bluuebunny/crossref_metadata_2025 huggingface dataset:
Insights Into Ferroptosis: Targeting Glycolysis to Treat Graves’ Orbitopathy
Authors: Ma Ruiqi , Gan Lu , Guo Jie , Peng Zhiyu , Wu Jihong , Harrison Andrew R , Qian Jiang
Published: March 2022

Context

Oxidative stress plays an indispensable role in pathogenesis of Graves’ orbitopathy (GO). Ferroptosis is a newly discovered form of cell death resulting from lipid peroxidation. Little is known about the role of ferroptosis in GO.

Objective

We aimed to identify the divergent role of ferroptosis in the GO and control orbital fibroblasts (OFs).

Methods

Orbital fat/connective tissues and serum immunoglobulins (Igs) were collected from GO and control subjects. Cell viability and lipid peroxidation were measured to evaluate ferroptosis sensitivity. Pyruvate dehydrogenase kinase 2 (PDK2) level and oxygen consumption rate were quantified to assess glycolysis status.

Results

Primary OFs were cultured from orbital tissues. Ferroptosis was induced by cystine deprivation and/or erastin treatment. The GO OFs possessed stronger resistance to ferroptosis than the control OFs. Selenium, a potential ferroptosis inhibitor, protected the control OFs from ferroptosis. Both transcriptomic and proteomic analyses indicated glycolytic shift in the GO OFs. Metabolic profiling, PDK2 quantification, and oxygen consumption assay confirmed enhanced glycolysis in the GO OFs. Inhibition of glycolysis by PDK2 knockdown and dichloroacetic acid (DCA) promoted ferroptosis sensitivity in the GO OFs. The ferroptosis-sensitizing effects of DCA were also observed when the GO OFs were treated with GO-Igs. IGF1R overexpression in the GO OFs contributed to glycolysis shift. IGF1R inhibitory antibodies facilitated ferroptosis induction in the GO OFs, but the effects were less remarkable under GO-Igs treatment.

Conclusion

These study findings establish that glycolysis facilitates ferroptosis resistance in the GO OFs, providing insights into the therapeutic role of glycolysis for GO treatment.
The Rhetorics of Plot Function: Henry James's ficelle, Vladimir Nabokov's “Perry,” and James Phelan's “Synthetic Function” Reconsidered
Authors: Mikkonen Kai
Published: March 2022

This article discusses the literary character's plot function as an element of the author's rhetorical strategy, and in relation to the reader's active role in responding to that strategy. The main focus will be on characterological instances in narrative fiction that facilitate the development of the novel's plot by way of the character's movement, perspective, or moving perspective. These considerations will be brought to bear on James Phelan's rhetorical approach to the fictional character's basic functions, also known as the mimetic-thematic-synthetic model (MTS model). More precisely, this article will look harder at Phelan's so-called synthetic component of character, that is, those aspects that foreground the character as a construct (rather than as a possible person or a theme), to argue that much more work can be done with this category. In the course of this discussion, Henry James's notion of a ficelle and Vladimir Nabokov's term perry will serve as complementary ideas and as a counterpoint to Phelan's synthetic component. Hence this article will ask: how can we (re)integrate the plot-helper function into the rhetorical character theory?
A network of transcription factors governs the dynamics of NODAL/Activin transcriptional responses
Authors: Coda Davide M. , Patel Harshil , Gori Ilaria , Gaarenstroom Tessa E. , Song Ok-Ryul , Howell Michael , Hill Caroline S.
Published: March 2022

SMAD2, an effector of the NODAL/Activin signalling pathway, regulates developmental processes by sensing distinct chromatin states and interacting with different transcriptional partners. However, the network of factors that controls SMAD2 chromatin binding and shapes its transcriptional programme over time is poorly characterised. Here, we combine ATAC-seq with computational footprinting to identify temporal changes in chromatin accessibility and transcription factor activity upon NODAL/Activin signalling. We show that SMAD2 binding induces chromatin opening genome wide. We discover footprints for FOXI3, FOXO3 and ZIC3 at the SMAD2-bound enhancers of the early response genes, Pmepa1 and Wnt3, respectively, and demonstrate their functionality. Finally, we determine a mechanism by which NODAL/Activin signalling induces delayed gene expression, by uncovering a self-enabling transcriptional cascade whereby activated SMADs, together with ZIC3, induce the expression of Wnt3. The resultant activated WNT pathway then acts together with the NODAL/Activin pathway to regulate expression of delayed target genes in prolonged NODAL/Activin signalling conditions.

