The Effects of Age and Reading Experience on the Lifespan Neurodevelopment for Reading Comprehension.

Reading comprehension is a vital cognitive skill that individuals use throughout their lives. The neurodevelopment of reading comprehension across the lifespan, however, remains underresearched. Furthermore, factors such as maturation and experience significantly influence functional brain development. Given the complexity of reading comprehension, which incorporates lower-level word reading process and higher-level semantic integration process, our study aims to investigate how age and reading experience influence the neurobiology underpinning these two processes across the lifespan. fMRI data of 158 participants aged from 7 to 77 years were collected during a passive word viewing task and a sentence comprehension task to engage the lower- and higher-level processes, respectively. We found that the neurodevelopment of the lower-level process was primarily influenced by age, showing increased activation and connectivity with age in parieto-occipital and middle/inferior frontal lobes related to morphological-semantic mapping while decreased activation in the temporoparietal regions linked to phonological processing. However, the brain function of the higher-level process was primarily influenced by reading experience, exhibiting a greater reliance on the frontotemporal semantic network with enhanced sentence-level reading performance. Furthermore, reading experience did not significantly affect the brain function of children, but had a positive effect on young adults in the lower-level process and on middle-aged and older adults in the higher-level process. These findings indicate that the brain function for lower- and higher-level processes of reading comprehension is differently affected by maturation and reading experience, and the experience effect is contingent on age regarding the two processes.

Proteomic analysis of plasma exosomes to differentiate malignant from benign pulmonary nodules.

BACKGROUND: It is difficult to distinguish benign pulmonary nodules (PNs) from malignant PNs by conventional examination. Therefore, novel biomarkers that can identify the nature of PNs are needed. Exosomes have recently been identified as an attractive alternative approach since tumor-specific molecules can be found in exosomes isolated from biological fluids. METHODS: Plasma exosomes were extracted via the exoEasy reagent method. The major proteins from plasma exosomes in patients with PNs were identified via labelfree analysis and screened for differentially expressed proteins. A GO classification analysis and KEGG pathway analysis were performed on plasma exosomal protein from patients with benign and malignant PNs. RESULTS: Western blot confirmed that protein expression of CD63 and CD9 could be detected in the exosome extract. Via a search of the human Uniprot database, 736 plasma exosome proteins from patients with PNs were detected using high-confidence peptides. There were 33 differentially expressed proteins in the benign and malignant PNs. Of these, 12 proteins were only expressed in the benign PNs group, while 9 proteins were only expressed in the malignant PNs group. We further obtained important information on signaling pathways and nodal proteins related to differential benign and malignant PNs via bioinformatic analysis methods such as GO, KEGG, and String. CONCLUSIONS: This study provides a new perspective on the identification of novel detection strategies for benign and malignant PNs. We hope our findings can provide clues for the identification of benign and malignant PNs.

Impact of post-operative serum albumin level on anastomotic leakage after transthoracic oesophagectomy for oesophageal squamous cell carcinoma.

BACKGROUND: The correlation of post-operative serum albumin level with the occurrence of anastomotic leakage (AL) in oesophageal squamous cell carcinoma (ESCC) remains unclear. The aim of this study was to evaluate the impact of post-operative serum albumin level on AL after transthoracic oesophagectomy. METHODS: Patients with ESCC who underwent transthoracic oesophagectomy between 2013 and 2017 in Fudan University Shanghai Cancer Center were included. The correlation of post-operative serum albumin level with the occurrence and short-term outcomes of AL was analysed. RESULTS: Patients with serum albumin level of <35 g/L on the first post-operative day were identified with higher frequency of AL in the whole study population (10.3% versus 6.1%; P < 0.001), intrathoracic anastomosis subgroup (7.1% versus 3.9%; P = 0.002) and cervical anastomosis subgroup (24.1% versus 16.0%; P = 0.042). Multivariate analysis showed that low albumin level was an independent risk factor of AL in the overall population (odds ratio (OR) 1.842; P < 0.001), intrathoracic anastomosis subgroup (OR 1.815; P = 0.006) and cervical anastomosis subgroup (OR 1.946; P = 0.013). In patients with AL, low albumin level was associated with poorer short-term outcomes. For patients with low albumin level on the first post-operative day, the probability of AL was significantly reduced if the level in the first post-operative week was improved to the normal range (5.9% versus 14.9%; P < 0.001). CONCLUSION: Serum albumin level on the first post-operative day was an independent predictor of AL in patients with ESCC receiving transthoracic oesophagectomy. Increase of albumin level to the normal range post-operatively could reduce the risk of AL.

