bluuebunny/crossref_metadata_2025_split huggingface dataset:
Automated Quantification of Brain Lesion Volume From Post-trauma MR Diffusion-Weighted Images
Authors: Mistral Thomas , Roca Pauline , Maggia Christophe , Tucholka Alan , Forbes Florence , Doyle Senan , Krainik Alexandre , Galanaud Damien , Schmitt Emmanuelle , Kremer Stéphane , Kastler Adrian , Troprès Irène , Barbier Emmanuel L. , Payen Jean-François , Dojat Michel 
Published: February 2022

ObjectivesDetermining the volume of brain lesions after trauma is challenging. Manual delineation is observer-dependent and time-consuming and cannot therefore be used in routine practice. The study aimed to evaluate the feasibility of an automated atlas-based quantification procedure (AQP) based on the detection of abnormal mean diffusivity (MD) values computed from diffusion-weighted MR images.MethodsThe performance of AQP was measured against manual delineation consensus by independent raters in two series of experiments based on: (i) realistic trauma phantoms (n = 5) where low and high MD values were assigned to healthy brain images according to the intensity, form and location of lesion observed in real TBI cases; (ii) severe TBI patients (n = 12 patients) who underwent MR imaging within 10 days after injury.ResultsIn realistic TBI phantoms, no statistical differences in Dice similarity coefficient, precision and brain lesion volumes were found between AQP, the rater consensus and the ground truth lesion delineations. Similar findings were obtained when comparing AQP and manual annotations for TBI patients. The intra-class correlation coefficient between AQP and manual delineation was 0.70 in realistic phantoms and 0.92 in TBI patients. The volume of brain lesions detected in TBI patients was 59 ml (19–84 ml) (median; 25–75th centiles).ConclusionsOur results support the feasibility of using an automated quantification procedure to determine, with similar accuracy to manual delineation, the volume of low and high MD brain lesions after trauma, and thus allow the determination of the type and volume of edematous brain lesions. This approach had comparable performance with manual delineation by a panel of experts. It will be tested in a large cohort of patients enrolled in the multicenter OxyTC trial (NCT02754063).
Diagnostic Impact of Monitoring Visual Evoked Potentials to Prevent Visual Complications During Endovascular Treatment for Intracranial Aneurysm
Authors: Nakagawa Ichiro , Park HunSoo , Kotsugi Masashi , Yokoyama Shohei , Omoto Kouji , Myochin Kaoru , Takeshima Yasuhiro , Matsuda Ryosuke , Nishimura Fumihiko , Yamada Shuichi , Takatani Tsunenori , Nakase Hiroyuki 
Published: February 2022

IntroductionThe present study aimed to determine the incidence of intraprocedural visual-evoked potential (VEP) changes and to identify correlations with intraprocedural ischemic complications during endovascular treatment in patients with intracranial aneurysm related to visual function.MethodsThis study analyzed data from 104 consecutive patients who underwent endovascular coil embolization to treat intracranial aneurysms related to visual function under VEP and transcranial motor evoked potential (MEP) monitoring. We analyzed associations between significant changes in MEP and VEP, defined as a &gt;50% decrease in amplitude, and both intraprocedural complications and postoperative neurological deficits. Factors associated with postoperative neurological deficits were also assessed.ResultsTreated aneurysms were predominantly located in the internal carotid artery (95%). Five (5%) were located in the posterior cerebral artery (PCA). Significant decreases in intraprocedural VEP occurred in four patients (4%), although one of those four patients did not show concomitant MEP decreases during procedures. Immediate salvage procedures avoided postoperative visual disturbances. All VEP decreases were transient and not associated with postoperative visual impairment. One of three cases who underwent intraoperative balloon occlusion test showed tolerance to balloon occlusion of the proximal PCA under VEP assessment; parent artery occlusion was performed without postoperative visual disturbance in that case.ConclusionAlthough significant VEP decreases occurred 4% during neuro-endovascular aneurysm treatment related to visual function, intraprocedural VEP monitoring identifies ischemic changes associated with visual pathways and facilitates prompt initiation of salvage procedures.
Long-Term Deutetrabenazine Treatment for Tardive Dyskinesia Is Associated With Sustained Benefits and Safety: A 3-Year, Open-Label Extension Study
Authors: Hauser Robert A. , Barkay Hadas , Fernandez Hubert H. , Factor Stewart A. , Jimenez-Shahed Joohi , Gross Nicholas , Marinelli Leslie , Wilhelm Amanda , Alexander Jessica , Gordon Mark Forrest , Savola Juha-Matti , Anderson Karen E. 
Published: February 2022

