bluuebunny/crossref_metadata_2025_split huggingface dataset:
CircGSAP alleviates pulmonary microvascular endothelial cells dysfunction in pulmonary hypertension via regulating miR-27a-3p/BMPR2 axis
Authors: Sun Yuanyuan , Jiang Rong , Hu Xiaoyi , Gong Sugang , Wang Lan , Wu Wenhui , Li Jinling , Kang Xinyang , Xia Shijin , Liu Jinming , Zhao Qinhua , Yuan Ping 
Published: November 2022

Abstract
Background
Our previous study showed that circular RNA-gamma-secretase-activating protein (circGSAP) was down-regulated in pulmonary microvascular endothelial cells (PMECs) in response to hypoxia, and regulated the cell cycle of PMECs via miR-942-5p sponge in pulmonary hypertension (PH). However, the mechanism whether circGSAP affects the dysfunction of PEMCs through other microRNAs (miRNAs) remains largely unknown. Therefore, we aimed to demonstrate the underlying mechanisms of circGSAP regulating PMECs dysfunction by absorbing other miRNAs to regulate target genes in idiopathic pulmonary arterial hypertension (IPAH).

Methods
Quantitative real-time polymerase chain reaction, immunofluorescence staining, Cell Counting Kit-8, Calcein-AM/PI staining, Transwell assay, dual-luciferase reporter assay, and ELISA were used to elucidate the roles of circGSAP.

Results
Here we showed that plasma circGSAP levels were significantly decreased in patients with IPAH and associated with poor outcomes. In vivo, circGSAP overexpression improved survival, and alleviated pulmonary vascular remodeling of monocrotaline-induced PH (MCT-PH) rats. In vitro, circGSAP overexpression inhibited hypoxia-induced PMECs proliferation, migration and increased mortality by absorbing miR-27a-3p. BMPR2 was identified as a miR-27a-3p target gene. BMPR2 silencing ameliorated the effect of the miR-27a-3p inhibitor on PMECs proliferation,migration and mortality. The levels of BMPR2 were upregulated in circGSAP-overexpressed PMECs and lung tissues of MCT-PH rats.

Conclusion
Our findings demonstrated that circGSAP alleviated the dysfunction of PMECs via the increase of BMPR2 by competitively binding with miR-27a-3p, and mitigated pulmonary vascular remodeling of MCT-PH rats, providing potential therapeutic strategies for IPAH.
Targeted blocking of CCR2 and CXCR2 improves the efficacy of transarterial chemoembolization of hepatocarcinoma
Authors: Tian Zhiqiang , Hou Xiaojuan , Liu Wenting , Shao Changchun , Gao Lu , Jiang Jinghua , Zhang Li , Han Zhipeng , Wei Lixin 
Published: November 2022

Abstract
Background
Transarterial chemoembolization (TACE) has been shown to prolong survival in patients with unresectable hepatocellular carcinoma (HCC); however, the long-term survival remains dismal. Targeting macrophage and neutrophil infiltration is a promising strategy. The CCL2/CCR2 and CXCLs/CXCR2 axes are required for recruitment of macrophages and neutrophils, respectively, in HCC. We investigated the feasibility of CCL2/CCR2 and CXCLs/CXCR2 as therapeutic targets in combination with TACE for treating HCC.

Methods
Expression of CCL2/CCR2 and CXCLs/CXCR2 was analyzed in the primary rat HCC model and one HCC cohort. The relationship between expression levels, neutrophil and macrophage infiltration, hepatocarcinogenesis progression in the rat model, and survival of HCC patients was assessed. The anti-tumor effects of blocking the CCL2/CCR2 and CXCLs/CXCR2 axes by CCR2 and CXCR2 antagonists in combination with TACE were evaluated in HCC rats. The numbers of macrophages, neutrophils, and hepatic progenitor cells were further determined to explore the underlying mechanisms.

Results
High macrophage and neutrophil infiltration and CXCL8 expression were associated with poor prognosis in the TCGA liver cancer dataset. High expression of CCL2/CCR2 and CXCL8/CXCR2 in clinical HCC specimens was associated with reduced survival. Expression of CCL2/CCR2 and CXCL1/CXCR2 was correlated with hepatocarcinogenesis progression in the primary rat HCC model. Blockade of CCL2/CCR2 and CXCLs/CXCR2 enhanced the anti-tumor effect of TACE treatment in this model. Blocking the CCL2/CCR2 and CXCLs/CXCR2 axes with CCR2 and CXCR2 antagonists in TACE-treated rats reduced macrophage and neutrophil infiltration and hepatic progenitor cell activation and thus overcame TACE resistance in HCC.

