bluuebunny/crossref_metadata_2025 huggingface dataset:
Osteoprotegerin/Receptor Activator of Nuclear Factor-Kappa B Ligand/Receptor Activator of Nuclear Factor-Kappa B Axis in Obesity, Type 2 Diabetes Mellitus, and Nonalcoholic Fatty Liver Disease
Authors: Vachliotis Ilias D. , Polyzos Stergios A.
Published: May 2023

Purpose of Review

To summarize evidence on the potential involvement of the osteoprotegerin (OPG)/receptor activator of nuclear factor-kappa B (NF-κΒ) ligand (RANKL)/receptor activator of NF-κΒ (RANK) axis in the pathogenesis of metabolic diseases.

Recent Findings

The OPG-RANKL-RANK axis, which has been originally involved in bone remodeling and osteoporosis, is now recognized as a potential contributor in the pathogenesis of obesity and its associated comorbidities, i.e., type 2 diabetes mellitus and nonalcoholic fatty liver disease. Besides bone, OPG and RANKL are also produced in adipose tissue and may be involved in the inflammatory process associated with obesity. Metabolically healthy obesity has been associated with lower circulating OPG concentrations, possibly representing a counteracting mechanism, while elevated serum OPG levels may reflect an increased risk of metabolic dysfunction or cardiovascular disease. OPG and RANKL have been also proposed as potential regulators of glucose metabolism and are potentially involved in the pathogenesis of type 2 diabetes mellitus. In clinical terms, type 2 diabetes mellitus has been consistently associated with increased serum OPG concentrations. With regard to nonalcoholic fatty liver disease, experimental data suggest a potential contribution of OPG and RANKL in hepatic steatosis, inflammation, and fibrosis; however, most clinical studies showed reduction in serum concentrations of OPG and RANKL.

Summary

The emerging contribution of the OPG-RANKL-RANK axis to the pathogenesis of obesity and its associated comorbidities warrants further investigation by mechanistic studies and may have potential diagnostic and therapeutic implications.
Assessing Student Engagement in Collaborative Learning: Development and Validation of New Measure in China
Authors: Xu Bing , Stephens Jason M. , Lee Kerry
Published: May 2023

Collaborative learning (CL) is widely used in higher education around the world because it is associated with increases in students’ knowledge and social skills. Low student engagement in CL activities has been identified as a common issue, while there is no CL-specific engagement scale to measure and understand engagement in such settings. Additionally, although western countries have been investigating student engagement since the 1950s, there have been comparatively few studies of this important construct in China. To address these imbalances, the present paper adopted a mixed methods approach to developing and validating a Chinese CL engagement scale. In the quantitative study, Chinese university students (N = 405) completed an anonymous online survey to assess their engagement in CL activities. Results from exploratory and confirmatory factor analyses supported a hierarchical (second-order) three-factor model of student engagement (behavioural, cognitive and emotional engagement), consistent with the tripartite conception of student engagement in Western countries. Participants were further divided into three unique groups based on engagement scores, and in the qualitative study, 12 participants from three groups were interviewed about CL experiences. Interviews served to further validate the quantitative results. The significance, limitations, and implications of these findings are discussed.
Yang–Mills-scalar-matter fields in the quantum Hopf fibration
Authors: Moncada Gustavo Amilcar Saldaña
Published: May 2023

In this paper we present solutions to the non-commutative geometrical version of the Yang–Mills-scalar-matter theory in the Hopf fibration $$S^1\hookrightarrow S^3\rightarrow S^2$$

S
1

↪

S
3

→

S
2

using the 3D-calculus.
Is it only about technology? The interplay between educational technology for mathematics homework, teaching practice, and students’ activities
Authors: Radović Slaviša
Published: May 2023

Current research on the use of digital technology in education has overgrown. It is becoming clear that technology will not unfold its pedagogical potential outlined in the literature on its own. To harness its full benefits, it is paramount to thoroughly understand the educational context and underlying pedagogical principles. This research reports how an educational technology can support students’ knowledge development from homework mathematics learning practices for 11 to 14 year-old students. The article describes the shift learning goals from producing the correct answer to understanding how to address current and future mathematical challenges as an important interaction between educational technology, teaching practices and student learning activities. The study revealed specific features of technology integration with mathematics teaching and learning practices. The findings highlighted the effectiveness of digital support for homework activities, indicating that there were benefits only when students and teachers used the full range of features and engaged in the process. Finally, the report provides practical tips and ground rules that can contribute to the successful implementation of educational technology for homework activities.
I Wear a Fitbit™; Therefore, I Am a Bitfit: Exploring the Impact of a Fitbit™ Device on Exercise and Work-Related Wellbeing
Authors: Lasikiewicz Nicola , Scudds Annie
Published: May 2023

