bluuebunny/crossref_metadata_2025 huggingface dataset:
Hysterectomy is not associated with increased risk of urinary incontinence—a northern Finland birth cohort 1966 study
Authors: Salo Heini , Manninen Roosa , Terho Anna , Laru Johanna , Sova Henri , Koivurova Sari , Rossi Henna‐Riikka
Published: July 2024

Introduction

Hysterectomy has been suggested to increase the risk of urinary incontinence (UI), although evidence is controversial. In our population‐based cohort study, we aimed to assess the independent effect of hysterectomy on the risk of de novo UI.

Material and Methods

This is a population‐based cohort study on the women of the Northern Finland Birth Cohort 1966 (n = 5889). We identified all hysterectomies among the cohort (n = 461) using the national Care Register for Health Care and classified them according to surgical approach into laparoscopic (n = 247), vaginal (n = 107), and abdominal hysterectomies (n = 107). Women without hysterectomy formed the reference group (n = 3495). All women with UI diagnoses and operations were identified in the register, and women with preoperative UI diagnosis (n = 36) were excluded from the analysis to assess de novo UI. Data on potential confounding factors were collected from registers and the cohort questionnaire. Incidences of different UI subtypes and UI operations were compared between the hysterectomy and the reference groups, and further disaggregated by different hysterectomy approaches. Logistic regression models were used to analyze the association between hysterectomy and UI, with adjustments for several UI‐related covariates.

Results

We found no significant difference in the incidence of UI diagnoses or the rate of subsequent UI operations between the hysterectomy and the reference groups (24 [5.6%] vs. 166 [4.7%], p = 0.416 and 14 [3.3%] vs. 87 [2.5%], p = 0.323). Hysterectomy was not significantly associated with the risk of any subtype of UI (overall UI: OR 1.20, 95% CI 0.77–1.86; stress UI (SUI): OR 1.51, 95% CI 0.89–2.55; other UI: OR 0.80, 95% CI 0.36–1.74). After adjusting for preoperative pelvic organ prolapse (POP) diagnoses, the risk was decreased (overall UI: OR 0.54, 95% CI 0.32–0.90; other than SUI: OR 0.40, 95% CI 0.17–0.95). Regarding different hysterectomy approaches, the risks of overall UI and SUI were significantly increased in vaginal, but not in laparoscopic or abdominal hysterectomy. However, adjusting for preoperative POP diagnosis abolished these risks.

Conclusions

Hysterectomy is not an independent risk factor for de novo UI. Instead, underlying POP appears to be a significant risk factor for the incidence of UI after hysterectomy.
Why are socioeconomic health inequalities unacceptable? Studying the influence of explanatory framings on cognitive appraisals
Authors: Bridger Emma K. , Tufte‐Hewett Angela , Comerford David , Nettle Daniel
Published: July 2024

Studies of aversion to health inequality have found that this is often greater when health outcomes are presented as varying with socioeconomic conditions. We sought to understand better why this is by studying the cognitive appraisals made about health inequality when presented with distinct explanatory framings. Across two pre‐registered studies (N = 1321), UK and US participants judged the acceptability of life expectancy differences attributed to distinct framings: income, education, social class, neighborhood, lifestyle choices, and genetics. Health inequality was least acceptable when attributed to the four socioeconomic framings, and most acceptable for lifestyle choices and genetics. Six appraisal dimensions—complexity, malleability, inevitability, and extent driven by biological, psychological, and sociocultural causes—varied with framing and predicted views on health inequality. These dimensions could explain most of the drop in acceptability for health inequality attributed to socioeconomic factors relative to a condition with no framing. This work illustrates for the first time the cognitive appraisals and causal intuitions that link different explanatory framings to views on health inequality. These framings are viewed as least acceptable because they reduce the perceived involvement of biological causes while increasing the perception that sociocultural and psychological factors contribute to health inequality.

Public significance statement: Academics use different socioeconomic variables to describe health inequalities. We show that different explanatory framings change appraisals about the causes, malleability, and inevitability of health inequalities. Socioeconomic explanations (income, education, social class, and neighborhood) reduce acceptability because they reduce the perception that health is biologically caused and increase the perceived role of socio‐cultural factors. Public support for intervention on health inequalities will be best served by framings that emphasize these differences
The clinical pharmacology and therapeutics course for graduating medical students at Dartmouth: Preparation for internship and residency
Authors: Nierenberg David W. , Lewis Lionel D.
Published: July 2024

Aims

This manuscript is a description of the clinical pharmacology and therapeutics (CPT) course that is required to be taken, and passed, by all medical students at the Geisel School of Medicine at Dartmouth during their final year of training, prior to entering their internship/residency.

Methods

We present a detailed CPT course curriculum, which includes the novel use of simulated expected professional activities (EPAs) and an analysis of the level of confidence the students who took the course had at the beginning and at the end of the course in performing the three simulated EPAs.

Results

The course currently consists of 31 h of presentations on what are considered major clinical pharmacology topics and is led by two clinical pharmacologists at Dartmouth (D.W.N. and L.D.L.) supplemented by therapeutic area specialist faculty. In addition, the Dartmouth CPT course incorporates three required simulated entrustable professional activities (EPAs) focused on drug prescribing. These are written exercises, completed outside scheduled class hours, and submitted to and evaluated by the course directors with individual feedback to each medical student. We present preliminary data on the benefits of using these simulated EPAs in undertaking what we consider are three pivotal prescribing skills.

