Automatic classification of spinal osteosarcoma and giant cell tumor of bone using optimized DenseNet.

Objective: This study aims to explore an optimized deep-learning model for automatically classifying spinal osteosarcoma and giant cell tumors. In particular, it aims to provide a reliable method for distinguishing between these challenging diagnoses in medical imaging. Methods: This research employs an optimized DenseNet model with a self-attention mechanism to enhance feature extraction capabilities and reduce misclassification in differentiating spinal osteosarcoma and giant cell tumors. The model utilizes multi-scale feature map extraction for improved classification accuracy. The paper delves into the practical use of Gradient-weighted Class Activation Mapping (Grad-CAM) for enhancing medical image classification, specifically focusing on its application in diagnosing spinal osteosarcoma and giant cell tumors. The results demonstrate that the implementation of Grad-CAM visualization techniques has improved the performance of the deep learning model, resulting in an overall accuracy of 85.61%. Visualizations of images for these medical conditions using Grad-CAM, with corresponding class activation maps that indicate the tumor regions where the model focuses during predictions. Results: The model achieves an overall accuracy of 80% or higher, with sensitivity exceeding 80% and specificity surpassing 80%. The average area under the curve AUC for spinal osteosarcoma and giant cell tumors is 0.814 and 0.882, respectively. The model significantly supports orthopedics physicians in developing treatment and care plans. Conclusion: The DenseNet-based automatic classification model accurately distinguishes spinal osteosarcoma from giant cell tumors. This study contributes to medical image analysis, providing a valuable tool for clinicians in accurate diagnostic classification. Future efforts will focus on expanding the dataset and refining the algorithm to enhance the model's applicability in diverse clinical settings.

Intrinsic Wave Velocity Propagation: A Novel Parameter for Assessing the Effect of Anthracycline Chemotherapy Agents on Cardiac Diastolic Function in Breast Cancer Patients.

OBJECTIVE: Anthracycline chemotherapeutic agents have significant cardiotoxicity. The present study emphasized the effect of anthracycline chemotherapy drugs on left ventricular (LV) myocardial stiffness in breast cancer patients by measuring the intrinsic wave velocity propagation (IVP), and evaluating the potential clinical value of IVP in detecting early LV diastolic function impairment. METHODS: A total of 68 newly diagnosed breast cancer patients, who were treated with anthracycline-based chemotherapy, were analyzed. Transthoracic echocardiography was performed at baseline (T0), and after 1, 2, 3, 4 and 8 chemotherapeutic cycles (T1, T2, T3, T4 and T5, respectively). Then, the IVP, LV strain parameters [global longitudinal strain (GLS), longitudinal peak strain rate at systole (LSRs), longitudinal peak strain rate at early diastole (LSRe), longitudinal peak strain rate at late diastole (LSRa), and the E/LSRe ratio], and conventional echocardiographic parameters were obtained and further analyzed. A relative reduction of >15% in GLS was considered a marker of early LV subclinical dysfunction. RESULTS: Compared to the T0 stage, IVP significantly increased at the T1 stage. However, there were no significant changes in GLS, LSRs, or LSRe between the T0 and T1 stages. These parameters significantly decreased from the T2 stage. LSRa started to significantly decrease at the T5 stage, and the E/LSRe ratio started to significantly increase at the T3 stage (all P<0.05). At the T0 stage, IVP (AUC=0.752, P<0.001) had a good predictive value for LV subclinical dysfunction after chemotherapy. CONCLUSIONS: IVP is a potentially sensitive parameter for the early clinical assessment of anthracycline-related cardiac diastolic impairment.

Genetic detection of two novel LRP5 pathogenic variants in patients with familial exudative vitreoretinopathy.

