bluuebunny/crossref_metadata_2025 huggingface dataset:
Dispersion Influence of Electroacoustic Transducer Parameters in the Design Process of Miniature Loudspeaker Arrays and Omnidirectional Sound Sources
Authors: Chojnacki Bartlomiej
Published: July 2024

Electroacoustic transducers represent one of the crucial materials used in the construction of loudspeaker arrays. The dispersion in their parameters may influence the performance of a speaker set. Parametric loudspeaker arrays and omnidirectional sound sources have been used for years. However, the possible influence of transducer manufacturing tolerances on the arrays’ performance has not been investigated. In previous research, the sources of possible dispersion in acoustic measurements carried out with omnidirectional sources were studied, pointing out that the problems with sound sources may be a significant reason behind the small measurement repeatability in standards. This paper investigated the measurement of several common types of miniature speakers, using 10 pieces of each type and investigating the influence of their parameter dispersion in electric and acoustic ways. Numerical simulations of omnidirectional sound sources were performed to investigate the drivers’ dispersion influence sensitivity. The results provided proof of the small-signal parameter dispersion reaching 20% of the variation. The acoustic measurements show that the loudspeakers may differ in sensitivity parameters by up to 4 dB in 10 transducer tests. The analysis of an example multitransducer array indicated that a dispersion of a sensitivity higher than 1 dB might lead to significant misperformance in constructed arrays and measurement deviations with this type of array.
Quality Assurance of Point and 2D Shear Wave Elastography through the Establishment of Baseline Data Using Phantoms
Authors: Gallet Jacqueline , Sassaroli Elisabetta , Yuan Qing , Aljabal Areej , Park Mi-Ae
Published: July 2024

Ultrasound elastography has been available on most modern systems; however, the implementation of quality processes tends to be ad hoc. It is essential for a medical physicist to benchmark elastography measurements on each system and track them over time, especially after major software upgrades or repairs. This study aims to establish baseline data using phantoms and monitor them for quality assurance in elastography. In this paper, we utilized two phantoms: a set of cylinders, each with a composite material with varying Young’s moduli, and an anthropomorphic abdominal phantom containing a liver modeled to represent early-stage fibrosis. These phantoms were imaged using three ultrasound manufacturers’ elastography functions with either point or 2D elastography. The abdominal phantom was also imaged using magnetic resonance elastography (MRE) as it is recognized as the non-invasive gold standard for staging liver fibrosis. The scaling factor was determined based on the data acquired using MR and US elastography from the same vendor. The ultrasound elastography measurements showed inconsistency between different manufacturers, but within the same manufacturer, the measurements showed high repeatability. In conclusion, we have established baseline data for quality assurance procedures and specified the criteria for the acceptable range in liver fibrosis phantoms during routine testing.
End-to-End Autonomous Driving Decision Method Based on Improved TD3 Algorithm in Complex Scenarios
Authors: Xu Tao , Meng Zhiwei , Lu Weike , Tong Zhongwen
Published: July 2024

The ability to make informed decisions in complex scenarios is crucial for intelligent automotive systems. Traditional expert rules and other methods often fall short in complex contexts. Recently, reinforcement learning has garnered significant attention due to its superior decision-making capabilities. However, there exists the phenomenon of inaccurate target network estimation, which limits its decision-making ability in complex scenarios. This paper mainly focuses on the study of the underestimation phenomenon, and proposes an end-to-end autonomous driving decision-making method based on an improved TD3 algorithm. This method employs a forward camera to capture data. By introducing a new critic network to form a triple-critic structure and combining it with the target maximization operation, the underestimation problem in the TD3 algorithm is solved. Subsequently, the multi-timestep averaging method is used to address the policy instability caused by the new single critic. In addition, this paper uses Carla platform to construct multi-vehicle unprotected left turn and congested lane-center driving scenarios and verifies the algorithm. The results demonstrate that our method surpasses baseline DDPG and TD3 algorithms in aspects such as convergence speed, estimation accuracy, and policy stability.
Experimental and Density Functional Theory Simulation Research on PdO–SnO2 Nanosheet Ethanol Gas Sensors
Authors: Wu Hao , Zhang Jianwei , Zhu Huichao , Li Xiaogan , Liu Hongxu , Tang Zhenan , Yao Guanyu , Yu Jun
Published: July 2024

Pure SnO2 and 1 at.% PdO–SnO2 materials were prepared using a simple hydrothermal method. The micromorphology and element valence state of the material were characterized using XRD, SEM, TEM, and XPS methods. The SEM results showed that the prepared material had a two-dimensional nanosheet morphology, and the formation of PdO and SnO2 heterostructures was validated through TEM. Due to the influence of the heterojunction, in the XPS test, the energy spectrum peaks of Sn and O in PdO–SnO2 were shifted by 0.2 eV compared with SnO2. The PdO–SnO2 sensor showed improved ethanol sensing performance compared to the pure SnO2 sensor, since it benefited from the large specific surface area of the nanosheet structure, the modulation effect of the PdO–SnO2 heterojunction on resistance, and the catalyst effect of PdO on the adsorption of oxygen. A DFT calculation study of the ethanol adsorption characteristics of the PdO–SnO2 surface was conducted to provide a detailed explanation of the gas-sensing mechanism. PdO was found to improve the reducibility of ethanol, enhance the adsorption of ethanol’s methyl group, and increase the number of adsorption sites. A synergistic effect based on the continuous adsorption sites was also deduced.
Parking Lot Traffic Prediction Based on Fusion of Multifaceted Spatio-Temporal Features
Authors: Zhang Lechuan , Wang Bin , Zhang Qian , Zhu Sulei , Ma Yan
Published: July 2024

