bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of an escape room game on college nursing students’ learning attitude and game flow experiences in teaching safe medication care for the elderly: an intervention educational study
Authors: Chen Dong , Liu Fang , Zhu Chongkuan , Tai Chunling , Zhang Yuhuan , Wang Xiaoyu 
Published: December 2023

Abstract
Background
In the context of an aging population, the Gerontological Nursing course is becoming more and more important. Escape room games have been shown to have a positive effect on nursing education, but they have not been applied in the Gerontological Nursing course. The purpose of this study was to investigate the effects of adding an escape room game-based learning activity at the end of classroom teaching in a Gerontological Nursing course on nursing students’ learning attitude and game flow experience.

Methods
In April 2023, a total of 84 nursing students from two classes at a medical school in Northeast China were selected for the study, and the classes were divided into a test group (n = 41) and a control group (n = 43). Both groups received regular classroom teaching on “Safe Medication Care for the Elderly”, and the test group participated in an escape room game at the end of the classroom teaching. General information about the nursing students in both groups was collected prior to participation; learning attitude were measured before and after participation; and game flow experience was measured before and after participation in the test group. Data were analyzed using independent samples t-tests and paired samples t-tests.

Results
There was no statistically significant difference in the general information and learning attitude of nursing students between the two groups before participation. After participation, the total learning attitude score of nursing students in the test group was (73.17 ± 1.67) and that of the control group was (61.63 ± 2.66), and the difference was statistically significant (p < 0.001, Cohen’s d = 5.196). The game flow experience of nursing students in the test group before and after participation was (63.27 ± 2.48) and (81.29 ± 2.49), respectively, and the difference between before and after was statistically significant (p < 0.001, Cohen’s d = 5.253).

Conclusions
During the teaching process of the Gerontological Nursing course, an escape room game added at the end of classroom teaching can improve nursing students’ learning attitude and also help them to have a good game flow experience. These findings suggest that teaching activities based on the escape room game have considerable practical application value.
“We literally worked in parking lots, cars, garages, and separately set up party tents”: qualitative study on the experiences of GPs in the frame of the SARS-CoV-2 pandemic in Austria
Authors: Rabady Susanne , Mayrhofer Mira , Szabo Nathalie , Erber Patrick , Hoffmann Kathryn 
Published: December 2023

Abstract
Background
Primary care is internationally recognised as one of the cornerstones of health care. During the COVID-19 pandemic, primary care physicians were assigned a variety of tasks and thus made a significant contribution to a country’s pandemic response. They were expected to perform a variety of tasks, such as diagnosing and treating people with COVID-19, maintaining health care for all other patients, as well as several public health tasks, such as diagnostic testing and vaccination, protecting patients and staff from infection, and serving as community trusted persons. In Austria, there are no structured levels of care, no definition of the role of the general practitioner during a pandemic is given, and no specific support structures are present. The aim of this study was to assess the views and experiences of primary care physicians regarding supportive and hindering factors for pandemic preparedness in Austria.

Methods
Qualitative study using semi-structured interviews. A total of 30 general practitioners were interviewed, with particular attention to an equitable distribution in small, medium and large primary care facilities. Qualitative content analysis was performed.

Results
Interviewees described a wide range of infection control, organisational and communication measures that they had implemented. They made changes to practise equipment, found makeshift solutions when supplies were scarce, and established communication and information pathways when official communication lines were inadequate.

