bluuebunny/crossref_metadata_2025 huggingface dataset:
DeepIndoorCrowd: Predicting crowd flow in indoor shopping malls with an interpretable transformer network
Authors: Chu Chen , Zhang Hengcai , Wang Peixiao , Lu Feng
Published: August 2023

Accurate and interpretable prediction of crowd flow would benefit business management and public security. The existing studies are challenged to adapt to the indoor environment due to its complex and dynamic spatial interaction patterns. In this study, we propose a crowd flow predicting method for indoor shopping malls, which simultaneously features temporal variables and semantic factors to suit the shopping mall environment. A deep learning model named DeepIndoorCrowd is presented. The model aims at capturing temporal dependencies and the semantic pattern in crowd flow to generate an accurate multi‐horizon prediction. With a multi‐term temporal dependency capturing structure, the model is effective in learning both daily and weekly patterns of the indoor crowd flow in a shopping mall and is able to provide the temporal interpretation of the prediction result. Moreover, a semantic‐temporal fusion module is introduced to utilize the semantic information of stores in prediction, which has proved to be effective in enhancing the model's ability to learn temporal patterns. Experiments were conducted on a real‐world dataset to verify the proposed approach. The ablation study demonstrates that the DeepIndoorCrowd can effectively improve the efficiency and accuracy of the prediction up to 18.7%. In addition, some interesting indoor crowd flow patterns were discovered by analyzing the model's interpretation of the prediction result. The proposed prediction method provides an intuitive way of modeling indoor crowd flow, and the experiment's outcome can help indoor managers better understand stores' flow traffic.
Natural variation in Arabidopsis responses to Plasmodiophora brassicae reveals an essential role for Resistance to Plasmodiophora brasssicae 1 (RPB1)
Authors: Ochoa Juan Camilo , Mukhopadhyay Soham , Bieluszewski Tomasz , Jędryczka Małgorzata , Malinowski Robert , Truman William
Published: August 2023

Despite the identification of clubroot resistance genes in various Brassica crops our understanding of the genetic basis of immunity to Plasmodiophora brassicae infection in the model plant Arabidopsis thaliana remains limited. To address this issue, we performed a screen of 142 natural accessions and identified 11 clubroot‐resistant Arabidopsis lines. Genome‐wide association analysis identified several genetic loci significantly linked with resistance. Three genes from two of these loci were targeted for deletion by CRISPR/Cas9 mutation in resistant accessions Est‐1 and Uod‐1. Deletion of Resistance to Plasmodiophora brassicae 1 (RPB1) rendered both lines susceptible to the P. brassicae pathotype P1+. Further analysis of rpb1 knock‐out Est‐1 and Uod‐1 lines showed that the RPB1 protein is required for activation of downstream defence responses, such as the expression of phytoalexin biosynthesis gene CYP71A13. RPB1 has recently been shown to encode a cation channel localised in the endoplasmic reticulum. The clubroot susceptible Arabidopsis accession Col‐0 lacks a functional RPB1 gene; when Col‐0 is transformed with RPB1 expression driven by its native promoter it is capable of activating RPB1 transcription in response to infection, but this is not sufficient to confer resistance. Transient expression of RPB1 in Nicotiana tabacum induced programmed cell death in leaves. We conclude that RPB1 is a critical component of the defence response to P. brassicae infection in Arabidopsis, acting downstream of pathogen recognition but required for the elaboration of effective resistance.
EXPERIMENTAL INVESTIGATION STRATEGIES TO AUGMENT THE DIESEL ENGINE PERFORMANCE AND REDUCTION OF EMISSION CHARACTERISTICS BY THE EFFECT OF WASTE PLASTIC OIL
Authors: Jude Roy J. Nishanth , Premkumar P. , Iqbal S. Mohamed , Balaji A.
Published: August 2023

The need for biomass to waste plastic oil (WPO) in recent years, as the desire to diversify feedstock and reduce industrial emissions has grown. The technologies for converting biomass to conventional WPO are investigated in this paper. Biomass likes as cow dung and kitchen waste was used as a feed for the anaerobe to generate biogas. This biogas can be effectively utilized for heating purpose of synthesis WPO from waste plastic. WPO conversion process fly ash is used as catalyst with 0.1 cat/pol. WPO blend with different percentages with diesel like 25 % to 100 % WPO ((WPO 25), (WPO 50), (WPO 75) and (WPO 100) ) by volume with pure diesel and run the KIRLOSKAR TV -1 engine. At various engine loads, the impact of WPO blends on engine performance and exhaust emissions were investigated. The results are validated to those of a standard diesel fuel operation. WPO has a greater fuel concept and brake thermal efficiency than diesel. The engine functioned better with WPO25 mix.  It is discovered that the NOx, HC, CO2, and smoke emissions are greater than those of diesel.
Multi-Input Multi-Output Robust Control of Turbofan Engines Based on Off-Equilibrium Linearization Linear Parameter Varying Model
Authors: Tang Yifeng , Li Yan , Yang Wenchong , Zhou Wenxiang , Huang Jinquan , Cui Tao
Published: August 2023