Workplace wellbeing initiatives supporting mental health often utilise wearable activity trackers to promote physical activity. However, evidence regarding their efficacy is limited. The current study explored the potential for a Fitbit™ to increase engagement in exercise and to moderate the effect of exercise on work-related wellbeing in full-time workers. Participants recorded their work-related wellbeing and physical activity for two consecutive weeks, one wearing a Fitbit™. Results indicated that participants engaged in fewer minutes of exercise when wearing a Fitbit™, and that exercise alone was not associated with better work-related wellbeing. Participants were more frustrated when they exercised but were not wearing a Fitbit™. Participants also reported greater temporal demand when wearing a Fitbit™, which was exacerbated when not engaging in exercise. However, Fitbit™ wear was also associated with greater work-related satisfaction, regardless of whether they had engaged in exercise that day. Our findings imply that wearing a Fitbit™ can moderate the impact of exercise on work-related wellbeing, suggesting that it is not the activity tracker or exercise alone, but the interaction between the two which is key. The potential for wearable trackers to be effective in improving health and wellbeing is more complex than previously anticipated and warrants further investigation.
Cadmium Reduction in Spring Wheat: Root Exudate Composition Affects Cd Partitioning Between Roots and Shoots
Authors: Affholder M. C. , Moazzami A. A. , Weih M. , Kirchmann H. , Herrmann A. M.
Published: May 2023

Cadmium (Cd) in cereals is one of the major sources of Cd intake by human diets, and solutions to reduce Cd concentrations in wheat still need to be developed. Plant breeding, by selecting low-Cd varieties, can be an important tool to reduce Cd in crops. Knowing the genotypic variation in Cd accumulation and furthering our understanding of the impact of root exudates composition on Cd accumulation in crops may provide valuable information for plant breeding. In this study, we selected nine spring wheat varieties and analysed the accumulation and distribution of Cd in shoots, roots, root surfaces and kernels in relation to their qualitative and quantitative composition of root exudates, determined by 1H-NMR (Proton Nuclear Magnetic Resonance). Results showed that the Cd concentration in shoots at an early stage could be used as a predictor for Cd concentration in kernels. Total Cd uptake was not correlated to the mobility of Cd in the rhizosphere, but total Cd was negatively correlated to Cd adsorbed at the root surface. Furthermore, (i) exudation of organic acids (primarily succinate and acetate) increased Cd concentration in shoots, and (ii) exudation of nucleosides, DNA (deoxyribonucleic acid) degradation products, increased Cd adsorption at the root surface. Therefore, root exudates composition should be taken into account when selecting for low-Cd wheat traits.
An Analytical Approach for Dispatch Operations of Emergency Medical Services: A Case Study of COVID-19
Authors: Liu Jing , Ouyang Ruilin , Chou Chun-An , Griffin Jacqueline
Published: May 2023

Emergency medical services (EMS) aims to deliver timely ambulatory care to incidents in communities. However, the operations of EMS may contend with suddenly increasing demands resulting from unexpected disasters such as disease outbreaks (e.g., COVID-19) or hurricanes. To this end, it usually requires better strategical decisions to dispatch, allocate, and reallocate EMS resources to meet the demand changes over time in terms of demographic and geographic distribution of incidents. In this study, we focus on the operation of the EMS resources (i.e., ambulance dispatch) in response to a demand disruption amid the COVID-19 pandemic. Specifically, we present a analytical framework to (1) analyze the underlying demographic and geographic patterns of emergency incidents and EMS resources; (2) develop a mathematical programming model to identify potential demand gaps of EMS coverage across different districts; and (3) provide a remedial reallocation solution to the EMS system with the existing ambulance capacity. The proposed method is validated with emergency response incident data in New York City for the first COVID-19 surge from March to April 2020. We found that it takes a long incident response time to scenes which reflects unexpected incident demands during COVID-19 surge. To cover such disruptive demands, ambulances need to be reallocated between service districts while meeting the response time standard. The proposed framework can be potentially applied to similar disruptive scenarios in the future and other operational systems disrupted by other disasters.

Highlights

We propose an analytical framework using optimization modeling and simulation techniques for EMS resource allocation in response to a demand disruption amid the COVID-19 pandemic.

We propose mathematical programming models to identify potential demand gaps of EMS coverage across different districts.

We provide a remedial reallocation solution to the EMS system with the existing ambulance capacity.
Molecular mechanism of ferulic acid and its derivatives in tumor progression
Authors: Bao Xingxun , Li Wei , Jia Ruixue , Meng Dandan , Zhang Hairong , Xia Lei
Published: May 2023

Cancer is a significant disease that poses a major threat to human health. The main therapeutic methods for cancer include traditional surgery, radiotherapy, chemotherapy, and new therapeutic methods such as targeted therapy and immunotherapy, which have been developed rapidly in recent years. Recently, the tumor antitumor effects of the active ingredients of natural plants have attracted extensive attention. Ferulic acid (FA), (3-methoxy-4-hydroxyl cinnamic), with the molecular formula is C10H10O4, is a phenolic organic compound found in ferulic, angelica, jujube kernel, and other Chinese medicinal plants but is also, abundant in rice bran, wheat bran, and other food raw materials. FA has anti-inflammatory, analgesic, anti-radiation, and immune-enhancing effects and also shows anticancer activity, as it can inhibit the occurrence and development of various malignant tumors, such as liver cancer, lung cancer, colon cancer, and breast cancer. FA can cause mitochondrial apoptosis by inducing the generation of intracellular reactive oxygen species (ROS). FA can also interfere with the cell cycle of cancer cells, arrest most cancer cells in G0/G1 phase, and exert an antitumor effect by inducing autophagy; inhibiting cell migration, invasion, and angiogenesis; and synergistically improving the efficacy of chemotherapy drugs and reducing adverse reactions. FA acts on a series of intracellular and extracellular targets and is involved in the regulation of tumor cell signaling pathways, including the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT), B-cell lymphoma-2 (Bcl-2), and tumor protein 53 (P53) pathways and other signaling pathways. In addition, FA derivatives and nanoliposomes, as platforms for drug delivery, have an important regulatory effect on tumor resistance. This paper reviews the effects and mechanisms of antitumor therapies to provide new theoretical support and insight for clinical antitumor therapy.
The language of power and the power of language. Analysis of propaganda’s narrative in Fahrenheit 451
Authors: Forni Lorena
Published: May 2023

