bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of increased feed supply and different fattening strategies for an Ethiopian sheep population by system dynamics modelling
Authors: Gebre K. T. , Wurzinger M. , Gizaw S. , Haile A. , Rischkowsky B. , Sölkner J.
Published: August 2020

Context
The productivity of Ethiopian smallholder farms is considered to be low owing to different factors such as feed shortage, lack of breeding strategies, disease prevalence and missing marketing strategies.

Aim
The main objective of the study was to develop a dynamic, stochastic herd model by adopting system dynamic modelling methodology for evaluation of the effect of increased feed availability (forage production) in combination with different fattening strategies on herd dynamics and profitability of an Ethiopian sheep population.

Methods
Forage production utilising part of smallholder farmers’ cropland was built into a dynamic simulation model. Two alternative feed-supply systems were evaluated: turning 25% and 50% of the current cropland into area used for forage production. The simulation period was 20 years, the first 10 years representing the baseline fattening scenario (culled rams fattened). For the last 10 years, genetic selection was introduced and two scenarios were evaluated: fattening of culled rams (Scenario I) and fattening of young rams (Scenario II).

Key results
Increasing the feed supply resulted in an increase to the herd size when the model balanced dry matter supply and demand of the herd. Fattening of young rams (Scenario II) with genetic selection was significantly more profitable than the baseline and Scenario I in both of the simulated alternative feed-supply systems. This can be used for regular cash generation, which might reduce disposal of animals at lower price in cases of need for emergency cash.

Conclusions
Overall, the simulation model demonstrates that production of improved forage crops should be combined with selective breeding and an appropriate finishing strategy. The competition for resources (land and labour) with crop production, forage seed shortage and extended family size are other challenges raised by smallholder farmers for the feasibility of the two alternative feed-supply systems.
A pathogenic and clonally expanded B cell transcriptome in active multiple sclerosis
Authors: Ramesh Akshaya , Schubert Ryan D. , Greenfield Ariele L. , Dandekar Ravi , Loudermilk Rita , Sabatino Joseph J. , Koelzer Matthew T. , Tran Edwina B. , Koshal Kanishka , Kim Kicheol , Pröbstel Anne-Katrin , Banerji Debarko ,   University of California, San Francisco MS-EPIC Team, Guo Chu-Yueh , Green Ari J. , Bove Riley M. , DeRisi Joseph L. , Gelfand Jeffrey M. , Cree Bruce A. C. , Zamvil Scott S. , Baranzini Sergio E. , Hauser Stephen L. , Wilson Michael R.
Published: August 2020

Significance

B cells serve as a key weapon against infectious diseases. They also contribute to multiple autoimmune diseases, including multiple sclerosis (MS) where depletion of B cells is a highly effective therapy. We describe a comprehensive profile of central nervous system (CNS)-specific transcriptional B cell phenotypes in MS at single-cell resolution with paired immune repertoires. We reveal a polyclonal immunoglobulin M (IgM) and IgG1 cerebrospinal fluid B cell expansion polarized toward an inflammatory, memory and plasmablast/plasma cell phenotype, with differential up-regulation of specific proinflammatory pathways. We did not find evidence that CNS B cells harbor a neurotropic virus. These data support the targeting of activated resident B cells in the CNS as a potentially effective strategy for control of treatment-resistant chronic disease.
Visualization of human T lymphocyte-mediated eradication of cancer cells in vivo
Authors: He Xingkang , Yin Xin , Wu Jing , Wickström Stina L. , Duo Yanhong , Du Qiqiao , Qin Shuhang , Yao Shuzhong , Jing Xu , Hosaka Kayoko , Wu Jieyu , Jensen Lasse D. , Lundqvist Andreas , Salter Alexander I. , Bräutigam Lars , Tao Wei , Chen Yuguo , Kiessling Rolf , Cao Yihai
Published: August 2020

Significance

The clinical efficacy of immunotherapy in cancer patients is limited. We have developed a zebrafish model that allows us to visualize the metastatic cancer cell-killing effect by tumor-infiltrating lymphocytes and chimeric antigen receptor T cells in vivo at the single-cell level. This in vivo model accurately predicts clinical efficacy of T cell-mediated cancer therapy. Our data provide an in vivo platform for validating antimetastatic effects by human T cell-mediated immunotherapy. Based on our findings, it is highly recommended that anticancer effects of T cells isolated from cancer patients or genetically propagated T cells should be evaluated in this in vivo animal model before clinical application. If so, millions of cancer patients might benefit from our work.
Statistical prediction of the future impairs episodic encoding of the present
Authors: Sherman Brynn E. , Turk-Browne Nicholas B.
Published: August 2020

Significance

We use memory to recall the past and make predictions about the future. However, these functions can conflict: Recalling a past experience involves returning to a specific moment in time, but this exact experience will never occur again because the world and observer have changed. Rather, it is often adaptive to focus on aspects of the world that repeat across experiences and are likely to generalize. Encoding individual experiences (episodic memory) and extracting regularities across experiences (statistical learning) require fundamentally different kinds of learning, yet both have been linked to the same brain region, the hippocampus. Here we reveal the consequence of this codependence: Predicting what comes next from statistical learning prevents encoding of the current experience into episodic memory.
Bilateral key comparison CCT-K6.2 on humidity standards in the frost-point temperature range from −80 °C to −30 °C
Authors: Meyer Christopher , Abe Hisashi
Published: August 2020

A Consultative Committee on Thermometry (CCT) Key Comparison of frost point temperatures was carried out by the National Institute of Standards and Technology (NIST, USA) and the National Metrology Institute of Japan (NMIJ, Japan) between December 2015 and November, 2016. The results of this comparison are reported here, along with descriptions of the humidity laboratory standards for NIST and NMIJ/AIST and the uncertainty budget for these standards. This report also describes the protocol for the comparison and presents the data acquired. The results are analyzed, determining degree of equivalence between the frost-point standards of NIST and NMIJ.

