Clinicopathological Features and Molecular Signatures of Lateral Neck Lymph Node Metastasis in Papillary Thyroid Microcarcinoma.

BACKGRUOUND: The predictive factors for lateral neck lymph node metastasis (LLNM) in papillary thyroid microcarcinoma (PTMC) remain undetermined. This study investigated the clinicopathological characteristics, transcriptomes, and tumor microenvironment in PTMC according to the LLNM status. We aimed to identify the biomarkers associated with LLNM development. METHODS: We retrospectively reviewed the medical records of patients with PTMC from two independent institutions between 2018 and 2022 (n=597 and n=467). We compared clinicopathological features between patients without lymph node metastasis (N0) and those with LLNM (N1b). Additionally, laser capture microdissection and RNA sequencing were performed on primary tumors from both groups, including metastatic lymph nodes from the N1b group (n=30; 20 primary tumors and 10 paired LLNMs). We corroborated the findings using RNA sequencing data from 16 BRAF-like PTMCs from The Cancer Genome Atlas. Transcriptomic analyses were validated by immunohistochemical staining. RESULTS: Clinicopathological characteristics, such as male sex, multifocality, extrathyroidal extension, lymphatic invasion, and central node metastasis showed associations with LLNM in PTMCs. Transcriptomic profiles between the N0 and N1b PTMC groups were similar. However, tumor microenvironment deconvolution from RNA sequencing and immunohistochemistry revealed an increased abundance of tumor-associated macrophages, particularly M2 macrophages, in the N1b group. CONCLUSION: Patients with PTMC who have a male sex, multifocality, extrathyroidal extension, lymphatic invasion, and central node metastasis exhibited an elevated risk for LLNM. Furthermore, infiltration of M2 macrophages in the tumor microenvironment potentially supports tumor progression and LLNM in PTMCs.

Different Molecular Phenotypes of Progression in BRAF- and RAS-Like Papillary Thyroid Carcinoma.

BACKGRUOUND: Papillary thyroid carcinoma (PTC) can be classified into two distinct molecular subtypes, BRAF-like (BL) and RASlike (RL). However, the molecular characteristics of each subtype according to clinicopathological factors have not yet been determined. We aimed to investigate the gene signatures and tumor microenvironment according to clinicopathological factors, and to identify the mechanism of progression in BL-PTCs and RL-PTCs. METHODS: We analyzed RNA sequencing data and corresponding clinicopathological information of 503 patients with PTC from The Cancer Genome Atlas database. We performed differentially expressed gene (DEG), Gene Ontology, and molecular pathway enrichment analyses according to clinicopathological factors in each molecular subtype. EcoTyper and CIBERSORTx were used to deconvolve the tumor cell types and their surrounding microenvironment. RESULTS: Even for the same clinicopathological factors, overlapping DEGs between the two molecular subtypes were uncommon, indicating that BL-PTCs and RL-PTCs have different progression mechanisms. Genes related to the extracellular matrix were commonly upregulated in BL-PTCs with aggressive clinicopathological factors, such as old age (≥55 years), presence of extrathyroidal extension, lymph node metastasis, advanced tumor-node-metastasis (TNM) stage, and high metastasis-age-completeness of resection- invasion-size (MACIS) scores (≥6). Furthermore, in the deconvolution analysis of tumor microenvironment, cancer-associated fibroblasts were significantly enriched. In contrast, in RL-PTCs, downregulation of immune response and immunoglobulin-related genes was significantly associated with aggressive characteristics, even after adjusting for thyroiditis status. CONCLUSION: The molecular phenotypes of cancer progression differed between BL-PTC and RL-PTC. In particular, extracellular matrix and cancer-associated fibroblasts, which constitute the tumor microenvironment, would play an important role in the progression of BL-PTC that accounts for the majority of advanced PTCs.

Cancer family caregivers' quality of life and the meaning of leisure.

In this study, the authors examined cancer family caregivers' life experience and the meaning of leisure, focusing on their difficulties and the role of leisure. We found four main themes related to cancer family caregivers' life and leisure experiences: stressors, adapting, the need of leisure, and leisure experiences. Our results showed that the caregivers experienced high levels of psychological and physical stress and conflicts while caring for cancer patients, resulting in a poor quality of life. They believed that leisure activity is necessary and can improve their quality of life; however, they felt a sense of guilt while engaging in personal activities.

Piperonylic acid stimulates keratinocyte growth and survival by activating epidermal growth factor receptor (EGFR).

Epidermal growth factor (EGF) stimulates cell growth, proliferation, and survival. The biological benefits of EGF have been utilized in medical uses for improving wound healing as well as in today's skin cosmetics. EGF has been found in urine, saliva, milk, and plasma, but its efficient isolation remains a difficult task. With technical advances, recombinant protein purification technique has been used for EGF production. However, the recombinant EGF is still expensive and keeping it with stable activity is difficult to be used widely. Thus, a molecule that can mimic the EGF activity would be a useful alternative of EGF. Herein, we have discovered that a natural small molecule piperonylic acid shows EGF-like activity in HaCaT keratinocytes. Piperonylic acid induced EGF receptor (EGFR) activation and resulted in serial activation of the downstream modulators. The activated signaling pathway eventually up-regulated gene expression of egr-1, c-fos, c-jun, and c-myc, which are involved in cell growth and survival. Moreover, piperonylic acid showed promoting role in keratinocyte growth and survival from UVB-induced cellular damages. This study has revealed the EGF-like activity of piperonylic acid and proposed that the piperonylic acid could be a promising component for skin wound healing agents or cosmetic ingredient.

Real-Time Location Tracking of Multiple Construction Laborers.

A real-time location (RTL) system was developed to improve safety for multiple laborers in confined construction sites. The RTL system can monitor the location and movement of multiple laborers in real time. A portable RTL system with a low-battery mode was developed to accommodate various constraints in the construction site. A conventional RTL system that uses radio signal strength indicators (RSSIs) has high error, so an accelerometer with Bluetooth Low Energy (BLE) was added, and a calculation process is suggested. Field tests were performed for validation in underground construction and bridge overlay sites. The results show that the accelerometer and BLE can be used as effective sensors to detect the movement of laborers. When the sensor is fixed, the average error ranges 0.2-0.22 m, and when the sensor is moving, the average error ranges 0.1-0.47 m.