Spinal cord and brain atrophy patterns in neuromyelitis optica spectrum disorder and multiple sclerosis.

BACKGROUND: Spinal cord and brain atrophy are common in neuromyelitis optica spectrum disorder (NMOSD) and relapsing-remitting multiple sclerosis (RRMS) but harbor distinct patterns accounting for disability and cognitive impairment. METHODS: This study included 209 NMOSD and 304 RRMS patients and 436 healthy controls. Non-negative matrix factorization was used to parse differences in spinal cord and brain atrophy at subject level into distinct patterns based on structural MRI. The weights of patterns were obtained using a linear regression model and associated with Expanded Disability Status Scale (EDSS) and cognitive scores. Additionally, patients were divided into cognitive impairment (CI) and cognitive preservation (CP) groups. RESULTS: Three patterns were observed in NMOSD: (1) Spinal Cord-Deep Grey Matter (SC-DGM) pattern was associated with high EDSS scores and decline of visuospatial memory function; (2) Frontal-Temporal pattern was associated with decline of language learning function; and (3) Cerebellum-Brainstem pattern had no observed association. Patients with CI had higher weights of SC-DGM pattern than CP group. Three patterns were observed in RRMS: (1) DGM pattern was associated with high EDSS scores, decreased information processing speed, and decreased language learning and visuospatial memory functions; (2) Frontal-Temporal pattern was associated with overall cognitive decline; and (3) Occipital pattern had no observed association. Patients with CI trended to have higher weights of DGM and Frontal-Temporal patterns than CP group. CONCLUSION: This study estimated the heterogeneity of spinal cord and brain atrophy patterns in NMOSD and RRMS patients at individual level, and evaluated the clinical relevance of these patterns, which may contribute to stratifying participants for targeted therapy.

A Fully Automated Deep-Learning Model for Predicting the Molecular Subtypes of Posterior Fossa Ependymomas Using T2-Weighted Images.

PURPOSE: We aimed to develop and validate a deep learning (DL) model to automatically segment posterior fossa ependymoma (PF-EPN) and predict its molecular subtypes [Group A (PFA) and Group B (PFB)] from preoperative MR images. EXPERIMENTAL DESIGN: We retrospectively identified 227 PF-EPNs (development and internal test sets) with available preoperative T2-weighted (T2w) MR images and molecular status to develop and test a 3D nnU-Net (referred to as T2-nnU-Net) for tumor segmentation and molecular subtype prediction. The network was externally tested using an external independent set [n = 40; subset-1 (n = 31) and subset-2 (n =9)] and prospectively enrolled cases [prospective validation set (n = 27)]. The Dice similarity coefficient was used to evaluate the segmentation performance. Receiver operating characteristic analysis for molecular subtype prediction was performed. RESULTS: For tumor segmentation, the T2-nnU-Net achieved a Dice score of 0.94 ± 0.02 in the internal test set. For molecular subtype prediction, the T2-nnU-Net achieved an AUC of 0.93 and accuracy of 0.89 in the internal test set, an AUC of 0.99 and accuracy of 0.93 in the external test set. In the prospective validation set, the model achieved an AUC of 0.93 and an accuracy of 0.89. The predictive performance of T2-nnU-Net was superior or comparable to that of demographic and multiple radiologic features (AUCs ranging from 0.87 to 0.95). CONCLUSIONS: A fully automated DL model was developed and validated to accurately segment PF-EPNs and predict molecular subtypes using only T2w MR images, which could help in clinical decision-making.

"Soap bubble" sign as an imaging marker for posterior fossa ependymoma Group B.

PURPOSE: To investigate the predictive value of the "soap bubble" sign on molecular subtypes (Group A [PFA] and Group B [PFB]) of posterior fossa ependymomas (PF-EPNs). METHODS: MRI scans of 227 PF-EPNs (internal retrospective discovery set) were evaluated by two independent neuroradiologists to assess the "soap bubble" sign, which was defined as clusters of cysts of various sizes that look like "soap bubbles" on T2-weighted images. Two independent cohorts (external validation set [n = 31] and prospective validation set [n = 27]) were collected to validate the "soap bubble" sign. RESULTS: Across three datasets, the "soap bubble" sign was observed in 21 PFB cases (7.4% [21/285] of PF-EPNs and 12.9% [21/163] of PFB); none in PFA. Analysis of the internal retrospective discovery set demonstrated substantial interrater agreement (1st Rating: κ = 0.71 [0.53-0.90], 2nd Rating: κ = 0.83 [0.68-0.98]) and intrarater agreement (Rater 1: κ = 0.73 [0.55-0.91], Rater 2: κ = 0.74 [0.55-0.92]) for the "soap bubble" sign; all 13 cases positive for the "soap bubble" sign were PFB (p = 0.002; positive predictive value [PPV] = 100%, negative predictive value [NPV] = 44%, sensitivity = 10%, specificity = 100%). The findings from the external validation set and the prospective validation set were similar, all cases positive for the "soap bubble" sign were PFB (p < 0.001; PPV = 100%). CONCLUSION: The "soap bubble" sign represents a highly specific imaging marker for the PFB molecular subtype of PF-EPNs.

