bluuebunny/crossref_metadata_2025 huggingface dataset:
Effectiveness of a Triple Antiarrhythmic Drug Strategy for Arrhythmia Recurrence after Persistent Atrial Fibrillation Ablation
Authors: Jin Shuyu , Chen Haowei , Fang Xianhong , Liao Hongtao , Zhan Xianzhang , Fu Lu , Jiang Junrong , Ye Xingdong , Liu Huiyi , Chen Yanlin , Pu Sijia , Wu Shulin , Deng Hai , Lin Weidong , Xue Yumei
Published: October 2024

Background and objective

Treating recurrent atrial arrhythmias after persistent atrial fibrillation (PeAF) ablation is often challenging. This single‐center, prospective study aimed to observe the effectiveness of different combinations of oral antiarrhythmic drugs (AADs) in reverting to sinus rhythm (SR) in patients with recurrent atrial arrhythmias after PeAF ablation.

Methods

Forty‐five patients who experienced recurrent atrial arrhythmias after PeAF ablation were included. Based on their medication regimens, patients were divided into two groups, with the study group being a triple‐drug group (digoxin combined with amiodarone/ propafenone and β‐blocker), and the control group being a non‐triple‐drug group.

Results

The rate of reversion to SR was significantly higher in the study group (n = 29) than in the control group (n = 16) at 3 weeks (34.48% vs. 0%, p < 0.01) and 1 month (44.84% vs. 6.25%, p = 0.02) after initiating AADs. No patients with asymptomatic bradycardia were observed in either group.

Conclusions

For patients with recurrent atrial arrhythmias after PeAF ablation, a regimen of low‐dose digoxin combined with amiodarone/propafenone and β‐blocker may effectively improve short‐term reversion rates.
Under Pressure: Employee Work Stress, Supervisory Mentoring Support, and Employee Career Success
Authors: Erdogan Berrin , Kudret Selin , Campion Emily D. , Bauer Talya N. , McCarthy Julie , Cheng Bonnie Hayden
Published: October 2024

Despite consistent findings that stressed employees benefit from social support, these employees do not always have access to such support. We propose and test a conceptual model suggesting employee work stress will negatively affect supervisory career and psychosocial mentoring support. Drawing from social exchange theory, we predict this will indirectly affect employee career success (lower career satisfaction and promotability ratings, fewer promotions), and that the relationship between employee work stress and lower supervisory mentoring support can be explained by lower levels of work engagement experienced by, and attributed to, stressed employees. We tested our model across three studies. In Study 1, we collected four waves of multisource field data (254 employees, 127 managers, and company records) at a large postal organization in the United Kingdom (UK). Employee work stress was negatively related to supervisor career and psychosocial mentoring support, and indirectly affected career satisfaction and manager promotability ratings of employees via supervisor career mentoring support. Cross‐lagged panel analyses in a supplemental study additionally supported the proposed directionality of relationships. Study 2 included data across three waves from employees in Hong Kong (n = 137) and showed that employee work stress had indirect effects on supervisor career and psychosocial mentoring via lower employee engagement. In Study 3, using data from supervisors in the UK (n = 240) we showed that supervisor perceived employee stress had indirect effects on their provision of supervisor career and psychosocial mentoring support via lower perceived employee engagement.
Fatal Hyperacute Liver Failure due to Varicella Zoster Virus Immediately After Living‐Donor Liver Transplantation: A Case Report and Review of the Literature
Authors: Toda Takeo , Kaneko Junichi , Ikemura Masako , Tanaka Mariko , Miyata Akinori , Nishioka Yujiro , Ichida Akihiko , Kawaguchi Yoshikuni , Akamatsu Nobuhisa , Hasegawa Kiyoshi
Published: October 2024

Background

Although acute hepatitis caused by varicella zoster virus mostly develops in immunocompromised patients, hyperacute liver failure is very rare. To our knowledge, there are no previous reports on liver transplant patients.

Methods

We report the first case of fatal hyperacute liver failure due to varicella zoster virus immediately after living‐donor liver transplantation without cutaneous lesions and review the literature.

Result

The present case exhibited rapid development and progression of acute liver failure from postoperative days 11–13, despite being seropositive for varicella zoster virus but unvaccinated and on immunosuppression before transplantation. Especially in solid organ transplantation, only six cases of severe acute liver failure that included hepatic encephalopathy and/or impaired consciousness and sudden extremely high (> 4000 U/L) serum aspartate aminotransferase levels have been reported in heart, lung, and kidney transplant patients.

