chapter, we provide an exercise, references, and further readings.
Theoretical Representations of the Built Environment
Authors: van Nes Akkelies , Yamu Claudia
Published: July 2021

In this chapter, we show what and how space syntax has contributed to theoriesand general knowledge of the built environment. First, we provide an introduction to two established researchtraditions, positivismand hermeneutics. The aim is to demonstrate through modal logic what the possibilities and limitations are for gaining general understandings and making theoretical explanations from space syntax research. Modal logic uses expressions to test the explanatory power of statements. Second, we show what space syntax adds to the debate about spatialintegrationand spatial segregation as seen in relation to market and socialrationality. We will focus on the spatial aspects and discuss these in relation to declining versus vital neighbourhoods, crime, anti-socialbehaviour, cultures, political ideologies, gender, and the use of space. Third, we give some reflections on what space syntax has contributed in regards to a comprehensive architecture theory. Finally, at the end, we add as an epilogue a thought experiment on how space syntax theories can be applied within the compact city debate. Exercises are provided at the end of this chapter.
Gravitational perturbations from NHEK to Kerr
Authors: Castro Alejandra , Godet Victor , Simón Joan , Song Wei , Yu Boyang
Published: July 2021

Abstract

We revisit the spectrum of linear axisymmetric gravitational perturbations of the (near-)extreme Kerr black hole. Our aim is to characterise those perturbations that are responsible for the deviations away from extremality, and to contrast them with the linearized perturbations treated in the Newman-Penrose formalism. For the near horizon region of the (near-)extreme Kerr solution, i.e. the (near-)NHEK background, we provide a complete characterisation of axisymmetric modes. This involves an infinite tower of propagating modes together with the much subtler low-lying mode sectors that contain the deformations driving the black hole away from extremality. Our analysis includes their effects on the line element, their contributions to Iyer-Wald charges around the NHEK geometry, and how to reconstitute them as gravitational perturbations on Kerr. We present in detail how regularity conditions along the angular variables modify the dynamical properties of the low-lying sector, and in particular their role in the new developments of nearly-AdS2 holography.
Chiral composite asymmetric dark matter
Authors: Ibe Masahiro , Kobayashi Shin , Watanabe Keiichi
Published: July 2021

Abstract

The asymmetric dark matter (ADM) scenario solves the baryon-dark matter coincidence problem when the dark matter (DM) mass is of$$ \mathcal{O}(1) $$O1GeV. Composite ADM models based on QCD-like strong dynamics are particularly motivated since the strong dynamics naturally provides the DM mass of$$ \mathcal{O}(1) $$O1GeV and the large annihilation cross-section simultaneously. In those models, the sub-GeV dark photon often plays an essential role in transferring the excessive entropy in the dark sector into the visible sector, i.e., the Standard Model sector. This paper constructs a chiral composite ADM model where the U(1)Dgauge symmetry is embedded into the chiral flavor symmetry. Due to the dynamical breaking of the chiral flavor symmetry, the model naturally provides the masses of the dark photon and the dark pions in the sub-GeV range, both of which play crucial roles for a successful ADM model.
Diluted mass gap in strongly coupled non-local Yang-Mills
Authors: Frasca Marco , Ghoshal Anish
Published: July 2021

Abstract

We investigate the non-perturbative regimes in the class of non-Abelian theories that have been proposed as an ultraviolet completion of 4-D Quantum Field Theory (QFT) generalizing the kinetic energy operators to an infinite series of higher-order derivatives inspired by string field theory. We prove that, at the non-perturbative level, the physical spectrum of the theory is actually corrected by the “infinite number of derivatives” present in the action. We derive a set of Dyson-Schwinger equations in differential form, for correlation functions till two-points, the solution for which are known in the local theory. We obtain that just like in the local theory, the non-local counterpart displays a mass gap, depending also on the mass scale of non-locality, and show that it is damped in the deep UV asymptotically. We point out some possible implications of our result in particle physics and cosmology and discuss aspects of non-local QCD-like scenarios.
On the orthogonality of generalized eigenspaces for the Ornstein–Uhlenbeck operator
Authors: Casarino Valentina , Ciatti Paolo , Sjögren Peter
Published: August 2021

