bluuebunny/crossref_metadata_2025_split huggingface dataset:
Histone deacetylase 8 inhibition prevents the progression of peritoneal fibrosis by counteracting the epithelial-mesenchymal transition and blockade of M2 macrophage polarization
Authors: Zhou Xun , Chen Hui , Shi Yingfeng , Li Jinqing , Ma Xiaoyan , Du Lin , Hu Yan , Tao Min , Zhong Qin , Yan Danying , Zhuang Shougang , Liu Na 
Published: February 2023

BackgroundPeritoneal dialysis (PD) is an effective replacement therapy for end-stage renal disease patients. However, long-term exposure to peritoneal dialysate will lead to the development of peritoneal fibrosis. Epigenetics has been shown to play an important role in peritoneal fibrosis, but the role of histone deacetylases 8 (HDAC8) in peritoneal fibrosis have not been elucidated. In this research, we focused on the role and mechanisms of HDAC8 in peritoneal fibrosis and discussed the mechanisms involved.MethodsWe examined the expression of HDAC8 in the peritoneum and dialysis effluent of continuous PD patients. Then we assessed the role and mechanism of HDAC8 in peritoneal fibrosis progression in mouse model of peritoneal fibrosis induced by high glucose peritoneal dialysis fluid by using PCI-34051. In vitro, TGF-β1 or IL-4 were used to stimulate human peritoneal mesothelial cells (HPMCs) or RAW264.7 cells to establish two cell injury models to further explore the role and mechanism of HDAC8 in epithelial-mesenchymal transition (EMT) and macrophage polarization.ResultsWe found that HDAC8 expressed highly in the peritoneum from patients with PD-related peritonitis. We further revealed that the level of HDAC8 in the dialysate increased over time, and HDAC8 was positively correlated with TGF-β1 and vascular endothelial growth factor (VEGF), and negatively correlated with cancer antigen 125. In mouse model of peritoneal fibrosis induced by high glucose dialysate, administration of PCI-34051 (a selective HDAC8 inhibitor) significantly prevented the progression of peritoneal fibrosis. Treatment with PCI-34051 blocked the phosphorylation of epidermal growth factor receptor (EGFR) and the activation of its downstream signaling pathways ERK1/2 and STAT3/HIF-1α. Inhibition of HDAC8 also reduced apoptosis. In vitro, HDAC8 silencing with PCI-34051 or siRNA inhibited TGF-β1-induced EMT and apoptosis in HPMCs. In addition, continuous high glucose dialysate or IL-4 stimulation induced M2 macrophage polarization. Blockade of HDAC8 reduced M2 macrophage polarization by inhibiting the activation of STAT6 and PI3K/Akt signaling pathways. ConclusionsWe demonstrated that HDAC8 promoted the EMT of HPMCs via EGFR/ERK1/2/STAT3/HIF-1α, induced M2 macrophage polarization via STAT6 and PI3K/Akt signaling pathways, and ultimately accelerated the process of peritoneal fibrosis.
Grain-boundary segregation and superior mechanical properties in a multicomponent L12 Ni46.5Co24Fe8Al12.5Ti9 superlattice alloy
Authors: Liu Weihong , Chen Keyu , Yu Chunyan 
Published: February 2023

Ni3Al superlattice alloys with the L12 structure have garnered much attention due to their attractive high-temperature mechanical properties; however, their grain-boundary brittleness and low ductility in the ambient temperature range have greatly restricted their widespread application. In this study, we developed an L12 structure multicomponent Ni46.5Co24Fe8Al12.5Ti9 (at. %) superlattice alloy that notably suppressed the room-temperature intergranular brittleness and exhibited a large tensile elongation of 17.1% ± 5.2% together with a high ultimate tensile strength of 1,080.2 ± 57.4 MPa. Multiple microstructural examinations reveal an L12 equiaxed-grain microstructure, with the presence of a minor B2 phase. Moreover, the co-segregation of Fe and Co atoms, and the associated reduction or elimination of the L12 chemical order at the grain-boundary regions were characterized, which were proved to be the root cause of the suppression of intergranular brittleness and the high tensile ductility. Further theoretical calculations show that alloying of Fe and Co to binary Ni3Al reduced the ordering energy, which promoted intergranular segregation and associated disordering. This observation demonstrated that the elimination or reduction of interfacial chemical order is an effective ductilizing method for superlattice alloys.
The mast cell exosome-fibroblast connection: A novel pro-fibrotic pathway
Authors: Savage Alexandria , Risquez Cristobal , Gomi Kazunori , Schreiner Ryan , Borczuk Alain C. , Worgall Stefan , Silver Randi B. 
Published: February 2023

