bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between atherogenic index of plasma and prehypertension or hypertension among normoglycemia subjects in a Japan population: a cross-sectional study
Authors: Tan Mingjuan , Zhang Yongliang , Jin Ling , Wang Youli , Cui Weiwei , Nasifu Lubanga , He Bangshun 
Published: June 2023

Abstract
Objective
The atherogenic index of plasma (AIP), consisting of triglycerides and high-density lipoprotein cholesterol, is applied to estimate the cardiovascular disease risk. The evidence regarding the association between AIP and prehypertension or hypertension remains inconclusive. This study was conducted to investigate the association of AIP and prehypertension or hypertension in normoglycemic subjects in Japan.

Methods
In the present cross-sectional study, 15,453 normoglycemic participants aged 18 years or older in Gifu, Japan, were evaluated. The selected participants were separated into four groups in the light of AIP quartiles, ranging from the lowest quartile (Q1) to the highest quartile (Q4). And the association between AIP and prehypertension or hypertension was explored with multivariate logistic regression by gradually adjusting model.

Results
Among the 15,453 participants, aged of 43.7 ± 8.9 years, and of whom 45.5% were females, the prevalence rates of prehypertension or hypertension were 27.68% (4,278) and 6.23% (962) respectively. In multivariate logistic regression analyses, participants in the highest AIP quartile had an increase risk in prehypertension and hypertension, compared with participants the lowest one, the odds ratios (OR) were 1.15 (95%CI: 1.00–1.13, P = 0.045) for prehypertension and 1.54 (95%CI:1.16–2.04, P = 0.003) for hypertension after adjusting confounders. In subgroup analyses, the high risk of hypertension was also observed for female participants in the highest AIP quartile (Q4) (OR = 2.19, 95%CI: 1.37–3.49, P = 0.001), especially between the ages of 40 and 60 years (OR = 2.20, 95%CI: 1.24–3.88, P = 0.007).

Conclusions
Higher AIP is significantly and positively associated with the risk of prehypertension or hypertension in normoglycemic subjects in Gifu, Japan, which was more pronounced in the female population, especially between the years of 40 and 60.
Association between fatty liver index and blood coagulation markers: a population-based study
Authors: Iglesias Morcillo Maximilian , Freuer Dennis , Peters Anette , Heier Margit , Teupser Daniel , Meisinger Christine , Linseisen Jakob 
Published: June 2023

Abstract
Background
Population-based studies investigating the association between blood coagulation markers and non-alcoholic fatty liver disease (NAFLD) are rare. Thus, we aimed to investigate the relationship between the Fatty Liver Index (FLI) as a measure of hepatic steatosis and plasma concentrations of antithrombin III, D-dimer, fibrinogen D, protein C, protein S, factor VIII, activated partial thromboplastin time (aPTT), quick value and international thromboplastin time (INR) in the general population.

Methods
After the exclusion of participants with anticoagulative treatment, 776 participants (420 women and 356 men, aged 54–74 years) of the population-based KORA Fit study with analytic data on hemostatic factors were included in the present analysis. Linear regression models were used to explore the associations between FLI and hemostatic markers, adjusted for sex, age, alcohol consumption, education, smoking status, and physical activity. In a second model, additional adjustments were made for the history of stroke, hypertension, myocardial infarction, serum non-HDL cholesterol levels, and diabetes status. In addition, analyses were stratified by diabetes status.

Results
In the multivariable models (with or without health conditions), significantly positive associations with FLI were obtained for plasma concentrations of D-dimers, factor VIII, fibrinogen D, protein C, protein S, and quick value, while INR and antithrombin III were inversely associated. These associations were weaker in pre-diabetic subjects and largely disappeared in diabetic patients.

