bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanism of mTOR/RILP-regulated autophagic flux in increased susceptibility to myocardial ischemia-reperfusion in diabetic mice
Authors: Zhao Jiyao , Shi Wei , Zheng Yan , Wang Junjie , Yuan Muzhao , Anwar Yultuz , He Yuxuan , Ma Haiping , Wu Jianjiang 
Published: January 2025

BackgroundThe increased myocardial vulnerability that occurs in diabetic patients following an ischemia-reperfusion injury (I/RI) represents a significant perioperative safety risk. A comprehensive understanding of the intrinsic mechanisms underlying this phenomenon is therefore of paramount importance.PurposesThe objective of this study is to investigate the potential mechanism of action between impaired autophagic flux and increased vulnerability in diabetic myocardium. This will provide a foundation for the clinical search for effective preventive and curative measures.MethodsThe transcriptomic alterations in autophagy-related genes following myocardial exposure to I/RI were analyzed by single-cell sequencing. This was followed by the validation of potential mechanisms of action between impaired autophagic flux and increased susceptibility at the cellular and animal levels, respectively.ResultsAfter I/RI in diabetic myocardium, there was a significant increase in the number of CM1 subgroups and a specific downregulation of 239 autophagy-related genes led by RILP. HE staining revealed that myocardial injury was exacerbated in diabetic mice subjected to I/RI. Transmission electron microscopy revealed that the accumulation of autophagic vesicles in cardiomyocytes of diabetic mice resulted in impaired autophagic flux. qRT-PCR revealed that the expression of RILP was significantly reduced in diabetic mice subjected to I/RI. WB showed that P62 was significantly increased and RILP was significantly decreased in diabetic mice subjected to I/RI compared to healthy mice. Inhibition of mTOR during hypoxia/reoxygenation (H/R) injury restored RILP expression and attenuated cellular injury in cardiomyocytes cultured with high glucose.ConclusionFollowing I/RI in diabetic myocardium, an increase in the CM1 subpopulation and a reduction in RILP expression result in impaired autophagic flux. Regulation of the mTOR/RILP pathway can restore impaired autophagic flux and improve myocardial vulnerability, thereby exerting cardioprotective effects.
Targeted ErbB4 receptor activation prevents D-galactose-induced neuronal senescence via inhibiting ferroptosis pathway
Authors: Dao Ji-Ji , Zhang Wei , Liu Chong , Li Qian , Qiao Chen-Meng , Cui Chun , Shen Yan-Qin , Chen Shuang-Xi , Zhao Wei-Jiang 
Published: January 2025

BackgroundNeuronal senescence is a common pathological feature of various neurodegenerative diseases, with ferroptosis playing a significant role. This study aims to investigate the role of ErbB4 receptor activation in preventing D-Galactose (D-gal)-induced neuronal senescence.MethodsMice subjected to D-gal-induced aging were administered a small molecule ErbB4 receptor agonist (E4A), identified via virtual screening, melatonin, or a combination of both. Behavioral assessments were conducted to evaluate therapeutic efficacy in memory and cognitive functions. Immunofluorescence staining, western blot, and biochemical assays were primarily employed to assess changes in both senescence- and ferroptosis-related molecules in mouse hippocampal tissues in response to each treatment. Additionally, mouse hippocampal HT22 neuronal cell cultures were utilized to corroborate the in vivo findings.ResultsThe targeted activation of ErbB4 receptor by E4A significantly ameliorated the behavioral deficits induced by D-gal in mice, demonstrating an effect comparable to that of melatonin, a natural inhibitor of in vivo senescence and ferroptosis. Both E4A and melatonin mitigated D-gal-induced aging in hippocampal neurons of mice. This was evidenced by the upregulation of Lamin B1 and the downregulation of P53, P21, P16, GFAP, and Iba-1 expression levels. Moreover, D-gal treatment markedly decreased the protein expression of the ferroptosis inhibitor Nrf2 while augmenting the expression of the ferroptosis promoter TFRC. These alterations were partially reversed by the individual administration of E4A and melatonin. In vitro studies further corroborated that D-gal treatment significantly and concurrently induced the expression of senescence markers and ferroptosis promoters. However, both E4A and melatonin were able to significantly reverse these changes. Additionally, E4A markedly ameliorated Erastin-induced ferroptosis in mouse hippocampal neuronal cells.ConlusionOur findings suggest that targeted activation of ErbB4 receptor may be a viable strategy for treating neuronal senescence by inhibiting ferroptosis, thereby offering a potential therapeutic avenue for senescence-associated neurodegenerative diseases.
Cannabinoid receptor 2 selective agonist ameliorates adjuvant-induced arthritis by modulating the balance between Treg and Th17 cells
Authors: Tian Na , Yang Cui , Du Yu , Chen Miao , Li Bin , Li Dan , Dai Sheng-Ming 
Published: January 2025