We study the orthogonality of the generalized eigenspaces of an Ornstein–Uhlenbeck operator $${\mathscr {L}}$$
L
in $$\mathbb {R}^N$$

R

N

, with drift given by a real matrix B whose eigenvalues have negative real parts. If B has only one eigenvalue, we prove that any two distinct generalized eigenspaces of $${\mathscr {L}}$$
L
are orthogonal with respect to the invariant Gaussian measure. Then we show by means of two examples that if B admits distinct eigenvalues, the generalized eigenspaces of $${\mathscr {L}}$$
L
may or may not be orthogonal.
German forecasters’ narratives: How informative are German business cycle forecast reports?
Authors: Müller Karsten
Published: July 2021

Based on German business cycle forecast reports covering 10 German institutions for the period 1993–2017, the paper analyses the information content of German forecasters’ narratives for German business cycle forecasts. The paper applies textual analysis to convert qualitative text data into quantitative sentiment indices. First, a sentiment analysis utilizes dictionary methods and text regression methods, using recursive estimation. Next, the paper analyses the different characteristics of sentiments. In a third step, sentiment indices are used to test the efficiency of numerical forecasts. Using 12-month-ahead fixed horizon forecasts, fixed-effects panel regression results suggest some informational content of sentiment indices for growth and inflation forecasts. Finally, a forecasting exercise analyses the predictive power of sentiment indices for GDP growth and inflation. The results suggest weak evidence, at best, for in-sample and out-of-sample predictive power of the sentiment indices.
A partition-enhanced least-squares collocation approach (PE-LSC)
Authors: Zingerle P. , Pail R. , Willberg M. , Scheinert M.
Published: July 2021

We present a partition-enhanced least-squares collocation (PE-LSC) which comprises several modifications to the classical LSC method. It is our goal to circumvent various problems of the practical application of LSC. While these investigations are focused on the modeling of the exterior gravity field the elaborated methods can also be used in other applications. One of the main drawbacks and current limitations of LSC is its high computational cost which grows cubically with the number of observation points. A common way to mitigate this problem is to tile the target area into sub-regions and solve each tile individually. This procedure assumes a certain locality of the LSC kernel functions which is generally not given and, therefore, results in fringe effects. To avoid this, it is proposed to localize the LSC kernels such that locality is preserved, and the estimated variances are not notably increased in comparison with the classical LSC method. Using global covariance models involves the calculation of a large number of Legendre polynomials which is usually a time-consuming task. Hence, to accelerate the creation of the covariance matrices, as an intermediate step we pre-calculate the covariance function on a two-dimensional grid of isotropic coordinates. Based on this grid, and under the assumption that the covariances are sufficiently smooth, the final covariance matrices are then obtained by a simple and fast interpolation algorithm. Applying the generalized multi-variate chain rule, also cross-covariance matrices among arbitrary linear spherical harmonic functionals can be obtained by this technique. Together with some further minor alterations these modifications are implemented in the PE-LSC method. The new PE-LSC is tested using selected data sets in Antarctica where altogether more than 800,000 observations are available for processing. In this case, PE-LSC yields a speed-up of computation time by a factor of about 55 (i.e., the computation needs only hours instead of weeks) in comparison with the classical unpartitioned LSC. Likewise, the memory requirement is reduced by a factor of about 360 (i.e., allocating memory in the order of GB instead of TB).
Bioactivites of Penicillium citrinum isolated from a medicinal plant Swertia chirayita
Authors: Sharma Hemant , Rai Arun Kumar , Chettri Rajen , Nigam Poonam Singh
Published: August 2021

Endophytes associated with plants have the property to produce active biomolecules with their possible applications in agro-industrial sectors. This study provides a project work on analyzing various activities of fungal endophytes isolated from Swertia chirayita of Sikkim Himalayan region. Among several fungal endophytes screened, isolate UTCRF6 was found most active with the secretion of enzymes protease, cellulase, amylase and chitinase, as well as other metabolites Indoleacetic acid and siderophores. This endophyte was found active in restricting the growth of phyto-pathogens, including strains of Fusarium solani, Colletotrichum gloeosporioides, Alternaria alternata, Pestalotiopsis theae and Sclerotinia sclerotiorum. Morphological and molecular studies of this endophytic fungus showed similarity with Penicillium citrinum.