Conclusion
General practitioners took on essential tasks and showed a high level of understanding of their role in the pandemic response. This was achieved mainly at an informal level and with high personal commitment. Their functioning in the absence of structural regulations and support shows that they had a clear intrinsic understanding of their responsibilities. To ensure reliability and sustainability and to reduce their burden, it will be necessary to clarify the role and tasks of a general practitioner and to provide the necessary support. This concerns both infrastructural support and communication and information strategies. As part of the reform to strengthen primary care, primary care needs to be seen, valued and involved in decision-making processes.
Transition of allele-specific DNA hydroxymethylation at regulatory loci is associated with phenotypic variation in monozygotic twins discordant for psychiatric disorders
Authors: Ye Junping , Huang Zhanwang , Li Qiyang , Li Zhongwei , Lan Yuting , Wang Zhongju , Ni Chaoying , Wu Xiaohui , Jiang Tingyun , Li Yujing , Yang Qiong , Lim Junghwa , Ren Cun-Yan , Jiang Meijun , Li Shufen , Jin Peng , Chen Jian-Huan , Zhao Cunyou 
Published: December 2023

Abstract
Background
Major psychiatric disorders such as schizophrenia (SCZ) and bipolar disorder (BPD) are complex genetic mental illnesses. Their non-Mendelian features, such as those observed in monozygotic twins discordant for SCZ or BPD, are likely complicated by environmental modifiers of genetic effects. 5-Hydroxymethylcytosine (5hmC) is an important epigenetic mark in gene regulation, and whether it is linked to genetic variants that contribute to non-Mendelian features remains largely unexplored.

Methods
We combined the 5hmC-selective chemical labeling method (5hmC-seq) and whole-genome sequencing (WGS) analysis of peripheral blood DNA obtained from monozygotic (MZ) twins discordant for SCZ or BPD to identify allelic imbalances in hydroxymethylome maps, and examined association of allele-specific hydroxymethylation (AShM) transition with disease susceptibility based on Bayes factors (BF) derived from the Bayesian generalized additive linear mixed model. We then performed multi-omics integrative analysis to determine the molecular pathogenic basis of those AShM sites. We finally employed luciferase reporter, CRISPR/Cas9 technology, electrophoretic mobility shift assay (EMSA), chromatin immunoprecipitation (ChIP), PCR, FM4-64 imaging analysis, and RNA sequencing to validate the function of interested AShM sites in the human neuroblastoma SK-N-SH cells and human embryonic kidney 293T (HEK293T) cells.

Results
We identified thousands of genetic variants associated with AShM imbalances that exhibited phenotypic variation-associated AShM changes at regulatory loci. These AShM marks showed plausible associations with SCZ or BPD based on their effects on interactions among transcription factors (TFs), DNA methylation levels, or other epigenomic marks and thus contributed to dysregulated gene expression, which ultimately increased disease susceptibility. We then validated that competitive binding of POU3F2 on the alternative allele at the AShM site rs4558409 (G/T) in PLLP-enhanced PLLP expression, while the hydroxymethylated alternative allele, which alleviated the POU3F2 binding activity at the rs4558409 site, might be associated with the downregulated PLLP expression observed in BPD or SCZ. Moreover, disruption of rs4558409 promoted neural development and vesicle trafficking.

Conclusion
Our study provides a powerful strategy for prioritizing regulatory risk variants and contributes to our understanding of the interplay between genetic and epigenetic factors in mediating SCZ or BPD susceptibility.
Comparison of plugin and redundant marker sets to analyze gait kinematics between different populations
Authors: Ji Run , Lee Wayne Yuk-wai , Guan Xinyu , Yan Bin , Yang Lei , Yang Jiemeng , Wang Ling , Tao Chunjing , Kuai Shengzheng , Fan Yubo 
Published: December 2023

Abstract
Background
Gait model consists of a marker set and a segment pose estimation algorithm. Plugin marker set and inverse kinematic algorithm (IK.) are prevalent in gait analysis, especially musculoskeletal motion analysis. Adding extra markers for the plugin marker set could increase the robustness to marker misplacement, motion artifacts, and even markers occlusion. However, how the different marker sets affect the gait analysis's kinematic output is unclear. Therefore, this study aims to investigate the effect of marker sets on the kinematic output during level walking in different populations.

