bluuebunny/crossref_metadata_2025_split huggingface dataset:
FBXL16: a new regulator of neuroinflammation and cognition in Alzheimer’s disease through the ubiquitination-dependent degradation of amyloid precursor protein
Authors: Qu Liqun , Tang Yong , Wu Jianhui , Yun Xiaoyun , Lo Hang Hong , Song Linlin , Wang Xingxia , Wang Huimiao , Zhang Ruilong , Liu Menghan , Wang Cairen , Ng Jerome P. L. , Fu Xianjun , Wong Io Nam , Wong Vincent Kam Wai , Law Betty Yuen Kwan 
Published: November 2024

Abstract
Background
Activating the ubiquitin-proteasome system to dismantle disease- related proteins such as tau, β-amyloid, APP, and α-synuclein is an important focus in the research of neurodegenerative proteinopathy. By analyzing the serum RNA extracted from wild-type and Alzheimer’s disease (AD) transgenic mice at different ages (4, 8, and 12 months), this study revealed a new protective role of FBXL16 in AD, primarily through facilitating the degradation of disease-related proteins via the ubiquitin proteasome system.

Methods
Proteomic analysis were conducted using protein lysates from HEK293 cells overexpressing FBXL16 to identify potential interacting proteins that interact with FBXL16. Subsequent experiments demonstrated that FBXL16 promotes the proteasomal degradation of the APP protein, as evidenced by co-immunoprecipitation with MG132 and cycloheximide (CHX), immunohistochemistry (IHC) and immunocytochemistry (ICC). Memory and cognitive improvements were observed in 3×Tg AD mice through the use of a lentivirus-mediated approach to generate a brain-specific AD mouse model overexpressing FBXL16 via stereotaxic injection. Furthermore, a brain-specific conditional knockout (cko) FBXL16 mouse model was generated and employed to further confirm the functional role of FBXL 16 in AD via various behavioral tests including Morris water maze and Y-maze.

Results
The level of FBXL16 in the brains of transgenic APP/PSEN mice with AD decreased with age. Accelerated degradation of APP was observed when FBXL16 was overexpressed in the hippocampi of these AD mice via a lentivirus. This process led to notable improvements in cognitive impairments and reductions in neuroinflammation. Further studies using proteomics and bioinformatics techniques identified transcription factors and binding proteins associated with FBXL16, providing deeper insights into the potential role of FBXL16 in the regulation of AD. Finally, the in vivo effects of FBXL16 deficiency were further substantiated in cko mice, which overexpress Aβ but specifically lack FBXL16 in the brain region.

Conclusions
These findings suggest that FBXL16 could be a new regulator of AD. These findings provide a foundation for further research into drug development and potential therapeutic strategies to combat other related neurodegenerative proteinopathies.
High detection rate of circulating-tumor DNA from cerebrospinal fluid of children with central nervous system germ cell tumors
Authors: Nakano Yoshiko , Burns Ian , Nobre Liana , Siddaway Robert , Rana Mansuba , Nesvick Cody , Bondoc Andrew , Ku Michelle , Yuditskiy Richard , Ku Dennis T. L. , Shing Matthew M. K. , Cheng Kevin K. F. , Ng Ho-Keung , Das Anirban , Bennett Julie , Ramaswamy Vijay , Huang Annie , Malkin David , Ertl-Wagner Birgit , Dirks Peter , Bouffet Eric , Bartels Ute , Tabori Uri , Hawkins Cynthia , Liu Anthony P. Y. 
Published: November 2024