BackgroundDeutetrabenazine is a vesicular monoamine transporter 2 inhibitor approved for the treatment of tardive dyskinesia (TD) in adults. In two 12-week pivotal studies, deutetrabenazine demonstrated statistically significant improvements in Abnormal Involuntary Movement Scale (AIMS) scores, with favorable safety/tolerability in TD patients. This study reports long-term efficacy and safety of deutetrabenazine in a 3-year, single-arm, open-label extension (OLE) study.MethodsPatients who completed the pivotal studies could enroll in this single-arm OLE study, titrating up to 48 mg/day based on dyskinesia control and tolerability. Efficacy was assessed based on change from baseline in total motor AIMS score, Clinical Global Impression of Change (CGIC) and Patient Global Impression of Change (PGIC), and quality of life (QOL) assessments. Safety evaluation included adverse event (AE) incidence, reported using exposure-adjusted incidence rates, and safety scales.Results343 patients enrolled in the study (6 patients were excluded). At Week 145 (mean dose: 39.4 ± 0.83 mg/day), mean ± SE change from baseline in total motor AIMS score was −6.6 ± 0.37 and 67% of patients achieved ≥50% improvement in total motor AIMS score. Based on CGIC and PGIC, 73% and 63% of patients achieved treatment success, respectively. QOL improvements were also observed. Deutetrabenazine was generally well tolerated, with low rates of mild-to-moderate AEs and no new safety signals; most safety scales remained unchanged over time.ConclusionsLong-term deutetrabenazine treatment was associated with sustained improvement in AIMS scores, indicative of clinically meaningful long-term benefit, and was generally well tolerated. Results suggest deutetrabenazine may provide increasing benefit over time without increases in dose.
Up-Regulated Expression of Interferon-Gamma, Interleukin-6 and Tumor Necrosis Factor-Alpha in the Endolymphatic Sac of Meniere's Disease Suggesting the Local Inflammatory Response Underlies the Mechanism of This Disease
Authors: Huang Chao , Wang Qin , Pan Xueying , Li Wei , Liu Wei , Jiang Wenqi , Huang Li , Peng Anquan , Zhang Zhiwen 
Published: February 2022

BackgroundImmune mediated inflammatory changes affecting the endolymphatic sac (ES) may underlie the pathology of Meniere's disease (MD). The aim of the present study was to explore the differentially expressed cytokines in ES luminal fluid (ELF) of patients with MD, and the correlation between the expression of cytokines in the ELF with that in the serum was determined by quantitatively analyzing the cytokines in human ELF and serum.MethodsHuman ELF, serum and ES tissues were collected from patients with unilateral MD and patients with acoustic neuroma (AN) during surgery. The Simoa Cytokine 6-Plex Panel kit was used to analyze the levels of cytokines in the ELF and blood samples of the patients. Immunohistochemistry and immunofluorescence were subsequently used to validate the relative expression levels of the cytokines in MD.ResultsSignificant differences were identified in the expression levels of interferon-γ (IFN-γ) (P &lt; 0.001), interleukin (IL)-6 (P = 0.008) and tumor necrosis factor-α (TNF-α) (P = 0.036) in the luminal fluid of the ES comparing between the MD and AN groups. By contrast, the levels of IFN-γ, IL-10, IL-12p70, IL-17A, IL-6 and TNF-α in the serum of the MD group were not significantly different from those of either the AN group or healthy control subjects. In addition, no significant correlations in the expression levels of cytokines compared between the ELF and serum were found for the patients in either the MD or the AN group. Finally, the detection of positive expression of TNF-α, IL-6 and IFN-γ in the epithelial cells of the majority of ES specimens from patients with MD confirmed the up-regulated expression of these cytokines in the ES of patients with MD.ConclusionsThe identification of up-regulated expression levels of TNF-α, IL-6 and IFN-γ in the ELF in the present study has provided direct evidence for an increased immunologic activity in the microenvironment of the ES in patients with unilateral MD, may suggest the local inflammatory response underlies the mechanism of this disease.
Altered Brain Morphometry in Cerebral Small Vessel Disease With Cerebral Microbleeds: An Investigation Combining Univariate and Multivariate Pattern Analyses
Authors: Li Jing , Wen Hongwei , Wang Shengpei , Che Yena , Zhang Nan , Guo Lingfei 
Published: February 2022

