bluuebunny/crossref_metadata_2025 huggingface dataset:
Neutrophil DREAM promotes neutrophil recruitment in vascular inflammation
Authors: Li Jing , Kumari Tripti , Barazia Andrew , Jha Vishwanath , Jeong Si-Yeon , Olson Amber , Kim Mijeong , Lee Bum-Kyu , Manickam Vijayprakash , Song Zhimin , Clemens Regina , Razani Babak , Kim Jonghwan , Dinauer Mary C. , Cho Jaehyung
Published: November 2021

The interaction between neutrophils and endothelial cells is critical for the pathogenesis of vascular inflammation. However, the regulation of neutrophil adhesive function remains not fully understood. Intravital microscopy demonstrates that neutrophil DREAM promotes neutrophil recruitment to sites of inflammation induced by TNF-α but not MIP-2 or fMLP. We observe that neutrophil DREAM represses expression of A20, a negative regulator of NF-κB activity, and enhances expression of pro-inflammatory molecules and phosphorylation of IκB kinase (IKK) after TNF-α stimulation. Studies using genetic and pharmacologic approaches reveal that DREAM deficiency and IKKβ inhibition significantly diminish the ligand-binding activity of β2 integrins in TNF-α–stimulated neutrophils or neutrophil-like HL-60 cells. Neutrophil DREAM promotes degranulation through IKKβ-mediated SNAP-23 phosphorylation. Using sickle cell disease mice lacking DREAM, we show that hematopoietic DREAM promotes vaso-occlusive events in microvessels following TNF-α challenge. Our study provides evidence that targeting DREAM might be a novel therapeutic strategy to reduce excessive neutrophil recruitment in inflammatory diseases.
Topological wave energy harvesting in bistable lattices
Authors: Hwang Myungwon , Arrieta Andres F
Published: November 2021

In this paper, we present an input-independent energy harvesting mechanism exploiting topological solitary waves. This class of medium transforming solitons, or transition waves, entails energy radiation in the form of trailing phonons in discrete bistable lattices. We observe numerically and experimentally that the most dominant frequencies of these phonons are invariant to the input excitations as long as transition waves are generated. The phonon energy at each unit cell is clustered around a single invariant frequency, enabling input-independent resonant harvesting with conventional energy transduction mechanisms. The presented mechanism fundamentally breaks the link between the unit cell size and the metamaterial’s operating frequencies, offering a broadband solution to energy harvesting that is particularly robust for low-frequency input sources. We further investigate the effect of lattice discreteness on the energy harvesting potential, observing two performance gaps and a topological wave harvesting pass band where the potential for energy conversion increases almost monotonically. The observed frequency-invariant phonons are intrinsic to the discrete bistable lattices, enabling broadband energy harvesting to be an inherent metamaterial property.
Inhibition of spread of typical bipartite and genuine multiparty entanglement in response to disorder
Authors: Biswas George , Biswas Anindya , Sen Ujjwal
Published: November 2021

The distribution of entanglement of typical multiparty quantum states is not uniform over the range of the measure utilized for quantifying the entanglement. We intend to find the response to disorder in the state parameters on this non-uniformity for typical states. We find that the typical entanglement, averaged over the disorder, is taken farther away from uniformity, as quantified by decreased standard deviation, in comparison to the clean case. The feature is seemingly generic, as we see it for Gaussian and non-Gaussian disorder distributions, for varying strengths of the disorder, and for disorder insertions in one and several state parameters. The non-Gaussian distributions considered are uniform and Cauchy–Lorentz. Two- and three-qubit pure state Haar-uniform generations are considered for the typical state productions. We also consider noisy versions of the initial states produced in the Haar-uniform generations. A genuine multiparty entanglement monotone is considered for the three-qubit case, while concurrence is used to measure two-qubit entanglement.
Robustness tests for an optical time scale
Authors: Formichella V , Galleani L , Signorile G , Sesia I
Published: November 2021

Optical clocks have reached such an impressive accuracy and stability that the future redefinition of the second will be probably based on an optical transition. Consequently, building time scales based on optical clocks has become a key problem. Unfortunately, optical clocks are still laboratory prototypes and are not yet capable of long times of autonomous operation. It is hence critical to understand the impact of this limited optical clock availability on the generated time scale. In this work, after describing a simple and effective optical time scale algorithm, based on the steering of a flywheel oscillator towards the optical clock, we investigate in detail the impact of the limited availability of the optical clock on the performances of the steering algorithm and of the generated time scale through numerical simulations. In particular, we simulate a time scale generated by a hydrogen maser (with a flicker floor of 5.5 × 10−16) steered towards an optical clock, by considering six different scenarios for the availability of the latter, spanning from the ideal one, i.e. continuous operation of the optical clock, to the worst one, i.e. non-uniformly distributed frequency measurements with long unavailability periods. The results prove that the steering algorithm is robust and effective despite its very simple implementation, and it is capable of very good performances in all the considered scenarios, provided that the hydrogen maser behaves nominally. Specifically, they show that a time scale with an accuracy of a few hundreds of picoseconds can be easily realized in the ideal scenario, whereas in a more realistic scenario, with one measurement per week only, the time accuracy is nonetheless of a few nanoseconds, competing with the best time scales currently realized worldwide. The performances degradation due to a non-nominal maser behaviour is also discussed.
Luminescence performance of laser synthesized Al2O3:Eu3+ nanophosphors depending on synthesis conditions
Authors: Kostyukov A , Nashivochnikov A , Rakhmanova M , Snytnikov V
Published: November 2021