EGFR-mutant lung adenocarcinoma harboring co-mutational tumor suppressor genes predicts poor prognosis.

INTRODUCTION: EGFR mutations occur most frequently in patients with lung adenocarcinoma in East Asia. However, the prognostic and therapeutic impact of co-mutational status of EGFR and tumor suppressor genes is not fully understood. This study aims to provide a deeper understanding of lung adenocarcinoma patients with co-mutation of EGFR and tumor suppressor genes. METHODS: From November 2009 to May 2016, 675 patients with lung adenocarcinoma who underwent complete surgery were included in this study. Samples were collected and pathologically examined. Whole-exome sequencing was performed on 197 samples, while direct sequencing of major driver genes, including EGFR, KRAS, ERBB2 and BRAF and Ion-torrent targeted sequencing of tumor suppressor genes, including TP53, KEAP1, MGA, NF1, RB1, SMARCA4 and STK11, were performed on 478 samples. Tumor mutational burden was calculated and survival analyses were performed. RESULTS: The frequency of EGFR and TP53 mutation was 409 (60.6%) and 215 (31.9%), respectively. Co-mutation of EGFR and TP53 occured in 151 patients (22.4%), while co-mutation of EGFR and at least one tumor suppressor gene occured in 184 patients (27.3%). Compared with patients with only EGFR mutations, patients with co-mutations of EGFR and TP53 had a higher tumor mutational burden (p = 0.007) and worse recurrence-free survival (p = 0.010), while patients with co-mutations of EGFR and at least one tumor suppressor gene had a higher tumor mutational burden (p = 0.007), worse recurrence-free survival (p = 0.016) and worse overall survival (p = 0.018). CONCLUSIONS: Lung adenocarcinoma patients harboring EGFR and co-mutational tumor suppressor genes should be regarded as a unique subgroup.

Clinical relevance of mutant-allele tumor heterogeneity and lung adenocarcinoma.

BACKGROUND: Intra-tumor heterogeneity (ITH) plays an important role in the progressing of lung adenocarcinoma (LUAD). We used a mutant-allele tumor heterogeneity (MATH) algorithm to measure ITH and the correlation between ITH and clinical parameters and its prognosis. METHODS: We assessed 230 LUAD patients from The Cancer Genome Atlas (TCGA). We calculated the MATH values from whole-exome sequencing data and further investigated their correlation with clinical characteristics. RESULTS: The patients were divided into low and high MATH groups. People with high MATH were more likely to be female, smoking and EGFR mutation. And a high MATH may predict a poor prognosis. CONCLUSIONS: MATH is a new method for describing the internal heterogeneity of tumors in lung cancer. We used TCGA data to demonstrate that groups with higher MATH values are more likely to be female, smoker and EGFR mutations, and may have a poor prognosis.

FGB and FGG derived from plasma exosomes as potential biomarkers to distinguish benign from malignant pulmonary nodules.