AbstractCentral nervous system germ cell tumors (CNS-GCT) are malignant neoplasms that arise predominantly during adolescence and young adulthood. These tumors are typically sensitive to treatment, but resulting long-term health deficits are common. Additional clinical challenges include surgical risks associated with tumor biopsy, and need to determine treatment response for adapting radiotherapy protocols. The aim of this study was to establish the detectability of circulating-tumor DNA (ctDNA) from cerebrospinal fluid (CSF) of children with CNS-GCT as a potential biomarker. We obtained CSF from patients with CNS-GCT by lumbar puncture or intra-operatively. Cell-free DNA (cfDNA) was extracted and subjected to low-pass whole genome sequencing (LP-WGS). Copy-number alterations (CNAs) were inferred and served as a marker of measurable residual disease (MRD). Comparisons with imaging findings and tumor marker levels were made. A total of 29 CSF samples from 21 patients (16 with germinoma, 5 with non-germinomatous GCT) were sequenced. Twenty samples from 19 patients were collected at diagnosis, and 9 samples from 7 patients were collected during or after therapy. Among the diagnostic samples, CNAs were detected in samples from 17/19 patients (89%), which included 8 with marker-negative tumors. Specific clinical scenarios suggested that serial cfDNA analysis may carry utility in tracking treatment responses as well as clarifying indeterminate imaging findings. Our results provide evidence for the high-sensitivity in detecting ctDNA from CSF of CNS-GCT patients using LP-WGS, with potential utility for non-invasive diagnosis and disease monitoring in upcoming CNS-GCT studies.
A topic map based learning management system to facilitate meaningful grammar learning: the case of Japanese grammar learning
Authors: Wang Jingyun , Wynn Adam , Mendori Takahiko , Hwang Gwo-Jen 
Published: November 2024

AbstractThis study investigates the effect of studying with topic maps provided by a self-developed language learning support system on (a) learning perception, (b) learning achievement and (c) variation in learning attitude and motivation, from the perspective of prior learning attitude, motivation and learning style. An analysis was conducted on the learning data of 90 participants for examining pre-test and post-test scores, learning perception, learning style indicators, attitude and motivation rankings before and after the study of target Japanese grammar content with the support of the system. The findings suggest that learners with high attitude/motivation perceived greater development of the habit of “learning from the comparison of related knowledge” and felt more satisfied with the learning situation in the system environment. Furthermore, the learners' attitude towards Japanese grammar learning and their motivation toward Japanese language learning were significantly stronger after the learning activity. It is also observed that (a) learner attitude towards Japanese grammar after studying with the system only had a positive correlation to prior attitudes; and (b) learner motivation towards Japanese language after studying with the system correlated highly with prior motivation and perception of development of the habit of “learning from the comparison of related knowledge.” Finally, from a learning style perspective, the analysis result suggests that “Global learners” expressed a stronger feeling about the usefulness of the comparison function of the system and their increment in motivation after using the system was higher than for “Sequential learners.” Moreover, between learning style indicators in the Sequential/Global dimension and level of learner expertise in the reported mental load scale, a significant interaction effect was found.
Sex Differences in Performance and Performance-Determining Factors in the Olympic Winter Endurance Sports
Authors: Solli Guro Strøm , Sandbakk Øyvind , McGawley Kerry 
Published: November 2024

Abstract
Background
Most sex comparisons in endurance sports have been derived from performance-matched groups of female and male athletes competing over similar distances within summer sports. Corresponding analyses of sex differences in winter endurance sports have not previously been conducted. In the Olympic Winter Games (OWG), the endurance sports include cross-country skiing (XCS), biathlon (BIA), Nordic combined (NC), ski mountaineering (SkiMo) and long-track speed skating (SpSk). The aim of this narrative review is to provide a comprehensive analysis of the sex differences in performance and performance-determining factors in the OWG endurance sports.

Main Body
Sex differences in competition speeds are ~ 7–16% in XCS, 12–16% in BIA and 7–11% in SpSk, with race distances often shorter for women compared to men. No comparable data have been published for NC or SkiMo. Slower skiing speeds among women are associated with greater use of the diagonal and gear 2 sub-techniques in classic and skate skiing, respectively. In SpSk, slower skating speeds among women may be related to a less effective push-off being maintained throughout races. Laboratory data have revealed absolute and relative peak aerobic capacity to be 30–63% and 10–27% greater, respectively, in male versus female XCS, BIA, NC, SkiMo and SpSk athletes. There is limited evidence of sex differences in training characteristics, although women currently tend to complete more strength training than men in XCS and BIA. Of note, most data have been derived from studies performed in XCS, with almost no studies investigating sex differences in NC or SkiMo.

Conclusions
This review provides a comprehensive overview of sex differences in performance and performance-determining factors within and between OWG endurance sports, which provides a scientific basis for designing training programs and future studies. Due to the lack of research investigating sex differences in NC and SkiMo, these sports, in particular, would be worthy of further attention.

