Aberrant activation of the epidermal growth factor receptor (EGFR/ERBB1) by erythroblastic leukemia viral oncogene homolog (ERBB) ligands contributes to various tumor malignancies, including lung ...cancer and colorectal cancer (CRC). Epiregulin (EREG) is one of the EGFR ligands and is low expressed in most normal tissues. Elevated EREG in various cancers mainly activates EGFR signaling pathways and promotes cancer progression. Notably, a higher EREG expression level in CRC with wild-type Kirsten rat sarcoma viral oncogene homolog (KRAS) is related to better efficacy of therapeutic treatment. By contrast, the resistance of anti-EGFR therapy in CRC was driven by low EREG expression, aberrant genetic mutation and signal pathway alterations. Additionally, EREG overexpression in non-small cell lung cancer (NSCLC) is anticipated to be a therapeutic target for EGFR-tyrosine kinase inhibitor (EGFR-TKI). However, recent findings indicate that EREG derived from macrophages promotes NSCLC cell resistance to EGFR-TKI treatment. The emerging events of EREG-mediated tumor promotion signals are generated by autocrine and paracrine loops that arise from tumor epithelial cells, fibroblasts, and macrophages in the tumor microenvironment (TME). The TME is a crucial element for the development of various cancer types and drug resistance. The regulation of EREG/EGFR pathways depends on distinct oncogenic driver mutations and cell contexts that allows specific pharmacological targeting alone or combinational treatment for tailored therapy. Novel strategies targeting EREG/EGFR, tumor-associated macrophages, and alternative activation oncoproteins are under development or undergoing clinical trials. In this review, we summarize the clinical outcomes of EREG expression and the interaction of this ligand in the TME. The EREG/EGFR pathway may be a potential target and may be combined with other driver mutation targets to combat specific cancers.
In order to explore whether STEAM education in combination with elementary school curriculums can help students' learning performance, this study developed a digital learning system. This digital ...learning system combined STEAM concepts with elements of gamebased learning. This study developed the curriculum content based on the unit of transportation vehicles and presented it in a digital learning manner. In the experiment, the students were divided into an experimental group and a control group. The experimental group students were given the system developed in this study to assist their learning, and the control group students the lecturer-centered narrative curriculum. The study results show that the experimental group was superior to the control group in learning effectiveness. In the aspect of cognitive load, the cognitive load generated by the experimental group in their learning activities was also lower than that of the control group. By classifying students according to their learning styles, the visual type students had better learning effectiveness than the verbal type students when learning through the system developed by this graduate institute. As for the sequential type and global type students learning with the system developed, there were no significant differences in their learning effectiveness.
A significant volume of medical data remains unstructured. Natural language processing (NLP) and machine learning (ML) techniques have shown to successfully extract insights from radiology reports. ...However, the codependent effects of NLP and ML in this context have not been well-studied. Between April 1, 2015 and November 1, 2016, 9418 cross-sectional abdomen/pelvis CT and MR examinations containing our internal structured reporting element for cancer were separated into four categories: Progression, Stable Disease, Improvement, or No Cancer. We combined each of three NLP techniques with five ML algorithms to predict the assigned label using the unstructured report text and compared the performance of each combination. The three NLP algorithms included term frequency-inverse document frequency (TF-IDF), term frequency weighting (TF), and 16-bit feature hashing. The ML algorithms included logistic regression (LR), random decision forest (RDF), one-vs-all support vector machine (SVM), one-vs-all Bayes point machine (BPM), and fully connected neural network (NN). The best-performing NLP model consisted of tokenized unigrams and bigrams with TF-IDF. Increasing N-gram length yielded little to no added benefit for most ML algorithms. With all parameters optimized, SVM had the best performance on the test dataset, with 90.6 average accuracy and
F
score of 0.813. The interplay between ML and NLP algorithms and their effect on interpretation accuracy is complex. The best accuracy is achieved when both algorithms are optimized concurrently.
Little is known about the genetic basis of convergent traits that originate repeatedly over broad taxonomic scales. The myogenic electric organ has evolved six times in fishes to produce electric ...fields used in communication, navigation, predation, or defense. We have examined the genomic basis of the convergent anatomical and physiological origins of these organs by assembling the genome of the electric eel (Electrophorus electricus) and sequencing electric organ and skeletal muscle transcriptomes from three lineages that have independently evolved electric organs. Our results indicate that, despite millions of years of evolution and large differences in the morphology of electric organ cells, independent lineages have leveraged similar transcription factors and developmental and cellular pathways in the evolution of electric organs.
