bluuebunny/crossref_metadata_2025 huggingface dataset:
2D Nb2SiTe4 and Nb2GeTe4: promising thermoelectric figure of merit and gate-tunable thermoelectric performance
Authors: Wu Xuming , Gao Guoying , Hu Lei , Qin Dan
Published: March 2021

Recently, the experimentally synthesized Nb2SiTe4 was found to be a stable layered narrow-gap semiconductor, and the fabricated field-effect transistors (FETs) based on few-layers Nb2SiTe4 are good candidates for ambipolar devices and mid-infrared detection (Zhao et al 2019 ACS Nano
13 10705–10). Here, we use first-principles combined with Boltzmann transport theory and non-equilibrium Green’s function method to investigate the thermoelectric transport coefficients of monolayer Nb2XTe4 (X = Si, Ge) and the gate voltage effect on the thermoelectric performance of the FET based on monolayer Nb2SiTe4. It is found that both monolayers have large p-type Seebeck coefficients due to the ‘pudding-mold-type’ valence band structure, and they both exhibit anisotropic thermoelectric behavior with optimal thermoelectric figure of merit of 1.4 (2.2) at 300 K and 2.8 (2.5) at 500 K for Nb2SiTe4 (Nb2GeTe4). The gate voltage can effectively increase the thermoelectric performance for the Nb2SiTe4-based FET. The high thermoelectric figure of merit can be maintained in a wide temperature range under a negative gate voltage. Furthermore, the FET exhibits a good gate-tunable Seebeck diode effect. The present work suggests that Nb2XTe4 monolayers are promising candidates for 2D thermoelectric materials and thermoelectric devices.
Photolithographically-patterned C-MEMS graphene by carbon diffusion through nickel
Authors: Vaca Sveidy , Pilloni Oscar , Gómez Axel Rodríguez , Serkovic-Loli Laura N , Qureshi Naser , Oropeza-Ramos Laura
Published: March 2021

In recent years the most studied carbon allotrope has been graphene, due to the outstanding properties that this two-dimensional material exhibits; however, it turns out to be a difficult material to produce, pattern, and transfer to a device substrate without contamination. Carbon microelectromechanical systems are a versatile technology used to create nano/micro carbon devices by pyrolyzing a patterned photoresist, making them highly attractive for industrial applications. Furthermore, recent works have reported that pyrolytic carbon material can be graphitized by the diffusion of carbon atoms through a transition metal layer. In this work we take advantage of the latter two methods in order to produce multilayer graphene by improving the molecular ordering of photolithographically-defined pyrolytic carbon microstructures, through the diffusion (annealing) of carbon atoms through nickel, and also to eliminate any further transfer process to a device substrate. The allotropic nature of the final carbon microstructures was inspected by Raman spectroscopy (Average I
D/I
G of 0.2348 ± 0.0314) and TEM clearly shows well-aligned lattice planes of 3.34 Å fringe separation. These results were compared to measurements made on pyrolytic carbon (Average I
D/I
G of 0.9848 ± 0.0235) to confirm that our method is capable of producing a patterned multilayer graphene material directly on a silicon substrate.
Monte Carlo study on dose distributions from total skin electron irradiation therapy (TSET)
Authors: Ding George X , Osmundson Evan C , Shinohara Eric , Newman Neil B , Price Michael , Kirschner Austin N
Published: March 2021

Total skin electron therapy (TSET) has been used to treat mycosis fungoides since the 1950s. Practitioners of TSET rely on relatively crude, phantom-based point measurements for commissioning and treatment plan dosimetry. Using Monte Carlo simulation techniques, this study presents whole-body dosimetry for a patient receiving rotational, dual-field TSET. The Monte Carlo codes, BEAMnrc/DOSXYZnrc, were used to simulate 6 MeV electron beams to calculate skin dose from TSET. Simulations were validated with experimental measurements. The rotational dual-field technique uses extended source-to-surface distance with an acrylic beam degrader between the patient and incident beams. Simulations incorporated patient positioning: standing on a platform that rotates during radiation delivery. Resultant patient doses were analyzed as a function of skin depth-dose coverage and evaluated using dose-volume-histograms. Good agreement was obtained between simulations and measurements. For a cylinder with a 30 cm diameter, the depths that dose fell to 50% of the surface dose was 0.66 cm, 1.15 cm and 1.42 cm for thicknesses of 9 mm, 3 mm and without an acrylic scatter plate, respectively. The results are insensitive to cylinder diameter. Relatively uniform skin surface dose was obtained for skin in the torso area although large dose variations (>25%) were found in other areas resulting from partial beam shielding of the extremities. To achieve 95% mean dose to the first 5 mm of skin depth, the mean dose to skin depth of 5–10 mm and depth of 10–15 mm from the skin surface was 74% (57%) and 50% (25%) of the prescribed dose when using a 3 mm (9 mm) thickness scatter plate, respectively. As a result of this investigation on patient skin dose distributions we changed our patient treatments to use a 3 mm instead of a 9 mm thickness Acrylic scatter plate for clinically preferred skin depth dose coverage.
Loss of muscular force in isolated rat diaphragms is related to changes in muscle fibre size
Authors: Lieb Samuel , Schumann Stefan
Published: March 2021