IntroductionIn addition to the traditional activation of resident receptors by release of local mediators, new evidence favors the existence of exosomes in cell-to-cell communication that mediates delivery of specific cargo to modulate recipient cell function. We report that mast cell exosomes are an additional source of pro-fibrotic substances and constitute a unique pathway for the generation of excess collagen.MethodsWe use primary human lung fibroblasts (HLFs) to demonstrate the uptake of labeled exosomes isolated from the human mast cell line HMC-1 (MC-EXOs), previously shown to contain protein cargo in common with human mast cell exosomes.ResultsThe MC-EXO uptake by HLF is to the cytosol and increases both proline hydroxylation in HLF lysate and secreted collagen, within 24 h, which is sustained over 72 h, the same time required for transforming growth factor-β (TGF-β) to activate collagen synthesis in the HLFs. Unlike TGF-β, MC-EXO uptake does not induce fibrillar gene activation or invoke the Smad-nuclear transcription pathway. We show that MC-EXO uptake and TGF-β have an additive effect on collagen synthesis in HLF and postulate that MC-EXO uptake by HLFs is a contributing factor to excess collagen synthesis and represents a unique paradigm for understanding fibrosis.DiscussionIt is known that, in the lungs, mast cells are more activated and increase in number with inflammation, injury and viral infection associated with fibrosis. With the reported increased incidence of post-COVID-pulmonary fibrosis (PCPF), data from patients with severe COVID-19 are presented that show an increase in the mast cell number in lung parenchyma, the site of PCPF. Our findings provide a rationale for targeting multiple fibrogenic pathways in the management of lung fibrosis and the use of mast cell exosomes as a biomarker for the prognostic and diagnostic management of evolving fibrotic lung disease.
Naïve-memory regulatory T cells ratio is a prognostic biomarker for patients with acute ischemic stroke
Authors: Deng Gang , Tang Yue , Xiao Jun , Chen Xin , Chu Yun-Hui , Shang Ke , Zhou Luo-Qi , Qin Chuan , Wang Feng , Tian Dai-Shi 
Published: February 2023

BackgroundRegulatory T cells (Treg) have been identified as a key modulator of neuroinflammation in stroke. However, little is known about the association of Treg subpopulations with clinical outcome in patients with acute ischemic stroke (AIS).MethodsPatients within 1 week from stroke onset were prospectively enrolled in this study. Healthy controls were sex-and age-matched 1:1 to AIS patients. The frequencies of Treg and Treg subsets were analyzed by flow cytometry and compared with nonstroke control. Univariate and multivariate logistic regression analysis was performed to investigate the prognostic value of Treg subsets in stroke outcomes.ResultsA total of 328 patients and 328 controls were included in the study. Compared with controls, patients with AIS had higher levels of Treg frequency and memory Treg (mTreg) frequency, but lower levels of naïve Treg (nTreg) frequency and nTreg/mTreg ratio. One hundred twenty-six (38.4%) patients experienced unfavorable outcome (modified Rankin score 2–6). Multivariate regression analysis showed that nTreg/mTreg ratio was negatively associated with unfavorable 90-day outcome (the highest tertile versus the lowest tertile: odds ratio 0.13, 95% confidential interval [CI] 0.05–0.35). The risk estimation of unfavorable 90 day outcome can be significantly improved by adding nTreg/mTreg ratio to the conventional clinical parameters (continuous net reclassification improvement 91.26, 95% CI 69.04–113.5%, p &lt; 0.001; integrated discrimination improvement 22.38, 95% CI 17.16–27.59%, p &lt; 0.001).ConclusionThis study showed that patients with AIS had elevated Treg frequency and mTreg frequency, but reduced nTreg frequency and nTreg/mTreg ratio. Admission nTreg/mTreg ratio was an independent predictor of unfavorable 90 day outcome in AIS. However, large sample-size cohort studies are needed to confirm our findings.
Behavioral and biochemical effects of alcohol withdrawal in female C3H/HeNRj and C57BL/6JRj mice
Authors: Tonetto Simone , Weikop Pia , Brudek Tomasz , Thomsen Morgane 
Published: February 2023

