Overexpression of circular RNA hsa_circ_0008621 facilitates colorectal cancer progression and predicts poor prognosis.

Aim: To evaluate the potential role of serum and tissue hsa_circ_0008621 as a prognostic biomarker for CRC patients. Focused on the functional role of hsa_circ_0008621 in colorectal cancer (CRC). Methods: Serum and tissue hsa_circ_0008621 expression were quantified by qRT-PCR in 157 CRC patients, as well as 100 serums from healthy controls. Serum and tissue hsa_circ_0008621 expression was evaluated for their prognostic role in CRC patients using Kaplan-Meier curves and Multivariate Cox proportional hazards analysis. To further characterize the biological role of hsa_circ_0008621 expression in CRC, in vitro hsa_circ_0008621 inhibition was performed and the effects on cellular growth, migration, invasion, apoptosis, and glycolysis were explored. Next, the downstream molecules for hsa_circ_0008621 were predicted. Results: Hsa_circ_0008621 expression was significantly upregulated in CRC tissues and serums. Serum hsa_circ_0008621 levels were significantly up-regulated in advanced-staged samples. High serum hsa_circ_0008621 expression was associated with shorter overall survival and recurrence-free survival in CRC patients. Multivariate Cox regression analysis identified a high level of serum hsa_circ_0008621 expression as an independent prognostic factor with respect to overall survival and recurrence-free survival. Loss of function assays for hsa_circ_0008621 in vitro led to a significant decrease in cell proliferation, migration, invasion, and glycolysis, but an increase in cell apoptosis. Hsa_circ_0008621 can sponge miR-532-5p, which targets SLC16A3. Conclusion: High level of serum hsa_circ_0008621 is associated with poor survival in CRC and promotes CRC progression, suggesting it to be a promising non-invasive prognostic biomarker and novel therapeutic target in CRC patients.

Development and validation of machine learning models for predicting HER2-zero and HER2-low breast cancers.

OBJECTIVES: To develop and validate machine learning models for HER2-zero and -low using MRI features pre-neoadjuvant therapy (pre-NAT). METHODS: 516 breast cancer patients post-NAT surgery were randomly divided into training (n = 362) and internal validation sets (n = 154) for model building and evaluation. MRI features (tumor diameter, enhancement type, background parenchymal enhancement, enhancement pattern, percentage of enhancement, signal enhancement ratio, breast edema, and ADC) were reviewed. Logistic regression (LR), support vector machine (SVM), k-nearest neighbor (KNN), and extreme gradient boosting (XGBoost) models utilized MRI characteristics for HER2 status assessment in training and validation datasets. The best-performing model generated a HER2 score, subsequently correlated with pathological complete response (pCR) and disease-free survival (DFS). RESULTS: The XGBoost model outperformed LR, SVM, and KNN, achieving an area under the ROC curve (AUC) of 0.783(95% CI: 0.733-0.833) and 0.787(95% CI: 0.709-0.865) in the validation dataset. Its HER2 score for predicting pCR had an AUC of 0.708 in the training datasets and 0.695 in the validation dataset. Additionally, the low HER2 score was significantly associated with shorter DFS in the validation dataset (HR: 2.748,95% CI: 1.016-7.432, P = 0.037). CONCLUSIONS: The XGBoost model could help distinguish HER2-zero and HER2-low breast cancers, and has the potential to predict pCR and prognosis in breast cancer patients undergoing NAT. ADVANCES IN KNOWLEDGE: Human epidermal growth factor receptor 2 (HER2)-low-expressing breast cancer can benefit from the HER2 targeted therapy. Prediction of HER2-low expression is crucial for appropriate management. MRI features offer a solution to this clinical issue.

[Tumor-Like Primary Central Nervous System Vasculitis With Spina Involvement:Report of One Case].

Primary central nervous system vasculitis (PACNS) is a vasculitic disorder affecting small to medium-sized blood vessels primarily in the central nervous system,involving the brain,spinal cord,and meninges.Tumor-like PNCAS,a rare subtype of PACNS,is often misdiagnosed as intracranial malignancy,and that with spinal cord involvement is even more uncommon.The lack of specific clinical symptoms and imaging manifestations poses a challenge to the diagnosis of PACNS.This report presents a case of tumor-like PACNS with spinal cord involvement based on the pathological evidence,aiming to enrich the knowledge about this condition.