Conclusions

Early diagnosis of hyperacute liver failure due to varicella zoster virus is challenging because the disease progresses rapidly and skin lesions are absent.
The ideal worlds objection
Authors: Rumbold Benedict
Published: October 2024

The Ideal Worlds objection is an objection that purports to identify a potentially fatal flaw in some of our most influential moral theories: including, among others, rule consequentialism, Kant's Law of Nature Formula of the Categorical Imperative and Scanlonian contractualism. In this article, I offer an account of the objection, a survey of some of the ways defenders of affected theories have sought to avoid it, and the problems that those responses can encounter.
Unveiling the role of the ERD15 gene in wheat's tolerance to combined drought and salinity stress: a meta‐analysis of QTL and RNA‐Seq data
Authors: Shamloo‐Dashtpagerdi Roohollah , Tanin Mohammad Jafar , Aliakbari Massume , Saini Dinesh Kumar
Published: October 2024

The coexistence of drought and salinity stresses in field conditions significantly hinders wheat (Triticum aestivum L.) productivity. Understanding the molecular mechanisms governing response and tolerance to these stresses is crucial for developing resilient wheat varieties. Our research, employing a combination of meta‐QTL and meta‐RNA‐Seq transcriptome analyses, has uncovered the genome functional landscape of wheat in response to drought and salinity. We identified 118 meta‐QTLs (MQTLs) distributed across all 21 wheat chromosomes, with ten designated as the most promising. Additionally, we found 690 meta‐differentially expressed genes (mDEGs) shared between drought and salinity stress. Notably, our findings highlight the Early Responsive to Dehydration 15 (ERD15) gene, located in one of the most promising MQTLs, as a key gene in the shared gene network of drought and salinity stress. ERD15, differentially expressed between contrasting wheat genotypes under combined stress conditions, significantly regulates water relations, photosynthetic activity, antioxidant activity, and ion homeostasis. These findings not only provide valuable insights into the molecular genetic mechanisms underlying combined stress tolerance in wheat but also hold the potential to contribute significantly to the development of stress‐resilient wheat varieties.
Arbuscular mycorrhizal fungi alter carbon metabolism and invertase genes expressions of Populus simonii × P. nigra under drought stress
Authors: Tao Jing , Dong Fengxin , Wang Yihan , Xu Tingying , Chen Hui , Tang Ming
Published: October 2024

Arbuscular mycorrhizal fungi (AMF) play a crucial role in regulating the allocation of carbon between source and sink tissues in plants and in regulating their stress responses by changing the sucrose biosynthesis, transportation, and catabolism in plants. Invertase, a key enzyme for plant development, participates in the response of plants to drought stress by regulating sucrose metabolism. However, the detailed mechanisms by which INV genes respond to drought stress in mycorrhizal plants remain unclear. This study examined the sugar content, enzyme activity, and expression profiles of INV genes of Populus simonii × P. nigra (PsnINVs) under two inoculation treatments (inoculation or non‐inoculation) and two water conditions (well‐watered or drought stress). Results showed that under drought stress, AMF up‐regulated the expressions of PsnA/NINV1, PsnA/NINV2, PsnA/NINV3, and PsnA/NINV5 in leaves, which may be related to the enhancement of photosynthetic capacity. Additionally, AMF up‐regulated the expressions of PsnA/NINV6, PsnA/NINV10, and PsnA/NINV12 in leaves, which may be related to enhancing osmotic regulation ability and drought tolerance.
How beliefs about tampering with nature influence support for enhanced geothermal systems: A cross‐national study
Authors: Cousse Julia , McComas Katherine , Lambert Catherine , Balog‐Way Dominic , Trutnevyte Evelina
Published: October 2024

Many believe that enhanced geothermal systems (EGS) can greatly increase the extraction of geothermal energy worldwide, helping to decarbonize heat and electricity production. Effective communication is key to realizing the potential of EGS, yet we currently know little about how the public perceives this emerging technology. This exploratory study contributes to the literature with a cross‐national survey in the United States (n = 1003) and Switzerland (n = 1028), two countries with active EGS projects. Specifically, we explore how EGS support relates to beliefs about the deep underground and perceptions of EGS as tampering with nature. The results show that respondents tend to perceive the deep underground as part of nature, dangerous, and unpredictable. The majority are positive about using the deep underground as a resource, although there were variations regarding specific underground activities. In both countries, EGS support is greater for respondents who perceive the underground as something for human use, perceive more benefits than risks from EGS, and support their country's transition to renewable energy. In Switzerland, EGS support is positively related to trust in industry developers and negatively related to perceptions that EGS is tampering with nature. The results offer novel theoretical insights into perceptions of the deep underground in relation to energy development. From a practical standpoint, the results suggest that those seeking to develop EGS may want to consider how to familiarize individuals with current subsurface energy activities, including efforts to protect the underground from unwanted consequences of “tampering,” alongside engaging in discussions about the risks and benefits of EGS.
Out of sight but still in mind: Developing an expectation for surprises by formalizing unknowledge in a contemporary risk‐assessment framework
Authors: Derbyshire James , Aven Terje
Published: October 2024

Extreme events like the credit crunch, the September 11th attacks, the coronavirus pandemic, and Hamas’ attack on Israel each have in common that they should not have come as a surprise, yet still did. One reason surprises happen is that a risk assessment reflects the knowledge of the assessors, yet risk also includes uncertainties that extend beyond this knowledge. A risk assessment is thus susceptible to surprises as it focuses attention on what is known. Developing an expectation for surprises is key to their avoidance and requires that risk assessors specifically consider their “unknowledge”—that is, what they do not presently know about an event, outcome, or activity and its potential consequences and triggers. One way to emphasize the need for risk assessors to consider unknowledge is to explicitly include it as a separate component in risk‐assessment frameworks. This article formalizes the inclusion of unknowledge in a contemporary risk‐assessment framework.
The hysteretic Aw–Rascle–Zhang model
Authors: Corli Andrea , Fan Haitao
Published: October 2024