PurposeThe objective of this study was to evaluate whether altered gray matter volume (GMV) and white matter volume (WMV) are associated with the presence of cerebral microbleeds (CMBs) in cerebral small vessel disease (CSVD).Materials and MethodsIn this study, we included 26 CSVD patients with CMBs (CSVD-c), 43 CSVD patients without CMBs (CSVD-n) and 39 healthy controls. All participants underwent cognitive assessment testing. Both univariate analysis and multivariate pattern analysis (MVPA) approaches were applied to investigate differences in brain morphometry among groups.ResultsIn univariate analysis, GMV and WMV differences were compared among groups using voxel-based morphometry (VBM) with diffeomorphic anatomical registration through exponentiated lie algebra (DARTEL). Compared to healthy controls, the CSVD-c group and CSVD-n group showed significantly lower GMV than the control group in similar brain clusters, mainly including the right superior frontal gyrus (medial orbital), left anterior cingulate gyrus, right inferior frontal gyrus (triangular part) and left superior frontal gyrus (medial), while the CSVD-n group also showed significantly lower WMV in the cluster of the left superior frontal gyrus (medial). No significant GMV or WMV differences were found between the CSVD-c group and the CSVD-n group. Specifically, we applied the multiple kernel learning (MKL) technique in MVPA to combine GMV and WMV features, yielding an average of &gt;80% accuracy for three binary classification problems, which was a considerable improvement over the individual modality approach. Consistent with the univariate analysis, the MKL weight maps revealed default mode network and subcortical region damage associated with CSVD compared to controls. On the other hand, when classifying the CSVD-c group and CSVD-n group in the MVPA analysis, we found that some WMVs were highly weighted regions (left olfactory cortex and right middle frontal gyrus), which hinted at the presence of different white matter alterations in the CSVD-c group.ConclusionOur findings not only suggested that the localized alterations in GMV and WMV appeared to be associated with the pathophysiology of CSVD but also indicated that altered brain morphometry could be a potential discriminative pattern to detect CSVD at the individual level.
Application of Three-Dimensional Pseudocontinuous Arterial Spin Labeling Perfusion Imaging in the Brains of Children With Autism
Authors: Tang Shilong , Liu Xianfan , Ran Qiying , Nie Lisha , Wu Lan , Pan Zhengxia , He Ling 
Published: February 2022

ObjectiveTo explore the application of three-dimensional pseudocontinuous arterial spin labeling (3D-PCASL) perfusion imaging in the brains of children with autism and to understand the characteristics of cerebral blood perfusion in children with autism.MethodsA total of 320 children with autism (160 men and 160 women) aged between 2 and 18 years and 320 age- and sex-matched healthy children participated in the study. All children were scanned by 3.0 T magnetic resonance axial T1 fluid-attenuated inversion recovery (FLAIR), T2 FLAIR, 3D-T1, and 3D-PCASL sequences. After postprocessing, cerebral blood flow (CBF) values in each brain region of children with autism and healthy children at the same age were compared and analyzed. Furthermore, CBF characteristics in each brain region of autistic children at various ages were determined.ResultsThe CBF values of the frontal lobe, hippocampus, temporal lobe, and caudate nucleus of children with autism are lower than those of healthy children (P &lt; 0.05). Additionally, as the ages of children with autism increase, the number of brain regions with decreased CBF values gradually increases. A receiver operating characteristic (ROC) analysis results show that the CBF values of the frontal lobe, hippocampus, temporal lobe, and caudate nucleus can distinguish children with autism [area under the ROC curve (AUC) &gt; 0.05, P &lt; 0.05].ConclusionThe 3D-PCASL shows lower brain CBF values in children with autism.Clinical Trial Registrationwww.ClinicalTrials.gov, identifier: ChiCTR2000034356.
DNA Methylation Markers and Prediction Model for Depression and Their Contribution for Breast Cancer Risk
Authors: Wang Ning , Sun Jing , Pang Tao , Zheng Haohao , Liang Fengji , He Xiayue , Tang Danian , Yu Tao , Xiong Jianghui , Chang Suhua 
Published: February 2022