This article has an associated First Person interview with the first author of the paper.
Context-dependent relationships between swimming, terrestrial jumping, and body composition in the amphibious fish Kryptolebias marmoratus
Authors: Turko Andy J. , Rossi Giulia S. , Blewett Tamzin A. , Currie Suzanne , Taylor D. Scott , Wright Patricia A. , Standen Emily M.
Published: March 2022

Understanding the mechanisms that create phenotypic variation within and among populations is a major goal of physiological ecology. Variation may be a consequence of functional trade-offs (i.e. improvement in one trait comes at the expense of another trait) or alternatively may reflect the intrinsic quality of an organism (i.e. some individuals are simply better overall performers than others). There is evidence for both ideas in the literature, suggesting that environmental context may mediate whether variation results from trade-offs or differences in individual quality. We tested this overarching “context-dependence” hypothesis by comparing the aquatic and terrestrial athletic performance of the amphibious fish Kryptolebias marmoratus captured from two contrasting habitats, a large pond and small burrows. Overall, pond fish were superior terrestrial athletes but burrow fish were better burst swimmers, suggestive of a performance trade-off at the population level. Within each population, however, there was no evidence of a performance trade-off. In burrow fish, athletic performance was positively correlated with muscle content and body condition, consistent with the individual quality hypothesis. In pond fish, there was only a relationship between glycolytic white muscle and aquatic burst performance. Notably, pond fish were in better body condition, which may mask relationships between condition and athletic performance. Overall, our data highlight that population-level trends are insufficient evidence for the existence of phenotypic trade-offs in the absence of similar within-population patterns. Furthermore, we only found evidence for the individual quality hypothesis in one population, suggesting that patterns of phenotypic covariance are context dependent.
Analysis of Bi-Isotropic Media using Hybrid Boundary Element Method
Authors: Peric Mirjana T. , Ilić Saša S. , Vučković Ana N. , Raičević Nebojša B.
Published: March 2022

This paper proposes the application of the hybrid boundary element method (HBEM) for analysis of bi-isotropic media of Tellegen type. In previous applications of this method it was possible to analyze only the electromagnetic problems in isotropic media. The main contribution of this paper is the modification of the method itself, in order to solve a large scale of quasi-static TEM problems in bi-isotropic media. Detailed theoretical analysis and HBEM procedure are described and applied. Characteristic parameters of a microstrip line with bi-isotropic substrate are analyzed. Obtained results have been compared with available numerical and software simulation results. A close results match can be noticed.
Research on EBE-FEM Parallel Algorithm Combined with Fast Color Marking Method Based on CUDA Platform
Authors: Yan Xiuke , Ren Xvdong , Lan Jinpeng , Ren Ziyan , Zhang Yanli
Published: March 2022

The element-by-element finite element method (EBE-FEM) parallel algorithm has been realized on Compute Unified Device Architecture (CUDA) platform in this paper. An improved fast color marking method (FCM) combined with tabu search algorithm is proposed to solve the problem that the elements sharing a node wait for accessing the same memory space in parallel computation. The elements in the same color can be processed at the same time without waiting. This method can get more even color grouping faster than the classical coloring method (CCM).  Combining it with the EBE parallel algorithm can achieve faster element-level operations. The validity and accuracy of the method has been verified by comparing the computed results with the analytical solution of the magnetic field produced by the solenoid. The parallel program is applied to analyze the main magnetic field of a single-phase transformer, which shows higher speedup performance.
Possible Leaky Wave Antennas for Propagation Therapy using SAR Analysis
Authors: Sarabi Masoud , Perger Warren F.
Published: March 2022

This paper presents an overview of design and functionality of three novel leaky wave antennas (LWAs) that are proposed as a possible hyperthermia system using LWA logic. LWAs are best known for their interesting property of frequency scanning. This makes them appealing for beam steering applications such as biomedical hyperthermia and radar applications. Regarding the biomedical hyperthermia application, the property of beam scanning could be used for treatment of tumors found in different regions and depths of a given tissue. The proposed antennas are as follows: (1) mushroom-typed leaky wave antenna, (2) two-dimensionally (2D) periodically slotted leaky wave antenna, (3) belt-shaped leaky wave antenna. Each antenna provides distinguished advantages for hyperthermia therapy which will be discussed in the corresponding sections. For example, the belt-shaped leaky wave antenna is a conformal antenna that could follow the cylindrical shape of the patient’s neck and focus the electromagnetic beam on the neck tumors. Two-dimensional LWAs such as mushroom-typed leaky wave antennas provide more beam steering flexibility compared to 1D types such as 1D slotted leaky wave antennas.
T-Junction Power Divider Based on Rectangular Microcoaxial Structure in W-band
Authors: Huang Zhao-Yu , Liu Bo-Yuan , Jiang Yun , Yuan Wen-Tao , Wang Qing-Ping , Hu Wei-Dong , Yuan Nai-Chang
Published: March 2022

In this paper, a W-band T-junction power divider based on rectangular microcoaxial structure is proposed. Rectangular microcoaxial line is a three dimensional (3D) structure with the merits of wide operation bandwidth, low loss and high integration, which is suitable for the design of radio frequency (RF) devices. A two-way power divider is designed based on the rectangular microcoaxial structure. And the two-way power divider is expanded into a four-way power divider to further illustrate the design method. Moreover, a back-to-back configuration including two identical two-way power divider is fabricated and measured. The insertion loss of the back-to-back configuration is about 0.11-1.18 dB in W band, which agrees with the simulation one reasonably and shows good performance.
New Approximate Expressions for Evaluating the Fields of a Vertical Magnetic Dipole in a Dissipative Half Space
Authors: Deng Hongyun , Xiao Gaobiao , Huang Shifeng
Published: March 2022