Characteristic cerebral perfusion pattern in neuronal intranuclear inclusion disease.

Background: Neuronal intranuclear inclusion disease (NIID), which pathogenesis remains largely unclear, is a neurodegenerative disease caused by GGC repeat expansion in NOTCH2NLC gene. As case studies have reported dynamic cortical perfusion changes in NIID, this study aimed to explore the cerebral perfusion pattern in NIID patients. Materials and methods: A total of 38 NIID patients and 34 healthy controls (HCs) were recruited, and 2 NIID patients who had had episodic symptoms within 2 months were excluded. Data on demographic characteristics and clinical features were collected. All participants underwent three-dimensional pseudo-continuous arterial spin labeling perfusion magnetic resonance imaging (MRI) scanning. Voxel-based comparisons of cerebral blood flow (CBF) were conducted. Results: NIID patients showed decreased perfusion in the cortex but increased perfusion in the deep brain regions compared with HCs. The regions with significant hypoperfusion were distributed in the bilateral frontal, temporal, parietal, and occipital gyri, with the left frontal gyrus being the most prominent. The regions with significant hyperperfusion included the bilateral basal ganglia, midbrain, pons, para-hippocampal, and parts of the bilateral cerebellum, fusiform, lingual, rectus, orbital, and cingulum anterior gyri, which were adjacent to the midline (all FDR-corrected p <0.05). When comparing the mean CBF value of the whole brain, no significant differences were observed between NIID patients and HCs (28.81 ± 10.1 vs. 27.99 ± 5.68 ml/100 g*min, p = 0.666). Voxel-based analysis showed no significant difference in cerebral perfusion between NIID patients with and without episodic symptoms. The perfusion within the bilateral middle frontal and anterior cingulate gyri showed positive correlations with MMSE and MoCA scores using age, sex, and education as covariates (p <0.005 uncorrected). Conclusion: NIID patients exhibited characteristic cortical hypoperfusion and deep brain hyperperfusion. The perfusion in the bilateral frontal lobe and cingulate gyrus was correlated with the severity of cognitive dysfunction. Cerebral perfusion change may be involved in NIID pathophysiology and serve as a potential indicator for monitoring NIID severity and progression.

Validating ORR and PFS as surrogate endpoints in phase II and III clinical trials for NSCLC patients: difference exists in the strength of surrogacy in various trial settings.

OBJECTIVE: This study aims to systematically validate the performance of surrogate endpoints in phase II and III clinical trials for NSCLC patients under various trial settings. METHODS: A literature search retrieved all registered phase II and III trials of NSCLC patients in which OS, with at least one of ORR and PFS, were reported. Associations between surrogate and true endpoints were assessed on two levels. On the arm level, three pairs of correlations, i.e., ORR vs. median OS, ORR vs. median PFS, and median PFS vs. median OS, were analysed using Spearman's rho. On the trial level, similarly, three pairs of correlations, i.e., ΔORR vs. HR of OS, ΔORR vs. HR of PFS, and HR of PFS vs. HR of OS, were analysed using Spearman's rho and weighted linear regression model respectively. Finally, sensitivity analyses were performed to explore surrogacy under various trial settings. RESULTS: At arm level, three pairs of correlations are all high (Spearman's rho = 0.700, 0.831, 0.755, respectively). At trial level, there is a low correlation between ΔORR and HR of OS, a high correlation between ΔORR and HR of PFS and a moderate correlation between HR of PFS and HR of OS (Spearman's rho = 0.462, 0.764, 0.584, respectively). In the sensitivity analysis, we find correlations between surrogate and true endpoints vary by different trial settings. It is noteworthy that the strength of surrogacy of these intermediate endpoints in targeted therapy is greater than that in immunotherapy. CONCLUSION: According to the arm-level and trial level-analysis, we suggest that in phase II and III trials of targeted therapy and immunotherapy for NSCLC patients: 1) ORR lacks validity for the surrogacy of OS, excluding in first-line therapy, and 2) ORR may be an appropriate surrogate endpoint for PFS, and 3) PFS may be considered a modest surrogacy for OS, with better performance in first-line therapy trials. Moreover, to provide more convincing evidence of surrogacy of the surrogate endpoints, patient-level analyses are in desperate need.