BackgroundAdjuvant-induced arthritis (AIA) serves as a classic model for rheumatoid arthritis (RA), typified by inflammatory cell infiltration and joint damage. This study explores the therapeutic efficacy of HU-308, a CB2 receptor-specific agonist, on inflammation and immune balance in AIA.MethodsAIA was induced in mice by CFA injection. AIA mice were treated with HU-308 or vehicle, and effects on paw swelling, spleen index, histopathology, and immune cell profiles were evaluated. Flow cytometry, in vitro differentiation assays, and Western blot analysis were performed to examine Th17 and Treg cells, as well as signaling pathways involved in their differentiation.ResultsHU-308 reduced paw swelling, lowered spleen index, and preserved joint integrity in AIA mice, mitigating inflammatory cell infiltration and bone erosion. Flow cytometry revealed that HU-308 restored the Th17/Treg imbalance in AIA, decreasing Th17 cell frequency and enhancing Treg cell infiltration. In vitro assays confirmed HU-308s role in promoting Treg differentiation and inhibiting Th17 polarization. Western blot analysis indicated that HU-308 modulated immune balance through the JAK/STAT5 and TGF-β/SMAD signaling pathways, increasing Foxp3 and TGF-β expression.ConclusionHU-308 demonstrates significant anti-inflammatory effects in AIA by restoring Th17/Treg balance and reducing joint damage. The findings indicate that HU-308 holds potential as an immunomodulatory agent for RA, providing valuable insights into CB2-mediated therapeutic strategies for autoimmune diseases.
Yishenyangsui granule for degenerative cervical myelopathy: a randomized, double-blind, placebo-controlled trial with long-term follow-up
Authors: Yin He , Chen Xin , Liu Zhiwei , Xu Bo , Jin Zhefeng , Liu Yan , Qi Baoyu , Tang Bin , Wang Ping , Xu Fanping , Wei Xu , Yu Jie , Zhu Liguo 
Published: January 2025

ObjectiveThis randomized controlled trial aims to evaluate the efficacy and safety of Yishenyangsui granule for treating Degenerative Cervical Myelopathy.Materials and methodsA randomized, double-blind, placebo-controlled clinical trial was conducted with 152 participants recruited from three centers and randomly assigned to receive either Yishenyangsui granule or placebo. The Japanese Orthopaedic Association (JOA) score and Neck Disability Index (NDI) score were evaluated for 32 weeks. Patient-reported outcomes including surgical treatment data, re-treatment data, and patient-reported condition were collected for long-term follow-up. This trial was approved by the ethics committee of WangJing Hospital of China Academy of Chinese Medical Sciences (WJEC-KT-2016-004-P001) and was registered at the Chinese Clinical Trials Registry (ChiCTR-INR-16009723) on 03 November 2016 (Check out at https://www.chictr.org.cn/indexEN.html for a more comprehensive overview).ResultsThe results showed that the improvement in JOA score at week 8 was significantly better in the Yishenyangsui granule group than in the placebo group (1.47 vs. 0.43; P &lt; 0.001). Furthermore, improvements in motor function of upper/lower extremities, sensory function of upper extremities, reading ability, and recreation domain scores were also significantly superior in the Yishenyangsui granule group compared to the placebo group (P &lt; 0.05). Long-term follow-up outcomes revealed no statistical differences between groups regarding surgical treatment data or patient-reported condition (P &gt; 0.05). However, there was a significant difference detected in re-treatment data between groups with a lower rate observed among those receiving Yishenyangsui granule compared to those receiving placebo [25 (43.10%) vs. 40 (68.97%); P = 0.033], indicating its effectiveness for treating mild-to-moderate Degenerative Cervical Myelopathy.ConclusionYishenyangsui granule was effective in treating mild to moderate Degenerative Cervical Myelopathy. The participants have improved long-term outcomes.Clinical Trials Registrationhttps://www.chictr.org.cn/indexEN.html, identifier ChiCTR-INR-16009723.
Cerebral microvascular density, blood-brain barrier permeability, and support for neuroinflammation indicate early aging in a Marfan syndrome mouse model
Authors: Curry-Koski Tala , Curtin Liam P. , Esfandiarei Mitra , Thomas Theresa Currier 
Published: January 2025