BACKGROUND: Familial exudative vitreoretinopathy (FEVR) is a genetic eye disorder that leads to abnormal development of retinal blood vessels, resulting in vision impairment. This study aims to identify pathogenic variants by targeted exome sequencing in 9 independent pedigrees with FEVR and characterize the novel pathogenic variants by molecular dynamics simulation. METHODS: Clinical data were collected from 9 families with FEVR. The causative genes were screened by targeted next-generation sequencing (TGS) and verified by Sanger sequencing. In silico analyses (SIFT, Polyphen2, Revel, MutationTaster, and GERP + +) were carried out to evaluate the pathogenicity of the variants. Molecular dynamics was simulated to predict protein conformation and flexibility transformation alterations on pathogenesis. Furthermore, molecular docking techniques were employed to explore the interactions and binding properties between LRP5 and DKK1 proteins relevant to the disease. RESULTS: A 44% overall detection rate was achieved with four variants including c.4289delC: p.Pro1431Argfs*8, c.2073G > T: p.Trp691Cys, c.1801G > A: p.Gly601Arg in LRP5 and c.633 T > A: p.Tyr211* in TSPAN12 in 4 unrelated probands. Based on in silico analysis and ACMG standard, two of them, c.4289delC: p.Pro1431Argfs*8 and c.2073G > T: p.Trp691Cys of LRP5 were identified as novel pathogenic variants. Based on computational predictions using molecular dynamics simulations and molecular docking, there are indications that these two variants might lead to alterations in the secondary structure and spatial conformation of the protein, potentially impacting its rigidity and flexibility. Furthermore, these pathogenic variants are speculated to potentially influence hydrogen bonding interactions and could result in an increased binding affinity with the DKK1 protein. CONCLUSIONS: Two novel genetic variants of the LRP5 gene were identified, expanding the range of mutations associated with FEVR. Through molecular dynamics simulations and molecular docking, the potential impact of these variants on protein structure and their interactions with the DKK1 protein has been explored. These findings provide further support for the involvement of these variants in the pathogenesis of the disease.

Impact of anti-VEGF therapy on distinctive retina layers in patients with macular edema secondary to branch retinal vein occlusion.

BACKGROUND: To explore the impact of anti-vascular epithelial growth factor (ant-VEGF) on the thickness of each retinal layer in patients with macular edema (ME) secondary to the branch retinal vein occlusion (BRVO). METHODS: This retrospective study included patients with ME secondary to monocular BRVO who received anti-VEGF therapy in Ningxia Eye Hospital between January-December 2020. RESULTS: Forty-three patients (25 males) were included, with 31 showed > 25% reduction in central retinal thickness (CRT) after anti-VEGF therapy (response group), and the others showed a ≤25% reduction in CRT (no-response group). The response group showed significantly smaller mean changes in the ganglion cell layer (GCL) (after 2 months) and inner plexiform layer (IPL) (after 1, 2, and 3 months) and significantly greater mean changes in the inner nuclear layer (INL) (after 2 and 3 months), outer plexiform layer (OPL) (after 3 months), outer nuclear layer (ONL) (after 2 and 3 months), and CRT (after 1 and 2 months) (all P < 0.05) as compared to the no-response group. The mean change in the thickness of each retinal layer IPL (P = 0.006) between the two groups was significantly different after controlling for a time and with a significant time trend (P < 0.001). Additionally, patients in the response group were more likely to have an improvement in IPL (43.68 ± 6.01 at 1 month and 41.52 ± 5.45 at 2 months vs. 39.9 ± 6.86 at baseline) after anti-VEGF therapy, while those in no response group might show improvement in GCL (45.75 ± 8.24 at 1 month, 40.00 ± 8.92 at 2 months, and 38.83 ± 9.93 at 3 months vs. 49.67 ± 6.83 at baseline). CONCLUSIONS: Anti-VEGF therapy might help restore the retinal structure and function in patients with ME secondary to BRVO, and those who have a response after anti-VEGF therapy are more likely to improve IPL, while those having no response might show improvement in GCL.

Genomic profiling reveals non-small cell lung cancer with common mutations of EGFR exon 20 and exon 21: a case report.

