bluuebunny/crossref_metadata_2025 huggingface dataset:
Consecutive false‐negative rRT‐PCR test results for SARS‐CoV‐2 in patients after clinical recovery from COVID‐19
Authors: Wang Guan , Yu Na , Xiao Weimin , Zhao Chen , Wang Zhenning
Published: June 2020

This study reviewed the serial real‐time reverse‐transcription polymerase chain reaction (rRT‐PCR) results of 37 patients admitted to our hospital in Wuhan, China, who had three or more sequential negative results before discharge. Of these 37 patients, 14 (~38%) had a positive rRT‐PCR result after a negative result during convalescence, and 5 (~14%) had a positive rRT‐PCR result after two consecutive negative results during convalescence. These results suggest that it may be necessary to require that patients have three consecutive negative results before discharge, to ensure that they do not spread infection among members of their household, or in the community. We believe that our study makes a significant contribution to the literature because it is not currently the standard of care to require patients to have three consecutive negative results before discharge. Our results suggest that a relatively high proportion of patients may continue to shed severe acute respiratory syndrome coronavirus 2 after they have clinically recovered, and thus may transmit the infection to others.
Characterization of the seasonal variation of soil moisture in Argentina
Authors: Fernández‐Long María Elena , Peretti Mercedes , Carnelos Danilo , Della‐Chiesa Tomás , Spescha Liliana
Published: June 2020

Soil moisture is an essential variable for both the agricultural production and the functioning of natural ecosystems, as well as one of the main variables regulating the climate system. Like precipitation, soil moisture has a marked annual cycle that depends mainly on the behaviour of precipitation and evapotranspiration. In this study, we developed a methodology that allows describing and characterizing the annual cycle of soil moisture in Argentina. For this purpose, we estimated soil moisture at 121 sites of Argentina by means of a simple hydrological balance (the BHOA, an acronym for its name in Spanish: “Balance Hidrológico Operativo para el Agro”) and analysed its intra‐annual variability by means of different indices. This methodology allowed recognizing five different annual behaviours, with a consistent geographical pattern throughout Argentina. The characterization was based mainly on the time of occurrence of the annual maximum and minimum values of soil moisture, and secondly by the annual soil moisture content and seasonality. The northwest and part of the centre of Argentina present the minimum soil moisture values in spring and the maximum ones in autumn, while the east and south present the minimum values in summer and the maximum ones in winter. In general, sites with higher soil water content were found to have lower seasonality and vice‐versa.
Evaluation of the van Deemter equation in terms of open‐ended flow to chromatography
Authors: Andersen Jens E.T. , Mukami Hawa W. , Maina Irene W.
Published: June 2020

Plate theory and adsorption theory are the main tools available for understanding chromatographic experiments. Both theories predict a Gaussian distribution of solute molecules within the tubular system. However, Gaussian concentration distributions are observed predominantly at slow linear flow rates, while asymmetric concentration distributions are observed at the linear flow rates most used in chromatography. Allegedly, this asymmetry originates from an inhomogeneous distribution of grain sizes in the column and column overload. However, it is an experimental fact that the distribution of chemicals within an injected volume of solute changes as a function of time, while the response is measured simultaneously. Accordingly, the obtained signal cannot be compared to the theory before some type of time‐based deconvolution of the data has been performed. Adjustments to high‐performance liquid chromatography data were thus proposed through empirical equations that describe the relevant time values, peak height, peak area, and parameters of the van Deemter equation. It was proposed that the transfer of solute from the front to the rear part of the pulse during laminar open‐ended flow occurs at rate that depends on the linear flow rate, and to a lesser extent, on properties of the response function.
Increased Expression of PD‐1 and PD‐L1 in Patients With Laryngotracheal Stenosis
Authors: Davis Ruth J. , Lina Ioan , Ding Dacheng , Engle Elizabeth L. , Taube Janis , Gelbard Alexander , Hillel Alexander T.
Published: June 2020

Objectives

Laryngotracheal stenosis (LTS) is a fibrotic condition of the upper airway. Recent evidence suggests dysregulated host immunity plays a role in LTS development and progression. The programmed death‐1 (PD‐1)/programmed death‐ligand 1 (PD‐L1) axis, targeted by paradigm‐shifting immunotherapies for cancer treatment, has also recently been implicated in the pathogenesis of fibrotic pulmonary disease. However, a role for the PD‐1/PD‐L1 axis in the proximal airway fibrosis seen in LTS patients has not been explored.

Study Design

Controlled ex vivo study.

Methods

Expression of PD‐1, PD‐L1, CD4, and CD8 were evaluated using immunohistochemical staining of cricotracheal resection specimens from postintubation iatrogenic laryngotracheal stenosis (iLTS), idiopathic subglottic stenosis (iSGS) patients, and normal controls derived from rapid autopsy (n = 8 per group). Fibroblasts derived from iLTS scar were also treated with transforming growth factor beta 1 (TGFβ1) and analyzed for PD‐L1 expression by quantitative real‐time polymerase chain reaction (n = 6).