BackgroundAlcohol use disorder (AUD) is a major problem of our society and is often characterized and worsened by relapse. Prolonged alcohol exposure leads to numerous biochemical alterations that, upon cessation of alcohol intake, cause an array of immediate and lasting withdrawal symptoms. Acute withdrawal and neuroinflammation can be harmful in themselves, and lasting withdrawal symptoms contribute to relapse. Here, we conducted an initial feasibility study assessing several behavioral and neurochemical factors in female C3H/HeNRj (C3H) and C57BL/6JRj (B6) mice to determine which strain showed the clearest alcohol withdrawal symptoms during long-term abstinence and neurochemical alterations following re-exposure.MethodsFemale C3H and B6 mice (n = 12 per group/strain) were intermittently exposed to alcohol-containing or control liquid diets for 3 weeks. Acute and prolonged withdrawal symptoms were assessed over a period of 3 weeks using a battery of behavioral test, comprised of alcohol self-administration, anhedonia, hyperalgesia, anxiety-like and depressive-like disturbances. Brain inflammation was measured by multiplex cytokine assay. Monoamine levels in the hippocampus and striatum, as well as exploratory analyses of cations levels in the cerebellum, were assessed by High-Performance Liquid Chromatography (HPLC).ResultsBoth C3H and B6 alcohol-exposed mice displayed decreased saccharin intake or preference and higher stress levels assessed by ultrasonic vocalizations (USVs) recordings. B6 but not C3H alcohol-exposed mice also exhibited a slower decline of alcohol oral self-administration (OSA), hyperalgesia, elevated brain TNF-α and elevated serotonin turnover.ConclusionOur findings highlight the suitability of the B6 strain to study the behavioral and neurochemical alterations caused by alcohol withdrawal and the potential efficacy of experimental treatments, not only in early detoxification, but also in prolonged abstinence. The feasibility of these assays is important because long-lasting withdrawal symptoms are often the main cause of relapse in alcohol-dependent patients.
Machine learning segmentation of core and penumbra from acute stroke CT perfusion data
Authors: Werdiger Freda , Parsons Mark W. , Visser Milanka , Levi Christopher , Spratt Neil , Kleinig Tim , Lin Longting , Bivard Andrew 
Published: February 2023

IntroductionComputed tomography perfusion (CTP) imaging is widely used in cases of suspected acute ischemic stroke to positively identify ischemia and assess suitability for treatment through identification of reversible and irreversible tissue injury. Traditionally, this has been done via setting single perfusion thresholds on two or four CTP parameter maps. We present an alternative model for the estimation of tissue fate using multiple perfusion measures simultaneously.MethodsWe used machine learning (ML) models based on four different algorithms, combining four CTP measures (cerebral blood flow, cerebral blood volume, mean transit time and delay time) plus 3D-neighborhood (patch) analysis to predict the acute ischemic core and perfusion lesion volumes. The model was developed using 86 patient images, and then tested further on 22 images.ResultsXGBoost was the highest-performing algorithm. With standard threshold-based core and penumbra measures as the reference, the model demonstrated moderate agreement in segmenting core and penumbra on test images. Dice similarity coefficients for core and penumbra were 0.38 ± 0.26 and 0.50 ± 0.21, respectively, demonstrating moderate agreement. Skull-related image artefacts contributed to lower accuracy.DiscussionFurther development may enable us to move beyond the current overly simplistic core and penumbra definitions using single thresholds where a single error or artefact may lead to substantial error.
Tui Na for painful peripheral neuropathy in people with human immunodeficiency virus: A randomized, double-blind, placebo-controlled trial protocol
Authors: Zhu Xingmei , Ge Song , Dune Linda , Yang Chao , Tian Chong , Wang Yong 
Published: February 2023