Al2O3:Eu3+ nanophosphors were prepared by laser vaporization method in a flowing mixture of Ar/He and O2. Luminescence properties of Al2O3:Eu3+ nanophosphors are predominantly determined by Eu3+ ions red emission with inhomogeneously broadened bands in the region of 550-750 nm corresponding to 5D0 →7FJ transitions of Eu3+ (J = 0 - 4). Hypersensitive electric dipole transition 5D0 →7F2 dominates in the spectrum and is responsible for the red emission. The effect of crystallite size on luminescence properties of Al2O3:Eu3+ nanocrystals was observed. It was shown that the introduction of oxygen during the synthesis improves the luminescence performance. The obtained chromaticity coordinates and high absolute QY (~ 14%) indicate the possibility of using red nanophosphors based on Al2O3:Eu3+.
High-Efficiency Mini-Slab Laser Based on Tm-doped Double Tungstate Crystal
Authors: Vatnik S M , Vedin I A , Kolker M D , Pavlyuk A A
Published: November 2021

We report on highly-efficient room-temperature lasing in 5at.%Tm:KLu(WO4)2 mini-slabs side-pumped by a 35W diode bar. QCW (duty cycle ∼ 14%) output power of 1.47 W at 1908 nm has been demonstrated with optical and slope efficiencies being of 33 and 43% respectively. In our experiments, we used samples of active elements produced in the slabs form with Brewster’s angle cut faces and original laser cavity design.
Fluorescence quantum efficiency of Ti3+:Al2O3 at cryogenic temperatures and excitation by laser diodes
Authors: Gribanov A , Nikolaev G , Mosin M , Yakovin D , Yakovin M
Published: November 2021

In this work the temperature dependences of the fluorescence of a titanium-sapphire crystal excited by radiation with λ=507 nm, λ=454 nm and λ=405 nm are measured. The quantum efficiency of fluorescence is determined. It was found for the first time that the quantum efficiency of fluorescence exceeds 100% in the cryogenic temperature range when the crystal is excited by radiation with λ = 454 nm. It is equal to (117 ± 5) % and (114 ± 5) % at T = 77 K for crystals grown by the Czochralski method and by gradient of temperature one, respectively.
Millimetre-wave range optical properties of BIBO
Authors: Nikolaev N A , Mamrashev A A , Antsygin V D , Ezhov D M , Lubenko D M , Svetlichnyi V A , Andreev Yu M , Losev V F
Published: November 2021

We present the thorough studies of optical properties of BiB3O6 (BIBO) crystal in the millimeter-wave (subterahertz) range. We observe a large birefringence Δn = nZ -nX = 1.5 and the values of absorption coefficients of all three axes to be less than 0.5 cm−1 at the frequency of 0.3 THz. The difference from visible range in angle ϕ between the dielectric axis z and crystallophysical axis X is found to be more than 6°. The simulated phase-matching curves in the xz plane of the crystal show the optimal value of the angle θ to be around 25.5°±1° for an efficient millimeter-wave generation under the pump of 1064 nm laser radiation.
Coexistence of light-induced thermocapillary and orientational effects in thin nematic films with a free surface
Authors: Shvetsov S.A. , Zolot’ko A.S. , Voronin G.A. , Emelyanenko A.V. , Statsenko P.A. , Trashkeev S.I.
Published: November 2021

The effect of nonlinear light action on a thin (∼10 µm) films of the nematic liquid crystal deposited onto the absorbing substrate is experimentally investigated. The dynamics of the orientational and thermocapillary effects is directly studied. The two types of orientational processes were found out. The first one appears for several hundreds of milliseconds when the light beam irradiation is turned on or off. The second one develops much slowly and does not relax during the light beam irradiation.
Laboratory modeling of a field-aligned currents system generated by a flow of inner magnetospheric plasma
Authors: Chibranov A , Berezutsky A , Efimov M , Zakharov Y , Miroshnichenko I , Posukh V , Rumenskikh M , Trushin P , Shaikhislamov I
Published: November 2021

For the first time in laboratory conditions, an experiment to simulate a system of field-aligned currents arising on planets such as Hot Jupiters in the presence of dense inner-magnetospheric plasma was carried out. The magnitude and transit time of field-aligned currents were measured as a function of the magnetic field using flat electrodes. The geometry of the expansion of plasma streams was pictured by gated camera. Also, in a first approximation, the efficiency of energy transfer from plasma flows to field-aligned currents was calculated. The results obtained create a basis for future laboratory experiments on this topic and improve existing numerical models.
Nonparametric Estimation of Multivariate Extreme Value Copulas with Known and Unknown Marginal Distributions
Authors: Samia Ayari , Boutahar Mohamed
Published: November 2021