Results

iLTS specimens exhibited increased expression of PD‐1, PD‐L1, and CD4 (all P < .0167) compared to controls, whereas iSGS specimens exhibited increased expression of PD‐1 and CD4 (P < .0167) compared to controls. PD‐1, PD‐L1, and CD4 showed periepithelial patterns of expression in both disease cohorts. TGFβ1 treatment of iLTS fibroblasts increased expression of PD‐L1 (the cognate ligand for PD‐1).

Conclusion

Expression of both PD‐1 and its ligand PD‐L1 are significantly greater in patients with iLTS compared to controls, and PD‐1 expression is also elevated in patients with iSGS. Given published evidence implicating the PD‐1/PD‐L1 axis in pulmonary fibrosis, this suggests a possible role for checkpoint inhibitors targeting the PD‐1/PD‐L1 axis for the treatment of LTS.

Level of Evidence

N/A Laryngoscope, 131:967–974, 2021
Variable clinical expression of Stickler Syndrome: A case report of a novel COL11A1 mutation
Authors: Brizola Evelise , Gnoli Maria , Tremosini Morena , Nucci Paolo , Bargiacchi Sara , La Barbera Andrea , Giglio Sabrina , Sangiorgi Luca
Published: June 2020

Background

Stickler Syndrome is a rare connective tissue disorder, characterized by clinical, and genetic heterogeneity. The clinical expression is highly variable, including moderate to severe myopia in childhood, hearing loss, facial dysmorphic features, cleft palate, and early osteoarthritis. COL2A1, COL11A1, and COL11A2 mutations account of the majority of autosomal dominant Stickler Syndrome and, in particular, a heterozygous mutation in COL11A1 gene is identified in about 10 to 20% of Stickler Syndrome patients.

Methods

Herein, we report a case of an 8‐year‐ old child with Stickler Syndrome, presenting with early‐onset of myopia with vitreal abnormalities, facial dysmorphic characteristics, and mild hearing loss later in childhood. To identify the underlying genetic cause, Whole Exome Sequencing was carried out for COL11A1 gene.

Results

A novel de novo heterozygous splice site variant (NM_001854: c.1845 + 5G> C) of the COL11A1 gene, which had not been previously reported, was identified by Whole Exome Sequencing.

Conclusion

We reported a novel COL11A1 mutation in a child with Stickler Syndrome presenting a phenotype of early‐onset of ocular anomalies and mild hearing loss later in childhood. Our findings confirm the variability of the expression of the disease, even in the contest of the same gene‐related disorder, thus, contributing to improve the knowledge on clinical and molecular basis of this rare disease.
Diffusion MRI detects early brain microstructure abnormalities in 2‐month‐old 3×Tg‐AD mice
Authors: Falangola Maria Fatima , Nie Xingju , Ward Ralph , McKinnon Emilie T. , Dhiman Siddhartha , Nietert Paul J. , Helpern Joseph A. , Jensen Jens H.
Published: June 2020

The 3×Tg‐AD mouse is one of the most studied animal models of Alzheimer's disease (AD), and develops both amyloid beta deposits and neurofibrillary tangles in a temporal and spatial pattern that is similar to human AD pathology. Additionally, abnormal myelination patterns with changes in oligodendrocyte and myelin marker expression are reported to be an early pathological feature in this model. Only few diffusion MRI (dMRI) studies have investigated white matter abnormalities in 3×Tg‐AD mice, with inconsistent results. Thus, the goal of this study was to investigate the sensitivity of dMRI to capture brain microstructural alterations in 2‐month‐old 3×Tg‐AD mice. In the fimbria, the fractional anisotropy (FA), kurtosis fractional anisotropy (KFA), and radial kurtosis (K┴) were found to be significantly lower in 3×Tg‐AD mice than in controls, while the mean diffusivity (MD) and radial diffusivity (D┴) were found to be elevated. In the fornix, K┴ was lower for 3×Tg‐AD mice; in the dorsal hippocampus MD and D┴ were elevated, as were FA, MD, and D┴ in the ventral hippocampus. These results indicate, for the first time, dMRI changes associated with myelin abnormalities in young 3×Tg‐AD mice, before they develop AD pathology. Morphological quantification of myelin basic protein immunoreactivity in the fimbria was significantly lower in the 3×Tg‐AD mice compared with the age‐matched controls. Our results demonstrate that dMRI is able to detect widespread, significant early brain morphological abnormalities in 2‐month‐old 3×Tg‐AD mice.
A variational discrete element method for quasistatic and dynamic elastoplasticity
Authors: Marazzato Frédéric , Ern Alexandre , Monasse Laurent
Published: June 2020

We propose a new discrete element method supporting general polyhedral meshes. The method can be understood as a lowest‐order discontinuous Galerkin method parametrized by the continuous mechanical parameters (Young's modulus and Poisson's ratio). We consider quasistatic and dynamic elastoplasticity, and in the latter situation, a pseudoenergy conserving time‐integration method is employed. The computational cost of the time‐stepping method is moderate since it is explicit and used with a naturally diagonal mass matrix. Numerical examples are presented to illustrate the robustness and versatility of the method for quasistatic and dynamic elastoplastic evolutions.
Moving Profiling Spatial Proteomics Beyond Discrete Classification
Authors: Crook Oliver M. , Smith Tom , Elzek Mohamed , Lilley Kathryn S.
Published: June 2020