With the rapid growth of population and vehicles, issues such as traffic congestion are becoming increasingly apparent. Parking guidance and information (PGI) systems are becoming more critical, with one of the most important tasks being the prediction of traffic flow in parking lots. Predicting parking traffic can effectively improve parking efficiency and alleviate traffic congestion, traffic accidents, and other problems. However, due to the complex characteristics of parking spatio-temporal data, high levels of noise, and the intricate influence of external factors, there are three challenges to predicting parking traffic in a city effectively: (1) how to better model the nonlinear, asymmetric, and complex spatial relationships among parking lots; (2) how to model the temporal autocorrelation of parking flow more accurately for each parking lot, whether periodic or aperiodic; and (3) how to model the correlation between external influences, such as holiday weekends, POIs (points of interest), and weather factors. In this context, this paper proposes a parking lot traffic prediction model based on the fusion of multifaceted spatio-temporal features (MFF-STGCN). The model consists of a feature embedding module, a spatio-temporal attention mechanism module, and a spatio-temporal convolution module. The feature embedding module embeds external features such as weekend holidays, geographic POIs, and weather features into the time series, the spatio-temporal attention mechanism module captures the dynamic spatio-temporal correlation of parking traffic, and the spatio-temporal convolution module captures the spatio-temporal features by using graph convolution and gated recursion units. Finally, the outputs of adjacent time series, daily series, and weekly series are weighted and fused to obtain the final prediction results, thus predicting the parking lot traffic flow more accurately and effectively. Results on real datasets demonstrate that the proposed model enhances prediction performance.
Civic Literacy and Disinformation in Democracies
Authors: Lilja Jannie , Eklund Niklas , Tottie Ester
Published: July 2024

The aim of this study is to explore civic literacy as an approach to counter disinformation in democracies. From group interviews, we elicit, categorize, and analyze diverse perspectives on disinformation in Sweden, previously upheld as a country with high civic literacy levels. We focus on people’s understandings of disinformation, their assessment of their own abilities to discern disinformation, and their ideas about how increased resilience to disinformation could be achieved. Our findings, based on input from 73 interviewees across Sweden, suggest that shared basic knowledge on disinformation is lacking. Moreover, there is a related weak understanding of what constitutes authentic information. Those with low awareness operate on a logic of beliefs, implying that measures to improve factuality and objectivity could not even be aspired for. Still, there are also constituents showing advanced understandings. The majority of respondents call for new measures to strengthen citizen knowledge and skills and generate many proposals to that end. Our results indicate that citizen competence needs to increase considerably to keep up with the rapidly evolving disinformation environment. A concerted drive to boost citizen knowledge and skills, tailored to different constituencies, is needed for the democratic system to work as intended.
Effect of Knee Angle, Contractile Activity, and Intensity of Force Production on Vastus Lateralis Stiffness: A Supersonic Shear Wave Elastography Pilot Study
Authors: Santos Rute , Valamatos Maria João , Mil-Homens Pedro , Armada-da-Silva Paulo A. S.
Published: July 2024

Supersonic shear image (SSI) ultrasound elastography provides a quantitative assessment of tissue stiffness using the velocity of shear waves. SSI’s great potential has allowed researchers in fields like biomechanics and muscle physiology to study the function of complex muscle groups in different conditions. The aim of this study is to use SSI to investigate changes in the stiffness of the vastus lateralis (VL) muscle as a consequence of passive elongation, isometric contraction, and repeated muscle activity. In a single session, 15 volunteers performed a series of isometric, concentric, and eccentric contractions. SSI images were collected from the VL to assess its stiffness before and after the contractions and at various knee angles. Two-way within-subjects ANOVA was used to test the effects of muscle contraction type and knee angle on VL stiffness. Linear regression analysis was employed to assess the relationship between muscle stiffness and the intensity of isometric contractions. After maximal contractions, VL stiffness increased by approximately 10% compared to baseline values, and following maximal isometric (p < 0.01) and eccentric contractions (p < 0.05). Yet, there was no change in VL shear modulus at the end of concentric contractions. The relaxed VL shear modulus increased with knee flexion both before and after the knee extensor contractions (p < 0.001). A linear relationship between the shear modulus and the degree of isometric contraction was observed, although with notable individual variation (R2 = 0.125). Maximal contractile activity produces modest increases in relaxed muscle stiffness. The SSI-measured shear modulus increases linearly with the degree of isometric contraction.
The Impact of Knowledge Spillovers on Economic Growth from a National Perspective: A Comprehensive Analysis
Authors: Arcos-Guanga Adriana , Flor-Unda Omar , Novillo-Villegas Sylvia , Acosta-Vargas Patricia
Published: July 2024

