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Esophageal cancer (EC) is a main cause of cancer-related deaths. However, genomic alterations and the clinical value of next-generation sequencing (NGS) in advanced or metastatic EC for precision therapy remain largely unclear. Herein, we performed comprehensive analyses on a cohort of 47 individuals with advanced or metastatic EC who underwent NGS between May 2017 and February 2020. Eventually, 227 mutated genes were identified in the cohort. TP53, NQO1, DPYD, GSTM1, XRCC1 and ERCC1 were the most mutated genes and associated with immune cell infiltration, autophagy and hypoxia. Patients who received NGS-guided treatments exhibited better objective remission rate (ORR) (72.22%), disease control rate (DCR) (88.89%), overall survival (OS) (P = .0019) and progression-free survival (PFS) (P = .0077) than those not receiving NGS-guided therapies. The multivariate analyses further demonstrated that the NGS-guided therapy was an independently prognostic factor (OS: hazard radio [HR] 0.31, 95% coincidence interval [CI] 0.1-0.97, P = .04). In conclusion, we depicted a comprehensive mutational landscape of 47 patients with locally advanced or metastatic EC and illustrated the utility of NGS testing to guide clinical management in improving ORR, DCR, OS and PFS.

Additive manufacturing is being adopted to produce metal parts directly from digital design with applications in automotive, aerospace, and biomedical products. Laser powder bed fusion (LPBF) process is a viable technology for this purpose that utilizes a high-power laser beam which follows layer-to-layer scanning of predefined paths on a metal powder bed. In situ monitoring of LPBF process is essential to detect the localized meltpool, its vicinity, and material spatter around it with a goal to control the health of the meltpool. Among many alternatives, high-fidelity video monitoring can provide cost-effective insights to the on-going process to detect changes in meltpool and its vicinity that can further be integrated into an adaptive control system. For this purpose, a high frame rate camera was employed for in situ viewing of meltpool regions during laser fusion of a super alloy, Inconel 625, powder material to be able to improve the process control capability. The size and shape of the meltpool and the heat affected region detected via in situ viewing represent the sources of information to detect possible anomalies and defects. These acquired video volumes were processed and analysed using statistical process control (SPC) charts. The results indicate that some occurrences of undermelting, overmelting, and material spatter can be detected that can then be correlated to localized defects, delamination, and layer separation.

Irritable bowel syndrome with diarrhea (IBS-D) is a chronic and relapsing inflammatory disorder in which pathogenesis has been shown to be in part the result of miRNA-mediated signaling. Here, we investigated the alleviatory role of miR-16 in IBS-D. First, we established an IBS-D mouse model using colonic instillation of acetic acid and developed an IBS-D cell model using lipopolysaccharide exposure. The experimental data demonstrated that miR-16 was underexpressed in the serum of IBS-D patients, as well as in the colorectal tissues of IBS-D mouse models and lipopolysaccharide-exposed intestinal epithelial cells. Next, miR-16 and TLR4 were overexpressed or inhibited to characterize their roles in the viability and apoptosis of intestinal epithelial cells, inflammation, and epithelial tight junction. We found that miR-16 overexpression increased the viability of intestinal epithelial cells, maintained tight junction integrity, and inhibited cell apoptosis and inflammation. We showed that miR-16 targeted TLR4 and inhibited the TLR4/NF-κB signaling pathway. Additionally, inhibition of NF-κB suppressed the long noncoding RNA XIST, thereby promoting enterocyte viability, inhibiting apoptosis and cytokine production, and maintaining tight junction integrity. In vivo experiments further verified the alleviatory effect of miR-16 on IBS-D symptoms in mice. Taken together, we conclude that miR-16 downregulates XIST through the TLR4/NF-κB pathway, thereby relieving IBS-D. This study suggests that miR-16 may represent a potential target for therapeutic intervention against IBS-D.