The conventional linear parameter varying (LPV) modeling for turbofan engines is performed at a set of equilibrium points, which may result in inaccurate description of dynamics of engines when the engine accelerates/decelerates in a broad range and operates away from the equilibria. Meanwhile, to ensure stable operation of turbofan engines, the engine pressure ratio (EPR) needs to be regulated when turning on afterburner. According to this complex multi-input multi-output (MIMO) problem mixed with disturbances, this paper proposes a hybrid H∞/H2 robust control framework based on off-equilibrium linearization. We first establish an off-equilibrium linearization based polynomial LPV model for the MIMO turbofan engine, and then design an H∞/H2 robust controller by solving sum-of-squares (SOS) programing. The simulation results show that the controller can simultaneously achieve fast dual command tracking and disturbance suppression when turning on afterburner. Furthermore, this control framework is superior to the equilibrium linearization-based controller in many aspects, which further proves the accuracy of the off-equilibrium based LPV model.
Vibro-Acoustic Responses and Pressure Signal Analysis for Early Surge Detection in a Turbocharger Compressor
Authors: Silvestri Paolo , Niccolini Marmont Du Haut Champ Carlo Alberto , Reggio Federico , Ferrari Mario Luigi , Massardo Aristide Fausto
Published: August 2023

High-speed centrifugal compressors may be exploited to pressurize fuel cell systems. Nonetheless, due to fuel cells significant interposed volumes, compressor behavior can lead to severe vibrations related to fluid-dynamic instabilities during part load operating conditions. In particular, surge strongly limits centrifugal compressors stable operating region when moving toward low mass flow rates due to a change in system working point. Therefore, compressor dynamic response must be adequately characterized for early surge detection. To this aim, a dedicated experimental activity was conducted on a vaneless diffuser turbocharger coupled to a solid oxide fuel cell emulator plant; compressor evolution toward surge was investigated. Several signal processing techniques were applied to pressure signals as well as vibro-acoustic responses to better predict compressor behavior and classify its status as stable or unstable. Cepstrum, cross-correlation, and wavelet transform have been identified as suitable techniques to define precursors able to early detect surge. By means of cross-correlation function, propagation phenomena in the ducts can be investigated to assess how they interact near compressor low-mass flowrate unstable conditions. Cepstrum provides a convenient way to determine pressure signal spectrum distortion in terms of further periodic components onset. These harmonic components are due to complex system responses generated by transient phenomena; indeed, cepstrum allows to identify hidden anomalous contributions in system response spectra which may arise in incipient surge conditions. Wavelet transform was performed on both structural and pressure response signals to observe their dominant energy contents temporal evolution; indeed, such spectral pattern time-dependent variation can detect the rise of unstable conditions. By exploiting all these techniques, a complete system identification is performed which allows a deeper investigation of the physical phenomena involved; moreover, a more complete set of surge precursors extracted from different probes' physical signals were defined. The results obtained provide original diagnostic insights for monitoring systems suited to perform early surge detection. Compressor instability prevention can extend its operating range, performance, and reliability to allow better integration with other plant components. Finally, cepstrum application for compressor instability identification can be regarded as a novel method in the fluid machinery field.
On the Performance of Hydrostatic Journal Bearings in Air, Water, and Liquid Nitrogen: Measurements and Predictions
Authors: Jung Hyunsung , Kim Kyuman , Ryu Keun
Published: August 2023

Turbopumps in reusable and low-cost liquid rocket engines require compact and simple hydrostatic (i.e., externally pressurized) bearings to support large static and dynamic loads at high shaft speeds with no bearing DN (diameter in millimeters times rpm) life limitation. Hydrostatic bearings are one of the key mechanical components for cryogenic turbopumps to improve their reliability and reusability. Hydrostatic bearings offer significantly enhanced durability with very low friction and wear while providing accurate rotor positioning as well as large load and static stiffness characteristics even working with low-viscosity liquids. This work measures static load characteristics of hydrostatic journal bearings in air (25 °C), water (from 25 °C to 70 °C), and liquid nitrogen (−197 °C). Air, water, and liquid nitrogen are used as test fluids for the test bearing to evaluate the effects of fluid properties and temperatures on the bearing performance. A complete set of applied static load, bearing eccentricity, and bearing supply pressure for each test fluid (i.e., air, water, and liquid nitrogen) is presented for the test hydrostatic bearing. Measurements show that the applied static load on the test bearing significantly affects the recorded journal eccentricity ratio, bearing flow rate, and bearing static stiffnesses. Predictions are in good agreement with measurements. The predictable performance of hydrostatic journal bearings in air, water, and liquid nitrogen can further their application in various cryogenic turbopumps for liquid rocket engines.
Generation of Entropy Waves by Fully Premixed Flames in a Non-Adiabatic Combustor With Hydrogen Enrichment
Authors: Eder Alexander J. , Dharmaputra Bayu , Désor Marcel , Silva Camilo F. , Garcia Alex M. , Schuermans Bruno , Noiray Nicolas , Polifke Wolfgang
Published: August 2023