Graphic abstract
On the cohomology rings of real flag manifolds: Schubert cycles
Authors: Matszangosz Ákos K.
Published: July 2021

We give an algorithm to compute the integer cohomology groups of any real partial flag manifold, by computing the incidence coefficients of the Schubert cells. For even flag manifolds we determine the integer cohomology groups, by proving that any torsion class has order 2 (generalizing a result of Ehresmann). We conjecture that this holds for any real flag manifold. We obtain results concerning which Schubert varieties represent integer cohomology classes, their structure constants and how to express them in terms of characteristic classes. For even flag manifolds and Grassmannians we also describe Schubert calculus. The Schubert calculus can be used to obtain lower bounds for certain real enumerative geometry problems (Schubert problems).
Aperiodic order and spherical diffraction, II: translation bounded measures on homogeneous spaces
Authors: Björklund Michael , Hartnick Tobias , Pogorzelski Felix
Published: July 2021

We study the auto-correlation measures of invariant random point processes in the hyperbolic plane which arise from various classes of aperiodic Delone sets. More generally, we study auto-correlation measures for large classes of Delone sets in (and even translation bounded measures on) arbitrary locally compact homogeneous metric spaces. We then specialize to the case of weighted model sets, in which we are able to derive more concrete formulas for the auto-correlation. In the case of Riemannian symmetric spaces we also explain how the auto-correlation of a weighted model set in a Riemannian symmetric space can be identified with a (typically non-tempered) positive-definite distribution on $$\mathbb {R}^n$$

R

n

. This paves the way for a diffraction theory for such model sets, which will be discussed in the sequel to the present article.
Individual differences in social play behaviour predict alcohol intake and control over alcohol seeking in rats
Authors: Lesscher Heidi M. B. , Achterberg E. J. Marijke , Siviy Stephen M. , Vanderschuren Louk J. M. J.
Published: August 2021

Rationale

Social play behaviour is a rewarding social activity displayed by young mammals, thought to be important for the development of brain and behaviour. Indeed, disruptions of social play behaviour in rodents have been associated with cognitive deficits and augmented sensitivity to self-administration of substances of abuse, including alcohol, later in life. However, the relation between social development and loss of control over substance use, a key characteristic of substance use disorders including alcohol use disorder (AUD), has not been investigated. Moreover, it remains unknown how inherent differences in playfulness relate to differences in the sensitivity to substance use and AUD.

Objective

The objective of this study is to determine how individual differences in juvenile social play behaviour predict alcohol intake and loss of control over alcohol seeking.

Methods

Juvenile male Lister hooded rats were characterized for their tendency to engage in social play behaviour. Subsequently, alcohol consumption and conditioned suppression of alcohol seeking were assessed in the tertiles of rats that showed the most and least social play.

Results

The rats that engaged most in social play behaviour consumed more alcohol than their less playful counterparts. However, whereas the most playful rats showed intact conditioned suppression of alcohol seeking, the least playful rats showed no such suppression.

Conclusion

Individual levels of playfulness predict the sensitivity to alcohol-directed behaviour. Highly playful rats are more prone to alcohol intake, yet show greater control over alcohol seeking. These findings increase our understanding of the relationship between social development and vulnerability to AUD.
Capture of carbon dioxide and hydrogen by engineered Escherichia coli: hydrogen-dependent CO2 reduction to formate
Authors: Leo Felix , Schwarz Fabian M. , Schuchmann Kai , Müller Volker
Published: July 2021

In times of global climate change and the fear of dwindling resources, we are facing different considerable challenges such as the replacement of fossil fuel–based energy carriers with the coincident maintenance of the increasing energy supply of our growing world population. Therefore, CO2 capturing and H2 storing solutions are urgently needed. In this study, we demonstrate the production of a functional and biotechnological interesting enzyme complex from acetogenic bacteria, the hydrogen-dependent CO2 reductase (HDCR), in the well-known model organism Escherichia coli. We identified the metabolic bottlenecks of the host organisms for the production of the HDCR enzyme complex. Here we show that the recombinant expression of a heterologous enzyme complex transforms E. coli into a whole-cell biocatalyst for hydrogen-driven CO2 reduction to formate without the need of any external co-factors or endogenous enzymes in the reaction process. This shifts the industrial platform organism E. coli more and more into the focus as biocatalyst for CO2-capturing and H2-storage.

