Retinal Vascular Image Segmentation Using Improved UNet Based on Residual Module.

In recent years, deep learning technology for clinical diagnosis has progressed considerably, and the value of medical imaging continues to increase. In the past, clinicians evaluated medical images according to their individual expertise. In contrast, the application of artificial intelligence technology for automatic analysis and diagnostic assistance to support clinicians in evaluating medical information more efficiently has become an important trend. In this study, we propose a machine learning architecture designed to segment images of retinal blood vessels based on an improved U-Net neural network model. The proposed model incorporates a residual module to extract features more effectively, and includes a full-scale skip connection to combine low level details with high-level features at different scales. The results of an experimental evaluation show that the model was able to segment images of retinal vessels accurately. The proposed method also outperformed several existing models on the benchmark datasets DRIVE and ROSE, including U-Net, ResUNet, U-Net3+, ResUNet++, and CaraNet.

Mutation-Driven S100A8 Overexpression Confers Aberrant Phenotypes in Type 1 CALR-Mutated MPN.

Numerous pathogenic CALR exon 9 mutations have been identified in myeloproliferative neoplasms (MPN), with type 1 (52bp deletion; CALRDEL) and type 2 (5bp insertion; CALRINS) being the most prevalent. Despite the universal pathobiology of MPN driven by various CALR mutants, it is unclear why different CALR mutations result in diverse clinical phenotypes. Through RNA sequencing followed by validation at the protein and mRNA levels, we found that S100A8 was specifically enriched in CALRDEL but not in CALRINS MPN-model cells. The expression of S100a8 could be regulated by STAT3 based on luciferase reporter assay complemented with inhibitor treatment. Pyrosequencing demonstrated relative hypomethylation in two CpG sites within the potential pSTAT3-targeting S100a8 promoter region in CALRDEL cells as compared to CALRINS cells, suggesting that distinct epigenetic alteration could factor into the divergent S100A8 levels in these cells. The functional analysis confirmed that S100A8 non-redundantly contributed to accelerated cellular proliferation and reduced apoptosis in CALRDEL cells. Clinical validation showed significantly enhanced S100A8 expression in CALRDEL-mutated MPN patients compared to CALRINS-mutated cases, and thrombocytosis was less prominent in those with S100A8 upregulation. This study provides indispensable insights into how different CALR mutations discrepantly drive the expression of specific genes that contributes to unique phenotypes in MPN.

The impact of sarcopenia on overall survival in patients with pan-RAS wild-type colorectal liver metastasis receiving hepatectomy.

Sarcopenia has been associated with conventional chemotherapy-related toxicity, postoperative complications and poor overall survival in patients with genotype-unselected metastatic colorectal cancer (mCRC). This study aimed to evaluate the prognostic implications of sarcopenia and its change after perioperative cetuximab plus doublet chemotherapy and hepatectomy in patients with RAS wild-type colorectal liver metastasis (CRLM). Patients with CRLM from 2007 to 2018 in Chang Gung Research Database were retrospectively analyzed. Baseline characteristics as well as skeletal muscle index (SMI) at baseline and dynamic changes after interventions were collected. A multivariate Cox proportional hazard model was used to evaluate the effect of each parameter on overall survival (OS), and the Kaplan-Meier method was used to establish survival curves. A two-sided p value < 0.05 was considered statistically significance. Of 214 RAS wild-type mCRC patients who received both cetuximab and doublet chemotherapy, 77 who received upfront or subsequent hepatectomy were included in this study. The median follow-up time was 2.3 years. The rate of sarcopenia was higher in the patients who received neoadjuvant cetuximab-containing regimens than in those who received upfront hepatectomy (95% versus 63%, p = 0.001). Increased SMI after perioperative systemic therapy remained independently associated with better OS in multivariate analysis [hazard ratio (HR) = 0.27/10% increase, p = 0.013). The patients with sarcopenia had a trend of worse OS than those without sarcopenia (median OS: 4.5 versus 3.6 years, log-rank p = 0.282). Improvement in sarcopenia ([SMI after intervention - initial SMI]/initial SMI × 100%) is an important prognostic factor for OS. Future research is warranted to investigate direct interventions for sarcopenia and the impact on OS.

The Genomic Landscape in Philadelphia-Negative Myeloproliferative Neoplasm Patients with Second Cancers.

Patients with myeloproliferative neoplasms (MPNs) are characterized by systemic inflammation. With the indolent nature of the diseases, second cancers (SCs) have emerged as a challenging issue in afflicted patients. Epidemiological studies have confirmed the excessive risk of SCs in MPNs, but little is known about their molecular basis. To explore further, we used whole exome sequencing to explore the genetic changes in the granulocytes of 26 paired MPN patients with or without SC. We noticed that MPN−SC patients harbor genomic variants of distinct genes, among which a unique pattern of co-occurrence or mutual exclusiveness could be identified. We also found that mutated genes in MPN−SC samples were enriched in immune-related pathways and inflammatory networks, an observation further supported by their increased plasma levels of TGF-ß and IL-23. Noteworthily, variants of KRT6A, a gene capable of mediating tumor-associate macrophage activity, were more commonly detected in MPN−SC patients. Analysis through OncodriveCLUST disclosed that KRT6A replaces JAK2V617F as the more prominent disease driver in MPN−SC, whereas a major mutation in this gene (KRT6A c.745T>C) in our patients is linked to human carcinoma and predicted to be pathogenic in COSMIC database. Overall, we demonstrate that inflammation could be indispensable in MPN−SC pathogenesis.