bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effectiveness of multidisciplinary interventions based on health belief model on musculoskeletal pain in the elderly living in nursing homes: a study protocol for a randomized controlled trial
Authors: Habibi Sogand , Tavafian Sedigheh Sadat , Maghbouli Reza , Montazeri Ali 
Published: June 2024

Abstract
Background
Due to the burden of musculoskeletal diseases in the elderly and the multifactorial nature of such conditions, controlling the pain caused by these disorders requires multidisciplinary approach. This approach requires the participation of the elderly in applying effective prevention measures. This study aims to design a multidisciplinary educational intervention based on health belief model (HBM) for elderly residents of nursing homes.

Methods
This is a parallel randomized clinical trial among elderly people aged 60 years and over living in a nursing home who suffer from musculoskeletal pain. Eligible participants will be divided into two groups including the intervention group who will receive a multidisciplinary intervention (vitamin D consumption, psycho-social stress management, and physiotherapy) and the control group who will receive usual care. Data collection instruments will include demographic data, the Depression, Anxiety, and Stress Scale (DASS), the visual analogue scale (VAS), and a self-designed questionnaire containing the HBM constructs. The interventions will be carried out by the educational team (general practitioner, psychologist, physiotherapist, and health education specialist). Interventions include changing the wrong beliefs of the elderly, taking 800 units of vitamin D daily, daily walking exercise by the elderly for at least 30 min and maintaining proper body posture during daily activities, muscle relaxation, relaxation techniques, regular exercise, examining their diet and eliminating stimulants (such as smoking and coffee), regular visits with friends and family, and deep breathing techniques. All questionnaires will be completed by the elderly before, after, 3, and 6 months after the intervention.

Discussion
The present study will evaluate the effect of an educational intervention based on a multifaceted pain control approach for elderly people who reside in nursing homes in order to reduce musculoskeletal pain in the elderly living in nursing homes. One of the features of this study is its focus on improving the health of elderly residents in nursing homes. Given the increase in the elderly population worldwide, the findings from the current trial might benefit elderly populations.

Trial registration
IRCT20220904055881N1. Registered on 11 February 2023.
Evolution of glial cells: a non-bilaterian perspective
Authors: Sheloukhova Larisa , Watanabe Hiroshi 
Published: June 2024

AbstractNervous systems of bilaterian animals generally consist of two cell types: neurons and glial cells. Despite accumulating data about the many important functions glial cells serve in bilaterian nervous systems, the evolutionary origin of this abundant cell type remains unclear. Current hypotheses regarding glial evolution are mostly based on data from model bilaterians. Non-bilaterian animals have been largely overlooked in glial studies and have been subjected only to morphological analysis. Here, we provide a comprehensive overview of conservation of the bilateral gliogenic genetic repertoire of non-bilaterian phyla (Cnidaria, Placozoa, Ctenophora, and Porifera). We overview molecular and functional features of bilaterian glial cell types and discuss their possible evolutionary history. We then examine which glial features are present in non-bilaterians. Of these, cnidarians show the highest degree of gliogenic program conservation and may therefore be crucial to answer questions about glial evolution.
Comprehensive meta-analysis of severe fever with thrombocytopenia syndrome virus infections in humans, vertebrate hosts and questing ticks
Authors: Xu Ao-Long , Xue Han , Li Yi , Wang Xu , Zheng Jin-Xin , Shi Fu-Yan , Cui Qing-Xia , Lu Yan , Cun De-Jiao , Li Lan-Hua 
Published: June 2024

Abstract
Background
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne zoonosis caused by the SFTS virus (SFTSV). Understanding the prevalence of SFTSV RNA in humans, vertebrate hosts and ticks is crucial for SFTS control.

Methods
A systematic review and meta-analysis were conducted to determine the prevalence of SFTSV RNA in humans, vertebrate hosts and questing ticks. Nine electronic databases were searched for relevant publications, and data on SFTSV RNA prevalence were extracted. Pooled prevalence was estimated using a random effects model. Subgroup analysis and multivariable meta-regression were performed to investigate sources of heterogeneity.