Background: Epidermal growth factor receptor (EGFR) gene is one of the most common driver genes for non-small cell lung cancer (NSCLC). The PIONEER study showed that 51.4% of unselected Asian patients with advanced lung adenocarcinoma have EGFR-sensitive mutations. EGFR mutations mainly occur in the first four [18-21] exons of the intracellular tyrosine kinase (TK) region. At present, there are more than 30 types of mutations in the TK region, including exon 19 deletion mutation (19Del) and exon 21 L858R mutation (L858R) which are the most common types of sensitive mutations, accounting for more than 90% of all EGFR mutations. About 10% of NSCLC patients with EGFR mutations are rare mutation types, including exon 18 point mutation (G719X), exon 20 point mutation (S768I), exon 19 point mutation (L747S), exon 21 point mutation (L833V), etc. About 1% of NSCLC patients have primary double mutations of EGFR. Case Description: In this present study, we identified a 59-year-old female patient with no smoking history had double mutations in EGFR exon 20 R776S mutation and exon 21 L858R mutation by next-generation sequencing (NGS). Conclusions: This observation may explore a new mechanism study for EGFR-TKIs and provide a new direction for clinical treatment of NSCLC.

Persistent Endothelial Dysfunction in Coronavirus Disease-2019 Survivors Late After Recovery.

BACKGROUND: Coronavirus disease 2019 (COVID-19) can result in an endothelial dysfunction in acute phase. However, information on the late vascular consequences of COVID-19 is limited. METHODS: Brachial artery flow-mediated dilation (FMD) examination were performed, and inflammatory biomarkers were assessed in 86 survivors of COVID-19 for 327 days (IQR 318-337 days) after recovery. Comparisons were made with 28 age-matched and sex-matched healthy controls and 30 risk factor-matched patients. RESULTS: Brachial artery FMD was significantly lower in the survivors of COVID-19 than in the healthy controls and risk factor-matched controls [median (IQR) 7.7 (5.1-10.7)% for healthy controls, 6.9 (5.5-9.4)% for risk factor-matched controls, and 3.5(2.2-4.6)% for COVID-19, respectively, p < 0.001]. The FMD was lower in 25 patients with elevated tumor necrosis factor (TNF)-α [2.7(1.2-3.9)] than in 61 patients without elevated TNF-α [3.8(2.6-5.3), p = 0.012]. Furthermore, FMD was inversely correlated with serum concentration of TNF-α (r = -0.237, p = 0.007). CONCLUSION: Survivors of COVID-19 have a reduced brachial artery FMD, which is inversely correlated with increased serum concentration of TNF-α. Prospective studies on the association of endothelial dysfunction with long-term cardiovascular outcomes, especially the early onset of atherosclerosis, are warranted in survivors of COVID-19.

ESR1 mediated circ_0004018 suppresses angiogenesis in hepatocellular carcinoma via recruiting FUS and stabilizing TIMP2 expression.

Angiogenesis has been certified to account for tumor pathobiology. Circular RNAs (circRNAs) have been demonstrated to be involved in angiogenesis-related diseases, including hepatocellular carcinoma (HCC). Nevertheless, the regulatory roles of most circRNAs remain obscure. This study aims to uncover the function of hsa_circ_0004018 on angiogenesis in HCC. Firstly, quantitative real-time RT-PCR (RT-qPCR) analyzed that circ_0004018 was definitely down-regulated in HCC. Western blot analysis was conducted to detect the protein level of fused protein in sarcoma (FUS) and TIMP metallopeptidase inhibitor 2 (TIMP2). Functional assays were carried out to assess the impacts of circ_0004018 on HCC. From the experimental results, we found that overexpression of circ_0004018 significantly inhibited angiogenesis in HCC. The regulatory mechanism of circ_0004018 in HCC was determined by chromatin immunoprecipitation (ChIP), luciferase reporter assays and RNA immunoprecipitation (RIP) assay. Therefore, we proved that estrogen receptor 1 (ESR1) mediated circ_0004018 regulated TIMP2 by recruiting FUS. A series of rescue assays verified that circ_0004018 participated in angiogenesis in HCC via modulating TIMP2. In summary, this paper disclosed that ESR1 activated circ_0004018 inhibited angiogenesis in HCC via binding to FUS and stabilizing TIMP2 expression.

