Development of an epileptic seizure prediction algorithm using R–R intervals with self-attentive autoencoder

Epilepsy is a neurological disorder that may affect the autonomic nervous system (ANS) from 15 to 20 min before seizure onset, and disturbances of ANS affect R–R intervals (RRI) on an electrocardiogram (ECG). This study aims to develop a machine learning algorithm for predicting focal epileptic seizures by monitoring R–R interval (RRI) data in real time. The developed algorithm adopts a self-attentive autoencoder (SA-AE), which is a neural network for time-series data. The results of applying the developed seizure prediction algorithm to clinical data demonstrated that it functioned well in most patients; however, false positives (FPs) occurred in specific participants. In a future work, we will investigate the causes of FPs and optimize the developing seizure prediction algorithm to further improve performance using newly added clinical data

Molecular liver cancer prevention in cirrhosis by organ transcriptome analysis and lysophosphatidic acid pathway inhibition

Cirrhosis is a milieu that develops hepatocellular carcinoma (HCC), the second most lethal cancer worldwide. HCC prediction and prevention in cirrhosis are key unmet medical needs. Here we have established an HCC risk gene signature applicable to all major HCC etiologies: hepatitis B/C, alcohol, and non-alcoholic steatohepatitis. A transcriptome meta-analysis of >500 human cirrhotics revealed global regulatory gene modules driving HCC risk and the lysophosphatidic acid pathway as a central chemoprevention target. Pharmacological inhibition of the pathway in vivo reduced tumors and reversed the gene signature, which was verified in organotypic ex vivo culture of patient-derived fibrotic liver tissues. These results demonstrate the utility of clinical organ transcriptome to enable a strategy, namely, reverse-engineering precision cancer prevention

Role of leukocyte cell-derived chemotaxin 2 as a biomarker in hepatocellular carcinoma

We sought to identify a secreted biomarker for β-catenin activation commonly seen in hepatocellular carcinoma (HCC). By examination of our previously published genearray of hepatocyte-specific β-catenin knockout (KO) livers, we identified secreted factors whose expression may be β-catenin-dependent. We verified expression and secretion of the leading factor in HCC cells transfected with mutated (Hep3BS33Y)-β- catenin. Serum levels of biomarker were next investigated in a mouse model of HCC with β-catenin gene (Ctnnb1) mutations and eventually in HCC patients. Leukocyte cell-derived chemotaxin-2 (LECT2) expression was decreased in KO livers. Hep3BS33Y expressed and secreted more LECT2 in media as compared to Hep3BWT. Mice developing HCC with Ctnnb1 mutations showed significantly higher serum LECT2 levels. However patients with CTNNB1 mutations showed LECT2 levels of 54.28±22.32 ng/mL (Mean ± SD; n = 8) that were insignificantly different from patients with non-neoplastic chronic liver disease (32.8±21.1 ng/mL; n = 15) or healthy volunteers (33.2±7.2 ng/mL; n = 11). Intriguingly, patients without β-catenin mutations showed significantly higher serum LECT2 levels (54.26 ± 22.25 ng/mL; n = 46). While β-catenin activation was evident in a subset of non-mutant β-catenin HCC group with high LECT2 expression, serum LECT2 was unequivocally similar between β-catenin-active and -normal group. Further analysis showed that LECT2 levels greater than 50 ng/ml diagnosed HCC in patients irrespective of β-catenin mutations with specificity of 96.1% and positive predictive value of 97.0%. Thus, LECT2 is regulated by β-catenin in HCC in both mice and men, but serum LECT2 reflects β-catenin activity only in mice. Serum LECT2 could be a potential biomarker of HCC in patients. © 2014 Okabe et al

Extraabdominal fibromatosis in retroperitoneal space

Abstract Background Fibromatosis or desmoid tumor covers a broad spectrum of benign fibrous tissue proliferations. It is characterized by infiltrative growth and a tendency towards recurrence; however, unlike sarcoma, it never metastasizes. Case presentation We report on a case of extraabdominal fibromatosis originating from the retroperitoneal space in a 43-year-old woman. Seven years earlier she had undergone ureterolysis and ureteroureterostomy for ureteral obstruction. Computed tomography revealed a tumor between the iliocostalis and the psoas muscle. Histopathological evaluation revealed uniform proliferation of spindle cells, with a moderate amount of collagen fibers, suggesting extraabdominal fibromatosis (desmoid tumor). The tumor was surgically resected, and since then, the patient has remained asymptomatic without any restrictions of daily living activities and without any signs of tumor recurrence during the two-year follow-up. Conclusions Complete resection is the treatment of choice. Adjuvant therapy using non steroidal anti-inflammatory agents, tamoxifen, interferon, anti-neoplastic agents, and radiotherapy, either alone or in combination finds application for unresectable or recurrent cases.</p

Molecular Liver Cancer Prevention in Cirrhosis by Organ Transcriptome Analysis and Lysophosphatidic Acid Pathway Inhibition

Shigeki Nakagawa, Lan Wei and Won MinSong are co-first author.International audienceCirrhosis is a milieu that develops hepatocellular carcinoma (HCC), the second most lethal cancer worldwide. HCC prediction and prevention in cirrhosis are key unmet medical needs. Here we have established an HCC risk gene signature applicable to all major HCC etiologies: hepatitis B/C, alcohol, and non-alcoholic steatohepatitis. A transcriptome meta-analysis of >500 human cirrhotics revealed global regulatory gene modules driving HCC risk and the lysophosphatidic acid pathway as a central chemoprevention target. Pharmacological inhibition of the pathway in vivo reduced tumors and reversed the gene signature, which was verified in organotypic ex vivo culture of patient-derived fibrotic liver tissues. These results demonstrate the utility of clinical organ transcriptome to enable a strategy, namely, reverse-engineering precision cancer prevention

Molecular liver cancer prevention in cirrhosis by organ transcriptome analysis and lysophosphatidic acid pathway inhibition

Cirrhosis is a milieu that develops hepatocellular carcinoma (HCC), the second most lethal cancer worldwide. HCC prediction and prevention in cirrhosis are key unmet medical needs. Here we have established an HCC risk gene signature applicable to all major HCC etiologies: hepatitis B/C, alcohol, and non-alcoholic steatohepatitis. A transcriptome meta-analysis of >500 human cirrhotics revealed global regulatory gene modules driving HCC risk and the lysophosphatidic acid pathway as a central chemoprevention target. Pharmacological inhibition of the pathway in vivo reduced tumors and reversed the gene signature, which was verified in organotypic ex vivo culture of patient-derived fibrotic liver tissues. These results demonstrate the utility of clinical organ transcriptome to enable a strategy, namely, reverse-engineering precision cancer prevention