Key points

• A functional HDCR enzyme complex was heterologously produced in E. coli.

• The metabolic bottlenecks for HDCR production were identified.

• HDCR enabled E. coli cell to capture and store H2and CO2in the form of formate.
Modelling [18F]LW223 PET data using simplified imaging protocols for quantification of TSPO expression in the rat heart and brain
Authors: MacAskill Mark G. , Wimberley Catriona , Morgan Timaeus E. F. , Alcaide-Corral Carlos J. , Newby David E. , Lucatelli Christophe , Sutherland Andrew , Pimlott Sally L. , Tavares Adriana A. S.
Published: August 2021

Purpose

To provide a comprehensive assessment of the novel 18 kDa translocator protein (TSPO) radiotracer, [18F]LW223, kinetics in the heart and brain when using a simplified imaging approach.

Methods

Naive adult rats and rats with surgically induced permanent coronary artery ligation received a bolus intravenous injection of [18F]LW223 followed by 120 min PET scanning with arterial blood sampling throughout. Kinetic modelling of PET data was applied to estimated rate constants, total volume of distribution (VT) and binding potential transfer corrected (BPTC) using arterial or image-derived input function (IDIF). Quantitative bias of simplified protocols using IDIF versus arterial input function (AIF) and stability of kinetic parameters for PET imaging data of different length (40–120 min) were estimated.

Results

PET outcome measures estimated using IDIF significantly correlated with those derived with invasive AIF, albeit with an inherent systematic bias. Truncation of the dynamic PET scan duration to less than 100 min reduced the stability of the kinetic modelling outputs. Quantification of [18F]LW223 uptake kinetics in the brain and heart required the use of different outcome measures, with BPTC more stable in the heart and VT more stable in the brain.

Conclusion

Modelling of [18F]LW223 PET showed the use of simplified IDIF is acceptable in the rat and the minimum scan duration for quantification of TSPO expression in rats using kinetic modelling with this radiotracer is 100 min. Carefully assessing kinetic outcome measures when conducting a systems level as oppose to single-organ centric analyses is crucial. This should be taken into account when assessing the emerging role of the TSPO heart-brain axis in the field of PET imaging.
Egg covering in cavity nesting birds may prevent nest usurpation by other species
Authors: Slagsvold Tore , Wiebe Karen L.
Published: July 2021

Some birds cover their eggs with nest material when they leave to forage. It has been suggested that such egg-covering aids thermoregulation or prevents predation but here we present a new hypothesis, that secondary cavity-nesting species cover their eggs to prevent nest usurpation by other birds. When the bottom of the cavity is dark, as when eggs are covered by nest material, it may be difficult for a prospecting competitor to see whether a defending nest owner or a predator is hiding inside the cavity. Competitors may therefore hesitate to enter dark cavities. We filmed 21 great tit (Parus major) nests during the egg-laying period and found that the female spent bouts of highly variable length outside the nest box (range 0.3–250 min,n = 51), so prospecting small passerines would have difficulty predicting whether an aggressive tit owner was in the box or would soon return. We presented prospecting male pied flycatchers (Ficedula hypoleuca) with a dyad of boxes (n = 93), each containing a great tit nest but only one with visible eggs. Flycatchers hesitated more to enter a nest box with no visible tit eggs than a box with exposed eggs. This was most evident for nest boxes with dark versus light interior paint, supporting the idea that better interior illumination makes prospecting birds more confident about entering an unfamiliar cavity. The usurpation and predation hypotheses are not mutually exclusive because both competitors and small predators may hesitate to enter dark, enclosed spaces if visibility is low.