Multi-Level Cross Residual Network for Lung Nodule Classification.

Computer-aided algorithm plays an important role in disease diagnosis through medical images. As one of the major cancers, lung cancer is commonly detected by computer tomography. To increase the survival rate of lung cancer patients, an early-stage diagnosis is necessary. In this paper, we propose a new structure, multi-level cross residual convolutional neural network (ML-xResNet), to classify the different types of lung nodule malignancies. ML-xResNet is constructed by three-level parallel ResNets with different convolution kernel sizes to extract multi-scale features of the inputs. Moreover, the residuals are connected not only with the current level but also with other levels in a crossover manner. To illustrate the performance of ML-xResNet, we apply the model to process ternary classification (benign, indeterminate, and malignant lung nodules) and binary classification (benign and malignant lung nodules) of lung nodules, respectively. Based on the experiment results, the proposed ML-xResNet achieves the best results of 85.88% accuracy for ternary classification and 92.19% accuracy for binary classification, without any additional handcrafted preprocessing algorithm.

Expression of ß-adrenergic receptor subtypes in human normal and dilated ureter.

BACKGROUND: Ureter peristalsis is a basic physiological function regulated by myogenic and neurogenic factors. The distribution and function of ß-adrenergic receptors (ß-AR) in the human ureter remain unknown. The aim of this study was to investigate the expression of ß-AR subtypes in the normal and dilated human ureter. METHODS: The upper, middle, and lower segments of normal and dilated ureters were collected from patients undergoing surgery for carcinoma of the kidney and upper urinary tract and ureteral stenosis. The mucosa and muscular layers were separated. Expression of ß1-AR, ß2-AR, and ß3-AR mRNA and protein levels were detected by real-time PCR, western blot, and immunohistochemistry. RESULTS: In both mucosa and muscular layers, the mRNA and protein expressions of ß1-AR, ß2-AR, and ß3-AR were lower in the dilated ureter compared with the normal ureter. ß1-AR mRNA was significantly decreased (by 76.64%; P < 0.01) in the mucosa layer of the middle segment of the dilated ureter. ß1-AR and ß3-AR mRNA were significantly decreased (by 75.53 and 53.62%, respectively; P < 0.01) in the muscular layer of the lower segment of the dilated ureter. Similar findings were observed for protein expression. CONCLUSIONS: The downregulation of ß-ARs after ureter dilation, particularly for ß1-AR and ß3-AR in the muscular layer, suggests a potential compensatory mechanism involving increased contraction of the ureter to push urine through the obstruction. Thus, ß-ARs may be a potential target for treatment of ureter obstruction.

TGF-ß1 promotes the migration and invasion of bladder carcinoma cells by increasing fascin1 expression.

Transforming growth factor-ß1 (TGF-ß1) is a multifunctional cytokine that is reported to regulate cellular motility and invasive capability during tumor progression. Fascin1, an actin-bundling protein, increases cell motility, migration and adhesion. To investigate the function of TGF-ß1 and test whether fascin1 is an important mediator of the tumor response to TGF-ß1 in bladder carcinoma cells, real-time RT-PCR and western blot analysis were used to test changes in fascin1 expression after TGF-ß1 (10 ng/ml) treatment in T24 and BIU87 cells. Small interfering RNA (siRNA) technique was performed to silence fascin1. Cell viability and biological behavior changes were evaluated by cell growth (MTT), wound-healing and Matrigel invasion assays. In the present study, we found that the mRNA and protein levels of fascin1 in the T24 and BIU87 cells were significantly increased after 10 ng/ml TGF-ß1 treatment (p<0.05). The proliferation of T24 cells (p=0.005) was also significantly increased, while no significant change was observed in BIU87 cells (p=0.318). In addition, the migratory and invasive potential of the two cell lines were promoted. Furthermore, we successfully silenced fascin1, and observed that fascin1 siRNA significantly attenuated the migration and invasiveness induced by TGF-ß1. The findings suggested that TGF-ß1 can promote invasion and migration of T24 and BIU87 bladder carcinoma cells, and the increase in fascin1 expression may be the key point of this impact of TGF-ß1.

