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Background: CD276 is a promising immune checkpoint molecule with significant therapeutic potential. Several clinical trials are currently investigating CD276-targeted therapies. Purpose: This study aims to assess the prognostic significance of CD276 expression levels and to predict its expression using a radiomic approach in breast cancer (BC). Methods: A cohort of 840 patients diagnosed with BC from The Cancer Genome Atlas was included in this study. The Cancer Imaging Archive provided 98 magnetic resonance imaging (MRI) scans, which were randomly allocated to training and validation datasets in a 7:3 ratio. The association between CD276 expression and patient survival was assessed using Cox regression analysis. Feature selection was performed using the maximum relevance minimum redundancy algorithm and recursive feature elimination. Subsequently, support vector machine (SVM) and logistic regression (LR) models were constructed to predict CD276 expression. Results: The expression of CD276 was found to be elevated in BC. It was an independent risk factor for overall survival (hazard ratio = 1.579, 95 % CI: 1.054–2.366). There were eight radiomic features selected in total. In both the training and validation subsets, the SVM and LR models demonstrated favorable predictive abilities with AUC values of 0.744 and 0.740 for the SVM model and 0.742 and 0.735 for the LR model. These results indicate that the radiomic models efficiently differentiate the CD276 expression status. Conclusions: CD276 expression levels can have an impact on cancer prognosis. The MRI-based radiomic signature described in this study can discriminate the CD276 expression status.

The corrosion of steel stirrups is recognized as a significant contributing factor to shear deterioration in reinforced concrete (RC) structures, leading to detrimental effects on structural performance and potential early failures during service. To investigate the effect of corrosion levels on the shear behavior of RC beams, a series of three-point bending tests were conducted in this study. Furthermore, finite element analyses were employed to duplicate the shear behavior and failure modes observed in the experiments. The numerical outcomes are aligned with experimental results, confirming the validity of the developed constitutive models. The findings reveal that a low corrosion level (5%) in steel stirrups exhibits a limited impact on the overall structural shear capacity (-4%-0.9%). However, a higher corrosion level (12%) in stirrups induces a more pronounced reduction in structural shear capacity. This reduction is particularly prominent in scenarios involving a high shear span-to-depth (av/d) ratio. The developed finite element model, incorporating comprehensive constitutive models for individual components, offers engineers a prospective approach for forecasting the long-term shear performance of corroded RC beams.

Prevalence of hearing loss in children with autism spectrum disorder (ASD) is uncertain, as it is more challenging to assess hearing function in children with developmental difficulties (DD). We aimed to determine the prevalence and profiles of hearing loss in preschool children with ASD in a Southeast-Asian population who passed newborn hearing screening. A retrospective study of preschool children with DD (ASD, Global Developmental Delay (GDD), and Speech and Language Delay (SLD)) attending the Child Development Unit (CDU) at our hospital was performed. Three hundred and thirty-three children (ASD: n = 129; GDD: n = 110; and SLD: n = 94) underwent hearing assessments. Of these, 10.8% of children (n = 36, comprising 15 with ASD, 12 with GDD and 9 with SLD) had confirmed hearing loss. Hearing loss was predominantly bilateral in children with ASD and GDD; in those with SLD, unilateral and bilateral hearing loss were equally common. Conductive hearing loss occurred as frequently as sensorineural hearing loss in children with ASD and SLD, but was the dominant subtype in those with GDD. Moderate to severe hearing loss (n = 2) was noted only in children with ASD. Children with ASD and GDD required significantly more audiology visits and procedures to obtain conclusive hearing test results, compared to those with SLD. The need to identify hearing loss and monitor for resolution is particularly important in vulnerable populations with communication deficits, such as in those with ASD.