Objective. Passivity of the diaphragm during prolonged mechanical ventilation can lead to ventilation-induced diaphragmatic dysfunction reasoned by a reduction of diaphragmatic muscle strength. Electrical stimulation may be utilised to modulate diaphragm muscle strength. Therefore we intended to investigate diaphragmatic muscle strength based on stimulation with electric impulses. Approach. Diaphragms of Wistar rats were excised, embedded in various incubation solutions and placed in a diaphragm force measurement device. Pressure amplitudes generated by the diaphragm in dependency of the embedding solution, stimulation frequency and time (360 min) were determined. Furthermore, the diaphragms were histologically evaluated. Main results. The ex vivo diaphragms evoked no pressure if embedded in incubation solutions with high potassium concentrations and up to >20 cmH2O if embedded in incubation solutions with extracellular potassium concentrations. Although vitality was well maintained after 360 min (78%) cultivation, the diaphragm’s force dropped by 90.8% after 240 min. The decline in the diaphragm’s force progressed faster if stimulation was performed every 20 min compared to every 120 min. The size of Type I muscle fibres was largest in diaphragms stimulated every 120 min. The fibre size of Type 2b/x muscle cells was lower in diaphragms after electrical stimulation compared to non-stimulated diaphragms. Significance. The force that the diaphragm can develop in ex vivo conditions depends on the incubation solution and the conditions of activation. Activity-related changes in the diaphragm’s muscular force are accompanied by specific changes in muscle fibre size.
AECG-DecompNet: abdominal ECG signal decomposition through deep-learning model
Authors: Rasti-Meymandi Arash , Ghaffari Aboozar
Published: March 2021

Objective. The accurate decomposition of a mother’s abdominal electrocardiogram (AECG) to extract the fetal ECG (FECG) is a primary step in evaluating the fetus’s health. However, the AECG is often affected by different noises and interferences, such as the maternal ECG (MECG), making it hard to evaluate the FECG signal. In this paper, we propose a deep-learning-based framework, namely ‘AECG-DecompNet’, to efficiently extract both MECG and FECG from a single-channel abdominal electrode recording. Approach. AECG-DecompNet is based on two series networks to decompose AECG, one for MECG estimation and the other to eliminate interference and noise. Both networks are based on an encoder-decoder architecture with internal and external skip connections to reconstruct the signals better. Main results. Experimental results show that the proposed framework performs much better than utilizing one network for direct FECG extraction. In addition, the comparison of the proposed framework with popular single-channel extraction techniques shows superior results in terms of QRS detection while indicating its ability to preserve morphological information. AECG-DecompNet achieves exceptional accuracy in the precision metric (97.4%), higher accuracy in recall and F
1 metrics (93.52% and 95.42% respectively), and outperforms other state-of-the-art approaches. Significance. The proposed method shows a notable performance in preserving the morphological information when the FECG within the AECG signal is weak.
Cyclic behavior and deformation mechanism of superelastic SMA U-shaped dampers under in-plane and out-of-plane loadings
Authors: Wang Bin , Zhu Songye , Casciati Fabio , Chen Kaixin , Jiang Huanjun
Published: March 2021

This study systematically investigates the cyclic behavior and deformation mechanism of superelastic shape memory alloy U-shaped dampers (SMA-UDs) that are intended for seismic resilient applications. The study first summarized the experimental investigations of a series of SMA-UD component tests under loadings in two directions (i.e. in-plane and out-of-plane directions). Test results demonstrated that SMA-UDs exhibit excellent self-centering (SC) capability and stable energy dissipation under both loadings. Subsequently, two detailed finite element models were validated through the comparisons with experimental results in terms of global hysteresis loops and deformation shapes. The insights into the SMA-UD behavior under different directional loadings were presented. The influences of different geometric parameters of the SMA-UDs on the deformation mechanism were further highlighted. Parametric studies were carried out to investigate the effects of the existence of adjacent plates and the perpendicular compression on the SMA-UD’s mechanical properties of practical interest in earthquake engineering. Results show that the adjacent plate has a positive role in the deformation mechanism of the SMA-UD under in-plane loading, whereas it has a slight effect on the SMA-UD under out-of-plane loading. The perpendicular compressive deformation undertaken by the SMA-UD itself can deteriorate its SC capability under in-plane loading. The results attained from this research are conducive to the design and applications of the SMA-UDs in engineering practice.
Nonreciprocal absorption characteristics of one-dimensional cylindrical magnetized plasma photonic crystals
Authors: Wang Qian-Yu , Liu Shuang , Gui Di , Zhang Hai-Feng
Published: March 2021

By combining the propagation matrix of planar magnetized plasma photonic crystals with that of the cylindrical non-magnetized medium, the transfer matrix equation of the cylindrical magnetized plasma photonic crystals is obtained. Applying this equation to the cylindrical structure, a quasi-periodic structure conforming to the Pell sequence is designed, which has good nonreciprocal property. Therefore, the absorptance of light propagating forward and backward in this structure are studied respectively. The concept of contrast ratio (D