A novel hyperbolic system of partial differential equations is introduced to model traffic flows. This system comprises three equations, with two being linearly degenerate; its main feature is the inclusion of a hysteretic term in a generalized Aw–Rascle–Zhang (ARZ) model. First, a maximum principle for the diffusive version of the model is proven. Then, it is demonstrated that a solution to the Riemann problem exists, which is unique among solutions that are monotone in velocity; all waves exploited in the construction have suitable viscous profiles. Through several examples it is shown how, as a consequence of different driving habits, the system can model the decay, emergence, or persistence of stop‐and‐go waves (a feature that is missing in the ARZ model), and such behavior is characterized by a simple geometric condition. Furthermore, the model allows the study of traffic flows with a mixture of drivers whose hysteresis loops are either clockwise or counterclockwise. In particular, the presence of sufficiently many of the former dampens speed oscillations.
Deep learning to capture leaf shape in plant images: Validation by geometric morphometrics
Authors: Hodač Ladislav , Karbstein Kevin , Kösters Lara , Rzanny Michael , Wittich Hans Christian , Boho David , Šubrt David , Mäder Patrick , Wäldchen Jana
Published: October 2024

Plant leaves play a pivotal role in automated species identification using deep learning (DL). However, achieving reproducible capture of leaf variation remains challenging due to the inherent “black box” problem of DL models. To evaluate the effectiveness of DL in capturing leaf shape, we used geometric morphometrics (GM), an emerging component of eXplainable Artificial Intelligence (XAI) toolkits. We photographed Ranunculus auricomus leaves directly in situ and after herbarization. From these corresponding leaf images, we automatically extracted DL features using a neural network and digitized leaf shapes using GM. The association between the extracted DL features and GM shapes was then evaluated using dimension reduction and covariation models. DL features facilitated the clustering of leaf images by source populations in both in situ and herbarized leaf image datasets, and certain DL features were significantly associated with biological leaf shape variation as inferred by GM. DL features also enabled leaf classification into morpho‐phylogenomic groups within the intricate R. auricomus species complex. We demonstrated that simple in situ leaf imaging and DL reproducibly captured leaf shape variation at the population level, while combining this approach with GM provided key insights into the shape information extracted from images by computer vision, a necessary prerequisite for reliable automated plant phenotyping.
LlbHLH87 interacts with LlSPT to modulate thermotolerance via activation of LlHSFA2 and LlEIN3 in lily
Authors: Wu Ze , Gong Xue , Zhang Yinyi , Li Ting , Xiang Jun , Fang Qianqian , Yu Junpeng , Ding Liping , Liang Jiahui , Teng Nianjun
Published: October 2024

Basic helix–loop–helix (bHLH) proteins comprise one of the largest families of transcription factors in plants, which play roles in plant development, secondary metabolism, and the response to biotic/abiotic stresses. However, the roles of bHLH proteins in thermotolerance are largely unknown. Herein, we identified a heat‐inducible member of the bHLH family in lily (Lilium longiflorum), named LlbHLH87, which plays a role in thermotolerance. LlbHLH87 was rapidly induced by transient heat stress, and its encoded protein was localized to the nucleus, exhibiting transactivation activity in both yeast and plant cells. Overexpression of LlbHLH87 in Arabidopsis enhanced basal thermotolerance, while silencing of LlbHLH87 in lily reduced basal thermotolerance. Further analysis showed that LlbHLH87 bound to the promoters of HEAT STRESS TRANSCRIPTION FACTOR A2 (LlHSFA2) and ETHYLENE‐INSENSITIVE 3 (LlEIN3) to directly activate their expression. In addition, LlbHLH87 interacted with itself and with SPATULA (LlSPT) protein. LlSPT was activated by extended heat stress and its protein competed for the homologous interaction of LlbHLH87, which reduced the transactivation ability of LlbHLH87 for target genes. Compared with that observed under LlbHLH87 overexpression alone, co‐overexpression of LlbHLH87 and LlSPT reduced the basal thermotolerance of lily to sudden heat shock, but improved its thermosensitivity to prolonged heat stress treatment. Overall, our data demonstrated that LlbHLH87 regulates thermotolerance via activation of LlEIN3 and LlHSFA2, along with an antagonistic interaction with LlSPT.
Knockdown of β‐conglycinin α′ and α subunits alters seed protein composition and improves salt tolerance in soybean
Authors: Yang Rufei , Ma Yujie , Yang Zhongyi , Pu Yixiang , Liu Mengyu , Du Jingyi , Xu Zhiri , Xu Zefei , Zhang Shanshan , Zhang Hengyou , Zhang Wei , Yu Deyue , Kan Guizhen
Published: October 2024