In this paper, a set of new asymptotic approximate expressions for evaluating the electromagnetic (EM) fields generated by a vertical magnetic dipole placed in a dissipative half space is proposed. The lateral wave that guarantees the continuity of the EM fields at the interface is discussed in detail. Using the spectral method, the integral expressions of the field components are obtained. The dominant part is extracted from the lateral wave for large radial distance so that all field components in this situation can be approximately expressed with explicit expressions, which makes the method efficient. Besides, the proposed method has no restriction condition on the parameter choices of different half spaces, so it can be applied in more general situations. Some calculation results and comparisons are given to validate the effectiveness of this extraction method.
Electromagnetic–AI-Based Design Optimization of SynRM Drives
Authors: Arkadan A.A. , Aawar N. Al
Published: March 2022

Characterization modules in electric machines and drives design optimization environments typically involve the use of electromagnetic finite element-state space models that require large number of iterations and computational time. It is shown in this work that the utilization of a Taguchi orthogonal arrays method in conjunction with a particle swarm optimization (PSO), search algorithm in a design optimization case study of a synchronous reluctance motor (SynRM) drive, resulted in about 80% reduction of computational time.
Triangular Ring Patch Antenna Analysis: Neuro-Fuzzy Model for Estimating of the Operating Frequency
Authors: Kayabasi Ahmet
Published: March 2022

In this study, a neuro-fuzzy (NF) analysis method is suggested for the estimation of the operating frequency of triangular ring patch antennas (TRPAs) that operate at ultra high band applications. Although the analysis of regular-shaped patch antennas (PAs) such as rectangular, triangle, and circle is easy, analysis of irregularly shaped patch antennas is difficult and time consuming. Here, this great effort and time has been eliminated by using an artificial intelligence technique such as NF. To create a data set for NF, 100 TRPAs with different physical and electrical properties (L, l, h, and εεrr) are simulated by using an electromagnetic simulator program. The currency and accuracy of the proposed approach is then confirmed on the measurement results of a prototype TRPA fabricated in this study. The results of NF model are compared with the simulation/measurement results and previously the method published in the literature.
Comparative Study on Improved and Traditional Equivalent Circuit of Long Primary Double-Sided Linear Induction Motor
Authors: Zhang Qian , Liu Hui-juan , Zhang Zhen-yang , Song Teng-fei , Wang Yu
Published: March 2022

Based on the quasi-two-dimensional (2D) field model of long primary double-sided linear induction motor (LPDLIM), an improved equivalent circuit model is proposed. First, the traditional equivalent circuit of LPDLIM is reviewed. Second, the skin effect correction coefficients for the secondary equivalent resistance and excitation reactance, and the secondary leakage inductance are derived. Moreover, an improved equivalent circuit model for LPDLIMs is presented, in which the leakage reactance of the secondary is considered, and the excitation reactance and secondary resistance are modified by the correction coefficients independently. Then, the slip frequency characteristics of various effect forces and variations of forces under different operations and mechanical air gap width are presented. Finally, the calculated forces by the proposed equivalent circuit are validated by the finite element method results and also compared with that of the traditional equivalent circuit model.
Convergence Acceleration of Infinite Series Involving the Product of Riccati–Bessel Function and Its Application for the Electromagnetic Field: Using the Continued Fraction Expansion Method
Authors: Fanghua Zheng , Qingyun Di , Zhe Yun , Ya Gao
Published: March 2022

A summation technique has been developed based on the continuous fractional expansion to accelerate the convergence of infinite series involving the product of Riccati–Bessel functions, which are common to electromagnetic applications. The series is transformed into a new and faster convergent sequence with a continued fraction form, and then the continued fraction approximation is used to accelerate the calculation. The well-known addition theorem formula for spherical wave function is used to verify the correctness of the algorithm. Then, some fundamental aspects of the practical application of continuous fractional expansion for Mie scattering theory and electromagnetic exploration are considered. The results of different models show that this new technique can be applied reliably, especially in the electromagnetic field excited by the vertical electric dipole (VED) source in the “earth-ionospheric” cavity. The comparison among the new technology, the Watson-transform, and the spherical harmonic series summation algorithm shows that this new technology only needs less than 120 series items which is already enough to obtain a small relative error, which greatly improves the convergence speed, and provides a new way to solve the problem.
Design of Planar Directional Coupler using 2-Bit Fragment Structures
Authors: Tao Yonghui , Zhang Wenjuan , Sidén Johan , Wang Gang
Published: March 2022

Automatic design of planar directional coupler can be implemented by multi-objective optimization searching for the optimal planar fragment-type structure (FTS). The 2-bit FTS description scheme may include necessary fine structures in fragments to enhance the FTS design. By coding the coupler design space on PCB in 2-bit FTS, defining the FTS design matrix, and searching for the optimal structure, directional coupler can be designed without any structure presetting or artificial intervention. The scheme is demonstrated by designing 10-dB wideband directional coupler with 2-bit FTS scheme. The designed directional couplers are fabricated and tested to show maximum directivity of 58 dB with 36% operation bandwidth.
Resonant absorption of electromagnetic waves by an induced inhomogeneity in a liquid metamaterial
Authors: Zharov Alexander , Fierro Vanessa , Celzard Alain
Published: March 2022