Main text

To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/.

The final report has been peer-reviewed and approved for publication by the CCT, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).
QCD corrections to

in Type-I THDM at electron positron colliders *
Authors: Yang Qiang , Zhang Ren-You , Long Ming-Ming , Wang Shao-Ming , Ma Wen-Gan , Zhu Jian-Wen , Jiang Yi
Published: August 2020

We investigate in detail the charged Higgs production associated with a W boson at electron-positron colliders within the framework of the Type-I two-Higgs-doublet model (THDM). We calculate the integrated cross section at the LO and analyze the dependence of the cross section on the THDM parameters and the colliding energy in a benchmark scenario of the input parameters of the Higgs sector. The numerical results show that the integrated cross section is sensitive to the charged Higgs mass, especially in the vicinity of

at a

collider, and decreases consistently with the increase of

in the low

region. The peak in the colliding energy distribution of the cross section arises from the resonance of the loop integrals, and it moves towards the low colliding energy with the increase of

. We also study the two-loop NLO QCD corrections to both the integrated cross section and the angular distribution of the charged Higgs boson and find that the QCD relative correction is also sensitive to the charged Higgs mass and strongly depends on the final-state phase space. For

, the QCD relative correction at a

collider varies in the range of [-10%, 11%] as

increases from 150 to 400 GeV.
Chiral magnetic effect in isobar collisions from stochastic hydrodynamics *
Authors: Liang Gui-Rong , Liao Jinfeng , Lin Shu , Yan Li , Li Miao
Published: August 2020

We studied the chiral magnetic effect in AuAu, RuRu, and ZrZr collisions at

. The axial charge evolution was modeled with stochastic hydrodynamics, and geometrical quantities were calculated with the Monte Carlo Glauber model. By adjusting the relaxation time of the magnetic field, we found our results are in good agreement with background subtracted data for AuAu collisions at the same energy. We also made predictions for RuRu and ZrZr collisions. We found a weak centrality dependence on initial chiral imbalance, which implies that the centrality dependence of chiral magnetic effect signals results mainly from the effects of the magnetic field and volume factor. Furthermore, our results show an unexpected dependence on system size. While the AuAu system has larger chiral imbalance and magnetic field, it was observed to have a smaller signal for the chiral magnetic effect due to the larger volume suppression factor.
Multiple configurations of neutron stars containing quark matter *
Authors: Wei Wei , Yang Shu-Hua , Bao Ze-Han , Zhang Chong , Gao Chang , Fan Wei-Ru
Published: August 2020

The main purpose of this study is to interpret the possibilities of hybrid star configurations under different phase transition paths and provide a general description of the conditions and features of the different configurations. We assume that there are two possible phase transition paths, i.e., from a nuclear phase to a 2flavor(2f)/3flavor(3f) quark phase directly, or first from a nuclear phase to a 2f quark phase, and then from that phase to a 3f quark phase sequentially. In addition, we consider Maxwell and Gibbs constructions based on the assumption of a first-order transition, which yields multiple configurations of hybrid stars: N-2f, N-3f, and N-2f-3f for a Maxwell construction, and N-2fmix-2f, N-3fmix-3f, N-2f3fmix, and N-2fmix-3f for a Gibbs construction. From the radii analysis of different hybrid star configurations with the same mass of

, the appearance of the quark matter (from nuclear to 2f or 3f quark matter) causes a radius difference of 0.5km~2km and provides the possibility of detection by NICER in the future. However, the sequential transition from 2f to 3f quark matter is difficult to detect because the transition does not lead to too high of a change in radius (far smaller than

). The dependence solely on the measurements of the stellar radii to probe the equation of state of dense matter in neutron stars causes difficulties. Multi-messenger observations can help us to infer the interior of a neutron star in the future.
Dirac quasinormal modes of Born-Infeld black hole spacetimes *
Authors: Ma Hong , Li Jin
Published: August 2020

Quasinormal modes (QNMs) for massless and massive Dirac perturbations of Born-Infeld black holes (BHs) in higher dimensions are investigated. Solving the corresponding master equation in accordance with hypergeometric functions and the QNMs are evaluated. We discuss the relationships between QNM frequencies and spacetime dimensions. Meanwhile, we also discuss the stability of the Born-Infeld BH by calculating the temporal evolution of the perturbation field. Both the perturbation frequencies and the decay rate increase with increasing dimension of spacetime n. This shows that the Born-Infeld BHs become more and more unstable at higher dimensions. Furthermore, the traditional finite difference method is improved, so that it can be used to calculate the massive Dirac field. We also elucidate the dynamic evolution of Born-Infeld BHs in a massive Dirac field. Because the number of extra dimensions is related to the string scale, there is a relationship between the spacetime dimension n and the properties of Born-Infeld BHs that might be advantageous for the development of extra-dimensional brane worlds and string theory.
Modeling, analysis, and code/data validation of DIII-D tokamak divertor experiments on ELM and non-ELM plasma tungsten sputtering erosion
Authors: Brooks J.N. , Sizyuk T. , Elder J.D. , Abrams T. , Hassanein A. , Rudakov D.L. , Wampler W.
Published: August 2020

