bluuebunny/crossref_metadata_2025_split huggingface dataset:
Empty Sella Syndrome as a Window Into the Neuroprotective Effects of Prolactin
Authors: Paul David A. , Strawderman Emma , Rodriguez Alejandra , Hoang Ricky , Schneider Colleen L. , Haber Sam , Chernoff Benjamin L. , Shafiq Ismat , Williams Zoë R. , Vates G. Edward , Mahon Bradford Z. 
Published: July 2021

Background: The goal of this study was to relate diffusion MR measures of white matter integrity of the retinofugal visual pathway with prolactin levels in a patient with downward herniation of the optic chiasm secondary to medical treatment of a prolactinoma.Methods: A 36-year-old woman with a prolactinoma presented with progressive bilateral visual field defects 9 years after initial diagnosis and medical treatment. She was diagnosed with empty-sella syndrome and instructed to stop cabergoline. Hormone testing was conducted in tandem with routine clinical evaluations over 1 year and the patient was followed with diffusion magnetic resonance imaging (dMRI), optical coherence tomography (OCT), and automated perimetry at three time points. Five healthy controls underwent a complementary battery of clinical and neuroimaging tests at a single time point.Results: Shortly after discontinuing cabergoline, diffusion metrics in the optic tracts were within the range of values observed in healthy controls. However, following a brief period where the patient resumed cabergoline (of her own volition), there was a decrease in serum prolactin with a corresponding decrease in visual ability and increase in radial diffusivity (p &lt; 0.001). Those measures again returned to their baseline ranges after discontinuing cabergoline a second time.Conclusions: These results demonstrate the sensitivity of dMRI to detect rapid and functionally significant microstructural changes in white matter tracts secondary to alterations in serum prolactin levels. The inverse relations between prolactin and measures of white matter integrity and visual function are consistent with the hypothesis that prolactin can play a neuroprotective role in the injured nervous system.
Change of Retinal Vessels in Different Sectors of the Parapapillary Area in Primary Open-Angle Glaucoma
Authors: Cheng Jingyi , Zhao Hongmei , Jiang Chunhui , Kong Xiangmei , Sun Xinghuai 
Published: July 2021

Purpose: To investigate the changes in the retinal vessels (RVs) in different sectors in patients with primary open-angle glaucoma (POAG), and their possible correlations with retinal nerve fiber layer thickness (RNFLT) and visual-field defects in the temporal parapapillary region.Methods: The RV diameters, RNFLTs, and visual-field parameters were measured. The temporal parapapillary region was divided into the temporal (T, 315°-45°), temporal superior (TS, 45°-90°), and temporal inferior sectors (TI, 270°-315°). The changes in the RV diameters in each sector were determined, and their relationships with RNFLT, the mean deviation (MD), and visual field sensitivity (VFS) were examined.Results: Fifty POAG patients (50 eyes) and 50 healthy subjects (50 eyes) were included. Compared with the healthy subjects, the POAG group had a significantly smaller accumulated parapapillary RV diameter (P &lt; 0.001), which was positively correlated with the MD and RNFLT. When the different temporal sectors were examined, the accumulated RV diameters were significantly smaller in the POAG group than in the healthy controls in the TI and T sectors, but not in the TS sector. The accumulated diameters in the TI and T sectors were correlated with the corresponding RNFLTs (all P &lt; 0.05), but only the accumulated diameter in the TI sector was correlated with the VFS.Conclusions: In POAG, the changes in the RVs differed between different temporal sectors, with the most prominent changes occurring in the TI and T sectors.
The Role of TRPC6 in Renal Ischemia/Reperfusion and Cellular Hypoxia/Reoxygenation Injuries
Authors: Hou Xin , Huang Mengjun , Zeng Xixi , Zhang Yanhong , Sun Anbang , Wu Qifang , Zhu Lin , Zhao Hu , Liao Yanhong 
Published: July 2021