The purpose of this paper is estimating the dependence function of multivariate extreme values copulas. Different nonparametric estimators are developed in the literature assuming that marginal distributions are known. However, this assumption is unrealistic in practice. To overcome the drawbacks of these estimators, we substituted the extreme value marginal distribution by the empirical distribution function. Monte Carlo experiments are carried out to compare the performance of the Pickands, Deheuvels, Hall-Tajvidi, Zhang and Gudendorf-Segers estimators. Empirical results showed that the empirical distribution function improved the estimators’ performance for different sample sizes.
Location Planning of Field Ammunition Depot for Multi-stage Supply Based on Dijstra Algorithm
Authors: Shi Xianming , Liu Haobang , Li Yuan , Zhu Bo , Liang Junpeng
Published: November 2021

The location of field ammunition depots is related to the efficiency and effectiveness of ammunition supply and support, and is affected by the changing needs of different stages of operations. In response to complex situations such as damage to transportation roads, repairs, and dynamic changes in demand in the course of combat, the fastest supply speed is the primary goal, while the satisfaction rate, balance, and cost factors of the ammunition supply at each demand point are taken into account to build a multi-stage supply Site selection planning model for field ammunition depot. Use Dijstra algorithm’s hierarchical sequence method to determine the shortest supply time, gradually increase the supply time, find the relationship between supply time, satisfaction rate, balance and cost, and find a satisfactory location plan. Finally, the simulation case calculations show that the model can cover some key dynamic changes during wartime, with strong adaptability and more scientific site selection.
Evaluations of An Algorithm for Large Multivariate Optimization
Authors: Tenne Yoel
Published: November 2021

Many simulation-driven engineering and scientific problems require finding an optimum of a function with many variables. Such settings pose a challenge for standard algorithms due to the large search space which in turn can lead to poor final results. Therefore this paper proposes a new simplified approach in which the dimension of the problem is dynamically reduced during the search to formulate a problem of lower size (dimension) which is easier to solve. A main novelty of the algorithm is its simplicity. Numerical experiments show the potential of this approach.
Modelling of Traffic Flows and Supply Chains Based on Geospatial Knowledge
Authors: Kolesnikov A , Kikin P , Panidi E
Published: November 2021

The field of logistics and transport operates with large amounts of data. The transformation of such arrays into knowledge and processing using machine learning methods will help to find additional reserves for optimizing transport and logistics processes and supply chains. This article analyses the possibilities and prospects for the application of machine learning and geospatial knowledge in the field of logistics and transport using specific examples. The long-term impact of geospatial-based artificial intelligence systems on such processes as procurement, delivery, inventory management, maintenance, customer interaction is considered.
Modeling of Integrated Spectral Energy Distributions of Stellar Populations with Various Binary Fractions
Authors: Li Zhongmu , Yan Chen
Published: November 2021

Binary stars are common in the universe, but binary fractions are various in different star clusters and galaxies. Studies have shown that binary fraction affects the integrated spectral energy distributions obviously, in particular in the UV band. It affects spectral fitting of many star clusters and galaxies significantly. However, previous works usually take a fixed binary fraction, i.e., 0.5, and this is far from getting accurate results. Therefore, it is important to model the integrated spectral energy distributions of stellar populations with various binary fractions. This work presents a modeling of spectral energy distributions of simple stellar populations with binary fractions of 0.3, 0.7, and 1.0. The results are useful for different kinds of spectral studies.
Simulation of Formation of Binary Compact Objects in Globular Cluster
Authors: Deng Yangyang , Li Zhongmu , Chen Wen
Published: November 2021

Binary compact objects are the special binary systems, which were composed of compact objects (i.e., white dwarf, neutron star and black hole). They contribute a lot to the sources of gravitational waves. The study of binary compact objects in star clusters and galaxies can provide a theoretical guidance for gravitational wave detection and improve the probability of detection effectively. We simulate the formation and fraction of binary compact objects in a small globular cluster, via NBODY6++GPU, an efficient N-body simulation code. We obtain the fractions of white dwarf binaries and neutron star binaries at different ages. The results show that the dynamic interactions among stars can also result in some binary compact objects besides binary evolution.
Modeling Prediction and Research on Leaf Moisturizing Effect of Tobacco Redrying
Authors: Li Keqiang , Li Ruidong , Huang Wenyong , Yang Zehui , Zhang Xiaobing , Liu Jianguo
Published: November 2021

This paper studies the influence of the process parameter setting of the hot-air leaf moisturizer on the quality index of the exit leaf during the secondary leaf conditioning of threshing and redrying, and establishes the corresponding prediction model. According to the characteristics of the characteristic process data of the secondary moisturizing, the prediction models of BP neural network and cyclic neural network are established. Call the current popular neural network writing framework TensorFlow’s high-level API interface to build the neural network structure. Gradually optimize the activation function, optimizer, number of hidden layer neurons and other key parameters in the neural network structure to make the prediction results of the test set reach the best state. By inputting the parameters of the front steam nozzle pressure, the front-end water flow rate, the hot air temperature, the return air temperature, the temperature of the feed blade, and the water combination of the feed blade, two key tobacco leaf evaluation indicators are predicted for the outlet leaf moisture and temperature. Based on the mean square error, root mean square error, and average absolute error of the prediction results as quantitative indicators, the three indicators of BP neural network are 7.17, 2.68, 1.83, and the three indicators of cyclic neural network are 4.70, 2.16, 1.74. It is concluded that the cyclic neural network has the best prediction effect. It has certain reference value for the tobacco factory to adjust the process parameters of the secondary leaf conditioning according to different conditions.
Injectable polyelectrolyte complex-nascent HAP biodegradable antibiotic delivery system for the treatment of osteomyelitis
Authors: George Liz Hannah , Arakkal Aswin , Sreedharan Prathapan , Sailaja G S
Published: November 2021