A Novel Fluorescent Probe for Nitroreductase Detection and Imaging of cancer Cells under Hypoxia Conditions.

Nitroreductase (NTR) is to be pivotal in the biodegradation of nitroaromatics. NTR is produced in tumor tissues under hypoxic conditions, which is one of the markers for early tumor diagnosis. In this study, a novel probe FD-NTR was developed for NTR detection. Probe FD-NTR can exhibit a specific reaction with NTR in the presence of NADH. The probe displayed satisfactory selectivity and sensitivity towards NTR with a calculated detection limit of 12 ng/mL. Under the conditions of low cytotoxic hypoxia, the FD-NTR probe has shown successful application in imaging both MCF-7 cells and tumor tissues, which indicated that the FD-NTR probe holds promising application prospects for detecting NTR in tumors.

Surgical resection due to poor outcome of the immunotherapy of a relapsed mediastinal liposarcoma: a case report.

The feasibility of surgery after immunotherapy for mediastinal liposarcoma remains uncertain. Besides, the case of immunotherapy for liposarcoma is still lacking. We report a case of recurrence after resection of a left mediastinal liposarcoma. After recurrence, one course of pembrolizumab plus anlotinib hydrochloride showed no tumor shrinkage, and genetic testing showed CDK4 amplification and PD-L1 TPS <1%; therefore, the plan was changed to one course of pembrolizumab plus palbociclib, but the tumor still did not shrink. Thus, second tumor resection was performed. In addition, the postoperative pathology was still well-differentiated liposarcoma. The significance of immunotherapy in liposarcoma still needs to be further explored. In the absence of surgical contraindications, secondary surgery might be feasible.

Marital status impacts survival of stage I non-small-cell lung cancer: a propensity-score matching analysis.

Aim: This population-based analysis aimed to explore the associations among marital status, prognosis and treatment of stage I non-small-cell lung cancer. Materials & methods: The propensity score matching (PSM), logistic regression and Cox proportional hazards model were used in this study. Results: A total of 13,937 patients were included. After PSM, 10579 patients were co-insured. The married were more likely to receive surgical treatment compared with the unmarried patients (OR: 1.841, p < 0.001), and patients who underwent surgery also tended to have better survival (HR: 0.293, p < 0.001). Conclusion: Compared with unmarried patients, a married group with stage I NSCLC had timely treatment and more satisfactory survival. This study highlights the importance of prompt help and care for unmarried patients.

Foreign body-intestinal canal angle guides management of ingested foreign bodies in the lower gastrointestinal tract.

BACKGROUND: Determining whether prompt surgery is required for patient with ingested foreign bodies is clinically important. PURPOSE: To evaluate the potential value of computed tomography (CT) in guiding the selection of surgical treatment for patients with ingested foreign bodies in the lower gastrointestinal tract. METHODS: Between January 2014 and December 2023, we analyzed the data of 58 patients (median age: 65.4 years; range, 31-96 years) with ingested foreign bodies in the lower gastrointestinal tract who underwent CT examinations. Patients were treated either conservatively (35 cases) or surgically (23 cases). The angle between the long axis of the foreign body and the intestinal canal (FB-IC angle) was measured. CT findings and clinical variables were evaluated to identify potential indicators for surgical treatment through univariate and multivariate logistic regression analyses. RESULTS: Univariate analysis revealed the FB-IC angle (P = 0.002), presence of free peritoneal gas (P = 0.002), white blood cell count (P = 0.018), and neutrophil count (P = 0.007) as significant factors associated with surgical treatment. Multivariate analysis demonstrated that the FB-IC angle (odds ratio, 1.033; P = 0.045) and the presence of free peritoneal gas (odds ratio, 41.335; P = 0.002) are independent indicators for surgical management. The FB-IC angle showed an area under the receiver operating characteristic curve of 0.755, with a cutoff value of 51.25 degrees. CONCLUSION: The FB-IC angle and presence of free peritoneal gas serve as potential predictive imaging markers for surgical intervention.