Significance statement

Some birds deposit a layer of material on top of the eggs when they leave the nest. Several hypotheses have been proposed for such egg covering, for example that it may insulate the eggs and reduce the risk of nest predation. We propose a new hypothesis, namely that secondary hole-nesting birds cover their eggs when they leave the nest to prevent usurpation of the cavity by other birds. Great tits that we filmed at the nest during the egg-laying period could be absent for long periods. To test the hypothesis, we presented male pied flycatchers, potential nest competitors, with a dyad of nest boxes, each containing a great tit nest but only one with visible tit eggs. In support of the prediction, prospecting flycatchers hesitated to enter dark cavities with dark floors relative to boxes with exposed, reflective eggs.
Primary renal sarcomas: imaging features and discrimination from non-sarcoma renal tumors
Authors: Uhlig Johannes , Uhlig Annemarie , Bachanek Sophie , Onur Mehmet Ruhi , Kinner Sonja , Geisel Dominik , Köhler Michael , Preibsch Heike , Puesken Michael , Schramm Dominik , May Matthias , De Visschere Pieter , Weber Marc-André , Surov Alexey
Published: July 2021

Objectives

To assess imaging features of primary renal sarcomas in order to better discriminate them from non-sarcoma renal tumors.

Methods

Adult patients diagnosed with renal sarcomas from 1995 to 2018 were included from 11 European tertiary referral centers (Germany, Belgium, Turkey). Renal sarcomas were 1:4 compared to patients with non-sarcoma renal tumors. CT/MRI findings were assessed using 21 predefined imaging features. A random forest model was trained to predict “renal sarcoma vs. non-sarcoma renal tumors” based on demographics and imaging features.

Results

n = 34 renal sarcomas were included and compared to n = 136 non-sarcoma renal tumors. Renal sarcomas manifested in younger patients (median 55 vs. 67 years, p < 0.01) and were more complex (high RENAL score complexity 79.4% vs. 25.7%, p < 0.01). Renal sarcomas were larger (median diameter 108 vs. 43 mm, p < 0.01) with irregular shape and ill-defined margins, and more frequently demonstrated invasion of the renal vein or inferior vena cava, tumor necrosis, direct invasion of adjacent organs, and contact to renal artery or vein, compared to non-sarcoma renal tumors (p < 0.05, each). The random forest algorithm yielded a median AUC = 93.8% to predict renal sarcoma histology, with sensitivity, specificity, and positive predictive value of 90.4%, 76.5%, and 93.9%, respectively. Tumor diameter and RENAL score were the most relevant imaging features for renal sarcoma identification.

Conclusion

Renal sarcomas are rare tumors commonly manifesting as large masses in young patients. A random forest model using demographics and imaging features shows good diagnostic accuracy for discrimination of renal sarcomas from non-sarcoma renal tumors, which might aid in clinical decision-making.

Key Points

• Renal sarcomas commonly manifest in younger patients as large, complex renal masses.

• Compared to non-sarcoma renal tumors, renal sarcomas more frequently demonstrated invasion of the renal vein or inferior vena cava, tumor necrosis, direct invasion of adjacent organs, and contact to renal artery or vein.

• Using demographics and standardized imaging features, a random forest showed excellent diagnostic performance for discrimination of sarcoma vs. non-sarcoma renal tumors (AUC = 93.8%, sensitivity = 90.4%, specificity = 76.5%, and PPV = 93.9%).
Estimating the Covariance Matrix of the Maximum Likelihood Estimator Under Linear Cluster-Weighted Models
Authors: Soffritti Gabriele
Published: July 2021