Conclusion

The Dartmouth CPT course is unique and is only mirrored by a small number of US medical schools. The students showed a significant improvement in their level of confidence in performing the three simulated EPAs at the end of the course.
Spatial tertiary lymphoid structures imply response to anti‐PD‐1 plus anlotinib in advanced non‐small cell lung cancer
Authors: Ma Jianli , Deng Yuwei , Zhang Minghui , Zhang Qingyuan
Published: July 2024

Despite breakthroughs of immunotherapy synergistically combined with blockade of vascular endothelial growth factor receptor, several patients with advanced non‐small cell lung cancer (NSCLC) experience non‐response or followed relapse. Organized lymphoid aggregates, termed tertiary lymphoid structures (TLSs), are found to be associated with improved response to immunotherapy. Here, we explore the landscapes of TLSs in tumour tissues from a real‐world retrospective study. Our investigation showed that with a median follow‐up of 11.2 months, the ORR was 28.6% (18/63, 95% CI 17.9–41.3) and the median PFS was 6.1 (95% CI 5.5–6.6) months in NSCLC patients treated with PD‐1 blockade combined with anlotinib. By multiplex immunofluorescence (mIF) analysis, spatially, more TLSs and high CD20+ B‐cell ratio in TLSs were associated with higher ORR. High density of intratumoral CD8+ T cells showed better ORR and PFS. The numbers of CD8+ T cells with a distance within 20 μm and 20–50 μm between tumour cells were higher in responders than non‐responders. But responders had significantly higher TLSs within 20 μm rather than within 20–50 μm of tumour cells than non‐responders. The inflamed immunophenotyping occupied higher proportions in responders and was associated with better PFS. Besides, tumour cells in non‐responders were found more temporal cell‐in‐cell structures than responders, which could protect inner cells from T‐cell attacks. Taken together, landscape of TLSs and proximity architecture may imply superior responses to PD‐1 blockade combined with anlotinib for patients with advanced non‐small cell lung cancer.
Reinforcement Learning in Modern Biostatistics: Constructing Optimal Adaptive Interventions
Authors: Deliu Nina , Williams Joseph Jay , Chakraborty Bibhas
Published: July 2024

In recent years, reinforcement learning (RL) has acquired a prominent position in health‐related sequential decision‐making problems, gaining traction as a valuable tool for delivering adaptive interventions (AIs). However, in part due to a poor synergy between the methodological and the applied communities, its real‐life application is still limited and its potential is still to be realised. To address this gap, our work provides the first unified technical survey on RL methods, complemented with case studies, for constructing various types of AIs in healthcare. In particular, using the common methodological umbrella of RL, we bridge two seemingly different AI domains, dynamic treatment regimes and just‐in‐time adaptive interventions in mobile health, highlighting similarities and differences between them and discussing the implications of using RL. Open problems and considerations for future research directions are outlined. Finally, we leverage our experience in designing case studies in both areas to showcase the significant collaborative opportunities between statistical, RL and healthcare researchers in advancing AIs.
A novel ARHGAP family gene signature for survival prediction in glioma patients
Authors: Huang Jin , Wang Gaosong , Zhang Jiahao , Liu Yuankun , Shen Yifan , Chen Gengjing , Ji Wei , Shao Junfei
Published: July 2024

ARHGAP family genes are often used as glioma oncogenic factors, and their mechanism of action remains unexplained. Our research entailed a thorough examination of the immune microenvironment and enrichment pathways across various glioma subtypes. A distinctive 6‐gene signature was developed employing the CGGA cohort, leading to insights into the disparities in clinical characteristics, mutation patterns, and immune cell infiltration among distinct risk categories. Additionally, a unique nomogram was established, grounded on ARHGAPs, with DCA curves illustrating the model's prospective clinical utility in guiding therapeutic strategies. Emphasizing the role of ARHGAP30, integral to our model, its impact on glioma severity and the credibility of our risk assessment model were substantiated through RT‐qPCR, Western blot analysis, and cellular functional assays. We identified 6 ARHGAP family genes associated with glioma prognosis. Analysis using the Kaplan–Meier method indicated a correlation between elevated risk levels and adverse outcomes in glioma patients. The risk score, linked with tumour staging and IDH mutation status, emerged as an independent factor predicting prognosis. Patients in the high‐risk category exhibited increased immune cell infiltration, enhanced tumour mutational burden, more pronounced expression of immune checkpoint genes, and a better response to ICB therapy. A nomogram, integrating the risk score with the pathological features of glioma patients, was developed. DCA analysis and cellular studies confirmed the model's potential to improve clinical treatment outcomes for patients. A novel ARHGAP family gene signature reveals the prognosis of glioma.
EU Industrial Policy and Convergent Development in EU Peripheries: An Assessment of the ‘Important Project of Common European Interest’ (IPCEI) Template
Authors: Lopes‐Valença Henrique
Published: July 2024

