Convolutional neural network applied to preoperative venous-phase CT images predicts risk category in patients with gastric gastrointestinal stromal tumors.

OBJECTIVE: The risk category of gastric gastrointestinal stromal tumors (GISTs) are closely related to the surgical method, the scope of resection, and the need for preoperative chemotherapy. We aimed to develop and validate convolutional neural network (CNN) models based on preoperative venous-phase CT images to predict the risk category of gastric GISTs. METHOD: A total of 425 patients pathologically diagnosed with gastric GISTs at the authors' medical centers between January 2012 and July 2021 were split into a training set (154, 84, and 59 with very low/low, intermediate, and high-risk, respectively) and a validation set (67, 35, and 26, respectively). Three CNN models were constructed by obtaining the upper and lower 1, 4, and 7 layers of the maximum tumour mask slice based on venous-phase CT Images and models of CNN_layer3, CNN_layer9, and CNN_layer15 established, respectively. The area under the receiver operating characteristics curve (AUROC) and the Obuchowski index were calculated to compare the diagnostic performance of the CNN models. RESULTS: In the validation set, CNN_layer3, CNN_layer9, and CNN_layer15 had AUROCs of 0.89, 0.90, and 0.90, respectively, for low-risk gastric GISTs; 0.82, 0.83, and 0.83 for intermediate-risk gastric GISTs; and 0.86, 0.86, and 0.85 for high-risk gastric GISTs. In the validation dataset, CNN_layer3 (Obuchowski index, 0.871) provided similar performance than CNN_layer9 and CNN_layer15 (Obuchowski index, 0.875 and 0.873, respectively) in prediction of the gastric GIST risk category (All P >.05). CONCLUSIONS: The CNN based on preoperative venous-phase CT images showed good performance for predicting the risk category of gastric GISTs.

MAP3K19 Promotes the Progression of Tuberculosis-Induced Pulmonary Fibrosis Through Activation of the TGF-ß/Smad2 Signaling Pathway.

Tuberculosis-induced pulmonary fibrosis (PF) is a chronic, irreversible interstitial lung disease, which severely affects lung ventilation and air exchange, leading to respiratory distress, impaired lung function, and ultimately death. As previously reported, epithelial-mesenchymal transition (EMT) and fibrosis in type II alveolar epithelial cells (AEC II) are two critical processes that contributes to the initiation and progression of tuberculosis-related PF, but the underlying pathological mechanisms remain unclear. In this study, through performing Real-Time quantitative PCR (RT-qPCR), Western blot, immunohistochemistry, and immunofluorescence staining assay, we confirmed that the expression levels of EMT and fibrosis-related biomarkers were significantly increased in lung tissues with tuberculosis-associated PF in vivo and Mycobacterium bovis Bacillus Calmette-Guérin (BCG) strain-infected AEC II cells in vitro. Besides, we noticed that the mitogen-activated protein kinase 19 (MAP3K19) was aberrantly overexpressed in PF models, and silencing of MAP3K19 significantly reduced the expression levels of fibronectin, collagen type I, and alpha-smooth muscle actin to decrease fibrosis, and upregulated E-cadherin and downregulated vimentin to suppress EMT in BCG-treated AEC II cells. Then, we uncovered the underlying mechanisms and found that BCG synergized with MAP3K19 to activate the pro-inflammatory transforming growth factor-beta (TGF-ß)/Smad2 signal pathway in AEC II cells, and BCG-induced EMT process and fibrosis in AEC II cells were all abrogated by co-treating cells with TGF-ß/Smad2 signal pathway inhibitor LY2109761. In summary, our results uncovered the underlying mechanisms by which the MAP3K19/TGF-ß/Smad2 signaling pathway regulated EMT and fibrotic phenotypes of AEC II cells to facilitate the development of tuberculosis-associated PF, and these findings will provide new ideas and biomarkers to ameliorate tuberculosis-induced PF in clinic.