Knowledge spillovers, driven by development and research projects, are crucial in generating new companies and services. They enhance innovation, improve competitiveness, and sustain the economic growth of nations. Hence, this paper aims to examine the relationship between knowledge spillovers and economic growth. It offers a comprehensive review of the scientific literature on the relationship between knowledge spillovers and economic growth, investigating the impact of economic cycles on knowledge spillover. Doing this provides valuable insights into how to leverage them at the different stages of the economic cycle. Hence, a PRIMA systematic review was conducted. Articles from the last 15 years were analyzed from repositories and scientific databases with a Cohen’s kappa coefficient of 0.8902. This review identifies and presents a systematic analysis of the impacts of favoring and hindering knowledge spillovers in the economic growth of a nation. These effects offer greater resilience to a nation after periods of recession. In addition, the case study of three countries is presented to illustrate the findings from the review. The results show that better utilizing knowledge spillovers to enhance economic growth depends on a functional compromise between the university, industry, and governments to understand and commit to knowledge-based economic development. Our study has implications for policymakers who aim to boost economic growth by promoting knowledge spillovers.
Mitigating UV-Induced Degradation in Solar Panels through ZnO Nanocomposite Coatings
Authors: Ghaffar Abdul , Channa Iftikhar Ahmed , Chandio Ali Dad
Published: July 2024

This study explores the enhancement of silicon-based solar cell performance and durability through the application of zinc oxide (ZnO) nanocomposite film coatings. Utilizing the sol–gel method, ZnO nanorods were synthesized and dispersed within a polyvinyl butyral (PVB) matrix, resulting in uniform nanocomposite films. Comprehensive characterization using X-ray Diffraction (XRD), Fourier-Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), UV-Visible spectroscopy, and contact angle measurements confirmed the effective integration and desirable properties of ZnO within the PVB matrix. The ZnO coatings demonstrated superior UV absorptivity, significantly blocking UV radiation at 355 nm while maintaining high transparency in the visible range. This led to improvements in key photovoltaic parameters, including short circuit current (Jsc), open-circuit voltage (Voc), efficiency (η), and fill factor (FF). Although a minor reduction in Isc was observed due to the ZnO layer’s influence on the light absorption spectrum, the overall efficiency and fill factor experienced notable enhancements. Furthermore, the thermal load on the solar cells was effectively reduced, mitigating UV-induced degradation and thereby prolonging the operational lifespan of the solar panels. Under damp heat conditions, the coated solar panels exhibited remarkable durability compared to their uncoated counterparts, underscoring the protective advantages of ZnO films. These findings highlight the potential of ZnO nanocomposite coatings to significantly boost the efficiency, reliability, and longevity of silicon-based solar panels, making them more viable for long-term deployment in diverse environmental conditions.
Spatiotemporal Characterization of the Three-Dimensional Morphology of Urban Buildings Based on Moran’s I
Authors: Shen Tao , Zhou Wenshiqi , Yuan Shuai , Huo Liang
Published: July 2024

The three-dimensional morphological analysis of urban buildings constitutes a pivotal component of urban planning and sustainable development. Nevertheless, the majority of current research is two-dimensional in nature, which constrains the comprehensive understanding of urban spatial–temporal evolution. The existing body of three-dimensional studies frequently fails to consider the temporal dimension of architectural change and lacks a detailed examination of micro areas such as communities and streets. In order to accurately identify the patterns of spatial–temporal evolution in urban architectural morphology, this study focuses on the Yau Tsim Mong District in Hong Kong, utilizing three-dimensional data. By innovatively integrating temporal factors, constructing a spatial–temporal weight matrix, and applying the spatial–temporal Moran’s I, this study conducts an in-depth quantitative analysis of Coverage, Staggeredness, and Duty Cycle at the community scale, neighborhood scale, and urban scale. From 2014 to 2023, the global spatial–temporal Moran’s I of key urban morphology indicators in Yau Tsim Mong District has exhibited a marked increase, underscoring the close interrelationship and significant optimization between urban morphology and overall development. The findings illustrate that urban architecture is undergoing a process of agglomeration and high homogeneity, with strategic shifts emphasizing efficient spatial utilization and refined design. The analysis at the neighborhood scale is of particular importance, as its independent and complete spatial structure effectively captures local dynamics, revealing high-value agglomeration and low-value dispersion characteristics. This suggests that buildings in the Yau Tsim Mong District are being constructed in a more compact manner at the neighborhood level, which reflects the precision and efficiency of urban planning and the rationality of spatial planning. These significant findings provide valuable references for the development planning and governance of sustainable cities. They enhance urban governance capabilities and promote the optimization of urban development strategies, ensuring steady progress on the path of efficiency, harmony, and sustainability.
Interconnected Eco-Consciousness: Gen Z Travelers’ Intentions toward Low-Carbon Transportation and Hotels
Authors: Ma Ying , Li Yangganxuan , Han Fang
Published: July 2024