We analyzed recent DIII-D tokamak tungsten divertor probe experiments using advanced, coupled, sputter erosion/redeposition, plasma, and surface response code packages. Modeling is done for ELMing H-mode, and L-mode plasmas, impinging on various size tungsten deposits on Divertor Material Evaluation System (DiMES) carbon probes. The simulations compute 3D, full kinetic, sub-gyromotion, impurity sputtering and transport, including changes in tungsten surface composition and response due to mixed deuterium and carbon ions irradiation. Per our analysis, ELM (edge localized mode) plasma sputtering in DIII-D mostly involves free-streaming high energy (∼500–1000 eV) D+ and C+6 ions, with high near-surface plasma density. L-Mode sputtering is due to impurity sputtering (C, W) only, with lower density. All cases show complete redeposition of tungsten on the divertor, with significant redeposition on the tungsten spots themselves, and low self-sputtering. Comparison of ELM plasma gross tungsten erosion simulation results with in-situ spectroscopic data is good, as are code/data comparisons of net erosion using post-exposure Rutherford backscattering (RBS) data for the L-mode probes. The analysis, extrapolated to a full tungsten divertor, implies low net erosion and negligible plasma contamination from sputtering. These results support the use of high-Z plasma facing surfaces in ITER and beyond.
Variations in the Ti-Ni sensor readings and rhythms of atmospheric electrical processes
Authors: Ya Erofeev V
Published: August 2020

The readings of a sensor based on a shape-memory metal and variations in atmospheric parameters were studied at the same time interval using a comparative analysis. The results obtained make it possible to identify a common external factor that simultaneously affects several dissimilar substances. The effect of the factor is the modulation of the electrical potential, including in the atmospheric environment.
Approbation of automatic allocation of thunderstorm foci in the south of Western Siberia according to WWLLN data according to the FRIS-Tax clustering algorithm
Authors: Yu Karanina S , Yu Belikova M , Kocheeva N A , Karanin A V
Published: August 2020

The article shows the ability of the FRiS-Tax algorithm to separate lightning discharge clusters and combine them into classes. Lightning discharge clusters are a model of an individual lightning cell. Classes (groups) of clusters of lightning discharges that are close in space and in time of action can be associated with a model of a multi-cell thunderstorm or a thunderstorm focus. Clustering of lightning discharges is carried out using normalization values specifying the linear dimensions of a thunderstorm cell (ρ*) and its lifetime (τ*). The experimental sample consisted of 3934 lightning discharges registered by WWLLN in the south of Western Siberia, August 7-8, 2017. The results of lightning discharge clustering are compared for two parameterization conditions: ρ1*=50 km, τ1*=30 min and ρ2*=15 km, τ2*=20 min For the first set of parameterization conditions, the resulting lightning discharge clusters represent zones of possible activity of a thunderstorm cell for one to two hours. Classes formed from these clusters describe the behavior of long lasting and vast thunderstorm foci. The clusters obtained for the second set of parameterization conditions better correspond to the linear sizes and lifetime of individual thunderstorm cells. An adjustment of the clustering algorithm is required to combine such clusters into classes corresponding to a multi-cell thunderstorm.
Study of the features of the distribution of the intensity of lightning activity during thunderstorms in the North Caucasus
Authors: Adzhieva A A , Shapovalov V A , Tumgoeva H A , Tokbaeva A A
Published: August 2020

Operational and reliable information about thunderstorms and lightning discharge parameters allows you to solve many problems of aviation, meteorology, energy, atmospheric physics, earth electricity and even near-Earth space. This article discusses issues related to the features of the development of thunderstorm processes and the parameters of lightning activity for the territory of the North Caucasus. The features of the risks associated with intense lightning activity are discussed. Information about electrical processes in the clouds and lightning parameters for 2009-2019 was obtained using the Vaisala LS 8000 network of lightning registers. The article gives a picture of the spatial distribution of the foci of the maximum intensity of lightning discharges in the North Caucasus and the distribution of the maximum value of the total absolute current of discharges per minute to the ground. The statistical features of the distribution of the intensity values of the discharges per minute by types of discharges encountered throughout the year were investigated. The performed analysis of these distributions made it possible to select the optimal approximating expressions for practical application in lightning protection. The main factors affecting the obtained characteristics of the spatial distribution of lightning activity are identified. Conclusions are drawn on the prospects for further research in order to obtain comprehensive information about electrical processes in the atmosphere of the region.
Single particle entanglement of a massive relativistic particle: Dirac bispinors and spin 1/2 states
Authors: Bittencourt Victor A S V , Blasone Massimo
Published: August 2020