Renal ischemia/reperfusion (I/R), a major cause of acute kidney injury (AKI), is a serious clinical event in patients during post-renal transplantation. I/R is associated with renal dysfunction and tubular apoptosis, and calcium (Ca2+) overload has been reported to be a crucial factor on tubular apoptosis in I/R injury (IRI). The canonical transient receptor potential channel 6 (TRPC6), a type of non-selective Ca2+ channel, is involved in many renal diseases. Our earlier study identified that TRPC6-mediated Ca2+ influx plays a novel role in suppressing cytoprotective autophagy triggered by oxidative stress in primary tubular epithelial cells (TECs). This study explored the potential beneficial impact of TRPC6 knockout (TRPC6−/−) and the relevant cellular mechanisms against I/R-induced AKI in mice. Measuring changes of renal function, apoptotic index, and autophagy in mouse kidneys that suffered 24 h reperfusion after 40 min ischemia and working in vitro with TECs that suffered 24 h reoxygenation after 24 h hypoxia, we found that 1) IRI tissues had increased TRPC6 expression and TRPC6 knockout significantly ameliorated renal damage induced by IRI; 2) TRPC6 knockout enhanced the level of autophagy and alleviated the depolarization of mitochondrial membrane potential (ψm, MMP) and apoptotic changes upon IRI; and 3) IRI tissues had increased p-AKT and p-ERK1/2 expressions, while TRPC6 knockout could markedly reduce the phosphorylation of AKT and ERK1/2. These discoveries suggest that, by reducing Ca2+ overload, the underlying protective mechanism of TRPC6−/− may be involved in down-regulation of PI3K/AKT and ERK signaling, which is likely to provide a new avenue for future AKI therapies.
Expression of TCF7L2 in Glioma and Its Relationship With Clinicopathological Characteristics and Patient Overall Survival
Authors: Jing Shiyuan , Chen Lei , Han Song , Liu Ning , Han MingYang , Yang Yakun , Yan Changxiang 
Published: July 2021

Background: The TCF7L2 gene is known as transcription factor 7-like 2 which has been identified as a novel transcription factor epithelial-mesenchymal transition (EMT) in tumor cells at 10q25.3. TCF7L2 may affect cancer progression and plays a central role in cancer proliferation, migration, and invasion. However, its clinical and prognostic value have not been researched in glioma. The purpose of our study was to research TCF7L2 expression and evaluate the clinical value of prognosis.Method: We collected glioma specimens including low-grade glioma (n = 46) and glioblastoma (n = 51) from September 2015 to September 2017. Expression of TCF7L2 in 97 specimens was detected by quantitative real-time PCR (qRT-PCR). The chi-square test was applied to analyze the relationship between TCF7L2 expression and clinicopathological characteristics. The overall survival (OS) was estimated by log-rank tests among strata, and the survival curves were drawn by Kaplan-Meier. Univariate and multivariate analysis were utilized to analyze the relationship between prognosis and clinicopathological characteristics including TCF7L2 expression.Results: Compared with the low-grade glioma group, the expression of TCF7L2 was significantly increased in the glioblastoma group (p = 0.001). TCF7L2 overexpression was associated with higher WHO grade (p = 0.001), isocitrate dehydrogenase (IDH) wild-type (p = 0.001), and lack of O(6)-methylguanine-DNA methyltransferase (MGMT) methylation (p = 0.001). Moreover, Kaplan-Meier analysis proved that overexpressed TCF7L2 was associated with poor OS (p = 0.010). The multivariate analysis suggested that TCF7L2 expression was an independent prognostic factor (p = 0.020).Conclusions: Our research proved that TCF7L2 was overexpressed in glioblastoma, and related with tumor long-term prognosis, which, therefore, could be an independent prognostic factor for glioma patients.
Perampanel and Visuospatial Skills in Children With Epilepsy
Authors: Operto Francesca Felicia , Vivenzio Valentina , Scuoppo Chiara , Padovano Chiara , Roccella Michele , Quatrosi Giuseppe , Pastorino Grazia Maria Giovanna 
Published: July 2021