Generation Z (Gen Z) is widely acknowledged for their heightened eco-consciousness. Nevertheless, a notable research gap persists in the empirical examination of eco-friendly preferences within this demographic group, particularly concerning low-carbon transportation and hotel selections. Utilizing structural equation modeling and data collected from 357 Gen Z travelers, this study investigates the interconnected factors influencing Gen Z travelers’ intentions toward adopting low-carbon transportation and making low-carbon hotel choices based on the theory of planned behavior (TPB). The results indicate that perceived value and environmental concern exert significant influence on the formation of attitudes, subjective norms, and perceived behavioral control among Gen Z travelers. As a result, these psychosocial constructs make a substantial contribution to the intention of Gen Z travelers of adopting low-carbon tourism behaviors. Additionally, the study uncovers a positive correlation between the propensity to use low-carbon transportation and the inclination to choose low-carbon hotels for accommodation. These findings underscore the interconnected facets of Gen Z’s preferences for low-carbon tourism, thereby indicating the prospect for collaborative efforts to bolster sustainability within the tourism industry.
Risk Assessment of Displaced Sediment by an Extreme Event Cyclone in a Peri-Urban Zone Using Bioassays and Analytical Chemistry
Authors: Tremblay Louis A. , Nakajima Daisuke , Endo Satoshi , Yagishita Mayuko , Ludlow Hannah , Mackay Ariana , Champeau Olivier
Published: July 2024

Hawke’s Bay in New Zealand was impacted by Cyclone Gabrielle in 2023, experiencing intense weather conditions and rainfall. Rivers and streams surged beyond their banks, displacing large amounts of sediment. The sewage treatment plant and industries in the Waitangi catchment, south of the city of Napier, were heavily impacted, making them potential sources of contaminants. The aim of this study was to investigate the risk of displaced sediments deposited south of Napier City, using bioassays and chemical analysis methods. Sediment samples were collected across a gradient between the coastline and the Waitangi Stream. The toxicity of chemically extracted or elutriate samples was assessed by Microtox®, mussel embryo–larval development, and aryl hydrocarbon and constitutive androstane receptor yeast two-hybrid assays. Targeted chemical analysis and automated identification and quantification system (AIQS-GC) methods were used to identify contaminants. The elutriates showed low toxicity and the yeast assays showed levels of activity like those previously reported. Chemical methods confirmed historical contamination by DDT and its metabolites DDE and DDD, as well as by plant sterols. Overall, the toxicity and chemicals detected are what would be expected from a typical agricultural soil. The risk posed by the displaced sediment in the Waitangi catchment can be considered low. Combining chemical and bioanalytical methods was an effective approach to investigate the potential risks of post-disaster contamination.
Association of Urinary Glyphosate with All-Cause Mortality and Cardiovascular Mortality among Adults in NHANES 2013–2018: Role of Alkaline Phosphatase
Authors: Gao Yongyue , Shu Shuge , Zhang Di , Wang Pu , Yu Xiangyu , Wang Yucheng , Yu Yongquan
Published: July 2024

Glyphosate is the most widely used herbicide in the world. This study aimed to evaluate the relationships among urinary glyphosate, all-cause mortality and cardiovascular diseases (CVD)-related mortality in the general US population of adults, and to determine the role of alkaline phosphatase (ALP), an inflammation marker that is associated with glyphosate exposure, in these relationships. Subjects from the National Health and Nutrition Examination Survey (NHANES) 2013–2018 cycles were included. Survey-weighted Cox regression analysis was applied to estimate the relationship of glyphosate with overall and CVD mortalities. Restricted cubic spline (RCS) analysis was utilized to detect the linearity of associations. The intermediary role of ALP was explored by mediation analysis. Our results found consistent and positive associations of glyphosate with all-cause mortality (HR: 1.29, 95%CI: 1.05–1.59) and CVD mortality (HR: 1.32, 95%CI: 1.02–1.70). RCS curves further validated linear and positive dose-dependent relationships between glyphosate and mortality-related outcomes. Moreover, serum ALP was identified as a mediator in these associations and explained 12.1% and 14.0% of the total associations between glyphosate and all-cause death and CVD death risk, respectively. Our study indicated that glyphosate was associated with increased all-cause and CVD mortality in humans. Increased ALP may play an essential role in these associations.
Stellar Flares, Superflares, and Coronal Mass Ejections—Entering the Big Data Era
Authors: Vida Krisztián , Kővári Zsolt , Leitzinger Martin , Odert Petra , Oláh Katalin , Seli Bálint , Kriskovics Levente , Greimel Robert , Görgei Anna Mária
Published: July 2024

Flares, sometimes accompanied by coronal mass ejections (CMEs), are the result of sudden changes in the magnetic field of stars with high energy release through magnetic reconnection, which can be observed across a wide range of the electromagnetic spectrum from radio waves to the optical range to X-rays. In our observational review, we attempt to collect some fundamental new results, which can largely be linked to the Big Data era that has arrived due to the expansion of space photometric observations over the last two decades. We list the different types of stars showing flare activity and their observation strategies and discuss how their main stellar properties relate to the characteristics of the flares (or even CMEs) they emit. Our goal is to focus, without claiming to be complete, on those results that may, in one way or another, challenge the “standard” flare model based on the solar paradigm.
Resilient Urban Communities: A Case Study of the Cvjetno Housing Estate, a Modern Period Predecessor in Urban Planning in Croatia
Authors: Kostešić Iva
Published: July 2024

