bluuebunny/crossref_metadata_2025_split huggingface dataset:
NOTCH1 mutation associates with impaired immune response and decreased relapse-free survival in patients with resected T1-2N0 laryngeal cancer
Authors: Gong Xiao-yang , Chen Hai-bin , Zhang Li-qing , Chen Dong-sheng , Li Wang , Chen Dong-hui , Xu Jin , Zhou Han , Zhao Le-le , Song Yun-jie , Xiao Ming-zhe , Deng Wang-long , Qi Chuang , Wang Xue-rong , Chen Xi 
Published: July 2022

BackgroundPatients with early-stage laryngeal cancer, even stage T1-2N0, are at considerable risk of recurrence and death. The genetic and immunologic characteristics of recurrent laryngeal cancer remain unclear.MethodsA total of 52 T1-2N0 laryngeal cancer patients were enrolled. Of these, 42 tissue samples were performed by targeted DNA sequencing, and 21 cases were performed by NanoString immuno-oncology targeted RNA sequencing to identify the distinct molecular bases and immunologic features associated with relapse in patients with early laryngeal cancer, respectively.ResultsTo the best to our knowledge, we present for the first time an overview of the genomic mutation spectrum of early-stage laryngeal cancers. A total of 469 genomic alterations were detected in 211 distinct cancer-relevant genes, and the genes found to be mutated in more than five patients (&gt;10%) included tumor protein p53 (TP53, 78.5%), FAT atypical cadherin 1 (FAT1, 26%), LDL receptor related protein 1B (LRP1B, 19%), cyclin dependent kinase inhibitor 2A (CDKN2A, 17%), tet methylcytosine dioxygenase 2 (TET2, 17%), notch receptor 1 (NOTCH1, 12%) and neuregulin 1 (NRG1, 12%). Recurrent laryngeal cancer demonstrated a higher tumor mutation burden (TMB), as well as higher LRP1B mutation and NOTCH1 mutation rates. Univariate and multivariate analyses revealed that high TMB (TMB-H) and NOTCH1 mutation are independent genetic factors that are significantly associated with shorter relapse-free survival (RFS). Simultaneously, the results of the transcriptome analysis presented recurrent tumors with NOTCH1 mutation displayed upregulation of the cell cycle pathway, along with decreased B cells score, T cells score, immune signature score and tumor-infiltrating lymphocytes (TILs) score. The Cancer Genome Atlas (TCGA)-laryngeal cancer dataset also revealed weakened immune response and impaired adhesion functions in NOTCH1-mutant patients.ConclusionsGenomic instability and impaired immune response are key features of the immunosurveillance escape and recurrence of early laryngeal cancer after surgery. These findings revealed immunophenotypic attenuation in recurrent tumors and provided valuable information for improving the management of these high-risk patients. Due to the small number of patients in this study, these differences need to be further validated in a larger cohort.
Prediction of Prognosis in Patients With Endometrial Carcinoma and Immune Microenvironment Estimation Based on Ferroptosis-Related Genes
Authors: Liu Shouze , Zhang Qianqian , Liu Wenhua , Huang Xianghua 
Published: July 2022

Background: Ferroptosis, a form of non-apoptotic cell death, has aroused worldwide interest in cancer researchers. However, the current study about the correlation between ferroptosis-related genes (FRGs) and endometrial cancer (EC) remains limited.Methods: First, the transcriptome profiling and clinical data of EC patients were downloaded from The Cancer Genome Atlas (TCGA) and Clinical Proteomic Tumor Analysis Consortium (CPTAC) program as the training group and testing group, respectively. FRGs were acquired through literature mining. Then, we used R 4.1.1 software to screen the differently expressed FRGs from TCGA, which was also connected with the prognosis of EC patients. Subsequently, the risk score of each tumor sample was identified by LASSO regression analysis, and we classified these samples into the high- and low-risk groups in the light of the median risk score. Receiver operating characteristic (ROC) curve analysis and Kaplan-Meier analysis were performed to assess the accuracy of this signature. Significantly, the data from CPTAC was used to validate the prediction model externally. Furthermore, we evaluated the immune microenvironment in this model via single-sample gene set enrichment analysis (ssGSEA).Results: Among the 150 FRGs, 6 differentially expressed genes (DEGs) based on TCGA had a relationship with the prognosis of EC patients, namely, TP53, AIFM2, ATG7, TLR4, PANX1 and MDM2. The survival curve indicated a higher survival probability in the low-risk group. Moreover, the FRGs-based signature acted well in the prediction of overall survival (OS). The results of external verification confirmed the prediction model we established. Finally, ssGSEA revealed significant differences in the abundance of 16 immune cells infiltration and the activity of 13 immune functions between different risk groups.Conclusion: We identified a novel ferroptosis-related gene signature which could concisely predict the prognosis and immunotherapy in EC patients.
Profiling morphologic MRI features of motor neuron disease caused by TARDBP mutations
Authors: Spinelli Edoardo Gioele , Ghirelli Alma , Riva Nilo , Canu Elisa , Castelnovo Veronica , Domi Teuta , Pozzi Laura , Carrera Paola , Silani Vincenzo , Chiò Adriano , Filippi Massimo , Agosta Federica 
Published: July 2022