Functional enhancement of acute infracted heart by coinjection of autologous adipose-derived stem cells with matrigel.

Recent clinical developments in tissue bioengineering have applications in acute cardiac ischemia and infarction and include the use of stem cells that combine injectable scaffold material. This study aimed to evaluate the effects of adipose-derived stem cells (ADSCs) that combine the Matrigel scaffold on cardiac morphology/functions. The autologous ADSCs myocardial infarction (MI) model was induced by the permanent ligation method of the left anterior descending coronary artery (LAD). MI-operated rats were randomly divided into PBS group, Matrigel group, PBS plus ADSCs group (PBS+ADSCs), and Matrigel plus ADSCs group (Matrigel+ADSCs). Matrigel was used as an injectable scaffold. Rats with a 1-week-old myocardial infarction were injected with 2 × 106 labeled ADSCs in the border area of the ischemic heart. Heart function was determined by echocardiography. The hemodynamics, cardiac structure, and graft characteristics were evaluated. The ADSCs were successfully isolated and identified, demonstrating a good proliferative status and cell retention in the Matrigel. ADSCs+Matrigel exhibited the most improved heart functions (LVESD, LVEDD, LVFS, LVEF) compared to those of other groups (p < 0.05). ADSCs+Matrigel significantly reduced infarct size compared to other groups (p < 0.05). Cotransplantation of ADSCs and Matrigel showed the best effect on maintaining the thickness of the ventricular wall compared to the other groups (p < 0.05). Engrafted ADSCs played a role in the formation of the neovasculature in myocardial infarction. ADSCs+Matrigel triggered the greatest enhancement in arteriole density than other groups (p < 0.05). Cotransplanting with ADSCs and Matrigel showed significantly higher levels of cardiac troponin T (cTnT), NK2-transcription factor related locus-5 (Nkx2.5), von Willebrand factor (vWF) than the other groups (p < 0.05). In conclusion, this study demonstrated that cotransplanting ADSCs with Matrigel resulted in improved cardiac morphology and cardiac function in the rat model of myocardial infarction.

On-Site Computed Tomography-Derived Fractional Flow Reserve to Guide Management of Patients With Stable Coronary Artery Disease: The TARGET Randomized Trial.

BACKGROUND: Computed tomography-derived fractional flow reserve (CT-FFR) using on-site machine learning enables identification of both the presence of coronary artery disease and vessel-specific ischemia. However, it is unclear whether on-site CT-FFR improves clinical or economic outcomes when compared with the standard of care in patients with stable coronary artery disease. METHODS: In total, 1216 patients with stable coronary artery disease and an intermediate stenosis of 30% to 90% on coronary computed tomographic angiography were randomized to an on-site CT-FFR care pathway using machine learning or to standard care in 6 Chinese medical centers. The primary end point was the proportion of patients undergoing invasive coronary angiography without obstructive coronary artery disease or with obstructive disease who did not undergo intervention within 90 days. Secondary end points included major adverse cardiovascular events, quality of life, symptoms of angina, and medical expenditure at 1 year. RESULTS: Baseline characteristics were similar in both groups, with 72.4% (881/1216) having either typical or atypical anginal symptoms. A total of 421 of 608 patients (69.2%) in the CT-FFR care group and 483 of 608 patients (79.4%) in the standard care group underwent invasive coronary angiography. Compared with standard care, the proportion of patients undergoing invasive coronary angiography without obstructive coronary artery disease or with obstructive disease not undergoing intervention was significantly reduced in the CT-FFR care group (28.3% [119/421] versus 46.2% [223/483]; P<0.001). Overall, more patients underwent revascularization in the CT-FFR care group than in the standard care group (49.7% [302/608] versus 42.8% [260/608]; P=0.02), but major adverse cardiovascular events at 1 year did not differ (hazard ratio, 0.88 [95% CI, 0.59-1.30]). Quality of life and symptoms improved similarly during follow-up in both groups, and there was a trend towards lower costs in the CT-FFR care group (difference, -¥4233 [95% CI, -¥8165 to ¥973]; P=0.07). CONCLUSIONS: On-site CT-FFR using machine learning reduced the proportion of patients with stable coronary artery disease undergoing invasive coronary angiography without obstructive disease or requiring intervention within 90 days, but increased revascularization overall without improving symptoms or quality of life, or reducing major adverse cardiovascular events. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03901326.