Thermoacoustic combustion instability is a major concern in gas turbine combustors with hydrogen-enriched fuels. Unsteady combustion not only generates acoustic waves but it may also result in fluctuations of burnt gas temperature, referred to as entropy waves. They are convected by the mean flow through the combustor and can cause indirect combustion noise when they are accelerated at the exit. In this work, we demonstrate that entropy waves occur in a fully premixed burner due to unsteady heat transfer at the combustion chamber wall. This mechanism of entropy generation is often neglected in the literature. This work shows an additional mechanism in CH4-H2-air flames, through which entropy may be created even in the fully premixed case. This is due to differential diffusion which generates local fluctuations in equivalence and carbon-to-hydrogen ratios. An adiabatic flame temperature is defined based on these two quantities to examine the influence of differential diffusion on the generation of entropy fluctuations. The generation of entropy waves is investigated by applying system identification (SI) to time series data obtained from a broadband forced large eddy simulation (LES) coupled with a heat conduction solver. The entropy transfer function (ETF) and flame transfer function (FTF) identified with LES/SI are then compared to experimental data obtained with tunable diode laser absorption spectroscopy with wavelength modulation spectroscopy (TDLAS-WMS) for measuring temperature fluctuations, and the multimicrophone method, respectively. After validating the computational setup, the entropy frequency response is identified at various positions within the combustion chamber, and the effects of generation and convective dispersion of entropy waves are qualitatively investigated. We show that a fully premixed turbulent system may exhibit significant entropy waves caused by wall heat losses and differential diffusion of hydrogen.
On Frequency/Time Invariance of Certain Temporal and Complex Transfer Functions for the One-Dimensional Interfacial Monochromatic Neutron Density Wave
Authors: Haidar Nassar H. S.
Published: August 2023

Optimization of dynamical multibeam neutron cancer therapy has recently been shown to be possible via employment of the beam frequencies of neutron waves as a control variable. The concepts of transfer functions (TF), addressed in this paper, can be essential ingredients of such optimization. Accordingly, the paper studies the dynamics of a one-dimensional (1D) monochromatic neutron density wave generated by time modulation of a boundary neutron current. It is demonstrated that a certain temporal transfer function (TTF) of both parabolic (diffusion) and low frequency hyperbolic (P−1 transport) interfacial neutron density wave happens to be frequency noninvariant with a vibrating boundary neutron current. It is proved that, only at high frequencies, both parabolic and hyperbolic interfacial neutron waves turn out to have a fully frequency-invariant and time-invariant temporal transfer function relative to such a vibrating neutron beam at the boundary. The frequency response of an associated complex transfer function is studied and demonstrated to change behavior, from a lag compensator to a fixed gain amplifier, with changing the frequency, neutron absorption and employed theory for neutron diffusion. A highlight of this paper is its illustration that mere continuity of these transfer functions can be a reflection of the correctness of the transport theory employed for modeling the neutron density waves.
Design and Optimization of a New Heterogeneous Printed Circuit Plate Heat Exchanger With Molten Salt Zigzag Passage and Supercritical CO2 Airfoil Fin Passage
Authors: Chen Zhansheng , Zhao Pinghui , Wan Teng , Jin Yixuan , Wang Xiaohu , Lei Mingzhun , Li Yuanjie , Peng Changhong
Published: August 2023

In the fusion power conversion system, a printed circuit heat exchanger (PCHE) between molten salt (MS) and supercritical carbon dioxide (sCO2) transfers huge heat between loops. To improve heat transfer efficiency, a new heterogeneous PCHE with MS zigzag passage and sCO2 airfoil fin passage was proposed. A one-dimensional simulation of the new PCHE was conducted to study the effects of the plate number and the length on its pressure drop, MS mass flowrate, capital cost, and operating cost. Then, a new single objective optimization of the total cost was performed by the genetic algorithm (GA) based on the Chinese Fusion Engineering Testing Reactor (CFETR) parameters. Finally, the new optimal PCHE was compared with the PCHE with MS straight passage and sCO2 airfoil fin passage. The results show that the length and the plate number of the PCHE have an important effect on the pressure drop and its cost. The optimal geometry scheme with the minimum cost is given for the application to CFETR. By comparison with the MS straight-passage PCHE, it is found that the total cost of the new PCHE is reduced by 5.7% and the volume of the heat exchanger is reduced by 10.7%.
Characterizing Shrouded Stator Cavity Flow on the Performance of a Single-Stage Axial Transonic Compressor
Authors: Shao Runzhu , He Xiao , Zhu Mingmin , Klausmann Fabian , Teng Jinfang
Published: August 2023

Shrouded stator cavity flow increases the stator total pressure loss, reduces the compressor isentropic efficiency, and thus limits the compressor pressure rise capability. This paper proposes a simplified cavity flow model that consists of flow injection at the stator inlet and flow suction at the stator outlet. Based on this model, a full-factorial parametric study on the leakage flow ratio and the leakage swirl angle is performed at different rotational speeds and incidences. In the first place, the effectiveness of the numerical method is validated against the experimental data based on the full-scale cavity geometry; then, the numerical simulations on the simplified cavity geometry are validated against that of the full-scale one. Results show that the leakage flow ratio plays a dominant role in determining the compressor performance penalty. The isentropic efficiency drops almost linearly with the leakage flow ratio due to deteriorated near-hub separations, and the slope becomes steeper at higher operating speeds and incidences. The leakage swirl angle only has a pronounced effect under a high leakage flow ratio. The efficiency penalty reduces with increasing swirl angle due to an alleviated tangential flow mixing and suppressed near-hub separations. The swirl angle effect is more pronounced at lower incidence conditions. These findings advance the fundamental understanding of shrouded stator cavity flow effects and provide useful guidance for cavity seal designs.
Effect of Assembly Uncertainties on Shock Propagation Through a Bolted Joint Under Impact Loading
Authors: Chen Hao , Hao Zhiming
Published: August 2023

