bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protocol of a randomised controlled multicentre trial investigating the effectiveness and safety of a wilderness programme on the mental and physical well-being of adolescents and young adults affected by cancer: the WAYA-2 study
Authors: Jong Miek C , Fernee Carina Ribe , Stenling Andreas , Lown E Anne , Berntsen Sveinung , Victorson David E , Jong Mats 
Published: May 2024

IntroductionAdolescents and young adults (AYAs) affected by cancer are an understudied group. Effective interventions are needed to support coping with the late effects of cancer, its treatment and to promote quality of life. Nature-based interventions may be promising in support of the self-management and health of AYAs affected by cancer. However, randomised controlled studies (RCTs) on the effectiveness of such interventions are lacking. We performed a first pilot RCT (n=42) that showed that it is feasible and safe to conduct such a study. Here, we propose a full-scale RCT to investigate the effectiveness and safety of a wilderness programme on the mental and physical health of AYAs affected by cancer.Methods and analysisParticipants are 150 AYAs affected by cancer, aged 16–39 years, who will be randomised to a wilderness (n=75) or a hotel stay (n=75). The wilderness programme is an 8-day intervention including a 6-day wilderness expedition. This is followed 3 months later by a 4-day intervention including a 2-day basecamp. Activities include hiking, backpacking, kayaking, rock climbing, mindfulness and bush-crafting. The comparison group is an 8-day hotel stay followed by a 4-day hotel stay (interventions include two travel days) at the same hotel after 3 months. Primary outcomes are psychological well-being and nature connectedness up to 1 year after the study start. Secondary outcomes are quality of life, physical activity and safety parameters.Ethics and disseminationThe Swedish Ethical Review Authority approved the study protocol on 27 September 2023 (reference: 2023-05247-01). The recruitment started on 19 February 2024 and the first part is planned to end on 31 December 2027. Study results will be disseminated by means of scientific publications, presentations at conferences, popular articles, interviews, chronicles and books. News items will be spread via social media, websites and newsletters.Trial registration numberISRCTN93856392.
Neutrophil extracellular traps activate hepatic stellate cells and monocytes via NLRP3 sensing in alcohol-induced acceleration of MASH fibrosis
Authors: Babuta Mrigya , Morel Caroline , de Carvalho Ribeiro Marcelle , Calenda Charles , Ortega-Ribera Martí , Thevkar Nagesh Prashanth , Copeland Christopher , Zhuang Yuan , Wang Yanbo , Cho Yeonhee , Joshi Radhika , Brezani Viliam , Hawryluk Danielle , Datta Aditi Ashish , Mehta Jeeval , Nasser Imad , Szabo Gyongyi 
Published: May 2024

Objective
Alcohol use in metabolic dysfunction-associated steatohepatitis (MASH) is associated with an increased risk of fibrosis and liver-related death. Here, we aimed to identify a mechanism through which repeated alcohol binges exacerbate liver injury in a high fat-cholesterol-sugar diet (MASH diet)-induced model of MASH.

Design
C57BL/6 mice received either chow or the MASH diet for 3 months with or without weekly alcohol binges. Neutrophil infiltration, neutrophil extracellular traps (NETs) and fibrosis were evaluated.

Results
We found that alcohol binges in MASH increase liver injury and fibrosis. Liver transcriptomic profiling revealed differential expression of genes involved in extracellular matrix reorganisation, neutrophil activation and inflammation compared with alcohol or the MASH diet alone. Alcohol binges specifically increased NET formation in MASH livers in mice, and NETs were also increased in human livers with MASH plus alcohol use. We discovered that cell-free NETs are sensed via Nod-like receptor protein 3 (NLRP3). Furthermore, we show that cell-free NETs in vitro induce a profibrotic phenotype in hepatic stellate cells (HSCs) and proinflammatory monocytes. In vivo, neutrophil depletion using anti-Ly6G antibody or NET disruption with deoxyribonuclease treatment abrogated monocyte and HSC activation and ameliorated liver damage and fibrosis. In vivo, inhibition of NLRP3 using MCC950 or NLRP3 deficiency attenuated NET formation, liver injury and fibrosis in MASH plus alcohol diet-fed mice (graphical abstract).