Feasibility of microwave remediation of simulative crude oil-contaminated soil assisted by bluecoke-based modifiers.

Microwave (MW) remediation of organics-contaminated soil technology offers the advantages of high efficiency and minimal damage, representing a new approach of soil thermal remediation. However, soil, being a weak MW-absorbing medium, struggles to convert MW energy into thermal energy, thus failing to attain the necessary temperature for thermal remediation. This paper prepared two new bluecoke (BC)-based modifiers (KHCO3@BC and KHCO3/MnO2@BC) to address temperature problem of MW remediation, as well as enhance soil quality. Their composition, structure and electromagnetic properties were analyzed to investigate their role in assisting with the MW remediation of an artificially crude oil-contaminated soil were investigated. Additionally, the industrial feasibility of MW remediation was addressed for the first time. The results showed that the KHCO3 and MnO2 particles in the two modifiers were covered on the BC surface and exhibited local agglomeration. Their carbon crystalline grain size increased, and the electromagnetic properties were weaker than those of the BC. Following 10 min of MW remediation assisted by KBC or KMnBC, the remediation temperatures exceeded 300 °C, with the removal rates of PHs reaching 76.16% and 88.31%, respectively. The organic matter content, soil potassium and mechanical fraction of the remediated soil were improved, but soil acidification still needed to be further addressed. The industrial application analysis indicated that the technical process and techno-economics of MW remediation of crude oil-contaminated soil were feasible, suggesting significant potential for the large-scale industrial application.

Bioinformatics Identification and Experimental Validation of a Prognostic Model for the Survival of Lung Squamous Cell Carcinoma Patients.

Lung squamous cell carcinoma (LUSC) kills more than four million people yearly. Creating more trustworthy tumor molecular markers for LUSC early detection, diagnosis, prognosis, and customized treatment is essential. Cuproptosis, a novel form of cell death, opened up a new field of study for searching for trustworthy tumor indicators. Our goal was to build a risk model to assess drug sensitivity, monitor immune function, and predict prognosis in LUSC patients. The 19 cuproptosis-related genes were found in the literature, and patient genomic and clinical information was collected using the Cancer Genomic Atlas (TCGA) database. The LUSC patients were grouped using unsupervised clustering techniques, and 7626 differentially expressed genes were identified. Using univariate COX analysis, LASSO regression analysis, and multivariate COX analysis, a prognostic model for LUSC patients was developed. The tumor immune escape was evaluated using the Tumor Immune Dysfunction and Exclusion (TIDE) method. The R packages 'pRRophetic,' 'ggpubr,' and 'ggplot2' were utilized to examine drug sensitivity. For modeling, a 6-cuproptosis-based gene signature was found. Patients with high-risk LUSC had significantly worse survival rates than those with low-risk conditions. The possibility of tumor immunological escape was increased in patients with higher risk scores due to more immune cell inactivation. For patients with high-risk LUSC, we discovered seven potent potential drugs (AZD6482, CHIR.99021, CMK, Embelin, FTI.277, Imatinib, and Pazopanib). In conclusion, the cuproptosis-based genes predictive risk model can be utilized to predict outcomes, track immune function, and evaluate medication sensitivity in LUSC patients.

MiR-1976/NCAPH/P65 axis inhibits the malignant phenotypes of lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is a malignancy with an abysmal survival rate. High metastasis is the leading cause of the low survival rate of LUAD. NCAPH, an oncogene, is involved in the carcinogenesis of LUAD. However, the regulation of NCAPH in LUAD remains controversial. In this work, we identified an up-regulation of NCAPH in LUAD tissues. Patients who expressed more NCAPH had shorter overall survival (OS). Furthermore, NCAPH overexpression promoted LUAD cell migration while inhibiting apoptosis. MiR-1976 and miR-133b were predicted to target NCAPH expression by searching TargetScan and linkedomics databases. Following that, we confirmed that miR-1976 suppressed NCAPH by directly targeting a 7-bp region of NCAPH 3' untranslated regions (UTR). In addition, increased expression of miR-1976 decreased the proliferation & migration and promoted apoptosis of LUAD cells, and the re-introduction of NCAPH reversed these influences. Furthermore, the xenograft and metastasis mouse models also confirmed that miR-1976 inhibited tumor growth and metastasis in vivo by targeting NCAPH. Finally, we found that MiR-1976 targeting NCAPH blocked the activation of NF-κB. In conclusion, miR-1976 inhibits NCAPH activity in LUAD and acts as a tumor suppressor. The miR-1976/NCAPH/NF-κB axis may, in the future, represent crucial diagnostic and prognostic biomarkers and promising therapeutic options.