IntroductionMarfan Syndrome (MFS) is a connective tissue disorder due to mutations in fibrillin-1 (Fbn1), where a Fbn1 missense mutation (Fbn1C1039G/+) can result in systemic increases in the bioavailability and signaling of transforming growth factor-β (TGF-β). In a well-established mouse model of MFS (Fbn1C1041G/+), pre-mature aging of the aortic wall and the progression of aortic root aneurysm are observed by 6-month-of-age. TGF-β signaling has been implicated in cerebrovascular dysfunction, loss of blood-brain barrier (BBB) integrity, and age-related neuroinflammation. We have reported that pre-mature vascular aging in MFS mice could extend to cerebrovasculature, where peak blood flow velocity in the posterior cerebral artery (PCA) of 6-month-old (6M) MFS mice was reduced, similarly to 12-month-old (12M) control mice. Case studies of MFS patients have documented neurovascular manifestations, including intracranial aneurysms, stroke, arterial tortuosity, as well as headaches and migraines, with reported incidences of pain and chronic fatigue. Despite these significant clinical observations, investigation into cerebrovascular dysfunction and neuropathology in MFS remains limited.MethodsUsing 6M-control (C57BL/6) and 6M-MFS (Fbn1C1041G/+) and healthy 12M-control male and female mice, we test the hypothesis that abnormal Fbn1 protein expression is associated with altered cerebral microvascular density, BBB permeability, and neuroinflammation in the PCA-perfused hippocampus, all indicative of a pre-mature aging brain phenotype. Glut1 immunostaining was used to quantify microvascular density, IgG staining to assess BBB permeability, and microglial counts to evaluate neuroinflammation.ResultsUsing Glut1 staining, 6M-MFS mice and 12M-CTRL similarly present decreased microvascular density in the dentate gyrus (DG), cornu ammonis 1 (CA1), and cornu ammonis 3 (CA3) regions of the hippocampus. 6M-MFS mice exhibit increased BBB permeability in the DG and CA3 as evident by Immunoglobulin G (IgG) staining. No differences were detected between 6M and 12M-CTRL mice. 6M-MFS mice show a higher number of microglia in the hippocampus compared to age-matched control mice, a pattern resembling that of 12M-CTRL mice.DiscussionThis study represents the first known investigation into neuropathology in a mouse model of MFS and indicates that the pathophysiology underlying MFS leads to a systemic pre-mature aging phenotype. This study is crucial for identifying and understanding MFS-associated neurovascular and neurological abnormalities, underscoring the need for research aimed at improving the quality of life and managing pre-mature aging symptoms in MFS and related connective tissue disorders.
Effects of dribbling restrictions in small-sided games on aerobic and anaerobic fitness in youth basketball players
Authors: Li Mingbang , Tan Liang , Wu Hong , Wu Jianwei 
Published: January 2025