Prediction of H3 K27M-mutant in midline gliomas by magnetic resonance imaging: a systematic review and meta-analysis.

PURPOSE: To summarize the predictive value of MRI for H3 K27M-mutant in midline gliomas using meta-analysis. METHODS: Systematic electronic searches of the PubMed, Embase, ISI Web of Science, and Cochrane Library up to Jun 31, 2021, were conducted by two experienced neuroradiologists with the keywords of "MRI," "Glioma," and "H3 K27M." The hierarchical summary receiver-operating characteristic (HSROC) model was used to calculate the pooled sensitivity, specificity, positive likelihood ratio (LR +), negative likelihood ratio (LR -), and diagnostic odds ratio (DOR). Coupled forest plots were used to evaluate the heterogeneity of the included studies. RESULTS: Of seven original studies with a total of 593 patients, 240 glioma patients were included, with 45.5-70.6% H3 K27M-mutant gliomas. Using MRI, a pooled sensitivity of 0.78 (95% CI, 0.66-0.87), specificity of 0.85 (95% CI, 0.76-0.91), LR + of 5.07 (95% CI, 3.19-8.08), LR - of 0.26 (95% CI, 0.16-0.42), and DOR of 19.80 (95% CI, 9.28-42.28) were achieved for H3 K27M-mutant prediction. Significant heterogeneity was observed among the studies in terms of sensitivity (Q = 16.83, df = 7, p = 0.02; I2 = 58.40 [95% CI, 25.83-90.97]), LR - (Q = 16.61, df = 7, p = 0.02; I2 = 57.87 [95% CI, 24.81-90.93]), and DOR (Q = 14.05, df = 7, p = 0.05; I2 = 50.18 [95% CI, 10.06-90.31]). CONCLUSIONS: This meta-analysis demonstrated a clinical value of MRI to predict H3 K27M-mutant in midline gliomas with a pooled sensitivity of 0.78 and specificity of 0.85.

Identifying patients with major depressive disorder based on tryptophan hydroxylase-2 methylation using machine learning algorithms.

OBJECTIVES: This study aimed to identify patients with major depressive disorder (MDD) by developing different machine learning (ML) models based on tryptophan hydroxylase-2 (TPH2) methylation and environmental stress. METHODS: The data were collected from 291 patients with MDD and 100 healthy control participants: individual basic information, the Negative Life Events Scale (NLES) scores, the Childhood Trauma Questionnaire (CTQ) scores and the methylation level at 38 CpG sites in TPH2. Information gain was used to select critical input variables. Support vector machine (SVM), back propagation neural network (BPNN) and random forest (RF) algorithms were used to build recognition models, which were evaluated by the 10-fold cross-validation. SHapley Additive exPlanations (SHAP) method was used to evaluate features importance. RESULTS: Gender, NLES scores, CTQ scores and 13 CpG sites in TPH2 gene were considered as predictors in the models. Three ML algorithms showed satisfactory performance in predicting MDD and the BPNN model indicated best prediction effects. CONCLUSION: ML models with TPH2 methylation and environmental stress were identified to possess great performance in identifying patients with MDD, which provided precious experience for artificial intelligence to assist traditional diagnostic methods in the future.

Relationship between demographic factors, health education, breast cancer-related knowledge, attitudes, and breast self-examination behavior among Chinese female college student: A structural equation analysis.

AIMS: This study aimed to create a structural equation model to evaluate the associations among demographic factors, health education, breast cancer-related knowledge, attitudes, and breast self-examination behavior among Chinese female college students. METHODS: A survey was undertaken using a self-administered questionnaire and targeting 2233 students from Eastern China. Structural equation modeling with the bootstrap approach was utilized to estimate the interrelationships and the strength of the associations among measured variables based on the hypothetical model. RESULTS: Among the total participants, 14.7% of the female college students reported having performed breast self-examination. The final structural equation model showed highly satisfactory fitness on indices. Breast self-examination behavior was significantly linked to demographic factors, breast cancer related-knowledge, attitudes, and health education. Health education had the greatest influence on breast self-examination behavior. In addition, breast cancer related-knowledge was significantly associated with demographic factors and health education. Health education and knowledge all significantly affected attitudes towards breast cancer. CONCLUSION: Breast self-examination behavior was influenced by demographic factors, breast cancer related-knowledge, attitudes towards breast cancer, and health education in a sample of female college students in China. Health education was the most important predictor of breast self-examination behavior.