Dexmedetomidine alleviates acute postoperative anxiety in rats by suppressing the NF-ĸB pathway.

Evidence suggests that surgical procedures can effect the central nervous system and lead to changes in mood and behavior, rarely understood about the role of acute inflammation in promoting acute anxiety postoperatively. This study was designed to explore the possible mechanism of dexmedetomidine (DEX, a2-adrenergic receptor agonist) for reducing acute postoperative anxiety, which may be related to the activation of nuclear factor kappa B (NF-κB) and downstream signal pathway in the hippocampus. Experiments were conducted with rat, the elevated plus-maze and open field test were performed to evaluate anxiety-like behavior. Inhibit DEX with Atipamezole (AT, α2-adrenergic receptor antagonist) and inhibit NF-κB with Pyrrolidinedithiocarbamate (PDTC, inhibit phosphorylation of IκB, prevent the activation of NF-κB), the level of interleukin-6 (IL-6), IL-1ß, IL-10 and Tumor necrosis factor-α (TNF-α); the nuclear translocation of NF-κB in the hippocampus and anxiety-like behavior were measured. Rats exhibited anxiety-like behavior at 6h and 12h after surgery. Preoperative administration of DEX significantly alleviated postoperative anxiety-like behavior. DEX premedication inhibited the nuclear translocation of NF-κB alleviate acute postoperative anxiety. These findings are the first to show that acute postoperative anxiety may be related to NF-κB nuclear translocation in the hippocampus in rats, which can be alleviated by DEX premedication.

Stem cell therapies: a new era in the treatment of multiple sclerosis.

Multiple Sclerosis (MS) is an immune-mediated condition that persistently harms the central nervous system. While existing treatments can slow its course, a cure remains elusive. Stem cell therapy has gained attention as a promising approach, offering new perspectives with its regenerative and immunomodulatory properties. This article reviews the application of stem cells in MS, encompassing various stem cell types, therapeutic potential mechanisms, preclinical explorations, clinical research advancements, safety profiles of clinical applications, as well as limitations and challenges, aiming to provide new insights into the treatment research for MS.

Carcinoembryonic antigen potentiates non-small cell lung cancer progression via PKA-PGC-1ɑ axis.

Carcinoembryonic antigen (CEA) is a tumor-associated antigen primarily produced by tumor cells. It has been implicated in various biological processes such as cell adhesion, proliferation, differentiation, and metastasis. Despite this, the precise molecular mechanisms through which CEA enhances tumor cell proliferation remain largely unclear. Our study demonstrates that CEA enhances the proliferation and migration of non-small cell lung cancer (NSCLC) while also inhibiting cisplatin-induced apoptosis in NSCLC cells. Treatment with CEA led to an increase in mitochondrial numbers and accumulation of lipid droplets in A549 and H1299 cells. Additionally, our findings indicate that CEA plays a role in regulating the fatty acid metabolism of NSCLC cells. Inhibiting fatty acid metabolism significantly reduced the CEA-mediated proliferation and migration of NSCLC cells. CEA influences fatty acid metabolism and the proliferation of NSCLC cells by activating the PGC-1α signaling pathway. This regulatory mechanism involves CEA increasing intracellular cAMP levels, which in turn activates PKA and upregulates PGC-1α. In NSCLC, inhibiting the PKA-PGC-1α signaling pathway reduces both fatty acid metabolism and the proliferation and migration induced by CEA, both in vitro and in vivo. These results suggest that CEA contributes to the promotion of proliferation and migration by modulating fatty acid metabolism. Targeting CEA or the PKA-PGC-1ɑ signaling pathway may offer a promising therapeutic approach for treating NSCLC.

Predictive Value of Plasma PCSK9 Levels for Degree of Atherosclerosis and Major Adverse Cardiovascular and Cerebrovascular Events in Older Adult Patients with Non-Alcoholic Fatty Liver Disease.