Industrial policy has been enjoying a significant comeback. In the European Union (EU), ‘important projects of common European interest’ (IPCEIs) have become a template for a new, value chain‐oriented EU industrial policy. But what does this mean for convergence between ‘peripheral’ and ‘core’ member states? Based on the understanding that convergent development requires opportunities for ‘learning in production’ to accumulate the technological capabilities that are necessary for economic upgrading within value chains, this article advances an in‐depth analysis of the implementation of this EU industrial policy template. It argues that IPCEIs have so far offered peripheral countries and their firms few opportunities for learning in production within value chains. In this light, there is a risk that IPCEIs might have limited or even detrimental effects on the prospects for convergence within the EU. The article concludes by considering how this template could be made more conducive to convergent development.
The HSP70 and IL‐1β of Nile tilapia as molecular adjuvants can enhance the immune protection of DNA vaccine against Streptococcus agalactiae infection
Authors: Xu Fei‐Fan , Deng Zhu‐Yang , Sheng Jun‐Jie , Zhu Bin
Published: July 2024

Globally, streptococcal disease caused by Streptococcus agalactiae is known for its high mortality rate, which severely limits the development of the tilapia breeding industry. As a third‐generation vaccine, DNA vaccines have shown great application prospects in the prevention and control of aquatic diseases, but their low immunogenicity limits their development. The combination of DNA vaccines and molecular adjuvants proved to be an effective method for inducing protective immunity. This study constructed recombinant plasmids encoding tilapia HSP70 and IL‐1β genes (pcHSP70 and pcIL‐1β) to verify their effectiveness as molecular adjuvants for S. agalactiae DNA vaccine (pcSIP) in the immunized tilapia model. The results revealed that serum‐specific IgM production, enzyme activities, and immune‐related gene expression in tilapia immunized with pcSIP plus pcHSP70 or pcIL‐1β were significantly higher than those in tilapia immunized with pcSIP alone. It is worth noting that combination with molecular adjuvants improved the immune protection of DNA vaccines, with a relative percentage survival (RPS) of 51.72% (pcSIP plus pcHSP70) and 44.83% (pcSIP plus pcIL‐1β), respectively, compared with that of pcSIP alone (24.14%). Thus, our study indicated that HSP70 and IL‐1β in tilapia are promising molecular adjuvants of the DNA vaccine in controlling S. agalactiae infection.
Antimicrobial and anthelmintic effects of copper nanoparticles against Koi carp parasites and their toxicity
Authors: dos Santos Gracienhe Gomes , Riofrio Liseth Vanessa Perengue , Sousa Ana Paula , Santos Paola Capistrano , Silva Alexandre Vaz , Lopes Emilly Monteiro , Costa Domickson Silva , Pereira Júnior Jucimauro de Araújo , Ferreira Giulia Beatrice , Silva Graziella Vivine Gonçalves de Matos , Tedesco Marilia , Nogueira Diego José , Jerônimo Gabriela Tomas , Martins Mauricio Laterça
Published: July 2024

This study investigated the in vitro antimicrobial and anthelmintic effect of copper nanoparticles (CuNPs) against the bacterium Aeromonas hydrophila, the monogeneans Dactylogyrus minutus, Dactylogyrus extensus, Gyrodactylus cyprini, and the cestode Schyzocotyle acheilognathi, as well as their toxicity to Cyprinus carpio Koi. In the antimicrobial in vitro test, the inhibition zone method and minimum inhibitory concentration (MIC) were performed. In order to determine the time and efficacy of monogenean parasite mortality, the parasites were exposed to CuNP concentrations of 20, 50, 100, 150, 200, and 300 mg L−1, and a control group with tank water and one with copper sulphate pentahydrate (CuSO4.5H2O) at a concentration of 0.3 mg L−1, performed in triplicate. The parasites were observed every 10 min for 300 min, and mortality was recorded. For the cestodes, parasites were immersed in CuNP concentrations of 50, 100, 150, and 300 mg L−1. At the end of the in vitro tests, the anthelmintic efficacy of each treatment was calculated. To assess the tolerance and toxicity in fish, they were exposed to CuNP concentrations of 0.6, 1.25, 2.5, 5, 10, 20, and 50 mg L−1 for 12 h. The MIC demonstrated that CuNPs effectively inhibited the growth of A. hydrophila up to a dilution of 12,500 mg L−1 and showed an inhibition zone of 14.0 ± 1.6 mm for CuNPs. The results of anthelmintic activity showed a dose‐dependent effect of concentration for both groups of parasites, with the most effective concentration being 300 mg L−1 in 120 min. In the toxicity test, the carps showed tolerance to lower concentrations. The study indicated that CuNPs were effective against the studied pathogens. However, it proved to be toxic to fish at high concentrations. The use of low concentrations is recommended still requires further investigation.
Physical activity initiated from midlife on risk of dementia and cognitive impairment: The Health and Retirement Study
Authors: Wei Jingkai , Lohman Matthew C. , Brown Monique J. , Hardin James W. , Xu Hanzhang , Yang Chih‐Hsiang , Merchant Anwar T. , Miller Maggi C. , Friedman Daniela B.
Published: July 2024

Background

Physical activity is associated with lower risk of dementia and cognitive impairment, but existing randomized controlled trials have shown conflicting results. As cognitive decline occurs decades before the onset of dementia, physical activity interventions initiated in late life may have missed the potential window for prevention. An ideal trial of physical activity initiated from midlife and lasts till incident dementia and cognitive impairment in late life is not feasible. We aimed to estimate the effectiveness of a hypothetical physical activity intervention initiated from midlife on reducing dementia and cognitive impairment by emulating target trials using observational data.