Bolted joints have been widely used in engineering structures because of their advantages of simplicity, economy, and assembly. However, material nonlinearities, interface nonlinearities and uncertainties in the assembly process will lead to the dynamic response to become very complex. This work investigated the effect of assembly uncertainties on shock propagation through a bolted lap joint under impact loading. The object of the study was a bolted lap joint subjected to separate Hopkinson pressure bar (SHPB) test. First, a high-fidelity finite element model of the bolted lap joint was developed, and the model was validated by comparing with the experimental results. The error between simulation and experimental results prompted the necessary to consider the uncertainty effect. Then, the effects of multiple uncertainties were considered to identify important input random variables related to the impact response of the joint. The results showed that the slip between the connected parts has the most significant effect on energy dissipation and stress wave propagation. Finally, useful conclusions for the design of bolted joints were obtained from the computational results and discussions.
Low temperature epitaxial growth of Cantor-nitride thin films by magnetic field assisted magnetron sputtering
Authors: G. Rao Smita , Illgner Pascal Manuel , Boyd Robert , Nagy Gyula , Djemia Philippe , Primetzhofer Daniel , Petrov Ivan , le Febvrier Arnaud , Eklund Per
Published: August 2023

Low-temperature epitaxial growth of multicomponent alloy-based thin films remains an outstanding challenge in materials science and is important for established fundamental properties of these complex materials. Here, Cantor nitride (CrMnFeCoNi)N thin films were epitaxially grown on MgO(100) substrates at low deposition temperature by magnetic-field-assisted dc-magnetron sputtering, a technique where a magnetic field is applied to steer the dense plasma to the substrate thereby influencing the flux of Ar-ions bombarding the film during growth. Without ion bombardment, the film displayed textured growth. As the ion flux was increased, the films exhibited epitaxial growth. The epitaxial relationship between film and substrate was found to be cube on cube (001)film||(001)MgO, [100]film||[100]MgO. The epitaxy was retained up to a thickness of approximately ∼100 nm after which the growth becomes textured with a 002 out-of-plane orientation. The elastic constants determined by Brillouin inelastic light scattering were found to be C11 = 320 GPa, C12 = 125 GPa, and C44 = 66 GPa, from which the polycrystalline Young’s modulus was calculated as 204 GPa and Poisson's ratio = 0.32, whereas available elastic properties still remained very scarce.
The Effects of an Acute Dose of New Zealand Blackcurrant Extract on 5-km Running Performance
Authors: Moss Samantha L. , Brindley Edward , Enright Kevin , Highton Jamie , Bott Richard
Published: August 2023

This study investigated the effects of an acute dose (900 mg) of New Zealand Blackcurrant (NZBC) extract on 5-km running performance, alongside associated physiological and metabolic responses. Sixteen trained male runners (age 26 ± 5 years, stature 173.4 ± 7.3 cm, body mass 73.7 ± 6.9 kg, maximal oxygen consumption [] 55.4 ± 6.1 ml·kg−1·min−1) ingested either capsules containing NZBC extract (3 × 300 mg CurraNZ, 315 mg anthocyanins) or a matched placebo (3 × 300 mg gluten-free flour) 2 hr before exercise in a double-blind, randomized, crossover design. Performance time, physiological, and metabolic responses were assessed in a 5-km time trial, preceded by 10-min exercise at the lactate threshold on a treadmill. NZBC extract did not alter the physiological or metabolic responses to exercise at the lactate threshold (oxygen uptake, respiratory exchange ratio, minute ventilation, carbohydrate oxidation, fat oxidation, heart rate, blood lactate, or rating of perceived exertion, p > .05). The 5-km time trial was completed in a faster time in the NZBC extract condition compared with placebo (NZBC: 1,308.96 ± 122.36 s, placebo: 1,346.33 ± 124.44, p = .001, d = −0.23, confidence interval range = [−0.46, 0.00 s]). No differences in physiological or metabolic responses were apparent between conditions for the 5-km time trial (p > .05). Ingesting 900 mg of NZBC extract as an acute dose improves performance in trained male runners without altering physiological or metabolic responses to exercise. Further research is needed to assess a wider range of possible mechanisms (e.g., cardiovascular function, metabolite profiles) to advance insight into improved performance following supplementation.
Endothelial RIPK1 protects artery bypass graft against arteriosclerosis by regulating SMC growth
Authors: Lu Yao , Leng Yiming , Li Yalan , Wang Jie , Wang Wei , Wang Ruilin , Liu Yuanyuan , Tan Qian , Yang Wenjing , Jiang Youxiang , Cai Jingjing , Yuan Hong , Weng Liang , Xu Qingbo
Published: August 2023

RIPK1 is crucial in the inflammatory response. The process of vascular graft remodeling is also involved in endothelial inflammation, which can influence the behavior of smooth muscle cells. However, the role of endothelial RIPK1 in arterial bypass grafts remains unknown. Here, we established an arterial isograft mouse model in wild-type and endothelial RIPK1 conditional knockout mice. Progressive vascular remodeling and neointima formation occurred in the graft artery, showing SMC accumulation together with endothelial inflammatory adhesion molecule and cytokine expression. Endothelial RIPK1 knockout exacerbated graft stenosis by increasing secretion of N-Shh. Mechanistically, RIPK1 directly phosphorylated EEF1AKMT3 at Ser
26
, inhibiting its methyltransferase activity and global protein synthesis, which further attenuated N-Shh translation and secretion. Consistently, treatment with the Hedgehog pathway inhibitor GDC0449 markedly alleviated RIPK1 knockout–induced graft stenosis. Our results demonstrated that endothelial RIPK1 played a protective role in arterial bypass graft vascular remodeling, highlighting that targeting Hedgehog pathway may be an attractive strategy for graft failure in the future.
The relationship between ionic-electronic coupling and transport in organic mixed conductors
Authors: Keene Scott T. , Rao Akshay , Malliaras George G.
Published: August 2023