Conclusion
In this population-based study, an increased FLI is clearly related to changes in the blood coagulation system, possibly increasing the risk of thrombotic events. Due to a generally more pro-coagulative profile of hemostatic factors, such an association is not visible in diabetic subjects.
Health-related quality of life in children with developmental coordination disorder: a systematic review
Authors: Weber Meyene Duque , Draghi Tatiane Targino Gomes , Rohr Liz Araújo , Cavalcante Neto Jorge Lopes , Tudella Eloisa 
Published: June 2023

AbstractThe aims of this study were (1) to synthesize evidence of the general health-related quality of life in children with DCD compared to their typically developing peers, and (2) to verify which domains of HRQOL are more compromised in children with DCD. A systematic search was carried out to identify cross-sectional studies that evaluated self-perception and/or the parent's perception of the HRQOL in children with and without DCD as an outcome. The methodological quality of the studies was assessed, and the effect size calculated. Initial searches in the databases identified 1092 articles. Of these, six were included. Most of the articles (5/6) included noted that children with DCD show a significantly lower HRQOL than their typically developing peers. Regarding the most compromised HRQOL domains, the results are heterogeneous. Most studies (3/6) had moderate methodological quality, and two studies were classified as high methodological quality. Effect sizes ranged from low to high.
Circulating LPS from gut microbiota leverages stenosis-induced deep vein thrombosis in mice
Authors: Liu Cheng , Zhou Ying , Gao Huihui , Zhang Zeping , Zhou Yu , Xu Zifeng , Zhang Chenhong , Xu Zhen , Zheng Huajun , Ma Yan-Qing 
Published: June 2023

Abstract
Objective and design
An accumulating body of evidence has shown that gut microbiota is involved in regulating inflammation; however, it remains undetermined if and how gut microbiota plays an important role in modulating deep venous thrombosis (DVT), which is an inflammation-involved thrombotic event.

Subjects
Mice under different treatments were used in this study.

Methods and treatment
We induced stenosis DVT in mice by partially ligating the inferior vena cava. Mice were treated with antibiotics, prebiotics, probiotics, or inflammatory reagents to modulate inflammatory states, and their effects on the levels of circulating LPS and DVT were examined.

Results
Antibiotic-treated mice or germ-free mice exhibited compromised DVT. Treatment of mice with either prebiotics or probiotics effectively suppressed DVT, which was accompanied with the downregulation of circulating LPS. Restoration of circulating LPS in these mice with a low dose of LPS was able to restore DVT. LPS-induced DVT was blocked by a TLR4 antagonist. By performing proteomic analysis, we identified TSP1 as one of the downstream effectors of circulating LPS in DVT.

Conclusion
These results suggest that gut microbiota may play a nonnegligible role in modulating DVT by leveraging the levels of LPS in circulation, thus shedding light on the development of gut microbiota-based strategies for preventing and treating DVT.
Gauging innovation and health impact from biomedical research: survey results and interviews with recipients of EU-funding in the fields of Alzheimer’s disease, breast cancer and prostate cancer
Authors: Pistollato Francesca , Campia Ivana , Daskalopoulos Evangelos P. , Bernasconi Camilla , Desaintes Christian , Di Virgilio Sergio , Kyriakopoulou Christina , Whelan Maurice , Deceuninck Pierre 
Published: June 2023

AbstractBiomedical research on Alzheimer’s disease (AD), breast cancer (BC) and prostate cancer (PC) has globally improved our understanding of the etiopathological mechanisms underlying the onset of these diseases, often with the goal to identify associated genetic and environmental risk factors and develop new medicines. However, the prevalence of these diseases and failure rate in drug development remain high. Being able to retrospectively monitor the major scientific breakthroughs and impact of such investment endeavors is important to re-address funding strategies if and when needed. The EU has supported research into those diseases via its successive framework programmes for research, technological development and innovation. The European Commission (EC) has already undertaken several activities to monitor research impact. As an additional contribution, the EC Joint Research Centre (JRC) launched in 2020 a survey addressed to former and current participants of EU-funded research projects in the fields of AD, BC and PC, with the aim to understand how EU-funded research has contributed to scientific innovation and societal impact, and how the selection of the experimental models may have underpinned the advances made. Further feedback was also gathered through in-depth interviews with some selected survey participants representative of the diverse pre-clinical models used in the EU-funded projects. A comprehensive analysis of survey replies, complemented with the information derived from the interviews, has recently been published in a Synopsis report. Here we discuss the main findings of this analysis and propose a set of priority actions that could be considered to help improving the translation of scientific innovation of biomedical research into societal impact.
A comprehensive insight into the correlation between ncRNAs and the Wnt/β-catenin signalling pathway in gastric cancer pathogenesis
Authors: Akhavanfar Roozbeh , Shafagh Seyyed-Ghavam , Mohammadpour Behnood , Farahmand Yalda , Lotfalizadeh Mohammad Hassan , Kookli Keihan , Adili Ali , Siri Goli , Eshagh Hosseini Seyed Mahmoud 
Published: June 2023