Methods

The Health and Retirement Study was used to emulate target trials among noninstitutionalized participants aged 45 to 65 years with normal cognition who were physically inactive in the previous 2 years. Cognitive status was determined based on Langa–Weir classification of cognitive function (including immediate and delayed word recall tests, serial sevens subtraction, counting backward). Individuals were categorized as initiating physical activity or not, based on the self‐reported physical activity. Intention‐to‐treat and per‐protocol analysis were conducted with pooled logistic regression models with inverse‐probability of treatment and censoring weights to estimate risk ratios (RRs), and 95% confidence intervals (95% CIs) were calculated with 200 sets of bootstrapping.

Results

Among 1505 participants (average age 57.6 ± 4.8 years, 67% women, 76.5% White), 72 cases of dementia and 409 cases of cognitive impairment occurred. After 12 years of follow‐up, physical activity reduced dementia (RR = 0.70, 95% CI: 0.43, 0.99) for intention‐to‐treat analysis, and reduced dementia (RR = 0.51, 95% CI: 0.19, 0.99) and cognitive impairment (RR = 0.77, 95% CI: 0.61, 0.92) for per‐protocol analysis. No significant reduction was found among older adults.

Conclusions

Physical activity initiated during midlife may reduce dementia and cognitive impairment in late life, which highlights the importance of preventing cognitive outcomes at an earlier stage of life.
The soft channels of policy diffusion: Insights from local climate change adaptation policy
Authors: Schulze Kai
Published: July 2024

Diffusion has become both an important concept for studying policy spread and a popular governance approach, particularly where direct coercion is unavailable or undesirable. However, the prevailing mechanism‐centered concept is difficult to measure and poorly captures the governance potential of policy diffusion. To address these issues, this article presents a new channel‐centered framework that distinguishes between six soft policy diffusion channels: autonomous, collaborative, exemplary, persuasive, organized, and funded diffusion. The framework is probed by studying local climate change adaptation policy using original survey data collected from the administrations of 190 municipalities located in the central German state of Hessen. The regression results indicate that the local institutionalization of adaptation in Hessen is associated with several interventions by higher levels of government, including the provision of a policy model, a municipal climate network, and grant programs. However, the density of concrete adaptation measures is associated with noninstitutionalized exchanges between municipalities. External grants are also found to be more effective in institutionalizing adaptation in larger municipalities. These results demonstrate the usefulness of the framework for distinguishing and comparing different diffusion channels and suggest that different types of interventions may be required to effectively support adaptation policy development at the local level.
Brief of over 300 reproductive health researchers as Amici Curiae in FDA v. Alliance for Hippocratic Medicine
Authors: Barrow Amanda , Cohen Cathren , Serpico Jaclyn , Goodman Melissa , Grossman Daniel , Raifman Sarah , Upadhyay Ushma
Published: July 2024

On January 30, 2024, over 300 researchers filed an amicus brief in FDA v. Alliance for Hippocratic Medicine, a United States (US) Supreme Court case that could have severely impacted access to mifepristone, one of the two drugs commonly used in medication abortion. The researchers summarize the legal challenges to the US Food and Drug Administration's (FDA's) original approval of mifepristone in 2000 and its 2016 and 2021 decisions modifying mifepristone's Risk Evaluation and Mitigation Strategy (REMS) Program and label, the responses from the FDA and drug manufacturer to the challenges, and the potential implications of the Court's decision on access to mifepristone in the US. The researchers detail how the FDA relied on a robust scientific record analyzing tens of thousands of patient experiences that conclusively demonstrated the safety and effectiveness of the changes to the mifepristone REMS Program and label and urge the Supreme Court to rely on the clear scientific record and preserve access to mifepristone without reimposing restrictions. What follows is a reprint of this brief.
An integrated approach to analyze equitable access to food stores under disasters from human mobility patterns
Authors: Wei Zhiyuan , Mukherjee Sayanti
Published: July 2024

Limited access to food stores is often linked to higher health risks and lower community resilience. Socially vulnerable populations experience persistent disparities in equitable food store access. However, little research has been done to examine how people's access to food stores is affected by natural disasters. Previous studies mainly focus on examining potential access using the travel distance to the nearest food store, which often falls short of capturing the actual access of people. Therefore, to fill this gap, this paper incorporates human mobility patterns into the measure of actual access, leveraging large‐scale mobile phone data. Specifically, we propose a novel enhanced two‐step floating catchment area method with travel preferences (E2SFCA‐TP) to measure accessibility, which extends the traditional E2SFCA model by integrating actual human mobility behaviors. We then analyze people's actual access to grocery and convenience stores across both space and time under the devastating winter storm Uri in Harris County, Texas. Our results highlight the value of using human mobility patterns to better reflect people's actual access behaviors. The proposed E2SFCA‐TP measure is more capable of capturing mobility variations in people's access, compared with the traditional E2SFCA measure. This paper provides insights into food store access across space and time, which could aid decision making in resource allocation to enhance accessibility and mitigate the risk of food insecurity in underserved areas.
My circumstances, their circumstances: An actor‐observer distinction in the consequences of external attributions
Authors: Peretz‐Lange Rebecca , Gonzalez Guadalupe D. S. , Hess Yanine D.
Published: July 2024