In this study, we consider the scattering of a plane electromagnetic wave on a cylindrically inhomogeneous distribution of meta-atoms in a liquid metamaterial. The distribution inhomogeneity appears naturally as a result of the application of an electric potential to an electrode immersed in the liquid metamaterial, which leads to the appearance of inhomogeneity in the effective permittivity of such a medium. Consequently, in the considered type of metamaterial, the concentration-dependent effective permittivity can become negative in some region of space. In the vicinity of the interface between positive and negative permittivity, the behavior of the electromagnetic wave becomes singular, giving rise to effects such as resonant absorption, resonant scattering, and shielding of the central region. These effects can be controlled in real time by changing the applied electric potential and thus rearranging the liquid metamaterial.
SESAM mode-locked Yb:Sr3Y2(BO3)4 laser
Authors: Sun Shijia , Zeng Huang-Jun , Lin Zhang-Lang , Xue Wen-Ze , Zhang Ge , Lin Zhoubin , Petrov Valentin , Lin Haifeng , Loiko Pavel , Mateos Xavier , Zhao Yongguang , Teng Bing , Wang Li , Chen Weidong
Published: March 2022

We demonstrate the first sub-40 fs soliton pulse generation from a diode-pumped Yb:Sr3Y2(BO3)4 laser passively mode-locked by a semiconductor saturable absorber mirror. Pulses as short as 38 fs at a central wavelength of 1051.7 nm were achieved with an average output power of 115 mW and a pulse repetition rate of 67.7 MHz. The maximum average output power reached 303 mW at 1057.8 nm with a slightly longer pulse duration of 52 fs, which corresponded to a peak power of 76.9 kW and an optical efficiency of 25.3%.
Phase noise estimation based white light scanning interferometry for high-accuracy surface profiling
Authors: Ma Long , Zhao Yuan , Pei Xin , Liu Yu-zhe , Sun Feng-ming , Wu Sen
Published: March 2022

White light scanning interferometry (WLSI) has been an extremely powerful technique in precision measurements. In this work, a phase noise estimation based surface recovery algorithm is proposed, which can significantly improve the measurement accuracy by decreasing the noise level in phase map coming from the systemic and environmental disturbances. The noise existed in phase map is firstly researched in spectrum domain and defined as the linear combination of complex terms at each angular wavenumber. Afterwards, based on the theoretical linearity of the phase distribution, the surface features can be redefined through establishing the function with respect to phase noise. By applying least square estimation (LSE), a spectral coefficient is defined to determine the optimal estimation of phase noise that represents the best statistical consistency with the actual case, from which a more accurate surface after removing most phase noise will then be generated. In order to testify the noise elimination ability of the proposed method, a nano-scale step height standard (9.5nm±1.0nm) is scanned, and the measurement result 9.49nm with repeatability 0.17nm is successfully achieved. Moreover, a leading edge of an aero-engine blade is also tested to investigate the potential of this method in industrial inspections. The measurement comparison with AFM is also displayed.
Coaxial illumination module of the stimulated-emission-depletion nanoscope
Authors: Shi Jintao , Yu Jianqiang , Tian Zhan , Kou Xiaolong , Yang Hongwei , Liu Xiaolong , Yuan Jinghe , Fang Xiaohong
Published: March 2022

Stimulated-emission-depletion (STED) nanoscope achieves super-resolution imaging by using a donut-shaped depletion beam to darken the fluorophores around the excitation spot. As an important factor determining the resolution of imaging, the coaxiality between the excitation and the depletion beam is required to be maintained at the nanoscale, which is often degraded by various interference such as ambient vibration and temperatures etc. Here, we propose a specially designed STED illumination module to guarantee the coaxiality between the two beams while modulating the phase of the depletion beam. This STED illumination module can realize phase modulation, polarization adjustment, pulse delay and two beams coaxial at the same time. With the experiments, the module can guarantee the two beams are stably coaxial for a long time. We imaged fluorescence particles with diameter 40 nm and got images of 40 nm full width at half maximum. Adjacent microfilaments at 80 nm being clearly distinguished with our STED nonoscope demonstrates that it could be well applied to biological samples.
Diode-pumped SESAM mode-locked Yb:(Y,Gd)AlO3 laser
Authors: Xue Wen-Ze , Lin Zhang-Lang , Zeng Huang-Jun , Zhang Ge , Zhang Peixiong , Chen Zhenqiang , Li Zhen , Petrov Valentin , Loiko Pavel , Mateos Xavier , Lin Haifeng , Zhao Yongguang , Wang Li , Chen Weidong
Published: March 2022

We report on the continuous-wave (CW) and mode-locked (ML) laser performance of an Yb3+-doped yttrium-gadolinium orthoaluminate crystal, Yb:(Y,Gd)AlO3. Pumping by a single-transverse-mode fiber-coupled 976 nm InGaAs laser diode, the maximum output power in the CW regime amounted to 429 mW at 1041.8 nm corresponding to a slope efficiency of 51.1% and a continuous wavelength tuning across 84 nm (1011–1095 nm) was achieved. The self-starting ML operation of the Yb:(Y,Gd)AlO3 laser was stabilized by a semiconductor saturable absorber mirror. Soliton pulses as short as 43 fs were generated at 1052.3 nm with an average output power of 103 mW and a pulse repetition rate of ∼70.8 MHz. To the best of our knowledge, our result represents the first report on the passively mode-locked operation of a Yb:(Y,Gd)AlO3 laser, and the shortest pulse duration ever achieved from any Yb3+-doped orthorhombic perovskite aluminate crystals.
Computational design and optimization of nanostructured AlN deep-UV grating reflectors
Authors: Shapturenka Pavel , Devata Abhiram , DenBaars Steven P. , Nakamura Shuji , Gordon Michael J.
Published: March 2022