Soybean is an important plant source of protein worldwide. Increasing demands for soybean can be met by improving the quality of its seed protein. In this study, GmCG‐1, which encodes the β‐conglycinin α′ subunit, was identified via combined genome‐wide association study and transcriptome analysis. We subsequently knocked down GmCG‐1 and its paralogues GmCG‐2 and GmCG‐3 with CRISPR‐Cas9 technology and generated two stable multigene knockdown mutants. As a result, the β‐conglycinin content decreased, whereas the 11S/7S ratio, total protein content and sulfur‐containing amino acid content significantly increased. Surprisingly, the globulin mutant exhibited salt tolerance in both the germination and seedling stages. Little is known about the relationship between seed protein composition and the salt stress response in soybean. Metabonomics and RNA‐seq analysis indicated that compared with the WT, the mutant was formed through a pathway that was more similar to that of active salicylic acid biosynthesis; however, the synthesis of cytokinin exhibited greater defects, which could lead to increased expression of plant dehydrin‐related salt tolerance proteins and cell membrane ion transporters. Population evolution analysis suggested that GmCG‐1, GmCG‐2, and GmCG‐3 were selected during soybean domestication. The soybean accessions harboring GmCG‐1Hap1 presented relatively high 11S/7S ratios and relatively high salt tolerance. In conclusion, knockdown of the β‐conglycinin α and α′ subunits can improve the nutritional quality of soybean seeds and increase the salt tolerance of soybean plants, providing a strategy for designing soybean varieties with high nutritional value and high salt tolerance.
Herglotz's representation and Carathéodory's approximation
Authors: Bhattacharyya Tirthankar , Bhowmik Mainak , Kumar Poornendu
Published: October 2024

Herglotz's representation of holomorphic functions with positive real part and Carathéodory's theorem on approximation by inner functions are two well‐known classical results in the theory of holomorphic functions on the unit disc. We show that they are equivalent. On a multi‐connected domain , a version of Heglotz's representation is known. Carathéodory's approximation was not known. We formulate and prove it and then show that it is equivalent to the known form of Herglotz's representation. Additionally, it also enables us to prove a new Heglotz's representation in the style of Korányi and Pukánszky. Of particular interest is the fact that the scaling technique of the disc is replaced by Carathéodory's approximation theorem while proving this new form of Herglotz's representation. Carathéodory's approximation theorem is also proved for operator‐valued functions on a multi‐connected domain.
Visual placebo and nocebo effects
Authors: Piedimonte Alessandro , Volpino Valeria , Campaci Francesco , Deplano Martina , Borghesi Francesca , Pollo Antonella , Carlino Elisa
Published: October 2024

Placebo and nocebo effects modulate symptom perception through expectations and learning processes in various domains. Predominantly, their impact has been investigated on pain and physical performance. However, the influence of placebos and nocebos on visual system functionality has yet to be explored. The present study aimed to test whether placebo and nocebo effects can intervene in altering participants’ performance outcomes during a novel visual accuracy task and to examine the underlying neural mechanisms through EEG. After performing a baseline session, visual accuracy was said to be enhanced or disrupted by a sham transcranial electrical stimulation over the occipital lobe. Behavioural results showed a significant increase in visual accuracy for the placebo group, from the baseline session to the test session, whereas the nocebo group showed a decrease in visual accuracy. EEG analyses on the event‐related potential P300 component, conducted on both a centro‐parietal electrode patch and a parieto‐occipital, one displayed an increase in the amplitude of P300 for the placebo group, and a decrease in the nocebo group. These findings suggest for the first time that placebo and nocebo effects can influence visual perception and attentional processes linked to it. Overall, the present study contributes to understanding how expectations affect sensory perception beyond pain and the motor system, paving the way for investigating these phenomena in other sensory modalities such as auditory or olfactory perception.

image

Key points

Placebo and nocebo effects have been studied predominantly in pain and motor performance fields.

In a novel visual task, the impact of placebo and nocebo effects on the visual system has been evaluated, in both early components (stimuli‐related) and late components (attention‐related).

The placebo group showed an increase in visual accuracy and EEG‐evoked potential amplitudes, whereas the nocebo group showed a decrease in both.

This study shows how expectations and the related placebo and nocebo effects can shape basic stimuli sensory perception in the visual domain.
A Multichamber Pulsating-Flow Device With Optimized Spatial Shear Stress and Pressure for Endothelial Cell Testing
Authors: Campos Obed A. , Garcia-Herreros Antoni , Sánchez Antonio L. , Fineman Jeffrey R. , Pawlak Geno
Published: October 2024

Design and analysis are presented for a new device to test the response of endothelial cells to the simultaneous action of cyclic shear stresses and pressure fluctuations. The design consists of four pulsatile-flow chambers connected in series, where shear stress is identical in all four chambers and pressure amplitude decreases in successive chambers. Each flow chamber is bounded above and below by two parallel plates separated by a small gap. The design of the chamber planform must ensure that cells within the testing region experience spatially uniform time-periodic shear stress. For conditions typically encountered in applications, the viscous unsteady flow exhibits order-unity values of the associated Womersley number. The corresponding solution to the unsteady lubrication problem, with general nonsinusoidal flowrate, is formulated in terms of a stream function satisfying Laplace's equation, which can be integrated numerically to determine the spatial distribution of shear stresses for chambers of general planform. The results are used to optimize the design of a device with a hexagonal planform. Accompanying experiments using particle tracking velocimetry (PTV) in a fabricated chamber were conducted to validate theoretical predictions. Pressure readings indicate that intrachamber pressure variations associated with viscous pressure losses and acoustic fluctuations are relatively small, so that all cells in a given testing region experience nearly equal pressure forces.
A Novel Electric Vehicle Thermal Management System Based on Charging Station Heat Pump System During Fast Charging
Authors: Ye Li , Shang Fei , Shen Hongjie , Shi Anning , Li Haodong , Lou Yanyan
Published: October 2024