People may attribute social phenomena to either internal causes (e.g., people's ability, intelligence, effort, or personality) or external causes (e.g., people's circumstances, access to opportunities, treatment by others). In this review, we focus on external attributions, which have been widely characterized as positive because they help people view marginalized groups and rejected individuals sympathetically. We argue, however, that there exists an important actor‐observer distinction in the consequences of external attributions, giving them the potential to yield both positive and negative consequences: When observers attribute others' setbacks or rejections to external causes, this may help them adopt a sympathetic view. However, when actors attribute their own setbacks or rejections to external causes, this view may harm their mental wellbeing, motivation, or self‐concept. We identify this actor‐observer distinction in three domains: social disparities, social rejection, and academic setbacks. Finally, we discuss some implications of this actor‐observer difference and directions for future research.
Covariation of phonological features in Standardised Scottish English
Authors: Li Zeyu , Gut Ulrike , Meer Philipp
Published: July 2024

Scottish English has characteristic phonological features including rhoticity, the /ʍ/‐/w/ contrast and the lack of the nurse merger. However, recent studies have found ongoing changes in Scottish English phonology such as the gradual loss of rhoticity, the merging of /ʍ/‐/w/ and a partial merger of the nurse vowels. This paper investigates possible covariation between these features across speakers of Standardised Scottish English. The speech of 30 speakers taken from ICE‐Scotland was analysed for their realisations of the nurse lexical set,  and rhotics. Underlying structural covariation among these variables was investigated using Principal Components Analysis. The results show covariation between the overall rate of the traditional /ʍ/ variant and rhoticity but not with the realisation of nurse. More generally, Standardised Scottish English appears to comprise a range of individual covariation patterns that combine more traditional and more modern pronunciation variants to varying degrees.
Homeomorphism groups of 2‐manifolds with the virtual Rokhlin property
Authors: Lanier Justin , Vlamis Nicholas G.
Published: July 2024

We introduce and motivate the definition of the virtual Rokhlin property for topological groups. We then classify the 2‐manifolds whose homeomorphism groups have the virtual Rokhlin property. We also establish the analogous result for mapping class groups of 2‐manifolds.
DXA-derived abdominal fat-free mass to predict MRI skeletal muscle mass in postmenopausal women
Authors: Walker E. , Chalke A.M. , Bland V.L. , Lind K.E. , Chen Z. , Blew R.M. , Odegaard A.O. , Thomson C.A. , Caan B. , Nicholas J.S. , Valencia C.I. , Roe D.J. , Allison M. , Schnatz P.F , Wactawski-Wende J. , Bea J.W.
Published: July 2024

Dual-energy X-ray absorptiometry (DXA) is more available than gold-standard magnetic resonance imaging (MRI), but DXA ability to estimate abdominal skeletal muscle mass (SMM) is unknown. DXA-derived abdominal fat-free mass (FFM; Hologic QDR2000 or QDR4500w) was correlated with single-slice MRI SMM at L4 ( N = 69; r QDR2000 = 0.71, QDR4500w = 0.69; p < 0.0001). Linear regression to predict SMM, including DXA FFM, BMI, and age, resulted in an R-squared of 0.72 and 0.65 for QDR2000 and QDR4500. Bland-Altman limits of agreement were ±21 and ±31 g for 2–3 standard deviations from the mean difference. DXA predicted abdominal SSM is a moderate proxy for MRI abdominal SMM.
Digital identities in the metaverse: Privacy, security, and user authentication in virtual financial systems
Authors: Garg Kapil
Published: July 2024

The advent of the metaverse has ushered in a new era of digital interaction, commerce, and finance. As users increasingly immerse themselves in virtual spaces, the need for robust digital identities becomes paramount. This study investigates the intricate interplay of privacy, security, and user authentication within the context of digital identities in the metaverse, with a particular focus on virtual financial systems. Employing a cross-case analysis method within the qualitative research paradigm, the study extensively examines real-world instances to extract valuable insights, identify challenges, and propose potential solutions in navigating this dynamic landscape. This approach allows for a comprehensive examination of overarching patterns and trends across case studies, revealing persistent challenges in digital identity management. The study delves into the complexities of pseudonymity in virtual engagement, emphasizing the crucial balance required for user trust and accountability. Furthermore, it uncovers commonalities in successful implementations, spotlighting the transformative role of blockchain technology, exemplified by IBM Blockchain World Wire, and the growing trend of biometric authentication, as seen in the FIDO use case. The successful cases examined demonstrate that a user-friendly experience and scalability are integral to the adoption of advanced security technologies. Industry leaders should take note of the global trends in digital transactions, emphasizing efficiency, transparency and cross-border security. Additionally, the study offers forward-looking insights with implications for future research and practice, advocating for continued exploration of the nuanced dynamics between user privacy, trust-building mechanisms and accountability in the ever-evolving metaverse landscape.
Increasing the Measured Effective Quantum Volume with Zero Noise Extrapolation
Authors: Pelofske Elijah , Russo Vincent , Larose Ryan , Mari Andrea , Strano Dan , Bärtschi Andreas , Eidenbenz Stephan , Zeng William
Published: July 2024