In the era of personalized medicine, the emphasis of health care is shifting from populations to individuals. Artificial intelligence (AI) is capable of learning without explicit instruction and has ...emerging applications in medicine, particularly radiology. Whereas much attention has focused on teaching radiology trainees about AI, here our goal is to instead focus on how AI might be developed to better teach radiology trainees. While the idea of using AI to improve education is not new, the application of AI to medical and radiological education remains very limited. Based on the current educational foundation, we highlight an AI-integrated framework to augment radiology education and provide use case examples informed by our own institution's practice. The coming age of "AI-augmented radiology" may enable not only "precision medicine" but also what we describe as "precision medical education," where instruction is tailored to individual trainees based on their learning styles and needs.
Background
Hyperinflammation with dysregulated production of galectins and cytokines may develop in COVID-19 or adult-onset Still’s disease (AOSD). Given the similar clinical features in both ...diseases, it is necessary to identify biomarkers that can differentiate COVID-19 from AOSD. However, the related data remain scarce currently.
Methods
In this cross-sectional study, plasma levels of galectin-3, galectin-9, and soluble TIM-3 (sTIM-3) were determined by ELISA in 55 COVID-19 patients (31 non-severe and 24 severe), 23 active AOSD patients, and 31 healthy controls (HC). The seropositivity for SARS-CoV-2 was examined using an immunochromatographic assay, and cytokine profiles were determined with the MULTIPLEX platform.
Results
Significantly higher levels of galectin-3, galectin-9, IL-1β, IL-1Ra, IL-10, IFN-α2, IL-6, IL-18, and TNF-α were observed in severe COVID-19 and active AOSD patients compared with HC (all p<0.001). AOSD, but not COVID-19, showed significantly higher IFN-γ and IL-17A compared with HC (both p<0.01). Moreover, active AOSD patients had 68-fold higher IL-18 levels and 5-fold higher ferritin levels than severe COVID-19 patients (both p<0.001). IL-18 levels at the cut-off value 190.5pg/mL had the highest discriminative power for active AOSD and severe COVID-19, with AUC 0.948, sensitivity 91.3%, specificity 95.8%, and accuracy of 91.5% (p<0.005). Multivariate regression analysis revealed IL-18 as a significant predictor of active AOSD (p<0.05).
Conclusion
Active AOSD patients share features of hyperinflammation and cytokine storm with severe COVID-19 patients but possess a distinct cytokine profile, including elevated IL-18, IL-6, IFN-γ, and IL-17A. IL-18 is a potential discriminator between AOSD and COVID-19 and may significantly predict active AOSD.
Obesity is a predictor of the development of systolic and diastolic heart failure (HF), but once established, patients with HF and obesity have better outcomes than their leaner counterparts, a ...phenomenon termed the “obesity paradox.” We sought to investigate the impact of adipose tissue quantity and distribution, measured by way of computed tomography, on outcomes in patients with HF. Patients admitted for acute decompensated HF between January 2017 to December 2018 were retrospectively analyzed. Body composition measurements were made on computed tomography of the abdomen/pelvis. Visceral, subcutaneous, and intermuscular adipose tissues were measured at the mid-third lumbar vertebra, along with skeletal muscle and waist circumference. Paracardial (pericardial and epicardial) adipose tissue was measured at the mid-eight thoracic vertebra. Visceral adipose tissue index (VATI) and subcutaneous adipose tissue index (SATI), along with skeletal muscle index, were indexed for patient height. A total of 200 patients were included, 44.5% female. Body mass index and waist circumference did not significantly predict outcomes. Patients with high SATI (highest sex-stratified tertile) had significantly better survival (hazard ratio 0.58, 95% confidence interval 0.39 to 0.87, p = 0.009), whereas high VATI was nonsignificant. Patients were further divided into 4 groups based on both VATI and SATI. One- and 4-year mortality risks were lowest in those with low VATI high SATI compared with the other groups; this persisted after multivariable adjustment for covariates, including albumin and skeletal muscle index. In conclusion, the “obesity paradox” appears to be largely driven by subcutaneous adipose tissue, independent of nutrition or skeletal muscle.