ObjectiveMutations in the TARDBP gene are a rare cause of genetic motor neuron disease (MND). Morphologic MRI characteristics of MND patients carrying this mutation have been poorly described. Our objective was to investigate distinctive clinical and MRI features of a relatively large sample of MND patients carrying TARDBP mutations.MethodsEleven MND patients carrying a TARDBP mutation were enrolled. Eleven patients with sporadic MND (sMND) and no genetic mutations were also selected and individually matched by age, sex, clinical presentation and disease severity, along with 22 healthy controls. Patients underwent clinical and cognitive evaluations, as well as 3D T1-weighted and diffusion tensor (DT) MRI on a 3 Tesla scanner. Gray matter (GM) atrophy was first investigated at a whole-brain level using voxel-based morphometry (VBM). GM volumes and DT MRI metrics of the main white matter (WM) tracts were also obtained. Clinical, cognitive and MRI features were compared between groups.ResultsMND with TARDBP mutations was associated with all possible clinical phenotypes, including isolated upper/lower motor neuron involvement, with no predilection for bulbar or limb involvement at presentation. Greater impairment at naming tasks was found in TARDBP mutation carriers compared with sMND. VBM analysis showed significant atrophy of the right lateral parietal cortex in TARDBP patients, compared with controls. A distinctive reduction of GM volumes was found in the left precuneus and right angular gyrus of TARDBP patients compared to controls. WM microstructural damage of the corticospinal tract (CST) and inferior longitudinal fasciculi (ILF) was found in both sMND and TARDBP patients, compared with controls, although decreased fractional anisotropy of the right CST and increased axial diffusivity of the left ILF (p = 0.017) was detected only in TARDBP mutation carriers.ConclusionsTARDBP patients showed a distinctive parietal pattern of cortical atrophy and greater damage of motor and extra-motor WM tracts compared with controls, which sMND patients matched for disease severity and clinical presentation were lacking. Our findings suggest that TDP-43 pathology due to TARDBP mutations may cause deeper morphologic alterations in both GM and WM.
Research trends of the neuroimaging in aphasia: A bibliometric analysis and visualization analysis from 2004 to 2021
Authors: Huang Jiaqin , Cao Yun , Zhang Danli , Lei Xiaojing , Chang Jingling 
Published: July 2022

ObjectivesTo review the current research status of the neuroimaging of aphasia, and reveal the hotspots and frontiers of research in this field.MethodsWe searched articles related to the neuroimaging research on aphasia since Web of Science (WOS) database construction and extracted the data. CiteSpace and VOSviewer were used for the country/institution analysis, journal analysis, discipline analysis, burst keyword analysis and cited-reference cluster analysis.ResultsOf the studies retrieved from WOS, 2922 studies that related to the neuroimaging of aphasia were screened and finally included 2799 articles for research. The United States of America and University of California San Francisco were the main countries and institutions in this field. Brain had the highest impact factor in both published and cited journals. Through the discipline and topic analysis of this field, the most common category was Neurosciences and Neurology. The keyword with the strongest citation strength was “functional connectivity,” and the recent burst keywords were “functional connectivity” and “network.” The co-citation network showed seven clusters greater than 100. Among the top 5 clusters, the most recently formed cluster, Cluster #2 (progressive supranuclear palsy), had an average year of 2017. The literature in the top 5 clusters mainly focused on 3 aspects, specifically, the discovery of language processing models, injury and recovery mechanisms of post-stroke aphasia (PSA), and diagnosis of primary progressive aphasia (PPA) variants.ConclusionThe results of this bibliometric study revealed the following three research hotspots in the neuroimaging of aphasia: clarifying the connotation of the most recognized language processing model, the dual-stream model, exploring the injury mechanism based on the dual-stream model and the recovery mechanism involving the left and right hemispheres of PSA, and determining the diagnostic criteria for PPA variants. A major research trend is to combine new neuroimaging technology, such as PET tracer technology, to realize the visual presentation of disease-specific proteins to improve the pathological diagnostic criteria of PPA variants. Accordingly, a visualized analysis of literature that uses CiteSpace provides a more rapid, repeatable and flexible method, which is more conducive to capturing research hotspots and emerging trends.
Effects and Mechanisms of Acupuncture on Diarrhea-Predominant Irritable Bowel Syndrome: A Systematic Review
Authors: Zhang Gezhi , Zhang Tao , Cao Zeng , Tao Zijing , Wan Tianhao , Yao Mengxi , Su Xiaolan , Wei Wei 
Published: July 2022