Introduction: Perampanel (PER) is a non-competitive AMPA glutamate receptor antagonist approved for focal and generalized seizures as add-on therapy. PER does not seem to negatively affect the cognitive profile in children and adolescents, but its influence on visuospatial abilities is still to be assessed. The aim of our study was to assess visuospatial skills through a standardized neuropsychological evaluation in adolescents taking PER for 12 months.Methods: Our sample included 46 adolescents aged 12–18 years with focal and generalized drug-resistant epilepsy already in therapy with one or two antiseizure medications. Changes in visuospatial perception and memory were assessed by the Rey–Osterrieth Complex Figure Test at baseline (before taking PER) and after 12 months of pharmacological treatment. Executive functions and non-verbal intelligence were also assessed at baseline.Results: After 12 months of PER therapy, the mean scores on the Rey–Osterrieth Complex Figure Test remained almost unchanged for both visuospatial perception and visuospatial memory skills. At baseline, visuospatial memory was related to executive function, and visuospatial perception was related to executive function and non-verbal intelligence.Conclusions: Adjunctive treatment with PER did not negatively affect visuospatial skills. No adverse event effects have been reported after 12 months of follow-up, and this suggests a good tolerability in the middle-to-long term.
Altered Gray Matter Volume and Functional Connectivity in Patients With Vestibular Migraine
Authors: Zhe Xia , Zhang Xiaoling , Chen Li , Zhang Li , Tang Min , Zhang Dongsheng , Li Longchao , Lei Xiaoyan , Jin Chenwang 
Published: July 2021

SubjectsVestibular migraine (VM) is the most common neurological cause of vertigo in adults. Previous neuroimaging studies have reported structural alterations in areas associated with pain and vestibular processing. However, it is unclear whether altered resting-state functional connectivity (FC) exists in brain regions with structural abnormalities in patients with VM.MethodsResting-state functional magnetic resonance imaging (MRI) and three-dimensional T1-weighed MRI were performed in 30 patients with VM and 30 healthy controls (HCs). Patients underwent an evaluation of migraine and dizziness severity. FC and voxel-based morphometry (VBM) were performed using DPABI 4.3 and CAT12, respectively. The association between changes in gray matter (GM) volume or FC and clinical parameters was also analyzed.ResultsCompared with HCs, patients with VM demonstrated a reduced GM volume in the bilateral parietoinsular vestibular cortex (PIVC), right middle frontal gyrus, and precuneus. The GM volume of the left PIVC was negatively associated with Dizziness Handicap Inventory score in patients with VM. Taking this region as a seed region, we further observed increased FC between the left primary somatosensory cortex (S1)/inferior parietal lobule (IPL) and the left PIVC in patients with VM.ConclusionFC between regions with a decline in GM volume (the PIVC and S1/IPL) is altered in patients with VM, suggesting that abnormalities in vestibular cortical network could be useful for understanding the underlying mechanisms of VM.
Estimating the Minimal Number of Repeated Examinations for Random Responsiveness With the Coma Recovery Scale—Revised as an Example
Authors: Yang Hao , Ye Chengyin , Liu Xiaochen , Sun Lingxiu , Wang Anqi , Wang Jing , Hu Nantu , Hu Xiaohua , Gosseries Olivia , Laureys Steven , Di Haibo , Fang Jiqian 
Published: July 2021

Objective: The aim of this study was to develop a general method to estimate the minimal number of repeated examinations needed to detect patients with random responsiveness, given a limited rate of missed diagnosis.Methods: Basic statistical theory was applied to develop the method. As an application, 100 patients with disorders of consciousness (DOC) were assessed with the Coma Recovery Scale–Revised (CRS-R). DOC patients were supposed to be examined for 13 times over 20 days, while anyone who was diagnosed as a minimally conscious state (MCS) in a round would no longer be examined in the subsequent rounds. To test the validation of this method, a series of the stochastic simulation was completed by computer software under all the conditions of possible combinations of three kinds of distributions for p, five values of p, and four sizes of the sample and repeated for 100 times.Results: A series of formula was developed to estimate the probability of a positive response to a single examination given by a patient and the minimal number of successive examinations needed based on the numbers of patients detected in the first i (i =1, 2,.) rounds of repeated examinations. As applied to the DOC patients assessed with the CRS-R, with a rate of missed diagnosis &lt; 0.0001, the estimate of the minimal number of examinations was six in traumatic brain injury patients and five in non-traumatic brain injury patients. The outcome of the simulation showed that this method performed well under various conditions possibly occurring in practice.Interpretation: The method developed in this paper holds in theory and works well in application and stochastic simulation. It could be applied to any other kind of examinations for random responsiveness, not limited to CRS-R for detecting MCS; this should be validated in further research.
Frequent Genetic Alterations and Their Clinical Significance in Patients With Thymic Epithelial Tumors
Authors: Xu Song , Li Xiongfei , Zhang Hongyi , Zu Lingling , Yang Lingqi , Shi Tao , Zhu Shuai , Lei Xi , Song Zuoqing , Chen Jun 
Published: July 2021