Ray Bradbury’s book is a narrative, in a dystopian context, of how the language of power manages to be pervasive, to infiltrate reality, in people’s experiences, in the consciousness of an entire society, so as to powerfully transform the meanings of commonly used words, as well as the normative qualifications of acts and professions. A reflection will be proposed on some “semantic spies” present in Fahrenheit 451, to highlight the centrality of some uses of language, aimed at influencing not only the behaviour of the members but also at modifying some institutions, manipulating rules and procedures, for the benefit of those who social control operates by administering power. The proposed intervention will deal with the specific function of propaganda language. Finally, a reflection on the power of the word will be proposed, as a tool capable of fully understanding the present and allowing all individuals to lay the foundations for new social, legal and political realities for the future.
CYP2C19 Polymorphism in Ischemic Heart Disease Patients Taking Clopidogrel After Percutaneous Coronary Intervention in Egypt
Authors: Shawky Ahmed , Sabit Hussein , Nazih Mahmoud , Baraka Khalid , El-Zawahry Mokhtar
Published: May 2023

Background

Cardiovascular diseases (CVDs) are considered a leading cause of death worldwide. Allelic variation in theCYP2C19gene leads to a dysfunctional enzyme, and patients with this loss-of-function allele will have an impaired clopidogrel metabolism, which eventually results in major adverse cardiovascular events (MACE). Ischemic heart disease patients (n = 102) who underwent percutaneous cardiac intervention (PCI) followed by clopidogrel were enrolled in the present study.

Methods

The genetic variations in theCYP2C19gene were identified using the TaqMan chemistry-based qPCR technique. Patients were followed up for 1 year to monitor MACE, and the correlations between the allelic variations inCYP2C19and MACE were recorded.

Results

During the follow-up, we reported 64 patients without MACE (29 with unstable angina (UA), 8 with myocadiac infarction (MI), 1 patient with non-STEMI, and 1 patient with ischemic dilated cardiomyopathy (IDC)). Genotyping ofCYP2C19in the patients who underwent PCI and were treated with clopidogrel revealed that 50 patients (49%) were normal metabolizers for clopidogrel with genotypeCYP2C19*1/*1and 52 patients (51%) were abnormal metabolizers, with genotypesCYP2C19*1/*2(n = 15),CYP2C19*1/*3(n = 1),CYP2C19*1/*17(n = 35), andCYP2C19*2/*17(n = 1). Demographic data indicated that age and residency were significantly associated with abnormal clopidogrel metabolism. Moreover, diabetes, hypertension, and cigarette smoking were significantly associated with the abnormal metabolism of clopidogrel. These data shed light on the inter-ethnic variation in metabolizing clopidogrel based on theCYP2C19allelic distribution.

Conclusion

This study, along with other studies that address genotype variation of clopidogrel-metabolizing enzymes, might pave the way for further understanding of the pharmacogenetic background of CVD-related drugs.
Distributions of random variables involved in discrete censored δ-shock models
Authors: Chadjiconstantinidis Stathis , Eryilmaz Serkan
Published: May 2023

Suppose that a system is affected by a sequence of random shocks that occur over certain time periods. In this paper we study the discrete censored
$\delta$
-shock model,
$\delta \ge 1$
, for which the system fails whenever no shock occurs within a
$\delta$
-length time period from the last shock, by supposing that the interarrival times between consecutive shocks are described by a first-order Markov chain (as well as under the binomial shock process, i.e., when the interarrival times between successive shocks have a geometric distribution). Using the Markov chain embedding technique introduced by Chadjiconstantinidis et al. (Adv. Appl. Prob.32, 2000), we study the joint and marginal distributions of the system’s lifetime, the number of shocks, and the number of periods in which no shocks occur, up to the failure of the system. The joint and marginal probability generating functions of these random variables are obtained, and several recursions and exact formulae are given for the evaluation of their probability mass functions and moments. It is shown that the system’s lifetime follows a Markov geometric distribution of order
$\delta$
(a geometric distribution of order
$\delta$
under the binomial setup) and also that it follows a matrix-geometric distribution. Some reliability properties are also given under the binomial shock process, by showing that a shift of the system’s lifetime random variable follows a compound geometric distribution. Finally, we introduce a new mixed discrete censored
$\delta$
-shock model, for which the system fails when no shock occurs within a
$\delta$
-length time period from the last shock, or the magnitude of the shock is larger than a given critical threshold
$\gamma >0$
. Similarly, for this mixed model, we study the joint and marginal distributions of the system’s lifetime, the number of shocks, and the number of periods in which no shocks occur, up to the failure of the system, under the binomial shock process.
Dual-stage radial–tangential vortex tilting reverses radial vorticity and contributes to leading-edge vortex stability on revolving wings
Authors: Chen Long , Zhou Chao , Werner Nathaniel H. , Cheng Bo , Wu Jianghao
Published: May 2023