The spatial subcellular proteome is a dynamic environment; one that can be perturbed by molecular cues and regulated by post‐translational modifications. Compartmentalization of this environment and management of these biomolecular dynamics allows for an array of ancillary protein functions. Profiling spatial proteomics has proved to be a powerful technique in identifying the primary subcellular localization of proteins. The approach has also been refashioned to study multi‐localization and localization dynamics. Here, the analytical approaches that have been applied to spatial proteomics thus far are critiqued, and challenges particularly associated with multi‐localization and dynamic relocalization is identified. To meet some of the current limitations in analytical processing, it is suggested that Bayesian modeling has clear benefits over the methods applied to date and should be favored whenever possible. Careful consideration of the limitations and challenges, and development of robust statistical frameworks, will ensure that profiling spatial proteomics remains a valuable technique as its utility is expanded.
Structural compliance: A new metric for protein flexibility
Authors: Scaramozzino Domenico , Khade Pranav M. , Jernigan Robert L. , Lacidogna Giuseppe , Carpinteri Alberto
Published: June 2020

Proteins are the active players in performing essential molecular activities throughout biology, and their dynamics has been broadly demonstrated to relate to their mechanisms. The intrinsic fluctuations have often been used to represent their dynamics and then compared to the experimental B‐factors. However, proteins do not move in a vacuum and their motions are modulated by solvent that can impose forces on the structure. In this paper, we introduce a new structural concept, which has been called the structural compliance, for the evaluation of the global and local deformability of the protein structure in response to intramolecular and solvent forces. Based on the application of pairwise pulling forces to a protein elastic network, this structural quantity has been computed and sometimes is even found to yield an improved correlation with the experimental B‐factors, meaning that it may serve as a better metric for protein flexibility. The inverse of structural compliance, namely the structural stiffness, has also been defined, which shows a clear anticorrelation with the experimental data. Although the present applications are made to proteins, this approach can also be applied to other biomolecular structures such as RNA. This present study considers only elastic network models, but the approach could be applied further to conventional atomic molecular dynamics. Compliance is found to have a slightly better agreement with the experimental B‐factors, perhaps reflecting its bias toward the effects of local perturbations, in contrast to mean square fluctuations. The code for calculating protein compliance and stiffness is freely accessible at https://jerniganlab.github.io/Software/PACKMAN/Tutorials/compliance.
Variation of Topological Edge States of 2D Honeycomb Lattice Photonic Crystals
Authors: Peng Yuchen , Yan Bei , Xie Jianlan , Liu Exian , Li Hang , Ge Rui , Gao Feng , Liu Jianjun
Published: June 2020

Herein, the photonic quantum spin Hall effect is realized in a dielectric 2D honeycomb lattice photonic crystal (PC) with scatterers having various shapes, by stretching and shrinking the honeycomb unit cell. The topological edge states and their unidirectional transmission as scatterers with triangular, pentagonal, and heptagonal shapes are studied. The unidirectional transmission in an inverted Ω‐shaped waveguide, when different types of defects are incorporated, is realized to verify the characteristics of the topological protection. Moreover, flat band can be realized by varying the shape of several scatterers near the combined junction of PCs with different topological states, and the variation trend of flat band is evaluated with the increase in the edge number of varied scatterers from four to seven at different times. Moreover, a slow‐light waveguide is designed to further demonstrate the influence of the shape of scatterers on topological edge states for light transmission. Furthermore, the novel optical phenomenon of static state is realized; that is, light is not able to transmit but is trapped at the original position. This can increase the adjustability of the topological edge states and provide more potential applications for integrated photonic devices.
Increasing the Diversity and Understanding of Semiconductor Nanoplatelets by Colloidal Atomic Layer Deposition
Authors: Reichhelm Annett , Hübner René , Damm Christine , Nielsch Kornelius , Eychmüller Alexander
Published: June 2020

Nanoplatelets (NPLs) are a remarkable class of quantum confined materials with size‐dependent optical properties, which are determined by the defined thickness of the crystalline platelets. To increase the variety of species, the colloidal atomic layer deposition method is used for the preparation of increasingly thicker CdSe NPLs. By growing further crystalline layers onto the surfaces of 4 and 5 monolayers (MLs) thick NPLs, species from 6 to 13 MLs are achieved. While increasing the thickness, the heavy‐hole absorption peak shifts from 513 to 652 nm, leading to a variety of NPLs for applications and further investigations. The thickness and number of MLs of the platelet species are determined by high‐resolution transmission electron microscopy (HRTEM) measurements, allowing the interpretation of several contradictions present in the NPL literature. In recent years, different assumptions are published, leading to a lack of clarity in the fundamentals of this field. Regarding the ongoing scientific interest in NPLs, there is a certain need for clarification, which is provided in this study.
Overview of biological effects of Quercetin on ovary
Authors: Rashidi Zahra , Khosravizadeh Zahra , Talebi Ali , Khodamoradi Kajal , Ebrahimi Reyhane , Amidi Fardin
Published: June 2020