Deep-ultraviolet (DUV) optoelectronics require innovative light collimation and extraction schemes for wall-plug efficiency improvements. In this work, we computationally survey material limitations and opportunities for intense, wavelength-tunable DUV reflection using AlN-based periodic hole and pillar arrays. Refractive-index limitations for underlayer materials supporting reflection were identified, and MgF2 was chosen as a suitable low-index underlayer for further study. Optical resonances giving rise to intense reflection were then analyzed in AlN/MgF2 nanostructures by varying film thickness, duty cycle, and illumination incidence angle, and were categorized by the emergence of Fano modes sustained by guided mode resonances (holes) or Mie-like dipole resonances (pillars). The phase-offset conditions between complementary modes that sustain high reflectance (%R) were related to a thickness-to-pitch ratio (TPR) parameter, which depended on the geometry-specific resonant mechanism involved (e.g., guided mode vs. Mie dipole resonances) and yielded nearly wavelength-invariant behavior. A rational design space was constructed by pointwise TPR optimization for the entire DUV range (200-320 nm). As a proof of concept, this optimized phase space was used to design reflectors for key DUV wavelengths and achieved corresponding maximum %R of 85% at λ = 211 nm to >97% at λ = 320 nm.
Microwave-photonics iterative nonlinear gain model for optoelectronic oscillators
Authors: Xiao Ye , Dai Yitang , Shi Nuannuan , Li Wei , Zhu Ninghua , Li Ming
Published: March 2022

The nonlinear dynamic behavior of optoelectronic oscillators (OEOs), which is important for the OEO based applications, is investigated in detail by a Microwave-photonics Iterative Nonlinear Gain (MING) model in this paper. We connect the oscillating processes with the trajectories of an iterated map based on a determined nonlinear mapping relation referred to as open-loop input to output amplitude mapping relation (IOAM). The results show that the envelope dynamic is determined by the slope of IOAM at a special point called fixed point. Linear features dominate the loop if the slope is relatively large, and the nonlinear features emerge and become increasingly significant with the decreasing of the slope. Linear features of homogeneity and monotonicity are gradually lost. Furthermore, OEO is even unstable when the slope is less than a general threshold value of −1. The behavior of OEO loops with the different slope values are discussed by simulations and are experimentally confirmed. Moreover, the proposed model also applies to the OEO with an externally injected microwave signal, the bifurcation phenomena caused by injected signal are experimentally evidenced.
Flat optical phased array receiver incorporating an on-chip metalens concentrator
Authors: Im Chul-Soon , Lee Woo-Bin , Gwon Ji-Yeong , Lee Sang-Shin
Published: March 2022

We propose and design a flat optical phased array (OPA) receiver that consists of a grating antenna, a free-propagation region (FPR) incorporating an on-chip metalens concentrator (OCMC), and an output port of a tapered waveguide. By concatenating the OCMC-integrated FPR with the antenna, the proposed OPA allows light coupled at a slanted ψ angle to be conveyed to the output, thereby resolving the challenges of phase-controlled light detection. To impose a space-dependent phase on the incident light from the antenna, the OCMC is constructed by laterally arranging subwavelength slot meta-atoms with varying slot lengths, which are created in the core layer of a slab and uniformly quantized at 16 phase levels. Hence, without the aid of phase modulators, the light beam emerging from the grating antenna can be focused on the output port through angle-tolerant coupling along the lateral direction. The miniaturized OCMC was confirmed to play a pivotal role in achieving enhanced in-plane coupling efficiency over the field of view.
Periodic synchronisation of dengue epidemics in Thailand over the last 5 decades driven by temperature and immunity
Authors: García-Carreras Bernardo , Yang Bingyi , Grabowski Mary K. , Sheppard Lawrence W. , Huang Angkana T. , Salje Henrik , Clapham Hannah Eleanor , Iamsirithaworn Sopon , Doung-Ngern Pawinee , Lessler Justin , Cummings Derek A. T.
Published: March 2022

The spatial distribution of dengue and its vectors (spp.Aedes) may be the widest it has ever been, and projections suggest that climate change may allow the expansion to continue. However, less work has been done to understand how climate variability and change affects dengue in regions where the pathogen is already endemic. In these areas, the waxing and waning of immunity has a large impact on temporal dynamics of cases of dengue haemorrhagic fever. Here, we use 51 years of data across 72 provinces and characterise spatiotemporal patterns of dengue in Thailand, where dengue has caused almost 1.5 million cases over the last 30 years, and examine the roles played by temperature and dynamics of immunity in giving rise to those patterns. We find that timescales of multiannual oscillations in dengue vary in space and time and uncover an interesting spatial phenomenon: Thailand has experienced multiple, periodic synchronisation events. We show that although patterns in synchrony of dengue are similar to those observed in temperature, the relationship between the two is most consistent during synchronous periods, while during asynchronous periods, temperature plays a less prominent role. With simulations from temperature-driven models, we explore how dynamics of immunity interact with temperature to produce the observed patterns in synchrony. The simulations produced patterns in synchrony that were similar to observations, supporting an important role of immunity. We demonstrate that multiannual oscillations produced by immunity can lead to asynchronous dynamics and that synchrony in temperature can then synchronise these dengue dynamics. At higher mean temperatures, immune dynamics can be more predominant, and dengue dynamics more insensitive to multiannual fluctuations in temperature, suggesting that with rising mean temperatures, dengue dynamics may become increasingly asynchronous. These findings can help underpin predictions of disease patterns as global temperatures rise.
Quantitative input–output dynamics of a c-di-GMP signal transduction cascade in Vibrio cholerae
Authors: Bridges Andrew A. , Prentice Jojo A. , Fei Chenyi , Wingreen Ned S. , Bassler Bonnie L.
Published: March 2022