The quantitative evaluation of restocking and stock replenishment is essential for providing operational feedback and implementing adaptive management for future restoration projects. Since 2010, approximately 700 million juvenile shrimp (Penaeus penicillatus) have been released into Xiamen Bay, Fujian Province, China, each year, through stock replenishment programs. The recruited shrimp were sampled through three-year bottom trawl surveys from 2014 to 2017. The biological characteristics and catch equation were used to evaluate the effect of restocking and stock replenishment. The analysis uses the FAO-ICLARM Stock Assessment Tool (FISAT II) program. In general, there are two sources of recruitments—one from spawning brood stock and the other from released juvenile shrimp. We constructed an evaluation model for an effect evaluation based on Baranov’s catch equation to separate the initial recruitment volume using survey data. The relationship between body weight and total length was W = 1.638 TL2.9307. There is no statistically significant difference between males and females. The von Bertalanffy growth parameters derived for prawns, using FiSAT II, were L∞ = 209.6 mm and K = 0.51 per year. In spring 2014, the initial resource amount was 49,200, while the ratio of effective recruitment and parent amount was 3.92. The survival rate of the released shrimp larvae, 1.88‱, seems to be very unsatisfactory. The resource amount in summer and autumn is higher than in winter and spring. Obviously, the restocking effect is lower and the programs need to be improved. To improve the restocking effect, the replenishment performance should be adjusted to reduce the mortality rate and increase its release effectiveness. Therefore, corresponding implementations are recommended, including standard extensive culture, reduction in stress during transportation, and temporary culture.

This paper aimed to explore the mechanical properties of a cement-based material with carbon nanotube (CNT) under drying and freeze-thaw environments. Mercury Intrusion Porosimetry and Scanning Electron Microscopy were used to analyze the pore structure and microstructure of CNT/cement composite, respectively. The experimental results showed that multi-walled CNT (MWCNT) could improve to different degrees the mechanical properties (compressive and flexural strengths) and physical performances (shrinkage and water loss) of cement-based materials under drying and freeze-thaw conditions. This paper also demonstrated that MWCNT could interconnect hydration products to enhance the performance of anti-microcracks for cement-based materials, as well as the density of materials due to CNT’s filling action.

Trichosanthes kirilowii Maxim. is one of the original plants for traditional Chinese medicines Trichosanthis Fructus, Trichosanthis Semen, Trichosanthis Pericarpium and Trichosanthis Radix. Amino acids, nucleosides and carbohydrates are usually considered to have nutritional value and health-care efficacy. In this study, methods involving high-performance liquid chromatography coupled with evaporative light scattering detector (HPLC-ELSD), UV-visible spectrophotometry and ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS) were established for quantifying carbohydrates (fructose, glucose, stachyose, raffinose and polysaccharide), fourteen nucleosides and twenty one amino acids. Moreover, sixty-three samples from nine different parts, including pericarp, seed, fruit pulp, stem, leaf, main root, main root bark, lateral root and lateral root bark of T. kirilowii from different cultivated varieties were examined. The established methods were validated with good linearity, precision, repeatability, stability, and recovery. The results showed that the average content of total amino acids in roots (15.39 mg/g) and root barks (16.38 mg/g) were relatively higher than for others. Contents of nucleosides in all parts of T. kirilowii were below 1.5 mg/g. For carbohydrates, fruit pulp has a higher content than others for glucose (22.91%), fructose (20.63%) and polysaccharides (27.29%). By using partial least-squared discriminate analysis (PLS-DA), Variable importance in the projection (VIP) plots and analysis of variance (ANOVA) analysis, the characteristic components of the different organs (fruit, stems and leaves, roots) were found. This analysis suggested there were potential medicinal and nutritive health care values in various parts of the T. kirilowii, which provided valuable information for the development and utilization of T. kirilowii.

Abstract In lung disease, persistence of KRT8-expressing aberrant basaloid cells in the alveolar epithelium is associated with impaired tissue regeneration and pathological tissue remodeling. We analyzed single cell RNA sequencing datasets of human interstitial lung disease and found the profibrotic Interleukin-11 (IL11) cytokine to be highly and specifically expressed in aberrant KRT8+ basaloid cells. IL11 is similarly expressed by KRT8+ alveolar epithelial cells lining fibrotic lesions in a mouse model of interstitial lung disease. Stimulation of alveolar epithelial cells with IL11 causes epithelial-to-mesenchymal transition and promotes a KRT8-high state, which stalls the beneficial differentiation of alveolar type 2 (AT2)-to-AT1 cells. Inhibition of IL11-signaling in AT2 cells in vivo prevents the accumulation of KRT8+ cells, enhances AT1 cell differentiation and blocks fibrogenesis, which is replicated by anti-IL11 therapy. These data show that IL11 inhibits reparative AT2-to-AT1 differentiation in the damaged lung to limit endogenous alveolar regeneration, resulting in fibrotic lung disease.