The ratio of gastric tube length to thorax length: a vital factor affecting leak after esophageal cervical anastomosis.

BACKGROUND: Esophagogastric anastomotic leak (AL) is a severe complication following esophageal resection. This study aims to explore preliminarily whether the ratio of the gastric conduit length to the thorax length can be regarded as a potential prognostic variable for AL, and if so, a cut-off value can be found to divide the patients into distinct risk groups. METHODS: We retrospectively reviewed the clinical data of 273 patients who underwent esophagectomy. The gastric conduit length, the thorax length, and other covariates were collected. Logistic regression was first conducted to probe the rationality of the ratio as a risk indicator of AL. Then the dichotomizing analysis was applied to find the optimal cut-off value. RESULTS: The incidence of AL was 12.5% (34/273). The coefficient of the ratio in the logistic regression equation was -7.901 with P<0.001, which indicated that the larger the ratio, the smaller the risk of AL. Further smoothed scatter plots revealed that a potential step function of the ratio of AL incidence exists, of which the steep part ranges from 1.74 to 1.90. Results of the accurate cut-off value search through a minimum P value approach give the optimal dichotomization point of 1.79. CONCLUSIONS: The ratio of the gastric conduit length to the thorax length can reflect the tension in the anastomosis. The research proposes that surgeons can control the length of the gastric conduit during reconstruction to reduce the tension in the anastomosis and thus lead to a decrease in the incidence of AL.

Relationship between oral health-related knowledge, attitudes, practice, self-rated oral health and oral health-related quality of life among Chinese college students: a structural equation modeling approach.

BACKGROUND: This study aimed to evaluate the associations among oral health-related knowledge, attitudes, practice (KAP), self-rated oral health and oral health-related quality of life (OHRQoL) among Chinese college students. METHODS: Of the 2000 participants, 1751 (87.55%) students answered an online questionnaire between October 2019 and January 2020. The questionnaire included demographic characteristics, knowledge, attitudes, and practice related to oral health, self-rated oral health, and OHRQoL. Structural equation modelling was applied to assess the associations among study variables. RESULTS: Among the total students, oral health-related knowledge and attitudes were satisfactory, while the oral health practice was not optimistic. The final model showed satisfactory fitness to the data. Oral health knowledge was associated with attitudes directly and positively. Attitudes toward oral health had a direct and positive effect on practice. Oral health knowledge had an indirect effect on practice through attitudes. Oral health practice was directly associated with self-rated oral health. Oral health knowledge, practice, and self-rated oral health all affected OHRQoL directly and positively, while attitudes had a direct negative impact on OHRQoL. CONCLUSIONS: OHRQoL was influenced by oral health knowledge, attitudes, practice, and self-rated oral health. Our findings support the KAP theory. Limitations of the KAP model were also found.

First-line atezolizumab plus chemotherapy in advanced non-squamous non-small cell lung cancer: a cost-effectiveness analysis from China.

Objective: To assess the cost-effectiveness of atezolizumab in combination with carboplatin plus nab-paclitaxel-based chemotherapy versus chemotherapy alone for first-line treatment of advanced non-squamous non-small cell lung cancer (NSCLC) from the Chinese healthcare system perspective.Methods: A Markov model was developed based on the IMpower130 clinical trial. Drug costs and health state utility were obtained from the literature. Outcomes included life-years (LYs), quality-adjusted life-years (QALYs), lifetime costs, and incremental cost-effectiveness ratio (ICER). One-way and probabilistic sensitivity analyses were performed to evaluate the model uncertainty.Results: When compared to chemotherapy alone, atezolizumab plus chemotherapy provides an additional 0.34 LY and 0.19 QALY, and has an ICER of $180,560.15 per additional LY gained and that of $325,328.71 per QALY gained. Sensitivity analysis revealed that the results were most sensitive to changes in atezolizumab cost. Probabilistic sensitivity analysis showed that there was a 0% probability that atezolizumab plus chemotherapy was cost-effective at willingness-to-pay values of $30,828 per QALY. If the WTP threshold increased to $325,000 per QALY, atezolizumab plus chemotherapy has a 50% chance to be cost-effective.Conclusions: From the Chinese healthcare system perspective, atezolizumab combination is not cost-effective for first-line therapy of advanced non-squamous NSCLC.

Structural equation modeling to detect predictors of breast self-examination behavior: Implications for intervention planning.

