bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractDespite 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

SummaryIn 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

AbstractARHGAP 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

AbstractIndustrial 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

AbstractGlobally, 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

AbstractThis 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

AbstractBackgroundPhysical 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.MethodsThe 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.ResultsAmong 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.ConclusionsPhysical 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

AbstractDiffusion 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

AbstractOn 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

AbstractLimited 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

AbstractPeople 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

AbstractScottish 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, <wh‐> 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

AbstractWe 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.
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

Abstract

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.