C
), calculated from the absorption of the forward and backward propagation of electromagnetic waves in the structure, is used to compare the degree of difference between the two. It is found that the nonreciprocal propagation becomes larger with the increase of the azimuth modulus and the relative dielectric constant of the medium, increases first, and then decreases with the increase of the incident angle, but does not change obviously when the plasma collision frequency and the cyclotron frequency of the plasma are getting larger. The absorptance decreases with the increase of azimuth modulus, relative dielectric constant, and plasma cyclotron frequency, and becomes better with the increase of the plasma collision frequency. However, when the incident angle gets larger, the absorptance becomes better at first and then gets worse.
Saturable higher nonlinearity effects on the modulational instabilities in three-core triangular configuration couplers
Authors: Mohanraj P , Sivakumar R
Published: March 2021

This paper demonstrates the possibility to observe the modulational instability (MI) regions due to modified nonlinear saturability over and above other high-order nonlinearities for the triangular configuration of a three-core oppositely directed coupler. In this configuration, two channels are positive-refractive-index material, and one is a negative-index material. The governing equations are the modified coupled nonlinear Schrödinger equations, to which we add the higher-order nonlinearity terms and coupling terms. This equation is further modified with the saturable nonlinearity term. In the presence of several nonlinearities, we derive the dispersion relation for the optical coupler under consideration. We use a linear stability analysis to study the modulation stability characteristic gain in both the normal and anomalous group-velocity dispersion regimes. We have widely varied the parameter range of the physical system parameters to accommodate different possibilities. In the normal region, the saturable nonlinearity aids in increasing the bandwidth of the MI region, while in the anomalous regime, the bandwidth reduces. In the normal dispersion case, the simultaneous presence of all nonlinearities in the optical coupler does not provide a suitable scope for pulse propagation. On the other hand, in the anomalous regime, these nonlinearities favor for pulse propagation.
Gridded soil surface nitrogen surplus on grazing and agricultural land: Impact of land use maps
Authors: Kaltenegger Katrin , Erb Karl-Heinz , Matej Sarah , Winiwarter Wilfried
Published: March 2021

Excess N application on agricultural land greatly impacts the environment in multiple ways, driven by population growth and improving quality of human diets. Therefore, it is essential to quantify the sources of the emissions of N compounds and their determinants (e.g. biological N fixation (BNF), mineral fertilizer, manure N and N deposition) to develop adequate mitigation measures. Here we aim at comprehensively mapping and quantifying N fluxes on agricultural land to analyze these sources on different scales. As underlying grazing land maps used for such calculations are fairly different in terms of methodology and definition and thus spatial extent and pattern, we investigate how this diversity in grazing land maps affects quantification of N indicators. We compared three different global grazing land maps and analyzed the propagation of differences to discrepancies in N indicators calculated from them. We discovered that (i) area differences propagated to high discrepancies in N surplus mostly in Asia, and to a minor extent also in Europe and Northern Africa. (ii) BNF constitutes an important translator for differences on grazing land to N indicators, while also being a source of further uncertainty, which warrants further scrutiny. (iii) A more inclusive definition of grazing land results in overall less N surplus given the larger areas included but allows to provide a more comprehensive estimate of the influence of human activity on the N cycle. This study is the first to provide an in-depth analysis of the effect of grazing land and agricultural land area differences on various N budget terms and N indicator calculation, highlighting opportunities for further research, and the importance of a comprehensive accounting of N surplus when using an inclusive definition of grazing land.
The impact of chaotic saddles on the synchronization of complex networks of discrete-time units
Authors: Medeiros Everton S , Medrano-T Rene O , Caldas Iberê L , Feudel Ulrike
Published: March 2021

A chaotic saddle is a common nonattracting chaotic set well known for generating finite-time chaotic behavior in low and high-dimensional systems. In general, dynamical systems possessing chaotic saddles in their state-space exhibit irregular behavior with duration lengths following an exponential distribution. However, when these systems are coupled into networks the chaotic saddle plays a role in the long-term dynamics by trapping network trajectories for times that are indefinitely long. This process transforms the network’s high-dimensional state-space by creating an alternative persistent desynchronized state coexisting with the completely synchronized one. Such coexistence threatens the synchronized state with vulnerability to external perturbations. We demonstrate the onset of this phenomenon in complex networks of discrete-time units in which the synchronization manifold is perturbed either in the initial instant of time or in arbitrary states of its asymptotic dynamics. The role of topological asymmetries of Erdös–Rényi and Barabási–Albert graphs are investigated. Besides, the required coupling strength for the occurrence of trapping in the chaotic saddle is unveiled.
New features of doubly transient chaos: complexity of decay
Authors: Károlyi György , Tél Tamás
Published: March 2021

In dissipative systems without any driving or positive feedback all motion stops ultimately since the initial kinetic energy is dissipated away during time evolution. If chaos is present, it can only be of transient type. Traditional transient chaos is, however, supported by an infinity of unstable orbits. In the lack of these, chaos in undriven dissipative systems is of another type: it is termed doubly transient chaos as the strength of transient chaos is diminishing in time, and ceases asymptotically. Here we show that a clear view of such dynamics is provided by identifying KAM tori or chaotic regions of the dissipation-free case, and following their time evolution in the dissipative dynamics. The tori often smoothly deform first, but later they become disintegrated and dissolve in a kind of shrinking chaos. We identify different dynamical measures for the characterization of this process which illustrate that the strength of chaos is first diminishing, and after a while disappears, the motion enters the phase of ultimate stopping.
Non-unitary quantum electronics: Novel functions from the edge of the quantum world
Authors: Mannhart J , Boschker H , Bredol P
Published: March 2021