AbstractDuring the past decades, gastric cancer (GC) has emerged as one of the most frequent malignancies with a growing rate of prevalence around the world. Despite considerable advances in therapeutic methods, the prognosis and management of patients with gastric cancer (GC) continue to be poor. As one of the candidate molecular targets in the treatment of many types of cancer, the Wnt/β-catenin pathway includes a family of proteins that have important functions in adult tissue homeostasis and embryonic development. The aberrant regulation of Wnt/β-catenin signaling is strongly correlated with the initiation and development of numerous cancers, including GC. Therefore, Wnt/β-catenin signaling has been identified as one of the main targets for extending therapeutic approaches for GC patients. Non-coding RNAs (ncRNAs), including microRNAs and long ncRNAs, are important components of epigenetic mechanisms in gene regulation. They play vital roles in various molecular and cellular processes and regulate many signaling pathways, such as Wnt/β-catenin pathways. Insights into these regulatory molecules involved in GC development may lead to the identification of potential targets for overcoming the limitations of current therapeutic approaches. Consequently, this review aimed to provide a comprehensive overview of ncRNAs interactions involved in Wnt/β-catenin pathway function in GC with diagnostic and therapeutic perspectives.
Implementation of elementary school physical education quantity and quality law through school district audit, feedback, and coaching
Authors: Thompson Hannah R. , Madsen Kristine A. , Zamek Maya , McKenzie Thomas L. , Dzewaltowski David A. 
Published: June 2023

Abstract
Background
To address low state physical education (PE) quantity and quality law implementation in elementary schools, the New York City Department of Education (NYCDOE) delivered a multilevel intervention (PE Works; 2015-2019), which included a district-led audit of school PE-law implementation, feedback, and coaching with principals. Using the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) implementation science framework, we assessed the primary multilevel drivers of success for this approach in increasing adherence to PE quantity and quality law.

Methods
We conducted in-depth, semi-structured interviews with district-level personnel (n=17), elementary school administrators (n=18), and PE teachers (n=6) in 2020-21.

Results
Interview results suggested several key RE-AIM drivers of successful PE law implementation. Reach: Ensure higher-need schools receive the necessary initial support to improve PE and later focus on lower-need schools. Effectiveness: Provide support tailored to school needs, not penalties, to improve PE. Adoption: Increase the priority of PE at both district and school levels (e.g., audit and feedback, themselves, appear to elevate PE’s priority). Streamline data collection and feedback reports; collecting/reporting too much information is burdensome and leads to lack of focus. Involve qualified (i.e., skilled in both school administration and PE programming/pedagogy) district-level personnel to work collaboratively with schools. Implementation: Build strong, trusting district-school relationships. Maintenance: Provide ongoing district-level support to schools and involve parents to advocate for quality PE.

Conclusions
PE audits, feedback, and coaching (PEAFC) can guide schools in establishing long-term plans for successfully implementing PE-related law. Future research should examine the impact of PEAFC elsewhere (e.g., secondary schools, other districts).
ST6GALNAC4 promotes hepatocellular carcinogenesis by inducing abnormal glycosylation
Authors: Man Da , Jiang Yifan , Zhang Deguo , Wu Jingjing , Ding Bo , Liu Hanqing , Xu Guangming , Lu Jiahua , Ru Junnan , Tong Rongliang , Zheng Shusheng , Chen Diyu , Wu Jian 
Published: June 2023