Conclusions
The results demonstrate the translational potential of immunotherapy targeting the CCL2/CCR2 and CXCLs/CXCR2 axes in combination with TACE therapy for the treatment of HCC.
Lactic acid modified rare earth-based nanomaterials for enhanced radiation therapy by disturbing the glycolysis
Authors: Liu Hu , Wang Han , Ni Dalong , Xu Youjia 
Published: November 2022

AbstractDeficient deposition of X-rays and strong capacity of repairing damage DNA of cancer cells limit the effect of radiation therapy (RT). Herein, we synthesize CsLu2F7 nanoparticles with lactic acid (LA) ligands (CsLu2F7-LA) to overcome these limitations. The high-Z atoms of Lu and Cs can deposit more X-rays for generating enhanced hydroxyl radicals (·OH). Meanwhile, the LA ligand will guide CsLu2F7-LA to target monocarboxylic acid transporter (MCT) and impede the transportation of free LA, leading to decreased glycolysis and DNA damage repair. Consequently, the curative effect of RT will be enhanced and the strategy of LA accumulation induced radiosensitization is proved by in vivo and in vitro experiments, which will bring prospects for enhanced RT with nanomedicine.
Convergent validity of EQ-5D with core outcomes in dementia: a systematic review
Authors: Hussain Hannah , Keetharuth Anju , Rowen Donna , Wailoo Allan 
Published: November 2022

Abstract
Objectives
To explore through a systematic review, the convergent validity of EQ-5D (EQ-5D-3L and EQ-5D-5L (total score and dimensions)) with core outcomes in dementia and investigate how this may be impacted by rater-type; with the aim of informing researchers when choosing measures to use in dementia trials.

Methods
To identify articles relevant to the convergent validity of EQ-5D with core dementia outcomes, three databases were electronically searched to September 2022. Studies were considered eligible for inclusion within the review if they included individual level data from people with dementia of any type, collected self and/or proxy reported EQ-5D and collected at least one core dementia outcome measure. Relevant data such as study sample size, stage of dementia and administration of EQ-5D was extracted, and a narrative synthesis was adopted.

Results
The search strategy retrieved 271 unique records, of which 30 met the inclusion criteria for the review. Twelve different core outcome measures were used to capture dementia outcomes: cognition, function, and behaviour/mood across the studies. Most studies used EQ-5D-3L (n = 27). Evidence related to the relationship between EQ-5D and measures of function and behaviour/mood was the most robust, with unanimous directions of associations, and more statistically significant findings. EQ-5D dimensions exhibited associations with corresponding clinical outcomes, whereby relationships were stronger with proxy-EQ-5D (than self-report).

Conclusion
Measuring health-rated quality of life in dementia populations is a complex issue, particularly when considering balancing the challenges associated with both self and proxy report. Published evidence indicates that EQ-5D shows evidence of convergent validity with the key dementia outcomes, therefore capturing these relevant dementia outcomes. The degree of associations with clinical measures was stronger when considering proxy-reported EQ-5D and differed by EQ-5D dimension type. This review has revealed that, despite the limited targeted psychometric evidence pool and reliance on clinical and observational studies, EQ-5D exhibits convergent validity with other dementia outcome measures.
Job strain and burnout in Spanish nurses during the COVID-19: resilience as a protective factor in a cross-sectional study
Authors: Molero Jurado María del Mar , Martos Martínez África , Pérez-Fuentes María del Carmen , Castiñeira López Héctor , Gázquez Linares José Jesús 
Published: November 2022

Abstract
Background
Nurses are frequently exposed to chronic stress in the workplace generating harmful effects such as job strain and burnout. On the contrary, resilience has been shown to be a beneficial variable. The objective of this study was to analyze the relationship between dimensions of the Job Demand Control-Support model, resilience and burnout in nurses, and examine the mediating role of resilience between job strain and burnout.

Methods
A descriptive, cross-sectional study reported in line with the STROBE guidelines. Active nurses were invited to complete an online questionnaire in September, 2020. With snowball sampling, 1013 nurses, with a mean age of 34.71, filled out the Job Content Questionnaire, the Maslach Burnout Inventory and the Resilience Scale.

Results
The results showed the existence of four groups of professionals based on job strain. The nurses in the “High Strain” group (high demands and low control) showed higher scores in emotional exhaustion and cynicism, while those in the “Active Job” group scored higher in personal realization and resilience. The findings showed that job strain affects burnout in nurses, and this effect is mediated by resilience.