The paper analyzes the concept of resilience in the context of the Cvjetno housing estate in Zagreb, Croatia, a recognized cultural and historical complex. While extensive literature exists on the estate’s architectural and historical significance, limited research explores its resilience. This study aims to fill this gap by examining the Cvjetno estate’s planned resilience to natural hazards and socioeconomic challenges. It investigates the estate’s design, historical context, and physical characteristics through archival documents, historical records, and field research. The analysis focuses on the estate’s planned resilience to natural disasters, particularly flooding from the nearby river Sava and seismic risks due to its location in a seismically active area. Based on the literature on resilient communities, the study draws on dimensions, characteristics, and qualities of resilience, and explores how the Cvjetno estate exemplifies these traits. Future research could explore and compare similar mid-20th century European settlements to enhance the understanding of urban resilience during the modern era.
Enhanced Anti-Tumor Response Elicited by a Novel Oncolytic Pseudorabies Virus Engineered with a PD-L1 Inhibitor
Authors: Xiang Guangtao , Wang Mengdong , Wang Pu , Li Rifei , Gao Chao , Li Yue , Liang Xinxin , Liu Yun , Xu Aotian , Tang Jun
Published: July 2024

Oncolytic viruses combined with immunotherapy offer significant potential in tumor therapy. In this study, we engineered a further attenuated pseudorabies virus (PRV) vaccine strain that incorporates a PD-L1 inhibitor and demonstrated its promise as an oncolytic virus in tumor therapy. We first showed that the naturally attenuated PRV vaccine strain Bartha can efficiently infect tumor cells from multiple species, including humans, mice, and dogs in vitro. We then evaluated the safety and anti-tumor efficacy of this vaccine strain and its different single-gene deletion mutants using the B16-F10 melanoma mouse model. The TK deletion strain emerged as the optimal vector, and we inserted a PD-L1 inhibitor (iPD-L1) into it using CRISPR/Cas9 technology. Compared with the control, the recombinant PRV (rPRV-iPD-L1) exhibited more dramatic anti-tumor effects in the B16-F10 melanoma mouse model. Our study suggests that PRV can be developed not only as an oncolytic virus but also a powerful vector for expressing foreign genes to modulate the tumor microenvironment.
The Mechanism of Action of the Active Ingredients of Coptidis rhizoma against Porcine Epidemic Diarrhea Was Investigated Using Network Pharmacology and Molecular Docking Technology
Authors: Zou Hong , Niu Zheng , Tang Zhangchen , Cheng Peng , Yin Yanling , Luo Gan , Huang Shilei
Published: July 2024

The objective of this study was to elucidate the mechanism of action of the active components of Coptidis rhizoma against porcine epidemic diarrhea and to provide a theoretical foundation for further development of novel anti-PED therapeutic agents based on Coptidis rhizoma. The potential targets of Coptidis rhizoma against PEDV were identified through a comprehensive literature review and analysis using the TCMSP pharmacological database, SwissDrugDesign database, GeneCards database, and UniProt database. Subsequently, the STRING database and Cytoscape 3.7.1 software were employed to construct a protein–protein interaction (PPI) network and screen key targets. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were conducted on the identified targets. Molecular docking studies were performed using AutoDock 1.5.7 software to analyze the binding energy and modes of interaction between the active components of Coptidis rhizoma and the target proteins. The PyMOL 2.5.0a0 software was employed to visualize the docking results. Through comprehensive analysis, 74 specific targets of active components of Coptidis rhizoma against PEDV were identified. The core gene targets were screened, and an interaction network diagram was subsequently generated. Ultimately, 14 core targets were identified, with STAT3, ESR1, CASP3, and SRC exhibiting the most significant interactions. GO enrichment analysis revealed a total of 215 molecular items, including 48 biological function items, 139 biological process items, and 28 cellular component items. KEGG enrichment analysis identified 140 signaling pathways. Molecular docking analysis demonstrated that epiberberine and palmatine exhibited high binding affinity with STAT3 protein, worenine showed high binding affinity with ESR1 protein, obacunone exhibited high binding affinity with CASP3 protein, and epiberberine, obacunone, berberine, and berberruine exhibited high binding affinity with SRC protein. A network pharmacology and molecular docking technology approach was employed to screen six important active components of Coptidis rhizoma and four important potential targets against PEDV infection. The findings indicated that the active components of Coptidis rhizoma could serve as promising pharmaceutical agents for the prevention and control of PEDV, with significant potential for clinical application.
Phylogenetic Network Analyses Reveal the Influence of Transmission Clustering on the Spread of HIV Drug Resistance in Quebec from 2002 to 2022
Authors: Brenner Bluma G. , Ibanescu Ruxandra-Ilinca , Oliveira Maureen , Margaillan Guillaume , Lebouché Bertrand , Thomas Réjean , Baril Jean Guy , Lorgeoux René-Pierre , Roger Michel , Routy Jean-Pierre ,   the Montreal Primary HIV Infection (PHI) Cohort Study Group
Published: July 2024