Novel categories of electronic devices and quantum materials are obtained by pipelining the unitary evolution of electron quantum states as described by Schrödinger’s equation with non-unitary processes that interrupt the coherent propagation of electrons. These devices and materials reside in the fascinating transition regime between quantum mechanics and classical physics. The devices are designed such that a nonreciprocal unitary state evolution, achieved by means of a broken inversion symmetry, is interrupted by individual inelastic scattering events caused by defects coupled to an environment. Two-terminal non-unitary quantum devices, for example, feature nonreciprocal conductance in linear response. Thus, they are exemptions to Onsager’s reciprocal relation, and they challenge the second law of thermodynamics. Furthermore, materials and metamaterials featuring such functionalities may be realized by embedding such nanostructures into their unit cells.
A Hybrid Evaluation-Optimization Trial to Evaluate an Intervention Targeting the Intersection of Alcohol and Sex in College Students and Simultaneously Test an Additional Component Aimed at Preventing Sexual Violence
Authors: Tanner Amanda E , Guastaferro Kate M , Rulison Kelly L , Wyrick David L , Milroy Jeffrey J , Bhandari Sandesh , Thorpe Shemeka , Ware Samuella , Miller Alicia M , Collins Linda M
Published: March 2021

Background

Using the multiphase optimization strategy (MOST), we previously developed and optimized an online behavioral intervention, itMatters, aimed at reducing the risk of sexually transmitted infections (STI) among first-year college students by targeting the intersection of alcohol use and sexual behaviors.

Purpose

We had two goals: (a) to evaluate the optimized itMatters intervention and (b) to determine whether the candidate sexual violence prevention (SVP) component (included at the request of participating universities) had a detectable effect and therefore should be added to create a new version of itMatters. We also describe the hybrid evaluation-optimization trial we conducted to accomplish these two goals in a single experiment.

Methods

First year college students (N = 3,098) at four universities in the USA were individually randomized in a hybrid evaluation-optimization 2 × 2 factorial trial. Data were analyzed using regression models, with pre-test outcome variables included as covariates in the models. Analyses were conducted separately with (a) immediate post-test scores and (b) 60-day follow-up scores as outcome variables.

Results

Experimental results indicated a significant effect of itMatters on targeted proximal outcomes (norms) and on one distal behavioral outcome (binge drinking). There were no significant effects on other behavioral outcomes, including the intersection of alcohol and sexual behaviors. In addition, there were mixed results (positive short-term effect; no effect at 60-day follow-up) of the SVP component on targeted proximal outcomes (students’ self-efficacy to reduce/prevent sexual violence and perceived effectiveness of protective behavioral strategies).

Conclusions

The hybrid evaluation-optimization trial enabled us to evaluate the individual and combined effectiveness of the optimized itMatters intervention and the SVP component in a single experiment, conserving resources and providing greatly improved efficiency.

Trial Registration

NCT04095065.
Analyzing the costs of developing and operating an integrated health-system specialty pharmacy: The case of a centralized insurance navigation process for specialty clinic patients
Authors: Rim Matthew H , Thomas Karen C , Barrus Stephanie A , Ryther Ashley M K , Clawson Antoine , Ferrara Francesca , Jackson Christopher G
Published: March 2021

Purpose

Direct and indirect costs related to the growth of specialty pharmacy services and the insurance navigation process for specialty clinic patients are discussed, and development and implementation of a pharmacy-driven and system-wide prior authorization (PA) processing center within a health system are described.

Expensive specialty drugs require PA. Due to the concentration of specialists, health systems with multiple specialties experience higher PA burden and resulting care delays. Although clinic staff typically handle PA requests, health-system specialty pharmacies are well positioned to support patients, clinic staff, and physicians by assuming responsibility for the PA process entirely. University of Utah Health established its Pharmacy Ambulatory Clinical Care Center (PAC3) to centralize PA processing for selected specialty and primary care clinics within the health system. In fiscal year 2019, the PAC3 team (10 pharmacy technician and 1.5 pharmacist full-time equivalents) completed over 13,000 PAs. The pharmacy labor cost increase was significant; however, the benefits gained from increased services, quality, and financial strength surpassed all costs associated with the implementation and maintenance of the pharmacy operation. Other tangible benefits included decreased delays in therapy initiation, increased patient satisfaction, increased clinic visits, and increased staff and provider satisfaction and engagement.