Key Points

This narrative review provides a novel and comprehensive analysis of sex differences in performance and performance-determining factors in the Olympic winter endurance sports.

Sex differences in competition speeds are ~ 7–16% in cross-country skiing, biathlon and speed skating, while no comparable data were available for Nordic combined or ski mountaineering.

Since men have historically skied and skated over greater distances than women in cross-country skiing, biathlon and speed skating competitions, the “true” sex differences in performance are likely larger than the differences reported in the literature, therefore exceeding the differences typically reported for summer endurance sports.

Most information about sex differences in Olympic winter endurance sports is based on studies performed in cross-country skiing. The conspicuous lack of information on Nordic combined and ski mountaineering warrants further research in these sports.
Extubation timing and risk of extubation failure in aneurysmal subarachnoid hemorrhage patients
Authors: Yang Jun , Lu Junlin , Li Runting , Lin Fa , Chen Yu , Han Heze , Li Ruinan , Li Zhipeng , Zhang Haibin , Yuan Kexin , Li Hongliang , Zhang Linlin , Shi Guangzhi , Wang Shuo , Chen Xiaolin 
Published: November 2024

Abstract
Background
The extubation time is critical during the intensive care unit stay in aneurysmal subarachnoid hemorrhage (aSAH) patients. The current conventional parameters for predicting extubation failure (EF) and extubation time may not be suitable for this population. Here, we aimed to identify factors associated with EF in aSAH patients.

Methods
From a single-center observational study on aSAH patients with computed tomography angiography from 2019 to 2021, patients who received microsurgery were enrolled and divided into two groups according to whether EF occurred. Multivariable logistic regression was conducted to evaluate disease severity, medical history, and extubation time differences between patients with and without EF.

Results
Of 335 patients included, EF occurred with a rate of 0.14. Delayed cerebral ischemia (67.4% vs. 13.5%) and acute hydrocephalus (6.5% vs. 1.4%) were frequently observed in patients with EF. Also, patients who develop EF presented higher disability (65.9% vs. 17.4%) and mortality (10.9% vs. 0.7%) rates. Multivariable analysis demonstrated that age (OR 1.038; 95% CI 1.004–1.073; P = 0.028), onset to admission time (OR 0.731; 95% CI 0.566–0.943; p = 0.016), WFNS grade > 3 (OR 4.309; 95% CI 1.639–11.330; p = 0.003), and extubation time < 24 h (OR 0.097; 95% CI 0.024–0.396; p = 0.001) were significantly associated with EF occurrence.

Conclusions
These data provide further evidence that older aSAH patients with onset to admission time < 2 days and WFNS grade > 3 have a high risk of developing EF, which is amplified by the ultra-early extubation. Moreover, in patients with two or more risk factors, a prolonged intubation recommendation requires consideration to avoid the EF.
How the U.S. presidential election impacts global health: governance, funding, and beyond
Authors: Liu Yuming , Hall Brian J. , Ren Minghui 
Published: November 2024

AbstractThe United States plays a crucial role in shaping global health through its policy decisions and engagements. Historically, bipartisan support underpinned U.S. involvement in multilateral and bilateral global health initiatives in advancing its national health, security interests, and foreign policy. However, recent decades have witnessed increased politicization and polarization of global health and fluctuating stances between Republican and Democratic administrations. This commentary speculates the potential implications of the 2024 presidential election on global health, focusing on how ideological differences between parties and previous administrative actions might affect U.S.’s strategies in addressing key global health issues, including governance, funding allocation, sexual and reproductive health policies, responses to humanitarian crises, and efforts to combat climate change. The election may be a critical juncture that could determine whether the U.S. global health strategies will continue to reflect the globalist and liberal policies typically associated with recent Democratic administrations or shift back to the isolationist tendencies observed during Trump’s presidency. The outcome will significantly determine the direction of U.S. global health policy and its broader implications for global health equity and security. The conclusions emphasize the necessity of maintaining strong international cooperation and commitment to health as a global public good.
Fire versus herbivory for oak woodland restoration: burning achieves short-term structural and compositional objectives whereas browsing alone fails to reduce stem densities and promote ground flora
Authors: Beebe Gina R. , Pile Knapp Lauren S. , Stambaugh Michael C. , Dey Daniel C. , Davidson Brian , Maddox Dacoda , Kabrick John M. 
Published: November 2024