BackgroundPeripheral neuropathy (PN), including numbness, loss of sensation, paresthesia, a burning sensation, and stabbing pain in extremities, is a common complication in people with human immunodeficiency virus (PHIV). Medications commonly used to treat HIV-related PN are not effective and lead to many side effects. HIV-related PN symptoms may be alleviated or treated with a series of therapeutic Chinese foot massages (TCFM), which are non-invasive and relatively safe. However, relevant studies are lacking.Study designThis proposed trial is a prospective, two-arm, parallel, double-blinded, randomized controlled trial.AimThis proposed trial aims to assess the effectiveness of TCFM on HIV-related PN in people with HIV (PHIV).OutcomesThe primary outcomes, measured at baseline, end of TCFM/placebo, and twelve weeks after, include (1), lower extremity pain, (2) lower extremity functioning, and (3) health-related quality of life. The secondary outcomes, measured throughout the trial process, include (1) recruitment and completion rate (No. of referred, No. of eligible, No. of enrolled, No. of withdrawals, trial recruitment rate, and trial completion rate), (2) participants' safety (No. and severity of adverse events), (3) treatment adherence (average time of each message session, No. of completed sessions, and No. of missed sessions), and (4) compliance (No. of participants completing the trial following the initial group assignment).Sample sizeAn estimated 142 participants in total, or 71 participants in each arm, will be needed for this trial.Trial statusThis trial was registered at ClinicalTrials.gov of the National Institute of Health on Oct 26, 2022 (ClinicalTrials.gov Identifier: NCT05596123). The researchers expect to recruit participants starting in Feb. 2023 and ending in Feb 2025.
Intraoperative microelectrode recording under general anesthesia guided subthalamic nucleus deep brain stimulation for Parkinson's disease: One institution's experience
Authors: Qian Kang , Wang Jiajing , Rao Jing , Zhang Peng , Sun Yaqiang , Hu Wenqing , Hao Jie , Jiang Xiaobing , Fu Peng 
Published: February 2023

ObjectiveMicroelectrode recording (MER) guided subthalamic nucleus deep brain stimulation (STN-DBS) under local anesthesia (LA) is widely applied in the management of advanced Parkinson's disease (PD). Whereas, awake DBS under LA is painful and burdensome for PD patients. We analyzed the influence of general anesthesia (GA) on intraoperative MER, to assess the feasibility and effectiveness of GA in MER guided STN-DBS.MethodsRetrospective analysis was performed on the PD patients, who underwent bilateral MER guided STN-DBS in Wuhan Union Hospital from July 2019 to December 2021. The patients were assigned to LA or GA group according to the anesthetic methods implemented. Multidimensional parameters, including MER signals, electrode implantation accuracy, clinical outcome and adverse events, were analyzed.ResultsA total of 40 PD patients were enrolled in this study, including 18 in LA group and 22 in GA group. There were no statistically significant differences in patient demographics and baseline characteristics between two groups. Although, the parameters of MER signal, including frequency, inter-spike interval (ISI) and amplitude, were obviously interfered under GA, the waveforms of MER signals were recognizable and shared similar characteristics with LA group. Both LA and GA could achieve effective electrode implantation accuracy and clinical outcome. They also shared similar adverse events postoperatively.ConclusionGA is viable and comparable to LA in MER guided STN-DBS for PD, regarding electrode implantation accuracy, clinical outcome and adverse events. Notably, GA is more friendly and acceptable to the patients who are incapable of enduring intraoperative MER under LA.
Linking resting-state network fluctuations with systems of coherent synaptic density: A multimodal fMRI and 11C-UCB-J PET study
Authors: Fang Xiaotian T. , Volpi Tommaso , Holmes Sophie E. , Esterlis Irina , Carson Richard E. , Worhunsky Patrick D. 
Published: February 2023