Results
In all three planes, there are significant differences (P < 0.05) between marker sets in some kinematic variables at the hip, knee, and ankle. In different populations, the kinematic variables that show significant differences varied. When comparing the kinematic differences between populations using the two marker sets separately, the range of motion (ROM) of hip flexion was only found to be a significant difference using the redundant marker set, while the peak internal rotation at the knee was only found a significant difference using plugin marker set. In addition, the redundant marker set shows less intra-subject variation than the plugin marker set.

Conclusion
The findings in this study demonstrate the importance of marker set selection since it could change the result when comparing the kinematic differences between populations. Therefore, it is essential to increase the caution in explaining the result when using different marker sets. It is crucial to use the same marker set, and the redundant marker set might be a better choice for gait analysis.
QALYs and rare diseases: exploring the responsiveness of SF-6D, EQ-5D-5L and AQoL-8D following genomic testing for childhood and adult-onset rare genetic conditions in Australia
Authors: Pan Tianxin , Wu You , Buchanan James , Goranitis Ilias 
Published: December 2023

Abstract
Background
Genomic testing transforms the diagnosis and management of rare conditions. However, uncertainty exists on how to best measure genomic outcomes for informing healthcare priorities. Using the HTA-preferred method should be the starting point to improve the evidence-base. This study explores the responsiveness of SF-6D, EQ-5D-5L and AQoL-8D following genomic testing across childhood and adult-onset genetic conditions.

Method
Self-reported patient-reported outcomes (PRO) were obtained from: primary caregivers of children with suspected neurodevelopmental disorders (NDs) or genetic kidney diseases (GKDs) (carers’ own PRO), adults with suspected GKDs using SF-12v2; adults with suspected complex neurological disorders (CNDs) using EQ-5D-5L; and adults with dilated cardiomyopathy (DCM) using AQol-8D. Responsiveness was assessed using the standardised response mean effect-size based on diagnostic (having a confirmed genomic diagnosis), personal (usefulness of genomic information to individuals or families), and clinical (clinical usefulness of genomic information) utility anchors.

Results
In total, 254 people completed PRO measures before genomic testing and after receiving results. For diagnostic utility, a nearly moderate positive effect size was identified by the AQoL-8D in adult DCM patients. Declines in physical health domains masked any improvements in mental or psychosocial domains in parents of children affected by NDs and adult CNDs and DCM patients with confirmed diagnosis. However, the magnitude of the changes was small and we did not find statistically significant evidence of these changes. No other responsiveness evidence related to diagnostic, clinical, and personal utility of genomic testing was identified.

Conclusion
Generic PRO measures may lack responsiveness to the diagnostic, clinical and personal outcomes of genomics, but further research is needed to establish their measurement properties and relevant evaluative space in the context of rare conditions. Expected declines in the physical health of people experiencing rare conditions may further challenge the conventional application of quality of life assessments.
Cirsiliol induces autophagy and mitochondrial apoptosis through the AKT/FOXO1 axis and influences methotrexate resistance in osteosarcoma
Authors: Luo Mengliang , Su Zexin , Gao Haotian , Tan Jianye , Liao Rongdong , Yang Jiancheng , Lin Lijun 
Published: December 2023

Abstract
Background
Osteosarcoma (OS) is the most common primary malignant bone tumor in children and adolescents, with poor outcomes for patients with metastatic disease or chemotherapy resistance. Cirsiliol is a recently found flavonoid with anti-tumor effects in various tumors. However, the effects of cirsiliol in the regulation of aggressive behaviors of OS remain unknown.

Methods
The effect of cirsiliol on the proliferation of OS cells was detected using a cell counting kit-8 (CCK-8) assay and 5-ethynyl-2′-deoxyuridine (EdU) staining, while cell apoptosis was detected using flow cytometry. Immunofluorescence was applied to visualize the expression level of the mitochondria, lysosomes and microtubule-associated protein light chain 3 (LC3). A computational molecular docking technique was used to predict the interaction between cirsiliol and the AKT protein. The impact of cirsiliol on resistance was investigated by comparing it between a methotrexate (MTX)-sensitive OS cell line, U2OS, and a MTX-resistant OS cell line, U2OS/MTX. Finally, in situ xenogeneic tumor models were used to validate the anti-tumor effect of cirsiliol in OS.