Risk prediction model establishment with tri-phasic CT image features for differential diagnosis of adrenal pheochromocytomas and lipid-poor adenomas: Grouping method.

Objectives: The purpose of this study was to establish a risk prediction model for differential diagnosis of pheochromocytomas (PCCs) from lipid-poor adenomas (LPAs) using a grouping method based on tri-phasic CT image features. Methods: In this retrospective study, we enrolled patients that were assigned to a training set (136 PCCs and 183 LPAs) from two medical centers, along with an external independent validation set (30 PCCs and 54 LPAs) from another center. According to the attenuation values in unenhanced CT (CTu), the lesions were divided into three groups: group 1, 10 HU < CTu ≤ 25 HU; group 2, 25 HU < CTu ≤ 40 HU; and group 3, CTu > 40 HU. Quantitative and qualitative CT imaging features were calculated and evaluated. Univariate, ROC, and binary logistic regression analyses were applied to compare these features. Results: Cystic degeneration, CTu, and the peak value of enhancement in the arterial and venous phase (DEpeak) were independent risk factors for differential diagnosis of adrenal PCCs from LPAs. In all subjects (groups 1, 2, and 3), the model formula for the differentiation of PCCs was as follows: Y = -7.709 + 3.617*(cystic degeneration) + 0.175*(CTu ≥ 35.55 HU) + 0.068*(DEpeak ≥ 51.35 HU). ROC curves were drawn with an AUC of 0.95 (95% CI: 0.927-0.973) in the training set and 0.91 (95% CI: 0.860-0.929) in the external validation set. Conclusion: A reliable and practical prediction model for differential diagnosis of adrenal PCCs and LPAs was established using a grouping method.

Risk stratification of 2- to 5-cm gastric stromal tumors based on clinical and computed tomography manifestations.

OBJECTIVE: To evaluate the risk stratification of 2- to 5-cm gastric stromal tumors (GSTs) by analyzing their clinical and computed tomography (CT) manifestations with the goal of providing imaging evidence for rational selection of surgical methods. METHODS: This study involved 223 patients with pathologically diagnosed GSTs of 2 to 5 cm in diameter. According to the pathological results and malignant risk category, the patients were divided into a low-risk biological behavior group (very low and low risk) and high-risk biological behavior group (intermediate and high risk). The clinical and CT manifestations were compared between the groups. The chi-square test was used to analyze categorical variables, and the independent-samples t test was used to analyze continuous variables. Multivariate logistic regression and receiver operating characteristic curve analysis were performed for statistically significant variables. RESULTS: The tumor contour, necrosis, surface ulceration, and long diameter were significantly different between the low-risk group and the high-risk group (P < 0.05). Multivariate logistic regression analysis showed that the tumor contour and long diameter were independent risk factors. The area under the curve was 0.82, and the accuracy, sensitivity, and specificity were 0.78, 77.4 %, and 79.7 %, respectively. CONCLUSIONS: The risk associated with 2- to 5-cm GSTs can be preoperatively predicted in an indirect manner through analysis of clinical and CT manifestations, and this model has high diagnostic value.

Building Radiomics Models Based on Triple-Phase CT Images Combining Clinical Features for Discriminating the Risk Rating in Gastrointestinal Stromal Tumors.

