Discovery of widespread transcription initiation at microsatellites predictable by sequence-based deep neural network

Using the Cap Analysis of Gene Expression (CAGE) technology, the FANTOM5 consortium provided one of the most comprehensive maps of transcription start sites (TSSs) in several species. Strikingly, ~72% of them could not be assigned to a specific gene and initiate at unconventional regions, outside promoters or enhancers. Here, we probe these unassigned TSSs and show that, in all species studied, a significant fraction of CAGE peaks initiate at microsatellites, also called short tandem repeats (STRs). To confirm this transcription, we develop Cap Trap RNA-seq, a technology which combines cap trapping and long read MinION sequencing. We train sequence-based deep learning models able to predict CAGE signal at STRs with high accuracy. These models unveil the importance of STR surrounding sequences not only to distinguish STR classes, but also to predict the level of transcription initiation. Importantly, genetic variants linked to human diseases are preferentially found at STRs with high transcription initiation level, supporting the biological and clinical relevance of transcription initiation at STRs. Together, our results extend the repertoire of non-coding transcription associated with DNA tandem repeats and complexify STR polymorphism

Hidden Viral Sequences in Public Sequencing Data and Warning for Future Emerging Diseases

RNA viruses cause numerous emerging diseases, mostly due to transmission from mammalian and avian reservoirs. Large-scale surveillance of RNA viral infections in these animals is a fundamental step for controlling viral infectious diseases. Metagenomic analysis is a powerful method for virus identification with low bias and has contributed substantially to the discovery of novel viruses. Deep-sequencing data have been collected from diverse animals and accumulated in public databases, which can be valuable resources for identifying unknown viral sequences. Here, we screened for infections of 33 RNA viral families in publicly available mammalian and avian sequencing data and found approximately 900 hidden viral infections. We also discovered six nearly complete viral genomes in livestock, wild, and experimental animals: hepatovirus in a goat, hepeviruses in blind mole-rats and a galago, astrovirus in macaque monkeys, parechovirus in a cow, and pegivirus in tree shrews. Some of these viruses were phylogenetically close to human-pathogenic viruses, suggesting the potential risk of causing disease in humans upon infection. Furthermore, infections of five novel viruses were identified in several different individuals, indicating that their infections may have already spread in the natural host population. Our findings demonstrate the reusability of public sequencing data for surveying viral infections and identifying novel viral sequences, presenting a warning about a new threat of viral infectious disease to public health. IMPORTANCE Monitoring the spread of viral infections and identifying novel viruses capable of infecting humans through animal reservoirs are necessary to control emerging viral diseases. Massive amounts of sequencing data collected from various animals are publicly available, and these data may contain sequences originating from a wide variety of viruses. Here, we analyzed more than 46, 000 public sequencing data and identified approximately 900 hidden RNA viral infections in mammalian and avian samples. Some viruses discovered in this study were genetically similar to pathogens that cause hepatitis, diarrhea, or encephalitis in humans, suggesting the presence of new threats to public health. Our study demonstrates the effectiveness of reusing public sequencing data to identify known and unknown viral infections, indicating that future continuous monitoring of public sequencing data by metagenomic analyses would help prepare and mitigate future viral pandemics

Possibilities of bronchofiberscopy under general anesthesia : (Bronchofiberscopy under general anesthesia in the diagnosis of peripheral cancer of the lung)

Les auteurs ont rapporté les résultats d'une étude portant sur 559 cas de cancer du poumon étudiés pendant 19 ans de pratique bronchoscopique. Ils notent que dans 116 cas de cancer d'origine périphérique, les techniques bronchoscopiques traditionnelles ne sont pas suffisantes pour faire le diagnostic. Il montrent l'intérêt des examens cytologiques des frottis obtenus par la technique du brossage sélectif de la muqueuse, de la biopsie bronchique par pince et de la biopsie transbronchique à l'aiguille

Focal Aneurysm Wall Enhancement in Vessel Wall Imaging as a Surrogate Marker for Predicting Aneurysm Instability

Background The establishment of a risk stratification method for unruptured intracranial aneurysms (UIAs) remains an interdisciplinary challenge. The present study attempted to identify unstable UIAs using magnetic resonance vessel wall imaging in prospective data sets. Hemodynamic parameters in unstable UIAs were also examined to clarify the mechanisms by which segmented aneurysm wall enhancement (AWE) affects longitudinal morphological changes. Methods Patients with UIAs who underwent contrast‐enhanced vessel wall imaging between 2017 and 2022 and were followed up for more than 6 months were included. Two readers independently rated AWE patterns (no, focal, and circumferential AWE) on vessel wall imaging and morphological changes on time‐of‐flight magnetic resonance angiography. Computational fluid dynamics studies were performed on unstable UIAs to evaluate the hemodynamic features of evolved or ruptured points in aneurysm walls. Results Aneurysm growth was observed in 13 of 114 UIAs in the present study during a median follow‐up of 34 months. Of the 13 growing UIAs, their AWE patterns were as follows: no AWE in 6 and focal AWE (FAWE) in 7 UIAs. Univariable Cox regression analysis showed that aneurysm size and FAWE were associated with aneurysm growth. On multivariable Cox regression analysis, FAWE (hazard ratio, 4.59 [95% CI, 1.29–16.3]; P=0.019) was independently associated with aneurysm growth. Kaplan–Meier curve revealed significant differences between AWE patterns and UIA growth (P<0.001). Aneurysms ruptured in the 4 UIAs with FAWE during the follow‐up and all rupture points corresponded to nonenhanced lesions in aneurysm walls. Nonenhanced areas had higher wall shear stress than enhanced areas (1.59±1.02 versus 0.53±0.32; P=0.022). Conclusion FAWE may be associated with aneurysm growth and rupture during follow‐up. A comprehensive analysis of nonenhanced areas of UIAs with FAWE using vessel wall imaging and computational fluid dynamics provides insights into the mechanisms underlying aneurysm instability

Clinical application of exosomal microRNAs in peritoneal fluids of gastric cancer patients with peritoneal metastases

The purpose of this study is to explore the exosomal microRNAs obtained from peritoneal fluids of gastric cancer patients, which are specific for peritoneal metastasis （PM） and could be a predictive marker of disease status in PM. Exosomes were isolated from peritoneal fluids of patients of gastric cancer with PM. Presence of isolated extracellular vesicles （EVs） from peritoneal fluid specimens were confirmed using a transmission electron microscope showed that many EVs were approximately 100 nm in diameter, which were equivalent to exosome fractions. We carried out RNA extraction and comprehensive array analysis of exosomal microRNAs and have identified that 86 microRNAs were significantly up- or down-regulated in all 4 specimens and that out of them, miR-323-3p was highly expressed in all 4 cases. In this way, we have established an experimental system for measuring exosomal microRNAs in peritoneal lavage specimens. Next, we plan to apply this analysis for additional peritoneal lavage specimens obtained from gastric cancer patients with or without PM and to identify specific microRNAs, which could be predictive biomarkers for the disease status of PM in gastric cancer