Conclusion

Increased PA requests associated with specialty drugs have placed considerable stress and staff burden on specialty clinics within health systems. However, development and implementation of an efficient PA processing infrastructure within a health-system specialty pharmacy may reduce the burden, increase financial strength, and improve the patient experience.
Pick Your President: Why and How Parties Should Seek to Agree on a Presiding Arbitrator
Authors: Leikin Eric , Treichl Clemens
Published: March 2021

It is common wisdom that selecting a suitable presiding arbitrator is vital to securing efficient proceedings and a high-quality award. As a corollary of party autonomy, the parties’ right to choose their arbitrators is subject only to few limitations, yet relatively little guidance exists for parties attempting to jointly choose the arbitral president in a structured and efficient way. This article seeks to expand on the limited guidance available. It begins by briefly examining the underlying legal framework and setting out various objectives that can serve as a yardstick in fashioning a procedure for selecting presiding arbitrators. This general analysis is followed by a proposal of a concrete, standard ‘list’ procedure which is easily adaptable to different arbitration settings and case configurations.
Decreasing Surgical Site Infections in Plastic Surgery: A Systematic Review and Meta-analysis of Level 1 Evidence
Authors: ElHawary Hassan , Hintermayer Matthew A , Alam Peter , Brunetti Vanessa C , Janis Jeffrey E
Published: March 2021

Background

Although many interventions are implemented to prevent surgical site infections (SSIs) in plastic surgery, their supporting evidence is inconsistent.

Objectives

The goal of this study was to assess the efficacy of methods for decreasing SSIs in plastic surgery.

Methods

A systematic review and meta-analysis were performed to compare the effects of SSI prevention methods. All the studies were assessed for quality of evidence according to the GRADE assessment.

Results

Fifty Level 1 randomized controlled trials were included. The most common interventions for preventing SSIs were antibiotic prophylaxis, showering, prepping, draping, and the use of dressings. Current evidence suggests that antibiotic prophylaxis is largely unnecessary and overused in many plastic surgical procedures, with the exception of head and neck oncologic, oral craniofacial, and traumatic hand surgeries.

Conclusions

Efficacy of antibiotic prophylaxis in plastic surgery is dependent on surgery type. There is a lack evidence that showering and prepping with chlorohexidine and povidone reduces SSIs.

Level of Evidence: 1
MUFFIN: multi-scale feature fusion for drug–drug interaction prediction
Authors: Chen Yujie , Ma Tengfei , Yang Xixi , Wang Jianmin , Song Bosheng , Zeng Xiangxiang
Published: March 2021

Motivation

Adverse drug–drug interactions (DDIs) are crucial for drug research and mainly cause morbidity and mortality. Thus, the identification of potential DDIs is essential for doctors, patients and the society. Existing traditional machine learning models rely heavily on handcraft features and lack generalization. Recently, the deep learning approaches that can automatically learn drug features from the molecular graph or drug-related network have improved the ability of computational models to predict unknown DDIs. However, previous works utilized large labeled data and merely considered the structure or sequence information of drugs without considering the relations or topological information between drug and other biomedical objects (e.g. gene, disease and pathway), or considered knowledge graph (KG) without considering the information from the drug molecular structure.

Results

Accordingly, to effectively explore the joint effect of drug molecular structure and semantic information of drugs in knowledge graph for DDI prediction, we propose a multi-scale feature fusion deep learning model named MUFFIN. MUFFIN can jointly learn the drug representation based on both the drug-self structure information and the KG with rich bio-medical information. In MUFFIN, we designed a bi-level cross strategy that includes cross- and scalar-level components to fuse multi-modal features well. MUFFIN can alleviate the restriction of limited labeled data on deep learning models by crossing the features learned from large-scale KG and drug molecular graph. We evaluated our approach on three datasets and three different tasks including binary-class, multi-class and multi-label DDI prediction tasks. The results showed that MUFFIN outperformed other state-of-the-art baselines.

Availability and implementation

The source code and data are available at https://github.com/xzenglab/MUFFIN.
Use of gene expression profiling to identify candidate genes for pretherapeutic patient classification in acute appendicitis
Authors: Kiss N , Minderjahn M , Reismann J , Svensson J , Wester T , Hauptmann K , Schad M , Kallarackal J , von Bernuth H , Reismann M
Published: March 2021

Background

Phlegmonous and gangrenous appendicitis represent independent pathophysiological entities with different clinical courses ranging from spontaneous resolution to septic disease. However, reliable predictive methods for these clinical phenotypes have not yet been established. In an attempt to provide pathophysiological insights into the matter, a genomewide gene expression analysis was undertaken in patients with acute appendicitis.

Methods

Peripheral blood mononuclear cells were isolated and, after histological confirmation of PA or GA, analysed for genomewide gene expression profiling using RNA microarray technology and subsequent pathway analysis.

Results

Samples from 29 patients aged 7–17 years were included. Genomewide gene expression analysis was performed on 13 samples of phlegmonous and 16 of gangrenous appendicitis. From a total of 56 666 genes, 3594 were significantly differently expressed. Distinct interaction between T and B cells in the phlegmonous appendicitis group was suggested by overexpression of T cell receptor α and β subunits, CD2, CD3, MHC II, CD40L, and the B cell markers CD72 and CD79, indicating an antiviral mechanism. In the gangrenous appendicitis group, expression of genes delineating antibacterial mechanisms was found.