We aimed to build radiomics models based on triple-phase CT images combining clinical features to predict the risk rating of gastrointestinal stromal tumors (GISTs). A total of 231 patients with pathologically diagnosed GISTs from July 2012 to July 2020 were categorized into a training data set (82 patients with high risk, 80 patients with low risk) and a validation data set (35 patients with high risk, 34 patients with low risk) with a ratio of 7:3. Four diagnostic models were constructed by assessing 20 clinical characteristics and 18 radiomic features that were extracted from a lesion mask based on triple-phase CT images. The receiver operating characteristic (ROC) curves were applied to calculate the diagnostic performance of these models, and ROC curves of these models were compared using Delong test in different data sets. The results of ROC analyses showed that areas under ROC curves (AUC) of model 4 [Clinic + CT value of unenhanced (CTU) + CT value of arterial phase (CTA) + value of venous phase (CTV)], model 1 (Clinic + CTU), model 2 (Clinic + CTA), and model 3 (Clinic + CTV) were 0.925, 0.894, 0.909, and 0.914 in the training set and 0.897, 0.866, 0,892, and 0.892 in the validation set, respectively. Model 4, model 1, model 2, and model 3 yielded an accuracy of 88.3%, 85.8%, 86.4%, and 84.6%, a sensitivity of 85.4%, 84.2%, 76.8%, and 78.0%, and a specificity of 91.2%, 87.5%, 96.2%, and 91.2% in the training set and an accuracy of 88.4%, 84.1%, 82.6%, and 82.6%, a sensitivity of 88.6%, 77.1%, 74.3%, and 85.7%, and a specificity of 88.2%, 91.2%, 91.2%, and 79.4% in the validation set, respectively. There was a significant difference between model 4 and model 1 in discriminating the risk rating in gastrointestinal stromal tumors in the training data set (Delong test, p < 0.05). The radiomic models based on clinical features and triple-phase CT images manifested excellent accuracy for the discrimination of risk rating of GISTs.

Computed tomography characteristics of adrenal ganglioneuroma: a retrospective analysis of 30 pathologically-confirmed cases.

OBJECTIVE: To investigate the computed tomography (CT) characteristics of adrenal ganglioneuromas (AGNs) and to determine the ability of CT scanning to distinguish between large (>3 cm) and small (≤3 cm) AGNs. METHODS: This retrospective study searched the electronic medical record system of a hospital between January 2008 and July 2019 in order to identify patients with pathologically-confirmed AGNs that underwent three phases of CT scanning. The CT features were compared between large and small AGNs. RESULTS: A total of 30 patients with pathologically-confirmed AGNs were included in the study. The majority of patients (76.7%; 23 of 30) were asymptomatic and there were nonspecific symptoms in seven patients. The 'pointed peach' sign appeared in more than half of the patients (53.3%; 16 of 30). The CT value of the arterial phase, progressive enhancement, morphology and calcification in the CT images were found to be significantly different between large and small AGNs. Progressive enhancement was more likely to occur in small AGNs. Most large AGNs had irregular shapes, while small AGNs were likely to be round or oval with a smooth border. Calcifications were noted in large AGNs (42.9%; six of 14). CONCLUSION: CT scanning can show many of the key imaging characteristics of AGNs used to distinguish between large and small AGNs.

Lower Posttraumatic α-Synuclein Level Associated With Altered Default Mode Network Connectivity Following Acute Mild Traumatic Brain Injury.

This study aimed to investigate the changes of α-synuclein in serum and its relationship with default mode network (DMN) connectivity after acute mild traumatic brain injury (mild TBI). Fifty-two patients with mild TBI at the acute phase and 47 matched healthy controls were enrolled in the study. All participants received resting-state functional magnetic resonance imaging (fMRI) and neuropsychological assessments. Relations between the levels of α-synuclein in serum and clinical assessments were obtained using multivariate linear regression. Results showed that the patients with lower α-synuclein presented more complaints on post-concussion symptoms and depression. Moreover, patients with high levels of α-synuclein exhibited significantly decreased functional connectivity in the left precuneus and increased functional connectivity in both the left anterior cingulate cortex and ventro-medial prefrontal cortex (MPFC) compared with patients with low levels of α-synuclein. These findings supported that α-synuclein may modulate the functional connectivity within the DMN and suggest the feasibility of using α-synuclein as an objective biomarker for diagnosis and prognosis of mild TBI.