Over the last few decades, using natural products has been increased to treat different diseases. Today, great attention has been pointed toward the usage of natural products such as flavonoids, especially Quercetin (QUR), in the treatment of diseases. QUR as a natural antioxidant has been traditionally used to prevent or treat a variety of diseases such as cancer, cardiovascular disease, polycystic ovary syndrome (PCOS), obesity, chronic inflammation, and reproductive system dysfunction. Several studies demonstrated that QUR acts as an anti‐inflammatory, anti‐apoptotic, antioxidant, and anticancer agent. With this in view, in this study, we intended to describe an overview of the biological effects of QUR on the ovary. QUR improves the quality of oocytes and embryos. It affects the proliferation and apoptosis and decreases the oxidative stress in granulosa cells (GCs). Furthermore, QUR can be used as a complementary and alternative therapy in ovarian cancer and it has beneficial effects in the treatment of PCOS patients. It seems that QUR as a supplementary factor has different activities for the treatment of different disorders and it also has bidirectional activities. However, further investigations are needed for understanding the efficacy of QUR in the treatment and improvement of gynecological patients.
A simple immersed boundary forcing for flows over steep and complex orography
Authors: Allen T. , Zerroukat M.
Published: June 2020

Simulation and parametrization of flow over the Earth's orographic features is an important element of any climate or weather model. With increasing resolution, especially in the limited‐area context, the orographic features are not only becoming better resolved but, importantly for numerical stability, the slopes are becoming ever steeper and the currently employed terrain‐following coordinates can cause convergence issues as the curvilinear terms become relatively large. This paper discusses this specific issue and suggests a possible solution based upon an immersed boundary forcing method for representing steep and complex terrain. The method is simple and straightforward to incorporate into any atmospheric model.
What can we learn from N2O isotope data? – Analytics, processes and modelling
Authors: Yu Longfei , Harris Eliza , Lewicka‐Szczebak Dominika , Barthel Matti , Blomberg Margareta R.A. , Harris Stephen J. , Johnson Matthew S. , Lehmann Moritz F. , Liisberg Jesper , Müller Christoph , Ostrom Nathaniel E. , Six Johan , Toyoda Sakae , Yoshida Naohiro , Mohn Joachim
Published: June 2020

The isotopic composition of nitrous oxide (N2O) provides useful information for evaluating N2O sources and budgets. Due to the co‐occurrence of multiple N2O transformation pathways, it is, however, challenging to use isotopic information to quantify the contribution of distinct processes across variable spatiotemporal scales. Here, we present an overview of recent progress in N2O isotopic studies and provide suggestions for future research, mainly focusing on: analytical techniques; production and consumption processes; and interpretation and modelling approaches.

Comparing isotope‐ratio mass spectrometry (IRMS) with laser absorption spectroscopy (LAS), we conclude that IRMS is a precise technique for laboratory analysis of N2O isotopes, while LAS is more suitable for in situ/inline studies and offers advantages for site‐specific analyses. When reviewing the link between the N2O isotopic composition and underlying mechanisms/processes, we find that, at the molecular scale, the specific enzymes and mechanisms involved determine isotopic fractionation effects. In contrast, at plot‐to‐global scales, mixing of N2O derived from different processes and their isotopic variability must be considered. We also find that dual isotope plots are effective for semi‐quantitative attribution of co‐occurring N2O production and reduction processes. More recently, process‐based N2O isotopic models have been developed for natural abundance and 15N‐tracing studies, and have been shown to be effective, particularly for data with adequate temporal resolution.

Despite the significant progress made over the last decade, there is still great need and potential for future work, including development of analytical techniques, reference materials and inter‐laboratory comparisons, further exploration of N2O formation and destruction mechanisms, more observations across scales, and design and validation of interpretation and modelling approaches. Synthesizing all these efforts, we are confident that the N2O isotope community will continue to advance our understanding of N2O transformation processes in all spheres of the Earth, and in turn to gain improved constraints on regional and global budgets.
Graphical calibration curves and the integrated calibration index (ICI) for survival models
Authors: Austin Peter C. , Harrell Frank E. , van Klaveren David
Published: June 2020

In the context of survival analysis, calibration refers to the agreement between predicted probabilities and observed event rates or frequencies of the outcome within a given duration of time. We aimed to describe and evaluate methods for graphically assessing the calibration of survival models. We focus on hazard regression models and restricted cubic splines in conjunction with a Cox proportional hazards model. We also describe modifications of the Integrated Calibration Index, of E50 and of E90. In this context, this is the average (respectively, median or 90th percentile) absolute difference between predicted survival probabilities and smoothed survival frequencies. We conducted a series of Monte Carlo simulations to evaluate the performance of these calibration measures when the underlying model has been correctly specified and under different types of model mis‐specification. We illustrate the utility of calibration curves and the three calibration metrics by using them to compare the calibration of a Cox proportional hazards regression model with that of a random survival forest for predicting mortality in patients hospitalized with heart failure. Under a correctly specified regression model, differences between the two methods for constructing calibration curves were minimal, although the performance of the method based on restricted cubic splines tended to be slightly better. In contrast, under a mis‐specified model, the smoothed calibration curved constructed using hazard regression tended to be closer to the true calibration curve. The use of calibration curves and of these numeric calibration metrics permits for a comprehensive comparison of the calibration of competing survival models.
Immobilization of Horseradish Peroxidase on Modified Nylon‐6 Fibers
Authors: Alatawi Fatema S. , Elsayed Nadia H. , Monier Mohammed
Published: June 2020