Organic mixed ionic-electronic conductors (OMIECs) directly convert between ionic and electronic charge through electrochemical (de)doping, enabling a wide range of applications in bioelectronics, neuromorphic computing, and energy storage and conversion. While both ionic and electronic transport are individually well characterized, their combined transport has been difficult to describe self-consistently. We use in situ measurements of electrochemical (de)doping of an archetypal OMIEC to inform a quasi-field drift-diffusion model, which accurately captures experimentally measured ion transport across a range of potentials. We find that the chemical potential of holes, which is modulated by changes in doping level, represents a major driving force for mixed charge transport. Using numerical simulations at device-relevant time scales and potentials, we find that the competition between hole drift and diffusion leads to diffuse space charge regions despite high charge densities. This effect is unique to mixed conducting systems where mobile ionic charges can compensate the accumulation or depletion of electronic charge, thereby screening electrostatic driving forces.
A temperature-tolerant CRISPR base editor mediates highly efficient and precise gene editing in
Drosophila
Authors: Doll Roman M. , Boutros Michael , Port Fillip
Published: August 2023

CRISPR nucleases generate a broad spectrum of mutations that includes undesired editing outcomes. Here, we develop optimized C-to-T base editing systems for the generation of precise loss- or gain-of-function alleles in
Drosophila
and identify temperature as a crucial parameter for efficiency. We find that a variant of the widely used APOBEC1 deaminase has attenuated activity at 18° to 29°C and shows considerable dose-dependent toxicity. In contrast, the temperature-tolerant evoCDA1 domain mediates editing of typically more than 90% of alleles and is substantially better tolerated. Furthermore, formation of undesired mutations is exceptionally rare in
Drosophila
compared to other species. The predictable editing outcome, high efficiency, and product purity enables near homogeneous induction of STOP codons or alleles encoding protein variants in vivo. Last, we demonstrate how optimized expression enables conditional base editing in marked cell populations. This work substantially facilitates creation of precise alleles in
Drosophila
and provides key design parameters for developing efficient base editing systems in other ectothermic species.
Control of soft robots with inertial dynamics
Authors: Haggerty David A. , Banks Michael J. , Kamenar Ervin , Cao Alan B. , Curtis Patrick C. , Mezić Igor , Hawkes Elliot W.
Published: August 2023

Soft robots promise improved safety and capability over rigid robots when deployed near humans or in complex, delicate, and dynamic environments. However, infinite degrees of freedom and the potential for highly nonlinear dynamics severely complicate their modeling and control. Analytical and machine learning methodologies have been applied to model soft robots but with constraints: quasi-static motions, quasi-linear deflections, or both. Here, we advance the modeling and control of soft robots into the inertial, nonlinear regime. We controlled motions of a soft, continuum arm with velocities 10 times larger and accelerations 40 times larger than those of previous work and did so for high-deflection shapes with more than 110° of curvature. We leveraged a data-driven learning approach for modeling, based on Koopman operator theory, and we introduce the concept of the static Koopman operator as a pregain term in optimal control. Our approach is rapid, requiring less than 5 min of training; is computationally low cost, requiring as little as 0.5 s to build the model; and is design agnostic, learning and accurately controlling two morphologically different soft robots. This work advances rapid modeling and control for soft robots from the realm of quasi-static to inertial, laying the groundwork for the next generation of compliant and highly dynamic robots.
A blood-based marker of mitochondrial DNA damage in Parkinson’s disease
Authors: Qi Rui , Sammler Esther , Gonzalez-Hunt Claudia P. , Barraza Ivana , Pena Nicholas , Rouanet Jeremy P. , Naaldijk Yahaira , Goodson Steven , Fuzzati Marie , Blandini Fabio , Erickson Kirk I. , Weinstein Andrea M. , Lutz Michael W. , Kwok John B. , Halliday Glenda M. , Dzamko Nicolas , Padmanabhan Shalini , Alcalay Roy N. , Waters Cheryl , Hogarth Penelope , Simuni Tanya , Smith Danielle , Marras Connie , Tonelli Francesca , Alessi Dario R. , West Andrew B. , Shiva Sruti , Hilfiker Sabine , Sanders Laurie H.
Published: August 2023

Parkinson’s disease (PD) is the most common neurodegenerative movement disorder, and neuroprotective or disease-modifying interventions remain elusive. High-throughput markers aimed at stratifying patients on the basis of shared etiology are required to ensure the success of disease-modifying therapies in clinical trials. Mitochondrial dysfunction plays a prominent role in the pathogenesis of PD. Previously, we found brain region–specific accumulation of mitochondrial DNA (mtDNA) damage in PD neuronal culture and animal models, as well as in human PD postmortem brain tissue. To investigate mtDNA damage as a potential blood-based marker for PD, we describe herein a PCR-based assay (Mito DNA
DX
) that allows for the accurate real-time quantification of mtDNA damage in a scalable platform. We found that mtDNA damage was increased in peripheral blood mononuclear cells derived from patients with idiopathic PD and those harboring the PD-associated leucine-rich repeat kinase 2 (
LRRK2
) G2019S mutation in comparison with age-matched controls. In addition, mtDNA damage was elevated in non–disease-manifesting
LRRK2
mutation carriers, demonstrating that mtDNA damage can occur irrespective of a PD diagnosis. We further established that
Lrrk2
G2019S knock-in mice displayed increased mtDNA damage, whereas
Lrrk2
knockout mice showed fewer mtDNA lesions in the ventral midbrain, compared with wild-type control mice. Furthermore, a small-molecule kinase inhibitor of LRRK2 mitigated mtDNA damage in a rotenone PD rat midbrain neuron model and in idiopathic PD patient–derived lymphoblastoid cell lines. Quantifying mtDNA damage using the Mito DNA
DX
assay may have utility as a candidate marker of PD and for measuring the pharmacodynamic response to LRRK2 kinase inhibitors.
TREM1 activation of myeloid cells promotes antitumor immunity
Authors: Juric Vladislava , Mayes Erin , Binnewies Mikhail , Lee Tian , Canaday Pamela , Pollack Joshua L. , Rudolph Joshua , Du Xiaoyan , Liu Victoria M. , Dash Subhadra , Palmer Rachael , Jahchan Nadine S. , Ramoth Åsa Johanna , Lacayo Sergio , Mankikar Shilpa , Norng Manith , Brassell Chris , Pal Aritra , Chan Christopher , Lu Erick , Sriram Venkataraman , Streuli Michel , Krummel Matthew F. , Baker Kevin P. , Liang Linda
Published: August 2023