Pediatric Cardiac Shear Wave Elastography for Quantitative Assessment of Myocardial Stiffness: A Pilot Study in Healthy Controls.

The long-term goal of this study is to assess chemotherapy-induced cardiotoxicity for pediatric cancer patients using cardiac ultrasound shear wave (SW) elastography. This pilot study aimed to systematically investigate the feasibility of using cardiac SW elastography in children and provide myocardial stiffness control data for cancer patients. Twenty healthy volunteers (ages 5-18) were recruited. A novel cardiac SW elastography sequence with pulse-inversion harmonic imaging and time-aligned sequential tracking was developed for this study. Cardiac SW elastography produces and detects transient SWs propagating in the myocardium in late-diastole, which can be used to quantify myocardial stiffness. The parasternal long-axis (L-A) and short-axis (S-A) views of the interventricular septum (IVS) were feasible for pediatric cardiac SW elastography. The L-A and S-A views of the basal and mid IVS provided better success rates than those of the apical IVS. Success rates decreased with increased body mass index (BMI), but did not differ with age or gender. Two-dimensional SW speed measurements were 1.26, 1.22, 1.71 and 1.67 m/s for L-A base, L-A mid, S-A base and S-A mid IVS, respectively. All S-A SW speed values were significantly higher (p < 0.01) than L-A values due to myocardial anisotropy. No SW speed difference was observed for different ages and genders. This pilot study demonstrated, for the first time, the feasibility of using cardiac SW elastography to measure quantitative myocardial stiffness in children, and established control SW speed values for using SW elastography to assess chemo-induced cardiotoxicity for pediatric cancer patients. The results showed that the myocardial anisotropy needs to be accounted for when comparing SW speed from different imaging axes.

Use of carotid plaque neovascularization at contrast-enhanced US to predict coronary events in patients with coronary artery disease.

PURPOSE: To determine whether carotid plaque neovascularization as assessed with contrast-enhanced ultrasonography (US) can help predict future coronary events in patients with stable coronary artery disease (CAD). MATERIALS AND METHODS: The study was approved by the hospital ethics committee, and informed consent was obtained from all patients. Three hundred twelve consecutive patients (228 men; mean age, 63 years ± 9; age range, 42-88 years) with both CAD and at least one carotid plaque thicker than 2.0 mm underwent both standard and contrast-enhanced carotid US. Patients with stable CAD were followed up for 8-47 months (mean, 33 months ± 9) or until a coronary event occurred. Statistical analysis was performed with the Student t test, χ(2) analysis, Kaplan-Meier method, and Cox proportional hazards regression models. RESULTS: Contrast material enhancement of plaque was seen in 42 of 51 patients (82%) with acute coronary syndrome (ACS) and 114 of 261 patients (43.7%) with stable CAD (P < .001). Coronary events occurred during the follow-up period in 24 of 111 patients (21.6%) with contrast material enhancement of plaque and only seven of 137 patients (5.1%) without enhancement (P< .001). In 248 patients with stable CAD and follow-up, Kaplan-Meier analysis demonstrated a significantly higher probability of developing coronary events in patients with contrast material enhancement of plaque than in those without contrast material enhancement (P < .001). The presence of contrast material enhancement of plaque was a significant and independent predictor of future coronary events in patients with stable CAD (odds ratio: 3.90; 95% confidence interval: 1.60, 9.46; P = .003). CONCLUSION: Contrast material enhancement of plaque is more common in patients with ACS than in those with stable CAD and is a significant and independent predictor of future coronary events in patients with stable CAD, suggesting that noninvasive contrast-enhanced carotid US may be used as a method for risk stratification of patients with stable CAD.