Results
The pooled prevalence of SFTSV RNA in humans was 5.59% (95% confidence interval [CI] 2.78–9.15%) in those in close contact (close contacts) with infected individuals (infected cases) and 0.05% (95% CI 0.00–0.65%) in healthy individuals in endemic areas. The SFTSV infection rates in artiodactyls (5.60%; 95% CI 2.95–8.96%) and carnivores (6.34%; 95% CI 3.27–10.23%) were higher than those in rodents (0.45%; 95% CI 0.00–1.50%). Other animals, such as rabbits, hedgehogs and birds, also played significant roles in SFTSV transmission. The genus Haemaphysalis was the primary transmission vector, with members of Ixodes, Dermacentor, and Amblyomma also identified as potential vectors. The highest pooled prevalence was observed in adult ticks (1.03%; 95% CI 0.35–1.96%), followed by nymphs (0.66%; 95% CI 0.11–1.50%) and larvae (0.01%; 95% CI 0.00–0.46%). The pooled prevalence in ticks collected from endemic areas (1.86%; 95% CI 0.86–3.14%) was higher than that in ticks collected in other regions (0.41%; 95% CI 0.12–0.81%).

Conclusions
Latent SFTSV infections are present in healthy individuals residing in endemic areas, and close contacts with SFTS cases are at a significantly higher risk of infection. The type of animal is linked to infection rates in vertebrate hosts, while infection rates in ticks are associated with the developmental stage. Further research is needed to investigate the impact of various environmental factors on SFTSV prevalence in vertebrate hosts and ticks.

Graphical Abstract
Quantitative US fat fraction for noninvasive assessment of hepatic steatosis in suspected metabolic-associated fatty liver disease
Authors: Yin Haohao , Fan Yunling , Yu Jifeng , Xiong Bing , Zhou Boyang , Sun Yikang , Wang Lifan , Zhu Yuli , Xu Huixiong 
Published: June 2024

Abstract
Objectives
To evaluate the agreement between quantitative ultrasound system fat fraction (USFF) and proton magnetic resonance spectroscopy (1H-MRS) and the diagnostic value of USFF in assessing metabolic-associated fatty liver disease (MAFLD).

Methods
The participants with or suspected of MAFLD were prospectively recruited and underwent 1H-MRS, USFF, and controlled attenuation parameter (CAP) measurements. The correlation between USFF and 1H-MRS was assessed using Pearson correlation coefficients. The USFF diagnostic performance for different grades of steatosis was evaluated using receiver operating characteristic curve analysis (ROC) and was compared with CAP, visual hepatic steatosis grade (VHSG).

Results
A total of 113 participants (mean age 44.79 years ± 13.56 (SD); 71 males) were enrolled, of whom 98 (86.73%) had hepatic steatosis (1H-MRS ≥ 5.56%). USFF showed a good correlation (Pearson r = 0.76) with 1H-MRS and showed a linear relationship, which was superior to the correlation between CAP and 1H-MRS (Pearson r = 0.61). The USFF provided high diagnostic performance for different grades of hepatic steatosis, with ROC from 0.84 to 0.98, and the diagnostic performance was better than that of the CAP and the VHSG. The cut-off values of the USFF were different for various grades of steatosis, and the cut-off values for S1, S2, and S3 were 12.01%, 19.98%, and 22.22%, respectively.

Conclusions
There was a good correlation between USFF and 1H-MRS. Meanwhile, USFF had good diagnostic performance for hepatic steatosis and was superior to CAP and VHSG. USFF represents a superior method for noninvasive quantitative assessment of MAFLD.

Critical relevance statement
Quantitative ultrasound system fat fraction (USFF) accurately assesses liver fat content and has a good correlation with magnetic resonance spectroscopy (1H-MRS) for the assessment of metabolic-associated fatty liver disease (MAFLD), as well as for providing an accurate quantitative assessment of hepatic steatosis.

Key Points

Current diagnostic and monitoring modalities for metabolic-associated fatty liver disease have limitations.

USFF correlated well with 1H-MRS and was superior to the CAP.

USFF has good diagnostic performance for steatosis, superior to CAP and VHSG.