A battery thermal management system based on a charging station heat pump system is proposed to improve battery charging efficiency during high-power direct current charging. The system provides coolant of appropriate temperature through the charging station heat pump system. It enables the battery to be charged at the optimal temperature for charging, which improves the charging efficiency and reduces the charging time. The two system models are modeled and analyzed using numerical simulation software, and the temperature characteristics and charging time of the proposed system and the original battery thermal management system based on the electric vehicle heat pump system are analyzed under five different temperature conditions. The results show that the proposed system has a higher efficiency, through different ambient temperatures, we can find that at a low temperature of −20 °C, compared with the original system, the efficiency of the system is particularly significant, and can save 24.6％ charging time. At various ambient temperatures, the maximum temperature of the battery can be maintained at 50 °C to maintain a good state. Comparing the charging time for the power battery at each stage, the proposed system mainly reduces the charging time in the range of 0–20% of the battery state of charge compared to the original system.
Unsteady Flow Structure of Rotating Instability in a 1.5-Stage Axial Compressor
Authors: Fujisawa Nobumichi , Ohta Yutaka , Yamagami Mai , Goto Takashi , Kato Dai
Published: October 2024

The unsteady flow structure of the rotating instability (RI) in a 1.5-stage axial compressor is investigated through experimental and numerical analyses. In the tested compressor, the total pressure rise of the rotor stagnates at a certain flow coefficient before it increases again toward a lower flowrate in a case involving a wide tip clearance. The RI appears beyond this stagnant point as the compressor is throttled. The RI indicates a gentle hump in the frequency spectra of wall pressure or the flow velocity near the tip in a range of approximately 20–40% of the blade-passing frequency. As the flowrate decreases, the mode order of the RI increases, in contrast to the more commonly reported tendency, while the propagation velocity remains constant. These features are well captured by detached eddy simulation (DES) of the half-annulus model, with which the unsteady flow structure is further investigated. At its onset, RI is formed by the collision of the tip leakage vortex onto the pressure surface of the adjacent blade and subsequent vortex segmentation. This vortex structure spans two blade passages and propagates in the direction opposite to the rotor rotation. As the compressor is throttled, RI becomes more dominated by the circumferential propagation of vortex breakdown of tip leakage vortices, which occur simultaneously among neighboring passages with slight phase differences. The mechanism is discussed in relation to the temporal change in the blade tip loading. The frequency of vortex shedding increases with the reduction in flowrate and thus the increase in the number of RI disturbances.
Nonmonotonic rheology and stress heterogeneity in confined granular suspensions
Authors: Hu Haitao , Zhao Yiqiu , Zhao Weiwei , Qiao Ligen , Xu Qin
Published: October 2024

We systematically investigated the impact of boundary confinement on the shear-thickening rheology of dense granular suspensions. Under highly confined conditions, dense suspensions were found to exhibit size-dependent or even rarely reported nonmonotonic (S-shaped) flow curves in steady states. By performing in situ boundary stress microscopy measurements, we observed enhanced flow heterogeneities in confined suspensions, where concentrated high-stress domains propagated stably either along or against the shear direction. By comparing the boundary stress microscopy results with macroscopic flow responses, we revealed the connection between nonmonotonic rheology and stress heterogeneity in confined suspensions. These findings suggest the possibility of controlling suspension rheology by imposing different boundary confinements.
Navigating Physical Activity Promotion and Policy in the Post-COVID-19-Pandemic Era
Authors: Richards Justin , Siefken Katja , Pratt Michael , Bauman Adrian , Mejía-Grueso Juliana , Woods Catherine B. , Wendel-Vos Wanda , Hinckson Erica , Salvo Deborah , Hallal Pedro C. , Ramírez Varela Andrea
Published: October 2024

Background: There is limited evidence on the priorities and opportunities associated with promoting population physical activity (PA) participation for the post-COVID-19-pandemic future. Purpose: This study assessed government-led PA promotion efforts before and during the COVID-19 pandemic, along with post-COVID-19-pandemic priorities and recommendations. Methods: Two separate cross-sectional surveys conducted in 2023. Survey 1 was targeted at the Global Observatory for Physical Activity (GoPA!) Country Contacts. Survey 2 also included key international informants representing influential stakeholders in PA policy implementation. Results: There were 68 respondents to Survey 1, collectively representing 61 countries. An additional 37 people, including representatives from 14 key international stakeholders responded to Survey 2. Eighty-two percent of countries had national PA policies. COVID-19 widely disrupted PA policy implementation. Less than 40% of countries integrated PA into their COVID-19 response plan and more than 75% reported policies that restricted PA participation. Although most respondents indicated that government PA priorities did not change due to the COVID-19 pandemic, one in five countries reported that cross-sectoral partnership had become more important during this period. Less than a third of postpandemic governments reported as highly engaged despite the widespread proliferation of PA policies and plans prior to the pandemic. There were variations according to country, region, and income. Conclusions: Elevating PA promotion on the public health agenda is crucial for the post-COVID-19-pandemic era. At a policy level, it is critical to focus on adequate resourcing, cross-sectoral partnerships, integrated interventions, and inequities in participation. These factors have become increasingly important in the postpandemic PA policy landscape.
Comparison of Exercise Protocols for Diagnosing Pediatric Unexplained Dyspnea on Exertion
Authors: Brown Elliott , Foster Karla , Gover Iesha , Powell Adam , Hardie William D.
Published: October 2024