BackgroundMajor depressive disorder (MDD) has become a leading cause of disability worldwide. However, the diagnosis of the disorder is dependent on clinical experience and inventory. At present, there are no reliable biomarkers to help with diagnosis and treatment. DNA methylation patterns may be a promising approach for elucidating the etiology of MDD and predicting patient susceptibility. Our overarching aim was to identify biomarkers based on DNA methylation, and then use it to propose a methylation prediction score for MDD, which we hope will help us evaluate the risk of breast cancer.MethodsMethylation data from 533 samples were extracted from the Gene Expression Omnibus (GEO) database, of which, 324 individuals were diagnosed with MDD. Statistical difference of DNA Methylation between Promoter and Other body region (SIMPO) score for each gene was calculated based on the DNA methylation data. Based on SIMPO scores, we selected the top genes that showed a correlation with MDD in random resampling, then proposed a methylation-derived Depression Index (mDI) by combining the SIMPO of the selected genes to predict MDD. A validation analysis was then performed using additional DNA methylation data from 194 samples extracted from the GEO database. Furthermore, we applied the mDI to construct a prediction model for the risk of breast cancer using stepwise regression and random forest methods.ResultsThe optimal mDI was derived from 426 genes, which included 245 positive and 181 negative correlations. It was constructed to predict MDD with high predictive power (AUC of 0.88) in the discovery dataset. In addition, we observed moderate power for mDI in the validation dataset with an OR of 1.79. Biological function assessment of the 426 genes showed that they were functionally enriched in Eph Ephrin signaling and beta-catenin Wnt signaling pathways. The mDI was then used to construct a predictive model for breast cancer that had an AUC ranging from 0.70 to 0.67.ConclusionOur results indicated that DNA methylation could help to explain the pathogenesis of MDD and assist with its diagnosis.
Tspan9 Induces EMT and Promotes Osteosarcoma Metastasis via Activating FAK-Ras-ERK1/2 Pathway
Authors: Shao Shijie , Piao Lianhua , Wang Jiangsong , Guo Liwei , Wang Jiawen , Wang Luhui , Tong Lei , Yuan Xiaofeng , Han Xu , Fang Sheng , Zhu Junke , Wang Yimin 
Published: February 2022

ObjectAt present, there are few effective treatment options available to patients suffering from osteosarcoma (OS). Clarifying the signaling pathways that govern OS oncogenesis may highlight novel approaches to treating this deadly form of cancer. Recent experimental evidence suggests that the transmembrane protein tetraspanin-9 (Tspan9) plays a role in tumor development. This study was thus formulated to assess the molecular role of Tspan9 as a regulator of OS cell metastasis.MethodsGene expression in OS cell lines was evaluated via qRT-PCR, while CCK-8, colony formation, Transwell, and wound healing assays were used to explore the in vitro proliferative, invasive, and migratory activities of OS cells. The relationship between Tspan9 and in vivo OS cell metastasis was assessed by injecting these cells into the tail vein of nude mice. Interactions between the Tspan9 and integrin β1 proteins were explored through mass spectrometric and co-immunoprecipitation, and Western blotting to assess the functional mechanisms whereby Tspan9 shapes OS pathogenesis.ResultsBoth primary OS tumors and OS cell lines commonly exhibited Tspan9 upregulation, and the knockdown of this tetraspanin suppressed the migration, invasion, and epithelial-mesenchymal transition (EMT) activity in OS cells, whereas Tspan9 overexpression resulted in opposite phenotypes. Tumor lung metastasis were significantly impaired in mice implanted with HOS cells in which Tspan9 was downregulated as compared to mice implanted with control HOS cells. Tspan9 was also found to interact with β1 integrin and to contribute to OS metastasis via the amplification of integrin-mediated downstream FAK/Ras/ERK1/2 signaling pathway.ConclusionThese data suggest that Tspan9 can serve as a promising therapeutic target in OS.
Transcriptional Expressions of ALDH1A1/B1 as Independent Indicators for the Survival of Thyroid Cancer Patients
Authors: Cui Ying , Liu Yao , Mu Lan , Li Yang , Wu Gang 
Published: February 2022