Myeloid cells in the tumor microenvironment (TME) can exist in immunosuppressive and immunostimulatory states that impede or promote antitumor immunity, respectively. Blocking suppressive myeloid cells or increasing stimulatory cells to enhance antitumor immune responses is an area of interest for therapeutic intervention. Triggering receptor expressed on myeloid cells-1 (TREM1) is a proinflammatory receptor that amplifies immune responses. TREM1 is expressed on neutrophils, subsets of monocytes and tissue macrophages, and suppressive myeloid populations in the TME, including tumor-associated neutrophils, monocytes, and tumor-associated macrophages. Depletion or inhibition of immunosuppressive myeloid cells, or stimulation by TREM1-mediated inflammatory signaling, could be used to promote an immunostimulatory TME. We developed PY159, an afucosylated humanized anti-TREM1 monoclonal antibody with enhanced FcγR binding. PY159 is a TREM1 agonist that induces signaling, leading to up-regulation of costimulatory molecules on monocytes and macrophages, production of proinflammatory cytokines and chemokines, and enhancement of T cell activation in vitro. An antibody against mouse TREM1, PY159m, promoted antitumor efficacy in syngeneic mouse tumor models. These results suggest that PY159-mediated agonism of TREM1 on tumoral myeloid cells can promote a proinflammatory TME and offer a promising strategy for immunotherapy.
The Influence of Frictional Treatment and Low-Temperature Plasma Carburizing on the Structure and Phase Composition of Metastable Austenitic Steel
Authors: Savrai R. A. , Skorynina P. A. , Makarov A. V. , Men’shakov A. I. , Gaviko V. S.
Published: August 2023

The features of the structure and phase composition of corrosion-resistant austenitic chromium–nickel steel (16.80 wt % Cr, 8.44 wt % Ni) subjected to carburizing in electron beam plasma at temperatures of 350 and 500°C, frictional treatment with a sliding indenter, and a combination of frictional treatment and plasma carburizing have been considered. It has been established that plasma carburizing results in the formation of a modified surface layer consisting of carbon-saturated austenite and carbides (Cr23C6, Fe3C); in this case, the formation of γC-phase occurs only at a temperature of 350°C. The depth of a modified layer increases with an increase in the carburizing temperature. It has been shown that it is useful to perform combined frictional treatment and plasma carburizing at a carburizing temperature of 350°C, since in this case the deformation-induced structure formed as a result of frictional treatment is preserved, and the precipitated carbides remain highly dispersed. In this case, frictional treatment should provide the formation of the deepest possible diffusion-active layer with a dispersed structure.
Asthma, classical conditioning, and the autonomic nervous system – a hypothesis for why children wheeze
Authors: Connett Gary James
Published: August 2023

Paediatric asthma is an increasing global healthcare problem for which current treatments are not always effective. This review explores how abnormal triggering of the autonomic diving reflex might be important in explaining research findings and the real-world experience of asthma. It hypothesises that the way in which stress during pregnancy is associated with childhood asthma could be through effects on the developing nervous system. This results in increased parasympathetic responsiveness and specifically, excessive triggering of the diving reflex in response to wetting and cooling of the face and nose as occurs with upper airway infections and allergic rhinitis. In aquatic mammals the reflex importantly includes the contraction of airway smooth muscle to minimise lung volume and prevent nitrogen narcosis from diving at depth. Misfiring of this reflex in humans could result in the pathological airway narrowing that occurs in asthma. The diving reflex, and possibly also smooth muscle, is a vestigial remnant of our aquatic past. The hypothesis further suggests that classically conditioned reflex responses to neutral cues and contexts that were present at the same time as the stimuli that initially caused symptoms, become of themselves ongoing triggers of recurrent wheeze. Symptoms occurring in this way, irrespective of the presence of allergens and ongoing airway sensitisation, explain why allergen avoidance is poorly effective in alleviating wheeze and why asthma is made worse by stress. Interventions to suppress the diving reflex and to prevent reflex conditioned wheezing could result in more effective asthma management.
Parental perspectives about information and deferred versus two-stage consent in studies of neonatal asphyxia
Authors: Maiwald Christian A , Rovers Charlotte , Janvier Annie , Sturm Heidrun , Michaelis Martina , Marckmann Georg , Ehni Hans-Joerg , Poets Christian F , Rüdiger Mario , Franz Axel R
Published: August 2023

Objective

The ALBINO Trial (NCT03162653) investigates effects of very early postnatal allopurinol on neurocognitive outcome following perinatal asphyxia where prenatal informed consent (IC) is impossible. Ethically and legally, waiver of consent and/or deferred consent (DC) is acceptable in such an emergency. Short oral/two-step consent (SOC, brief information and oral consent followed by IC) has recently been investigated.