Nylon‐6 fibers were chemically modified via graft copolymerization reaction to being functionalized and utilized as a carrier for the immobilization of horseradish peroxidase (HRP). First, polyethyl acrylate (PEA) was grafted onto the nylon‐6 fibers and the inserted ester groups were transformed to hydrazide groups by treatment with hydrazine hydrate. Then, the obtained hydrazide‐containing fibers were activated by glutaraldehyde, which permits the coupling with the HRP protein macromolecules. The modification, activation and HRP immobilization steps were characterized using elemental analysis and FTIR spectra. Also, the morphology of the fibers was visualized by scanning electron microscope (SEM). The optimum pH of the HRP enzyme was found to shift to a higher value compared to the free enzyme. In addition, despite the same optimum temperature displayed by both free and immobilized HRP, the residual activity of the immobilized enzyme was higher than that of the free one at higher temperatures revealing the enhanced thermal stability upon immobilization process. Moreover, the kinetic studies indicated a lower enzyme‐substrate affinity upon immobilization. However, the immobilized HRP maintained more than 89% and 55% of its original activity after 5 and 10 reuse cycles, respectively, which could be promising results in the future application in the environmental and biotechnological fields.
Development of Deep Learning Models for Predicting the Effects of Exposure to Engineered Nanomaterials on Daphnia magna
Authors: Karatzas Pantelis , Melagraki Georgia , Ellis Laura‐Jayne A. , Lynch Iseult , Varsou Dimitra‐Danai , Afantitis Antreas , Tsoumanis Andreas , Doganis Philip , Sarimveis Haralambos
Published: June 2020

This study presents the results of applying deep learning methodologies within the ecotoxicology field, with the objective of training predictive models that can support hazard assessment and eventually the design of safer engineered nanomaterials (ENMs). A workflow applying two different deep learning architectures on microscopic images of Daphnia magna is proposed that can automatically detect possible malformations, such as effects on the length of the tail, and the overall size, and uncommon lipid concentrations and lipid deposit shapes, which are due to direct or parental exposure to ENMs. Next, classification models assign specific objects (heart, abdomen/claw) to classes that depend on lipid densities and compare the results with controls. The models are statistically validated in terms of their prediction accuracy on external D. magna images and illustrate that deep learning technologies can be useful in the nanoinformatics field, because they can automate time‐consuming manual procedures, accelerate the investigation of adverse effects of ENMs, and facilitate the process of designing safer nanostructures. It may even be possible in the future to predict impacts on subsequent generations from images of parental exposure, reducing the time and cost involved in long‐term reproductive toxicity assays over multiple generations.
Intrinsic Effect of Nanoparticles on the Mechanical Rupture of Doubled‐Shell Colloidal Capsule via In Situ TEM Mechanical Testing and STEM Interfacial Analysis
Authors: Pham Sang T. , Tieu Kiet A. , Wan Shanhong , Hao Jingcheng , Nguyen Huynh H. , Mitchell David R. G. , Sencadas Vitor
Published: June 2020

The discovery of Pickering emulsion templated assembly enables the design of a hybrid colloidal capsule with engineered properties. However, the underlying mechanisms by which nanoparticles affect the mechanical properties of the shell are poorly understood. Herein, in situ mechanical compression on the transmission electron microscope and aberration‐corrected scanning transmission microscope are unprecedentedly implemented to study the intrinsic effect of nanoparticles on the mechanical properties of the calcium carbonate (CaCO3)‐decorated silica (SiO2) colloidal capsule. The stiff and brittle nature of the colloidal capsule is due to the interfacial chemical bonding between the CaCO3 nanoparticles and SiO2 inner shell. Such bonding strengthens the mechanical strength of the SiO2 shell (166 ± 14 nm) from the colloidal capsule compared to the thicker single SiO2 shell (310 ± 70 nm) from the silica hollow sphere. At elevated temperature, this interfacial bonding accelerates the formation of the single calcium silicate shell, causing shell morphology transformation and yielding significantly enhanced mechanical strength by 30.9% and ductility by 94.7%. The superior thermal durability of the heat‐treated colloidal capsule holds great potential for the fabrication of the functional additives that can be applied in the wide range of applications at elevated temperatures.
Bioacoustics in cognitive research: Applications, considerations, and recommendations
Authors: Gentry Katherine E. , Lewis Rebecca N. , Glanz Hunter , Simões Pedro I. , Nyári Árpád S. , Reichert Michael S.
Published: June 2020

The multifaceted ability to produce, transmit, receive, and respond to acoustic signals is widespread in animals and forms the basis of the interdisciplinary science of bioacoustics. Bioacoustics research methods, including sound recording and playback experiments, are applicable in cognitive research that centers around the processing of information from the acoustic environment. We provide an overview of bioacoustics techniques in the context of cognitive studies and make the case for the importance of bioacoustics in the study of cognition by outlining some of the major cognitive processes in which acoustic signals are involved. We also describe key considerations associated with the recording of sound and its use in cognitive applications. Based on these considerations, we provide a set of recommendations for best practices in the recording and use of acoustic signals in cognitive studies. Our aim is to demonstrate that acoustic recordings and stimuli are valuable tools for cognitive researchers when used appropriately. In doing so, we hope to stimulate opportunities for innovative cognitive research that incorporates robust recording protocols.