Conclusion

These results provide evidence for different and independent gene expression in phlegmonous and gangrenous appendicitis in general, but also suggest distinct immunological patterns for the respective entities. In particular, the findings are compatible with previous evidence of spontaneous resolution in phlegmonous and progressive disease in gangrenous appendicitis.
The hedgehog pathway suppresses neuropathogenesis in CD4 T cell-driven inflammation
Authors: Benallegue Nail , Kebir Hania , Kapoor Richa , Crockett Alexis , Li Cen , Cheslow Lara , Abdel-Hakeem Mohamed S , Gesualdi James , Miller Miles C , Wherry E John , Church Molly E , Blanco M Andres , Alvarez Jorge I
Published: March 2021

The concerted actions of the CNS and the immune system are essential to coordinating the outcome of neuroinflammatory responses. Yet, the precise mechanisms involved in this crosstalk and their contribution to the pathophysiology of neuroinflammatory diseases largely elude us. Here, we show that the CNS-endogenous hedgehog pathway, a signal triggered as part of the host response during the inflammatory phase of multiple sclerosis and experimental autoimmune encephalomyelitis, attenuates the pathogenicity of human and mouse effector CD4 T cells by regulating their production of inflammatory cytokines. Using a murine genetic model, in which the hedgehog signalling is compromised in CD4 T cells, we show that the hedgehog pathway acts on CD4 T cells to suppress the pathogenic hallmarks of autoimmune neuroinflammation, including demyelination and axonal damage, and thus mitigates the development of experimental autoimmune encephalomyelitis. Impairment of hedgehog signalling in CD4 T cells exacerbates brain-brainstem-cerebellum inflammation and leads to the development of atypical disease. Moreover, we present evidence that hedgehog signalling regulates the pathogenic profile of CD4 T cells by limiting their production of the inflammatory cytokines granulocyte-macrophage colony-stimulating factor and interferon-γ and by antagonizing their inflammatory program at the transcriptome level. Likewise, hedgehog signalling attenuates the inflammatory phenotype of human CD4 memory T cells. From a therapeutic point of view, our study underlines the potential of harnessing the hedgehog pathway to counteract ongoing excessive CNS inflammation, as systemic administration of a hedgehog agonist after disease onset effectively halts disease progression and significantly reduces neuroinflammation and the underlying neuropathology. We thus unveil a previously unrecognized role for the hedgehog pathway in regulating pathogenic inflammation within the CNS and propose to exploit its ability to modulate this neuroimmune network as a strategy to limit the progression of ongoing neuroinflammation.
Astrocytic glycogen accumulation drives the pathophysiology of neurodegeneration in Lafora disease
Authors: Duran Jordi , Hervera Arnau , Markussen Kia H , Varea Olga , López-Soldado Iliana , Sun Ramon C , del Río Jose Antonio , Gentry Matthew S , Guinovart Joan J
Published: March 2021

The hallmark of Lafora disease, a fatal neurodegenerative disorder, is the accumulation of intracellular glycogen aggregates called Lafora bodies. Until recently, it was widely believed that brain Lafora bodies were present exclusively in neurons and thus that Lafora disease pathology derived from their accumulation in this cell population. However, recent evidence indicates that Lafora bodies are also present in astrocytes. To define the role of astrocytic Lafora bodies in Lafora disease pathology, we deleted glycogen synthase specifically from astrocytes in a mouse model of the disease (malinKO). Strikingly, blocking glycogen synthesis in astrocytes—thus impeding Lafora bodies accumulation in this cell type—prevented the increase in neurodegeneration markers, autophagy impairment, and metabolic changes characteristic of the malinKO model. Conversely, mice that over-accumulate glycogen in astrocytes showed an increase in these markers. These results unveil the deleterious consequences of the deregulation of glycogen metabolism in astrocytes and change the perspective that Lafora disease is caused solely by alterations in neurons.
Emergence of blockchain-technology application in peer-to-peer electrical-energy trading: a review
Authors: Thukral Manish Kumar
Published: March 2021

Renewable-energy resources require overwhelming adoption by the common masses for safeguarding the environment from pollution. In this context, the prosumer is an important emerging concept. A prosumer in simple terms is the one who consumes as well as produces electricity and sells it either to the grid or to a neighbour. In the present scenario, peer-to-peer (P2P) energy trading is gaining momentum as a new vista of research that is viewed as a possible way for prosumers to sell energy to neighbours. Enabling P2P energy trading is the only method of making renewable-energy sources popular among the common masses. For making P2P energy trading successful, blockchain technology is sparking considerable interest among researchers. Combined with smart contracts, a blockchain provides secure tamper-proof records of transactions that are recorded in distributed ledgers that are immutable. This paper explores, using a thorough review of recently published research work, how the existing power sector is reshaping in the direction of P2P energy trading with the application of blockchain technology. Various challenges that are being faced by researchers in the implementation of blockchain technology in the energy sector are discussed. Further, this paper presents different start-ups that have emerged in the energy-sector domain that are using blockchain technology. To give insight into the application of blockchain technology in the energy sector, a case of the application of blockchain technology in P2P trading in electrical-vehicle charging is discussed. At the end, some possible areas of research in the application of blockchain technology in the energy sector are discussed.
PREVAIL IV: A Randomized, Double-Blind, 2-Phase, Phase 2 Trial of Remdesivir vs Placebo for Reduction of Ebola Virus RNA in the Semen of Male Survivors
Authors: Higgs Elizabeth S , Gayedyu-Dennis Dehkontee , Fischer II William A , Nason Martha , Reilly Cavan , Beavogui Abdoul Habib , Aboulhab Jamila , Nordwall Jacqueline , Lobbo Princess , Wachekwa Ian , Cao Huyen , Cihlar Tomas , Hensley Lisa , Lane H Clifford
Published: March 2021

Background

Ebola virus RNA persists in the semen of male Ebola survivors for months to years after the acute infection, and male-to-female sexual transmission of the virus is well documented. We investigated whether remdesivir can safely reduce persistence of seminal Ebola virus RNA.