Quantum volume is a full-stack benchmark for near-term quantum computers. It quantifies the largest size of a square circuit which can be executed on the target device with reasonable fidelity. Error mitigation is a set of techniques intended to remove the effects of noise present in the computation of noisy quantum computers when computing an expectation value of interest. Effective quantum volume is a proposed metric that applies error mitigation to the quantum volume protocol to evaluate the effectiveness not only of the target device but also of the error mitigation algorithm. Digital zero-noise extrapolation is an error mitigation technique that estimates the noiseless expectation value using circuit folding to amplify errors by known scale factors and then extrapolating computed expectation values to the zero-noise limit. Here we demonstrate that zero-noise extrapolation, with global and local unitary folding with fractional scale factors, in conjunction with dynamical decoupling, can increase the effective quantum volume over the vendor-measured quantum volume. Specifically, we measure the effective quantum volume of four IBM Quantum superconducting processor units, obtaining values that are larger than the vendor-measured quantum volume on each device. This is the first such increase reported.
Comparative Analysis of Multicriteria Decision‐Making Methods for Bus Washing Process Selection: A Case Study
Authors: Ávila Paulo , Mota Alzira , Oliveira Eliana , Castro Hélio , Pinto Ferreira Luís , Bastos João , Fernandes Nuno O. , Moreira Joaquim
Published: July 2024

Water is at the core of sustainable development, and its use for human activities, including vehicle washing, should be done in a sustainable way. There are several technical solutions for washing buses offering different performances, making it difficult to choose the one that best meets the requirements of each specific case. The literature on the topic hardly analyzes the choice of the best technical solution for washing buses and does not apply and compare the results of different multicriteria decision‐making (MCDM) methods for the problem. The unique information available is from the different suppliers in the market. Whereby, this work intends to give a technical‐scientific contribution to fulfill this gaps. Therefore, the main objectives of this work are (1) to select the best sustainable technical solutions for washing buses depending on the specific conditions for a case study and (2) to analyze how different multicriteria decision‐making methods behave in the selection process. To achieve these objectives, the problem was approached as a case study in a public transport company in Portugal and the methodology followed the next steps: started with the identification of the different types of commercial technical solutions for washing buses; the company’s experts selected four main criteria: water consumption, operating costs, quality of washing, and time spent; the criteria weights were determined using the fuzzy‐AHP method; then four representative MCDM methods were selected, namely, AHP, ELECTRE, TOPSIS, and SMART; the ranks obtained for the four methods were compared; and a sensitivity analysis was performed. Considering the input data for the criteria and their weights, the results for all the methods showed that the best and the worst solution was the same, mobile portico with a brush and porticoes with three brushes, respectively. Furthermore, the results of the sensitivity analysis performed with disturbances for the weights of each criterion presented that the results are slightly affected and the similarity in rankings for the four MCDM methods was validated by Spearman’s rank correlation coefficient (rs) and Kendall’s coefficient of concordance (W). Considering these results, the SMART method, the less complex one, showed no difference from the others. For that reason, simple methods, such as SMART, in line with other works in the literature perform well in most cases. As a final remark of this work, it can be said that the methodology employed in this project can also be deemed applicable to other similar companies seeking technical solutions for bus or truck washing. Furthermore, the application of the SMART method, the less complex one and the most understandable for people, showed no difference from the others, being able to be applied in similar situations.
The Pharmacological Mechanisms Underlying the Protective Effect of Ginsenoside Rg3 against Heart Failure
Authors: Jia Yanan , Gong Miao , Ke Zunping
Published: July 2024

Background. Heart failure represents the terminal stage of various cardiovascular diseases. This study aims to explore the pharmacological mechanisms underlying the protective effect of Ginsenoside Rg3 against heart failure. Methods. Potential targets of Ginsenoside Rg3 were identified using SwissTargetPrediction and the Comparative Toxicogenomics Database, while heart failure‐related genes were retrieved from the Comparative Toxicogenomics Database, Therapeutic Target Database, DisGeNET, and PharmGKB. Overlapping of Ginsenoside Rg3 targets with heart failure‐related genes identified drug‐disease interaction genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted on the drug‐disease interaction genes to elucidate their biological functions. A protein‐protein interaction network was constructed using the drug‐disease interaction genes, and the hub genes were identified by topological analysis. Additionally, we validate the expression of IL‐6 and TNF by real‐time PCR. Results. The intersection of Ginsenoside Rg3 targets and heart failure‐related genes yielded 15 drug‐disease interaction genes. Enrichment analysis highlighted the involvement of inflammation‐related GO terms and KEGG pathways, such as positive regulation of interleukin‐8 and ‐6 production, regulation of immune effector process, cytokine receptor binding, cytokine activity, adipocytokine signaling pathway, and IL‐17 signaling pathway, which are implicated in the cardioprotective effect. Topological analysis revealed four hub genes: STAT3, CASP3, TNF, and IL-6. The application of Ginsenoside Rg3 significantly reversed the elevated levels of IL‐6 and TNF in the isoproterenol‐treated H9c2 cell line. Conclusions. Our findings suggest that the cardioprotective effect of Ginsenoside Rg3 may be mediated through its anti‐inflammation properties. Further research is required to elucidate and validate the detailed cardioprotective mechanisms of Ginsenoside Rg3.
Robust Preview Control for Half‐Vehicle Active Suspension System of Hub‐Driven Electric Vehicles with Coupling Effects
Authors: Wu Hang , Jiang Yanjun , Guo Dong , Huang Jiaopeng , Huang Qinglan
Published: July 2024