Purpose: This study investigated the influence of plasma proprotein convertase subtilisin/kexin 9 (PCSK9) levels on the degree of atherosclerosis and major adverse cardiovascular and cerebrovascular events (MACCE) in older adults with non-alcoholic fatty liver disease. Methods: The degree of atherosclerosis severity was assessed by the standard Gensini score quartile method. According to the degree of atherosclerosis, patients were divided into mild (0-24 points; n=84), moderate (25-53 points; n=86), and severe groups (≥54 points; n=84) and then categorized as MACCE (n=30) or non-MACCE (n=224) according to 6-month follow-up data. The patients' age, sex, smoking history, medical history, and early morning fasting venous blood, for measuring biochemical indexes, were collected. Clinical data were compared between groups and the relationship between Gensini scores and PCSK9 was evaluated. Results: Compared with the mild group, the moderate and severe groups had higher high-sensitivity C-reactive protein(hs-CRP), PCSK9, triglycerides(TG), low-density lipoprotein cholesterol (LDL-C), and lipoprotein(a)[Lp(a)] levels and lower high-density lipoprotein cholesterol(HDL-C) levels (all P<0.05). Moreover, PCSK9 positively correlated with Gensini scores (r=0.657, P<0.01). The MACCE and non-MACCE groups had significantly different ages, statin use, Gensini scores, PCSK9, and LDL-C (all P<0.05). Multi-factorial Cox risk regression analysis showed the Gensini score (HR=1.018, 95% CI: 1.006~1.029) and PCSK9 (HR=1.147, 95% CI: 1.038~1.287) were independent risk factors for MACCE. Conclusion: The Gensini score and PCSK9 levels can be used as predictive indicators for the degree of illness and occurrence of MACCE in older NAFLD patients.

Upregulated lncRNA LINC01128 in colorectal cancer accelerates cell growth and predicts malignant prognosis through sponging miR-363-3p.

PURPOSE: Colorectal cancer (CRC) refers to high-mortality tumors arising in the colon or rectum with a high rate of recurrence. The involvement of long non-coding RNAs (lncRNAs) contributes to the treatment and prognosis evaluation of CRC, and brings a new direction for the radical cure of patients. To identify the pathological mechanism and regulation of lncRNA LINC01128 (LINC01128) on CRC cells, and analyze its potential prognostic value. METHODS: LINC01128 level in tissue and cell specimens from 122 CRC patients was evaluated by RT-qPCR. The clinical significance and prognostic value of LINC01128 in CRC were analyzed via Kaplan-Meier and Cox analysis. CCK8 and Transwell assays were used to study the function of LINC01128 in vitro. The relationship between LINC01128 and miR-363-3p was confirmed by luciferase reporter gene assay. RESULTS: The overexpression of LINC01128 is associated with TNM stage and lymph node metastasis in CRC patients. Silencing LINC01128 inhibited the proliferation and metastasis of CRC cells. In addition, LINC01128 directly targeted and negatively regulated the miR-363-3p expression, while miR-363-3p inhibitor restored the inhibitory function of LINC01128. CONCLUSION: As an independent prognostic factor of CRC, upregulation of LINC01128 predicts poor prognosis and accelerates tumor deterioration through miR-363-3p.

FGL1 and FGL2: emerging regulators of liver health and disease.

Liver disease is a complex group of diseases with high morbidity and mortality rates, emerging as a major global health concern. Recent studies have highlighted the involvement of fibrinogen-like proteins, specifically fibrinogen-like protein 1 (FGL1) and fibrinogen-like protein 2 (FGL2), in the regulation of various liver diseases. FGL1 plays a crucial role in promoting hepatocyte growth, regulating lipid metabolism, and influencing the tumor microenvironment (TME), contributing significantly to liver repair, non-alcoholic fatty liver disease (NAFLD), and liver cancer. On the other hand, FGL2 is a multifunctional protein known for its role in modulating prothrombin activity and inducing immune tolerance, impacting viral hepatitis, liver fibrosis, hepatocellular carcinoma (HCC), and liver transplantation. Understanding the functions and mechanisms of fibrinogen-like proteins is essential for the development of effective therapeutic approaches for liver diseases. Additionally, FGL1 has demonstrated potential as a disease biomarker in radiation and drug-induced liver injury as well as HCC, while FGL2 shows promise as a biomarker in viral hepatitis and liver transplantation. The expression levels of these molecules offer exciting prospects for disease assessment. This review provides an overview of the structure and roles of FGL1 and FGL2 in different liver conditions, emphasizing the intricate molecular regulatory processes and advancements in targeted therapies. Furthermore, it explores the potential benefits and challenges of targeting FGL1 and FGL2 for liver disease treatment and the prospects of fibrinogen-like proteins as biomarkers for liver disease, offering insights for future research in this field.