In this paper we study the single particle entanglement induced by a Lorentz boost. We described the particle as a solution of the free Dirac equation, a Dirac bispinor, and compare the induced momentum-spin entanglement with the result obtained in the widely considered framework of relativistic spin 1/2 states. The spin linear entropy for both approaches agree in the ultra relativistic limit. We also verify that the spin-momentum entanglement differers from the spin entropy for the bispinorial case, indicating a true multipartite entanglement involving the degrees of freedom of a Dirac bispinor state: momentum, spin and intrinsic parity. The fact that Dirac bispinors belongs to an irreducible representation of the complete Lorentz group, which also included parity as a symmetry, is the ultimate reason behind such non-trivial structure.
Weak Values and Quantum Information in Scattering Physics — New Theoretical and Experimental Effects
Authors: Aris Chatzidimitriou-Dreismann C
Published: August 2020

Weak Values (WV) and Two-State-Vector Formalism (TSVF) provide novel insights in various quantum physical and technological fields. In the first part of the paper we consider a new quantum effect of scattering accompanying an elementary collision of two quantum systems A and B, in which the latter interacts with a quantum environment. In clear contrast to a classical environment, the quantum case can exhibit counter-intuitive effects of momentum- and energy-transfer which contradict conventional expectations. Experimental evidence of a new effect—deficit of momentum transfer (equivalently: reduced effective mass) in a neutron-atom collision—is presented and theoretically interpreted. Here, non-relativistic incoherent inelastic neutron scattering (INS) is applied. INS on single H2 molecules confined in multi-walled carbon nanotube channels has been experimentally investigated. Interpreted within conventional theory, the results reveal a counter-intuitive reduced effective mass of the recoiling H2 molecule, i.e. M = 0.64 a.m.u. (atomic mass units). In contrast, this finding has a simple qualitative interpretation within WV and TSVF theory. In the second part of the paper we report on current experimental and theoretical investigations in the field of X-ray diffraction (XRD), which belongs to coherent scattering. Preliminary XRD results from cubic crystalline materials show a surprising variation of the measured lattice parameter (usually called “lattice constant”) with momentum transfer. A first theoretical model of the effect in the light of the new theory is presented. These findings give further evidence for the broad character and significance of the novel WV and TSVF theory.
Aspects of Quantum Black Holes
Authors: Kiefer Claus
Published: August 2020

Black holes play a key role for any quantum theory of gravity. The main reasons are black hole radiation and evaporation as well as black hole entropy. I review these issues and address the problem of information loss. I then discuss the status of black holes in full quantum gravity. Particular attention is focused on quantum geometrodynamics, the direct quantization of general relativity. This allows scenarios in which the black-hole singularity is avoided, in particular the collapse of a wave packet towards a black-hole like state and its re-expansion as a white hole.
Transient capture of electrons in magnetic fields, or: comets in the restricted three-body problem
Authors: Kramer Tobias
Published: August 2020

The motion of celestial bodies in astronomy is closely related to the orbits of electrons encircling an atomic nucleus. Bohr and Sommerfeld presented a quantization scheme of the classical orbits to analyze the eigenstates of the hydrogen atom. Here we discuss another close connection of classical trajectories and quantum mechanical states: the transient dynamics of objects around a nucleus. In this setup a comet (or an electron) is trapped for a while in the vicinity of an parent object (Jupiter or an atomic nucleus), but eventually escapes after many revolutions around the center of attraction.
Symmetry and Signs of Self-Organized Criticality in Living Organisms
Authors: Rivera Ana Leonor , Claudio Toledo-Roy Juan , Frank Alejandro
Published: August 2020

Symmetry methods have been of crucial importance to physics. Group theory and conservation laws have become the fundamental language of symmetries, going all the way from the realm of quantum mechanical phenomena to general relativity. However, these ideas have had less impact in the biological domain. In this paper we present a view of self-organized biological systems as characterized by and evolving towards critical points, in the language of phase transitions as seen in physical systems. Self-similar (or scale invariant) behavior seems to signal homeostatic dynamical equilibrium in living organisms. Deviations of this homeostatic balance is associated with illness and elderly.
The effect of variable stiffness of tuna-like fish body and fin on swimming performance
Authors: Luo Yang , Xiao Qing , Shi Guangyu , Pan Guang , Chen Daoyi
Published: August 2020

The work in this paper focuses on the examination of the effect of variable stiffness distributions on the kinematics and propulsion performance of a tuna-like swimmer. This is performed with the use of a recently developed fully coupled fluid-structure interaction solver. The two different scenarios considered in the present study are the stiffness varied along the fish body and the caudal fin, respectively. Our results show that it is feasible to replicate the similar kinematics and propulsive capability to that of the real fish via purely passive structural deformations. In addition, propulsion performance improvement is mainly dependent on the better orientation of the force near the posterior part of swimmers towards the thrust direction. Specifically, when a variable body stiffness scenario is considered, the bionic body stiffness profile results in better performance in most cases studied herein compared with a uniform stiffness commonly investigated in previous studies. Given the second scenario, where the stiffness is varied only in the spanwise direction of the tail, similar tail kinematics to that of the live scombrid fish only occurs in association with the heterocercal flexural rigidity profile. The resulting asymmetric tail conformation also yields performance improvement at intermediate stiffness in comparison to the cupping and uniform stiffness.
Zinc metal–organic framework with 3-pyridinecarboxaldehyde and trimesic acid as co-ligands for selective detection of Cr (VI) ions in aqueous solution
Authors: Adotey Enoch K , Amouei Torkmahalleh Mehdi , Balanay Mannix P
Published: August 2020

