bluuebunny/crossref_metadata_2025_split huggingface dataset:
The predictive value of the hs-CRP/HDL-C ratio, an inflammation-lipid composite marker, for cardiovascular disease in middle-aged and elderly people: evidence from a large national cohort study
Authors: Gao Yu , Wang Miyuan , Wang Ruiting , Jiang Jinchi , Hu Yueyao , Wang Wei , Wang Yong , Li Haijing 
Published: March 2024

Abstract
Background and aims
Cardiovascular disease (CVD) is associated with inflammation and abnormal lipid metabolism. However, a single inflammatory index or a single lipid index cannot accurately predict the prognosis of CVD independently because it is prone to be affected by various confounding factors.

Methods
This population-based cohort study included 6,554 participants from the China Health and Retirement Longitudinal Study (CHARLS) to investigate correlations. In the present study, the occurrence of CVD events such as stroke and heart disease was evaluated by considering self-reported diagnoses at the beginning of the study and during wave 4, and a restricted cubic spline model was used to investigate potential nonlinear relationships in addition to multivariate logistic regression models. Stratified analyses were performed to examine how sociodemographic characteristics may influence the results.

Results
Seven years of follow-up (2011–2018) revealed that 786 people (11.99%) developed CVD. According to the adjusted model, the high-sensitivity C-reactive protein (hs-CRP)-to-high-density lipoprotein cholesterol (HDL-C) ratio is a contributing factor to CVD risk (OR 1.31, 95% CI 1.05–1.64). In addition, a nonlinear relationship was observed between the hs-CRP/HDL-C ratio and the occurrence of new CVD, stroke, or cardiac issues (Poverall <0.05, Pnonlinear <0.05). Moreover, noteworthy associations between the hs-CRP/HDL-C ratio and age were detected in the stratified analysis (P = 0.048), indicating that younger participants had more negative effects of a high hs-CRP/HDL-C ratio.

Conclusions
According to the present cohort study, a high hs-CRP/HDL-C ratio is a significant risk factor for CVD, new stroke, and heart problems. Early intervention in patients with increased hs-CRP/HDL-C ratios may further reduce the incidence of CVD, in addition to focusing on independent lipid markers or independent inflammatory markers.
A novel extracellular vesicles production system harnessing matrix homeostasis and macrophage reprogramming mitigates osteoarthritis
Authors: Wang Tianqi , Zhao Hongqi , Zhang Yi , Liu Yanshi , Liu Jialin , Chen Ge , Duan Ke , Li Zhong , Hui Hoi Po James , Yan Jiyuan 
Published: February 2024

AbstractOsteoarthritis (OA) is a degenerative disease that significantly impairs quality of life. There is a pressing need for innovative OA therapies. While small extracellular vesicles (sEVs) show promising therapeutic effects against OA, their limited yield restricts clinical translation. Here, we devised a novel production system for sEVs that enhances both their yield and therapeutic properties. By stimulating mesenchymal stem cells (MSCs) using electromagnetic field (EMF) combined with ultrasmall superparamagnetic iron oxide (USPIO) particles, we procured an augmented yield of EMF-USPIO-sEVs. These vesicles not only activate anabolic pathways but also inhibit catabolic activities, and crucially, they promote M2 macrophage polarization, aiding cartilage regeneration. In an OA mouse model triggered by anterior cruciate ligament transection surgery, EMF-USPIO-sEVs reduced OA severity, and augmented matrix synthesis. Moreover, they decelerated OA progression through the microRNA-99b/MFG-E8/NF-κB signaling axis. Consequently, EMF-USPIO-sEVs present a potential therapeutic option for OA, acting by modulating matrix homeostasis and macrophage polarization.
Cost-effectiveness and budget impact analysis of Daratumumab, Lenalidomide and dexamethasone for relapsed-refractory multiple myeloma
Authors: Goudarzi Zahra , Shahtaheri Rahil Sadat , Najafpour Zhila , Hamedifar Haleh , Ebrahimi Hamidreza 
Published: February 2024

Abstract
Background
The prominent efficacy in terms of increasing progression-free survival (PFS) of Daratumumab, Lenalidomide and dexamethasone (DRd) triplet therapy versus Carfilzomib, Lenalidomide and dexamethasone (KRd) was proven previously in relapsed-refractory multiple myeloma (RRMM). However, the cost effectiveness of DRd versus KRd is unknown.