Conclusions
The findings of this study showed that a high level of resilience could exert a fundamental role in ensuring well-being and proper job performance by nurses. Nursing managers should see to the personable variables or competencies that provide and favor an opportunity for nurses to widen and improve their practice, in pursuance of satisfying and responding better to people’s needs and the systems they work for.
Neuronal nuclear calcium signaling suppression of microglial reactivity is mediated by osteoprotegerin after traumatic brain injury
Authors: Fröhlich Albrecht , Olde Heuvel Florian , Rehman Rida , Krishnamurthy Sruthi Sankari , Li Shun , Li Zhenghui , Bayer David , Conquest Alison , Hagenston Anna M. , Ludolph Albert , Huber-Lang Markus , Boeckers Tobias , Knöll Bernd , Morganti-Kossmann Maria Cristina , Bading Hilmar , Roselli Francesco 
Published: November 2022

Abstract
Background
Traumatic brain injury (TBI) is characterized by massive changes in neuronal excitation, from acute excitotoxicity to chronic hyper- or hypoexcitability. Nuclear calcium signaling pathways are involved in translating changes in synaptic inputs and neuronal activity into discrete transcriptional programs which not only affect neuronal survival and synaptic integrity, but also the crosstalk between neurons and glial cells. Here, we report the effects of blunting neuronal nuclear calcium signals in the context of TBI.

Methods
We used AAV vectors to express the genetically encoded and nuclear-targeted calcium buffer parvalbumin (PV.NLS.mCherry) or the calcium/calmodulin buffer CaMBP4.mCherry in neurons only. Upon TBI, the extent of neuroinflammation, neuronal death and synaptic loss were assessed by immunohistochemistry and targeted transcriptome analysis. Modulation of the overall level of neuronal activity was achieved by PSAM/PSEM chemogenetics targeted to parvalbumin interneurons. The functional impact of neuronal nuclear calcium buffering in TBI was assessed by quantification of spontaneous whisking.

Results
Buffering neuronal nuclear calcium unexpectedly resulted in a massive and long-lasting increase in the recruitment of reactive microglia to the injury site, which was characterized by a disease-associated and phagocytic phenotype. This effect was accompanied by a substantial surge in synaptic loss and significantly reduced whisking activity. Transcriptome analysis revealed a complex effect of TBI in the context of neuronal nuclear calcium buffering, with upregulation of complement factors, chemokines and interferon-response genes, as well as the downregulation of synaptic genes and epigenetic regulators compared to control conditions. Notably, nuclear calcium buffering led to a substantial loss in neuronal osteoprotegerin (OPG), whereas stimulation of neuronal firing induced OPG expression. Viral re-expression of OPG resulted in decreased microglial recruitment and synaptic loss. OPG upregulation was also observed in the CSF of human TBI patients, underscoring its translational value.

Conclusion
Neuronal nuclear calcium signals regulate the degree of microglial recruitment and reactivity upon TBI via, among others, osteoprotegerin signals. Our findings support a model whereby neuronal activity altered after TBI exerts a powerful impact on the neuroinflammatory cascade, which in turn contributes to the overall loss of synapses and functional impairment.
The role of the ZEB1–neuroinflammation axis in CNS disorders
Authors: Poonaki Elham , Kahlert Ulf Dietrich , Meuth Sven G. , Gorji Ali 
Published: November 2022

AbstractZinc finger E-box binding homeobox 1 (ZEB1) is a master modulator of the epithelial–mesenchymal transition (EMT), a process whereby epithelial cells undergo a series of molecular changes and express certain characteristics of mesenchymal cells. ZEB1, in association with other EMT transcription factors, promotes neuroinflammation through changes in the production of inflammatory mediators, the morphology and function of immune cells, and multiple signaling pathways that mediate the inflammatory response. The ZEB1–neuroinflammation axis plays a pivotal role in the pathogenesis of different CNS disorders, such as brain tumors, multiple sclerosis, cerebrovascular diseases, and neuropathic pain, by promoting tumor cell proliferation and invasiveness, formation of the hostile inflammatory micromilieu surrounding neuronal tissues, dysfunction of microglia and astrocytes, impairment of angiogenesis, and dysfunction of the blood–brain barrier. Future studies are needed to elucidate whether the ZEB1–neuroinflammation axis could serve as a diagnostic, prognostic, and/or therapeutic target for CNS disorders.
Neuroimmune proteins can differentiate between tauopathies
Authors: Cherry Jonathan D. , Baucom Zach H. , Eppich Kaleb G. , Kirsch Daniel , Dixon Erin R. , Tripodis Yorghos , Bieniek Kevin F. , Farrell Kurt , Whitney Kristen , Uretsky Madeline , Crary John F. , Dickson Dennis , McKee Ann C. 
Published: November 2022