The physics of leading-edge vortex (LEV) stability on flapping wings and autorotating seeds is still underexplored due to its complex dependency on Reynolds number (

$\textit {Re}$

), aspect ratio (AR) and Rossby number (Ro). Our previous study observed an interesting dual-stage vortex tilting between radial and tangential components in a stable LEV. Here, the establishment of this novel mechanism, i.e. dual-stage radial–tangential vortex tilting (DS-VT

$_{r-t}$

), is investigated and explained in detail using numerical methods. The contributions of other tangential vorticity transport terms are also considered. It is shown that the stable LEV region coincides mostly with a constant ratio of tangential and radial vorticity components. The DS-VT

$_{r-t}$

mechanism functions as a negative feedback loop for radial vorticity, thereby contributing to the LEV stability at

$\textit {Re} > 500$

. Specifically, this mechanism involves a dual-stage vortex tilting starting from negative radial component to positive tangential component, and then back to positive radial component, thereby leading to a

$180^{\circ }$

reversal of radial vorticity. The radial Coriolis acceleration can also assist the DS-VT

$_{r-t}$

by enhancing the tangential vorticity component and the reduction of radial vorticity inside the LEV via the second stage of DS-VT

$_{r-t}$

. The effects of

$\textit {Re}$

, AR and Ro on the constant radial–tangential vorticity ratio and DS-VT

$_{r-t}$

are then analysed. The coupled effects of AR and Ro are separated into rotational effects and those of tip and root vortices. Our results establish an evident relationship among the LEV stability, the constant radial–tangential vorticity ratio, and the DS-VT

$_{r-t}$

, thereby deepening the understanding in the vorticity transport of LEV formation and stability.
Hydrodynamic instabilities of a dual-mode air–SF6 interface induced by a cylindrically convergent shock
Authors: Liang Yu , Liu Lili , Luo Xisheng , Wen Chih-Yung
Published: May 2023

Shock-tube experiments are performed on the convergent Richtmyer–Meshkov (RM) instability of a multimode interface. The temporal growth of each Fourier mode perturbation is measured. The hydrodynamic instabilities, including the RM instability and the additional Rayleigh–Taylor (RT) effect, imposed by the convergent shock wave on the dual-mode interface, are investigated. The mode-coupling effect on the convergent RM instability coupled with the RT effect is quantified. It is evident that the amplitude growths of all first-order modes and second-order harmonics and their couplings depend on the variance of the interface radius, and are influenced by the mode-coupling from the very beginning. It is confirmed that the mode-coupling mechanism is closely related to the initial spectrum, including azimuthal wavenumbers, relative phases and initial amplitudes of the constituent modes. Different from the conclusion in previous studies on the convergent single-mode RM instability that the additional RT effect always suppresses the perturbation growth, the mode-coupling might result in the additional RT effect promoting the instability of the constituent Fourier mode. By considering the geometry convergence, the mode-coupling effect and other physical mechanisms, second-order nonlinear solutions are established to predict the RM instability and the additional RT effect in the cylindrical geometry, reasonably quantifying the amplitude growths of each mode, harmonic and coupling. The nonlinear solutions are further validated by simulations considering various initial spectra. Last, the temporal evolutions of the mixed mass and normalized mixed mass of a shocked multimode interface are calculated numerically to quantify the mixing of two fluids in the cylindrical geometry.
Resistive-force theory of slender bodies in viscosity gradients
Authors: Kamal Catherine , Lauga Eric
Published: May 2023

In many natural settings, spatial variations in a fluid's viscosity arise due to changes in its local physico-chemical environment. We consider the low-Reynolds-number dynamics of slender bodies in fluids with a linearly varying viscosity. Assuming the spatial change in viscosity to be small compared to the spatial deviation of the body but large relative to the body's aspect ratio, we derive the modifications to resistive-force theory in a fluid due to a constant viscosity gradient. At leading order in the body slenderness, the results are identical to the classical theory in a constant-viscosity fluid but with the viscosity taking everywhere its local, non-constant value. At next order in slenderness, non-local terms arise due to the non-zero viscosity gradient. We use our results to predict the motion of straight and toroidal filaments settling under the action of gravity. We show that viscosity gradients induce rigid-body rotation of the filaments at a rate proportional to the components of the gradients along the filaments. This result contrasts with constant-viscosity fluids where the filaments do not rotate. We demonstrate further that if the viscosity gradient acts in the direction opposite to the gravitational field, then the filaments rotate towards a stable orientation, whose value depends on the ratio between the viscosity gradients parallel and perpendicular to the gravitational field; otherwise, the filaments align in the direction of the gravitational field. Our work shows that viscosity gradients can exert new forces on slender bodies, which could, for example, be used to control their orientation and drift.
Lattice Boltzmann modelling of colloidal suspensions drying in porous media accounting for local nanoparticle effects
Authors: Qin Feifei , Fei Linlin , Zhao Jianlin , Kang Qinjun , Derome Dominique , Carmeliet Jan
Published: May 2023