AIM: Breast cancer is the most frequent malignant tumor among Chinese women. Breast self-examination (BSE) is a simple, effective method for early detection of screening and it is essential for the prevention and control of breast cancer. The aim of this study was to create a hypothetical model to determine the factors influencing women's BSE behavior in Eastern China. METHODS: A survey was conducted using an online questionnaire and targeting 1200 women aged 18-70 years in Eastern China. Collected data were analyzed using ibm spss 25.0 and amos 24.0 software. RESULTS: The final model showed a desirable fitness to sample data. A direct positive relationship exists between knowledge on risk factors and BSE. A direct positive association was found between positive attitudes and BSE, while negative attitudes have a direct negative impact on BSE. Objective factors not only had a significant direct impact on BSE, but also directly affected the positive attitudes. Positive attitudes play an intermediary role between objective factors and BSE. CONCLUSION: Knowledge on risk factors about breast cancer, attitudes toward BSE and objective factors are new predictors which may influence BSE by using the structural equation modeling method.

The relationship of tryptophan hydroxylase-2 methylation to early-life stress and its impact on short-term antidepressant treatment response.

INTRODUCTION: The gene tryptophan hydroxylase 2 (TPH2) encodes the associated rate-limiting enzyme in the biosynthesis 5-HT (serotonin). Early life stress and adult variability in TPH2 can correspond with diminished response to antidepressants for patients with major depressive disorder (MDD). DNA methylation is an epigenetic mechanism mediating gene expression, often tempered by environmental factors. Here, we investigate the influence of TPH2 methylation combined with stress on response to antidepressants within the first two weeks of treatment initiation. METHODS: 291 Han Chinese patients with major depressive disorder and 100 healthy controls comprised the study population. The Life Events Scale (LES) and the Childhood Trauma Questionnaire (CTQ) rated recent and early-life stress. The primary outcome equaled a reduction by ≥ 50% from the Hamilton Depression Rating Scale-17 (HAMD-17) after 2 weeks of treatment. The Illumina HiSeq platform assessed methylation status in 38 CpG sites located upstream and downstream of 11 TPH2 polymorphism sites. RESULTS: In 291 patients and 100 healthy controls, 3 CpG sites predict antidepressant treatment response per sex (TPH2-7-142, p=0.012; TPH2-1-43, p=0.033; TPH2-5-203, p=0.036). High-level CTQ scores relate significantly to DNA hypomethylation at CpG-site TPH2-8-237 in males (false discovery rate [FDR]-corrected p=0.038). Additionally, the interaction of hypermethylation in two CpG sites and elevated early-life stress may reduce antidepressant response (TPH2-5-203, FDR corrected p=0.010; TPH2-10-60, FDR corrected p=0.001). CONCLUSIONS: Our study suggests that TPH2 methylation and its interaction with early-life stress may impair antidepressant response, suggesting that pharmaco-epigenetic studies could identify epigenetic biomarkers for antidepressant response.

Effect of different therapeutic strategies on the clinical outcome of asymptomatic intralobar pulmonary sequestration.

OBJECTIVES: Pulmonary sequestration is a rare congenital pulmonary malformation. The aim of this study was to explore the effect of different therapeutic strategies on the clinical outcome of asymptomatic intralobar pulmonary sequestration. METHODS: We retrospectively reviewed the clinical data of 37 patients diagnosed with intralobar sequestration. All the patients were asymptomatic. Seventeen patients underwent video-assisted thoracoscopic surgery (VATS) once diagnosed and 20 patients chose to undergo observation. Of these 20 patients, 16 patients developed symptoms during the observation period and also underwent VATS; 4 patients never showed symptoms and did not have surgery. The 33 patients who had VATS were divided into 2 groups: group 1, patients who underwent VATS once diagnosed; group 2, patients who underwent VATS once symptoms appeared. Postoperative data and respiratory function data were compared between the 2 groups. RESULTS: Twenty of the patients were men and 17 were women (mean age 37.05 ± 7.89 years). Results of a comparative analysis of the 2 groups indicated that patients in group 1 had better values for median estimated blood loss, median duration of chest tube insertion, postoperative hospital stay and postoperative hospital stay than those in group 2. Postoperative complications were reported in 1 patient in group 1 and in 3 patients in group 2. Meanwhile, the loss of lung function between group 1 and group 2 was statistically significant, which also suggested that patients benefited from surgery once diagnosed. CONCLUSIONS: For asymptomatic intralobar sequestration, VATS could be effective and safe. The surgical intervention should be performed once the condition is diagnosed to avoid manifestations occurring and to preserve patients' quality of life.