AbstractHepatocellular carcinoma (HCC) is one of the most lethal tumor types worldwide. Glycosylation has shown promise in the study of tumor mechanisms and treatment. The glycosylation status of HCC and the underlying molecular mechanisms are still not fully elucidated. Using bioinformatic analysis we obtained a more comprehensive characterization of glycosylation of HCC. Our analysis presented that high glycosylation levels might correlate with tumor progression and poor prognosis. Subsequent Experiments identified key molecular mechanisms for ST6GALNAC4 promoting malignant progression by inducing abnormal glycosylation. We confirmed the contribution of ST6GALNAC4 to proliferation, migration, and invasion in vitro and in vivo. Mechanistic studies revealed that ST6GALNAC4 may be induced abnormal TGFBR2 glycosylation, resulting in the higher protein levels of TGFBR2 and TGF$$\beta$$βpathway increased activation. Our study also provided a further understand of immunosuppressive function of ST6GALNAC4 through T antigen-galectin3+ TAMs axis. This study has provided one such possibility that galectin3 inhibitors might be an acceptable treatment choice for HCC patients with high T antigen expression.
Randomized, double-blind, placebo-controlled study to evaluate the effect of treatment with an SPMs-enriched oil on chronic pain and inflammation, functionality, and quality of life in patients with symptomatic knee osteoarthritis: GAUDI study
Authors: Möller Ingrid , Rodas Gil , Villalón Jose María , Rodas Jose A. , Angulo Francisco , Martínez Nina , Vergés Josep 
Published: June 2023

Abstract
Background
Specialized pro-resolving mediators (SPMs), including 18-HEPE, 17-HDHA, and 14-HDHA are recognized as potentially therapeutic in inflammatory diseases because SPMs regulate the inflammation process, which leads to, for example; swelling and the sensation of pain. In osteoarthritis (OA), chronic pain is described as the symptom that reduces patients´ quality of life (QoL). The GAUDI study evaluated the efficacy of SPMs supplementation in reducing pain in the symptomatic knee of OA patients.

Methods
This randomized, multicenter, double-blind, and placebo-controlled parallel-group pilot study was performed in Spain and conducted on adults 18–68 years old diagnosed with symptomatic knee OA. Patients were enrolled in the study for up to 24 weeks, which included a 12-week intervention period and a follow-up visit on week 24. The primary endpoint was pain change measured through a Visual Analog Scale (VAS). Secondary endpoints included: Pain change evaluation, stiffness, and function according to the WOMAC index; assessment of constant, intermittent, and total pain according to the OMERACT-OARSI score; evaluation of changes in health-related QoL parameters; the use or not of concomitant, rescue, and anti-inflammatory medication; and safety and tolerability assessments.

Results
Patients were enrolled in the study from May 2018 to September 2021. VAS pain score was evaluated in the per protocol population (n = 51 patients), in which we observed a statistically significant reduction after 8 weeks (p = 0.039) and 12 weeks (p = 0.031) of treatment in patients consuming SPMs (n = 23 subjects) vs. placebo (n = 28 subjects). In line with the OMERACT-OARSI score, intermittent pain was reduced after 12 weeks with statistical significance (p = 0.019) in patients treated with SPMs (n = 23 subjects) vs. placebo (n = 28 subjects). Functional status as WOMAC score did not significantly change after SPMs or placebo consumption. Notably, patients consuming SPMs showed improvements in all five aspects of the EUROQoL-5, including a significant improvement in the usual-activities dimension. None of the patients required rescue medication, nor were any adverse events reported.

Conclusions
These findings suggest that sustained SPMs consumption reduces pain in OA patients while also improving their Quality of Life. These results also support the safety profile of SPMs supplementation.
Trial registration NCT05633849. Registered 1 December 1 2022. Retrospectively registered, https://clinicaltrials.gov/ct2/show/study/NCT05633849
Effectiveness of palbociclib with aromatase inhibitors for the treatment of advanced breast cancer in an exposure retrospective cohort study: implications for clinical practice
Authors: Alves da Costa Filipa , Cardoso Borges Fábio , Ramos Adriana , Mayer Alexandra , Brito Claudia , Ramos Catarina , Bernardo Catarina , Cossito Mariane , Furtado Cláudia , Ferreira Arlindo R. , Martins-Branco Diogo , da Costa Miranda Ana , Lourenço António 
Published: June 2023

Abstract
Background
New drugs for locally advanced or metastatic breast cancer have led to clinical benefits, aside with increasing costs to healthcare systems. The current financing model for health technology assessment (HTA) privileges real-world data. As part of the ongoing HTA, this study aimed to evaluate the effectiveness of palbociclib with aromatase inhibitors (AI) and compare it with the efficacy reported in PALOMA-2.