BackgroundIrritable bowel syndrome (IBS) is a common disorder of gut-brain interaction with challenging treatment. According to evidence-based studies, acupuncture is likely to be a promising therapy and subservient adjunct for IBS. Mechanism study of acupuncture based on related clinical trials of high quality, nevertheless, is still vacant.AimThis study aims to assess the results and qualities of current clinical evidence and conclude the relevant pathophysiological mechanisms and therapeutic effects of acupuncture on IBS with diarrhea (IBS-D).MethodsLiterature from four databases, namely, PubMed, Cochrane Library, EMBASE, and Web of Science, was systematically searched to obtain eligible randomized controlled trials (RCTs), which contained mechanism research of acupuncture treatment in IBS-D patients. Two independent reviewers completed data extraction and quality evaluation using the RevMan 5.4.1 software.ResultsTen trials that covered 19 items related to mechanism research were included in this review. Acupuncture was reported to improve IBS-D symptoms and quality of life, with positive effects in regulating brain-gut peptides, cerebral activities, neuroendocrine functions, psychological state, and inflammatory GI and hypersensitive intestinal tracts.ConclusionAcupuncture has potential influence on pathophysiology alterations such as regulating brain-gut peptides, altering cerebral connectivity and activity, promoting neuroendocrine functions and mental state, and mitigating inflammation as well as hypersensitivity of bowels in IBS-D patients, but further studies of high quality are still necessary.Systematic Review Registration[https://www.crd.york.ac.uk/PROSPERO], identifier [CRD42022320331].
Evaluation of the Dangerous Decibels Brazil Program in Workers Exposed to Noise
Authors: Bramati Luciana , Marques Jair Mendes , Gonçalves Claudia Giglio Oliveira , Welch David , Reddy Ravi , Lacerda Adriana Bender de Moreira 
Published: July 2022

IntroductionNoise-induced hearing loss can be avoided by taking preventive measures.ObjectiveTo assess the effectiveness of the Brazilian version of the Dangerous Decibels® program for noise-exposed workers, using the ecological model as an educational intervention plan.MethodNon-randomized interventional study with a quantitative, experimental trial design, conducted at a meatpacking company. The participants were divided into two groups—the first one (n = 132, divided into 6 subgroups) received the Dangerous Decibels® Brazil educational intervention (DDBEI) adapted to workers while the second group (n = 138, divided into 5 subgroups) received a conventional educational intervention (CEI). The interventions lasted 50 min. The Hearing Protection Assessment Questionnaire (HPA-5) was administered before and after the interventions. The five dimensions (attitude, behavior, knowledge, supports, and barriers) were compared using the Student’s t-test for paired data (&lt;0.05).ResultsAfter both the DDBEI and CEI training, workers improved significantly in barriers, supports, knowledge, attitudes, and behavior around noise. By chance, the CEI group scored lower in all measures than the DDBEI group before training, and though both groups improved, the difference was maintained after training.ConclusionThe Brazilian version of the Dangerous Decibels® program for noise-exposed workers was effective, influencing positively the factors at different levels of the ecological model. Though the DDBEI was no more effective than the CEI, the CEI participants began at much lower levels, so the effectiveness of the DDBEI may have been underestimated.
Prognostic values of serum alkaline phosphatase and globulin levels in patients undergoing intravenous thrombolysis
Authors: Zhu Hong-Jing , Sun Xin , Guo Zhen-Ni , Qu Yang , Sun Ying-Ying , Jin Hang , Wang Mei-Qi , Xu Bao-Feng , Yang Yi 
Published: July 2022