The mechanical‐electrical‐magnetic coupling effects caused by the air gap deformation in in‐wheel motors exacerbate motor magnetic force oscillation, deteriorating the in‐wheel motor operation and ride comfort. In order to enhance vehicle performances, it is imperative to mitigate these coupling effects during the design of hub‐driven electric vehicle suspensions. In this paper, the analytical investigation is conducted on the coupling effects between electromagnetic excitation and transient dynamics in EVs based on the half‐vehicle model. The dynamic responses of hub‐driven EVs considering coupling effects are explored under both open‐loop and closed‐loop systems at various speeds and road conditions. Numerical simulations demonstrate that the closed‐loop system with wheelbase preview robust control exhibits superior comprehensive performance in suppressing coupling effects of the rear wheel hub motor and enhancing ride comfort compared to the system without preview control. Furthermore, as vehicle speed increases, robust preview control effectively reduces fluctuations in pitch angle acceleration, pitch angle, and rear wheel rotor eccentricity. In addition, robust preview control yields better performance in reducing vehicle body centroid acceleration and rear wheel rotor eccentricity and enhancing motor and vehicle performance with increasing road roughness. This work provides a practical vibration model and control reference for studying the dynamic characteristics of hub‐driven EVs.
Pharmacologic Inhibition of EIF4A Blocks NRF2 Synthesis to Prevent Osteosarcoma Metastasis
Authors: Lizardo Michael M. , Hughes Christopher , Huang Yue Z. , Shyp Taras , Delaidelli Alberto , Zhang Hai-Feng , Shaool Sol Snir , Renner Annalena F. , Burwag Farez , Sayles Leanne C. , Lee Alex G. , Sweet-Cordero Alejandro , Sorensen Poul H.
Published: July 2024

Purpose:

Effective therapies for metastatic osteosarcoma (OS) remain a critical unmet need. Targeting mRNA translation in metastatic OS offers a promising option, as selective translation drives the synthesis of cytoprotective proteins under harsh microenvironmental conditions to facilitate metastatic competence.

Experimental Design:

We assessed the expression levels of eukaryotic translation factors in OS, revealing the high expression of the eukaryotic initiation factor 4A1 (EIF4A1). Using a panel of metastatic OS cell lines and patient-derived xenograft (PDX) models, EIF4A1 inhibitors were evaluated for their ability to block proliferation and reduce survival under oxidative stress, mimicking harsh conditions of the lung microenvironment. Inhibitors were also evaluated for their antimetastatic activity using the ex vivo pulmonary metastasis assay and in vivo metastasis models. Proteomics was performed to catalog which cytoprotective proteins or pathways were affected by EIF4A1 inhibition.

Results:

CR-1-31B, a rocaglate-based EIF4A1 inhibitor, exhibited nanomolar cytotoxicity against all metastatic OS models tested. CR-1-31B exacerbated oxidative stress and apoptosis when OS cells were co-treated with tert-butylhydroquinone, a chemical oxidative stress inducer. CR-1-31B potently inhibited OS growth in the pulmonary metastasis assay model and in experimental and spontaneous models of OS lung metastasis. Proteomic analysis revealed that tert-butylhydroquinone–mediated upregulation of the NRF2 antioxidant factor was blocked by co-treatment with CR-1-31B. Genetic inactivation of NRF2 phenocopied the antimetastatic activity of CR-1-31B. Finally, the clinical-grade EIF4A1 phase-1-to-2 inhibitor, zotatifin, similarly blocked NRF2 synthesis and the OS metastatic phenotype.

Conclusions:

Collectively, our data reveal that pharmacologic targeting of EIF4A1 is highly effective in blocking OS metastasis by blunting the NRF2 antioxidant response.
Figure S9 from N-Myristoytransferase Inhibition Causes Mitochondrial Iron Overload and Parthanatos in TIM17A-Dependent Aggressive Lung Carcinoma
Authors: Geroyska Sofia , Mejia Isabel , Chan Alfred A. , Navarrete Marian , Pandey Vijaya , Kharpatin Samuel , Noguti Juliana , Wang Feng , Srole Daniel , Chou Tsui-Fen , Wohlschlegel James , Nemeth Elizabeta , Damoiseaux Robert , Shackelford David B. , Lee Delphine J. , Díaz Begoña
Published: July 2024

The PARP inhibitor olaparib rescues death induced by NMTi treatment.
High-Dose Intravenous Vitamin C Combined with Docetaxel in Men with Metastatic Castration-Resistant Prostate Cancer: A Randomized Placebo-Controlled Phase II Trial
Authors: Paller Channing J. , Zahurak Marianna L. , Mandl Adel , Metri Nicole A. , Lalji Aliya , Heath Elisabeth , Kelly William K. , Hoimes Christopher , Barata Pedro , Taksey Jason , Garrison Dominique A. , Patra Kartick , Milne Ginger L. , Anders Nicole M. , Nauroth Julie M. , Durham Jennifer N. , Marshall Catherine H. , Markowski Mark C. , Eisenberger Mario A. , Antonarakis Emmanuel S. , Carducci Michael A. , Denmeade Samuel R. , Levine Mark
Published: July 2024