Assessment of myocardial perfusion and systolic function in patients with coronary artery disease after coronary artery bypass surgery by myocardial contrast echocardiography and two-dimensional strain echocardiography.

The clinically applied value of myocardial perfusion and systolic function in patients with coronary artery disease after coronary artery bypass surgery using real-time myocardial contrast echocardiography (RT-MCE) combined with two-dimensional strain echocardiography was assessed. Twenty patients underwent intravenous RT-MCE by intravenous injections of SonoVue before and after coronary artery bypass surgery. Two-dimensional images were recorded from the left ventricular four-chamber view, two-chamber view and the apical view before, and two weeks and three months after coronary artery bypass surgery, and the peak systolic longitudinal strain was measured. The results showed that myocardial perfusion was significantly increased after coronary artery bypass surgery in about 71.6% segments. In the group that myocardial perfusion was improved, the peak systolic longitudinal strain three months after bypass surgery was significantly higher than that before operation [(-15.78+/-5.91)% vs (-10.45+/-8.31)%, P<0.05]. However, the parameters did not change in the group without myocardial perfusion improvement [(-10.33+/-6.53)% vs (-9.41+/-6.09)%, P>0.05]. It was concluded that whether or not the improvement of myocardial perfusion can mirror the recovery trend of regional systolic function, two-dimensional strain echocardiography can observe dynamic change of regional systolic function. The combination of myocardial perfusion with two-dimensional strain echocardiography can more accurately assess the curative effectiveness of coronary artery bypass surgery.

Evaluation of epirubicin-induced cardiotoxicity by two-dimensional strain echocardiography in breast cancer patients.

The value of two-dimensional strain echocardiography for assessing left ventricular regional systolic function in breast cancer patients who were treated with epirubicin was evaluated. A total of 116 breast cancer patients were divided into 3 groups: Thirty-eight patients in group A were given epirubicin (Epi) of 120-340 mg/m(2), 42 patients in group B received epirubicin of > or = 360 mg/m(2), and 36 patients after surging without chemotherapy served as the control group C. High frame rate two-dimensional images were recorded from apical long-axis view, four-chamber view, two-chamber view of left ventricle. Peak systolic strain of left ventricular subendocardial myocardium was measured using two-dimensional strain software. The conventional echocardiographic parameters were also obtained. Conventional echocardiography showed there was no significant changes in conventional echocardiographic parameters among the three groups (P>0.05). Two-dimensional strain echocardiography revealed that the peak systolic strain of left ventricular subendocardial myocardium in group A was reduced in some segments as compared with the controls (P<0.05). The peak systolic strain of left ventricular subendocardial myocardium in group B was reduced significantly as compared with group C (P<0.05), but that was reduced in group B just in some of the segments as compared with group A (P<0.05). It was concluded that two-dimensional strain echocardiography could early and sensitively display the effects of epirubicin-induced cardiotoxicity on the systolic function of left ventricular subendocardial myocardium, and early monitor the epirubicin-induced cardiotoxicity.

Evaluation of atrial septal defect using real-time three-dimensional echocardiography: comparison with surgical findings.

The present study evaluated the application of three dimensional echocardigraphy (3DE) in the diagnosis of atrial septal defect (ASD) and the measurement of its size by 3DE and compared the size with surgical findings. Two-dimensional and real-time three dimensional echocardiography (RT3DE) was performed in 26 patients with atrial septal defect, and the echocardiographic data were compared with the surgical findings. Significant correlation was found between defect diameter by RT3DE and that measured during surgery (r=0.77, P<0.001). The defect area changed significantly during cardiac cycle. Percentage change in defect size during cardiac cycle ranged from 6%-70%. Our study showed that the size and morphology of atrial septal defect obtained with RT3DE correlate well with surgical findings. Therefore, RT3DE is a feasible and accurate non-invasive imaging tool for assessment of atrial septal size and dynamic changes.