Artificial intelligence-based tools with automated segmentation and measurement on CT images to assist accurate and fast diagnosis in acute pancreatitis.

OBJECTIVES: To develop an artificial intelligence (AI) tool with automated pancreas segmentation and measurement of pancreatic morphological information on CT images to assist improved and faster diagnosis in acute pancreatitis. METHODS: This study retrospectively contained 1124 patients suspected for AP and received non-contrast and enhanced abdominal CT examination between September 2013 and September 2022. Patients were divided into training (N = 688), validation (N = 145), testing dataset [N = 291; N = 104 for normal pancreas, N = 98 for AP, N = 89 for AP complicated with PDAC (AP&PDAC)]. A model based on convolutional neural network (MSAnet) was developed. The pancreas segmentation and measurement were performed via eight open-source models and MSAnet based tools, and the efficacy was evaluated using dice similarity coefficient (DSC) and intersection over union (IoU). The DSC and IoU for patients with different ages were also compared. The outline of tumour and oedema in the AP and were segmented by clustering. The diagnostic efficacy for radiologists with or without the assistance of MSAnet tool in AP and AP&PDAC was evaluated using receiver operation curve and confusion matrix. RESULTS: Among all models, MSAnet based tool showed best performance on the training and validation dataset, and had high efficacy on testing dataset. The performance was age-affected. With assistance of the AI tool, the diagnosis time was significantly shortened by 26.8% and 32.7% for junior and senior radiologists, respectively. The area under curve (AUC) in diagnosis of AP was improved from 0.91 to 0.96 for junior radiologist and 0.98 to 0.99 for senior radiologist. In AP&PDAC diagnosis, AUC was increased from 0.85 to 0.92 for junior and 0.97 to 0.99 for senior. CONCLUSION: MSAnet based tools showed good pancreas segmentation and measurement performance, which help radiologists improve diagnosis efficacy and workflow in both AP and AP with PDAC conditions. ADVANCES IN KNOWLEDGE: This study developed an AI tool with automated pancreas segmentation and measurement and provided evidence for AI tool assistance in improving the workflow and accuracy of AP diagnosis.

Identification and classification of glioma subtypes based on RNA-binding proteins.

BACKGROUND: Glioma is a common and aggressive primary malignant cancer known for its high morbidity, mortality, and recurrence rates. Despite this, treatment options for glioma are currently restricted. The dysregulation of RBPs has been linked to the advancement of several types of cancer, but their precise role in glioma evolution is still not fully understood. This study sought to investigate how RBPs may impact the development and prognosis of glioma, with potential implications for prognosis and therapy. METHODS: RNA-seq profiles of glioma and corresponding clinical data from the CGGA database were initially collected for analysis. Unsupervised clustering was utilized to identify crucial tumor subtypes in glioma development. Subsequent time-series analysis and MS model were employed to track the progression of these identified subtypes. RBPs playing a significant role in glioma progression were then pinpointed using WGCNA and Lasso Cox regression models. Functional analysis of these key RBP-related genes was conducted through GSEA. Additionally, the CIBERSORT algorithm was utilized to estimate immune infiltrating cells, while the STRING database was consulted to uncover potential mechanisms of the identified biomarkers. RESULTS: Six tumor subgroups were identified and found to be highly homogeneous within each subgroup. The progression stages of these tumor subgroups were determined using time-series analysis and a MS model. Through WGCNA, Lasso Cox, and multivariate Cox regression analysis, it was confirmed that BCLAF1 is correlated with survival in glioma patients and is closely linked to glioma progression. Functional annotation suggests that BCLAF1 may impact glioma progression by influencing RNA splicing, which in turn affects the cell cycle, Wnt signaling pathway, and other cancer development pathways. CONCLUSIONS: The study initially identified six subtypes of glioma progression and assessed their malignancy ranking. Furthermore, it was determined that BCLAF1 could serve as an RBP-related prognostic marker, offering significant implications for the clinical diagnosis and personalized treatment of glioma.