Sex differences in cerebral perfusion changes after mild traumatic brain injury: Longitudinal investigation and correlation with outcome.

Cerebral blood flow (CBF) is known to have marked developmental sex differences. We investigated whether gender differences exert modulatory effect on mild traumatic brain injury (mTBI) from both neuropsychological testing and brain CBF changes using a longitudinal design from acute stage to subacute 1 month post-injury. Our results supported that cognitive information processing speed (IPS), as one of core cognitive impairments following mTBI, were at least partially independent from other self-reported syndromes, such as post concussive symptom and posttraumatic stress disorder, and that it can be selectively impaired in specific male mTBI individuals. The gender difference of this cognitive domain in healthy control attenuated following mTBI and only male patients showed impaired language fluency accompanying with increased CBF changes compared with male controls. The increased CBF in the posterior parietal cortex (PPC) can predict much worse cognitive IPS performance in male patients. In contrast, female patients with mTBI displayed no impairments on any neuropsychological performance, and female sex may be a protective factor against neuropsychological impairments. Moreover, the significant interaction effect of time and gender exhibited in the left inferior frontal cortex (Broca's area). Simple effect test suggested gender differences in this area was mainly derived from the patients group at later subacute but not acute phase, for the reduced CBF at subacute mainly in the male patients. Thus, the current findings suggest that regional CBF may provide an objective biomarker for tracking gender modulatory effect on mTBI and its potentially pathological recovery process.

Preliminary Evidence of Sex Differences in Cortical Thickness Following Acute Mild Traumatic Brain Injury.

The main objective of this study was to evaluate sex differences in cortical thickness after acute mild traumatic brain injury (mTBI) and its associations with clinical outcomes. Thirty-two patients with mTBI at acute phase (2.4 ± 1.3 days post-injury) and 30 healthy controls were enrolled. All the participants underwent comprehensive neurocognitive assessments and MRI to assess cortical thickness. Significant sex differences were determined by using variance analysis of factorial design. Relations between the cortical thickness and clinical assessments were measured with the Spearman Correlation. Results revealed that patients with mTBI had significantly reduced cortical thickness in the left entorhinal cortex while increased cortical thickness in the left precuneus cortex and right lateral occipital cortex, compared with healthy controls. The interaction effect of the group × sex on cortical thickness was significant. Female patients had significant thicker cortical thickness in the left caudal anterior cingulate cortex (ACC) than male patients and had higher scores on Posttraumatic stress disorder Checklist-Civilian Version (PCL-C). Spearman correlational analysis showed a significantly positive correlations between the cortical thickness of the left caudal ACC and PCL-C ratings in female patients. Sex differences in cortical thickness support its potential as a neuroimaging phenotype for investigating the differences in clinical profiles of mild TBI between women and men.

Longitudinal Changes of Caudate-Based Resting State Functional Connectivity in Mild Traumatic Brain Injury.