BackgroundIn previous studies, alkaline phosphatase (ALP) level was a prognostic factor for patients with ischemic stroke, and globulin level was associated with hemorrhagic transformation (HT) after intravenous thrombolysis (IVT). However, the association between these serum biomarkers and prognosis in patients with acute ischemic stroke (AIS) who undergo IVT remains unclear. This study aimed to investigate the characteristics of serum ALP and globulin levels after IVT and to assess the relationship between these serum biomarkers and prognosis.Materials and methodsThis retrospective study used a prospectively collected database. We included patients with AIS who received recombinant tissue plasminogen activator (rt-PA) IVT. Demographic information, vascular risk factors, laboratory test results, and other stroke-related data were collected for analysis. Clinical outcomes included HT and 3-month poor outcome (modified Rankin Scale scores ≥ 2) after IVT. The association of ALP and globulin levels with HT and poor outcome was investigated using multivariate logistic regression analysis. An individualized prediction model based on ALP and globulin levels for functional outcomes was established.ResultsWe enrolled 750 patients in this study; 452 patients (60.3%) had poor outcome, and 117 patients (15.6%) had HT after IVT. After adjusting for all confounders, serum globulin level [OR = 1.055; 95% confidence intervals (CI): 1.006–1.107; P = 0.028] was independently associated with HT in patients with IVT. Serum ALP (OR = 1.009; 95% CI: 1.002–1.016; P = 0.010) and globulin levels (OR = 1.062; 95% CI: 1.020–1.107; P = 0.004) were associated with 3-month poor outcome in these patients. The constructed individualized prediction model for the 3-month poor outcome comprised the National Institutes of Health Stroke Scale (NIHSS) score, Trial of Org 10172 in Acute Stroke Treatment (TOAST), history of antihypertensive therapy, ALP and globulin levels. The area under the curve of the training and validation sets were 0.726 and 0.706, respectively, revealing that the model had good discriminating power. The P-values for the Hosmer-Lemeshow test in the training and validation sets were 0.978 and 0.148, respectively, indicating the model had good calibration.ConclusionThis study found that higher serum globulin levels were independently associated with HT. Additionally, higher serum ALP and globulin levels were independently associated with a poor outcome in patients after IVT.
Changes in serum angiogenic factors among patients with acute pain and subacute pain
Authors: Yang Xuewei , Yuan Chunmei , Wang Huanling , Wang Yunxia , Liu Mei , Li Zongjin , Zhang Jun 
Published: July 2022

Screening serum biomarkers for acute and subacute pain is important for precise pain management. This study aimed to examine serum levels of angiogenic factors in patients with acute and subacute pain as potential biomarkers. Serum samples were collected from 12 healthy controls, 20 patients with postherpetic neuralgia (PHN), 4 with low back pain (LBP), and 1 with trigeminal neuralgia (TN). Pain intensity in these patients was evaluated using the visual analog scale (VAS). The serum concentrations of 11 angiogenic biomarkers were examined by Milliplex Map Human Angiogenesis Magnetic Bead Panel 2. The pain assessment from VAS showed that all patients showed moderate and severe pain. Among 11 angiogenic factors, osteopontin (OPN), thrombospondin-2 (TSP-2), soluble platelet endothelial cell adhesion molecule-1 (sPECAM-1), soluble urokinase-type plasminogen activator receptor (suPAR), and soluble epidermal growth factor receptors (sErbB2) were up-regulated and soluble interleukin-6 receptor α (sIL-6Rα) were down-regulated in patients with pain compared to the healthy participants (all P-values were &lt; 0.005). Moreover, a linear regression model showed that the serum OPN concentration was correlated with pain intensity in patients with PHN (P = 0.03). There was no significant difference between the serum concentration of soluble epidermal growth factor receptors, sErbB3, soluble AXL, tenascin, and soluble neuropilin-1 in patients with acute and subacute pain and that of healthy controls. The results of this study provided new valuable insights into our understanding of angiogenic factors that may contribute to as mechanistic biomarkers of pain, and reveal the pathophysiological mechanism of pain.Clinical Trial Registration:www.chictr.org.cn, identifier ChiCTR2200061775.
Differentiation Between Granulomatous Lobular Mastitis and Breast Cancer Using Quantitative Parameters on Contrast-Enhanced Ultrasound
Authors: Yin Liang , Agyekum Enock Adjei , Zhang Qing , Pan Lei , Wu Ting , Xiao Xiudi , Qian Xiao-qin 
Published: July 2022