Abstract Background The stiffness of the tumor microenvironment (TME) directly influences cellular behaviors. Radiotherapy (RT) is a common treatment for solid tumors, but the TME can impact its efficacy. In the case of liver cancer, clinical observations have shown that tumors within a cirrhotic, stiffer background respond less to RT, suggesting that the extracellular matrix (ECM) stiffness plays a critical role in the development of radioresistance. Methods This study explored the effects of ECM stiffness and the inhibition of lysyl oxidase (LOX) isoenzymes on the radiation response of liver cancer in a millimeter-sized three-dimensional (3D) culture. We constructed a cube-shaped ECM-based millimeter-sized hydrogel containing Huh7 human liver cancer cells. By modulating the collagen concentration, we produced two groups of samples with different ECM stiffnesses to mimic the clinical scenarios of normal and cirrhotic livers. We used a single-transducer system for shear-wave-based elasticity measurement, to derive Young’s modulus of the 3D cell culture to investigate how the ECM stiffness affects radiosensitivity. This is the first demonstration of a workflow for assessing radiation-induced response in a millimeter-sized 3D culture. Results Increased ECM stiffness was associated with a decreased radiation response. Moreover, sonoporation-assisted LOX inhibition with BAPN (β-aminopropionitrile monofumarate) significantly decreased the initial ECM stiffness and increased RT-induced cell death. Inhibition of LOX was particularly effective in reducing ECM stiffness in stiffer matrices. Combining LOX inhibition with RT markedly increased radiation-induced DNA damage in cirrhotic liver cancer cells, enhancing their response to radiation. Furthermore, LOX inhibition can be combined with sonoporation to overcome stiffness-related radioresistance, potentially leading to better treatment outcomes for patients with liver cancer. Conclusions The findings underscore the significant influence of ECM stiffness on liver cancer’s response to radiation. Sonoporation-aided LOX inhibition emerges as a promising strategy to mitigate stiffness-related resistance, offering potential improvements in liver cancer treatment outcomes.

Identifying biomarkers in non-small cell lung cancer (NSCLC) can improve diagnosis and patient stratification. We evaluated plasmas and sera for interleukins (IL)-11, IL-6, IL-8, IL-17A, and IL-33 as biomarkers in primary NSCLC patients undergoing surgical treatment against normal volunteers. Exhaled-breath condensates (EBCs), a potential source without invasive procedures, were explored in normal individuals. Due to separate recruitment criteria and intrinsic cohort differences, the NSCLC and control cohorts were not well matched for age (median age: 65 vs. 40 years; p < 0.0001) and smoking status (p = 0.0058). Interleukins were first assessed through conventional ELISA. IL-11 was elevated in NSCLC plasma compared to controls (49.71 ± 16.90 vs. 27.67 ± 14.06 pg/mL, respectively, p < 0.0001) but undetectable in sera and EBCs by conventional ELISA. Therefore, high-sensitivity PCR-based IL-11 ELISA was repeated, albeit with concentration discrepancies. IL11 gene and protein upregulation by RT-qPCR and immunohistochemistry, respectively, were validated in NSCLC tumors. The lack of detection sensitivity across IL-6, IL-8, IL-17A, and IL-33 suggests the need for further, precise assays. Surprisingly, biomarker concentrations can be dissimilar across paired plasmas and sera. Our results identified a need to optimize detection limits for biomarker detection and caution against over-reliance on just one form of blood sample for biomarker assessment.

A challenge in accurately identifying and classifying left ventricular hypertrophy (LVH) is distinguishing it from hypertrophic cardiomyopathy (HCM) and Fabry disease. The reliance on imaging techniques often requires the expertise of multiple specialists, including cardiologists, radiologists, and geneticists. This variability in the interpretation and classification of LVH leads to inconsistent diagnoses. LVH, HCM, and Fabry cardiomyopathy can be differentiated using T1 mapping on cardiac magnetic resonance imaging (MRI). However, differentiation between HCM and Fabry cardiomyopathy using echocardiography or MRI cine images is challenging for cardiologists. Our proposed system named the MRI short-axis view left ventricular hypertrophy classifier (MSLVHC) is a high-accuracy standardized imaging classification model developed using AI and trained on MRI short-axis (SAX) view cine images to distinguish between HCM and Fabry disease. The model achieved impressive performance, with an F1-score of 0.846, an accuracy of 0.909, and an AUC of 0.914 when tested on the Taipei Veterans General Hospital (TVGH) dataset. Additionally, a single-blinding study and external testing using data from the Taichung Veterans General Hospital (TCVGH) demonstrated the reliability and effectiveness of the model, achieving an F1-score of 0.727, an accuracy of 0.806, and an AUC of 0.918, demonstrating the model’s reliability and usefulness. This AI model holds promise as a valuable tool for assisting specialists in diagnosing LVH diseases.