PurposeThymic epithelial tumors (TETs) are relatively rare neoplasms, including thymomas (types A, AB, B1, B2, and B3) and thymic carcinomas (TCs). The current knowledge about the biological properties of TETs is limited due to their low incidence. This study aimed to detect genetic alterations in TETs using next-generation sequencing(NGS) and explore their clinical significance in survival.MethodsTumor tissues and clinical data were collected from 34 patients with resected TETs in the Tianjin Medical University General Hospital between January 2011 and January 2019, and 56 cancer-associated genes were analyzed. The data of 123 TETs were retrieved from TCGA, and the information on their clinical and somatic mutations was explored.ResultsThe cohort comprised 34 TETs including 17 thymomas and 17 TCs. The NGS results indicated that 73.08% of TCs+type B3 TETs and 37.50% of non-TCs+type B3 TETs each exhibited gene mutations. For patients with type B3/C, TP53 was the most frequent mutation (19.23%), followed by CDKN2A (11.54%). Similarly, in 123 TETs from the TCGA cohort, TP53 mutations were more frequent in patients with type B3/C than in patients with non-type B3/C (11.53% vs 3.09%). Further, patients with TET with TP53 mutations in the present cohort and the TCGA cohort had a worse prognosis compared with those without TP53 mutations.ConclusionsGene mutation profiles between TCs+type B3 TETs and non-TCs+type B3 TETs were significantly different. The presence of TP53 mutations was more frequent in TCs+type B3 TETs than in non-TCs+type B3 TETs, which was associated with a worse prognosis.
The Enhanced Inhibitory Effect of Estrogen on PD-L1 Expression Following Nrf2 Deficiency in the AOM/DSS Model of Colitis-Associated Cancer
Authors: Kang Changhee , Song Chin-Hee , Kim Nayoung , Nam Ryoung Hee , Choi Soo In , Yu Jeong Eun , Nho Heewon , Choi Jin A. , Kim Jin Won , Na Hee Young , Lee Ha-Na , Surh Young-Joon 
Published: July 2021

Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a dual role in carcinogenesis. We previously reported that Nrf2 deficiency enhances the anti-tumorigenic effect of 17β-estradiol (E2) in an azoxymethane (AOM)/dextran sodium sulfate (DSS) model of colitis-associated cancer (CAC). Herein, we aimed to determine a possible explanation for our recent work and investigated the immune microenvironment represented by programmed death-ligand 1 (PD-L1) expression. One week after the AOM injection, mice were administered with DSS in drinking water for seven days; daily E2 injections were intraperitoneally administered during this period. The mice were sacrificed 16 weeks after AOM injection and analyzed for PD-L1 expression in the distal colon tissues using Western blotting and immunohistochemistry (IHC). Based on Western blotting results, PD-L1 expression was reduced in Nrf2 knockout (KO) female and E2-treated male mice when compared with their wild-type counterparts, following AOM/DSS treatment; this supports the association of PD-L1 expression with tumor progression. Additionally, this finding was in good agreement with the IHC results for PD-L1. Furthermore, we observed that PD-L1 is predominantly expressed in stromal cells rather than on epithelial cells in the colon. Western blotting revealed that PD-L1 expression in the colon positively correlates with expressions of inducible nitric oxide synthase (iNOS) (male, P = 0.002; female, P &lt;0.001) and cyclooxygenase-2 (COX-2) (male, P &lt;0.001; female, P &lt;0.001). Collectively, our findings indicate that estrogen ameliorates the immune microenvironment represented by PD-L1 expression and enhances its effect in the absence of Nrf2.
A Nomogram Based on Combining Clinical Features and Contrast Enhanced Ultrasound LI-RADS Improves Prediction of Microvascular Invasion in Hepatocellular Carcinoma
Authors: Zhou Hang , Sun Jiawei , Jiang Tao , Wu Jiaqi , Li Qunying , Zhang Chao , Zhang Ying , Cao Jing , Sun Yu , Jiang Yifan , Liu Yajing , Zhou Xianli , Huang Pintong 
Published: July 2021