Purpose: Clinicians evaluating pediatric patients with unexplained dyspnea on exertion (DOE) often obtain exercise testing with a treadmill-based exercise-induced bronchospasm (EIB) protocol measuring only changes in spirometry. We modified the EIB protocol to collect metabolic and lung volume endpoints as obtained in a cardiopulmonary exercise test (CPET). We tested the hypothesis that measuring metabolic data with the EIB protocol (EIB-CPET) would yield greater diagnostic information than the EIB protocol. Methods: Exercise test diagnosis for healthy children with DOE referred to the pulmonary exercise lab from January 2011 through July 2023 were retrospectively compared between those performing either the EIB or EIB-CPET protocols. Results: One hundred and twenty-seven patients with unexplained DOE were analyzed. Of the 72 patients tested on the EIB protocol, 49% had stridor and 5% with EIB. Of the 55 patients tested on the EIB-CPET protocol, 42% had stridor, 42% with normal physiologic limitation, 22% with dysfunctional breathing, 5% with deconditioning, 2% with EIB, and 2% with exercise-induced hypoxemia. Patients performing the EIB-CPET protocol had a significantly higher rate of any diagnosis compared with EIB (P = .0002). Conclusions: There is a greater diagnostic yield in children with unexplained DOE performing the EIB-CPET protocol compared with patients performing the EIB protocol.
Weaponizing Sport: Exploring the Legal and Policy Implications of Menstrual Tracking for Transgender and Nonbinary Athletes
Authors: Darvin Lindsey , Spagnuolo Tia , Schultz David
Published: October 2024

The intersection of gender identity, sports participation, and health care is increasingly under scrutiny within legal and policy spheres. Specifically, the practice of tracking U.S. high school athletes’ menstrual cycles sustains concerning implications for gender-based discrimination, particularly affecting transgender and nonbinary athletes. This paper examines the legal and policy implications of menstrual tracking in high school athletics, highlighting the potential violations of privacy rights and discrimination against athletes of diverse gender identities. By analyzing existing laws, regulations, and case law, the paper explores the complexities surrounding the practice of menstrual tracking and calls for more inclusive and equitable sports policies. Additionally, it addresses gaps in privacy protections under the Family Educational Rights and Privacy Act and Health Insurance Portability and Accountability Act, emphasizing the need for updated regulations to safeguard students’ health-related data in digital environments.
Synthesis of a dehydrodieugenol B derivative as a lead compound for visceral leishmaniasis—mechanism of action and
in vivo
pharmacokinetic studies
Authors: Amaral Maiara , Romanelli Maiara M. , Asiki Hannah , Bicker Joana , Lage Daniela P. , Freitas Camila S. , Taniwaki Noemi N. , Lago Joao Henrique G. , Coelho Eduardo A. F. , Falcão Amílcar , Fortuna Ana , Anderson Edward A. , Tempone Andre G.
Published: October 2024

Leishmaniasis is a parasitic neglected tropical disease, affecting 12 million people. Available treatments present several limitations, with an increasing number of resistance cases. In the search for new chemotherapies, the natural product dehydrodieugenol B was used as a scaffold for the synthesis of a series of derivatives, resulting in the discovery of the promising analog [4-(4-(5-allyl-3-methoxy-2-((4-methoxybenzyl)oxy)phenoxy)-3-methoxybenzyl)morpholine,
1
]. In this work, we investigated the effect of compound
1
on cell signaling in
Leishmania (L.) infantum
, culminating in cell death, as well as its immunomodulatory effect in the host cell. Additionally, we performed a pharmacokinetic profile study in an animal model. After treatment, compound
1
induced the alkalinization of acidocalcisomes and concomitant Ca
2+
release in the parasite. These events may induce depolarization of the mitochondrial potential, with successive collapse of the bioenergetic system, leading to a reduction of ATP and reactive oxygen species (ROS) levels. The analysis of total proteins and protein profile by matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF/MS) demonstrated that compound
1
also altered the parasite proteins after treatment. Transmission electron microscopy studies revealed ultrastructural damage to mitochondria; together, these data suggest that compound
1
may promote autophagic cell death. Additionally, compound
1
also induced an immunomodulatory effect in host cells, with a reduction of Th1 and Th2 cytokine response, characterizing an anti-inflammatory compound. The obtained pharmacokinetic profile in rats enhances the potential of the compound, with a mean plasma half-life (T
1/2
) of 21 h. These data reinforce the potential of compound
1
as a new lead for future efficacy studies.
Therapeutic drug monitoring of linezolid in Chinese premature neonates: a population pharmacokinetic analysis and dosage optimization
Authors: Duan Lu-fen , Li Jing-jing , Shen Li-rong , Chen Xiang-long , Yu Yan-xia , Yang Zu-ming , Zhang Qian , Cai Yan , Li Jia-hui , Wu Juan , Zhao Han-zhen , Xu Jin-hui , Feng Zong-tai , Tang Lian
Published: October 2024