Bacterial biofilms are multicellular communities that collectively overcome environmental threats and clinical treatments. To regulate the biofilm lifecycle, bacteria commonly transduce sensory information via the second messenger molecule cyclic diguanylate (c-di-GMP). Using experimental and modeling approaches, we quantitatively capture c-di-GMP signal transmission via the bifunctional polyamine receptor NspS-MbaA, from ligand binding to output, in the pathogen Vibrio cholerae. Upon binding of norspermidine or spermidine, NspS-MbaA synthesizes or degrades c-di-GMP, respectively, which, in turn, drives alterations specifically to biofilm gene expression. A long-standing question is how output specificity is achieved via c-di-GMP, a diffusible molecule that regulates dozens of effectors. We show that NspS-MbaA signals locally to specific effectors, sensitizing V. cholerae to polyamines. However, local signaling is not required for specificity, as changes to global cytoplasmic c-di-GMP levels can selectively regulate biofilm genes. This work establishes the input–output dynamics underlying c-di-GMP signaling, which could be useful for developing bacterial manipulation strategies.
Parameter inference for stochastic biochemical models from perturbation experiments parallelised at the single cell level
Authors: Davidović Anđela , Chait Remy , Batt Gregory , Ruess Jakob
Published: March 2022

Understanding and characterising biochemical processes inside single cells requires experimental platforms that allow one to perturb and observe the dynamics of such processes as well as computational methods to build and parameterise models from the collected data. Recent progress with experimental platforms and optogenetics has made it possible to expose each cell in an experiment to an individualised input and automatically record cellular responses over days with fine time resolution. However, methods to infer parameters of stochastic kinetic models from single-cell longitudinal data have generally been developed under the assumption that experimental data is sparse and that responses of cells to at most a few different input perturbations can be observed. Here, we investigate and compare different approaches for calculating parameter likelihoods of single-cell longitudinal data based on approximations of the chemical master equation (CME) with a particular focus on coupling the linear noise approximation (LNA) or moment closure methods to a Kalman filter. We show that, as long as cells are measured sufficiently frequently, coupling the LNA to a Kalman filter allows one to accurately approximate likelihoods and to infer model parameters from data even in cases where the LNA provides poor approximations of the CME. Furthermore, the computational cost of filtering-based iterative likelihood evaluation scales advantageously in the number of measurement times and different input perturbations and is thus ideally suited for data obtained from modern experimental platforms. To demonstrate the practical usefulness of these results, we perform an experiment in which single cells, equipped with an optogenetic gene expression system, are exposed to various different light-input sequences and measured at several hundred time points and use parameter inference based on iterative likelihood evaluation to parameterise a stochastic model of the system.
Social determinants of the changing tuberculosis prevalence in Việt Nam: Analysis of population-level cross-sectional studies
Authors: Foster Nicola , Nguyen Hai V. , Nguyen Nhung V. , Nguyen Hoa B. , Tiemersma Edine W. , Cobelens Frank G. J. , Quaife Matthew , Houben Rein M. G. J.
Published: March 2022

Background

An ecological relationship between economic development and reduction in tuberculosis prevalence has been observed. Between 2007 and 2017, Việt Nam experienced rapid economic development with equitable distribution of resources and a 37% reduction in tuberculosis prevalence. Analysing consecutive prevalence surveys, we examined how the reduction in tuberculosis (and subclinical tuberculosis) prevalence was concentrated between socioeconomic groups.

Methods and findings

We combined data from 2 nationally representative Việt Nam tuberculosis prevalence surveys with provincial-level measures of poverty. Data from 94,156 (2007) and 61,763 (2017) individuals were included. Of people with microbiologically confirmed tuberculosis, 21.6% (47/218) in 2007 and 29.0% (36/124) in 2017 had subclinical disease. We constructed an asset index using principal component analysis of consumption data. An illness concentration index was estimated to measure socioeconomic position inequality in tuberculosis prevalence. The illness concentration index changed from −0.10 (95% CI −0.08, −0.16; p = 0.003) in 2007 to 0.07 (95% CI 0.06, 0.18; p = 0.158) in 2017, indicating that tuberculosis was concentrated among the poorest households in 2007, with a shift towards more equal distribution between rich and poor households in 2017. This finding was similar for subclinical tuberculosis. We fitted multilevel models to investigate relationships between change in tuberculosis prevalence, individual risks, household socioeconomic position, and neighbourhood poverty. Controlling for provincial poverty level reduced the difference in prevalence, suggesting that changes in neighbourhood poverty contribute to the explanation of change in tuberculosis prevalence. A limitation of our study is that while tuberculosis prevalence surveys are valuable for understanding socioeconomic differences in tuberculosis prevalence in countries, given that tuberculosis is a relatively rare disease in the population studied, there is limited power to explore socioeconomic drivers. However, combining repeated cross-sectional surveys with provincial deprivation estimates during a period of remarkable economic growth provides valuable insights into the dynamics of the relationship between tuberculosis and economic development in Việt Nam.