Graphical Abstract
UBQLN1 links proteostasis and mitochondria function to telomere maintenance in human embryonic stem cells
Authors: Zhao Shuang , Li Jie , Duan Songqi , Liu Chang , Wang Hua , Lu Jiangtao , Zhao Nannan , Sheng Xiaoyan , wu Yiwei , Li Yanjun , Sun Baofa , Liu Lin 
Published: June 2024

Abstract
Background
Telomeres consist of repetitive DNA sequences at the chromosome ends to protect chromosomal stability, and primarily maintained by telomerase or occasionally by alternative telomere lengthening of telomeres (ALT) through recombination-based mechanisms. Additional mechanisms that may regulate telomere maintenance remain to be explored. Simultaneous measurement of telomere length and transcriptome in the same human embryonic stem cell (hESC) revealed that mRNA expression levels of UBQLN1 exhibit linear relationship with telomere length.

Methods
In this study, we first generated UBQLN1-deficient hESCs and compared with the wild-type (WT) hESCs the telomere length and molecular change at RNA and protein level by RNA-seq and proteomics. Then we identified the potential interacting proteins with UBQLN1 using immunoprecipitation-mass spectrometry (IP-MS). Furthermore, the potential mechanisms underlying the shortened telomeres in UBQLN1-deficient hESCs were analyzed.

Results
We show that Ubiquilin1 (UBQLN1) is critical for telomere maintenance in human embryonic stem cells (hESCs) via promoting mitochondrial function. UBQLN1 deficiency leads to oxidative stress, loss of proteostasis, mitochondria dysfunction, DNA damage, and telomere attrition. Reducing oxidative damage and promoting mitochondria function by culture under hypoxia condition or supplementation with N-acetylcysteine partly attenuate the telomere attrition induced by UBQLN1 deficiency. Moreover, UBQLN1 deficiency/telomere shortening downregulates genes for neuro-ectoderm lineage differentiation.

Conclusions
Altogether, UBQLN1 functions to scavenge ubiquitinated proteins, preventing their overloading mitochondria and elevated mitophagy. UBQLN1 maintains mitochondria and telomeres by regulating proteostasis and plays critical role in neuro-ectoderm differentiation.
Osteochondral organoids: current advances, applications, and upcoming challenges
Authors: Faeed Maryam , Ghiasvand Mahsa , Fareghzadeh Bahar , Taghiyar Leila 
Published: June 2024

AbstractIn the realm of studying joint-related diseases, there is a continuous quest for more accurate and representative models. Recently, regenerative medicine and tissue engineering have seen a growing interest in utilizing organoids as powerful tools for studying complex biological systems in vitro. Organoids, three-dimensional structures replicating the architecture and function of organs, provide a unique platform for investigating disease mechanisms, drug responses, and tissue regeneration. The surge in organoid research is fueled by the need for physiologically relevant models to bridge the gap between traditional cell cultures and in vivo studies. Osteochondral organoids have emerged as a promising avenue in this pursuit, offering a better platform to mimic the intricate biological interactions within bone and cartilage. This review explores the significance of osteochondral organoids and the need for their development in advancing our understanding and treatment of bone and cartilage-related diseases. It summarizes osteochondral organoids’ insights and research progress, focusing on their composition, materials, cell sources, and cultivation methods, as well as the concept of organoids on chips and application scenarios. Additionally, we address the limitations and challenges these organoids face, emphasizing the necessity for further research to overcome these obstacles and facilitate orthopedic regeneration.
Development of an animal health testing tool to reduce antimicrobial use on farms: perceptions, implications, and needs of Irish dairy farmers and farm veterinarians
Authors: McGrath Karen , Regan Áine , Kennedy Emer , Russell Tomás 
Published: June 2024

Abstract
Background
The threat of antimicrobial resistance is triggering the need for behavioural change towards antimicrobial use on Irish farms. Newly introduced veterinary medicine regulations are mandating the restricted and more prudent use of antimicrobials in the animal health sector. The need to reduce antimicrobials has placed a greater emphasis on the importance of animal health testing, however, issues with current testing practices are affecting diagnosis and subsequent drug usage. There is potential for digital technologies to address these issues and reduce antimicrobial use on farms, however, for these tools to be successful, they would need to be developed in collaboration with future end users.