An injectable osteoconductive polyelectrolyte complex (PEC)–hydroxyapatite (HAP) formulation capable of controlled delivery of ciprofloxacin has been developed from a novel biodegradable PEC and antibiotic loaded nascent hydroxyapatite (n-HAP) for the treatment of osteomyelitis. A single source (chitosan) derived polyelectrolytes were complexed in situ in the presence of n-HAP, pre-loaded with ciprofloxacin. The PEC-(n-HAP) nanoformulation (HPEC) was characterized by FT-IR, XRD, TGA and TEM analyses. HPEC combines functionalities of n-HAP (crystallinity and osteoconductivity) as well as PEC (biodegradable hydrophilic electrostatically bound macromolecular network) imparting better control over swelling and degradation kinetics favourable for drug release and transport of micronutrients. MTT assay and cytoskeleton staining (MG-63 cells) established cytocompatibility of HPEC. Early biomimetic mineralization of apatite was manifested under simulated physiological condition with a Ca/P of 1.23 (day 3) and 1.55 (day 6) complimented by in vitro biomineralization of MG-63 and human osteosarcoma (HOS) cells in a week (Alizarin Red S staining), which was further validated by calcium quantification. Antibacterial efficacy of HPEC has been evaluated by delivery kinetics of ciprofloxacin and by disc diffusion method against S. aureus and E. coli. The injectable system therefore possesses unique combination of functionalities: osteoconduction enriched with early biomineralization, antibacterial activity and is biodegradable; hence highly suitable for osteomyelitis treatment.
Added value of high-resolution climate projections over South Korea on the scaling of precipitation with temperature
Authors: Qiu Liying , Im Eun-Soon
Published: November 2021

This study evaluates the resolution dependency of scaling precipitation with temperature from the perspective of the added value of high-resolution (5 km) dynamical downscaling using various kinds of long-term climate change projections over South Korea. Three Coupled Model Intercomparison Project Phase 5 (global climate models (GCMs) with different climate sensitivities, and one pseudo global warming (PGW) experiment, are downscaled by Weather Research and Forecasting one-way double nested modeling system with convective parameterization for the reference (1976–2005) and future (2071–2100) periods under RCP8.5 scenario. A detailed comparison of the driving GCM/PGW, 20 km mother simulation, and 5 km nested simulation demonstrates improved representation of precipitation with increasing resolution not only in the spatial pattern and magnitude for both the mean and the extremes, but also in a more realistic representation of extreme precipitation’s sensitivities to temperature. According to the projected precipitation changes downscaled from both GCM ensemble and PGW, there will be intensified precipitation, particularly for the extremes, over South Korea under the warming, which is primarily contributed by convective precipitation increase that shows higher temperature sensitivity. This study also compares the extreme precipitation-temperature scaling relations within-epoch (apparent scaling) and between-epoch (climate scaling). It confirms that the magnitude and spatial pattern of the two scaling rates can be quite different, and the precipitation change over Korea under global warming is mainly controlled by thermodynamic factors.
Construction of genuinely entangled subspaces and the associated bounds on entanglement measures for mixed states
Authors: Antipin K V
Published: November 2021

Genuine entanglement is the strongest form of multipartite entanglement. Genuinely entangled pure states contain entanglement in every bipartition and as such can be regarded as a valuable resource in the protocols of quantum information processing. A recent direction of research is the construction of genuinely entangled subspaces (GESs)—the class of subspaces consisting entirely of genuinely entangled pure states. In this paper we present methods of construction of such subspaces including those of maximal possible dimension. The approach is based on the composition of bipartite entangled subspaces and quantum channels of certain types. The examples include maximal subspaces for systems of three qubits, four qubits, three qutrits. We also provide lower bounds on two entanglement measures for mixed states, the concurrence and the convex-roof extended negativity, which are directly connected with the projection on GESs.
Deep multi-task mining Calabi–Yau four-folds
Authors: Erbin Harold , Finotello Riccardo , Schneider Robin , Tamaazousti Mohamed
Published: November 2021

We continue earlier efforts in computing the dimensions of tangent space cohomologies of Calabi–Yau manifolds using deep learning. In this paper, we consider the dataset of all Calabi–Yau four-folds constructed as complete intersections in products of projective spaces. Employing neural networks inspired by state-of-the-art computer vision architectures, we improve earlier benchmarks and demonstrate that all four non-trivial Hodge numbers can be learned at the same time using a multi-task architecture. With 30% (80%) training ratio, we reach an accuracy of 100% for

h

(
1
,
1
)

and 97% for

h

(
2
,
1
)

(100% for both), 81% (96%) for

h

(
3
,
1
)

, and 49% (83%) for

h

(
2
,
2
)

. Assuming that the Euler number is known, as it is easy to compute, and taking into account the linear constraint arising from index computations, we get 100% total accuracy.
Prevalence, management and outcomes of unrecognized delirium in a National Sample of 1,493 older emergency department patients: how many were sent home and what happened to them?
Authors: Lee Jacques S , Tong Tiffany , Chignell Mark , Tierney Mary C , Goldstein Judah , Eagles Debra , Perry Jeffrey J , McRae Andrew , Lang Eddy , Hefferon Darren , Rose Louise , Kiss Alex , Borgundvaag Bjug , McLeod Shelley , Melady Don , Boucher Valérie , Sirois Marie-Josée , Émond Marcel
Published: November 2021

Background

Retrospective studies estimate Emergency Department (ED) delirium recognition at <20%; few prospective studies have assessed delirium recognition and outcomes for patients with unrecognized delirium.