Results
Cirsiliol inhibited cell proliferation and induced apoptosis in both U2OS and U2OS/MTX300 OS cells. In addition, treatment with cirsiliol resulted in G2 phase arrest in U2OS/MTX300 and U2OS cells. Cell fluorescence probe staining results showed impaired mitochondria and increased autophagy in OS cells after treatment with cirsiliol. Mechanistically, it was found that cirsiliol targeted AKT by reducing the phosphorylation of AKT, which further activated the transcriptional activity of forkhead Box O transcription factor 1 (FOXO1), ultimately affecting the function of OS cells. Moreover, in situ tumorigenesis experiments showed that cirsiliol inhibited the tumorigenesis and progression of OS in vivo.

Conclusions
Cirsiliol inhibits OS cell growth and induces cell apoptosis by reducing AKT phosphorylation and further promotes FOXO1 expression. These phenomena indicate that cirsiliol is a promising treatment option for OS.
Sex difference in incidence of major depressive disorder: an analysis from the Global Burden of Disease Study 2019
Authors: Li Sangzi , Zhang Xuan , Cai Yilu , Zheng Leilei , Pang Hu , Lou Lixia 
Published: December 2023

Abstract
Background
Major depressive disorder (MDD) is a leading mental disorder causing severe impairment. This study was aimed to evaluate sex difference in global MDD incidence by year, age, and socioeconomic status, according to the Global Burden of Disease Study 2019 (GBD 2019).

Methods
Global and national sex-specific incidence estimates of MDD, from 1990 to 2019, in different age groups, were extracted from the GBD 2019. Socioeconomic development index (SDI) as an indicator of national socioeconomic development was used. Absolute (female minus male) and relative (female to male ratio) sex difference in age-standardized incidence rates (ASRs), as well as risk ratios (RR and 95% confidence interval), were computed by year and age. Linear regression analyses were conducted to investigate socioeconomic-associated sex difference in incidence.

Results
Absolute and relative sex difference in ASRs showed a slight declining trend during 1990 and 2019, with absolute difference decreasing from 1818.23 to 1602.58, and relative difference decreasing from 1.71 to 1.61. Worldwide, females had a higher risk of MDD than males in 1990 (RR: 1.706 (1.705–1.706)) and 2019 (RR: 1.602 (1.619–1.620)). The highest RRs were observed in the Region of the Americas. Sex difference in incidence rates increased rapidly with age for those under 20 years old. The highest RR (1.913 (1.910–1.915)) was observed in the age group of 10–14. Relative sex difference had a significant positive relationship with SDI (standardized β = 0.267, P < 0.001).

Conclusions
Despite that slight improvement in sex difference in global MDD incidence has been achieved, sex difference still persists in the past decades, with females always having a higher incidence than males. Greater sex difference was found at younger ages and in more developed countries. The findings highlight the importance of making sex-specific health policy to reduce sex difference in MDD incidence.
Selective aortic arch perfusion: a first-in-human observational cadaveric study
Authors: Marsden Max , Barratt Jon , Donald-Simpson Helen , Wilkinson Tracey , Manning Jim , Rees Paul 
Published: December 2023

Abstract
Background
Selective aortic arch perfusion (SAAP) is a novel endovascular technique that combines thoracic aortic occlusion with extracorporeal perfusion of the brain and heart. SAAP may have a role in both haemorrhagic shock and in cardiac arrest due to coronary ischaemia. Despite promising animal studies, no data is available that describes SAAP in humans. The primary aim of this study was to assess the feasibility of selective aortic arch perfusion in humans. The secondary aim of the study was to assess the feasibility of achieving direct coronary artery access via the SAAP catheter as a potential conduit for salvage percutaneous coronary intervention.