Conclusion
Alcohol binges promote liver fibrosis via NET-induced activation of HSCs and monocytes in MASH. Our study highlights the potential of inhibition of NETs and/or NLRP3, as novel therapeutic strategies to combat the profibrotic effects of alcohol in MASH.
First-trimester use of antiseizure medications and the risk of miscarriage: a population-based cohort study
Authors: Forbes Harriet , Madley-Dowd Paul , Ahlqvist Viktor , Campbell Jennifer , Davies Neil M , Liebling Rachel , Lyall Kristen , Newschaffer Craig , Rast Jessica , Tomson Torbjörn , Zhong Caichen , Magnusson Cecilia , Rai Dheeraj , Lee Brian K 
Published: May 2024

BackgroundAntiseizure medications (ASMs) during the first trimester of pregnancy have been associated with an increased risk of miscarriage.MethodsWe carried out a population-based cohort study using routinely collected healthcare data from the UK, 1995–2018. Pregnancies were identified in the Clinical Practice Research Datalink and we estimated the HR of miscarriage associated with prescriptions of ASMs during the first trimester of pregnancy, using Cox regression, adjusting for potential confounders, including ASM indications.ResultsASMs were prescribed during the first trimester in 7832 (0.8%) of 1 023 787 included pregnancies. 14.5% of pregnancies with first-trimester exposure to ASMs ended in miscarriage, while 12.2% without ASM exposure in the first trimester ended in miscarriage; after adjustment, there was a 1.06-fold relative hazard of miscarriage (95% CI 1.00 to 1.13) in women with first-trimester ASM use. After restricting to women with specific ASM indications, this association was not evident in women with epilepsy (adjusted HR 0.98, 95% CI 0.89 to 1.08), but was observed in women with bipolar or other psychiatric conditions (1.08, 95% CI 1.00 to 1.16) although CIs overlapped. Compared with discontinuation of ASMs prior to pregnancy, there was no evidence of increased risk of miscarriage for first-trimester ASM use in women with bipolar or other psychiatric conditions (1.02, 95% CI 0.87 to 1.20).ConclusionWe found no clear evidence to suggest that first-trimester ASM use increased the risk of miscarriage. Taken together, our analyses suggest that apparent associations between first-trimester ASM use and miscarriage may be the result of confounding by the presence of a bipolar disorder or associated unmeasured variables.
Review of a large trauma registry in Addis Ababa, Ethiopia: insights into prehospital care and provider training for trauma quality improvement
Authors: Starr Nichole , Ayehu Mengistu , Zhuang Alex , Minalu Habtamu Tamiru , Alemu Genet Kifle , Fisseha Samuel , Chekol Sisay , Habtemariam Aklile , Hadis Makida , Alemtsehay Biruh , Mengiste Minale , Kefeni Bori Ashenafi 
Published: May 2024

BackgroundInjury is a major cause of death and disability in Ethiopia. ALERT Hospital, one of only three designated trauma centers in the country, has employed a basic trauma registry since its inception in 2016; however, these data had not been used. In joint efforts with the Federal Ministry of Health, we aimed to understand patient injury characteristics and predictors of mortality, to inform priorities in resource and training investments.MethodsData from 12 816 consecutive patients in the first 3 years of the trauma registry were reviewed retrospectively. Modified Early Warning Score was used at triage to indicate injury severity (red=critically injured, green=minor injury). No physiologic data for calculating Injury Severity Scores or in-hospital intervention data were available. Triage groups were compared and multivariate logistic regression conducted to determine predictors of in-emergency department (ED) mortality.ResultsMost patients presented with minor injuries with 64.7% triaged as ‘yellow’ and 16.4% triaged as ‘green’, and most (75.9%) referred from another facility. Of those who were critically injured, only 31.0% arrived by ambulance. Most injuries were soft tissue (51.1%) and fractures (23.0%); when stratified by triage category, most critical (‘red’) patients had sustained head injuries (52.7%). Arrival by ambulance (OR 2.20, p=0.017) and head injury (OR 3.11, p<0.001) were independent predictors of death in the ED.ConclusionThis study of injured patients presenting to an Ethiopian trauma center is one of the largest to date, highlighting the need for more accessible and streamlined prehospital trauma care. Opportunities for improvement include staff training in initial trauma management and implementation of a more comprehensive trauma registry containing physiologic, intervention, and outcomes data to support a robust quality improvement program. Efforts by the Federal Ministry of Health are ongoing to support these improvements in care.Level of EvidenceLevel 3, observational study
Social determinants of gastrointestinal malformation mortality in Brazil: a national study
Authors: Gerk Ayla , Rosendo Amanda , Telles Luiza , Miranda Arícia Gomes , Carroll Madeleine , Trindade Bruna Oliveira , Motter Sarah Bueno , Freire Esther , Hyman Gabriella , Ferreira Julia , Botelho Fabio , Ferreira Roseanne , Mooney David P , Bustorff-Silva Joaquim 
Published: May 2024