Objectives

To prospectively measure delirium recognition by ED nurses and physicians, document their confidence in diagnosis and disposition, actual dispositions, and patient outcomes.

Methods

Prospective observational study of people ≥65 years. We assessed delirium using the Confusion Assessment Method, then asked ED staff if the patient had delirium, confidence in their assessment, if the patient could be discharged, and contacted patients 1 week postdischarge. We report proportions and 95% confidence intervals (Cls).

Results

We enrolled 1,493 participants; mean age was 77.9 years; 49.2% were female, 79 (5.3%, 95% CI 4.2–6.5%) had delirium. ED nurses missed delirium in 43/78 cases (55.1%, 95% CI 43.4–66.4%). Nurses considered 12/43 (27.9%) patients with unrecognized delirium safe to discharge. Median confidence in their delirium diagnosis for patients with unrecognized delirium was 7.0/10. Physicians missed delirium in 10/20 (50.0%, 95% CI 27.2–72.8) cases and considered 2/10 (20.0%) safe to discharge. Median confidence in their delirium diagnosis for patients with unrecognized delirium was 8.0/10. Fifteen patients with unrecognized delirium were sent home: 6.7% died at 1 week follow-up vs. none in those with recognized delirium and 1.1% in the rest of the cohort.

Conclusion

Delirium recognition by nurses and physicians was sub-optimal at ~50% and may be associated with increased mortality. Research should explore root causes of unrecognized delirium, and novel strategies to systematically improve delirium recognition and patient outcomes.
Time Preference for Immediate Gratification: Associations With Low Medication Adherence and Uncontrolled Blood Pressure
Authors: Krousel-Wood Marie , Peacock Erin , Bradford W David , Mohundro Brice , Craig Leslie S , O’Connell Samantha , Bazzano Lydia , Shi Lizheng , Ford Milam
Published: November 2021

Background

In search of innovative approaches to the challenge of uncontrolled hypertension, we assessed the association between preference for immediate gratification (i.e., high discounting rate), low medication adherence, and uncontrolled blood pressure (BP) in adults with hypertension.

Methods

Using a probability discounting model and the Collier–Williams hypothetical discount rate framework, participants in this cross-sectional study reported their preference for a smaller amount of money available immediately (high discount rate; immediate gratification preference) vs. a larger amount available 1 year later (low discount rate; delayed gratification preference). Multivariable Poisson regression was used to test the association of high discounting rates with low antihypertensive medication adherence using the validated 4-item Krousel-Wood Medication Adherence Scale (K-Wood-MAS-4 score ≥1). Mediation of the association between high discounting rate and uncontrolled BP (systolic/diastolic BP ≥ 130/80 mm Hg) by low adherence was tested using the counterfactual approach.

Results

Among 235 participants (mean age 63.7 ± 6.7 years; 51.1% women; 41.9% Black), 50.6% had a high 1-year discount rate, 51.9% had low K-Wood-MAS-4 adherence, and 59.6% had uncontrolled BP. High discounting rates were associated with low adherence (adjusted prevalence ratio 1.58, 95% confidence interval (CI) 1.18, 2.12). Forty-three percent (95% CI 40.9%, 45.8%) of the total effect of high discount rate on uncontrolled BP was mediated by low adherence.

Conclusions

Adults with preference for immediate gratification had worse adherence; low adherence partially mediated the association of high discount rate with uncontrolled BP. These results support preference for immediate gratification as an innovative factor underlying low medication adherence and uncontrolled BP.
Biosimilar strategic implementation at a large health system
Authors: Kar Indrani , Kronz Margaret , Kolychev Evelina , Silverman Paula , Mendiratta Prateek , Tomlinson Benjamin K N , Prunty Jeremy , Copley Melissa , Patel Seema , Caudill Sara , Farah Lisa , Wesolowski Bryan , Crissinger Tyler , Kendig Colin , Szymczak Eric , Duraj Lindsey , Dumot John , Acheson Emily , Lyamkin Svetlana , King Michelle , Mocilnikar Allyson , Cunningham Kevin , Paulic Nikola , Botzki Uwe , Lerman Rachael , Strosaker Robyn , Osborne Shawn , Glotzbecker Brett
Published: November 2021

Purpose

This article highlights one health system’s response to the market influx of biosimilars with the establishment of a process for formulary review and selection of preferred agents and support for therapeutic interchanges.