Background: HIV drug resistance (HIV-DR) may jeopardize the benefit of antiretroviral therapy (ART) in treatment and prevention. This study utilized viral phylogenetics to resolve the influence of transmission networks on sustaining the spread of HIV-DR in Quebec spanning 2002 to 2022. Methods: Time trends in acquired (ADR) and transmitted drug resistance (TDR) were delineated in treatment-experienced (n = 3500) and ART-naïve persons (n = 6011) with subtype B infections. Similarly, non-B-subtype HIV-DR networks were assessed pre- (n = 1577) and post-ART experience (n = 488). Risks of acquisition of resistance-associated mutations (RAMs) were related to clustering using 1, 2–5, vs. 6+ members per cluster as categorical variables. Results: Despite steady declines in treatment failure and ADR since 2007, rates of TDR among newly infected, ART-naive persons remained at 14% spanning the 2007–2011, 2012–2016, and 2017–2022 periods. Notably, half of new infections among men having sex with men and heterosexual groups were linked in large, clustered networks having a median of 35 (14–73 IQR) and 16 (9–26 IQR) members per cluster, respectively. Cluster membership and size were implicated in forward transmission of non-nucleoside reverse transcriptase inhibitor NNRTI RAMs (9%) and thymidine analogue mutations (TAMs) (5%). In contrast, transmission of M184V, K65R, and integrase inhibitors (1–2%) remained rare. Levels of TDR reflected viral replicative fitness. The median baseline viremia in ART-naïve groups having no RAMs, NNRTI RAMs, TAMs, and M184VI were 46.088, 38,447, 20,330, and 6811 copies/mL, respectively (p < 0.0001). Conclusion: Phylogenetics emphasize the need to prioritize ART and pre-exposure prophylaxis strategies to avert the expansion of transmission cascades of HIV-DR.
Clinical–Epidemiological Profile of COVID-19 Patients Admitted during Three Waves of the Pandemic in a Tertiary Care Center, in Belém, Pará, Amazon Region of Brazil
Authors: Pereira Ana Beatriz Nunes , Pereira Fernando Sérgio Henriques , Araújo Júlio Éden Davi Lopes , Brasil Rangel Pereira , Oliveira Angélica Menezes Bessa , Lima Sandra Souza , Fonseca Ricardo Roberto de Souza , Laurentino Rogério Valois , Oliveira-Filho Aldemir Branco , Machado Luiz Fernando Almeida
Published: July 2024

Background: Coronavirus disease 2019 (COVID-19) is a disease with a broad clinical spectrum, which may result in hospitalization in healthcare units, intensive care, and progression to death. This study aimed to describe and compare the clinical and epidemiological profile of COVID-19 during the three waves of the disease, in patients admitted to a public hospital in the city of Belém, Pará, in the Amazon region of Brazil. Methods: This descriptive, observational, and cross-sectional study was population-based on individuals who were hospitalized with a diagnosis of COVID-19, confirmed by real-time reverse transcription-polymerase chain reaction (RT-PCR), and who were interviewed and monitored at the public hospital, from February 2020 to April 2022. Results: The prevalence was male patients, older than 60 years. The most frequent symptoms were dyspnea, cough, and fever. Systemic arterial hypertension was the most prevalent comorbidity followed by diabetes mellitus. Less than 15% of patients were vaccinated. The nasal oxygen cannula was the most used oxygen therapy interface followed by the non-rebreathing reservoir mask. Invasive mechanical ventilation predominated and the median time of invasive mechanical ventilation ranged from 2 to 6 days among waves. As for the hospital outcome, transfers prevailed, followed by deaths and discharges. Conclusion: The presence of comorbidities, advanced age, and male sex were important factors in the severity and need for hospitalization of these patients, and the implementation of the vaccination policy was an essential factor in reducing the number of hospital admissions.
In-Depth Comparison of Adeno-Associated Virus Containing Fractions after CsCl Ultracentrifugation Gradient Separation
Authors: Janc Mojca , Zevnik Kaja , Dolinar Ana , Jakomin Tjaša , Štalekar Maja , Bačnik Katarina , Kutnjak Denis , Žnidarič Magda Tušek , Zentilin Lorena , Fedorov Dmitrii , Dobnik David
Published: July 2024

Recombinant adeno-associated viruses (rAAVs) play a pivotal role in the treatment of genetic diseases. However, current production and purification processes yield AAV-based preparations that often contain unwanted empty, partially filled or damaged viral particles and impurities, including residual host cell DNA and proteins, plasmid DNA, and viral aggregates. To precisely understand the composition of AAV preparations, we systematically compared four different single-stranded AAV (ssAAV) and self-complementary (scAAV) fractions extracted from the CsCl ultracentrifugation gradient using established methods (transduction efficiency, analytical ultracentrifugation (AUC), quantitative and digital droplet PCR (qPCR and ddPCR), transmission electron microscopy (TEM) and enzyme-linked immunosorbent assay (ELISA)) alongside newer techniques (multiplex ddPCR, multi-angle light-scattering coupled to size-exclusion chromatography (SEC-MALS), multi-angle dynamic light scattering (MADLS), and high-throughput sequencing (HTS)). Suboptimal particle separation within the fractions resulted in unexpectedly similar infectivity levels. No single technique could simultaneously provide comprehensive insights in the presence of both bioactive particles and contaminants. Notably, multiplex ddPCR revealed distinct vector genome fragmentation patterns, differing between ssAAV and scAAV. This highlights the urgent need for innovative analytical and production approaches to optimize AAV vector production and enhance therapeutic outcomes.
Inequality in Childhood Immunization Coverage: A Scoping Review of Data Sources, Analyses, and Reporting Methods
Authors: Lyons Carrie , Nambiar Devaki , Johns Nicole E. , Allorant Adrien , Bergen Nicole , Hosseinpoor Ahmad Reza
Published: July 2024