Results
Using qualitative approaches (focus groups), this study engages with dairy farmers and farm veterinary practitioners to detail current challenges with animal health diagnosis and to explore the initial development of a rapid, on-farm animal health testing tool to address these challenges. Issues with timing and testing, the role of knowledge and experience, and veterinarian availability all affect the ability of farmers and veterinarians to diagnose animal health issues on farm. These issues are having negative implications including the increased and unnecessary use of antimicrobials. An on-farm testing tool would help mitigate these effects by allowing veterinarians to achieve rapid diagnosis, facilitating the timely and targeted treatment of animal illnesses, helping to reduce overall antimicrobial use on farms. However, engagement with end users has highlighted that if a tool like this is not developed correctly, it could have unintended negative consequences such as misdiagnosis, increased antimicrobial use, challenges to farmer-veterinarian relationships, and data misuse. This study outlines initial end user needs and requirements for a testing tool but suggests that in order to successfully design and develop this tool, co-design approaches such as Design Thinking should be applied; to mitigate future negative impacts, and to ensure a testing tool like this is designed specifically to address Irish dairy farmers and farm veterinarians’ values and needs, ensuring responsible and successful uptake and use.

Conclusions
Digital tools can be effective in reducing antimicrobial use on farms, however, to be successful, these tools should be designed in a user centred way.
Proneness to false memory generation predicts pseudoscientific belief endorsement
Authors: Martínez Naroa , Barberia Itxaso , Rodríguez-Ferreiro Javier 
Published: June 2024

AbstractAmong cognitive factors that can influence the endorsement of pseudoscientific beliefs, our study focuses on proneness to false memory generation. In this preregistered study, we presented 170 fluent English speakers residing in the USA with a misinformation task aimed at generating false memories. In this task, they first completed an event encoding stage, in which two events were narrated through sequentially presented pictures. One day later, they read a series of sentences relating the same events but which included several inaccurate descriptions aimed at producing a misinformation effect. Finally, we measured the influence of the misinformation manipulation over false memory generation. After completing the misinformation task, participants responded to a questionnaire measuring pseudoscientific beliefs. Our results showed a positive correlation between pseudoscience endorsement and false memory rates, which indicates that the latter might be a key factor influencing susceptibility to pseudoscience. To our knowledge, this is the first study showing a link between the tendency to believe in pseudoscience and variability regarding proneness to develop false memories. Practical implications for the design of new interventions to effectively reduce pseudoscientific beliefs and their negative impact on our society are discussed.
Microbiome signature, immune landscape and global methylation in early onset colorectal cancer.
Authors: Jin Ning , Hoyd Rebecca , Yilmaz Ayse Selen , Zhang Shiqi , Liu YunZhou , Grencewicz Dennis , Jagjit Singh Malvenderjit , Zhu Jiangjiang , Liu Bei , Mo Xiaokui , Spakowicz Daniel ,   exORIEN Consortium
Published: June 2024