Through assessment of available literature, insurance payor coverage, and manufacturer-anticipated approvals of biosimilars, a strategic stance was developed to guide biosimilar order preparation, review, adoption, and implementation. The electronic medical record (EMR) is prepared for biosimilar implementation at least 6 to 12 months ahead of anticipated formulary review. The review includes assessment of a class (reference product and available biosimilars) after at least 2 biosimilars become available. Key health-system departments and clinicians are enlisted to support review of clinical, safety, and economic implications. Implementation of a preferred product relies on standard education, formulary availability, and staff awareness to address any perceived patient safety concerns and gather provider support. The standard steps developed now apply to all future biosimilar reviews, adoption plans, and ongoing monitoring. Barriers evaluated include changes in payor coverage and challenges in preparation of the EMR for future biosimilars, meeting precertification team education needs, and providing operational support for pharmacy inventory.

Conclusion

To date, use of 5 preferred biosimilar products has led to significant cost savings to the institution, and the process has been endorsed by providers. The institution’s successes can be attributed to clear communication with stakeholders and the development of a deliberate process, led by a multidisciplinary leadership team, for managing formulary, safety, and operational barriers in a thoughtful and systematic manner.
nextNEOpi: a comprehensive pipeline for computational neoantigen prediction
Authors: Rieder Dietmar , Fotakis Georgios , Ausserhofer Markus , René Geyeregger , Paster Wolfgang , Trajanoski Zlatko , Finotello Francesca
Published: November 2021

Somatic mutations and gene fusions can produce immunogenic neoantigens mediating anticancer immune responses. However, their computational prediction from sequencing data requires complex computational workflows to identify tumor-specific aberrations, derive the resulting peptides, infer patients’ Human Leukocyte Antigen types and predict neoepitopes binding to them, together with a set of features underlying their immunogenicity. Here, we present nextNEOpi (nextflow NEOantigen prediction pipeline) a comprehensive and fully automated bioinformatic pipeline to predict tumor neoantigens from raw DNA and RNA sequencing data. In addition, nextNEOpi quantifies neoepitope- and patient-specific features associated with tumor immunogenicity and response to immunotherapy.

Availability and implementation

nextNEOpi source code and documentation are available at https://github.com/icbi-lab/nextNEOpi

Contact

dietmar.rieder@i-med.ac.at or francesca.finotello@uibk.ac.at

Supplementary information

Supplementary data are available at Bioinformatics online.
A2Sign: Agnostic Algorithms for Signatures—a universal method for identifying molecular signatures from transcriptomic datasets prior to cell-type deconvolution
Authors: Boldina Galina , Fogel Paul , Rocher Corinne , Bettembourg Charles , Luta George , Augé Franck
Published: November 2021

Motivation

Molecular signatures are critical for inferring the proportions of cell types from bulk transcriptomics data. However, the identification of these signatures is based on a methodology that relies on prior biological knowledge of the cell types being studied. When working with less known biological material, a data-driven approach is required to uncover the underlying classes and generate ad hoc signatures from healthy or pathogenic tissue.

Results

We present a new approach, A2Sign: Agnostic Algorithms for Signatures, based on a non-negative tensor factorization (NTF) strategy that allows us to identify cell-type-specific molecular signatures, greatly reduce collinearities and also account for inter-individual variability. We propose a global framework that can be applied to uncover molecular signatures for cell-type deconvolution in arbitrary tissues using bulk transcriptome data. We also present two new molecular signatures for deconvolution of up to 16 immune cell types using microarray or RNA-seq data.

Availability and implementation

All steps of our analysis were implemented in annotated Python notebooks (https://github.com/paulfogel/A2SIGN). To perform NTF, we used the NMTF package, which can be downloaded using Python pip install.

Supplementary information

Supplementary data are available at Bioinformatics online.
Scientists from Minority-Serving Institutions and Their Participation in Grant Peer Review
Authors: Gallo Stephen A , Sullivan Joanne H , Croslan DaJoie R
Published: November 2021

Funding disparities currently exist across racial groups for grant applicants and between minority-serving institutions (MSIs) and traditionally White institutions (TWIs), with implicit bias in grant review a likely source of these differences. A survey examining grant review participation was disseminated to thousands of MSI-based scientists, and their responses were compared with those in a previous study of predominantly TWI-based scientists. Despite similar levels of grant submission, only 45% of the MSI-based scientists had recently participated in grant review, which is much lower than the rate reported in the previous study. MSI-based scientists indicated not being invited and a general lack of time (largely because of teaching and service responsibilities) as barriers. Nevertheless, the majority of the MSI-based respondents were interested in reviewing and in training in grant reviewing. These results serve as a call to action for research funders to increase both invitations to review and training opportunities for MSI-based scientists.
Healthy, happy places—a more integrated approach to creating health and well-being through the built environment?
Authors: Turnbull Rachel
Published: November 2021

Introduction

This paper explores how the built environment impacts upon health and well-being and suggests that there are opportunities for more integrated working between professionals and citizens to create healthier, happier places.

Sources of data

Policy and practice guidance is presented from the urban planning and design fields. Evidence and data are presented from a range of disciplines on housing, green infrastructure and mental well-being.

Areas of agreement

There is an overwhelming agreement around the principles and rationale of incorporating health in planning and design processes.

Areas of controversy

These principles are not always implemented in practice. Challenges also exist around how different disciplines create and use evidence.

Growing points

More innovative ways of working which incorporates health, public health, planners, designers and citizens, which responds to the needs of communities, should be tested.

