A new xAI framework with feature explainability for tumors decision-making in Ultrasound data: comparing with Grad-CAM.

BACKGROUND AND OBJECTIVE: The value of implementing artificial intelligence (AI) on ultrasound screening for thyroid cancer has been acknowledged, with numerous early studies confirming AI might help physicians acquire more accurate diagnoses. However, the black box nature of AI's decision-making process makes it difficult for users to grasp the foundation of AI's predictions. Furthermore, explainability is not only related to AI performance, but also responsibility and risk in medical diagnosis. In this paper, we offer Explainer, an intrinsically explainable framework that can categorize images and create heatmaps highlighting the regions on which its prediction is based. METHODS: A dataset of 19341 thyroid ultrasound images with pathological results and physician-annotated TI-RADS features is used to train and test the robustness of the proposed framework. Then we conducted a benign-malignant classification study to determine whether physicians perform better with the assistance of an explainer than they do alone or with Gradient-weighted Class Activation Mapping (Grad-CAM). RESULTS: Reader studies show that the Explainer can achieve a more accurate diagnosis while explaining heatmaps, and that physicians' performances are improved when assisted by the Explainer. Case study results confirm that the Explainer is capable of locating more reasonable and feature-related regions than the Grad-CAM. CONCLUSIONS: The Explainer offers physicians a tool to understand the basis of AI predictions and evaluate their reliability, which has the potential to unbox the "black box" of medical imaging AI.

The Overexpression of miR-377 Aggravates Sepsis-Induced Myocardial Hypertrophy by Binding to Rcan2 and Mediating CaN Activity.

Sepsis remains a complicated and incompletely understood syndrome, and myocardial dysfunction is one of the main complications contributing to poor clinical outcomes. Accumulating evidence has revealed the critical involvement of the deregulated expression of specific microRNAs (miRNAs) in cardiac pathologies caused by sepsis. Intriguingly, miR-377 has been correlated with cardiomyocyte apoptosis, whereas its effect on myocardial hypertrophy remains to be illustrated. Thus, the current study sets out to explore the impact and underlying mechanism of miR-377 on myocardial hypertrophy induced by sepsis. The expression pattern of miR-377 was detected in myocardial tissues of septic mice induced by cecal ligation-perforation (CLP). We found that miR-377 was highly expressed in myocardial tissues of CLP-induced septic mice with cardiomyocyte hypertrophy. Besides, miR-377 inhibition could relieve cardiomyocyte hypertrophy and reduce inflammation in septic mice. Further, mechanistic studies found that miR-377 could target Rcan2 and then regulate calcineurin (CaN) activity via Ca2+/CaN signaling pathway. Collectively, our findings illuminate that miR-377 enhances myocardial hypertrophy caused by sepsis, by targeting Rcan2 and further regulating the Ca2+/CaN signaling pathway. This work highlights downregulation of miR-377 as a novel target for the management of sepsis-induced myocardial hypertrophy.

LINC00702-mediated DUSP1 transcription in the prevention of bladder cancer progression: Implications in cancer cell proliferation and tumor inflammatory microenvironment.

BACKGROUND: Long noncoding RNAs (lncRNAs) can mediate the biological processes during tumorigenesis which may be affected by tumor associated macrophages (TAMs). Hence, we aim to identify the functionality of LINC00702 in regulation of bladder cancer cells and M2-TAMs. METHODS: After induction of M2-TAMs from THP-1 monocyte, we evaluated effects of LINC00702 on bladder cancer cells and M2-TAMs, which were validated in a xenograft tumor mouse model. RESULTS: Low LINC00702 expression was determined in bladder cancer tissues. LINC00702 could promote DUSP1 transcription by recruiting JUND to its promoter. Ectopic LINC00702 expression suppressed the bladder cancer cell proliferation and secretion of inflammatory cytokines by M2-TAMs through up-regulation of DUSP1. The anti-tumor activity of LINC00702 was ultimately validated in vivo. CONCLUSION: LINC00702 promoted DUSP1 by recruiting JUND to inhibit the proliferation of bladder cancer cells and the secretion of inflammatory factors, thus modulating bladder cancer inflammatory microenvironment.

[Retracted] MicroRNA­874 inhibits growth, induces apoptosis and reverses chemoresistance in colorectal cancer by targeting X­linked inhibitor of apoptosis protein.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the western blotting data shown in Fig. 5D were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article had already been published elsewhere prior to its submission to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they agreed with the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [the original article was published on Oncology Reports 36: 542­550, 2016; DOI: 10.3892/or.2016.4810].