IntroductionImposing constraints such as limiting dribbling in smallsided games (SSGs) is known to increase physiological and locomotor demands. However, the long-term effects on physical adaptations remain unexplored. This experimental study aimed to compare the impact of free-play SSGs (freeD) and limited-dribbling SSGs (limitedD) in SSGs on the aerobic and anaerobic adaptations of youth basketball players.MethodsForty-five youth basketball players (aged 15.7 ± 0.6 years, with 4.2 ± 0.7 years of experience) were randomly assigned to two experimental groups (freeD and limitedD) and a control group (not exposed to SSG interventions). During the eight-week intervention, the experimental groups participated in additional SSG sessions twice a week, with session work time durations ranging from 12 to 16 min. Both experimental groups followed identical SSG formats, court dimensions, and training regimens, with the only difference being that one group participated in free play while the other group was prohibited from dribbling during progression. Aerobic capacity was assessed using the Yo-Yo Intermittent Recovery Test Level 1 (YYIRT), while the 30-second Wingate Test measured peak power output (PPO) and average power output (APO) at baseline and post-intervention. Statistical analysis was conducted using a mixed ANOVA to examine the interactions between time and group.ResultsComparisons of YYIRT between groups at post-intervention revealed that limitedD performed significantly better than both freeD (p = 0.035; d = 1.038) and the control group (p &lt; 0.001; d = 2.050), while freeD also showed significantly better performance (p = 0.021; d = 0.082) than the control group. Regarding PPO, limitedD was significantly better than the control group (p = 0.043; d = 0.943). Finally, for APO, limitedD was significantly better than both freeD (p = 0.043; d = 0.928) and the control group (p &lt; 0.001; d = 1.793), while freeD also exhibited significantly better performance than the control group (p = 0.046; d = 0.036).ConclusionsLimiting dribbling in basketball SSGs is more effective than free play. This makes it a potentially valuable strategy for designing SSGs in basketball training. Coaches may consider incorporating limited-dribbling conditions into SSGs to boost the intensity of training sessions, improve cardiovascular endurance, and enhance anaerobic power.
Studying engagement in educational settings: a mapping review on high-impact academic engagement research
Authors: Loyola-Carrillo Paola , Vega-Muñoz Alejandro , Salazar-Sepúlveda Guido , Gil-Marín Miseldra , Adsuar-Sala José 
Published: January 2025

IntroductionAcademic engagement provides opportunities and resources for students to engage in socio-educational interactions and learning. Our study provides an overview of high-impact research in academic engagement and the potential causes of its high valuation in the scientific community.MethodsWe conducted a mapping review using bibliometric analysis of 1,607 articles indexed in Web of Science, processed mainly by VOSviewer software.ResultsThe publication of selected articles grew exponentially year by year, presenting concentration levels of 1% in authorship, 49% in a single country, and 5% in journals, identified as outstanding Keywords plus® central aspects of academic engagement (classroom-social environment and school engagement), in addition, 6% were in highly cited articles.ConclusionThese highly cited articles (6%) are associated with authors with high levels of publication. The most cited current topics relate to the motivation and emotional aspects of academic engagement.
The curvilinear relationship between Framingham Steatosis Index and depression: insights from a nationwide study
Authors: Jiang Chunqi , Wang Bo , Wang Ning , Wang Jun , Qu Yinuo , Zhao Guang , Zhang Xin 
Published: January 2025

BackgroundThe Framingham Steatosis Index (FSI) serves as a diagnostic metric for fatty liver. While research has established a link between depression and fatty liver, the association with the Framingham Steatosis Index (FSI) remains undocumented. The aim of this study is to explore the potential correlation between FSI and depression, addressing this research void.MethodsOur data originates from the National Health and Nutrition Examination Survey (NHANES) database. We employed the PHQ-9 questionnaire for the evaluation of depressive symptoms. We investigated the association between FSI and depression using a weighted multiple logistic regression model and stratified analysis. Non-linear associations were explored using fitted smooth curves. A recursive method was employed to identify inflection points. Subgroup analyses were conducted to examine differences in the association between FSI and depression within subgroups.ResultsOur research encompassed a total of 19,697 participants. Multivariate logistic regression analysis, adjusted for potential confounding factors, demonstrated a significant positive association between FSI and depression, with OR of 1.14 (95% CI: 1.10, 1.18). Stratified analysis indicated that a significant positive correlation exists between FSI and depression among all groups except those with BMI below 30. The non-linear relationship was further confirmed by the restricted cubic splines analysis, which revealed an inflection point at an FSI value of 29.72. Below this threshold, there was no significant correlation, while above it, a positive correlation was observed. Subgroup analysis revealed statistically significant interactions between FSI and depression within the educational attainment groups.ConclusionOur study’s discovery is the curvilinear relationship between FSI and depression. Factors such as inflammation, hormonal levels, and metabolic disruptions could be the underlying mechanisms driving this relationship. This finding offers valuable insights that could inform the development of comprehensive intervention strategies for managing depression in clinical settings.
Pilot of a team-based quality improvement strategy to improve cardiovascular risk factors care in community mental health centers
Authors: Murphy Karly A. , Gennusa Joseph , Dalcin Arlene T. , Cook Courtney , Goldsholl Stacy , Fink Tyler , Daumit Gail L. , Wang Nae-Yuh , Thompson David , McGinty Emma E. 
Published: January 2025