This article is categorized under:

Neuroscience > Cognition

Psychology > Theory and Methods

Neuroscience > Behavior

Neuroscience > Cognition
Information geometry encoded in bulk geometry
Authors: Tsuchiya Asato , Yamashiro Kazushi
Published: June 2020

Abstract

We study how information geometry is described by bulk geometry in the gauge/gravity correspondence. We consider a quantum information metric that measures the distance between the ground states of a CFT and a theory obtained by perturbing the CFT. We find a universal formula that represents the quantum information metric in terms of back reaction to the AdS bulk geometry.
Intra-individual variance of bilateral femoro-tibial leg rotation: a CT study of 105 healthy subjects
Authors: Ries Christian , Boese Christoph Kolja , Ott Nadine , Doerner Jonas , Müller Lars Peter , Hackl Michael
Published: June 2020

Purpose

In cases of suspected rotational deformity of the lower limb, in particular in post-traumatic malalignment following closed nailing, there is a lack of adequate reference values. Available publications on leg rotation have either small sample sizes or do not include bilateral or whole leg rotation of healthy legs. This study aimed to determine side-specific reference values of lower limb rotation in a large healthy sample. This may be helpful in acute clinical settings as well as for medical expert opinion.

Methods

226 consecutive bilateral lower limb computed tomography (CT) angiographies were screened. 105 patients (210 legs) were included (40 females, 65 males, mean age 67 ± 12 years). Bilateral axial femoral and tibial rotation alignment were independently measured and overall leg rotation was computed by two methods. Distributions, sex, and side differences were analyzed.

Results

Two-sided pairedttests showed significant differences between right and left for all measurements. The left side showed a more pronounced mean anteversion in the femur of 2.2° (p = 0.002) and the right side higher mean external rotation in the tibia of 2.8° (p < 0.001). Overall leg rotation showed 5.1° more mean external rotation on the right side (p < 0.001) with both methods. Absolute side-to-side whole leg rotation difference was 9.5°. Absolute differences between both methods were 3.3°. The variance was high. 23 femora were retroverted, 1 tibia internally rotated, and 9 legs were overall internally rotated. No variables differed between female and male subjects except for femoral version (rightp = 0.003 and left p = 0.002). Correlation coefficients were high (rho 0.550–0.934, allp < 0.001).

Conclusion

There is a significant prevalence of side-to-side asymmetry in femoro-tibial torsion. Although side-to-side differences are not extraordinary, comparative axial femoro-tibial rotation alignment should always be interpreted with caution.

Level of evidence

Diagnostic, retrospective cohort study, level III.
Energy quantization for a singular super-Liouville boundary value problem
Authors: Jost Jürgen , Zhou Chunqin , Zhu Miaomiao
Published: June 2020

In this paper, we develop the blow-up analysis and establish the energy quantization for solutions to super-Liouville type equations on Riemann surfaces with conical singularities at the boundary. In other problems in geometric analysis, the blow-up analysis usually strongly utilizes conformal invariance, which yields a Noether current from which strong estimates can be derived. Here, however, the conical singularities destroy conformal invariance. Therefore, we develop another, more general, method that uses the vanishing of the Pohozaev constant for such solutions to deduce the removability of boundary singularities.
T cell immunity rather than antibody mediates cross-protection against Zika virus infection conferred by a live attenuated Japanese encephalitis SA14-14-2 vaccine
Authors: Wang Ran , Zhen Zida , Turtle Lance , Hou Baohua , Li Yueqi , Wu Na , Gao Na , Fan Dongying , Chen Hui , An Jing
Published: June 2020

Zika virus (ZIKV) and Japanese encephalitis virus (JEV) are closely related to mosquito-borne flaviviruses. Japanese encephalitis (JE) vaccine SA14-14-2 has been in the Chinese national Expanded Program on Immunization since 2007. The recent recognition of severe disease syndromes associated with ZIKV, and the identification of ZIKV from mosquitoes in China, prompts an urgent need to investigate the potential interaction between the two. In this study, we showed that SA14-14-2 is protective against ZIKV infection in mice. JE vaccine SA14-14-2 triggered both Th1 and Th2 cross-reactive immune responses to ZIKV; however, it was cellular immunity that predominantly mediated cross-protection against ZIKV infection. Passive transfer of immune sera did not result in significant cross-protection but did mediate antibody-dependent enhancement in vitro, though this did not have an adverse impact on survival. This study suggests that the SA14-14-2 vaccine can protect against ZIKV through a cross-reactive T cell response. This is vital information in terms of ZIKV prevention or precaution in those ZIKV-affected regions where JEV circulates or SA14-14-2 is in widespread use, and opens a promising avenue to develop a novel bivalent vaccine against both ZIKV and JEV.

Key points

• JEV SA14-14-2 vaccine conferred cross-protection against ZIKV challenge in mice.

• T cell immunity rather than antibody mediated the cross-protection.