There is an increasing need for the development of probes for the detection of hexavalent chromium since it is a known carcinogen, which can cause adverse effects on human health. Metal-organic frameworks (MOFs) have shown successful detection and removal of hazardous substances from aqueous media. This work presents the use of simple organic ligands such as 3-pyridinecarboxaldehyde and trimesic acid with Zn(II) ion to fabricate a new MOF that exhibits sensitive and selective luminescence quenching response towards CrO4
2− and Cr2O7
2− species in aqueous solution. The MOF showed a detection limit of 0.67 μM (0.078 ppm) as CrO4
2− species and 1.91 μM (0.41 ppm) as Cr2O7
2− species. Results reveal that the as-synthesized MOF could serve as a good luminescent sensor for CrO4
2− and Cr2O7
2− species in the contaminated aqueous phase.
Observation of above-room-temperature ferromagnetism in chemically stable layered semiconductor RhI3
Authors: Che Xiangli , Zhang Zhuang , Wang Dong , Zhao Wei , Wang Teng , Zhao Pei , Mu Gang , Huang Jian , Huang Fuqiang
Published: August 2020

Two-dimensional (2D) ferromagnetic semiconductors with a room-temperature Curie temperature (T
c) are required for next-generation spintronic devices, but the current candidates suffer from a low T
c and poor chemical stability. Here, a new layered compound RhI3 is discovered to be an above-room-temperature ferromagnetic semiconductor. This compound crystallizes in a monoclinic crystal system of space group C2/m, with the unit cell of a = 6.773(8) Å, b = 11.721(2) Å, c = 6.811(8) Å and β = 108.18(4) °. The structure consists of honeycomb rhodium layers separated by iodine–iodine van der Waals gap. Chemically stable RhI3 possesses an optical bandgap of 1.17 eV. Its robust ferromagnetism with a T
c of above 400 K, which is far higher than 61 K for the well-known CrI3 and the highest among the bulk 2D ferromagnetic semiconductors. The robust intrinsic ferromagnetic response is attributed to the Rh2+ and exchange interactions between I-p and Rh-d electrons induced by iodine vacancies. This work reveals that RhI3 is a prime candidate for spintronic devices above room temperature and provides a strategy to obtain high temperature 2D ferromagnetic semiconductors by introducing vacancies.
Evaluation and Comparison of Performance Parameters and Impact of Telepathology and Operator Experience on Endobronchial and Endoscopic Ultrasound-Guided Fine-Needle Aspiration
Authors: Hupp Meghan M , Khan Subhan , Dincer H Erhan , Mallery J Shawn , Shyne Michael T , Mettler Tetyana , Stewart Jimmie , Amin Khalid
Published: August 2020

Objectives

Endobronchial ultrasound- and endoscopic ultrasound-guided fine-needle aspiration (EBUS-/EUS-FNA) are minimally invasive techniques of diagnosing and staging malignancies. The procedures are difficult to master, requiring specific feedback for optimizing yield.

Methods

Over 2 years, EBUS-/EUS-FNA cases were gathered using the institutional pathology database. Patient and specimen characteristics were collected from the pathology database and electronic medical record.

Results

In 2 years, 789 unique FNA specimens were collected (356 EBUS and 433 EUS specimens). The cohort and each subgroup had excellent performance, which was enhanced by telepathology. The discrepancy rate was satisfactorily low. Hematolymphoid neoplasms are overrepresented in discrepant EBUS cases. The malignancy rates of cytology diagnostic categories were comparable to the literature.

Conclusions

Using diagnostic yield and concordance results allow for comprehensive evaluation of the entire process of EBUS-/EUS-FNAs. This study’s findings can influence patient management, training methods, and interpretation of results, while also acting as a model for others to investigate their own sources of inadequacy, discrepancy, and training gaps.
A Clinicopathologic Study on the Role of Estrogen, Progesterone, and Their Classical and Nonclassical Receptors in Cutaneous Neurofibromas of Individuals With Neurofibromatosis 1
Authors: Rozza-de-Menezes Rafaela E , Almeida Lilian M , Andrade-Losso Raquel M , de Souza Vieira Gustavo , Siqueira Orlando H K , Brum Carolina I , Riccardi Vincent M , Cunha Karin S
Published: August 2020

Objectives

To evaluate the expression of progesterone receptor (PR), estrogen receptor (ER), and G protein–coupled estrogen receptor 1 (GPER-1) in cutaneous neurofibromas (cNFs) and their correlation with demographic, clinical, and laboratory data of individuals with neurofibromatosis 1 (NF1). The association of PROGINS polymorphism and PR expression in cNFs, as well as the serum steroidal hormones and the number of cNFs, was investigated.

Methods

The sample comprised 80 large and 80 small cNFs from 80 individuals with NF1. PR, ER, GPER-1, and Ki-67 expression were investigated by immunohistochemistry in tissue micro- and macroarrays and quantified using a digital computer-assisted method. The number of cNFs, the levels of serum 17β estradiol and progesterone, and the PROGINS polymorphism were identified.

Results

Twelve (8.5%) small cNFs were weakly positive for ER, 131 (92.3%) cNFs expressed PR, and all (100%) cNFs expressed GPER-1. Large cNFs showed a higher expression of PR (P < .0001) and GPER-1 (P = .019) and had a higher intensity of staining for these receptors (P < .0001). The cell proliferation index was positively correlated with PR (P = .001). Persons with more cNFs had higher serum levels of progesterone (P = .001).