Objectives This study mainly uses machine learning (ML) to make predictions by inputting features during training and inference. The method of feature selection is an important factor affecting the accuracy of ML models, and the process includes data extraction, which is the collection of all data required for ML. It also needs to import the concept of feature engineering, namely, this study needs to label the raw data of the cardiac ultrasound dataset with one or more meaningful and informative labels so that the ML model can learn from it and predict more accurate target values. Therefore, this study will enhance the strategies of feature selection methods from the raw dataset, as well as the issue of data scrubbing. Methods In this study, the ultrasound dataset was cleaned and critical features were selected through data standardization, normalization, and missing features imputation in the field of feature engineering. The aim of data scrubbing was to retain and select critical features of the echocardiogram dataset while making the prediction of the ML algorithm more accurate. Results This paper mainly utilizes commonly used methods in feature engineering and finally selects four important feature values. With the ML algorithms available on the Azure platform, namely, Random Forest and CatBoost, a Voting Ensemble method is used as the training algorithm, and this study also uses visual tools to gain a clearer understanding of the raw data and to improve the accuracy of the predictive model. Conclusion This paper emphasizes feature engineering, specifically on the cleaning and analysis of missing values in the raw dataset of echocardiography and the identification of important critical features in the raw dataset. The Azure platform is used to predict patients with a history of heart disease (individuals who have been under surveillance in the past three years and those who haven’t). Through data scrubbing and preprocessing methods in feature engineering, the model can more accurately predict the future occurrence of heart disease in patients.

Abstract Mitochondrial dysfunction induced by acute cardiac ischemia–reperfusion (IR), may increase susceptibility to arrhythmias by perturbing energetics, oxidative stress production and calcium homeostasis. Although changes in mitochondrial morphology are known to impact on mitochondrial function, their role in cardiac arrhythmogenesis is not known. To assess action potential duration (APD) in cardiomyocytes from the Mitofusins-1/2 (Mfn1/Mfn2)-double-knockout (Mfn-DKO) compared to wild-type (WT) mice, optical-electrophysiology was conducted. To measure conduction velocity (CV) in atrial and ventricular tissue from the Mfn-DKO and WT mice, at both baseline and following simulated acute IR, multi-electrode array (MEA) was employed. Intracellular localization of connexin-43 (Cx43) at baseline was evaluated by immunohistochemistry, while Cx-43 phosphorylation was assessed by Western-blotting. Mfn-DKO cardiomyocytes demonstrated an increased APD. At baseline, CV was significantly lower in the left ventricle of the Mfn-DKO mice. CV decreased with simulated-ischemia and returned to baseline levels during simulated-reperfusion in WT but not in atria of Mfn-DKO mice. Mfn-DKO hearts displayed increased Cx43 lateralization, although phosphorylation of Cx43 at Ser-368 did not differ. In summary, Mfn-DKO mice have increased APD and reduced CV at baseline and impaired alterations in CV following cardiac IR. These findings were associated with increased Cx43 lateralization, suggesting that the mitofusins may impact on post-MI cardiac-arrhythmogenesis.

Repair processes in kidney are impaired in severe disease. Here, the authors show that in kidney failure, genetic or pharmacologic inhibition of IL11 releases the brake on regeneration, reverses tissue damage and restores kidney function.

Research elucidates the mechanism by which excitotoxicity in brain ischemia triggers neuronal death by L-glutamate neurotransmitter. Results show that neurons under prolonged oxygen glucose deprivation causes antiexcitotoxic therapy unmasksing a death mechanism mediated by calcium permeable cation conductance, in which TRPM7 channels play an important role.