Methods
We developed a Markov model by using an Iranian payer perspective and a 10-year time horizon to estimate the healthcare cost, Quality-adjusted life years (QALYs) and life years gain (LYG) for DRd and KRd triplet therapies. Clinical data were obtained from meta-analyses and randomized clinical trials (RCTs). One-way and probabilistic sensitivity analysis were performed to assess model uncertainty. Budget impact analysis of 5 years of treatment under the DRd triplet therapy was also analysed.

Results
DRd was estimated to be more effective compared to KRd, providing 0.28 QALY gain over the modelled horizon. DRd-treated patients incurred $264 in total additional costs. The incremental cost utility ratio (ICUR) and cost effectiveness ratio (ICER) were $956/QALY and $472/LYG respectively.
The budget impact analysis indicates that adding Daratumumab to Lenalidomide and dexamethasone regimen, in the first 5 years, will increase the healthcare system’s expenses by $6.170.582.

Conclusion
DRd triplet therapy compared to KRd is a cost-effective regimen for RRMM under Iran willingness-to-pay threshold.
3D-printed PCL framework assembling ECM-inspired multi-layer mineralized GO-Col-HAp microscaffold for in situ mandibular bone regeneration
Authors: Yang Yanqing , He Huan , Miao Fang , Yu Mingwei , Wu Xixi , Liu Yuanhang , Fu Jie , Chen Junwei , Ma Liya , Chen Xiangru , Peng Ximing , You Zhen , Zhou Chuchao 
Published: March 2024

Abstract
Background
In recent years, natural bone extracellular matrix (ECM)-inspired materials have found widespread application as scaffolds for bone tissue engineering. However, the challenge of creating scaffolds that mimic natural bone ECM’s mechanical strength and hierarchical nano-micro-macro structures remains. The purposes of this study were to introduce an innovative bone ECM-inspired scaffold that integrates a 3D-printed framework with hydroxyapatite (HAp) mineralized graphene oxide-collagen (GO-Col) microscaffolds and find its application in the repair of mandibular bone defects.

Methods
Initially, a 3D-printed polycaprolactone (PCL) scaffold was designed with cubic disks and square pores to mimic the macrostructure of bone ECM. Subsequently, we developed multi-layer mineralized GO-Col-HAp microscaffolds (MLM GCH) to simulate natural bone ECM's nano- and microstructural features. Systematic in vitro and in vivo experiments were introduced to evaluate the ECM-inspired structure of the scaffold and to explore its effect on cell proliferation and its ability to repair rat bone defects.

Results
The resultant MLM GCH/PCL composite scaffolds exhibited robust mechanical strength and ample assembly space. Moreover, the ECM-inspired MLM GCH microscaffolds displayed favorable attributes such as water absorption and retention and demonstrated promising cell adsorption, proliferation, and osteogenic differentiation in vitro. The MLM GCH/PCL composite scaffolds exhibited successful bone regeneration within mandibular bone defects in vivo.

Conclusions
This study presents a well-conceived strategy for fabricating ECM-inspired scaffolds by integrating 3D-printed PCL frameworks with multilayer mineralized porous microscaffolds, enhancing cell proliferation, osteogenic differentiation, and bone regeneration. This construction approach holds the potential for extension to various other biomaterial types.

Graphical Abstract
Gut microbiota dynamics and fecal SCFAs after colonoscopy: accelerating microbiome stabilization by Clostridium butyricum
Authors: Chen Zhenhui , Yu Lu , Liu Jiaxin , Kong Jingjing , Deng Xiaoshi , Guo Xiaotong , Shan Jiamin , Zhou Daixuan , Li Wendan , Lin Yangfan , Huang Wanwen , Zeng Weisen , Shi Xinlong , Bai Yang , Fan Hongying 
Published: March 2024

Abstract
Background
Colonoscopy is a classic diagnostic method with possible complications including abdominal pain and diarrhoea. In this study, gut microbiota dynamics and related metabolic products during and after colonoscopy were explored to accelerate gut microbiome balance through probiotics.