Methods

We recruited men with persistent seminal Ebola RNA in Liberia and Guinea. Participants were randomized 1:1 to receive intravenous remdesivir (GS-5734; Gilead Sciences) or matching placebo administered once daily by intravenous infusion over 1 hour on 5 consecutive days. Stratification was by country and number of positive (1 or 2) preenrollment semen tests. We evaluated the difference in mean assay negativity rate (ANR), that is, the proportion of negative tests for each participant in each group in the treatment (days 1–28) and follow-up (months 2–6) phases on an intention-to-treat basis.

Results

We enrolled 38 men from July 2016 through June 2018. The mean treatment phase ANRs were 85% (standard deviation [SD] = 24%) and 76% (SD = 30%) in the remdesivir and placebo arms, respectively (P = .270). The mean follow-up phase ANRs were 96% (SD = 10%) and 81% (SD = 29%) in the remdesivir and placebo arms, respectively (P = .041). The 5-day remdesivir regimen was well tolerated with no safety concerns.

Conclusions

In this small trial, remdesivir 100 mg/day for 5 days safely reduced the presence of Ebola virus RNA in the semen of Ebola survivors 2 to 6 months after administration. A larger follow-up study is necessary to confirm results.

Clinical Trials Registration . NCT02818582
Plasma Kynurenine-to-Tryptophan Ratio, a Highly Sensitive Blood-Based Diagnostic Tool for Tuberculosis in Pregnant Women Living With Human Immunodeficiency Virus (HIV)
Authors: Adu-Gyamfi Clement , Savulescu Dana , Mikhathani Lillian , Otwombe Kennedy , Salazar-Austin Nicole , Chaisson Richard , Martinson Neil , George Jaya , Suchard Melinda
Published: March 2021

Background

For pregnant women living with human immunodeficiency virus (HIV), concurrent active tuberculosis (TB) disease increases the risk of maternal mortality and poor pregnancy outcomes. Plasma indoleamine 2,3-dioxygenase (IDO) activity measured by kynurenine-to-tryptophan (K/T) ratio has been proposed as a blood-based TB biomarker. We investigated whether plasma K/T ratio could be used to diagnose active TB among pregnant women with HIV.

Methods

Using an enzyme-linked immunosorbent assay (ELISA), we measured K/T ratio in 72 pregnant women with and active TB and compared them to 117 pregnant women with HIB but without TB, matched by age and gestational age.

Results

Plasma K/T ratio was significantly elevated during pregnancy compared to sampling done after pregnancy (P < .0001). Pregnant women who had received isoniazid preventive therapy (IPT) before enrollment had decreased plasma K/T ratio compared to those who had not received IPT (P = .0174). Plasma K/T ratio was elevated in women with active TB at time of diagnosis compared to those without TB (P < .0001). Using a cutoff of 0.100, plasma K/T ratio gave a diagnostic sensitivity of 94% (95% confidence interval [CI]: 82–95), specificity of 90% (95% CI: 80–91), positive predictive value (PPV) 85% and negative predictive value (NPV) 98%. A receiver operating characteristic curve (ROC) gave an area under the curve of 0.95 (95% CI: .92–.97, P < .0001).

In conclusion, plasma K/T ratio is a sensitive blood-based diagnostic test for active TB disease in pregnant women living with HIV. Plasma K/T ratio should be further evaluated as an initial TB diagnostic test to determine its impact on patient care.
Simultaneous spontaneous arterial dissections in a 38-year-old woman presenting during the covid-19 pandemic: a case report
Authors: Hewitson Lynsey , Wong Chih , Aziz Shahid , Dastidar Amardeep
Published: March 2021

Background

Spontaneous coronary artery dissection (SCAD) is an increasingly recognized and important cause of acute myocardial infarction, particularly in women under 50, often with minimal risk factors. Many patients have underlying arteriopathy, most commonly in the form of fibromuscular dysplasia.

Case summary

A 38-year-old woman presented to the hospital with chest pain and elevated high-sensitivity Troponin. Invasive coronary angiography demonstrated SCAD of the left anterior descending artery. The same day the patient developed a severe progressive headache and subsequent imaging revealed a left vertebral artery dissection. She was managed conservatively with optimal medical therapy and was successfully discharged from hospital on Day 7.