A two-dimensional (2-D) double-distribution lattice Boltzmann method (LBM) is implemented to study isothermal drying of a colloidal suspension considering local nanoparticle effects. The two LBMs solve isothermal two-phase flow and nanoparticle transport, respectively. The three local nanoparticle effects on the fluid dynamics considered in this paper are viscosity increase, surface tension drop and local drying rate reduction. The proposed model is first validated by the study of the drying of a 2-D suspended colloidal droplet for two different Péclet numbers, where the evolution of the diameter squared agrees well with experimental results. The model is further validated looking at drying of a colloid in a 2-D capillary tube with two open ends. Compared with experimental results, the best agreement in terms of deposition profile and drying time is obtained when considering all three nanoparticle effects. Afterwards, we apply the model to investigate the complicated drying of a colloidal suspension in a 2-D porous asphalt, considering all three local nanoparticle effects. The drying dynamics, resultant nanoparticle transport, accumulation and deposition are first analysed for a base case. Then a parametric study is conducted varying the initial nanoparticle concentration, porous medium contact angle, nanoparticle contact angle and nanoparticle diffusion coefficient. The influence of these parameters on drying dynamics, drying rate, deposition process and final deposition configurations is analysed in detail, together with the mutual influence of local nanoparticle behaviour. Finally, a unified relation between the average drying rate and the studied parameters is proposed and verified, covering the full parameter ranges of simulations.
Subcritical transition to turbulence in quasi-two-dimensional shear flows
Authors: Camobreco Christopher J. , Pothérat Alban , Sheard Gregory J.
Published: May 2023

The transition to turbulence in conduits is among the longest-standing problems in fluid mechanics. Challenges in producing or saving energy hinge on understanding promotion or suppression of turbulence. While a global picture based on an intrinsically 3-D subcritical mechanism is emerging for 3-D turbulence, subcritical turbulence is yet to even be observed when flows approach two dimensions, e.g. under intense rotation or magnetic fields. Here, stability analysis and direct numerical simulations demonstrate a subcritical quasi-two-dimensional (quasi-2-D) transition from laminar flow to turbulence, via a radically different 2-D mechanism to the 3-D case, driven by nonlinear Tollmien–Schlichting waves. This alternative scenario calls for a new line of thought on the transition to turbulence and should inspire new strategies to control transition in rotating devices and nuclear fusion reactor blankets.
Kalikow decomposition for counting processes with stochastic intensity and application to simulation algorithms
Authors: Phi Tien Cuong , Löcherbach Eva , Reynaud-Bouret Patricia
Published: May 2023

We propose a new Kalikow decomposition for continuous-time multivariate counting processes, on potentially infinite networks. We prove the existence of such a decomposition in various cases. This decomposition allows us to derive simulation algorithms that hold either for stationary processes with potentially infinite network but bounded intensities, or for processes with unbounded intensities in a finite network and with empty past before zero. The Kalikow decomposition is not unique, and we discuss the choice of the decomposition in terms of algorithmic efficiency in certain cases. We apply these methods to several examples: the linear Hawkes process, the age-dependent Hawkes process, the exponential Hawkes process, and the Galves–Löcherbach process.
Management of attic retraction pockets
Authors: Honnurappa Vijayendra , Mahajan Nilesh , Vijayendra Vinay Kumar , Vassiliu Sofia , Redleaf Miriam
Published: May 2023

Objective

Attic retraction pockets, classified by degree of invasion and erosion, are reconstructed here as outlined by attic retraction pocket grade.

Method

Attic retraction pocket grade, surgical management, subsequent conditions of tympanic membrane and middle ear, and improvement of air–bone gap pure tone average were recorded.

Results

Our management strategy, based on attic retraction pocket grade, was applied to 200 ears: 44 grade I ears had non-surgical management and 156 grade II–V ears had surgical management. All 200 ears were followed up for 36–240 months, showing only 1 attic retraction pocket reformation and 1 adhesive otitis media (complication rate of 1 per cent), and improved air–bone gaps (p< 0.05). An earlier series of 50 grade IV attic retraction pockets used atticotomy with epitympanic reconstruction. These showed attic retraction pocket recurrence or cholesteatoma onset in 34 ears (68 per cent). When these ears were revised per protocol, there was no evidence of cholesteatoma thereafter.

Conclusion

Reconstruction of the ossicles and scutal defect according to attic retraction pocket grade shows long-term stability of the tympanic membrane, middle ear and hearing.
Development and external validation of a prognostic tool for nonsevere COVID-19 inpatients
Authors: Luo Ensi , Zhong Qingyang , Wen Yongtao , Cai Jie , Xie Xia , Zhou Lingjuan
Published: May 2023

To develop a machine learning model and nomogram to predict the probability of persistent virus shedding (PVS) in hospitalized patients with coronavirus disease 2019 (COVID-19), the clinical symptoms and signs, laboratory parameters, cytokines, and immune cell data of 429 patients with nonsevere COVID-19 were retrospectively reviewed. Two models were developed using the Akaike information criterion (AIC). The performance of these two models was analyzed and compared by the receiver operating characteristic (ROC) curve, calibration curve, net reclassification index (NRI), and integrated discrimination improvement (IDI). The final model included the following independent predictors of PVS: sex, C-reactive protein (CRP) level, interleukin-6 (IL-6) level, the neutrophil-lymphocyte ratio (NLR), monocyte count (MC), albumin (ALB) level, and serum potassium level. The model performed well in both the internal validation (corrected C-statistic = 0.748, corrected Brier score = 0.201) and external validation datasets (corrected C-statistic = 0.793, corrected Brier score = 0.190). The internal calibration was very good (corrected slope = 0.910). The model developed in this study showed high discriminant performance in predicting PVS in nonsevere COVID-19 patients. Because of the availability and accessibility of the model, the nomogram designed in this study could provide a useful prognostic tool for clinicians and medical decision-makers.
The plans for Tokyo Bay: the challenge of urban policy, 1950s–1990s
Authors: Hasegawa Junichi
Published: May 2023