Methods
The gut microbiota and fecal short-chain fatty acids (SCFAs) were analyzed in four healthy subjects before and after colonoscopy, along with seven individuals supplemented with Clostridium butyricum. We employed 16S rRNA sequencing and GC–MS to investigate these changes. We also conducted bioinformatic analysis to explore the buk gene, encoding butyrate kinase, across C. butyricum strains from the human gut.

Results
The gut microbiota and fecal short-chain fatty acids (SCFAs) of four healthy subjects were recovered on the 7th day after colonoscopy. We found that Clostridium and other bacteria might have efficient butyric acid production through bioinformatic analysis of the buk and assessment of the transcriptional level of the buk. Supplementation of seven healthy subjects with Clostridium butyricum after colonoscopy resulted in a quicker recovery and stabilization of gut microbiota and fecal SCFAs on the third day.

Conclusion
We suggest that supplementation of Clostridium butyricum after colonoscopy should be considered in future routine clinical practice.
Traditional Chinese Medicine Shi-Bi-Man ameliorates psoriasis via inhibiting IL-23/Th17 axis and CXCL16-mediated endothelial activation
Authors: Zhang Chenyang , Cao Xinran , Zhao Lixin , Ni Zitong , Du Haojie , Qu Jiao , Zhu Jianxia , Sun Haiyan , Sun Yang , Ouyang Zijun 
Published: March 2024

Abstract
Background
Psoriasis is a chronic inflammatory genetic disease, mainly manifesting in the skin. Conventional therapies, such as glucocorticosteroids and corticosteroids, have adverse effects that limit drug use. Hence, it is imperative to identify a new therapeutic strategy that exhibits a favorable safety profile. Shi-Bi-Man (SBM) is a safe herbal supplement sourced from various natural plants, including ginseng, angelica sinensis, polygonum multiflorum, and aloe vera.

Purpose
We aimed to find a potential treatment for psoriasis and investigate the underlying mechanism through which SBM alleviates psoriatic-like skin inflammation in mice.

Methods
We investigated the effects of supplementing with SBM through intragastric administration or smear administration in a murine model of imiquimod-induced psoriasis. The changes in body weight and Psoriasis Area and Severity Index (PASI) score were recorded throughout the entire process. Additionally, we used hematoxylin–eosin staining to observe the skin structure and performed single-cell RNA sequencing to explore the underlying mechanism of SBM in influencing the psoriasis-like phenotype. Immunofluorescence was conducted to verify our findings. Furthermore, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was employed to investigate the impact of Tetrahydroxy stilbene glycoside (TSG) on the expression levels of IL23 in HaCaT cells.

Results
SBM remarkably alleviated the psoriasis-like phenotype by inhibiting IL-23/Th17 cell axis. Single-cell RNA sequencing analysis revealed a decrease in the expression of Il17 and Il23 in keratinocytes and T cells, concomitant with a reduction in the proportion of Th17 cells. Meanwhile, the activation of endothelial cells was inhibited, accompanied by a decrease in the expression of Cxcl16. In vitro, the addition of TSG to HaCaT cells resulted in significant suppression of IL23 expression stimulated by tumor necrosis factor-alpha (TNF-α).
Pragmatic skills in people with Williams syndrome: the perception of families
Authors: Sepúlveda Esther Moraleda , Resa Patricia López 
Published: March 2024

Abstract
Background
One of the most challenging linguistic areas in people with Williams Syndrome throughout their evolutionary stage is the development of pragmatic skills. The research conducted so far highlights specific problems concerning adaptation to the linguistic context and interlocutors, language comprehension, as well as other aspects interfering with verbal communication. However, until now, most scientific evidence has been based on personal assessments of this group. In a complementary manner, the goal of this study was to discover the level of pragmatic skills of people with Williams Syndrome from the point of view of the families. The sample consisted of 34 families belonging to the Williams Syndrome Association of Spain. The assessment instrument was the pragmatic awareness questionnaire, which includes 26 items related to different aspects that are part of the pragmatic area on a Likert-type scale.

Results
The results indicate that, families consider there to be a regular to low level in all the areas assessed. The strong points seem to lie in the paralinguistic aspects, while the weakest factors are those related to the understanding of figurative language.