Methods

Mixed-methods analysis of parental opinions on DC versus SOC in the context of neonatal asphyxia in a survey at two German centres. Prospective parents (ProP), parents of healthy newborns (PNeo) and parents of asphyxiated infants (PAx) born between 2006 and 2016 were invited.

Results

108 of 422 parents participated (ProP:43; PNeo:35; PAx:30). Most parents trusted physicians, wanted preinterventional information and agreed that in emergencies interventions should begin immediately. Intergroup and intragroup variability existed for questions about DC and SOC. In the ALBINO Trial situation, 55% preferred SOC, and 26% reported DC without information might adversely affect their trust. Only 3% reported to potentially take legal action after DC. PAx were significantly more likely to support DC. PAx more frequently expressed positive emotions and appreciation for neonatal research. In open-ended questions, parents gave many constructive recommendations.

Conclusion

In this survey, parents expressed diverse opinions on consent, but the majority preferred SOC over DC. Parents who had experienced emergency admission of their asphyxiated neonates were more trusting. Obtaining parental perspectives is essential when designing studies, while being cognisant that these groups of parents may not represent the opinion of all parents.
Does prior concussion lead to biomechanical alterations associated with lateral ankle sprain and anterior cruciate ligament injury? A systematic review and meta-analysis
Authors: Chou Tsung-Yeh , Huang Yu-Lun , Leung Willie , Brown Cathleen N , Kaminski Thomas W , Norcross Marc F
Published: August 2023

Objective

To determine whether individuals with a prior concussion exhibit biomechanical alterations in balance, gait and jump-landing tasks with and without cognitive demands that are associated with risk of lateral ankle sprain (LAS) and anterior cruciate ligament (ACL) injury.

Design

Systematic review and meta-analysis.

Data sources

Five electronic databases (Web of Science, Scopus, PubMed, SPORTDiscus and CiNAHL) were searched in April 2023.

Eligibility criteria

Included studies involved (1) concussed participants, (2) outcome measures of spatiotemporal, kinematic or kinetic data and (3) a comparison or the data necessary to compare biomechanical variables between individuals with and without concussion history or before and after a concussion.

Results

Twenty-seven studies were included involving 1544 participants (concussion group (n=757); non-concussion group (n=787)). Individuals with a recent concussion history (within 2 months) had decreased postural stability (g=0.34, 95% CI 0.20 to 0.49, p<0.001) and slower locomotion-related performance (g=0.26, 95% CI 0.11 to 0.41, p<0.001), both of which are associated with LAS injury risk. Furthermore, alterations in frontal plane kinetics (g=0.41, 95% CI 0.03 to 0.79, p=0.033) and sagittal plane kinematics (g=0.30, 95% CI 0.11 to 0.50, p=0.002) were observed in individuals approximately 2 years following concussion, both of which are associated with ACL injury risk. The moderator analyses indicated cognitive demands (ie, working memory, inhibitory control tasks) affected frontal plane kinematics (p=0.009), but not sagittal plane kinematics and locomotion-related performance, between the concussion and non-concussion groups.

Conclusion

Following a recent concussion, individuals display decreased postural stability and slower locomotion-related performance, both of which are associated with LAS injury risk. Moreover, individuals within 2 years following a concussion also adopt a more erect landing posture with greater knee internal adduction moment, both of which are associated with ACL injury risk. While adding cognitive demands to jump-landing tasks affected frontal plane kinematics during landing, the altered movement patterns in locomotion and sagittal plane kinematics postconcussion persisted regardless of additional cognitive demands.

PROSPERO registration number

CRD42021248916.
Women’s preferences for pelvic floor screening in sport and exercise: a mixed-methods study integrating survey and interview data in Australian women
Authors: Dakic Jodie G , Hay-Smith E Jean C , Lin Kuan-Yin , Cook Jill L , Frawley Helena C
Published: August 2023

Objectives

One in two women experiencing pelvic floor (PF) symptoms stop playing sport or exercising. The study examines the perspective of women with PF symptoms to inform acceptable screening practices within sport and exercise settings.

Methods

Explanatory, sequential, mixed-methods design. Phase 1: survey of 18–65 years, symptomatic, Australian women (n=4556). Phase 2: semistructured interviews with a subset of survey participants (n=23). Integration occurred through connection of phases (study design, sampling) and joint display of data.

Results

Findings are represented in three threads: (1) ‘women (not) telling’; a majority of women had told no-one within a sport or exercise setting about their PF symptoms due to shame/embarrassment, lack of pelvic health knowledge and not wanting to initiate the conversation, (2) ‘asking women (screening for PF symptoms)’; women endorsed including PF symptom questions within existing sport and exercise screening practices but only when conducted in a respectful and considered manner and (3) ‘creating safety’; professionals can assist women to disclose by demonstrating expertise, trustworthiness and competency. If health and exercise professionals are provided with appropriate training, they could raise pelvic health awareness and promote a supportive and safe sport and exercise culture.