At the conclusion of the 1950s in Japan, plans to reclaim and develop Tokyo Bay were proposed by the Japan Housing Corporation's president and a private think tank on economic affairs. The vision was incompatible with dispersion, the basic direction of the state's policy, so it was quickly rejected, but its legacy lived on as the trans-Tokyo Bay highway in 1997. This article argues that the lack of an effective national policy led to contradictory initiatives and divisions among the stakeholders, leaving open the way for the large-scale reclamation and development of Tokyo Bay.
A rare ventriculoarterial connection: double outlet of both ventricles
Authors: Genc Halise Z. , Ozyilmaz Isa , Baş Serap , Kose Banu , Ozturk Erkut , Hatemi Ali C. , Tanidir Ibrahim C.
Published: May 2023

Ventriculoarterial connection is one of the important points of the segmental approach to congenital cardiac malformations. Double outlet of both ventricles is a rare form where both great arterial roots override the interventricular septum. In this article, we aimed to draw attention to this very rare form of ventriculoarterial connection by presenting an infant case diagnosed using echocardiography, CT angiography, and 3-dimensional modelling.
Inkjet-printed broadband FSS-based absorber with improved absorption characteristics
Authors: Tirkey Manish Mathew , Gupta Nisha
Published: May 2023

We present the design for a thin planar microwave absorber depicting near unity absorption over a wide bandwidth. The absorber consists of a single layer of resistive frequency selective surface inkjet printed over a paper substrate and suspended over a grounded foam. We have been able to achieve 99.99% absorption of normally incident radiations from 9.7 to 11.74 GHz at an extremely low level of −40 dB absorption bandwidth. The proposed absorber is thin (0.22λ0 at the center frequency), polarization-insensitive, and presents −10, −20, −30, and −40 dB fractional bandwidths as 89.83%, 55.41%, 33.30%, and 19.03%, respectively. It is worth mentioning that the design of an absorber with such steep slopes is highly stringent and requires special attention. Finally, we have experimentally demonstrated the perfect broadband absorption characteristics with a fabricated prototype.
Active Deformation Pattern in the Western Flank of the Central Taurides, Southern Margin of the Central Anatolian Plateau: Inferences From Geomorphic Markers and Kinematic Indicators
Authors: Aykut Tunahan , Yıldırım Cengiz , Uysal I. Tonguç
Published: May 2023

The southwestern margin of the Central Anatolian Plateau corresponds to the upper crust of the subduction between African and Anatolian plates, with a high relief of up to 2 km. This mountainous region has distinctive geomorphological features and presents a unique setting to investigate the mechanism of orogenic plateau margin development related to subduction and topographic evolution around the Eastern Mediterranean. We present new kinematic data from exposed fault planes and tectonic landforms from high‐resolution digital elevation models to elucidate the deformation pattern and its relation with the crustal deformation. We evaluate the deformation pattern based on the spatial distribution of kinematic analyses and geomorphic markers like low relief upland surfaces, disrupted karst basins, knickpoints, and deep bedrock incisions from watershed to shoreline. Our geomorphic analysis reveals a post‐orogenic transient actively deforming topography. The geomorphic markers constrain long‐term surface uplift pattern with a mean cumulative surface uplift of 1,710 ± 50 m and shows an increasing trend from west to east, from 1,600 ± 50 to 1,800 ± 50 m. Our results suggest a dome‐like uplift pattern in the west‐east direction across the southern margin that reaches up to maximum cumulative uplift values in the quadrangle of Alanya‐Başyayla‐Ermenek‐Gazipaşa. Our kinematic measurements along the youngest generation of faults revealed an active NE‐SW extensional deformation across a broad 200 km zone in the north of the subduction. Our findings have significant implications for understanding the morphotectonic evolution and post‐orogenic deformation in the plateau margins and geodynamic evolution of the Eastern Mediterranean.
Potential Role of Mid‐Latitude Seaway on Early Paleogene Atlantic Overturning Circulation
Authors: Zhu Chenguang , Zhang Zhongshi , Zhu Chenyu , Zhang Jian
Published: May 2023

The role of the mid‐latitude seaway between the proto‐Paratethys and the North Sea on the early Paleogene ocean circulation is examined with a state‐of‐art earth system model. The early Eocene simulations here demonstrate that the open mid‐latitude seaway captures most relatively fresh surface water from the Arctic and Greenland‐Norwegian Sea and prohibits them from leaking into the Labrador Sea, thus benefiting the Atlantic meridional overturning circulation (AMOC). However, the closure of the seaway triggers the AMOC reduction as more relatively fresh surface water enters the Labrador Sea, and the AMOC finally shuts down. Together with geological reconstructions, our results also provide insights into understanding the evolution of the Atlantic‐Arctic oceanic gateways during the Paleogene.
Towards a multilevel model of major depression: genes, immuno-metabolic function, and cortico-striatal signaling
Authors: Paul Elisabeth R. , Östman Lars , Heilig Markus , Mayberg Helen S. , Hamilton J. Paul
Published: May 2023