Conclusions

These findings emphasize the role of estrogen and progesterone in cNF development and suggest that these hormones may act on cNF cells via a noncanonical pathway through GPER-1.
Estimating differential latent variable graphical models with applications to brain connectivity
Authors: Na S , Kolar M , Koyejo O
Published: August 2020

Differential graphical models are designed to represent the difference between the conditional dependence structures of two groups, and thus are of particular interest for scientific investigations. Motivated by modern applications, this manuscript considers an extended setting where each group is generated by a latent variable Gaussian graphical model. Due to the existence of latent factors, the differential network is decomposed into sparse and low-rank components, both of which are symmetric indefinite matrices. We estimate these two components simultaneously using a two-stage procedure: (i) an initialization stage, which computes a simple, consistent estimator, and (ii) a convergence stage, implemented using a projected alternating gradient descent algorithm applied to a nonconvex objective, initialized using the output of the first stage. We prove that given the initialization, the estimator converges linearly with a nontrivial, minimax optimal statistical error. Experiments on synthetic and real data illustrate that the proposed nonconvex procedure outperforms existing methods.
A Whole-Brain and Cross-Diagnostic Perspective on Functional Brain Network Dysfunction
Authors: Spronk Marjolein , Keane Brian P , Ito Takuya , Kulkarni Kaustubh , Ji Jie Lisa , Anticevic Alan , Cole Michael W
Published: August 2020

A wide variety of mental disorders have been associated with resting-state functional network alterations, which are thought to contribute to the cognitive changes underlying mental illness. These observations appear to support theories postulating large-scale disruptions of brain systems in mental illness. However, existing approaches isolate differences in network organization without putting those differences in a broad, whole-brain perspective. Using a graph distance approach—connectome-wide similarity—we found that whole-brain resting-state functional network organization is highly similar across groups of individuals with and without a variety of mental diseases. This similarity was observed across autism spectrum disorder, attention-deficit hyperactivity disorder, and schizophrenia. Nonetheless, subtle differences in network graph distance were predictive of diagnosis, suggesting that while functional connectomes differ little across health and disease, those differences are informative. These results suggest a need to reevaluate neurocognitive theories of mental illness, with a role for subtle functional brain network changes in the production of an array of mental diseases. Such small network alterations suggest the possibility that small, well-targeted alterations to brain network organization may provide meaningful improvements for a variety of mental disorders.
Quantification of the Plasma Concentrations of Perampanel Using High-Performance Liquid Chromatography and Effects of the CYP3A4*1G Polymorphism in Japanese Patients
Authors: Ohkubo Sho , Akamine Yumiko , Ohkubo Tadashi , Kikuchi Yuka , Miura Masatomo
Published: August 2020

Here, we developed a novel high-performance liquid chromatography (HPLC) method for quantification of perampanel in clinical practice and investigated the relationships between the plasma concentrations of perampanel obtained by this HPLC method and the CYP3A4*1G polymorphism. The developed HPLC method was validated based on US Food and Drug Administration. The developed HPLC method could be performed with a plasma volume of only 200 μL and had a limit of quantification (LOQ) of 2.5 ng/mL. The coefficients of variation (CVs) for intra- and inter-day assays were less than 10.4 and 7.2%, respectively, and the accuracy was <2.4% for both assays. A total of 12 patients who received 2 mg perampanel had C0 values ranging from 70.5 to 451 ng/mL, and the CV showed a large variation of 51.4%. No correlations were observed between the dose-adjusted C0 and the CYP3A4*1G polymorphism. This method was superior to previously reported methods in terms of plasma volume and LOQ and was clinically applicable. Perampanel showed high variations in individual plasma concentrations; however, individual differences could not be predicted from analysis of the CYP3A4*1G polymorphism before perampanel administration. Therefore, after beginning perampanel treatment, the dose should be determined based on the observed plasma concentration.
A National Strategy to Diagnose Coronavirus Disease 2019–Associated Invasive Fungal Disease in the Intensive Care Unit
Authors: White P Lewis , Dhillon Rishi , Cordey Alan , Hughes Harriet , Faggian Federica , Soni Shuchita , Pandey Manish , Whitaker Harriet , May Alex , Morgan Matt , Wise Matthew P , Healy Brendan , Blyth Ian , Price Jessica S , Vale Lorna , Posso Raquel , Kronda Joanna , Blackwood Adam , Rafferty Hannah , Moffitt Amy , Tsitsopoulou Alexandra , Gaur Soma , Holmes Tom , Backx Matthijs
Published: August 2020

Background

Fungal coinfection is a recognized complication of respiratory virus infections, increasing morbidity and mortality, but can be readily treated if diagnosed early. An increasing number of small studies describing aspergillosis in coronavirus disease 2019 (COVID-19) patients with severe respiratory distress are being reported, but comprehensive data are lacking. The aim of this study was to determine the incidence, risk factors, and impact of invasive fungal disease in adult COVID-19 patients with severe respiratory distress.

Methods

An evaluation of a national, multicenter, prospective cohort evaluation of an enhanced testing strategy to diagnose invasive fungal disease in COVID-19 intensive care patients. Results were used to generate a mechanism to define aspergillosis in future COVID-19 patients.