Discussion

To our knowledge, this is the first case report of simultaneous spontaneous coronary and vertebral artery dissections not related to pregnancy. It highlights not only the importance of recognizing and accurately diagnosing SCAD, but also of appreciating the possibility of underlying arteriopathy: this is paramount to ensuring appropriate investigations, follow-up and assessment of any unexplained symptoms in this patient group.
Percutaneous coronary intervention in a patient with heparin resistance due to essential thrombocythaemia: a case report
Authors: Okabe Toshitaka , Yakushiji Tadayuki , Isomura Naoei , Ochiai Masahiko
Published: March 2021

Background 

Coronary artery disease is uncommon in patients with essential thrombocythaemia (ET); therefore, no treatment strategies have been established.

Case summary 

A 68-year-old man visited our hospital with worsening effort angina complicated with ET. Coronary angiography (CAG) revealed moderate stenosis of the left main trunk and left anterior descending artery (LAD). We planned to perform percutaneous coronary intervention (PCI) only after the patient’s platelet count had fallen below 600 000/μL. Platelet factor 4 levels were markedly elevated (355.0 ng/mL; the normal range is <20 ng/mL). We observed a de novo lesion in the proximal left circumflex artery and stenosis progression in the LAD at the time of the PCI, neither of which had been detected at the previous CAG. During the PCI procedure, argatroban was infused to maintain the activated clotting time (ACT) above 250 s. The PCI was performed successfully without any complications. Follow-up CAG showed no restenosis, and no bleeding complications were observed during the course.

Discussion 

In patients with ET, it may be useful to measure platelet factor 4 before PCI and to monitor ACT during the procedure. When heparin resistance is suspected based on blood coagulation tests, infusion of direct thrombin inhibitor during PCI may be considered, with anticoagulation monitoring by ACT.
Updating and Validating the U.S. Veterans Affairs Frailty Index: Transitioning From ICD-9 to ICD-10
Authors: Cheng David , DuMontier Clark , Yildirim Cenk , Charest Brian , Hawley Chelsea E , Zhuo Min , Paik Julie M , Yaksic Enzo , Gaziano J Michael , Do Nhan , Brophy Mary , Cho Kelly , Kim Dae H , Driver Jane A , Fillmore Nathanael R , Orkaby Ariela R
Published: March 2021

Background

The Veterans Affairs Frailty Index (VA-FI) is an electronic frailty index developed to measure frailty using administrative claims and electronic health records data in Veterans. An update to ICD-10 coding is needed to enable contemporary measurement of frailty.

Method

International Classification of Diseases, ninth revision (ICD-9) codes from the original VA-FI were mapped to ICD-10 first using the Centers for Medicaid and Medicare Services (CMS) General Equivalence Mappings. The resulting ICD-10 codes were reviewed by 2 geriatricians. Using a national cohort of Veterans aged 65 years and older, the prevalence of deficits contributing to the VA-FI and associations between the VA-FI and mortality over years 2012–2018 were examined.

Results

The updated VA-FI-10 includes 6422 codes representing 31 health deficits. Annual cohorts defined on October 1 of each year included 2 266 191 to 2 428 115 Veterans, for which the mean age was 76 years, 97%–98% were male, 78%–79% were White, and the mean VA-FI was 0.20–0.22. The VA-FI-10 deficits showed stability before and after the transition to ICD-10 in 2015, and maintained strong associations with mortality. Patients classified as frail (VA-FI > 0.2) consistently had a hazard of death more than 2 times higher than nonfrail patients (VA-FI ≤ 0.1). Distributions of frailty and associations with mortality varied with and without linkage to CMS data and with different assessment periods for capturing deficits.

Conclusions

The updated VA-FI-10 maintains content validity, stability, and predictive validity for mortality in a contemporary cohort of Veterans aged 65 years and older, and may be applied to ICD-9 and ICD-10 claims data to measure frailty.
Motor Imagery Deficits in High-Functioning Older Adults and Its Impact on Fear of Falling and Falls
Authors: Sakurai Ryota , Montero-Odasso Manuel , Suzuki Hiroyuki , Ogawa Susumu , Fujiwara Yoshinori
Published: March 2021

Background

Older adults at risk of falling or who have fear of falling (FoF) present a discrepancy between “imagined” and “performed” actions. Using the gait-related motor imagery paradigm, we investigated whether prediction accuracy in motor execution is associated with the onset of FoF and with prospective falls among older adults with FoF.

Methods

A cohort of 184 community-dwelling older adults was tested for imaginary and executed Timed Up and Go (TUG) tests at a fast pace at baseline. They were first asked to imagine performing TUG and estimate the time taken to complete it (iTUG) and then to perform the actual trial (aTUG); the difference between the 2 times was calculated. Prospective falls were monitored between baseline and 2-year follow-up of FoF assessment.

Results

At follow-up, 27 of 85 participants without FoF at baseline (31.8%) had developed FoF. Twenty-seven of 99 participants (27.2%) with FoF at baseline experienced falls. A significantly shorter iTUG duration, when compared with aTUG, was observed in those who developed FoF or experienced multiple prospective falls, indicating overestimation of their TUG performance. The adjusted logistic regression model showed that a greater ΔTUG (ie, tendency to overestimate) at baseline was associated with an increased risk of new-onset FoF among those without FoF at baseline and multiple prospective falls among those with FoF at baseline.

Conclusions

Deficits in motor imagery (ie, overestimation of physical capabilities), reflecting impairment in motor planning, could provide an additional explanation of the high risk of FoF and recurrent falls among people with FoF.