Areas timely for developing research

Health and public health professionals can contribute to the evidence base using objective measures to assess the impact of the built environment on mental health and well-being.
Improving Bitcoin Transaction Propagation Efficiency through Local Clique Network
Authors: Yan Kailun , Zhang Jilian , Wu Yongdong
Published: November 2021

Bitcoin is a popular decentralized cryptocurrency, and the Bitcoin network is essentially an unstructured peer-to-peer (P2P) network that can synchronize distributed database of replicated ledgers through message broadcasting. In the Bitcoin network, the average clustering coefficient of nodes is very high, resulting in low message propagation efficiency. In addition, average node degree in the Bitcoin network is also considerably large, causing high message redundancy when nodes use the gossip protocol to broadcast messages. These may affect message propagation speed, hindering Bitcoin from being applied to scenarios of high transactional throughputs. To illustrate, we have collected single-hop propagation data of transactions of 366 blocks from Bitcoin Core. The analysis results show that transaction verification and network delay are two major causes of low transaction propagation efficiency. In this paper, we propose a novel P2P network structure, called local clique network (LCN), for message broadcasting in the Bitcoin network. Specifically, to reduce transaction validation latency and message redundancy, in LCN local nodes (logically) form cliques, and only a few nodes in a clique broadcast messages to the other cliques, instead of each node sending messages to its neighboring nodes. We have conducted extensive experiments, and the results show that message redundancy is low in LCN, and message propagation speed increases significantly. Meanwhile, LCN exhibits excellent robustness when average node degree remains high in the Bitcoin network.
Prototheca-ID: a web-based application for molecular identification of Prototheca species
Authors: Dziurzyński Mikołaj , Decewicz Przemyslaw , Iskra Mateusz , Bakuła Zofia , Jagielski Tomasz
Published: November 2021

The genus Prototheca houses unicellular, achlorophyllous, yeast-like algae, widely distributed in the environment. Protothecae are the only known plants that have repeatedly been reported to infect vertebrates, including humans. Although rare, protothecosis can be clinically demanding, with an unpredictable and treatment-resistant behavior. Accurate identification of Prototheca species relies upon DNA sequence-based typing of the mitochondrially encoded CYTB gene. However, no bioinformatic tool for the processing and analyzing of protothecal sequence data exists. Moreover, currently available sequence databases suffer from a limited number of records and lack of or flawed sequence annotations, making Prototheca identification challenging and often inconclusive. This report introduces the Prototheca-ID, a user-friendly, web-based application providing fast and reliable speciation of Prototheca isolates. In addition, the application offers the users the possibility of depositing their sequences and associated metadata in a fully open Prototheca-ID database, developed to enhance research integrity and quality in the field of Protothecae and protothecosis.

Database URL: The Prototheca-ID application is available at https://prototheca-id.org
Cardiac magnetic resonance imaging improves prognostic stratification of patients with ST-elevation myocardial infarction and preserved ejection fraction
Authors: Reindl Martin , Stiermaier Thomas , Lechner Ivan , Tiller Christina , Holzknecht Magdalena , Mayr Agnes , Schwaiger Johannes P , Brenner Christoph , Klug Gert , Bauer Axel , Thiele Holger , Feistritzer Hans-Josef , Metzler Bernhard , Eitel Ingo , Reinstadler Sebastian J
Published: November 2021

Aims

To evaluate the prognostic validity of clinical risk factors as well as infarct characterization and myocardial deformation by cardiac magnetic resonance (CMR) in ST-elevation myocardial infarction (STEMI) patients with preserved left ventricular ejection fraction (LVEF) following primary percutaneous coronary intervention (PCI).

Methods and results

This multicentre, individual patient-data analysis from two large CMR trials included 1247 STEMI patients. Cardiac magnetic resonance examinations were conducted 3 [interquartile range (IQR) 2–4] days after PCI. LVEF, infarct size, microvascular obstruction (MVO), and myocardial strain values were measured. Primary endpoint was defined as composite of major adverse cardiovascular events (MACE) including death, re-infarction, and congestive heart failure. A preserved LVEF (defined as LVEF ≥50%) was observed in 724 patients (=58%). In the overall cohort, 97 patients experienced a MACE event [follow-up time 12 (IQR 12–13) months], and 34 MACE events occurred in the group with preserved LVEF (5% vs. 12% incidence rate in patients with LVEF < 50%). TIMI risk score [hazard ratio (HR) 1.28, 95% confidence interval (CI) 1.02–1.59; P = 0.03] and female gender (HR 2.24, 95% CI 1.10–4.57; P = 0.03) emerged as independent clinical determinants of MACE in the patient group with preserved LVEF. Among CMR parameters, the presence of MVO (HR 2.39, 95% CI 1.05–5.46; P = 0.04) and reduced global longitudinal strain (GLS; HR 1.12, 95% CI 1.02–1.23; P = 0.02) independently predicted MACE in the LVEF-preserved population. The addition of MVO and GLS to the clinical prognostic markers (TIMI risk score, female gender) increased (P = 0.02) the prognostic validity [AUC 0.76 (95% CI 0.73–0.79)] compared to the clinical markers alone [AUC 0.65 (0.62–0.69)].