The epithelial-to-mesenchymal transition (EMT) is involved in cancer metastasis; nevertheless, interferon (IFN)-γ induces anticancer activities by causing cell growth suppression, cytotoxicity, and ...migration inhibition. Regarding the poor response to exogenously administered IFN-γ as anticancer therapy, it was hypothesized that malignant cells may acquire a means of escaping from IFN-γ immunosurveillance, likely through an EMT-related process. A genomic analysis of human lung cancers revealed a negative link between the EMT and IFN-γ signaling, while compared to human lung adenocarcinoma A549 cells, IFN-γ-hyporesponsive AS2 cells exhibited mesenchymal characteristics. Chemically, physically, and genetically engineered EMT attenuated IFN-γ-induced IFN regulatory factor 1 transactivation. Poststimulation of transforming growth factor-β induced the EMT and also selectively retarded IFN-γ-responsive gene expression as well as IFN-γ-induced signal transducer and activator of transcription 1 activation, major histocompatibility complex I, and CD54 expression, cell migration/invasion inhibition, and direct/indirect cytotoxicity. Without changes in IFN-γ receptors, excessive oxidative activation of Src homology-2 containing phosphatase 2 (SHP2) in cells undergoing the EMT primarily caused cellular hyporesponsiveness to IFN-γ signaling and cytotoxicity, while combining an SHP2 inhibitor or antioxidant sensitized EMT-associated AS2 and mesenchymal A549 cells to IFN-γ-induced priming effects on tumor necrosis factor-related apoptosis-inducing ligand cytotoxicity. In cell line-derived xenograft models, combined treatment with IFN-γ and an SHP2 inhibitor induced enhanced anticancer activities. These results imply that EMT-associated SHP2 activation inhibits IFN-γ signaling, facilitating lung cancer cell escape from IFN-γ immunosurveillance.
•The malignant lung cancer cells acquire EMT to escape from IFN-γ immunosurveillance.•SHP2 in EMT cells determine cellular hyporesponsiveness to IFN-γ signaling and cytotoxicity.•Combined treatment with IFN-γ and an SHP2 inhibitor induced enhances anticancer therapy in vitro and in vivo.
The main challenge of ultrasound‐guided minimally invasive surgeries is to carry out treatments through small boreholes in the patient's body surface with sub‐millimetric accuracy and facility ...offered by ultrasound instruments. Thus, the phantoms' biomimetic appearances, acoustic characteristics, and mechanical properties are essential for healthcare professionals. In this study, gelatin and 3D‐printed photo‐resin phantoms were developed for hard and soft tissues, respectively. Using glutaraldehyde (GA) and formaldehyde (FA) to crosslink gelatin phantoms, the mechanical strength, ultrasound velocity, acoustic impedance, needle insertion forces, and antiseptic periods were improved, and the addition of silica nanoparticles raised the acoustic impedance. For 3D‐printed phantoms, the acoustic impedance ascended with hydrophilic polyethylene glycol diacrylate (PEGDA) oligomers. The additives applied in this study successfully made the gelatin and photo‐resin phantoms more mimetic to muscle and bone tissues, allowing their application in preoperative preparations.
3D‐printed photo‐resin phantoms were developed for hard and soft tissues. The additives of crosslinkers, nanoparticles, and reactive monomers improved the mechanical strength, acoustic properties, needle insertion forces, and antiseptic periods of phantoms efficiently.
Adipocytes are the most abundant stromal partners in breast tissue. However, the crosstalk between breast cancer cells and adipocytes has been given less attention compared to cancer-associated ...fibroblasts. Here we find, through systematic screening, that primary mammary gland-derived adipocytes (MGDAs) promote growth of breast cancer cells that express monocarboxylate transporter 2 (MCT2) both in vitro and in vivo. We show that β-hydroxybutyrate is secreted by MGDAs and is required to enhance breast cancer cells malignancy in vitro. Consistently, β-hydroxybutyrate is sufficient to promote tumorigenesis of a mouse xenograft model of MCT2-expressing breast cancer cells. Mechanistically we observe that upon co-culturing with MGDAs or treatment with β-hydroxybutyrate, breast cancer cells expressing MCT2 increase the global histone H3K9 acetylation and upregulate several tumour-promoting genes. These results suggest that adipocytes promote malignancy of MCT2-expressing breast cancer via β-hydroxybutyrate potentially by inducing the epigenetic upregulation of tumour-promoting genes.
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