Methods
A population-based retrospective exposure cohort study was conducted including all patients initiating treatment in Portugal with palbociclib under early access use and registered in the National Oncology Registry. The primary outcome was progression free survival (PFS). Secondary outcomes considered included time to palbociclib failure (TPF), overall survival (OS), time to next treatment (TTNT), and proportion of patients discontinuing treatment due to adverse events (AEs). The Kaplan–Meier method was used and median, 1- and 2-year survival rates were computed, with two-sided 95% confidence intervals (95%CI). STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) guidelines for reporting observational studies were used.

Results
There were 131 patients included. Median follow-up was 28.3 months (IQR: 22.7–35.2) and median duration of treatment was 17.5 months (IQR: 7.8–29.1). Median PFS was 19.5 months (95%CI 14.2–24.2), corresponding to a 1-year PFS rate of 67.9% (95%CI 59.2–75.2) and a 2-year PFS rate of 42.0% (95%CI 33.5–50.3). Sensitivity analysis showed median PFS would increase slightly when excluding those not initiating treatment with the recommended dose, raising to 19.8 months (95%CI 14.4–28.9). By considering only patients meeting PALOMA-2 criteria, we could observe a major difference in treatment outcomes, with a mean PFS of 28.8 months (95%CI 19.4–36.0). TPF was 19.8 months (95%CI 14.2–24.9). Median OS was not reached. Median TTNT was 22.5 months (95%CI 18.0–29.8). A total of 14 patients discontinued palbociclib because of AEs (10.7%).

Conclusions
Data suggest palbociclib with AI to have an effectiveness of 28.8 months, when used in patients with overlapping characteristics to those used in PALOMA-2. However, when used outside of these eligibility criteria, namely in patients with less favorable prognosis (e.g., presence of visceral disease), the benefits are inferior, even though still favorable.
Stem-loop structures control mRNA processing of the cellulosomal cip-cel operon in Ruminiclostridium cellulolyticum
Authors: Wang Na , Li Ping , Cheng Ying , Song Houhui , Xu Chenggang 
Published: June 2023

Abstract
Background
Anaerobic, mesophilic, and cellulolytic Ruminiclostridium cellulolyticum produces an efficient cellulolytic extracellular complex named cellulosome, which consist of a non-catalytic multi-functional integrating subunit, organizing the various catalytic subunits into the complex. Main components of cellulosome were encoded by the cip-cel operon in R. cellulolyticum, and their stoichiometry is controlled by the mechanism of selective RNA processing and stabilization, which allows to confer each processed RNA portion from the cip-cel mRNA on different fates due to their stability and resolve the potential contradiction between the equimolar stoichiometry of transcripts with a within a transcription unit and the non-equimolar stoichiometry of subunits.

Results
In this work, RNA processing events were found to occur at six intergenic regions (IRs) harboring stem-loop structures in cip-cel operon. These stem-loops not only stabilize processed transcripts at their both ends, but also act as cleavage signals specifically recognized by endoribonucleases. We further demonstrated that cleavage sites were often located downstream or 3′ end of their associated stem-loops that could be classified into two types, with distinct GC-rich stems being required for RNA cleavage. However, the cleavage site in IR4 was found to be located upstream of the stem-loop, as determined by the bottom AT-pair region of this stem-loop, together with its upstream structure. Thus, our findings reveal the structural requirements for processing of cip-cel transcripts, which can be potentially used to control the stoichiometry of gene expression in an operon.

Conclusions
Our findings reveal that stem-loop structures acting as RNA cleavage signals not only can be recognized by endoribonucleases and determine the location of cleavage sites but also determine the stoichiometry of their flanking processed transcripts by controlling stability in cip-cel operon. These features represent a complexed regulation of cellulosome in the post-transcriptional level, which can be exploited for designing synthetic elements to control gene expression.