High CTSL2 expression predicts poor prognosis in patients with lung adenocarcinoma.

Cathepsin like 2 (CTSL2) is a lysosomal cysteine protease, and may be associated with tumor metastasis. However, CTSL2 has not been reported as a biomarker in lung adenocarcinoma (LUAD). In this study, bioinformatics analysis using data from The Cancer Genome Atlas was performed. Wilcoxon rank-sum test and chi-square test were carried out. Kaplan-Meier and Cox regression were performed to evaluate the effect of CTSL2 expression in the overall survival. Our results indicated that CTSL2 in tumor was significantly higher than that in normal tissue (P < 0.001). High CTSL2 expression was significantly associated with age (P = 0.02), vital status (P < 0.001), and T classification (P = 0.03), and correlated with poor overall survival (HR = 1.62, 95% CI = 1.21-2.18, P = 0.001). CTSL2 expression was an independent risk factor for overall survival in patients with LUAD (HR = 1.52, 95% CI = 1.12-2.05, P = 0.006). A nomogram was plotted for illustration of CTSL2 expression on the risk of LUAD. Furthermore, in vitro cell experiments showed the CTSL2 promoted the proliferation and migration of A549 cells. In summary, high CTSL2 expression predicts poor prognosis in patients with LUAD.

Silencing LINC00482 inhibits tumor-associated inflammation and angiogenesis through down-regulation of MMP-15 via FOXA1 in bladder cancer.

Multiple studies have previously demonstrated that long intergenic non-coding RNAs (lincRNAs) play an important role in the development of bladder cancer. However, little is known regarding the underlying molecular mechanisms of LINC00482 functions in bladder cancer. The current study aimed to elucidate the role of LINC00482 in the progression of bladder cancer. The initial step was to detect the expressions of LINC00482 and MMP15 in bladder cancer cells and tissue. According to the results from the RT-qPCR, LINC00482 and MMP15 were both highly expressed in bladder cancer cells and tissue. The relationship among LINC00482, FOXA1 and MMP15 was studied via dual-luciferase reporter assay. LINC00482 was positively correlated with MMP15. LINC00482 promoted MMP15 expression by recruiting FOXA1. Using the gain- and loss-of-function approaches, silencing of LINC00482 resulted in the downregulation of VEGF and NF-κB protein levels, decreased expression of inflammatory factors, and inhibited angiogenesis. Silencing of LINC00482 also suppressed tumor-associated inflammation and angiogenesis in vivo, which was found to be reversed by the overexpression of MMP15. The present study demonstrated that LINC00482 induced the expression of MMP15 by interacting with FOXA1, thereby contributing to the inflammation and angiogenesis in bladder cancer.

Long non-coding RNASNHG17 promotes the progression of breast cancer by sponging miR-124-3p.

BACKGROUND: Small nucleolar RNA host gene 17 (SNHG17), a novel cancer-related long noncoding RNA (lncRNA), was reported to be responsible for processing and developing in several cancers. Nonetheless, the clinical significance and biological function of SNHG17 in human breast cancer (BC) remain rarely known. MATERIALS AND METHODS: 58 pairs of BC tissues and adjacent non-cancerous tissues were harvested to measure SNHG17 expression levels. SNHG17 was knockdown to study its biological behavior in BC cells. The microRNAs (miRNAs) that can bind to SNHG17 were predicated using Starbase2.0 and were tested using luciferase reporter activity and RIP assays. A xenograft model was established to investigate the impact of SNHG17 in tumor growth in vivo. RESULTS: An increased SNHG17 was observed in BC samples and cell lines compared with corresponding control. Increased SNHG17 was closely associated with poor prognosis.SNHG17 depletion suppressed cell proliferation, migration and invasion in vitro, as well as inhibited tumor growth in xenograft tumor models. Mechanistically, SNHG17 could function as an endogenous sponge of miR-124-3p in BC cells. Moreover, the repression of cell proliferation, migration and invasion induced by SNHG17 knockdown would reversed by miR-124-3p inhibitor. CONCLUSION: The present study demonstrated that the lncRNASNHG17 could regulate the progression of BC by sponging miR-124-3p.

MicroRNA-124 alleviates the lung injury in mice with septic shock through inhibiting the activation of the MAPK signaling pathway by downregulating MAPK14.