PurposesTo establish a predictive model incorporating clinical features and contrast enhanced ultrasound liver imaging and reporting and data system (CEUS LI-RADS) for estimation of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) patients.MethodsIn the retrospective study, 127 HCC patients from two hospitals were allocated as training cohort (n=98) and test cohorts (n=29) based on cutoff time-point, June 2020. Multivariate regression analysis was performed to identify independent indicators for developing predictive nomogram models. The area under receiver operating characteristic (AUC) curve was also determined to establish the diagnostic performance of different predictive models. Corresponding sensitivities and specificities of different models at the cutoff nomogram value were compared.ResultsIn the training cohort, clinical information (larger tumor size, higher AFP level) and CEUS LR-M were significantly correlated with the presence of MVI (all p&lt;0.05). By incorporating clinical information and CEUS LR-M, the predictive model (LR-M+Clin) achieved a desirable diagnostic performance (AUC=0.80 and 0.84) in both cohorts at nomogram cutoff score value of 89. The sensitivity of LR-M+Clin when predicting MVI in HCC patients was higher than that of the clinical model alone (86.7% vs. 46.7%, p=0.027), while specificities were 78.6% and 85.7% (p=0.06), respectively, in the test cohort. In addition, LR-M+Clin exhibited similar AUC and specificity, but a significantly higher sensitivity (86.7%) than those of LR-M alone and LR-5(No)+Clin (both sensitivities=73.3%, both p=0.048).ConclusionThe predictive model incorporating CEUS LR-M and clinical features was able to predict the MVI status of HCC and is a potential reliable preoperative tool for informing treatment.
Childhood Idiopathic Nephrotic Syndrome: Does the Initial Steroid Treatment Modify the Outcome? A Multicentre, Prospective Cohort Study
Authors: Pasini Andrea , Bertulli Cristina , Casadio Luca , Corrado Ciro , Edefonti Alberto , Ghiggeri GianMarco , Ghio Luciana , Giordano Mario , La Scola Claudio , Malaventura Cristina , Maringhini Silvio , Mastrangelo Antonio P. , Materassi Marco , Mencarelli Francesca , Messina Giovanni , Monti Elena , Morello William , Puccio Giuseppe , Romagnani Paola , Montini Giovanni ,   the NefroKid Study Group
Published: July 2021

Background: A great majority of children with idiopathic nephrotic syndrome will relapse after successful treatment of the initial episode. The possibility that different steroid dosing regimens at onset, adjusted for risk factors, can reduce the rate of relapse represents an interesting option to investigate.Objectives: To evaluate the effect of the initial steroid regimen, adjusted for time to remission (TTR), on the frequency of relapses and steroid dependence, and to verify the influence of prognostic factors on disease course.Methods: A multicentre, prospective, cohort study. Children with nephrotic syndrome, with TTR ≤ 10 days (Group A), were given a 20-week prednisone regimen (2,828 mg/m2) and those with a TTR &gt;10 days, a 22-week regimen (3,668 mg/m2) (Group B). Previously published retrospective data from the same centers were also evaluated. Main outcomes were: relapse rate, number of frequent relapsers + steroid dependent children and total prednisone dose after induction.Results: 143 children were enrolled. Rate of relapsed subjects (77 vs. 79%) and frequent relapsers + steroid dependent subjects (40 vs. 53%) did not differ between Groups A and B, or between the retrospective and prospective cohorts. The cumulative prednisone dose taken after the induction treatment was similar in both groups and in the retrospective and prospective cohorts. TTR was not associated with relapse risk. Age at onset and total serum protein were significantly lower in relapsing patients. At ROC analysis, the best cut-off was 5.3 years for age at onset and 4.2 g/dL for total serum protein. According to these cut-offs, older children with higher total serum protein had a higher relapse free survival rate (58%) than younger children with lower total serum protein (17%).Conclusions: TTR was not found to be a prognostic factor of relapse; because of this, different steroid regimens, adjusted for TTR, did not modify the relapse rate in any relevant measure. Conversely, younger age and low total serum protein were independent predictors of relapse risk, however this outcome was not modified by higher prednisone regimens.Clinical Trial Registration:https://www.ClinicalTrials.gov/, identifier: NCT01386957 (www.nefrokid.it).