IntroductionIn Brazil, approximately 5% are born with a congenital disorder, potentially fatal without surgery. This study aims to evaluate the relationship between gastrointestinal congenital malformation (GICM) mortality, health indicators, and socioeconomic factors in Brazil.MethodsGICM admissions (Q39–Q45) between 2012 and 2019 were collected using national databases. Patient demographics, socioeconomic factors, clinical management, outcomes, and the healthcare workforce density were also accounted for. Pediatric Surgical Workforce density and the number of neonatal intensive care units in a region were extracted from national datasets and combined to create a clinical index termed‘NeoSurg’. Socioeconomic variables were combined to create a socioeconomic index termed‘SocEcon’. Simple linear regression was used to investigate if the temporal changes of both indexes were significant. The correlation between mortality and the different indicators in Brazil was evaluated using Pearson’s correlation coefficient.ResultsOver 8 years, Brazil recorded 12804 GICM admissions. The Southeast led with 6147 cases, followed by the Northeast (2660), South (1727), North (1427), and Midwest (843). The North and Northeast reported the highest mortality, lowest NeoSurg, and SocEcon Index rates. Nevertheless, mortality rates declined across regions from 7.7% (2012) to 3.9% (2019), a 51.7% drop. The North and Midwest experienced the most substantial reductions, at 63% and 75%, respectively. Mortality significantly correlated with the indexes in nearly all regions (p<0.05).ConclusionOur study highlights the correlation between social determinants of health and GICM mortality in Brazil, using two novel indexes in the pediatric population. These findings provide an opportunity to rethink and discuss new indicators that could enhance our understanding of our country and could lead to the development of necessary solutions to tackle existing challenges in Brazil and globally.
Polymorphism of a planar neutral radical: magnetic and optical implications
Authors: Borg Genievieve C. , Young Harrison K.S. , Mills Michelle B. , Mastrandrea Jacob W. , Benner Florian , Demir Selvan , Lough Alan J. , Boyle Paul D. , Preuss Kathryn E. 
Published: May 2024

The synthesis and characterization of a new paramagnetic ligand, 4-( N′-methyl-2′-benzimidazolyl)-1,2,3,5-dithiadiazolyl (MebimDTDA), is presented. MebimDTDA exhibits polymorphism in the solid state. The red microcrystalline form (Form I-red) is diamagnetic below T = 370 K, consistent with typical multi-center two-electron bonding interactions (i.e., pancake bonds) between planar π-radicals. By contrast, the green–black crystalline form (Form II-green) exhibits paramagnetic properties consistent with the observed unusual crystal packing in which some, but not all, of the radicals are arranged in a typical pancake-bonded geometry. Crystallographic analysis, magnetic data, and computational methods are employed to elucidate the structure-property relationship, with an emphasis on the role of crystal packing.
Interpretable Clusters for Representing Citizens’ Sense of Belonging through Interaction with Cultural Heritage
Authors: Jiménez-Díaz Guillermo , Diaz-Agudo Belen , Emilio Bruni Luis , Kadastik Nele , Follo Anna , Damiano Rossana , Striani Manuel , Sanchez-Martin Angel , Lieto Antonio 
Published: May 2024

The EU H2020 project social cohesion, participation, and inclusion through cultural engagement (SPICE) focuses on developing, designing, and implementing new methods and digital tools for citizen curation. This article delineates several software tools developed within the project, presenting innovative approaches to represent and visualize citizens and communities resulting from their engagement with cultural heritage. Aligned with the central tenets of SPICE –particularly the notions of belonging and the interpretation reflection loop– the primary objective is to bolster citizens’ participation and inclusion in fostering social cohesion. This article describes how the SPICE tools can be utilized to guide the processes of interpretation and reflection on cultural heritage artifacts. The Community Model serves as a pivotal component, enabling the modeling of citizens and communities through the utilization of similarity functions for clustering citizens based on perspectives. The clustering algorithm is intricately crafted to generate coherent communities, iterating until all clusters are interpretable using demographic attributes, centroid-based representations, and similarity attributes. Authors posit that this model holds significant value in comprehending and structuring complex data within cultural heritage contexts.
To exemplify our approach, the article examines different attributes of individual citizens and citizen groups in the Galleria Civica d’Arte Moderna e Contemporanea (GAM) case study. Here, perspectives are delineated based on visitors’ demographic attributes and their emotional responses when engaging with artworks. These perspectives are then visualized using the VISIR tool, facilitating the exploration and revelation of connections between citizens and communities, thereby bridging the realms of citizen space and cultural heritage space.
FBXO32 Stimulates Protein Synthesis to Drive Pancreatic Cancer Progression and Metastasis
Authors: Su Dan , Wang Ruobing , Chen Guangyu , Ding Chen , Liu Yueze , Tao Jinxin , Wang Yuanyang , Qiu Jiangdong , Luo Wenhao , Weng Guihu , Yang Gang , Zhang Taiping 
Published: May 2024

Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer-related death worldwide, primarily due to its rapid progression. The current treatment options for PDAC are limited, and a better understanding of the underlying mechanisms responsible for PDAC progression is required to identify improved therapeutic strategies. In this study, we identified FBXO32 as an oncogenic driver in PDAC. FBXO32 was aberrantly upregulated in PDAC, and high FBXO32 expression was significantly associated with an unfavorable prognosis in patients with PDAC. FRG1 deficiency promoted FBXO32 upregulation in PDAC. FBXO32 promoted cell migration and invasion in vitro and tumor growth and metastasis in vivo. Mechanistically, FBXO32 directly interacted with eEF1A1 and promoted its polyubiquitination at the K273 site, leading to enhanced activity of eEF1A1 and increased protein synthesis in PDAC cells. Moreover, FBXO32-catalyzed eEF1A1 ubiquitination boosted the translation of ITGB5 mRNA and activated focal adhesion kinase (FAK) signaling, thereby facilitating focal adhesion assembly and driving PDAC progression. Importantly, interfering with the FBXO32–eEF1A1 axis or pharmaceutical inhibition of FAK by defactinib, an FDA-approved FAK inhibitor, substantially inhibited PDAC growth and metastasis driven by aberrantly activated FBXO32–eEF1A1 signaling. Overall, this study uncovers a mechanism by which PDAC cells rely on FBXO32-mediated eEF1A1 activation to drive progression and metastasis. FBXO32 may serve as a promising biomarker for selecting eligible patients with PDAC for treatment with defactinib.
Significance: FBXO32 upregulation in pancreatic cancer induced by FRG1 deficiency increases eEF1A1 activity to promote ITGB5 translation and stimulate FAK signaling, driving cancer progression and sensitizing tumors to the FAK inhibitor defactinib.
Evidence of Decreased Long-term Risk of Cervical Precancer after Negative Primary HPV Screens Compared with Negative Cytology Screens in a Longitudinal Cohort Study
Authors: Gottschlich Anna , Hong Quan , Gondara Lovedeep , Alam Md S. , Cook Darrel A. , Martin Ruth E. , Lee Marette , Melnikow Joy , Peacock Stuart , Proctor Lily , Stuart Gavin , Franco Eduardo L. , Krajden Mel , Smith Laurie W. , Ogilvie Gina S. 
Published: May 2024

Abstract

Background:
The growing use of primary human papillomavirus (HPV) cervical cancer screening requires determining appropriate screening intervals to avoid overtreatment of transient disease. This study examined the long-term risk of cervical precancer after HPV screening to inform screening interval recommendations.

Methods:
This longitudinal cohort study (British Columbia, Canada, 2008 to 2022) recruited women and individuals with a cervix who received 1 to 2 negative HPV screens (HPV1 cohort, N = 5,546; HPV2 cohort, N = 6,624) during a randomized trial and women and individuals with a cervix with 1 to 2 normal cytology results (BCS1 cohort, N = 782,297; BCS2 cohort, N = 673,778) extracted from the provincial screening registry. All participants were followed through the registry for 14 years. Long-term risk of cervical precancer or worse [cervical intraepithelial neoplasia grade 2 or worse (CIN2+)] was compared between HPV and cytology cohorts.

Results:
Cumulative risks of CIN2+ were 3.2/1,000 [95% confidence interval (CI), 1.6–4.7] in HPV1 and 2.7/1,000 (95% CI, 1.2–4.2) in HPV2 after 8 years. This was comparable with the risk in the cytology cohorts after 3 years [BCS1: 3.3/1,000 (95% CI, 3.1–3.4); BCS2: 2.5/1,000 (95% CI, 2.4–2.6)]. The cumulative risk of CIN2+ after 10 years was low in the HPV cohorts [HPV1: 4.7/1,000 (95% CI, 2.6–6.7); HPV2: 3.9 (95% CI, 1.1–6.6)].