Conclusion

In contemporary treated STEMI patients showing preserved LVEF, a CMR-based risk prediction approach assessing MVO and GLS provided strong prognostic value that was incremental to clinical outcome parameters.
The value of perioperative biomarker release for the assessment of myocardial injury or infarction in cardiac surgery
Authors: Schneider Ulrich , Mukharyamov Murat , Beyersdorf Friedhelm , Dewald Oliver , Liebold Andreas , Gaudino Mario , Fremes Stephen , Doenst Torsten
Published: November 2021

OBJECTIVES

Cardiac biomarkers are indicators of irreversible cell damage. Current myocardial infarction (MI) definitions require concomitant clinical characteristics. For perioperative MI, a correlation of biomarker elevations and mortality has been suggested. Definitions emerged relying on cardiac biomarker release only. This approach is questionable as several clinical and experimental scenarios exist where relevant biomarker release can occur apart from MI.

METHODS

We reviewed the clinical and basic science literature and revealed important aspects regarding the use and interpretation of cardiac biomarker release with special focus on their interpretation in the perioperative setting.

RESULTS

Ischaemic biomarkers may be released without cell death in multiple conditions, such as after endurance runs in athletes, temporary inotropic stimulation in animal models and flow variations in in vitro cell models. In addition, access through atrial tissue during cannulation or concomitant valve procedures adds sources of enzyme release that may not be related to ventricular ischaemia (i.e. MI). Such non-cell death-related mechanisms may explain the lack of poor correlations of enzyme release and long-term outcomes in recent trials. In addition, the 3 main biomarkers, troponin T, I and creatine kinase myocardial band, differ in their release kinetics, which may differentially trigger MI events in trial patients.

CONCLUSIONS

The identification of irreversible myocardial injury in cardiac surgery based only on biomarker release is unreliable. Cell death- and non-cell death-related mechanisms create a mix in the perioperative setting that requires additional markers for proper identification of MI. In addition, the 3 most common ischaemic biomarkers display different release kinetics adding to the confusion. We review the topic.
Discerning Josquin
Authors: Milsom John
Published: November 2021

This study describes and evaluates some newly identified polyphonic phenomena in Josquin’s most securely attributed works for five and six voices. By examining some characteristic touches of Josquin’s hand, it aims to shed new light on the later style of this celebrated yet enigmatic composer, and contributes to the debate about what makes Josquin sound like Josquin. Specifically, it looks at how Josquin sometimes interlocked passages of canon and stretto fuga against bass motion along the chain of 5ths, and then evolved this aspect of craft to the point where it contributes to the perceived tonality, modality and form of individual works. Extracts from nine pieces by Josquin are examined: five motets, three chansons, and the Credo of the Missa De beata virgine. Closest attention is paid to passages from Pater noster, Nimphes napées, Preter rerum seriem, Douleur me bat and Plaine de deuil.
Domains of spirituality and their importance to the health of 75 533 adolescents in 12 countries
Authors: Michaelson V , Šmigelskas K , King N , Inchley J , Malinowska-Cieślik M , Pickett W ,   for the HBSC Spiritual Health Writing Group, Michaelson V , Pickett W , Trothen T , Davison C , Kalman M , Jirásek I , Brooks F , Walsh S , Harel-Fisch Y , Smigelskas K , Pudule I , Gobina I , Mazur J , Malinowska-Cieslik M , Lesco G , Matochkina A , Inchley J , Whitehead R , Kolarcik P , Roberts C
Published: November 2021

Spirituality is an ancient concept with many contemporary applications to the field of health promotion. While recognized in the UN Convention on the Rights of the Child as a basic human right, definitional misunderstandings about what spirituality is, and is not, and the mechanisms by which it affects the health of young people, remain. In this cross-national analysis involving >75 000 adolescents from 12 countries, we examined the relative importance of each of four spiritual health domains (connections to self, others, nature and the transcendent) in the lives of young people, and how these connections relate to a standard indicator of positive mental health status. Descriptive and applied regression analyses confirmed two major findings: (i) boys and girls in all 12 countries ranked the importance of each of the four domains in the same order, with ‘connections to self’ identified as most important; and (ii) both direct and indirect pathways are evident that connect the remaining three domains to positive mental health status, but through strong connections to self. Based on our scale items, fostering a strong connection to self, which involves cultivating a sense of meaning, purpose and joy in the lives of adolescents, appears most fundamental to fostering optimal mental health. This may be achieved directly or, dependent upon context and culture, indirectly with emphasis on the connections afforded by the other three domains. Such findings provide important insights to guide the content of adolescent health promotion interventions.
Automatic discard registration in cluttered environments using deep learning and object tracking: class imbalance, occlusion, and a comparison to human review
Authors: van Essen Rick , Mencarelli Angelo , van Helmond Aloysius , Nguyen Linh , Batsleer Jurgen , Poos Jan-Jaap , Kootstra Gert
Published: November 2021

This paper presents and evaluates a method for detecting and counting demersal fish species in complex, cluttered, and occluded environments that can be installed on the conveyor belts of fishing vessels. Fishes on the conveyor belt were recorded using a colour camera and were detected using a deep neural network. To improve the detection, synthetic data were generated for rare fish species. The fishes were tracked over the consecutive images using a multi-object tracking algorithm, and based on multiple observations, the fish species was determined. The effect of the synthetic data, the amount of occlusion, and the observed dorsal or ventral fish side were investigated and a comparison with human electronic monitoring (EM) review was made. Using the presented method, a weighted counting error of 20% was achieved, compared to a counting error of 7% for human EM review on the same recordings.