Methods
Using perfused human cadavers, a prototype SAAP catheter was inserted into the descending aorta under fluoroscopic guidance via a standard femoral percutaneous access device. The catheter balloon was inflated and the aortic arch perfused with radio-opaque contrast. The coronary arteries were cannulated through the SAAP catheter.

Results
The procedure was conducted four times. During the first two trials the SAAP catheter was passed rapidly and without incident to the intended descending aortic landing zone and aortic arch perfusion was successfully delivered via the device. The SAAP catheter balloon failed on the third trial. On the fourth trial the left coronary system was cannulated using a 5Fr coronary guiding catheter through the central SAAP catheter lumen.

Conclusions
For the first time using a perfused cadaveric model we have demonstrated that a SAAP catheter can be easily and safely inserted and SAAP can be achieved using conventional endovascular techniques. The SAAP catheter allowed successful access to the proximal aorta and permitted retrograde perfusion of the coronary and cerebral circulation.
Utility of ultrasound in managing acute medical conditions in space: a scoping review
Authors: Asachi Parsa , Ghanem Ghadi , Burton Jason , Aintablian Haig , Chiem Alan 
Published: December 2023

Abstract
Background
In long-distance spaceflight, the challenges of communication delays and the impracticality of rapid evacuation necessitate the management of medical emergencies by onboard physicians. Consequently, these physicians must be proficient in tools, such as ultrasound, which has proven itself a strong diagnostic imaging tool in space. Yet, there remains a notable gap in the discourse surrounding its efficacy in handling acute medical scenarios. This scoping review aims to present an updated analysis of the evidence supporting the role of ultrasound in diagnosing acute conditions within microgravity environments.

Methods
A systematic search was executed across three bibliographic databases: PubMed, EMBASE (Embase.com), and the Web of Science Core Collection. We considered articles published up to February 25, 2023, that highlighted the application of ultrasound in diagnosing acute medical conditions in either microgravity or microgravity-simulated settings. Exclusions were made for review papers, abstracts, and in-vitro studies.

Results
After removing duplicates, and filtering papers by pre-determined criteria, a total of 15 articles were identified that discuss the potential use of ultrasound in managing acute medical conditions in space. The publication date of these studies ranged from 1999 to 2020. A relatively similar proportion of these studies were conducted either on the International Space Station or in parabolic flight, with one performed in supine positioning to simulate weightlessness. The included studies discuss acute pathologies, such as abdominal emergencies, decompression sickness, deep venous thrombosis, acute lung pathologies, sinusitis, musculoskeletal trauma, genitourinary emergencies, and ocular emergencies.

Conclusions
While ultrasound has shown promise in addressing various acute conditions, significant knowledge gaps remain, especially in gastrointestinal, cardiac, vascular, and reproductive emergencies. As we venture further into space, expanding our medical expertise becomes vital to ensure astronaut safety and mission success.
The sixth Japanese meeting on biological function and evolution through interactions between hosts and transposable elements
Authors: Ichiyanagi Kenji , Ikeda Yoko , Saito Kuniaki 
Published: December 2023

AbstractThe sixth Japanese meeting on host–transposon interactions, titled “Biological Function and Evolution through Interactions between Hosts and Transposable Elements,” was held on August 24th and 25th, 2023, at the National Institute of Genetics as well as online. This meeting was supported by the National Institute of Genetics and aimed to bring together researchers studying the diverse roles of TEs in genome function and evolution, as well as host defense systems against TE mobility, TE bursts during evolution, and intron mobility in mammals, insects, land plants, yeast, protozoa, and bacteria. Here, we have presented the highlights of the discussion.Organizers: Kenji Ichiyanagi, Yoko Ikeda, and Kuniaki Saito.