3580 Background: The incidence of colorectal cancer (CRC) in young adults (age at diagnosis < 50 years old) has been rapidly increasing. Approximately 20% of early-onset (EO) CRC cases are due to germline gene mutations. However, the etiology of sporadic EO CRC remains poorly understood. Research suggests that environmental factors such as Western diet may be associated with increased incidence of sporadic EO CRC. The gut microbiota decomposes and ferments dietary fibers to produce microbial metabolites, which play important roles in maintaining the intestinal epithelium integrity. A high-fat, low-fiber diet has been associated with intestinal dysbiosis, which disrupts intestinal bacterial homeostasis. An increased inflammation state characterizes dysbiosis and may promote an immunosuppressive tumor microenvironment (TME) and suppress antitumor immune surveillance. In addition, epigenetic modifications are influenced by environmental changes and therefore epigenetics may bridge the knowledge gap in understanding the development of sporadic EOCRC. Methods: We obtained RNA sequencing data from the Cancer Genome Atlas (TCGA) and the Oncology Research Information Exchange Network (ORIEN) from the Ohio State University biospecimen services to characterize intra-tumor microbiota composition, tumor-infiltrating lymphocytes (TILs) and differential pathways in EO CRC. We used Infinium HM450 methylation array in The Cancer Genome Atlas (TCGA) and performed genome-wide analyses using reduced representation bisulfite sequencing (RRBS) method to identify differentially methylated regions (DMRs) in EO CRC. Results: Gene expression analysis is consistent with Fusobacterium promoting inflammation in EO CRC. Intra-tumor microbes are positively correlated with M2 macrophages. Compared to late onset (LO) CRC, EO CRC patients have unique gene signatures of phagosome formation, S100 family signaling pathway and CREB signaling in neurons by using ingenuity pathway analysis (IPA). In addition, we found that methylation ages predicted by epigenetic clocks in EO CRC patients were 15 years older on average than their chronological ages, whereas methylation ages in late onset (LO) CRC patients were comparable with chronological ages. The enriched pathways based on DMRs associated with EO CRC have significant overlap with canonical pathways based on differentially expressed genes (DEGs), including CREB signaling in neurons and S100 family signaling pathways. Conclusions: These data suggest that pathogenic microbes may induce inflammation, which leads to accelerated aging in EO CRC.
Camrelizumab plus rivoceranib vs sorafenib as first-line therapy for unresectable hepatocellular carcinoma (uHCC): Final overall survival analysis of the phase 3 CARES-310 study.
Authors: Vogel Arndt , Chan Stephen Lam , Ren Zhenggang , Bai Yuxian , Gu Shanzhi , Lin Xiaoyan , Chen Zhendong , Jia Weidong , Jin Yongdong , Guo Yabing , Hu Xiaohua , Sultanbaev Alexander Valerievich , Pazgan-Simon Monika , Pisetska Margaryta , Nip Tsz Keung , Zhang Haisong , Du Jinghua , Cheng Ann-Lii , Kaseb Ahmed Omar , Qin Shukui ,   CARES-310 Study Group
Published: June 2024

4110 Background: The phase 3 CARES-310 trial is the first to demonstrate significant progression-free survival (PFS) and overall survival (OS) benefits with immunotherapy plus an anti-angiogenic tyrosine kinase inhibitor (TKI) over standard TKI as first-line treatment for uHCC. In the primary analysis of PFS (data cut-off [DCO], May. 10, 2021) and interim analysis of OS (DCO, Feb. 8, 2022), significant improvements were observed with camrelizumab (C; anti-PD-1 antibody) + rivoceranib (R; VEGFR2-TKI) vs. sorafenib (S). Here, we report updated data at the final analysis (FA), after an additional follow-up of ~16 mo. Methods: In this international, randomized, open-label, phase 3 trial, 543 patients with uHCC who had not previously received systemic treatment were randomized 1:1 to receive either C (200 mg, iv, q2w) + R (250 mg, po, qd) or S (400 mg, po, bid). As of Jun.14, 2023, 351 (65%) deaths occurred, and a protocol-specified FA was performed. Results: 272 patients were allocated to C+R and 271 to S. At DCO of FA, median follow-up was 22.1 mo in C+R group and 14.9 mo in S group. After end of study treatment, 36% of patients in C+R group and 42% in S group received subsequent targeted therapy; 17% and 36% received immunotherapy, respectively. Median OS was significantly prolonged with C+R vs . S (23.8 mo [95% CI 20.6-27.2] vs. 15.2 mo [95% CI 13.2-18.5]; hazard ratio (HR) 0.64 [95% CI 0.52-0.79]; 1-sided p <0.0001). OS rate with C+R vs.S was 49.0% vs. 36.2% at 24 mo, and 37.7% vs. 24.8% at 36 mo. OS benefits with C+R was generally consistent across subgroups, regardless of geographical region, race, and aetiology. Benefits in PFS, objective response rate (ORR) and duration of response (DoR) with C+R were also sustained after prolonged follow-up (Table). Safety data aligned with the interim OS analysis, with no new signals noted. Conclusions: At the protocol-specified FA, C+R continued to show clinically meaningful survival improvement compared with S, with manageable safety. The extended follow-up further confirmed the favorable benefit-to-risk profile of C+R, supporting it as a new first-line treatment option for uHCC. Clinical trial information: NCT03764293 . [Table: see text]