Results

One-hundred and thirty-five adults (median age: 57, M/F: 2.2/1) were screened. The incidence was 26.7% (14.1% aspergillosis, 12.6% yeast infections). The overall mortality rate was 38%; 53% and 31% in patients with and without fungal disease, respectively (P = .0387). The mortality rate was reduced by the use of antifungal therapy (mortality: 38.5% in patients receiving therapy vs 90% in patients not receiving therapy (P = .008). The use of corticosteroids (P = .007) and history of chronic respiratory disease (P = .05) increased the likelihood of aspergillosis.

Conclusions

Fungal disease occurs frequently in critically ill, mechanically ventilated COVID-19 patients. The survival benefit observed in patients receiving antifungal therapy implies that the proposed diagnostic and defining criteria are appropriate. Screening using a strategic diagnostic approach and antifungal prophylaxis of patients with risk factors will likely enhance the management of COVID-19 patients.
Valerie Gillies: Inscriptions in the Wind
Authors: Severin Laura
Published: August 2020

This article focuses on Valerie Gillies’s contribution to women’s poetry through an examination of her 2016 exhibition, A Garden of Time and Silence, with textile artist Anna S. King, at Dawyck Botanic Gardens in the Scottish Borders. While Gillies is an acclaimed print-page poet, this piece represents her skill at alternative uses of poetry. Throughout her career, Gillies has employed collaborative multimedia art to engage in contemporary political discussion, often on the environment, in order to challenge, more directly than is possible with print text, poetry’s gendered assumptions.
Standardized exercise training is feasible, safe, and effective in pulmonary arterial and chronic thromboembolic pulmonary hypertension: results from a large European multicentre randomized controlled trial
Authors: Grünig Ekkehard , MacKenzie Alison , Peacock Andrew J , Eichstaedt Christina A , Benjamin Nicola , Nechwatal Robert , Ulrich Silvia , Saxer Stéphanie , Bussotti Maurizio , Sommaruga Marinella , Ghio Stefano , Gumbiene Lina , Palevičiūtė Eglė , Jurevičienė Elena , Cittadini Antonio , Stanziola Anna A , Marra Alberto M , Kovacs Gabor , Olschewski Horst , Barberà Joan-Albert , Blanco Isabel , Spruit Martijn A , Franssen Frits M E , Vonk Noordegraaf Anton , Reis Abílio , Santos Mário , Viamonte Sofia Gonçalves , Demeyer Heleen , Delcroix Marion , Bossone Eduardo , Johnson Martin
Published: August 2020

Aims

This prospective, randomized, controlled, multicentre study aimed to evaluate efficacy and safety of exercise training in patients with pulmonary arterial (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH).

Methods and results

For the first time a specialized PAH/CTEPH rehabilitation programme was implemented in 11 centres across 10 European countries. Out of 129 enrolled patients, 116 patients (58 vs. 58 randomized into a training or usual care control group) on disease-targeted medication completed the study [85 female; mean age 53.6 ± 12.5 years; mean pulmonary arterial pressure 46.6 ± 15.1 mmHg; World Health Organization (WHO) functional class II 53%, III 46%; PAH n = 98; CTEPH n = 18]. Patients of the training group performed a standardized in-hospital rehabilitation with mean duration of 25 days [95% confidence interval (CI) 17–33 days], which was continued at home. The primary endpoint, change of 6-min walking distance, significantly improved by 34.1 ± 8.3 m in the training compared with the control group (95% CI, 18–51 m; P < 0.0001). Exercise training was feasible, safe, and well-tolerated. Secondary endpoints showed improvements in quality of life (short-form health survey 36 mental health 7.3 ± 2.5, P = 0.004), WHO-functional class (training vs. control: improvement 9:1, worsening 4:3; χ2  P = 0.027) and peak oxygen consumption (0.9 ± 0.5 mL/min/kg, P = 0.048) compared with the control group.

Conclusion

This is the first multicentre and so far the largest randomized, controlled study on feasibility, safety, and efficacy of exercise training as add-on to medical therapy in PAH and CTEPH. Within this study, a standardized specialized training programme with in-hospital start was successfully established in 10 European countries.
Age-Related Changes in Audiovisual Simultaneity Perception and Their Relationship With Working Memory
Authors: Chen Yi-Chuan , Yeh Su-Ling , Tang Pei-Fang
Published: August 2020

Objectives

Perceiving simultaneity of a visual and an auditory signal is critical for humans to integrate these multisensory inputs effectively and respond properly. We examined age-related changes in audiovisual simultaneity perception, and the relationships between this perception and working memory performances with aging.

Methods

Audiovisual simultaneity perception of young, middle-aged, and older adults was measured using a simultaneity judgment (SJ) task, in which a flash and a beep were presented at 1 of 11 stimulus-onset asynchronies (SOAs). Participants judged whether these two stimuli were perceived simultaneously. Precision of simultaneity perception, the SOA corresponding to the point of subjective simultaneity (PSS), and response errors at each SOA were estimated using model fitting. The precision and PSS are associated with multisensory perception per se, whereas the response error reflects executive ability when performing the SJ task. Visual working memory of the same middle-aged and older adults was measured using the Cambridge Neuropsychological Test Automated Battery (CANTAB) beforehand.

Results

Compared to young adults’ performances, middle-aged and older adults showed a decreased precision, a shift of PSS toward the visual-leading SOAs, and increased response errors at the visual-leading SOAs. Among these changes, only the increased response errors correlated with worse spatial recognition memory in middle-aged and older adults.