High-dose intravenous vitamin C (HDIVC) administered to produce pharmacologic concentrations shows promise in preclinical models and small clinical trials, but larger prospective randomized trials are lacking. We evaluated the clinical benefit of combining HDIVC with docetaxel in patients with progressive metastatic castration-resistant prostate cancer (mCRPC). In this double-blind, placebo-controlled phase II trial, 47 patients were randomized 2:1 to receive docetaxel (75 mg/m2 i.v.) with either HDIVC (1 g/kg) or placebo. Coprimary endpoints were PSA50 response and adverse event rates. Secondary endpoints included overall survival, radiographic progression-free survival, and quality of life measured using the Functional Assessment of Cancer Therapy-Prostate instrument. Correlative analyses included pharmacokinetics and oxidative stress markers. Eighty-nine percent of patients previously had three or more lines of therapy. The PSA50 response rate was 41% in the HDIVC group and 33% in the placebo group (P = 0.44), with comparable adverse event rates in both groups. There were no significant differences in Functional Assessment of Cancer Therapy-Prostate scores. The median radiographic progression-free survival was not significantly different between the HDIVC and placebo groups, with durations of 10.1 and 10.0 months (HR, 1.35; 95% confidence interval, 0.66–2.75; P = 0.40), respectively. The median overall survival was 15.2 months in the HDIVC group and 29.5 months in the placebo group (HR, 1.98; 95% confidence interval, 0.85–4.58; P = 0.11). HDIVC did not decrease F2-isoprostanes, indicators of oxidative stress. The study was suspended after prespecified interim analysis indicated futility in achieving primary endpoints. In this patient population, combining HDIVC with docetaxel did not improve PSA response, toxicity, or other clinical outcomes compared with docetaxel alone. Findings do not support the routine use of HDIVC in mCRPC treatment outside of clinical trials.

Significance:

This is the first randomized, placebo-controlled, double-blind trial to evaluate HDIVC in cancer treatment. The addition of HDIVC to docetaxel in patients with mCRPC does not improve PSA response, toxicity, or other clinical outcomes compared with docetaxel alone. The routine use of HDIVC in mCRPC treatment is not supported outside of clinical trials.
Genetic Testing of Patients with Inherited Retinal Diseases in the European Countries. An International Survey by the European Vision Institute
Authors: Calzetti Giacomo , Schwarzwälder Kerstin , Ottonelli Giorgia , Kaminska Karolina , Strauss Rupert Wolfgang , Baere Elfride De , Leroy Bart P. , Audo Isabelle , Zeitz Christina , Cursiefen Claus , Stingl Katarina , Boon Camiel J.F. , Marques João Pedro , Santos Cristina , Ayuso Garcia Carmen , Escher Pascal , Cordeiro M. Francesca , D'Esposito Fabiana , Charbel Issa Peter , Lotery Andrew , Lin Siying , Michaelides Michel , Rivolta Carlo , Scholl Hendrik P.N.
Published: July 2024

Introduction: The purpose of this project was to explore the current standards of clinical care genetic testing and counseling for patients with inherited retinal diseases (IRDs) from the perspective of leading experts in selected European countries. Also, to gather opinions on current bottlenecks and future solutions to improve patient care.
Methods: On the initiative of the European Vision Institute, a survey questionnaire with 41 questions was designed and sent to experts in the field from ten European countries. Each participant was asked to answer with reference to the situation in their own country.
Results: Sixteen questionnaires were collected by November 2023. IRD genetic tests are performed in clinical care settings for 80% or more of tested patients in 9 countries, and the costs of genetic tests in clinical care are covered by the public health service to the extent of 90% or more in 8 countries. The median proportion of patients who are genetically tested, the median rate of genetically solved patients among those who are tested, and the median proportion of patients receiving counseling are 51-70%, 61-80% and 61-80%, respectively. Improving the education of healthcare professionals who facilitate patient referrals to specialised centres, improving access of patients to more thorough genotyping, and increasing the number of available counselors were the most advocated solutions.
Conclusion: There is a significant proportion of IRD patients who are not genetically tested, whose genetic testing is inconclusive, or who do not receive counseling. Educational programs, greater availability of state-of-the-art genotyping and genetic counselors could improve healthcare for IRD patients.
The Protective Effect of Vitexin on Hypertensive Nephropathy Rats
Authors: Duan Tingting , Li Minyi , Lin Ziyang , Meng Lanqing , Li Mengqiu , Xia Tao , Zhang Xianlong , Lin Guixuan , Yan Lufeng , Liang Mingjie , Zhu Quan , Li Zhenghai , Yang Junzheng
Published: July 2024

Introduction: Vitexin is a natural flavonoid compound extracted from Vitex leaves or seeds, exhibiting various pharmacological activities including anticancer, antihypertensive, anti-inflammatory, and spasmolytic effects. However, its protective effects on hypertensive nephropathy (HN) and the underlying mechanisms remain unclear. Methods: Spontaneous hypertension rats were fed a high-sugar and high-fat diet for 8 weeks to induce the disease HN model. From the 5th week, the rats were administered vitexin via gavage. Blood pressure was measured biweekly using the tail-cuff method. Histopathological changes were assessed using HE staining, and biochemical analyses were performed to evaluate the effects of vitexin on HN rats. The underlying mechanisms of vitexin treatment were investigated through western blotting. Results: The data demonstrated that vitexin significantly lowered systolic, diastolic, and mean arterial pressures and ameliorated histopathological changes in HN rats. Biochemical analyses revealed that vitexin reduced the levels of creatinine (Cr), blood urea nitrogen (BUN), total cholesterol (TC), triglycerides (TG), total protein (TP), low-density lipoprotein cholesterol (LDL-C), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), malondialdehyde (MDA), and advanced glycation end products (AGEs), while increasing the levels of albumin (ALB) and superoxide dismutase (SOD). Western blotting results indicated that vitexin treatment decreased the expression of TNF-α, IL-6, and nuclear factor kappa-B (NF-κB), while increasing the expression of SOD. Conclusion: The findings of this study suggest that vitexin exerts protective effects against HN, providing pharmacological evidence for its potential use in HN treatment.