Conclusions

We found that with equitable economic growth and a reduction in tuberculosis burden, tuberculosis became less concentrated among the poor in Việt Nam.
Analysis of accumulated SARS-CoV-2 seroconversion in North Carolina: The COVID-19 Community Research Partnership
Authors: Williamson John C. , Wierzba Thomas F. , Santacatterina Michele , Munawar Iqra , Seals Austin L. , Pittman Ballard Christine Ann , Alexander-Miller Martha , Runyon Michael S. , McCurdy Lewis H. , Gibbs Michael A. , Ahmed Amina , Lagarde William H. , Maguire Patrick D. , King-Thiele Robin , Hamrick Terri , Ihmeidan Abdalla , Henderson Shakira , Gallaher T. Ryan , Uschner Diane , Edelstein Sharon L. , Herrington David M. , Sanders John W. ,   on behalf of the North Carolina sites of the COVID-19 Community Research Partnership
Published: March 2022

Introduction

The COVID-19 Community Research Partnership is a population-based longitudinal syndromic and sero-surveillance study. The study includes over 17,000 participants from six healthcare systems in North Carolina who submitted over 49,000 serology results. The purpose of this study is to use these serology data to estimate the cumulative proportion of the North Carolina population that has either been infected with SARS-CoV-2 or developed a measurable humoral response to vaccination.

Methods

Adult community residents were invited to participate in the study between April 2020 and February 2021. Demographic information was collected and daily symptom screen was completed using a secure, HIPAA-compliant, online portal. A portion of participants were mailed kits containing a lateral flow assay to be used in-home to test for presence of anti-SARS-CoV-2 IgM or IgG antibodies. The cumulative proportion of participants who tested positive at least once during the study was estimated. A standard Cox proportional hazards model was constructed to illustrate the probability of seroconversion over time up to December 20, 2020 (before vaccines available). A separate analysis was performed to describe the influence of vaccines through February 15, 2021.

Results

17,688 participants contributed at least one serology result. 68.7% of the population were female, and 72.2% were between 18 and 59 years of age. The average number of serology results submitted per participant was 3.0 (±1.9). By December 20, 2020, the overall probability of seropositivity in the CCRP population was 32.6%. By February 15, 2021 the probability among healthcare workers and non-healthcare workers was 83% and 49%, respectively. An inflection upward in the probability of seropositivity was demonstrated around the end of December, suggesting an influence of vaccinations, especially for healthcare workers. Among healthcare workers, those in the oldest age category (60+ years) were 38% less likely to have seroconverted by February 15, 2021.

Conclusions

Results of this study suggest more North Carolina residents may have been infected with SARS-CoV-2 than the number of documented cases as determined by positive RNA or antigen tests. The influence of vaccinations on seropositivity among North Carolina residents is also demonstrated. Additional research is needed to fully characterize the impact of seropositivity on immunity and the ultimate course of the pandemic.
Promoting mechanism of serum amyloid a family expression in mouse intestinal epithelial cells
Authors: Wakai Masaki , Hayashi Ryohei , Ueno Yoshitaka , Onishi Kana , Takasago Takeshi , Uchida Takuro , Takigawa Hidehiko , Yuge Ryo , Urabe Yuji , Oka Shiro , Kitadai Yasuhiko , Tanaka Shinji
Published: March 2022

Serum amyloid A (SAA) is an acute phase inflammatory protein that we previously described as a robust biomarker of colorectal inflammation in patients with ulcerative colitis (UC) in clinical remission. However, what induces SAA expression in UC remains unclear. This study demonstrates that SAA is significantly expressed in the intestinal tract of UC mouse models when compared with C-reactive protein, another inflammatory biomarker. Moreover, interleukin-6 and tumor necrosis factor-α were found to promote SAA1 expression, as were Toll-like receptor ligands flagellin and lipopolysaccharide. Furthermore, results suggested that the nuclear factor-kappa B (NF-κB) pathway may be involved in the promotion of SAA1 expression by flagellin, which was inhibited by treatment with 5-aminosalicylic acid (5-ASA). Therefore, the flagellin/NF-κB/SAA1 axis may represent one of the mechanisms by which 5-ASA suppresses intestinal inflammation.
Intravenous antibiotics at the index emergency department visit as an independent risk factor for hospital admission at the return visit within 72 hours
Authors: Lin Shao-Yung , Sung Chih-Wei , Huang Edward Pei-Chuan , Chen Chi-Hsin , Fan Cheng-Yi , Lee Hsin-Yu , Huang Chien-Tai , Huang Yu-Sheng , Zhuang Bo-Yu , Liu Cheng-Heng , Chang Jia-How
Published: March 2022

Introduction

Although infection was the most common symptom in patients returning to the ED, whether intravenous antibiotic administration at the index visit could serve as an indicator of patients with infectious diseases at high risk for hospital admission after returning to the ED within a short period of time remains unclear. The study aimed to investigate the potential risk factors for hospital admission in patients returning to the ED within 72 hours with a final diagnosis of infectious diseases.