IntroductionPopulations with serious mental illness are less likely to receive evidence-based care for cardiovascular disease (CVD) risk factors. We sought to characterize the implementation of an adapted team-based quality improvement strategy to improve mental health providers’ delivery of evidence-based CVD risk factor care.MethodsIn a 12-month, single arm pre/post pilot study in four behavioral health homes embedded within psychiatric rehabilitation programs, sites implemented an adapted Comprehensive Unit Safety Program (CUSP). Primary measures examined changes in organizational quality improvement culture and provider self-efficacy for CVD risk factor care. Secondary measures examined changes in acceptability, appropriateness, and feasibility of CUSP and receipt of guideline-concordant care for hypertension, dyslipidemia, and diabetes.ResultsProvider self-efficacy to coordinate care for hypertension and diabetes improved, but organizational quality improvement culture did not change. Acceptability, appropriateness, and feasibility were rated highly but did not change pre/post CUSP. The percentage who reached goals per national guidelines improved for those with dyslipidemia but not for those with hypertension or diabetes. CUSP teams implemented processes to build staff capacity, standardize communication, elicit feedback, and deliver education on coordination for CVD risk factors.ConclusionThis pilot study showed no effects of CUSP on organizational quality improvement culture or provider self-efficacy, the mechanisms by which CUSP is expected to improve care processes. Long term investments are needed to support organizational quality improvement work and providers’ efficacy to delivery - evidence-based CVD risk factor care delivery.Clinical Trial Registrationhttp://www.ClinicalTrials.gov, identifier NCT04696653.
Effect and prediction of long-term weather and pollutant exposure on hemorrhagic fever with renal syndrome: based on statistical models
Authors: Hou Weiming 
Published: January 2025

BackgroundPrevious studies have typically explored daily lagged relationships between hemorrhagic fever with renal syndrome (HFRS) and meteorology, with a limited seasonal exploration of monthly lagged relationships, interactions, and the role of pollutants in multiple predictions of hemorrhagic fever.MethodsOur researchers collected data on HFRS cases from 2005 to 2018 and meteorological and contaminative factors from 2015 to 2018 for the northeastern region. First, we applied the moving epidemic method (MEM) to estimate the epidemic threshold and intensity level. Then, we used a distributed lag non-linear model (DLNM) and a generalized additive model (GAM) with a maximum lag of 6 months to evaluate the lagged and interaction effects of meteorological and pollution factors on the HFRS cases. Multiple machine learning models were then applied after Spearman’s rank correlation coefficient analysis was performed to screen for environmental factors in the Northeastern region.ResultsThere was a yearly downward trend in the incidence of HFRS in the northeastern region. High prevalence threshold years occurred from 2005 to 2007 and from 2012 to 2014, and the epidemic months were mainly concentrated in November. During the low prevalence threshold period, the main lag factor was low wind direction. In addition, the meteorological lag effect was pronounced during the high prevalence threshold period, where the main lag factors were cold air and hot dew point. Low levels of the AQI and PM10 and high levels of PM2.5 showed a dangerous lag effect on the onset of HFRS, while extremely high levels of PM2.5 appeared to have a protective effect. High levels of the AQI and PM10, as well as low levels of PM2.5, showed a protective lag effect. The model of PM2.5 and the AQI interaction pollution is better. The support vector machine (SVM)-radial algorithm outperformed other algorithms when pollutants are used as predictor variables.ConclusionThis is the first mathematically based study of the seasonal threshold of HFRS in northeastern China, allowing for accurate estimation of the epidemic level. Our findings suggest that long-term exposure to air pollution is a risk factor for HFRS. Therefore, we should focus on monitoring pollutants in cold conditions and developing HFRS prediction models.