Additional file 1. Additional materials, mehtods and figure

Background Serum Deprivation Protein Response (SDPR) plays an important role in formation of pulmonary alveoli. However, the functions and values of SDPR in lung cancer remain unknown. We explored prognostic value, expression pattern, and biological function of SDPR in non-small cell lung cancer (NSCLC) and KRAS-mutant lung cancers. Methods SDPR expression was evaluated by quantitative real-time PCR (RT-qPCR), immunohistochemistry (IHC), and Western blot on human NSCLC cells, lung adenocarcinoma tissue array, KRAS-mutant transgenic mice, TCGA and GEO datasets. Prognostic values of SDPR were evaluated by Kaplan–Meier and Cox regression analysis. Bioinformatics implications of SDPR including SDPR-combined transcription factors (TFs) and microRNAs were predicted. In addition, correlations between SDPR, immune checkpoint molecules, and tumor infiltration models were illustrated. Results SDPR expression was downregulated in tumor cells and tissues. Low SDPR expression was an independent factor that correlated with shorter overall survival of patients both in lung cancer and KRAS-mutant subgroups. Meanwhile, ceRNA network was constructed to clarify the regulatory and biological functions of SDPR. Negative correlations were found between SDPR and immune checkpoint molecules (PD-L1, TNFRSF18, TNFRSF9, and TDO2). Moreover, diversity immune infiltration models were observed in NSCLC with different SDPR expression and copy number variation (CNV) patterns. Conclusions This study elucidated regulation network of SDPR in KRAS-mutant NSCLC, and it illustrated correlations between low SDPR expression and suppressed immune system, unfolding a prognostic factor and potential target for the treatment of lung cancer, especially for KRAS-mutant NSCLC.

Genomic profiling has revolutionized treatment options for patients with oncogene-driven cancers, such as epidermal growth factor receptor (EGFR) mutant carcinoma. Rearranged during transfection (RET) rearrangement, as one of the main activated oncogenes, has been well studied and found to be involved in the malignant behavior of carcinogenesis, resulting in acquired resistance to EGFR tyrosine kinase inhibitors and inducing an intrinsic resistance to immunotherapy. Thus, targeted therapies have been investigated against RET arrangement cancers, including several multi-kinase inhibitors and selective RET inhibitors. However, modest efficacy, a relatively high rate of toxicity, and poor effectiveness against brain metastasis are common limitations of multi-targeted novel molecular inhibitors. A promising prospect was shown recently in selective RET inhibitors in several ongoing clinical trials. In this review, we reviewed the concurrent dilemmas of targeted therapies against RET arrangement cancer from preclinical and clinical studies and proposed several clinical considerations for clinical practice prospectively.

Breast cancer is a highly heterogeneous disease at the molecular level and >90% of mortalities are due to metastasis and its associated complications. The present study determined the impact of molecular subtypes on metastatic behavior and overall survival (OS) of patients with metastatic breast cancer. The influence of molecular subtypes on the sites and number of metastases in 166 patients with metastatic breast cancer from a single center were assessed; and the influence of molecular subtypes on the sites and number of metastases and OS in 15,322 metastatic cases among 329,770 patients with primary breast cancer from the Surveillance, Epidemiology and End Results database were assessed. Analysis of both datasets revealed that different molecular subtypes exhibited differences in the prevalence of different metastatic sites and number of metastases. A larger proportion of bone metastasis was observed in the hormone receptor (HR)+/human epidermal growth factor receptor 2 (HER2)+ subtype than in other subtypes, more lung metastasis was observed in the HR-/HER2+ subtype and more liver metastasis occurred in the HR+/HER2+ and HR-/HER2+ subtypes. Single-site metastasis was more common for the HR+/HER2− subtype than in other subtypes, while 2–3 sites of metastases were more common for the HR+/HER2+ subtype and ≥4 sites of metastases were more frequent in the HR-/HER2+ and HR-/HER2- subtypes. The mean OS of patients with primary breast cancer in the HR+/HER2− subtype group was the longest (78.5 months), while the HR-/HER2- group had the shortest mean OS (69.1 months). The mean OS of the metastatic HR+/HER2+ group was the longest (46.0 months), while the mean OS of the metastatic HR-/HER2- group was the shortest (18.5 months). In conclusion, the results of the present study suggested that different molecular subtypes of breast cancer have different metastatic behavior, as well as mean OS.

Motivation We introduce PRINCESS, a privacy-preserving international collaboration framework for analyzing rare disease genetic data that are distributed across different continents. PRINCESS leverages Software Guard Extensions (SGX) and hardware for trustworthy computation. Unlike a traditional international collaboration model, where individual-level patient DNA are physically centralized at a single site, PRINCESS performs a secure and distributed computation over encrypted data, fulfilling institutional policies and regulations for protected health information. Results To demonstrate PRINCESS’ performance and feasibility, we conducted a family-based allelic association study for Kawasaki Disease, with data hosted in three different continents. The experimental results show that PRINCESS provides secure and accurate analyses much faster than alternative solutions, such as homomorphic encryption and garbled circuits (over 40 000× faster). Availability and Implementation https://github.com/achenfengb/PRINCESS_opensource Supplementary information Supplementary data are available at Bioinformatics online.