Biological assay and imaging techniques have made visible a great deal of the machinery of mental illness. Over fifty years of investigation of mood disorders using these technologies has identified several biological regularities in these disorders. Here we present a narrative connecting genetic, cytokine, neurotransmitter, and neural-systems-level findings in major depressive disorder (MDD). Specifically, we connect recent genome-wide findings in MDD to metabolic and immunological disturbance in this disorder and then detail links between immunological abnormalities and dopaminergic signaling within cortico-striatal circuitry. Following this, we discuss implications of reduced dopaminergic tone for cortico-striatal signal conduction in MDD. Finally, we specify some of the flaws in the current model and propose ways forward for advancing multilevel formulations of MDD most efficiently.
The chemokine monocyte chemoattractant protein-1/CCL2 is a promoter of breast cancer metastasis
Authors: Yoshimura Teizo , Li Chunning , Wang Yuze , Matsukawa Akihiro
Published: May 2023

Breast cancer is the most prevalent cancer worldwide, and metastasis is the leading cause of death in cancer patients. Human monocyte chemoattractant protein-1 (MCP-1/CCL2) was isolated from the culture supernatants of not only mitogen-activated peripheral blood mononuclear leukocytes but also malignant glioma cells based on its in vitro chemotactic activity toward human monocytes. MCP-1 was subsequently found to be identical to a previously described tumor cell-derived chemotactic factor thought to be responsible for the accumulation of tumor-associated macrophages (TAMs), and it became a candidate target of clinical intervention; however, the role of TAMs in cancer development was still controversial at the time of the discovery of MCP-1. The in vivo role of MCP-1 in cancer progression was first evaluated by examining human cancer tissues, including breast cancers. Positive correlations between the level of MCP-1 production in tumors and the degree of TAM infiltration and cancer progression were established. The contribution of MCP-1 to the growth of primary tumors and metastasis to the lung, bone, and brain was examined in mouse breast cancer models. The results of these studies strongly suggested that MCP-1 is a promoter of breast cancer metastasis to the lung and brain but not bone. Potential mechanisms of MCP-1 production in the breast cancer microenvironment have also been reported. In the present manuscript, we review studies in which the role of MCP-1 in breast cancer development and progression and the mechanisms of its production were examined and attempt to draw a consensus and discuss the potential use of MCP-1 as a biomarker for diagnosis.
Anomalous anisotropic magnetoresistance in the topological semimetal HoPtBi
Authors: Chen Jie , Li Hang , Guo Tengyu , Chen Peng , Zheng Dongfeng , Yu Guoqiang , Lau Yong-Chang , Xi Xuekui , Wang Wenhong
Published: May 2023

Discovering and understanding anomalous anisotropic magnetoresistance (AMR) effects are important aspects of studying the nature of modulated transport. The anisotropic transport coefficients of topological systems are often useful for mapping hidden phases and characterizing topological phase transitions and the evolution of topological electrons. Here, we report an unusual change in the AMR effect in HoPtBi. Remarkably, the AMR exhibits transitions from a quasi-twofold to fourfold symmetry and finally forms a stable rotated fourfold symmetry with increasing magnetic fields. The evolution analysis from the three-dimensional (3D) mapping experiments confirms that it is an intrinsic 3D effect. Fourier transformation analysis indicates that the superposition of C2, C4, and C6 signals with phase angle transitions leads to the novel AMR. All transitions are summarized as symmetry rotation or the inversion of peaks and valleys. By combining the features of band structures and AMR, we evaluate the possible origin of this symmetry rotation and attribute it to the topological band change. This work provides insight into the anomalous AMR effect of topological materials and is useful for understanding the evolution of topological bands in a magnetic field. We propose that other rare-earth half-Heusler alloys can potentially exhibit similar phenomena.
Observation of directional leaky polaritons at anisotropic crystal interfaces
Authors: Ni Xiang , Carini Giulia , Ma Weiliang , Renzi Enrico Maria , Galiffi Emanuele , Wasserroth Sören , Wolf Martin , Li Peining , Paarmann Alexander , Alù Andrea
Published: May 2023

Extreme anisotropy in some polaritonic materials enables light propagation with a hyperbolic dispersion, leading to enhanced light-matter interactions and directional transport. However, these features are typically associated with large momenta that make them sensitive to loss and poorly accessible from far-field, being bound to the material interface or volume-confined in thin films. Here, we demonstrate a new form of directional polaritons, leaky in nature and featuring lenticular dispersion contours that are neither elliptical nor hyperbolic. We show that these interface modes are strongly hybridized with propagating bulk states, sustaining directional, long-range, sub-diffractive propagation at the interface. We observe these features using polariton spectroscopy, far-field probing and near-field imaging, revealing their peculiar dispersion, and – despite their leaky nature – long modal lifetime. Our leaky polaritons (LPs) nontrivially merge sub-diffractive polaritonics with diffractive photonics onto a unified platform, unveiling opportunities that stem from the interplay of extreme anisotropic responses and radiation leakage.
Using mass spectrometry imaging to map fluxes quantitatively in the tumor ecosystem
Authors: Schwaiger-Haber Michaela , Stancliffe Ethan , Anbukumar Dhanalakshmi S. , Sells Blake , Yi Jia , Cho Kevin , Adkins-Travis Kayla , Chheda Milan G. , Shriver Leah P. , Patti Gary J.
Published: May 2023