Immunization through vaccines among children has contributed to improved childhood survival and health outcomes globally. However, vaccine coverage among children is unevenly distributed across settings and populations. The measurement of inequalities is essential for understanding gaps in vaccine coverage affecting certain sub-populations and monitoring progress towards achieving equity. Our study aimed to characterize the methods of reporting inequalities in childhood vaccine coverage, inclusive of the settings, data source types, analytical methods, and reporting modalities used to quantify and communicate inequality. We conducted a scoping review of publications in academic journals which included analyses of inequalities in vaccination among children. Literature searches were conducted in PubMed and Web of Science and included relevant articles published between 8 December 2013 and 7 December 2023. Overall, 242 publications were identified, including 204 assessing inequalities in a single country and 38 assessing inequalities across more than one country. We observed that analyses on inequalities in childhood vaccine coverage rely heavily on Demographic Health Survey (DHS) or Multiple Indicator Cluster Surveys (MICS) data (39.3%), and papers leveraging these data had increased in the last decade. Additionally, about half of the single-country studies were conducted in low- and middle-income countries. We found that few studies analyzed and reported inequalities using summary measures of health inequality and largely used the odds ratio resulting from logistic regression models for analyses. The most analyzed dimensions of inequality were economic status and maternal education, and the most common vaccine outcome indicator was full vaccination with the recommended vaccine schedule. However, the definition and construction of both dimensions of inequality and vaccine coverage measures varied across studies, and a variety of approaches were used to study inequalities in vaccine coverage across contexts. Overall, harmonizing methods for selecting and categorizing dimensions of inequalities as well as methods for analyzing and reporting inequalities can improve our ability to assess the magnitude and patterns of inequality in vaccine coverage and compare those inequalities across settings and time.
A Simple and Versatile Method for Ex Vivo Monitoring of Goat Vaginal Mucosa Transduction by Viral Vector Vaccines
Authors: Minesso Sergio , Odigie Amienwanlen Eugene , Franceschi Valentina , Cotti Camilla , Cavirani Sandro , Tempesta Maria , Donofrio Gaetano
Published: July 2024

Goat may represent a valid large animal model for human pathogens and new vaccines testing. Appropriate vaccine administration is a critical component of a successful immunization program. The wrong route of administration may reduce the efficacy of the vaccine, whereas the proper administration strategy can enhance it. Viral vectors have been employed successfully for goat and sheep immunization; however, no data concerning the vaginal route are available. A viral vector’s ability to transduce the site of inoculation is of primary interest. In this study, a fast and reliable ex vivo assay for testing the transduction capability of an Ad5-based vector when intravaginally administered was developed. An Ad5 vector delivering an expression cassette with a bicistronic reporter gene, Ad5-CMV-turboGFP-IRES-Luc2, was constructed. We demonstrated Ad5-CMV-turboGFP-IRES-Luc2’s ability to transduce caprine vaginal mucosa by ex vivo bioluminescent imaging (BLI) employing a simple CCD camera apparatus for chemiluminescence western immunoblotting. These data, though simple, provide valuable insights into developing a vaginal immunization strategy using a viral vector-based vaccine to protect against pathogens causing genital diseases.
Immunogenicity and Protective Efficacy of Aerosolized Live-Attenuated Yellow Fever 17D Vaccine in Mice
Authors: Zhu Feng , Sun Meng-Xu , Zhao Suo-Qun , Qin Cheng-Feng , Wang Jin-Hua , Deng Yong-Qiang
Published: July 2024

Yellow fever (YF), caused by the yellow fever virus (YFV), continually spreads and causes epidemics worldwide, posing a great threat to human health. The live-attenuated YF 17D vaccine (YF-17D) has been licensed for preventing YFV infection and administrated via the intramuscular (i.m.) route. In this study, we sought to determine the immunogenicity and protective efficacy of aerosolized YF-17D via the intratracheal (i.t.) route in mice. YF-17D stocks in liquids were successfully aerosolized into particles of 6 μm. Further in vitro phenotype results showed the aerosolization process did not abolish the infectivity of YF-17D. Meanwhile, a single i.t. immunization with aerosolized YF-17D induced robust humoral and cellular immune responses in A129 mice, which is comparable to that received i.p. immunization. Notably, the aerosolized YF-17D also triggered specific secretory IgA (SIgA) production in bronchoalveolar lavage. Additionally, all immunized animals survived a lethal dose of YFV challenge in mice. In conclusion, our results support further development of aerosolized YF-17D in the future.
A Comprehensive Review on the Intricate Interplay between COVID-19 Immunization and the New Onset of Pemphigus Foliaceus
Authors: Bălăceanu-Gurău Beatrice , Dumitrascu Adrian , Giurcăneanu Călin , Tatar Raluca , Gurău Cristian-Dorin , Orzan Olguța Anca
Published: July 2024