Abstract
Background
Tauopathies are a group of neurodegenerative diseases where there is pathologic accumulation of hyperphosphorylated tau protein (ptau). The most common tauopathy is Alzheimer’s disease (AD), but chronic traumatic encephalopathy (CTE), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and argyrophilic grain disease (AGD) are significant health risks as well. Currently, it is unclear what specific molecular factors might drive each distinct disease and represent therapeutic targets. Additionally, there is a lack of biomarkers that can differentiate each disease in life. Recent work has suggested that neuroinflammatory changes might be specific among distinct diseases and offers a novel resource for mechanistic targets and biomarker candidates.

Methods
To better examine each tauopathy, a 71 immune-related protein multiplex ELISA panel was utilized to analyze anterior cingulate grey matter from 127 individuals neuropathologically diagnosed with AD, CTE, PSP, CBD, and AGD. A partial least square regression analysis was carried out to perform unbiased clustering and identify proteins that are distinctly correlated with each tauopathy correcting for age and gender. Receiver operator characteristic and binary logistic regression analyses were then used to examine the ability of each candidate protein to distinguish diseases. Validation in postmortem cerebrospinal fluid (CSF) from 15 AD and 14 CTE cases was performed to determine if candidate proteins could act as possible novel biomarkers.

Results
Five clusters of immune proteins were identified and compared to each tauopathy to determine if clusters were specific to distinct disease. Each cluster was found to correlate with either CTE, AD, PSP, CBD, or AGD. When examining which proteins were the strongest driver of each cluster, it was observed the most distinctive protein for CTE was CCL21, AD was FLT3L, and PSP was IL13. Individual proteins that were specific to CBD and AGD were not observed. CCL21 was observed to be elevated in CTE CSF compared to AD cases (p = 0.02), further validating the use as possible biomarkers. Sub-analyses for male only cases confirmed the results were not skewed by gender differences.

Conclusions
Overall, these results highlight that different neuroinflammatory responses might underlie unique mechanisms in related neurodegenerative pathologies. Additionally, the use of distinct neuroinflammatory signatures could help differentiate between tauopathies and act as novel biomarker candidate to increase specificity for in-life diagnoses.
The relationship between negative life events and non-suicidal self-injury (NSSI) among Chinese junior high school students: the mediating role of emotions
Authors: Jiang Zhongliang , Wang Zhiyi , Diao Qidi , Chen Jie , Tian Geng , Cheng Xiaojing , Zhao Miao , He Long , He Qiang , Sun Jin , Liu Jintong 
Published: November 2022

Abstract
Background
Adolescent non-suicidal self-injury (NSSI) is common and adolescence is the most common period of first self-injury, and the occurrence of NSSI is influenced by negative life events and emotional symptoms. The mediating role of emotional symptoms in the interaction between negative life events and NSSI has not been carefully investigated yet.

Methods
For middle school students in three schools in a Chinese province, the Adolescents Self-Harm Scale was used to investigate NSSI, the Adolescent Self-Rating Life Events Check List was used to investigate adolescent negative life events, and the Self-Rating Anxiety Scale and Self-Rating Depression Scale were used to assess their emotional symptoms. After the description of general data and the test for differences between groups, the relationship between negative life events, emotional symptoms and NSSI was analyzed using Pearson correlation analysis. Structural equation modeling was used to analyze the mediating role of emotions in negative life events and NSSI.

Results
A total of 2376 junior high school students completed this survey, which revealed an annual NSSI prevalence of 37.1% (n = 881) and a higher prevalence of NSSI among girls and rural adolescents. Among adolescents who developed NSSI, 67.4% (N = 594) used multiple means of self-injury. The most common means of self-injury was hair pulling (51.0%), and the most common NSSI purpose and external factors/events were venting bad emotions or feelings (57.5%) and poor academic performance (44.9%), respectively. Negative life events, emotional symptoms and NSSI were positively associated (P < 0.05). Structural equation modeling with negative life events, emotional symptoms and NSSI as variables showed that the model-fit index matched the data well, with RMSEA = 0.073, AGFI = 0.945, GFI = 0.980, CFI = 0.985, NFI = 0.982, TLI = 0.968, IFI = 0.985, and negative life events, emotional symptoms (anxiety, depression) and NSSI all had direct effects with standardized path coefficients of 0.16, 0.19, and 0.23, respectively, with negative life events playing an indirect role in NSSI through emotional symptoms and emotional symptoms playing an incomplete mediating role in negative life events and NSSI.