In recent years, the research into cluster-weighted models has been intense. However, estimating the covariance matrix of the maximum likelihood estimator under a cluster-weighted model is still an open issue. Here, an approach is developed in which information-based estimators of such a covariance matrix are obtained from the incomplete data log-likelihood of the multivariate Gaussian linear cluster-weighted model. To this end, analytical expressions for the score vector and Hessian matrix are provided. Three estimators of the asymptotic covariance matrix of the maximum likelihood estimator, based on the score vector and Hessian matrix, are introduced. The performances of these estimators are numerically evaluated using simulated datasets in comparison with a bootstrap-based estimator; their usefulness is illustrated through a study aiming at evaluating the link between tourism flows and attendance at museums and monuments in two Italian regions.
Instability and results after non-operative treatment of large anterior glenoid rim fractures: is there a correlation between fragment size or displacement and recurrence?
Authors: Königshausen Matthias , Pätzholz Simon , Coulibaly Marlon , Nicolas Volkmar , Vandemeulebroecke Marc , Schildhauer Thomas Armin , Seybold Dominik
Published: August 2021

Introduction

There is little data available on non-operative treatment of anterior glenoid rim fractures (GRF). Nothing is known about fracture size and displacement in comparison to clinical outcomes and instability in a mainly middle-aged patient population. The aim of this study was to demonstrate the results of non-operative treatment in anterior glenoid rim fractures with the special focus on potential instability/recurrence.

Methods

The inclusion criteria were non-operatively treated anterior GRF of at least ≥ 5 mm width using the age- and gender-matched Constant/Murley score (a.-/g.-CMS) and the Western Ontario Instability Index (WOSI). Radiographic parameters (fracture morphology, displacement, major tuberosity fractures and Hill–Sachs lesion using initial CT and radiographs) and the proportion of the fractured glenoid were detected (2D-CT-circle-method) and osteoarthritis (A.P. and axial radiographs) was classified according to Samilson/Prieto. Proportion of fractured glenoid and medial displacement were correlated with the recurrence rate and the clinical scores.

Results

N = 36 patients could be followed-up after a mean of 4.4 years [12–140 month, average age: 58 (± 13, 33–86) years]. The a.-/g.-CMS was 93 (± 11, 61–100) points, and the WOSI was 81% (± 22%, 35–100%) on average. The mean intraarticular displacement was 4 mm (± 3 mm; 0–14 mm). The 2D-circle-method showed a mean glenoid fracture involvement of 21% (± 11, 10–52%). Two cases of frozen shoulders and one case with biceps pathology were associated with the trauma. Within the followed-up patient group re-instability has occurred in n = 2 patients (6%) within the first two weeks after trauma. Osteoarthritis was found in n = 11 cases. There was no correlation between the scores and the fracture size/displacement [(a.-/g.-CMS vs. displacement: r = − 0.08; p = 0.6; vs. size: r = − 0.29; p = 0.2); (WOSI vs. displacement: r = − 0.14; p = 0.4; vs. size: r = − 0.37; p = 0.06)], but very large (≥ 21%) fractures with displacement ≥ 4 mm showed slightly worse results without significant difference (a.-/g.-CMS p = 0.2; WOSI p = 0.2). The apprehension test was negative in all patients at final follow-up.

Conclusion

Non-operative treatment of anterior GRF was associated with overall good results within a mainly middle-aged larger patient group. Re-instability is rare and is not associated with fragment size but can occur in the first weeks after trauma. Size and dislocation of the fracture is not a criterion for the prognosis of potential instability.

Level of evidence

Level IV, retrospective case series.
A novel electrosurgical divider: performance in a self-controlled tonsillectomy study
Authors: Besser Gerold , Grasl Stefan , Meyer Elias L. , Schnoell Julia , Bartosik Tina J. , Brkic Faris F. , Heiduschka Gregor
Published: August 2021

Purpose

Tonsillectomies are among the most common surgeries in otorhinolaryngology. A novel electrosurgical temperature-controlled instrument (device) promises rapid tonsillectomies and might reduce postoperative pain, but comparative studies to assess performance are warranted.

Methods

This randomized self-controlled clinical trial was conducted from October 2019 to October 2020 at the Department of Otorhinolaryngology, Head and Neck Surgery of the Medical University of Vienna. Forty-eight patients underwent a tonsillectomy with the device on one side and using cold-steel with localized bipolar cauterization on the other side (control). Main outcomes were the time for tonsil removal (per side) and the time to stop bleeding (per side). Secondary measurements were postoperative pain, assessed once on day 0 and five times on days 1, 3, 5, 7, and 10. Postoperative bleeding episodes and consequences were recorded.