Mild traumatic brain injury (mild TBI) is associated with dysfunctional brain network and accumulating evidence is pointing to the caudate as a vulnerable hub region. However, little is known about the longitudinal changes in the caudate-based resting-state functional connectivity following mild TBI. In the current study, 50 patients with mild TBI received resting-state functional magnetic resonance imaging as well as neuropsychological assessments within 7 days post-injury (acute phase) and 1 month later (subacute phase). Thirty-six age- and gender- matched healthy controls underwent the same protocol. The caudate was segmented into the dorsal and ventral sub-regions based on their related functionally distinct neural circuits and separate functional connectivity was investigated. Results indicated that patients with mild TBI at acute phase exhibited reduced left dorsal caudate-based functional connectivity with ventral lateral prefrontal cortex, dorsal anterior cingulate cortex, and inferior parietal lobule, which mainly distributed in the cognitive control network, and reduced right ventral caudate-based functional connectivity with the dorsal lateral prefrontal cortex, dorsal anterior cingulate cortex (dACC), and bilateral ventral anterior cingulate cortex (vACC), which mainly distributed in the executive network and emotional processing network. Furthermore, patients with mild TBI presented the reduced functional connectivity between the left dorsal caudate and the ventral lateral prefrontal cortex (vlPFC) compared with healthy controls at acute phase while this difference became no significance and return to the normal level following 1 month post-injury subacute phase. Similarly, the functional connectivity between the right ventral caudate and anterior cingulate cortex (both dorsal and ventral part) showed the reduced strength in patients compared with healthy controls only at the acute phase but presented no significant difference at subacute phase following mild TBI. Along the same line, patients with mild TBI presented the impaired performance on the information processing speed and more complaints on the pain impact index at acute phase compared with healthy controls but showed no significant difference at the follow-up 1 month post-injury subacute phase. The longitudinal changes of caudate-based dysfunction connectivity could serve as a neuroimaging biomarker following patients with mild TBI, with the evidence that the abnormal caudate-based functional connectivity at acute phase have returned to the normal level accompanying with the recovery of the neuropsychological syndromes following patients with mild TBI at subacute phase.

Efficacy and safety of nucleoside analogs on blocking father-to-infant vertical transmission of hepatitis B virus.

The aim of the present study was to observe the efficacy and safety of nucleoside analogs in inhibiting father-to-infant vertical transmission of hepatitis B virus (HBV). Nucleoside analogs compete with HBV DNA polymerase substrate to inhibit DNA polymerase, thus preventing the replication of HBV DNA. A case group and control group were recruited for the study. Between March 2006 and March 2012 at the Liver Disease Center of Qinhuangdao Third Hospital, a total of 201 couples were recruited for the case group. In each case, the father tested positive the following HBV markers: Hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), antibodies against the hepatitis B core antigen (anti-HBc) and HBV DNA. In total, 189 male patients presented with abnormal liver function (94.0%; 189/201). Prior to pregnancy, all the males in the case group were required to test negative for HBV DNA and exhibit normal liver function, while the females were required to test positive for antibodies against HBsAg (anti-HBs). In total, 188 couples comprised the control group. The couples were recruited between March 2006 and March 2012 in the Prenatal Clinic of Qinhuangdao Women's and Children's Hospital. The fathers tested positive for HBsAg, HBeAg, anti-HBc and HBV DNA. With regard to the females, HBsAg tests were all negative and anti-HBs tests were positive. In the case group, there were no HBsAg-positive or HBV DNA-positive newborns, while anti-HBs tests were all positive; thus, the father-to-infant HBV vertical transmission was successfully inhibited. In the control group, 147/188 newborns tested positive for anti-HBs at birth, accounting for 78.2%. In addition, 28 newborns were positive for HBV DNA (14.9%), and 19 newborns tested positive for HBsAg (10.1%). Statistically significant differences were observed between the two groups with regard to these parameters. However, no statistically significant differences in gestational age, birth weight, birth height, 1- and 8-min Apgar scores, presence of jaundice, other internal and surgical diseases, delivery mode and other birth information were observed when comparing the case group with the control group. Furthermore, there were no fetal malformations or stillbirths in the two groups. In the HBV DNA-positive fathers prior to pregnancy, antiretroviral therapy resulted in a reduced virus load. Therefore, blocking father-to-infant HBV vertical transmission maximally was important. The use of antiviral nucleoside analogs prior to pregnancy was shown to be safe. When the benefits outweighed the risks, the fathers who wanted to have a child continued to use antiviral therapy. However, the sample size of the present study was small, and an increased number of cases and longer follow-up times are required. In addition, the use of nucleoside analogs requires further in-depth assessment from the point of view of prenatal and postnatal care.