Conclusion
The prevalence of NSSI was higher among Chinese junior high school students. Both negative life events and emotional symptoms were direct risk factors for NSSI. In addition, negative life events were also indirect risk factors for NSSI, and emotional symptoms played an incomplete mediating role in the relationship between the effects of negative life events and NSSI. This indicates that the combination of reducing the frequency of negative life events while maintaining individual emotional stability during adolescent development can effectively reduce the prevalence of NSSI in adolescents.
Relationship between measurements of ipsilateral capitellum and prosthetic radial head size
Authors: Sun Weitong , Jiang Xieyuan , Zha Yejun , Gong Maoqi , Li Ting , Hua Kehan , Xiao Dan , Lu Shuai 
Published: November 2022

Abstract
Background
Selecting the correct size of head component is challenging in radial head arthroplasty, particularly in comminuted fractures. This study aimed to investigate the relationship between measurements of the ipsilateral capitellum and the prosthetic radial head size, which may be used to predict the size of the radial head prosthesis preoperatively.

Methods
Our study enrolled all patients who underwent radial head arthroplasty at Beijing Jishuitan Hospital. Demographic, injury-related and radiographic data were collected. The prosthetic radial head size was recorded from the surgical notes. Three-dimensional models of preoperative CT scans were reconstructed, on which the lateral capitellar diameter, the capitellar width and the width between the capitellum and trochlea were measured. The correlations between measurements of the ipsilateral capitellum and the prosthetic radial head size were evaluated, and linear regression equations were established.

Results
The study enrolled 37 patients, with an average age of 42.8 ± 11.5 years and a male–female ratio of 20:17. The median diameter of the radial head prostheses was 22 (20, 22) mm. The average lateral capitellar diameter was 20.71 ± 1.93 mm, the mean capitellar width was 14.90 ± 1.40 mm, and the mean width between the capitellum and trochlea was 19.29 ± 1.78 mm. The lateral capitellar diameter (R = 0.820, P < 0.001), the capitellar width (R = 0.726, P < 0.001) and the width between the capitellum and trochlea (R = 0.626, P < 0.001) were significantly positively correlated with the size of the radial head prosthesis. The linear regression equation between the lateral capitellar diameter and the size of the radial head prosthesis was calculated and defined as follows: D = 7.44 + 0.67*d (D: diameter of radial head prosthesis; d: lateral capitellar diameter; and adjusted R2 = 0.719, P < 0.001).

Conclusions
There are positive correlations between the anatomical parameters of the ipsilateral capitellum and the prosthetic radial head size. The lateral capitellar diameter can be measured on three-dimensional CT preoperatively to predict the size of the radial head prosthesis intraoperatively.
Age-related changes in mechanical properties of semitendinosus tendon used for anterior cruciate ligament reconstruction
Authors: Akazawa Takuto , Miyamoto Naokazu , Nishio Hirofumi , Miyamoto-Mikami Eri , Kinoshita Mayuko , Kobayashi Yohei , Nagao Masashi , Takazawa Yuji 
Published: November 2022

Abstract
Background
Hamstring tendons are a popular choice for autografts in anterior cruciate ligament (ACL) reconstruction. However, there is increasing evidence that hamstring tendon autografts carry a high risk of revision and residual instability in young patients. To elucidate the reasons for the inferior outcome of the reconstructed ACL with hamstring tendon autografts in young patients, we investigated the Young’s modulus and the extent of cyclic loading-induced slackening of the semitendinosus tendon used for ACL reconstruction across a broad range of ages.

Methods
Twenty-six male patients (aged 17–53 years), who were scheduled for ACL reconstruction surgery using the semitendinosus tendon autograft, participated in this study. The distal portion of the harvested semitendinosus tendon, which was not used to construct the autograft, was used for cyclic tensile testing to calculate the Young’s modulus and the extent of slackening (i.e., increase in slack length).

Results
Spearman correlation analysis revealed that the Young’s modulus of the semitendinosus tendon was positively correlated with the patient’s age (ρ = 0.559, P = 0.003). In contrast, the extent of tendon slackening did not correlate with the patient’s age.

Conclusions
We demonstrated that the Young’s modulus of the semitendinosus tendon increases with age, indicating that the semitendinosus tendon used for ACL reconstruction is compliant in young patients.