This study aimed to develop a pharmacokinetic model of linezolid in premature neonates and evaluate and optimize the administration regimen. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to detect the blood concentration data of 54 premature neonates after intravenous administration of linezolid, and the relevant clinical data were collected. The population pharmacokinetic (PPK) model was established by nonlinear mixed effects modeling. Based on the final model parameters, the optimal administration regimen of linezolid in premature neonates with different body surface areas (BSA) was simulated and evaluated. The pharmacokinetic properties of linezolid in premature neonates are best described by a single-compartment model with primary elimination. The population typical values for apparent volume of distribution and clearance were 0.783 L and 0.154 L/h, respectively. BSA was a statistically significant covariate with clearance (CL) and volume of distribution (V
d
). Monte Carlo simulations showed that the optimal administration regimen for linezolid in premature neonates was 6 mg/kg q8h for BSA 0.11 m
2
, 7 mg/kg q8h for BSA 0.13 m
2
, and 9 mg/kg q8h for BSA 0.15 m
2
with minimum inhibitory concentration (MIC) ≤1 mg/L, 7 mg/kg q8h for BSA 0.11 m
2
, 8 mg/kg q8h for BSA 0.13 m
2
, and 10 mg/kg q8h for BSA 0.15 m
2
with MIC = 2 mg/L. A pharmacokinetic model was developed to predict the blood concentration on linezolid in premature neonates. Based on this model, the optimal administration regimen of linezolid in premature neonates needs to be individualized according to different BSA levels.
Clinical performance evaluation of the BioFire Joint Infection Panel
Authors: Lee Rose A.
Published: October 2024

The BioFire Joint Infection (JI) Panel offers a significant advancement in the rapid diagnosis of joint infections by facilitating the simultaneous detection of multiple bacterial and fungal pathogens, as well as resistance markers, directly from synovial fluid samples. An article published in the
Journal of Clinical Microbiology
by Moran et al. (J Clin Microbiol 62:e00182-24, 2024,
https://doi.org/10.1128/jcm.00182-24
) presents both prospective and retrospective analyses of the panel’s real-world clinical application. The study highlights the panel’s benefits, such as its rapid turnaround time and ability to identify challenging pathogens, while also discussing its limitations, particularly in detecting certain off-panel organisms.
Retinoic acid-induced differentiation and oxidative stress inhibitors increase resistance of human neuroblastoma cells to La Crosse virus-induced cell death
Authors: Policastro Paul F. , Schneider Christine A. , Winkler Clayton W. , Leung Jacqueline M. , Peterson Karin E.
Published: October 2024

La Crosse Virus (LACV) encephalitis patients are at risk for long-term deficits in cognitive function due to neuronal apoptosis following virus infection. However, the specific etiology underlying neuronal damage remains elusive. In this study, we examined how differentiation and mitotic inhibition of neuroblastoma cells influence their susceptibility to LACV infection and cell death. Treatment of SH-SY5Y cells with retinoic acid induced a neuronal cell phenotype which was similarly susceptible to LACV infection as untreated cells but had significantly delayed virus-induced cell death. Protein and RNA transcript analysis showed that retinoic acid-treated cells had decreased oxidative stress responses to LACV infection compared to untreated cells. Modulation of oxidative stress in untreated cells with specific compounds also delayed cell death, without substantially impacting virus production. Thus, the oxidative stress response of neurons to virus infection may be a key component of neuronal susceptibility to virus-induced cell death.

IMPORTANCE

Encephalitic viruses like La Crosse Virus (LACV) infect and kill neurons. Disease onset and progression is rapid meaning the time frame to treat patients before significant and long-lasting damage occurs is limited. Examining how neurons, the primary cells infected by LACV in the brain, resist virus-induced cell death can provide avenues for determining which pathways to target for effective treatments. In the current study, we studied how changing neuroblastoma growth and metabolism with retinoic acid treatment impacted their susceptibility to LACV-induced cell death. We utilized this information to test compounds for preventing death in these cells.
The multifaceted roles of phosphoethanolamine-modified lipopolysaccharides: from stress response and virulence to cationic antimicrobial resistance
Authors: Schumann Anna , Gaballa Ahmed , Wiedmann Martin
Published: October 2024

Lipopolysaccharides (LPS) are an integral part of the outer membrane of Gram-negative bacteria and play essential structural and functional roles in maintaining membrane integrity as well as in stress response and virulence. LPS comprises a membrane-anchored lipid A group, a sugar-based core region, and an O-antigen formed by repeating oligosaccharide units. 3-Deoxy-D-
manno
-octulosonic acid-lipid A (Kdo
2
-lipid A) is the minimum LPS component required for bacterial survival. While LPS modifications are not essential, they play multifaceted roles in stress response and host-pathogen interactions. Gram-negative bacteria encode several distinct LPS-modifying phosphoethanolamine transferases (PET) that add phosphoethanolamine (pEtN) to lipid A or the core region of LPS. The
pet
genes differ in their genomic locations, regulation mechanisms, and modification targets of the encoded enzyme, consistent with their various roles in different growth niches and under varied stress conditions. The discovery of mobile colistin resistance genes, which represent lipid A-modifying
pet
genes that are encoded on mobile elements and associated with resistance to the last-resort antibiotic colistin, has led to substantial interest in PETs and pEtN-modified LPS over the last decade. Here, we will review the current knowledge of the functional diversity of pEtN-based LPS modifications, including possible roles in niche-specific fitness advantages and resistance to host-produced antimicrobial peptides, and discuss how the genetic and structural diversities of PETs may impact their function. An improved understanding of the PET group will further enhance our comprehension of the stress response and virulence of Gram-negative bacteria and help contextualize host-pathogen interactions.
Correlation of patient symptoms with SARS-CoV-2 Omicron variant viral loads in nasopharyngeal and saliva samples and their influence on the performance of rapid antigen testing
Authors: Shiraishi Kenichiro , Chong Yong , Goto Takeyuki , Ishimaru Toshiyuki , Shimono Nobuyuki , Ikematsu Hideyuki , Akashi Koichi
Published: October 2024