Conclusions:
Risk of CIN2+ 8 years after a negative screen in the HPV cohorts was comparable with risk after 3 years in the cytology cohorts (the benchmark for acceptable risk).

Impact:
These findings suggest that primary HPV screening intervals could be extended beyond the current 5-year recommendation, potentially reducing barriers to screening.
Mapping the Single-Cell Differentiation Landscape of Osteosarcoma
Authors: Truong Danh D. , Weistuch Corey , Murgas Kevin A. , Admane Prasad , King Bridgette L. , Chauviere Lee Jes , Lamhamedi-Cherradi Salah-E. , Swaminathan Jyothishmathi , Daw Najat C. , Gordon Nancy , Gopalakrishnan Vidya , Gorlick Richard G. , Somaiah Neeta , Deasy Joseph O. , Mikos Antonios G. , Tannenbaum Allen , Ludwig Joseph 
Published: May 2024

Abstract

Purpose:
The genetic intratumoral heterogeneity observed in human osteosarcomas poses challenges for drug development and the study of cell fate, plasticity, and differentiation, which are processes linked to tumor grade, cell metastasis, and survival.

Experimental Design:
To pinpoint errors in osteosarcoma differentiation, we transcriptionally profiled 31,527 cells from a tissue-engineered model that directs mesenchymal stem cells toward adipogenic and osteoblastic fates. Incorporating preexisting chondrocyte data, we applied trajectory analysis and non-negative matrix factorization to generate the first human mesenchymal differentiation atlas.

Results:
This “roadmap” served as a reference to delineate the cellular composition of morphologically complex osteosarcoma tumors and quantify each cell’s lineage commitment. Projecting a bulk RNA-sequencing osteosarcoma dataset onto this roadmap unveiled a correlation between a stem-like transcriptomic phenotype and poorer survival outcomes.

Conclusions:
Our study quantifies osteosarcoma differentiation and lineage, a prerequisite to better understanding lineage-specific differentiation bottlenecks that might someday be targeted therapeutically.
Virtual Position Guided Strategy for Particle Swarm Optimization Algorithms on Multimodal Problems
Authors: Li Chao , Sun Jun , Li Li-Wei , Shan Min , Palade Vasile , Wu Xiaojun 
Published: May 2024

Abstract
Premature convergence is a thorny problem for particle swarm optimization (PSO) algorithms, especially on multimodal problems, where maintaining swarm diversity is crucial. However, most enhancement strategies for PSO, including the existing diversity-guided strategies, have not fully addressed this issue. This paper proposes the virtual position guided (VPG) strategy for PSO algorithms. The VPG strategy calculates diversity values for two different populations and establishes a diversity baseline. It then dynamically guides the algorithm to conduct different search behaviors, through three phases—divergence, normal, and acceleration—in each iteration, based on the relationships among these diversity values and the baseline. Collectively, these phases orchestrate different schemes to balance exploration and exploitation, collaboratively steering the algorithm away from local optima and towards enhanced solution quality. The introduction of “virtual position” caters to the strategy's adaptability across various PSO algorithms, ensuring the generality and effectiveness of the proposed VPG strategy. With a single hyperparameter and a recommended usual setup, VPG is easy to implement. The experimental results demonstrate that the VPG strategy is superior to several canonical and the state-of-the-art strategies for diversity guidance, and is effective in improving the search performance of most PSO algorithms on multimodal problems of various dimensionalities.
First-Person Experience in Virtual Reality Sport Advertisements: Transportation of Embodied Empathy
Authors: Uhm Jun-Phil , Lee Hyun-Woo , Kim Sanghoon , Han Jin-Wook 
Published: May 2024

Abstract
Virtual reality (VR) has emerged as a powerful marketing tool by eliciting novel and enjoyable consumer experiences. To help shape the future of sport advertisements and influence consumers' purchasing decisions, this study aims to investigate the effects of sport advertisements implemented with VR. Drawing on embodiment theory and transportation theory, we (1) conceptualized embodied empathy according to VR context and (2) examined a model involving psychological processes of embodied empathy, a sense of presence, and attitudes. The results showed that the effect of embodied empathy on consumers' attitude toward brand is mediated by a sense of presence and the attitude toward the advertisement, in a causal sequence. This study contributes in several ways to our understanding of VR in sport advertisements and suggests important practical implications.