Conclusions
Therefore, it is necessary to continue insisting on the importance of language intervention in this group throughout its development to improve its level of linguistic competence.
Impact of hyperoxia on the gut during critical illnesses
Authors: Dai Ninan , Gu Juan , Luo Yanhong , Tao Yuanfa , Chou Yuehting , He Ying , Qin Han , Chen Tao , Fu Xiaoyun , Chen Miao , Xing Zhouxiong 
Published: March 2024

AbstractMolecular oxygen is typically delivered to patients via oxygen inhalation or extracorporeal membrane oxygenation (ECMO), potentially resulting in systemic hyperoxia from liberal oxygen inhalation or localized hyperoxia in the lower body from peripheral venoarterial (VA) ECMO. Consequently, this exposes the gastrointestinal tract to excessive oxygen levels. Hyperoxia can trigger organ damage due to the overproduction of reactive oxygen species and is associated with increased mortality. The gut and gut microbiome play pivotal roles in critical illnesses and even small variations in oxygen levels can have a dramatic influence on the physiology and ecology of gut microbes. Here, we reviewed the emerging preclinical evidence which highlights how excessive inhaled oxygen can provoke diffuse villous damage, barrier dysfunction in the gut, and gut dysbiosis. The hallmark of this dysbiosis includes the expansion of oxygen-tolerant pathogens (e.g., Enterobacteriaceae) and the depletion of beneficial oxygen-intolerant microbes (e.g., Muribaculaceae). Furthermore, we discussed potential impact of oxygen on the gut in various underlying critical illnesses involving inspiratory oxygen and peripheral VA-ECMO. Currently, the available findings in this area are somewhat controversial, and a consensus has not yet to be reached. It appears that targeting near-physiological oxygenation levels may offer a means to avoid hyperoxia-induced gut injury and hypoxia-induced mesenteric ischemia. However, the optimal oxygenation target may vary depending on special clinical conditions, including acute hypoxia in adults and neonates, as well as particular patients undergoing gastrointestinal surgery or VA-ECMO support. Last, we outlined the current challenges and the need for future studies in this area. Insights into this vital ongoing research can assist clinicians in optimizing oxygenation for critically ill patients.
PHF5A promotes esophageal squamous cell carcinoma progression via stabilizing VEGFA
Authors: Chang Zhiwei , Jia Yongxu , Gao Ming , Song Lijie , Zhang Weijie , Zhao Ruihua , Yu Dandan , Liu Xiaolei , Li Jing , Qin Yanru 
Published: March 2024

Abstract
Background
Esophageal squamous cell carcinoma (ESCC) is the main subtype of esophageal cancer. Current therapeutic effect is far from satisfaction. Hence, identifying susceptible genes and potential targets is necessary for therapy of ESCC patients.

Methods
Plant homeodomain (PHD)-finger domain protein 5 A (PHF5A) expression in ESCC tissues was examined by immunohistochemistry. RNA interference was used for in vitro loss-of-function experiments. In vivo assay was performed using xenograft mice model by subcutaneous injection. Besides, microarray assay and co-immunoprecipitation experiments were used to study the potential downstream molecules of PHF5A in ESCC. The molecular mechanism between PHF5A and vascular endothelial growth factor A (VEGFA) was explored by a series of ubiquitination related assays.

Results
We found that PHF5A was highly expressed in ESCC tissues compared to normal tissues and that was correlated with poor prognosis of ESCC. Loss-of-function experiments revealed that PHF5A silence remarkably inhibited cell proliferation, migration, and induced apoptosis as well as cell cycle arrest. Consistently, in vivo assay demonstrated that PHF5A deficiency was able to attenuate tumor growth. Furthermore, molecular studies showed that PHF5A silencing promoted VEGFA ubiquitination by interacting with MDM2, thereby regulating VEGFA protein expression. Subsequently, in rescue experiments, our data suggested that ESCC cell viability and migration promoted by PHF5A were dependent on intact VEGFA. Finally, PI3K/AKT signaling rescue was able to alleviate shPHF5A-mediated cell apoptosis and cell cycle arrest.