Searching Reproducible Brain Features using NeuroMark: Templates for Different Age Populations and Imaging Modalities.

A primary challenge to the data-driven analysis is the balance between poor generalizability of population-based research and characterizing more subject-, study- and population-specific variability. We previously introduced a fully automated spatially constrained independent component analysis (ICA) framework called NeuroMark and its functional MRI (fMRI) template. NeuroMark has been successfully applied in numerous studies, identifying brain markers reproducible across datasets and disorders. The first NeuroMark template was constructed based on young adult cohorts. We recently expanded on this initiative by creating a standardized normative multi-spatial-scale functional template using over 100,000 subjects, aiming to improve generalizability and comparability across studies involving diverse cohorts. While a unified template across the lifespan is desirable, a comprehensive investigation of the similarities and differences between components from different age populations might help systematically transform our understanding of the human brain by revealing the most well-replicated and variable network features throughout the lifespan. In this work, we introduced two significant expansions of NeuroMark templates first by generating replicable fMRI templates for infants, adolescents, and aging cohorts, and second by incorporating structural MRI (sMRI) and diffusion MRI (dMRI) modalities. Specifically, we built spatiotemporal fMRI templates based on 6,000 resting-state scans from four datasets. This is the first attempt to create robust ICA templates covering dynamic brain development across the lifespan. For the sMRI and dMRI data, we used two large publicly available datasets including more than 30,000 scans to build reliable templates. We employed a spatial similarity analysis to identify replicable templates and investigate the degree to which unique and similar patterns are reflective in different age populations. Our results suggest remarkably high similarity of the resulting adapted components, even across extreme age differences. With the new templates, the NeuroMark framework allows us to perform age-specific adaptations and to capture features adaptable to each modality, therefore facilitating biomarker identification across brain disorders. In sum, the present work demonstrates the generalizability of NeuroMark templates and suggests the potential of new templates to boost accuracy in mental health research and advance our understanding of lifespan and cross-modal alterations.

Validation of the 9th edition of the TNM staging system for non-small cell lung cancer with lobectomy in stage IA-IIIA.

OBJECTIVES: The 9th edition of tumour-node-metastasis (TNM) staging for lung cancer was announced by Prof Hisao Asamura at the 2023 World Conference on Lung Cancer in Singapore. The purpose of this study was to externally validate and compare the latest staging of lung cancer. METHODS: We collected 19 193 patients with stage IA-IIIA non-small cell lung cancer (NSCLC) who underwent lobectomy from the Surveillance, Epidemiology and End Results database. Survival analysis by TNM stages was compared using the Kaplan-Meier method and further analysed using univariable and multivariable Cox regression analyses. Receiver operating characteristic curves were used to assess model accuracy, Akaike information criterion, Bayesian information criterion and consistency index were used to compare the prognostic, predictive ability between the current 8th and 9th edition TNM classification. RESULTS: The 9th edition of the TNM staging system can better distinguish between IB and IIA patients on the survival curve (P < 0.0001). In both univariable and multivariable regression analysis, the 9th edition of the TNM staging system can differentiate any 2 adjacent staging patients more evenly than the 8th edition. The 9th and the 8th edition TNM staging have similar predictive power and accuracy for the overall survival of patients with NSCLC [TNM 9th vs 8th, area under the curve: 62.4 vs 62.3; Akaike information criterion: 166 182.1 vs 166 131.6; Bayesian information criterion: 166 324.3 vs 166 273.8 and consistency index: 0.650 (0.003) vs 0.651(0.003)]. CONCLUSIONS: Our external validation demonstrates that the 9th edition of TNM staging for NSCLC is reasonable and valid. The 9th edition of TNM staging for NSCLC has near-identical prognostic accuracy to the 8th edition.