Results

Device tonsillectomies were performed significantly faster than controls; the mean surgical time difference was 209 s (p < 0.001, 95% CI 129; 288). Intraoperative blood loss was significantly lower on the device side (all p < 0.05). Postoperative measurements of pain and bleeding were similar for both sides. Two return-to-theatre secondary bleeding events were recorded for the control side.

Conclusion

The novel electrosurgical temperature-controlled divider reduced the tonsillectomy surgical time and intraoperative blood loss, with no apparent negative effects on postoperative pain or bleeding, compared to a cold-steel tonsillectomy with localized bipolar cauterization. In time-restricted settings, the device could be beneficial, particularly after familiarization with device handling.

Trial registration

ClinicalTrials.gov Identifier: NCT03793816.
Disentangling the PIGD classification for the prediction of cognitive impairment in de novo Parkinson’s disease
Authors: Urso Daniele , Leta Valentina , Batzu Lucia , Yousaf Tayyabah , Farrell Chloe , van Wamelen Daniel J. , Ray Chaudhuri K.
Published: August 2021

Background

Postural Instability and Gait difficulties (PIGD) subtype has been associated with worse cognitive performance in Parkinson’s disease (PD).

Objective

To investigate whether PIGD subtype classification or PIGD-related clinical features predict the development of cognitive decline in de novo PD patients.

Methods

Data from 422 PD patients with de novo PD were obtained from the PPMI database. At follow-up (up to 6 years), patients were categorized as having cognitive impairment or not. Multivariate Cox survival analysis was carried out including motor subtype and individual MDS-UPDRS items defining PIGD phenotype as predictors. Previously validated clinical predictors of cognitive impairment were included in the model as covariates. Occurrence of cognitive impairment at follow-up was used as the time-to-event and Kaplan–Meier curve was generated.

Results

At baseline, 76 patients were classified as PIGD, 299 tremor-dominant and 47 as indeterminate. Development of cognitive impairment was not associated with PIGD subtype (p = 0.252). When individual MDS-UPDRS items were interrogated in the model, postural instability proved to be an independent predictor of cognitive impairment (HR = 2.045; 95%CI: 1.068–3.918; p = 0.031), while gait difficulties were not associated with cognitive decline (p = 0.870).

Conclusions

Our findings suggest that postural instability, as assessed by MDS-UPDRS III, may serve as a possible indicator of the risk of developing cognitive impairment in de novo PD patients rather than the PIGD phenotype.
Pitfalls in quantifying exploration in reward-based motor learning and how to avoid them
Authors: van Mastrigt Nina M. , van der Kooij Katinka , Smeets Jeroen B. J.
Published: August 2021

When learning a movement based on binary success information, one is more variable following failure than following success. Theoretically, the additional variability post-failure might reflect exploration of possibilities to obtain success. When average behavior is changing (as in learning), variability can be estimated from differences between subsequent movements. Can one estimate exploration reliably from such trial-to-trial changes when studying reward-based motor learning? To answer this question, we tried to reconstruct the exploration underlying learning as described by four existing reward-based motor learning models. We simulated learning for various learner and task characteristics. If we simply determined the additional change post-failure, estimates of exploration were sensitive to learner and task characteristics. We identified two pitfalls in quantifying exploration based on trial-to-trial changes. Firstly, performance-dependent feedback can cause correlated samples of motor noise and exploration on successful trials, which biases exploration estimates. Secondly, the trial relative to which trial-to-trial change is calculated may also contain exploration, which causes underestimation. As a solution, we developed the additional trial-to-trial change (ATTC) method. By moving the reference trial one trial back and subtracting trial-to-trial changes following specific sequences of trial outcomes, exploration can be estimated reliably for the three models that explore based on the outcome of only the previous trial. Since ATTC estimates are based on a selection of trial sequences, this method requires many trials. In conclusion, if exploration is a binary function of previous trial outcome, the ATTC method allows for a model-free quantification of exploration.
Novel RGAG1-BCOR gene fusion revealed in a somatic soft tissue sarcoma with a long follow-up
Authors: Vasella Mauro , Wagner Ulrich , Fritz Christine , Seidl Kati , Giudici Luca , Exner Gerhard Ulrich , Moch Holger , Wild Peter Johannes , Bode-Lesniewska Beata
Published: July 2021