Material and methods

This retrospective cohort study analyzed return visits to the ED from January to December 2019. Adult patients aged >20 years who had a return visit to the ED within 72 hours with an infectious disease were included herein. In total, 715 eligible patients were classified into the intravenous antibiotics and non-intravenous antibiotics group (reference group). The outcome studied was hospital admission to general ward and intensive care unit (ICU) at the return visits.

Results

Patients receiving intravenous antibiotics at index visits had significantly higher risk—approximately two times—for hospital admission at the return visits than those did not (adjusted odds ratio = 2.47, 95% CI = 1.34–4.57, p = 0.004). For every 10 years increase in age, the likelihood for hospital admission increased by 38%. Other factors included abnormal respiratory rate and high C-reactive protein levels.

Conclusions

Intravenous antibiotic administration at the index visit was an independent risk factor for hospital admission at return visits in patients with an infection disease. Physicians should consider carefully before discharging patients receiving intravenous antibiotics.
Characterization of grazing behaviour microstructure using point-of-view cameras
Authors: Sales-Baptista Elvira , Ferraz-de-Oliveira Maria Isabel , Terra-Braga Marina , de Castro José António Lopes , Serrano João , d’Abreu Manuel Cancela
Published: March 2022

Grazing patterns, intake structure, and diet selection are dynamic responses to animals’ feeding environment. This study uses video sequences from animal-borne cameras to capture time- and scale-dependent grazing behaviour variables related to sward explanatory conditions. We observed grazing ‘through’ the sheep’s eyes using point-of-view (POV) cameras coupled with event logging software. Time-specific sward features were measured by sampling ‘really’ grazed patches identified by applying a global navigation satellite system (GNSS) precision-grazing approach. Sward variables on a Mediterranean native sward were measured for two years during the active spring plant-growth cycle. Overall, the results demonstrate that POV cameras were able to capture grazing behaviour fine-tuning to changes in sward characteristics. Sheep compensate for the decrease in sward quantity and nutritive value by increasing the size and duration at each behavioural scale (i.e., meal, bout, and station) while increasing the bout rate and decreasing the station rate. Diet composition also changed as sward matured. The proportion of forbs in the diet remained high in early and late spring, and forbs and legumes were preferred to grasses in early spring. Grazing selectivity was more pronounced in late spring, with sheep favouring the middle stratum of the sward’s vertical structure, preferring green vegetative material, while enlarging the feeding niches’ span and spending more time at each niche, consequently reducing the station rate. Although data collected by individual animal-borne POV cameras were representative of the flock behaviour, they may underestimate the total grazing time outside major meals. The results indicate that the use of animal-borne video cameras is suitable for assessing variations in sheep grazing behaviour patterns in complex swards.
Cross-cultural adaptation and measurement properties of the Malay Shoulder Pain and Disability Index
Authors: Ho Caryn-Ann , Yun Ling Jerri Chiu , Abdul Karim Samihah
Published: March 2022

Objective

The purpose of this study is to cross-culturally adapt the Shoulder Pain and Disability Index from English to Malay, and to evaluate the measurement properties of the Malay version among Malay speakers with shoulder pain.

Methods

Cross-cultural adaptation of the Malay version of Shoulder Pain and Disability Index (M-SPADI) was conducted according to international guidelines. 260 participants (Shoulder pain = 130, No shoulder pain = 130) completed the M-SPADI, the Numerical Rating Scale (NRS), and measurement of shoulder active range of motion (AROM). 54 participants repeated M-SPADI within a mean of 9.2 days.

Results

Cross-cultural adaptation of M-SPADI had no major issues. The M-SPADI had good face validity; item and scale content validity indexes (I-CVI, S-CVI) were >0.79 except for Disability Item 3 (I-CVI = 0.75), and exploratory factor analysis showed that M-SPADI had a bidimensional structure. There was a strong positive correlation between M-SPADI and NRS (rPain = 0.845, rDisability = 0.722, rTotal = 0.795, p <0.001) and a negative correlation between M-SPADI and shoulder AROM with the following correlation ranges (rPain = -0.316 to -0.637, rDisability = -0.419 to -0.708, rTotal = -0404 to -0.697, p<0.001). M-SPADI’s total score was higher in participants with shoulder pain (Mdn: 33.8, IQR = 37.3) compared to no shoulder pain (Mdn:0, IQR = 0.8) and the difference was statistically significant (U = 238.5, z = -13.89, p<0.001). M-SPADI had no floor or ceiling effects (floor/ceiling <15%), high internal consistency (Cronbach’s αPain = 0.914, Cronbach’s αDisability = 0.945) and good to excellent test-retest reliability (ICCPain = 0.922, ICCDisability = 0.859, ICCTotal = 0.895).

Conclusion

M-SPADI has a bi-dimensional structure with no floor or ceiling effects, established face, content and construct validity, internal consistency, and test-retest reliability. M-SPADI is a reliable and valid tool for assessing Malay-speaking individuals with shoulder pain in clinical and research settings.