Evaluating SARS-CoV-2 viral loads in nasopharyngeal (NP) and saliva samples, factors affecting viral loads, and the performance of rapid antigen testing (RAT) have not been comprehensively conducted during SARS-CoV-2 Omicron epidemic. This prospective study included outpatients enrolled during Omicron variant period in Japan. Paired NP swab and saliva samples were collected to measure viral loads by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The correlation between viral loads and clinical symptoms was examined. The performance of an immunochromatography-based RAT kit was also assessed. A total of 153 patients tested within 3 days of symptom onset were included. The mean viral load was 5.60 log
10
copies/test and 3.65 log
10
copies/test in NP and saliva samples, respectively, resulting in a significant difference (
P
< 0.0001). Fever over 37°C (axillary temperature) and total number of symptoms other than fever were identified as independent factors positively correlated with the viral loads in both NP and saliva samples. RAT sensitivity using NP and saliva samples was 92% and 68%, respectively, using positive RT-qPCR results as the reference. The sensitivity of RAT using NP and saliva samples was significantly higher in patients with fever ≥37°C and/or at least one symptom than in those with fever <37°C and/or no symptoms (97% vs 83% in NP swabs; 80% vs 50% in saliva). Distinct symptoms, including fever ≥37°C, may reflect high Omicron variant viral loads. Rapid antigen testing, not only using nasopharyngeal swabs but also using saliva, would be useful for COVID-19 diagnosis as point-of-care testing, particularly for symptomatic patients.

IMPORTANCE

We examined nasopharyngeal and salivary viral loads using samples collected from outpatients with SARS-CoV-2 infection during the Omicron epidemic in Japan and explored the outpatient factors correlated with viral loads. In addition, we evaluated the performance of an authorized rapid antigen testing (RAT) kit using nasopharyngeal and saliva samples with RT-PCR testing as the reference. Intriguingly, a correlation between fever and other symptoms and SARS-CoV-2 viral loads in nasopharyngeal and saliva samples was observed based on one COVID-19 outpatient visit. RAT sensitivity was influenced by viral loads. Nevertheless, nasopharyngeal RAT is considered useful for SARS-CoV-2 point-of-care diagnosis. In patients with distinct symptoms, including high-grade fever, salivary RAT could be a practical diagnostic tool because of the higher estimated viral loads. After the Omicron epidemic, outpatients with mild COVID-19 have become the main focus of diagnosis and treatment. Our study provides valuable information regarding the point-of-care diagnosis of these patients.
Comparison of a hepatitis C core antigen assay to nucleic acid amplification testing for detection of hepatitis C viremia in a US population
Authors: Gunsolus Ian L. , Prostko John , Pearce Sandra , Degaga Biniam , Eickstead Scott , Taylor Russ , Grieshaber Jessica , Richard Kyle , Hoffman Anne , Pekalska Aneta , Daghfal David
Published: October 2024

The prevalence of hepatitis C virus (HCV) infection in the United States has increased over the past decade despite the development of effective direct-acting antiviral treatments. To meet the World Health Organization’s (WHO) goal of eliminating HCV infection by 2030, transmission events must be reduced. Currently, infection screening relies on detection of HCV antibodies, with nucleic acid amplification testing (NAAT) used to confirm HCV viremia and monitor changes in viral load. However, the seroconversion window for detection of HCV antibodies is long, averaging 6 weeks, with delayed seroconversion common in co-infected and immunosuppressed populations. Testing for HCV core antigen, which is present approximately 5 weeks before HCV antibodies, holds promise for earlier detection of HCV infection. It may also hold promise as a cheaper, more accessible, and more rapid alternative to NAAT for infection confirmation. Here, we evaluated the agreement between a research-use HCV Core Antigen Assay and NAAT among US patients receiving clinically indicated NAAT. Among 412 specimens, the overall concordance was 97.1%, with a positive percent agreement of 95.5%. Discrepancies primarily occurred among patients with chronic HCV and low viral loads; 11/12 discrepancies showed viral loads <4,000 IU/mL. Among patients being screened for HCV infection (i.e., excluding those undergoing NAAT for serial monitoring of a previously diagnosed infection), the positive percent agreement was 97.0%. Among patients undergoing serial testing, changes in HCV Core Antigen Assay signal-to-cut-off values were generally correlated with changes in the viral load. Results suggest that the research-use HCV Core Antigen Assay studied here may reliably detect and/or confirm HCV infection.

IMPORTANCE

A research-use HCV Core Antigen Assay showed high concordance with nucleic acid amplification testing for the detection of current hepatitis C infection. The assay may enable more rapid and lower-cost detection and/or confirmation of hepatitis C infection.