Abstract
Background
Declines in ecologically beneficial fire, coincident with alterations to native herbivory and intensive land use, have led to dynamic changes in woodland structure and composition, leading to midstory densification and reductions in ground flora abundance and diversity. Frequent, low intensity fire is key to achieving woodland restoration objectives and prescribed burns are often used to meet management goals. For a variety of reasons, the use of prescribed fire is often limited. Further, growing season prescribed burning is often suggested to have a greater impact on woody stems than dormant season applications, but its implementation is difficult. Targeted herbivory may emulate many aspects of prescribed fire holding the potential to diversify management strategies for restoration. We designed a replicated, experimental study to evaluate targeted browsing and prescribed burning for achieving restoration objectives, specifically, a two layered oak woodland with a diverse and abundant native ground flora. The six treatments included: (1) spring browsing, (2) fall browsing, (3) dormant-season and fall browsing, (4) dormant-season prescribed fire, (5) spring browsing plus dormant-season prescribed fire, and (6) an untreated control.

Results
Results suggest that fire had an overriding effect on the reduction of midstory stems that was not comparable to the browsing treatments. Burning reduced leaf litter, increased bare soil exposure and forb coverage. Browsing may reduce the accumulation of woody stems when compared to the control, but this effect was not statistically meaningful. Differences in browsing seasonality and frequent browsing were also not statistically important but trends suggest a greater influence of spring browsing for meeting woodland objectives. Browsing may also exert compositional changes to woodlands because of forage preferences by goats.

Conclusions
To achieve woodland objectives in the short-term, fire is necessary to quickly reduce midstory densities, increase light availability, consume leaf litter, and thereby promote native ground flora abundance and diversity which may not be achieved with targeted browsing alone. Further, the interaction of fire and herbivory suggest that browsing preferences may influence structural and compositional outcomes associated with pyric herbivory regimes in woodlands that require further investigation.
Identification of dynamic properties of a flooded ballast layer using impact excitation technique and minimization algorithm
Authors: Wangtawesap Ratabhat , Chintanapakdee Chatpan , Ngamkhanong Chayut 
Published: November 2024

AbstractIn recent times, the railway sector has faced a pressing need to expand its railway network, resulting in the widespread adoption of ballasted tracks. These tracks are favored for their ease of construction, making them a cost-effective solution for the railway industry. However, with global warming causing more volatile weather conditions leading to multiple occurrences of flooding in Thai railway structures. Ballast dynamic properties play a crucial role in the analysis of the performance and safety of the railway system. In response to these challenges, this study investigates how flooding affects the dynamic behavior of ballasted track structures. The impact hammering method is frequently used to evaluate the dynamic properties of ballasted tracks. However, previous studies have often simplified the analysis by treating the sleeper-ballast system as a single-degree-of-freedom (SDOF) system. This simplification overlooks the spatial variability in the conditions of the ballast layer. To achieve a more accurate representation, our study employs a multi-degree-of-freedom (MDOF) model, which considers the variability in the stiffness properties of the sleepers. The model for the sleeper-ballast system is constructed based on Timoshenko beam theory resting on an elastic foundation. Simulation of flooding on the ballast layer is conducted using a self-built wooden and acrylic box containing a full-scale track structure. This paper utilizes an instrumented impact hammering method, allowing for a comprehensive assessment of the dynamic properties of the ballast layer. To identify the dynamic characteristics of the ballast, a minimization algorithm is applied. The findings of this research indicate that as the water level rises, the stiffness decreases. This study provides crucial insights into how flooding impacts the dynamic properties of ballasted tracks, offering insights that can be applied to enhance the safety analysis of ballasted tracks in the future.
Comparative analysis of bone health and glycemic control in postmenopausal women: insights from clinical data
Authors: Atere Adedeji D. , Oyewole Ebunoluwa O. , Kosamat Yekeen A. , Joseph Gregory U. 
Published: November 2024

Abstract
Background
Menopause leads to significant physiological and biochemical alterations that impact different aspects of health, such as bone mineral metabolism and glycemic control. It is imperative to comprehend these alterations in order to identify potential health hazards and develop preventative measures. This comparative cross-sectional study aimed to evaluate bone-associated markers and glycemic control indices in postmenopausal women (PMP).