Tumors are comprised of a multitude of cell types spanning different microenvironments. Mass spectrometry imaging (MSI) has the potential to identify metabolic patterns within the tumor ecosystem and surrounding tissues, but conventional workflows have not yet fully integrated the breadth of experimental techniques in metabolomics. Here, we combine MSI, stable isotope labeling, and a spatial variant of Isotopologue Spectral Analysis to map distributions of metabolite abundances, nutrient contributions, and metabolic turnover fluxes across the brains of mice harboring GL261 glioma, a widely used model for glioblastoma. When integrated with MSI, the combination of ion mobility, desorption electrospray ionization, and matrix assisted laser desorption ionization reveals alterations in multiple anabolic pathways. De novo fatty acid synthesis flux is increased by approximately 3-fold in glioma relative to surrounding healthy tissue. Fatty acid elongation flux is elevated even higher at 8-fold relative to surrounding healthy tissue and highlights the importance of elongase activity in glioma.
Insulator-to-metal-like transition in thin films of a biological metal-organic framework
Authors: Sindhu Pooja , Ananthram K. S. , Jain Anil , Tarafder Kartick , Ballav Nirmalya
Published: May 2023

Temperature-induced insulator-to-metal transitions (IMTs) where the electrical resistivity can be altered by over tens of orders of magnitude are most often accompanied by structural phase transition in the system. Here, we demonstrate an insulator-to-metal-like transition (IMLT) at 333 K in thin films of a biological metal-organic framework (bio-MOF) which was generated upon an extended coordination of the cystine (dimer of amino acid cysteine) ligand with cupric ion (spin-1/2 system) – without appreciable change in the structure. Bio-MOFs are crystalline porous solids and a subclass of conventional MOFs where physiological functionalities of bio-molecular ligands along with the structural diversity can primarily be utilized for various biomedical applications. MOFs are usually electrical insulators (so as our expectation with bio-MOFs) and can be bestowed with reasonable electrical conductivity by the design. This discovery of electronically driven IMLT opens new opportunities for bio-MOFs, to emerge as strongly correlated reticular materials with thin film device functionalities.
saRNA vaccine expressing membrane-anchored RBD elicits broad and durable immunity against SARS-CoV-2 variants of concern
Authors: Komori Mai , Nogimori Takuto , Morey Amber L. , Sekida Takashi , Ishimoto Keiko , Hassett Matthew R. , Masuta Yuji , Ode Hirotaka , Tamura Tomokazu , Suzuki Rigel , Alexander Jeff , Kido Yasutoshi , Matsuda Kenta , Fukuhara Takasuke , Iwatani Yasumasa , Yamamoto Takuya , Smith Jonathan F. , Akahata Wataru
Published: May 2023

Several vaccines have been widely used to counteract the global pandemic caused by SARS-CoV-2. However, due to the rapid emergence of SARS-CoV-2 variants of concern (VOCs), further development of vaccines that confer broad and longer-lasting protection against emerging VOCs are needed. Here, we report the immunological characteristics of a self-amplifying RNA (saRNA) vaccine expressing the SARS-CoV-2 Spike (S) receptor binding domain (RBD), which is membrane-anchored by fusing with an N-terminal signal sequence and a C-terminal transmembrane domain (RBD-TM). Immunization with saRNA RBD-TM delivered in lipid nanoparticles (LNP) efficiently induces T-cell and B-cell responses in non-human primates (NHPs). In addition, immunized hamsters and NHPs are protected against SARS-CoV-2 challenge. Importantly, RBD-specific antibodies against VOCs are maintained for at least 12 months in NHPs. These findings suggest that this saRNA platform expressing RBD-TM will be a useful vaccine candidate inducing durable immunity against emerging SARS-CoV-2 strains.
Computational design of dynamic receptor—peptide signaling complexes applied to chemotaxis
Authors: Jefferson Robert E. , Oggier Aurélien , Füglistaler Andreas , Camviel Nicolas , Hijazi Mahdi , Villarreal Ana Rico , Arber Caroline , Barth Patrick
Published: May 2023

Engineering protein biosensors that sensitively respond to specific biomolecules by triggering precise cellular responses is a major goal of diagnostics and synthetic cell biology. Previous biosensor designs have largely relied on binding structurally well-defined molecules. In contrast, approaches that couple the sensing of flexible compounds to intended cellular responses would greatly expand potential biosensor applications. Here, to address these challenges, we develop a computational strategy for designing signaling complexes between conformationally dynamic proteins and peptides. To demonstrate the power of the approach, we create ultrasensitive chemotactic receptor—peptide pairs capable of eliciting potent signaling responses and strong chemotaxis in primary human T cells. Unlike traditional approaches that engineer static binding complexes, our dynamic structure design strategy optimizes contacts with multiple binding and allosteric sites accessible through dynamic conformational ensembles to achieve strongly enhanced signaling efficacy and potency. Our study suggests that a conformationally adaptable binding interface coupled to a robust allosteric transmission region is a key evolutionary determinant of peptidergic GPCR signaling systems. The approach lays a foundation for designing peptide-sensing receptors and signaling peptide ligands for basic and therapeutic applications.