BackgroundAldehyde dehydrogenase (ALDH) 1 is an important enzyme involved in the regulation of several cellular mechanisms via aldehyde detoxification. High ALDH1 levels were correlated with tumorigenesis and stemness maintenance in cancer.MethodsWe used UALCAN, Human Protein Atlas, Kaplan–Meier plotter, TISIDB, TIMER, and KOBAS databases to investigate the expression and role of ALDH1 in thyroid cancer progression. In addition, quantitative real-time polymerase chain reaction was performed to detect the expression of the target genes in thyroid cancer cell lines and cancer tissues.ResultsExpression of ALDH1A1/B1 was significantly decreased based on individual cancer stages and tumor histology, and high levels of ALDH1A1/B1 were associated with poor overall survival in thyroid cancer patients. Moreover, ALDH1A1/B1 expression was negatively correlated with immune-stimulating genes, major histocompatibility complex, chemokines, and receptors.ConclusionsThese results suggest that ALDH1A1/B1 might serve as potential prognostic biomarkers for thyroid cancer diagnosis.
NCAPG as a Novel Prognostic Biomarker in Glioma
Authors: Jiang Xiulin , Shi Yulin , Chen Xi , Xu Haitao , Liu Bohu , Zhou Fan , Huang Xiaobin , Cho William C. , Li Lihua , Pu Jun 
Published: February 2022

BackgroundNon-SMC condensin I complex subunit G (NCAPG) is expressed in various human cancers, including gliomas. However, its biological function in glioma remains unclear. The present study was designed to determine the biological functions of NCAPG in glioma and to evaluate the association of NCAPG expression with glioma progression.MethodsClinical data on patients with glioma were obtained from The Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA), the Gene Expression Omnibus (GEO), and the Rembrandt and Gravendeel databases. The correlations among NCAPG expression, pathological characteristics, and clinical outcome were evaluated. In addition, the correlations of NCAPG expression with immune cell infiltration and glioma progression were analyzed.ResultsNCAPG expression was higher in gliomas than in adjacent normal tissues. Higher expression of NCAPG in gliomas correlated with poorer prognosis, unfavorable histological features, absence of mutations in the isocitrate dehydrogenase gene (IDH), absence of chromosome 1p and 19q deletions, and responses to chemoradiotherapy. Univariate and multivariate Cox analysis demonstrated, in addition to patient age, tumor grade, absence of IDH mutations, and absence of chromosome 1p and 19q deletions, NCAPG expression was independently prognostic of overall survival, disease-free survival, and progression-free survival in patients with glioma. In addition, high expression of NCAPG correlated with tumor infiltration of B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and dendritic cells. Gene set enrichment analysis (GSEA) indicated that high NCAPG expression was associated with cell proliferation and immune response-related signaling pathways. NCAPG knockdown in glioma cell lines significantly reduced cell survival, proliferation, and migration.ConclusionNCAPG expression correlates with glioma progression and immune cell infiltration, suggesting that NCAPG expression may be a useful prognostic biomarker for glioma.
Prognostic Significance of Galectin-1 but Not Galectin-3 in Patients With Lung Adenocarcinoma After Radiation Therapy
Authors: Huang Chun-Chieh , Chuang I-Chieh , Su Yu-Li , Luo Hao-Lun , Chang Ya-Chun , Chen Jo-Ying , Hsiao Chang-Chun , Huang Eng-Yen 
Published: February 2022

IntroductionTo investigate the role of tumor galectin-1 and galectin-3 in patients with lung adenocarcinoma after definitive radiation therapy.MethodsA total of 41 patients with localized lung adenocarcinoma undergoing thoracic radiation therapy without concurrent chemotherapy were enrolled. Their paraffin-embedded lung tissues were sent for immunohistochemical staining for galectin-1 and galectin-3. The clinical treatment outcomes, including overall (OS), locoregional progression-free (LRPFS), and distant metastasis-free (DMFS) survivals, were evaluated. Univariable and multivariable Cox regression analyses were applied.ResultsOverexpression of tumor galectin-1 and galectin-3 were found in 26.8% and 19.5% of patients, respectively. Overexpression of tumor galectin-1 was the most significant prognosticator to predict worse LRPFS in both univariable (p = 0.007) and multivariable analyses (p = 0.022). Besides, patients with overexpression of tumor galectin-1 had a trend of worse OS (p = 0.066) than those with low expression in multivariable analysis, and worse DMFS (p = 0.035) in univariable analysis. The overexpression of tumor galectin-3 had no significant effect on survival outcomes.ConclusionsThe overexpression of tumor galectin-1, but not galectin-3, is associated with poor LRPFS of patients with lung adenocarcinoma after thoracic radiation therapy. Future research on the mechanism of galectin-1 affecting radiation response in lung adenocarcinoma may be worth exploring.