Methods
A sample of 100 women aged 30 years or older was randomly selected and categorized into three groups: PMP (n = 60), premenopausal (PRM) (n = 20), and women in the reproductive age group (RWA) (n = 20). Venous blood samples were collected, and fasting blood glucose (FBG), calcium, phosphorus, uric acid, and alkaline phosphatase (ALP) levels were analyzed using standard laboratory techniques. The insulin and estrogen levels were evaluated using enzyme-linked immunosorbent assay (ELISA), and Homeostasis model assessment of insulin resistance (HOMA-IR), Quantitative insulin sensitivity check index (QUICKI), and Fasting insulin resistance index (FIRI) were calculated. A significance level of p < 0.05 was used in the statistical analysis conducted using SPSS version 25.0.

Results
The PMP and PRM groups showed significantly greater mean values of FBG, insulin, and HOMA-IR when compared to RWA (p < 0.05), while these groups had lower QUICKI levels. Similar trends were noted for bone-associated markers, with significant differences among the groups (p < 0.05). The correlation results showed that QUICKI had positive correlations with both ALP and phosphorus, while FBG and FIRI had negative connections with both.

Conclusion
Postmenopausal women demonstrated higher levels of glycemic control indices and bone-related markers compared to premenopausal and reproductive-age women, indicating potential risks for osteoporosis and obesity.
Serum Metabolomic Profiling of Incident Type 2 Diabetes Mellitus in the Multi-ethnic Study of Atherosclerosis and Rotterdam Study
Authors: Jiang Xuanwei , Zhu Fang , Graça Gonçalo , Du Xihao , Ran Jinjun , Ahmadizar Fariba , Wood Alexis C , Zhou Yanqiu , Scholtens Denise M , Farzaneh Ali , Ikram M Arfan , Kuang Alan , le Roux Carel W , Gadgil Meghana D , Cornelis Marilyn C , Taylor Kent D , Guo Xiuqing , Ghanbari Mohsen , Rasmussen-Torvik Laura J , Tracy Russell P , Bertoni Alain G , Rotter Jerome I , Herrington David M , Greenland Philip , Kavousi Maryam , Zhong Victor W 
Published: November 2024

Abstract

Objective
This study aimed to investigate serum metabolomic biomarkers associated with incident type 2 diabetes mellitus (T2DM) and evaluate their performance in improving T2DM risk prediction.

Methods
Untargeted proton nuclear magnetic resonance (1H NMR) spectroscopy-based metabolomics analyses were conducted in the Multi-Ethnic Study of Atherosclerosis (MESA; n = 3460; discovery cohort) and The Rotterdam Study (RS; n = 1556; replication cohort). Multivariable cause-specific hazards models were used to analyze the associations between 23 571 serum metabolomic spectral variables and incident T2DM. Replicated metabolites required an false discovery rate-adjusted P &lt; .01 in MESA, P &lt; .05 in RS, and consistent direction of association. Pathway and network analyses were conducted to elucidate biological mechanisms underlying T2DM development. The utility of the replicated metabolites in improving T2DM risk prediction was assessed based on the Framingham Diabetes Risk Score. A 2-sample Mendelian randomization was conducted to assess causal associations.

Results
Nineteen metabolites were significantly associated with incident T2DM. Pathway analyses revealed disturbances in aminoacyl-tRNA biosynthesis, metabolism of branched-chain amino acids (BCAAs), glycolysis/gluconeogenesis, and glycerolipid metabolism. Network analyses identified interactions with upstream regulators including p38 mitogen-activated protein kinases, c-Jun N-terminal kinase, and mammalian target of rapamycin signaling pathways. Adding replicated metabolites to the Framingham Diabetes Risk Score showed modest to moderate improvements in prediction performance in MESA and RS, with Δ C-statistic of 0.05 [95% confidence interval (CI), 0.04-0.07] in MESA and 0.03 (95% CI, 0.01-0.05) in RS. Genetically increased BCAAs and mannose were associated with T2DM.

Conclusion
1H NMR measured metabolites involved in aminoacyl-tRNA biosynthesis, BCAA metabolism, glycolysis/gluconeogenesis, and glycerolipid metabolism were significantly associated with incident T2DM and provided modest to moderate predictive utility beyond traditional risk factors.