BCOR-rearranged sarcomas are rare and belong to the Ewing-like sarcomas (ELS). Their morphology and histopathological features make the diagnosis challenging. We present a case, initially diagnosed as an unusual extraskeletal myxoid chondrosarcoma (EMC). A 54-year-old male patient developed an asymptomatic swelling of the lower leg. Imaging showed a 9.5-cm large intramuscular soft tissue mass. Due to its morphological and immunohistochemical profile on biopsy, it was initially diagnosed as an EMC. The patient was treated by complete resection and adjuvant radiotherapy and remained free of tumor at 7 years follow-up. Using next-generation sequencing (NGS), we retrospectively identified RGAG1-BCOR gene fusion (confirmed by RT-PCR), which has not been described in somatic soft tissue tumors so far. This finding broadens the spectrum of partner genes in the BCOR-rearranged sarcomas in a tumor with a well-documented, long clinical follow-up.
Die Rechte zukünftiger Kinder im Kontext pränataler Diagnostik
Authors: Schmitz Dagmar , Düwell Marcus
Published: August 2021

Das Gendiagnostikgesetz (GenDG) verbietet seit 2010 die pränatale Diagnostik spätmanifestierender Erkrankungen (§ 15(2) GenDG). In seiner Begründung bezog sich der Gesetzgeber in Analogie zu internationalen Empfehlungen für den pädiatrischen Bereich vor allem auf das Recht des heranwachsenden Kindes bzw. des späteren Erwachsenen auf Nichtwissen. Mit diesem gesetzlichen Verbot hat Deutschland einen viel diskutierten Sonderweg in der Regulierung genetischer Pränataldiagnostik eingeschlagen. Seither jedoch hat sich nicht nur die Perspektive auf prädiktive Testungen im Kindesalter verändert. In zunehmendem Maße generieren auf das gesamte Genom abzielende Diagnostikangebote auch andere vorgeburtlich genetische Informationen, die – in ähnlicher Weise wie diejenigen zu spätmanifestierenden Erkrankungen eine potenzielle Gefahr für das Recht auf Nichtwissen der späteren Person darstellen. Es soll daher im Rahmen dieses Beitrages überprüft werden, inwiefern das deutsche Diagnostikverbot und dessen Bezug auf das Recht auf Nichtwissen des späteren Kindes eine tragfähige Basis zur Regulierung gendiagnostischer Untersuchungen in der Pränatalmedizin insgesamt darstellt bzw. zukünftig darstellen kann.

Untersucht wird der Argumentationsgang des Diagnostikverbotes im Hinblick auf spätmanifestierende Erkrankungen vor dem Hintergrund der Entwicklungen in der prädiktiven (genomischen) Diagnostik. Eine Analyse des normativen Begründungsrahmens zeigt, dass nach wie vor deutlicher Klärungsbedarf hinsichtlich der philosophisch-ethischen Fundierung wie auch hinsichtlich der Interpretation eines Rechts auf Nichtwissen eines (zukünftigen) Kindes im Kontext von genetischer Diagnostik besteht. Darüber hinaus müssen auch Interessen des (zukünftigen) Kindes an eventuell möglich werdender pränataler Behandlung oder Prävention von Erkrankungen in die Abwägung miteinbezogen werden.

Um zukünftigen Herausforderungen genomischer Pränataldiagnostik und -therapie begegnen zu können, müsste dringend geklärt werden, inwiefern Rechte zukünftiger Personen tatsächlich in der speziellen Situation der Schwangerschaft relevant sein können und mit welchen Pflichten diese für den Gesetzgeber, aber insbesondere auch für zukünftige Eltern und Ärzte einhergehen. Der Menschenrechtsdiskurs könnte hierfür eine tragfähige Basis und hilfreiche Strategien liefern.