Autoimmune bullous diseases (AIBDs) are characterized by the formation of vesicles, bullous lesions, and mucosal erosions. The autoantibodies target the cellular anchoring structures from the surface of epidermal keratinocyte named desmosomes, leading to a loss of cellular cohesion named acantholysis. AIBDs are classified into intraepidermal or subepidermal types based on clinical features, histological characteristics, and immunofluorescence patterns. Pemphigus foliaceus (PF) is an acquired, rare, autoimmune skin condition associated with autoantibodies that specifically target desmoglein-1, leading to a clinical presentation characterized by delicate cutaneous blisters, typically sparing the mucous membranes. Several factors, including genetic predisposition, environmental triggers, malignancies, medication use, and vaccination (for influenza, hepatitis B, rabies, tetanus, and more recently, severe acute respiratory syndrome Coronavirus 2 known as SARS-CoV-2), can potentially trigger the onset of pemphigus. With the advent of vaccines playing a pivotal role in combatting the 2019 coronavirus disease (COVID-19), extensive research has been conducted globally to ascertain their efficacy and potential cutaneous adverse effects. While reports of AIBDs post-COVID-19 vaccination exist in the medical literature, instances of PF following vaccination have been less commonly reported worldwide. The disease’s pathophysiology is likely attributed to the resemblance between the ribonucleic acid (RNA) antigen present in these vaccines and cellular nuclear matter. The protein produced by the BNT-162b2 messenger ribonucleic acid (mRNA) vaccine includes immunogenic epitopes that could potentially trigger autoimmune phenomena in predisposed individuals through several mechanisms, including molecular mimicry, the activation of pattern recognition receptors, the polyclonal stimulation of B cells, type I interferon production, and autoinflammation. In this review, we present a comprehensive examination of the existing literature regarding the relationship between COVID-19 and PF, delving into their intricate interactions. This exploration improves the understanding of both pemphigus and mRNA vaccine mechanisms, highlighting the importance of close monitoring for PF post-immunization.
Preclinical Safety Assessment of the EBS-LASV Vaccine Candidate against Lassa Fever Virus
Authors: Matassov Demetrius , DeWald Lisa Evans , Hamm Stefan , Nowak Rebecca M. , Gerardi Cheryl S. , Latham Theresa E. , Xu Rong , Luckay Amara , Chen Tracy , Tremblay Marc , Shearer Jeffry , Wynn Melissa , Eldridge John H. , Warfield Kelly , Spurgers Kevin
Published: July 2024

There are currently no prophylactic vaccines licensed to protect against Lassa fever caused by Lassa virus (LASV) infection. The Emergent BioSolutions (EBS) vaccine candidate, EBS-LASV, is being developed for the prevention of Lassa fever. EBS-LASV is a live-attenuated recombinant Vesicular Stomatitis Virus (rVSV)-vectored vaccine encoding the surface glycoprotein complex (GPC) from LASV and has two attenuating vector modifications: a gene shuffle of the VSV N gene and a deletion of the VSV G gene. Preclinical studies were performed to evaluate EBS-LASV’s neurovirulence potential following intracranial (IC) injection and to determine the biodistribution and vector replication following intramuscular (IM) inoculation in mice. In addition, the potential EBS-LASV toxicity was assessed using repeated-dose IM EBS-LASV administration to rabbits. All mice receiving the IC injection of EBS-LASV survived, while mice administered the unattenuated control vector did not. The vaccine was only detected in the muscle at the injection site, draining lymph nodes, and the spleen over the first week following IM EBS-LASV injection in mice, with no detectable plasma viremia. No toxicity was observed in rabbits receiving a three-dose regimen of EBS-LASV. These studies demonstrate that EBS-LASV is safe when administered to animals and supported a first-in-human dose-escalation, safety, and immunogenicity clinical study.
Leveraging Immunofocusing and Virus-like Particle Display to Enhance Antibody Responses to the Malaria Blood-Stage Invasion Complex Antigen PfCyRPA
Authors: Björnsson Kasper H. , Bassi Maria R. , Knudsen Anne S. , Aves Kara-Lee , Morella Roig Èlia , Sander Adam F. , Barfod Lea
Published: July 2024

A vaccine protecting against malaria caused by Plasmodium falciparum is urgently needed. The blood-stage invasion complex PCRCR consists of the five malarial proteins PfPTRAMP, PfCSS, PfRipr, PfCyRPA, and PfRH5. As each subcomponent represents an essential and highly conserved antigen, PCRCR is considered a promising vaccine target. Furthermore, antibodies targeting the complex can block red blood cell invasion by the malaria parasite. However, extremely high titers of neutralizing antibodies are needed for this invasion-blocking effect, and a vaccine based on soluble PfRH5 protein has proven insufficient in inducing a protective response in a clinical trial. Here, we present the results of two approaches to increase the neutralizing antibody titers: (A) immunofocusing and (B) increasing the immunogenicity of the antigen via multivalent display on capsid virus-like particles (cVLPs). The immunofocusing strategies included vaccinating with peptides capable of binding the invasion-blocking anti-PfCyRPA monoclonal antibody CyP1.9, as well as removing non-neutralizing epitopes of PfCyRPA through truncation. Vaccination with PfCyRPA coupled to the AP205 cVLP induced nearly two-fold higher IgG responses compared to vaccinating with soluble PfCyRPA protein. Immunofocusing using a linear peptide greatly increased the neutralizing capacity of the anti-PfCyRPA antibodies. However, significantly lower total anti-PfCyRPA titers were achieved using this strategy. Our results underline the potential of a cVLP-based malaria vaccine including full-length PfCyRPA, which could be combined with other leading malaria vaccine antigens presented on cVLPs.