Introduction: Resting-state network (RSN) connectivity is a widely used measure of the brain’s functional organization in health and disease; however, little is known regarding the underlying neurophysiology of RSNs. The aim of the current study was to investigate associations between RSN connectivity and synaptic density assessed using the synaptic vesicle glycoprotein 2A radioligand 11C-UCB-J PET.Methods: Independent component analyses (ICA) were performed on resting-state fMRI and PET data from 34 healthy adult participants (16F, mean age: 46 ± 15 years) to identify a priori RSNs of interest (default-mode, right frontoparietal executive-control, salience, and sensorimotor networks) and select sources of 11C-UCB-J variability (medial prefrontal, striatal, and medial parietal). Pairwise correlations were performed to examine potential intermodal associations between the fractional amplitude of low-frequency fluctuations (fALFF) of RSNs and subject loadings of 11C-UCB-J source networks both locally and along known anatomical and functional pathways.Results: Greater medial prefrontal synaptic density was associated with greater fALFF of the anterior default-mode, posterior default-mode, and executive-control networks. Greater striatal synaptic density was associated with greater fALFF of the anterior default-mode and salience networks. Post-hoc mediation analyses exploring relationships between aging, synaptic density, and RSN activity revealed a significant indirect effect of greater age on fALFF of the anterior default-mode network mediated by the medial prefrontal 11C-UCB-J source.Discussion: RSN functional connectivity may be linked to synaptic architecture through multiple local and circuit-based associations. Findings regarding healthy aging, lower prefrontal synaptic density, and lower default-mode activity provide initial evidence of a neurophysiological link between RSN activity and local synaptic density, which may have relevance in neurodegenerative and psychiatric disorders.
Global research trends in palliative care for breast cancer from 2012 to 2022: A scientometric analysis
Authors: Sun Yixian , Wu Jinyao , Tian Huiting , Qiu Xiuhua , Fang Ying , Xiao Yingjie , Zheng Jiehua , Zhou Yanqiong 
Published: February 2023

PurposeWe used bibliometric methods to evaluate the global scientific output of palliative care breast cancer research and to explore the current status and further research directions in the field over the past decade.MethodsAll relevant publications from the year 2012 to 2022 were retrieved from Web of Science. We applied VOSviewer and Bibliometrix R v4.2.1 to obtain information on subject domains, annual publication output and citations, countries and authors with the highest productivity, influential journals and articles, and popular keywords.ResultsIn total, 1529 publications were included in the final analysis. Health services and supportive care, pain and symptom management were the focus of the research in the field. From the year 2017 to 2021, the annual publication output was abundant and peaked in 2018. The systematic review by Fitzmaurice et al. in 2017 was the most-cited publication. The United States was the leading country with the maximum number of publications, citations, and link strengths with other countries. The most contributing institution was University of Toronto. E. Bruera was the most prolific author, ranking first among the authors in both the H and M index. The journal with the most publications was Palliative &amp; Supportive Care. Keywords analysis indicated that exploring the significant degree of palliative care to reduce anxiety and depression in breast cancer patients may be a good research direction. In addition, how to assess the optimal timing of palliative care interventions and further exploring the specific contradiction between insufficient medical resources and palliative care are also possible research directions.ConclusionPalliative care plays an important role in the treatment of breast cancer. With the help of a scientometric analysis in this field, researchers can clarify the current research status and hotspots worth fully exploring.
Developing mRNA signatures as a novel prognostic biomarker predicting high risk multiple myeloma
Authors: Wang Jing , Guo Lili , Lv Chenglan , Zhou Min , Wan Yuan 
Published: February 2023

BackgroundMultiple myeloma (MM) remains an essentially incurable disease. This study aimed to establish a predictive model for estimating prognosis in newly diagnosed MM based on gene expression profiles.MethodsRNA-seq data were downloaded from the Multiple Myeloma Research Foundation (MMRF) CoMMpass Study and the Genotype-Tissue Expression (GTEx) databases. Weighted gene coexpression network analysis (WGCNA) and protein-protein interaction network analysis were performed to identify hub genes. Enrichment analysis was also conducted. Patients were randomly split into training (70%) and validation (30%) datasets to build a prognostic scoring model based on the least absolute shrinkage and selection operator (LASSO). CIBERSORT was applied to estimate the proportion of 22 immune cells in the microenvironment. Drug sensitivity was analyzed using the OncoPredict algorithm.ResultsA total of 860 newly diagnosed MM samples and 444 normal counterparts were screened as the datasets. WGCNA was applied to analyze the RNA-seq data of 1589 intersecting genes between differentially expressed genes and prognostic genes. The blue module in the PPI networks was analyzed with Cytoscape, and 10 hub genes were identified using the MCODE plug-in. A three-gene (TTK, GINS1, and NCAPG) prognostic model was constructed. This risk model showed remarkable prognostic value. CIBERSORT assessment revealed the risk model to be correlated with activated memory CD4 T cells, M0 macrophages, M1 macrophages, eosinophils, activated dendritic cells, and activated mast cells. Furthermore, based on OncoPredict, high-risk MM patients were sensitive to eight drugs.ConclusionsWe identified and constructed a three-gene-based prognostic model, which may provide new and in-depth insights into the treatment of MM patients.