Conclusion
PHF5A is a tumor promoter in ESCC, which is dependent on VEGFA and PI3K/AKT signaling. PHF5A might serve as a potential therapeutic target for ESCC treatment.
Study protocol: a core outcome set for perioperative exercise clinical effectiveness trials for lung cancer patients
Authors: Zhou Wanjun , Zhang Yawen , Wang Zhiwei , Zhang Liang , Zhang Xinqiong 
Published: March 2024

Abstract
Background
Outcome assessment in perioperative exercise trials for lung cancer is heterogeneous, often omitting those that are important and patient-relevant. This heterogeneity hinders the synthesis of evidence. To address this issue, a core outcome set, an agreed-upon standardized set of outcomes to be measured and reported, is required to reduce heterogeneity among outcome measurements. This study protocol describes the methodology, aiming to develop a core outcome set for perioperative exercise intervention trials for lung cancer in clinical practice.

Methods
The project will follow the standard methodology recommended by the Core Outcome Measures in Effectiveness Trials (COMET) initiative, which is divided into four steps. Stage I: Conducting a scoping review of outcomes reported in clinical trials and protocols to develop a list of potential outcome domains. Stage II: Conducting semi-structured interviews to obtain important outcomes for patients. Stage III: Choosing the most important outcomes by conducting two rounds of the Delphi exercise. Stage IV: Achieving a consensus in a face-to-face meeting to discuss the final core outcome set.

Discussion
This is the first project identified for the core outcome set of perioperative exercise trials in lung cancer, which will enhance the quality, comparability, and usability of future trials and positively impact perioperative exercise and the care of patients with lung cancer.

Trials registration
Core Outcome Measurement in Effectiveness Trials (COMET) Initiative database registration: https://www.comet-initiative.org/Studies/Details/2091
Farmers’ futures: an application of the Delphi method in the context of Finnish agriculture
Authors: Sorvali Jaana , Varho Vilja , Rikkonen Pasi , Kaseva Janne , Peltonen-Sainio Pirjo 
Published: March 2024

AbstractIn Finland, agriculture is practiced in variable growing conditions that are further challenged by climate change and under external pressure caused by international competition, changing consumer preferences and demands, and the renewal of the European Union Common Agriculture Policy and Paris Agreement climate targets. Futures studies in agriculture have focused on scenario building with expert panels, though usually without farmers’ involvement. This study focuses on farmers’ views of shaping the future of Finnish agriculture. It builds on the disaggregative Delphi method and combines interviews and a representative survey of Finnish farmers. The study is based on a bottom-up process in which a farmer panel of 20 farms defined their views of the future in a semi-structured thematic interview. The views were turned into statements in a structured survey sent to the second panel, which comprised all Finnish farmers who had received agricultural subsidies in 2016, with 4401 respondents. The results were analyzed using quantitative factor analysis, which produced five future images for Finnish agriculture. The images were shown to the original farmer panel for reflection. They considered the probability of each future image and their own role in it. Technology solves as a future image was most favored by farmers, followed by Ecological and specializing small-scale production image. Business-as-usual was the least likely future images according to the interviewed farmers. This paper describes the process and discusses both methodological benefits and pitfalls, as well as farmers’ future views of the forthcoming decades.
Chinese English language learners’ vocabulary retention: Investigating the effectiveness of neuro/metacognitive and socio-cultural strategies
Authors: Hu Wei , Luo Yipeng 
Published: March 2024

Abstract
Background
The acquisition of a rich vocabulary is foundational to language proficiency. In the pedagogical pursuit of effective vocabulary teaching, educators explore diverse methodologies. Researchers investigated the impact of different neurocognitive, metacognitive, and socio-cultural strategies on enhancing vocabulary learning, particularly among Chinese English Language Learners.

Objectives
The study aims to determine the effectiveness of techniques derived from these theories compared to traditional teaching methods in enhancing vocabulary recall and recognition among English language learners.

Methodology
A quasi-experimental pre-test/post-test design was employed for the experimental and control groups, comprising 90 Chinese EFL learners selected from educational institutions in 2022–2023. The experimental group (n = 45) received instruction involving visual imagery, multisensory rotation, circle rotation, and mind mapping over eight sessions, while the control group (n = 45) received traditional teaching methods.

Findings
Statistical analysis, utilizing covariance and analysis of variance with SPSS software version 22, revealed significant improvements in recall and vocabulary recognition within and between the experimental and control groups.

Conclusions
The results indicate that incorporating techniques based on Neuro-Cognitive, Multimedia, Socio-Cultural, and Metacognitive theories positively influences vocabulary recall and recognition. This suggests the efficacy of these innovative methods in enhancing English language learning, highlighting their potential for broader integration into EFL instruction.