Conclusion

Women with PF symptoms support health and exercise professionals initiating conversations about PF health to normalise the topic, and include PF symptoms among other pre-exercise screening questions. However, women should be informed on the relevance and potential benefits of PF screening prior to commencing. Safe screening practices require building trust by providing information, gaining consent, displaying comfort and genuine interest, and being knowledgeable within one’s scope of practice to the provision of advice, exercise modifications and referral as appropriate.
Association between perinatal mortality and morbidity and customised and non-customised birthweight centiles in Denmark, Finland, Norway, Wales, and England: comparative, population based, record linkage study
Authors: Kilpi Fanny , Jones Hayley E , Magnus Maria Christine , Santorelli Gillian , Højsgaard Schmidt Lise Kristine , Urhoj Stine Kjaer , Nelson Scott M , Tuffnell Derek , French Robert , Magnus Per Minor , Nybo Andersen Anne-Marie , Martikainen Pekka , Tilling Kate , Lawlor Deborah A
Published: August 2023

Objectives

To compare the risk of adverse perinatal outcomes according to infants who are born small for gestational age (SGA; <10th centile) or large for gestational age (LGA; >90th centile), as defined by birthweight centiles that are non-customised (ie, standardised by sex and gestational age only) and customised (by sex, gestational age, maternal weight, height, parity, and ethnic group).

Design

Comparative, population based, record linkage study with meta-analysis of results.

Setting

Denmark, Finland, Norway, Wales, and England (city of Bradford), 1986-2019.

Participants

2 129 782 infants born at term in birth registries.

Main outcome measures

Stillbirth, neonatal death, infant death, admission to neonatal intensive care unit, and low Apgar score (<7) at 5 minutes.

Results

Relative to those infants born average for gestational age (AGA), both SGA and LGA births were at increased risk of all five outcomes, but observed relative risks were similar irrespective of whether non-customised or customised charts were used. For example, for SGA versus AGA births, when non-customised and customised charts were used, relative risks pooled over countries were 3.60 (95% confidence interval 3.29 to 3.93) versus 3.58 (3.02 to 4.24) for stillbirth, 2.83 (2.18 to 3.67) versus 3.32 (2.05 to 5.36) for neonatal death, 2.82 (2.07 to 3.83) versus 3.17 (2.20 to 4.56) for infant death, 1.66 (1.49 to 1.86) versus 1.54 (1.30 to 1.81) for low Apgar score at 5 minutes, and (based on Bradford data only) 1.97 (1.74 to 2.22) versus 1.94 (1.70 to 2.21) for admission to the neonatal intensive care unit. The estimated sensitivity of combined SGA or LGA births to identify the three mortality outcomes ranged from 31% to 34% for non-customised charts and from 34% to 38% for customised charts, with a specificity of 82% and 80% with non-customised and customised charts, respectively.

Conclusions

These results suggest an increased risk of adverse perinatal outcomes of a similar magnitude among SGA or LGA term infants when customised and non-customised centiles are used. Use of customised charts for SGA/LGA births—over and above use of non-customised charts for SGA/LGA births—is unlikely to provide benefits in terms of identifying term births at risk of these outcomes.
Antenatal, intrapartum and infant azithromycin to prevent stillbirths and infant deaths: study protocol for SANTE, a 2×2 factorial randomised controlled trial in Mali
Authors: Driscoll Amanda J , Haidara Fadima Cheick , Tapia Milagritos D , Deichsel Emily L , Samake Ousmane S , Bocoum Tiecoura , Bailey Jason A , Fitzpatrick Meagan C , Goldenberg Robert L , Kodio Mamoudou , Moulton Lawrence H , Nasrin Dilruba , Onwuchekwa Uma , Shaffer Allison M , Sow Samba O , Kotloff Karen L
Published: August 2023

Introduction

In high mortality settings, prophylactic azithromycin has been shown to improve birth weight and gestational age at birth when administered antenatally, to reduce the incidence of neonatal infections when administered intrapartum, and to improve survival when administered in infancy. Questions remain regarding whether azithromycin can prevent stillbirths, and regarding the optimal strategy for the delivery of azithromycin to pregnant women and their infants.

Methods and analysis

Sauver avec l’Azithromycine en Traitant les Femmes Enceintes et les Enfants (SANTE) is a 2×2 factorial, individually randomised, placebo-controlled, double-masked trial in rural Mali. The primary aims are: (1A) to assess the efficacy of antenatal and intrapartum azithromycin on a composite outcome of stillbirths and infant mortality through 6–12 months and (1B) to assess the efficacy of azithromycin administered concurrently with the first and third doses of pentavalent vaccines (Penta-1/3) on infant mortality through 6–12 months. Pregnant participants (n=49 600) and their infants are randomised 1:1:1:1 to one of four treatment arms: (1) mother and infant receive azithromycin, (2) mother and infant receive placebo, (3) mother receives azithromycin and infant receives placebo or (4) mother receives placebo and infant receives azithromycin. Pregnant participants receive three single 2 g doses: two antepartum and one intrapartum. Infants receive a single 20 mg/kg dose at the Penta-1 and 3 visits. An additional cohort of 12 000 infants is recruited at the Penta-1 visit and randomised 1:1 to receive azithromycin or placebo at the same time points. The SANTE trial will inform guidelines and policies regarding the administration of antenatal and infant azithromycin using routine healthcare delivery platforms.

Ethics and dissemination

This trial was approved by the Institutional Review Board at the University of Maryland School of Medicine (Protocol #HP-00084242) and the Faculté de Médecine et d’Odonto-Stomatologie in Mali. The findings of this trial will be published in open access peer-reviewed journals.

Trial registration number

NCT03909737.