Previous proteomic analysis (label-free) of plasma exosomes revealed that the expression of FGG and FGB was significantly higher in the malignant pulmonary nodules group, compared to the benign pulmonary nodules group. The present study was performed to evaluate the role of plasma exosomal proteins FGB and FGG in the diagnosis of benign and malignant pulmonary nodules. We examined the expression levels of FGB and FGG in plasma exosomes from 63 patients before surgery. Postoperative pathological diagnosis confirmed that 43 cases were malignant and 20 cases were benign. The ROC curve was used to describe the sensitivity, specificity, area under the curve (AUC) of the biomarker and the corresponding 95% confidence interval. We confirmed that the expression levels of FGB and FGG were higher in the plasma exosomes of malignant group than in the benign group. The sensitivity and AUC of FGB combined with FGG detection to determine the nature of pulmonary nodules are superior to single FGB or FGG detection. FGB and FGG might represent novel and sensitive biomarker to distinguish benign from malignant pulmonary nodules.

Preoperative brain MRI for clinical stage IA lung cancer: is routine scanning rational?

PURPOSE: Early detection and control of lung cancer brain metastases (BMs) are important. However, several guideline recommendations are inconsistent with regard to routine preoperative brain MRI, especially in patients with clinical stage IA lung cancer. Our study evaluated the value of preoperative brain MRI in patients with clinical stage IA lung cancer. METHODS: A retrospective analysis of patients with lung cancer was performed using a prospectively collected database. Clinical data and the results of brain MRI were collected and analyzed. RESULTS: Patients with pathologically proved primary lung cancer who underwent an MRI at initial diagnosis were identified (3392 patients). In total, 170 patients (5.0%) were diagnosed with BMs. The increased frequency of BMs was significantly associated with advanced clinical stage (P = 0.000) and pathological type (P = 0.011). BMs were detected in 11 out of 1595 patients with clinical stage IA lung cancer (0.7%). BMs were more common in patients with clinical stage cT1c lung cancer (1.9%) than those with clinical stage cT1a or cT1b (0.1%, odds ratio = 21.30, 95% confidence interval: 2.7-166.9, P = 0.000). All patients with stage IA lung cancer and BMs had solid lung lesions (P = 0.002). CONCLUSIONS: Preoperative brain MRI might help identify BMs in patients with lung cancer that has progressed beyond stage IA. In patients with clinical stage IA lung cancer, we do not recommend preoperative brain MRI, but it may potentially be beneficial in those with solid T1c cancers.

A model based on endoscopic morphology of submucosal esophageal squamous cell carcinoma for determining risk of metastasis on lymph nodes.

BACKGROUND: It is important to identify patients with esophageal squamous cell carcinoma (ESCC) in T1b stage that are the least likely to metastasize on the lymph nodes, to undergo endoscopic resection, especially for the patients unfit for esophagectomy. The relationship between endoscopic morphology and frequency of nodal metastasis has never been well studied. The aims of the study were to investigate the predictive value of endoscopic morphology for lymphatic metastasis, and to develop a risk stratification model in submucosal (T1b) ESCC. METHODS: Pathologic variables of patients with T1b ESCC who underwent esophagectomy from 2006 through 2016 were collected and divided into training sets (patients between 2006 and 2011) and validation sets (patients between 2012 and 2016). The endoscopic morphology of the tumor was determined by analyzing endoscopic reports according to the Paris classification. The correlation between the clinicopathological factors and nodal metastasis was examined. A prediction model was developed to estimate the risk of metastasis using these predictors. RESULTS: A total of 175 patients were included in this study. A tumor with an endoscopic shape of flat type (0-II type as Paris classification was defined) was significantly related to lower risk of lymphatic metastasis with the frequency of 15.5% (OR: 3.049, 95% CI: 1.363-6.819, P=0.005). The combination of endoscopic morphology with other pathologic characteristics including lymphovascular invasion, length of tumor, depth of tumor invasion into submucosa, and tumor differentiation improved the predictive value of the nodal metastasis. The risk stratification model was developed with a C-index of 0.726 (95% CI: 0.702-0.751), which identified a low risk subgroup with a lymph node rate of 7.2%. CONCLUSIONS: Our results suggest that when a tumor is in flat shape (0-II type) it is related to a less lymphatic metastasis, and the combination of the endoscopic morphology with the other four pathologic variables can yield a more robust approach to predict the risk of lymphatic metastasis in submucosal ESCC.