• It provides important information in terms of ZIKV prevention or precaution.
De-escalation of empiric broad spectrum antibiotics in hematopoietic stem cell transplant recipients with febrile neutropenia
Authors: Rearigh Lindsey , Stohs Erica , Freifeld Alison , Zimmer Andrea
Published: June 2020

Febrile neutropenia (FN) is a common serious complication in patients undergoing hematopoietic stem cell transplantation (HSCT) requiring urgent evaluation and initiation of empiric broad spectrum antibiotics (BSA). The appropriate duration of BSA for FN in patients with negative cultures and no identifiable infection remains undefined. We retrospectively analyzed allogenic and autologous HSCT patients with FN and negative infectious work-up at our facility from 2012 to 2018. The early de-escalation group (EDG) included those who had BSA de-escalation to fluoroquinolone prophylaxis at least 24 h prior to absolute neutrophil count (ANC) recovery after the patient was fever-free for at least 48 h. Among 297 patients undergoing their first HSCT who experienced FN with negative infectious work-up, 83 patients were de-escalated early with the remaining 214 in the standard of care group (SCG) whose BSA were continued until ANC was > 500. Duration of broad-spectrum antibiotics was shorter in EDG compared to SCG (3.86 days vs. 4.62 days, p = 0.03). Rates of mortality, new infections, and clinical decompensation requiring intensive care unit transfer and/or pressor use within 30 days were all similar between the two groups (0% vs. 0.4% p = 1.00, 0% vs. 1.4% p = 0.56, 13.2% vs. 8.4% p = 0.27). This indicates that it is safe to de-escalate antibiotics prior to ANC recovery, leading to less BSA exposure.
Effect of food on the pharmacokinetics of the WEE1 inhibitor adavosertib (AZD1775) in patients with advanced solid tumors
Authors: Någård Mats , Ah-See Mei-Lin , So Karen , Vermunt Marit , Thistlethwaite Fiona , Labots Mariette , Roxburgh Patricia , Ravaud Alain , Campone Mario , Valkenburg-van Iersel Liselot , Ottesen Lone , Li Yan , Mugundu Ganesh
Published: June 2020

Purpose

To support future dosing recommendations, the effect of food on the pharmacokinetics of adavosertib, a first-in-class, small-molecule reversible inhibitor of WEE1 kinase, was assessed in patients with advanced solid tumors.

Methods

In this Phase I, open-label, randomized, two-period, two-sequence crossover study, the pharmacokinetics of a single 300 mg adavosertib dose were investigated in fed versus fasted states.

Results

Compared with the fasted state, a high-fat, high-calorie meal (fed state) decreased adavosertib maximum plasma concentration (Cmax) by 16% and systemic exposure (area under the plasma concentration–time curve [AUC]) by 6%; AUC0–t decreased by 7% and time to maximum plasma concentration was delayed by 1.97 h (P = 0.0009). The 90% confidence interval of the geometric least-squares mean treatment ratio for AUC and AUC0–t was contained within the no-effect limits (0.8–1.25), while that of Cmax crossed the lower bound of the no-effect limits. Adverse events (AEs) related to adavosertib treatment were reported by 20 (64.5%) of the 31 patients treated in this study. Grade ≥ 3 AEs were reported by four (12.9%) patients (one in the fed state, three in the fasted state); two of these AEs were considered treatment-related by the investigator. Three serious AEs were reported in three (9.7%) patients; these were not considered treatment-related. No patients discontinued because of treatment-related AEs, and no new safety signals were reported.

Conclusion

A high-fat meal did not have a clinically relevant effect on the systemic exposure of adavosertib, suggesting that adavosertib can be administered without regard to meals.
Genome protection: histone H4 and beyond
Authors: Kumar Kundan , Moirangthem Romila , Kaur Rupinder
Published: June 2020

Histone proteins regulate cellular factors’ accessibility to DNA, and histone dosage has previously been linked with DNA damage susceptibility and efficiency of DNA repair pathways. Surplus histones are known to impede the DNA repair process by interfering with the homologous recombination-mediated DNA repair in Saccharomyces cerevisiae. Here, we discuss the recent finding of association of methyl methanesulfonate (MMS) resistance with the reduced histone H4 gene dosage in the pathogenic yeast Candida glabrata. We have earlier shown that while the low histone H3 gene dosage led to MMS susceptibility, the lack of two H4-encoding ORFs, CgHHF1 and CgHHF2, led to resistance to MMS-induced DNA damage. This resistance was linked with a higher rate of homologous recombination (HR). Taking these findings further, we review the interactome analysis of histones H3 and H4 in C. glabrata. We also report that the arginine residue present at the 95th position in the C-terminal tail of histone H4 protein is required for complementation of the MMS resistance in the Cghhf1Δhhf2Δ mutant, thereby pointing out a probable role of this residue in association with HR factors. Additionally, we present evidence that reduction in H4 protein levels may constitute an important part of varied stress responses in C. glabrata. Altogether, we present an overview of histone H4 dosage, HR-mediated repair of damaged DNA and stress resistance in this opportunistic human fungal pathogen.
Up to 5-year retention of abatacept in Belgian patients with moderate-to-severe rheumatoid arthritis: a sub-analysis of the international, observational ACTION study
Authors: Westhovens R. , Connolly S. E. , Margaux J. , Vanden Berghe M. , Maertens M. , Van den Berghe M. , Elbez Y. , Chartier M. , Baeke F. , Robert S. , Malaise M.
Published: June 2020