ObjectiveTo investigate the Contrast-enhanced ultrasound (CEUS) imaging characteristics of granulomatous lobular mastitis (GLM) and the value of differentiating GLM from breast cancer.Materials and methodsThe study included 30 women with GLM (mean age 36.7 ± 5 years [SD]) and 58 women with breast cancer (mean age 48. ± 8 years [SD]) who were scheduled for ultrasound-guided tissue biopsy. All patients were evaluated with conventional US and CEUS prior to the biopsy. In both groups, the parameters of the quantitative and qualitative analysis of the CEUS were recorded and compared. The receiver-operating-characteristics curves (ROC) were created. Sensitivity, specificity, cut-off, and area under the curve (AUC) values were calculated.ResultsTTP values in GLM were statistically higher than in breast cancer (mean, 27.63 ± 7.29 vs. 20.10 ± 6.11), but WIS values were lower (mean, 0.16 ± 0.05 vs. 0.28 ± 0.17). Rich vascularity was discovered in 54.45% of breast cancer patients, but only 30.00% of GLM patients had rich vascularity. The AUC for the ROC test was 0.791 and 0.807, respectively. The optimal cut-off value for TTP was 24.5s, and the WIS cut-off value was 0.185dB/s, yielding 73.33% sensitivity, 84.48% specificity, and 86.21% sensitivity, 70% specificity respectively in the diagnosis of GLM. The lesion scores reduced from 4 to 3 with the addition of CEUS for the patients with GLM. However, the scores did not change for the patients with breast cancer.ConclusionCEUS could help distinguish GLM from breast cancer by detecting higher TTP and WIS values, potentially influencing clinical decision-making for additional biopsies.
ELOVLs Predict Distinct Prognosis Value and Immunotherapy Efficacy In Patients With Hepatocellular Carcinoma
Authors: Zhang Yu , Pang Shujie , Sun Bo , Zhang Minbo , Jiao Xiaoxiao , Lai Linying , Qian Yiting , Yang Ning , Yang Wenzhuo 
Published: July 2022

BackgroundHepatocellular carcinoma (HCC) is a primary malignancy of the liver with high prevalence worldwide and poor prognosis. It has been verified that elongation of very-long-chain fatty acids gene family (ELOVLs), a group of genes that responsible for elongation of saturated and polyunsaturated fatty acids, participate in the pathogenesis and development of multiplex disease including cancers. However, the functions and prognosis of ELOVLs in HCC are still indistinguishable.MethodsFirst, we searched the mRNA expression and survival data of ELOVLs in patients with HCC via the data of The Cancer Genome Atlas (TCGA). The prognosis value of ELOVLs on HCC was assessed by Kaplan–Meier plotter and Cox regression analysis. reverse transcription quantitative- polymerase chain reaction (RT-qPCR), Western blot (WB), and immunohistochemistry were applied to assess the specific mRNA and protein expression of ELOVLs in HCC clinical specimens of our cohort. Then, the functional enrichment of ELOVL1 especially the pathways relating to the immune was conducted utilizing the Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) analysis. Additionally, TIMER, CIBERSOR, and tumor immune dysfunction and exclusion (TIDE) were employed to evaluate the relationship between ELOVL1 and immune responses. Last, the correlation of ELOVL1 with genome heterogeneity [microsatellite instability (MSI), tumor mutational burden (TMB), mutant-allele tumor heterogeneity (MATH), homologous recombination deficiency (HRD), purity, ploidy, loss of heterozygosity (LOH), and neoantigens] and mutational landscape were also evaluated basing on the date in TCGA.ResultsSignificant expression alteration was observed in ELOVLs family at the pan-cancer level. In liver cancer, ELOVL1 and ELOVL3 were strongly associated with poor prognosis of HCC by survival analysis and differential expression analysis. Immunohistochemistry microarray, WB, and RT-qPCR confirmed that ELOVL1 but not ELOVL3 played an important role in HCC. Mechanistically, functional network analysis revealed that ELOVL1 might be involved in the immune response. ELOVL1 could affect immune cell infiltration and immune checkpoint markers such as PD-1 and CTLA4 in HCC. Meanwhile, high expression of ELOVL1 would be insensitive to immunotherapy. Correlation analysis of immunotherapy markers showed that ELOVL1 has been associated with MSI, TMB, and oncogene mutations such as TP53.ConclusionELOVLs play distinct prognostic value in HCC. ELOVL1 could predict the poor prognosis and might be a potential indicator of immunotherapy efficacy in HCC patients.