OBJECTIVE: Acute lung injury (ALI) is a severe lung disease with high mortality rate. Research has highlighted that the immune response to ALI is associated with significant changes in the expression of several microRNAs (miRNAs) in the lungs. In our research, we speculated that miR-124 moderated the severity of ALI through comprehensive suppression of the mitogen-activated protein kinase (MAPK) signaling pathway activation by targeting MAPK14. METHODS: A mouse model of ALI was established by array of experiments. The expression of MAPK14 and miR-124 was assessed in the tissues of ALI mice and the expression of inflammatory cytokines in ALI mice was determined. The expression of the related kinases in the MAPK signaling pathway and key cytokines in the pro-inflammatory response were assessed by a series of experiments. Immunohistochemistry and TUNEL staining were adopted to detect lung tissue cell proliferation and apoptosis in mice with ALI. RESULTS: MiR-124 was poorly expressed and MAPK14 was highly expressed in tissues of ALI mice. Overexpression of miR-124 or silence of MAPK14 alleviated the symptoms of ALI by down-regulating inflammatory cytokines expression, which could intrinsically suppress the expression of associated proteins in the MAPK signaling pathway and the downstream pro-inflammatory response factors, promote proliferation and inhibit apoptosis of lung tissue cells. Overexpression of MAPK14 inverted the phenotypic changes induced by overexpressing miR-124. CONCLUSION: These results indicated that miR-124 could alleviate the symptoms of ALI by inhibiting the activation of MAPK signaling pathway via subsequent targeting of MAPK14. Additionally, miR-124 may serve as a useful biomarker to alleviate the severity of septic shock-induced lung injury.

A Large Number of Metastatic Subcutaneous Nodules: A Complication of Percutaneous Biopsy for Atypical Renal Cell Carcinoma.

A 68-year-old man underwent ultrasound-guided needle biopsy of a suspicious renal mass. Just two weeks later, a large number of subcutaneous nodules was found in patient's chest-back, neck and axilla. pathology analysis was found to be metastatic subcutaneous nodules, These features suggest that tumor seeding have occurred during the needle biopsy. Despite needle tract seeding is a rare event, this rare complication should be taken into consideration before contemplating its use in a patient.

Ureteral stent removal using an extraction string after uncomplicated ureteroscopy: a cost-benefit analysis.

PURPOSE: Some urologists used the extraction strings for removal of ureteral stent without cystoscopy. While some urologists may have concern about perceived risks, including accidental dislodgement, infection, renal?colic?and lower urinary tract symptoms. Therefore, we performed a retrospective study to help address this conflict. MATERIALS AND METHODS: Patients who had an indwelling ureteral stent with(n=58) or without(n=82) extraction strings inserted after ureteroscopy for unilateral ureteral stones were enrolled. For ureteral stent removal, the strings were pulled by physician, no string-stents were removed by cystoscopic. Postoperative morbidity was assessed. Patients' medical expense due to postoperative morbidity was collected. RESULTS: Patients with extraction string had shorter stent dwell time((5.3±1.8 versus 11.2±3.2 day, P= .001)  and  less cost (8.97±3.07 versus 455±0 CNY, P = .001)) for ureteral stent removal. However, six patients with extraction string had an accidental dislodgement, additional medical expenses were 345±137.9 CNY. There was no difference in the cost due to urinary tract infection, renal?colic?and LUTS between the two groups. The overall cost in patients without an extraction string was significantly more than in patients with an extraction string (86.7±167.7 versus 507.9±147.8 CNY, p =.008). CONCLUSION: Despite an increase in stent dislodgement related risks  to the extraction string, it results in significant cost savings for patients, and most of patients remove with extraction strings might benefit from it.  INTRODUCTION Nowadays, most of urologists place an indwelling ureteral stent following uncomplicated ureteroscopy(URS). However, ureteral stent may impact quality of life (QoL) of patients. And the additional suffering due to cystoscopic extraction is even more painful. Current ureteral stents are manufactured with a string attached to the distal end, allowing for removal without cystoscopy, which may lead to a reduction of the dwell time(usually less than one week)[1-8]. Although stent extraction strings have many advantages, more than two-thirds of urologists remove extraction strings prior to their insertion[9]. Surgeons who do not adopt?this?method?may have concern about perceived risks, including accidental dislodgement, infection, renal?colic?and lower urinary tract symptoms(LUTS). But how about incidence?rate of the risk aforementioned??does this increase the patient's financial burden compared with patients remove without extraction strings? Whether patients remove with extraction strings might benefit from it? Therefore, we performed a retrospective study to help address these questions by comparing patients those who underwent ureteric stent placement with and without extraction strings after URS for stone disease.