Discussion

Age-related decrements in audiovisual simultaneity perception start from middle age and are manifested in both perceptual and executive parameters. Furthermore, higher-order executive ability is plausibly a common cause for age-related degenerations in the audiovisual simultaneity perception and visual working memory.
Improving Local Service Delivery to Prevent Falls in Community-Dwelling Older Adults: Translating Research to Practice
Authors: Gagen Travis M , Bulzacchelli Maria T
Published: August 2020

Unintentional falls are the leading cause of both fatal and nonfatal injuries among Americans 65 years of age and older and place an enormous burden on the health care system. As the population continues to age, preventing falls will be increasingly important for reducing morbidity, mortality, and medical costs. Evidence-based fall prevention interventions for older adults exist, but widespread adoption of these interventions is needed. Local health departments, Area Agencies on Aging, first responders, and health care professionals can all play important roles in implementing fall prevention programs. This article presents a conceptual model for local delivery of fall prevention programs for community-dwelling older adults. This model can serve as a guide for translating existing fall prevention research into practice.
Conserved UBE3A subcellular distribution between human and mice is facilitated by non-homologous isoforms
Authors: Zampeta F Isabella , Sonzogni Monica , Niggl Eva , Lendemeijer Bas , Smeenk Hilde , de Vrij Femke M S , Kushner Steven A , Distel Ben , Elgersma Ype
Published: August 2020

The human UBE3A gene, which is essential for normal neurodevelopment, encodes three Ubiquitin E3 ligase A (UBE3A) protein isoforms. However, the subcellular localization and relative abundance of these human UBE3A isoforms are unknown. We found, as previously reported in mice, that UBE3A is predominantly nuclear in human neurons. However, this conserved subcellular distribution is achieved by strikingly distinct cis-acting mechanisms. A single amino-acid deletion in the N-terminus of human hUBE3A-Iso3, which is homologous to cytosolic mouse mUBE3A-Iso2, results in its translocation to the nucleus. This singe amino-acid deletion is shared with apes and Old World monkeys and was preceded by the appearance of the cytosolic hUBE3A-Iso2 isoform. This hUBE3A-Iso2 isoform arose after the lineage of New World monkeys and Old World monkeys separated from the Tarsiers (Tarsiidae). Due to the loss of a single nucleotide in a non-coding exon, this exon became in frame with the remainder of the UBE3A protein. RNA-seq analysis of human brain samples showed that the human UBE3A isoforms arise by alternative splicing. Consistent with the predominant nuclear enrichment of UBE3A in human neurons, the two nuclear-localized isoforms, hUBE3A-Iso1 and -Iso3, are the most abundantly expressed isoforms of UBE3A, while hUBE3A-Iso2 maintains a small pool of cytosolic UBE3A. Our findings provide new insight into UBE3A localization and evolution and may have important implications for gene therapy approaches in Angelman syndrome.
Pharmacokinetic and pharmacodynamic analysis of baloxavir marboxil, a novel cap-dependent endonuclease inhibitor, in a murine model of influenza virus infection
Authors: Ando Yoshinori , Noshi Takeshi , Sato Kenji , Ishibashi Toru , Yoshida Yuki , Hasegawa Takahiro , Onishi Motoyasu , Kitano Mitsutaka , Oka Ryoko , Kawai Makoto , Yoshida Ryu , Sato Akihiko , Shishido Takao , Naito Akira
Published: August 2020

Background

Baloxavir acid, the active form of the orally available prodrug baloxavir marboxil, is a novel cap-dependent endonuclease inhibitor of influenza virus. Baloxavir marboxil has been shown to rapidly reduce virus titres compared with oseltamivir in clinical studies.

Objectives

We investigated the relationship between pharmacokinetic (PK) parameters and antiviral activity of baloxavir acid based on virus titre reduction in lungs of infected mice.

Methods

BALB/c mice infected with a sub-lethal dose of influenza A(H1N1), A(H1N1)pdm09, A(H3N2) or type B virus were treated on day 5 with oral baloxavir marboxil (0.5–50 mg/kg q12h), subcutaneous baloxavir acid (0.25–8 mg/kg/day), oseltamivir phosphate (5 or 50 eq mg/kg q12h) or other antivirals for 1 day. Lung virus titres were assessed 24 h after initial antiviral dosing. PK testing was performed at up to 24 h post-dosing of baloxavir marboxil or baloxavir acid in A/WSN/33-infected mice and the PK/pharmacodynamic (PD) relationship was evaluated for baloxavir acid.

Results

Oral baloxavir marboxil administration showed dose-dependent virus titre reductions in lungs of mice infected with the different types/subtypes of influenza viruses 24 h post-dosing. Baloxavir marboxil at 15 mg/kg q12h resulted in ≥100-fold and ≥10-fold reductions in influenza A and B virus titres, respectively, compared with oseltamivir phosphate. PK/PD analysis showed that the plasma concentration at the end of the dosing interval (Cτ) or the plasma concentration at 24 h after initial dosing (C24) was the PK parameter predicting the virus titres at 24 h post-dosing of baloxavir acid.

Conclusions

PK/PD analysis of baloxavir acid based on virus titre reduction in this mouse model could be helpful in predicting and maximizing virological outcomes in clinical settings.