Favorable efficacy and safety profiles have been demonstrated for abatacept in patients with rheumatoid arthritis (RA) in randomized controlled trials, but these data require validation during long-term follow-ups in routine clinical practice. This study explored long-term safety and retention rates in RA patients treated with intravenous abatacept in the Belgian cohort of the international AbataCepT In rOutiNe clinical practice (ACTION) study (NCT02109666). This non-interventional, observational, longitudinal study included Belgian patients aged ≥ 18 years with moderate-to-severe RA who started intravenous abatacept treatment as first- or second/further-line biologic therapy in routine clinical practice. Between October 2010 and December 2012, 141 patients were enrolled in this cohort, of whom 135 evaluable patients (6 biologic-naïve; 129 previously exposed to ≥ 1 prior biologic disease modifying anti-rheumatic drugs) were eligible for the descriptive analysis; 131/135 were included in the effectiveness analysis. Mean disease duration was 10.5 years (standard deviation 9.7) before abatacept initiation. RA patients presented with high disease activity and comorbidity rate, having failed multiple previous treatment options. In this cohort, the 5-year abatacept retention rate was 34% (95% confidence interval, 23−45%) per protocol, and 51% (95% confidence interval, 40−61%) when temporary discontinuations of abatacept > 84 days (n = 24) were not considered as treatment discontinuations. After 5 years of abatacept treatment, clinical outcomes were favorable [good/moderate European League Against Rheumatism (EULAR) responses in 91.7% patients]. No new safety signals were detected for abatacept in routine clinical practice. In this difficult-to-treat Belgian RA population, high retention rates, good clinical outcomes and favorable safety profile were observed with abatacept.
Antarctic fur seal (Arctocephalus gazella) annual migration and temporal patterns of on-shore occurrence of leucistic individuals on King George Island
Authors: Grebieniow Anna , Korczak-Abshire Małgorzata , Gasek Anna , Górecka-Bruzda Aleksandra
Published: June 2020

Non-invasive tracking the on-shore occurrence of the atypically pigmented animals and determination of land residency duration of leucistic seals would help us find out more about the rotation of the migrating population. During seven austral summer seasons (2011–2018), by counting the animals every 10 days at the Cape Lions Rump shore, King George Island, South Shetlands, in the Antarctic Specially Protected Area No. 151 and the adjacent ice-free land (31.52 km2) we registered fourteen leucistic individuals per a total of 43,919 animals. Moreover, daily monitoring of local fauna resulted in further 33 leucistic animals (together 47, in all seasons). Whilst the results of 10-day censuses of the total population were similar inter-seasonally, a tendency for increased occurrence of leucistic individuals in successive seasons was revealed. Generally, the number of animals increased significantly as season progressed. Since leucistic individuals stayed on-shore for 1–2 days usually, it can be hypothesised that the observation of migrating Antarctic fur seals every 3 days does not involve the same individuals. Also, additional every 5-day censuses taken in one season in ASPA 151 resulted in a higher seasonal number of animals, which proves that more frequent counts help us estimate population abundance more efficiently. Thus, every 5-day counts are proposed as a feasible and justified method of population monitoring.
The role of the “beret” sign and other markers in ultrasound diagnostic of the acrania–exencephaly–anencephaly sequence stages
Authors: Szkodziak Piotr , Krzyżanowski Jarosław , Krzyżanowski Arkadiusz , Szkodziak Filip , Woźniak Sławomir , Czuczwar Piotr , Kwaśniewska Anna , Paszkowski Tomasz
Published: June 2020

Introduction

Neural tube defects (NTDs) are a group of heterogeneous congenital anomalies of the central nervous system (CNS). Acrania is a non-NTD congenital disorder related to the CNS. It can transform into anencephaly through the acrania–exencephaly–anencephaly sequence (AEAS). In AEAS, the cerebral tissue is not protected and is gradually destroyed due to exposure to the harmful effect of amniotic fluid and mechanical injuries. These lead to exencephaly and then into anencephaly. In contrast to primary anencephaly (NTDs), this type of anencephaly authors suggests calling secondary anencephaly.

Objective

Analysis of the known prenatal ultrasonography (US) signs associated with AEAS. Simultaneously, the authors propose a new sign in the differentiation of acrania from exencephaly and anencephaly, called the “beret” sign.

Methods

It is a two-centre retrospective observational study. As part of the study, 4060 US scans were analyzed.

Results

In 10 cases, the absence of calvarium was diagnosed, allowing recognition of either AEAS stages or primary anencephaly. In 5 cases, cerebral structures were enclosed by an inertial rippled thin membrane, with a smooth outer contour. Between the described membrane and the brain structures, a thin anechoic space corresponding to cerebrospinal fluid was observed. This sign was defined as the “beret” sign. In these cases, acrania was diagnosed. In three cases calvarium was missing. The brain structures had an irregular appearance, did not wave and remained motionless. The outer contour was unequal as if divided into lobes. Amniotic fluid was anechoic. Exencephaly was diagnosed in these cases. In two cases calvarium, brain structures, and meninges were missing. The “frog eyes” sign and slightly echogenic amniotic fluid were visible. In this case, anencephaly was diagnosed.

Conclusions

The “beret” sign seems to be a promising tool in the diagnosis of acrania. Furthermore, echogenicity of amniotic fluid could be useful during differentiation between primary and secondary anencephaly.