Protective Effect of Amygdalin on LPS-Induced Acute Lung Injury by Inhibiting NF-κB and NLRP3 Signaling Pathways.

The acute lung injury (ALI) is a leading cause of morbidity and mortality in critically ill patients. Amygdalin is derived from the bitter apricot kernel, an efficacious Chinese herbal medicine. Although amygdalin is used by many cancer patients as an antitumor agent, there is no report about the effect of amygdalin on acute lung injury. Here we explored the protective effect of amygdalin on ALI using lipopolysaccharide (LPS)-induced murine model by detecting the lung wet/dry ratio, the myeloperoxidase (MPO) in lung tissues, inflammatory cells in the bronchoalveolar lavage fluid (BALF), inflammatory cytokines production, as well as NLRP3 and NF-κB signaling pathways. The results showed that amygdalin significantly reduced LPS-induced infiltration of inflammatory cells and the production of TNF-α, IL-1ß, and IL-6 in the BALF. The activity of MPO and lung wet/dry ratio were also attenuated by amygdalin. Furthermore, the western blotting analysis showed that amygdalin remarkably inhibited LPS-induced NF-κB and NLRP3 activation. These findings indicate that amygdalin has a protective effect on LPS-induced ALI in mice. The mechanism may be related to the inhibition of NF-κB and NLRP3 signaling pathways.

MicroRNA-874 inhibits growth, induces apoptosis and reverses chemoresistance in colorectal cancer by targeting X-linked inhibitor of apoptosis protein.

MicroRNA-874 (miR-874) is downregulated and acts as a tumor suppressor in several types of cancers, whereas the biological function of miR-874 in colorectal cancer (CRC) remains unclear. The aims of the present study were to investigate the clinical significance, biological effects, and the underlying mechanisms of miR-874 in CRC. Reverse transcription-quantitative PCR (RT-qPCR) was used to detect miR-874 expression in CRC cell lines and tissue samples. MTT and colony formation assays and flow cytometry were performed to analyze the effects of miR-874 expression on growth, apoptosis and the chemoresistance of CRC cells. Regulation of putative miR-874 targets was determined by dual-luciferase reporter assays. RT-qPCR and western blot assays were performed to detected the levels of X-linked inhibitor of apoptosis protein (XIAP) mRNA and protein expression. It was found that expression of miR-874 was downregulated in CRC tissues and cell lines, and its expression was significantly negatively correlated with TNM stage and lymph node metastasis of the CRC patients. Functional assays revealed that restoration of miR-874 inhibited proliferation, reduced colony formation, enhanced apoptosis, as well as decreased the 5-fluorouracil (5-FU) resistance of the CRC cells. Through luciferase activity assay, RT-qPCR and western blot analysis, XIAP was shown to be a direct target of miR-874. In addition, XIAP expression was significantly increased in the CRC tissues and cell lines, and was inversely correlated with miR-874 expression. Importantly, downregulation of XIAP in CRC cells had an effect similar to that of miR-874 overexpression. Taken together, these data showed that miR-874 inhibits growth, increases apoptosis and enhances chemosensitivity in CRC cells by targeting XIAP, suggesting that miR-874 may be a potential molecular target for the treatment of human CRC.

Contactin 1 as a potential biomarker promotes cell proliferation and invasion in thyroid cancer.

Contactin 1 (CNTN1) as a member of the immunoglobulin superfamily plays important role in the development of nervous system. Recent studies find that elevated CNTN1 can promote the metastasis of cancer. However, the expression and function of CNTN1 in thyroid cancer are still unknown. Here, we firstly find CNTN1 is a new gene which can be regulated by RET/PTC3 (Ret proto-oncogene and Ret-activating protein ELE1) rearrangement gene and the protein level of CNTN1 is increasing in thyroid cancer. Besides this change is positively associated with the TNM stage and tumor size. Moreover, we confirm that knockdown of CNTN1 significantly inhibits the tumor proliferation, invasiveness and represses the expression of cyclin D1 (CCND1). In conclusion, CNTN1 will be a potential diagnosis biomarker and therapy target for thyroid cancer.