Learning to detect chest radiographs containing lung nodules using visual attention networks

Machine learning approaches hold great potential for the automated detection of lung nodules in chest radiographs, but training the algorithms requires vary large amounts of manually annotated images, which are difficult to obtain. Weak labels indicating whether a radiograph is likely to contain pulmonary nodules are typically easier to obtain at scale by parsing historical free-text radiological reports associated to the radiographs. Using a repositotory of over 700,000 chest radiographs, in this study we demonstrate that promising nodule detection performance can be achieved using weak labels through convolutional neural networks for radiograph classification. We propose two network architectures for the classification of images likely to contain pulmonary nodules using both weak labels and manually-delineated bounding boxes, when these are available. Annotated nodules are used at training time to deliver a visual attention mechanism informing the model about its localisation performance. The first architecture extracts saliency maps from high-level convolutional layers and compares the estimated position of a nodule against the ground truth, when this is available. A corresponding localisation error is then back-propagated along with the softmax classification error. The second approach consists of a recurrent attention model that learns to observe a short sequence of smaller image portions through reinforcement learning. When a nodule annotation is available at training time, the reward function is modified accordingly so that exploring portions of the radiographs away from a nodule incurs a larger penalty. Our empirical results demonstrate the potential advantages of these architectures in comparison to competing methodologies

Assessment of the immunomodulatory properties of the probiotic strain Lactobacillus paracasei K5 in vitro and in vivo

Lactobacillus paracasei K5 is a lactic acid bacteria (LAB) strain that has been isolated from dairy products. Previous studies have established its probiotic potential in a series of in vitro tests, including molecular characterization, safety profiling, and tolerability of the gastrointestinal tract conditions. To characterize its beneficial actions on the host, we have shown previously that L. paracasei K5 adheres to Caco-2 cells and exerts anti-proliferative effects through the induction of apoptosis. In the present study, we focused on the immunomodulatory potential of this strain. We employed the dorsal-air-pouch mouse model of inflammation and recorded an eight-fold increase in the recruitment of immune cells in mice treated with the probiotic strain, compared to the control group. Analysis of the exudates revealed significant changes in the expression of pro-inflammatory mediators on site. Treatment of Caco-2 cells with L. paracasei K5 induced significant upregulation of cytokines interleukin-1α (IL-1α), ΙL-1β, IL-6, tumor necrosis factor-alpha (TNF-α), the chemokine C-X-C motif ligand 2 (CXCL2), and the inflammation markers soluble intercellular adhesion molecule (sICAM) and metallopeptidase inhibitor-1 (TIMP-1). Transient induction of the Toll-like receptors (TLRs) 2, 4, 6, and 9 expression levels was recorded by real-time PCR analysis. These results highlight the immunomodulatory potential of this strain and further support its probiotic character

Increased apoptotic activity on inflammatory human placentas in spontaneous abortions during the first and second trimester of gestation: a histochemical and immunohistochemical study

The aim of this study was to investigate the role of apoptotic markers on inflammatory human placentas from spontaneous abortions during the first and second trimester of gestation and compare them to those without inflammation. Paraffin-embedded specimens from 76 placentas were investigated by conventional histology and immunohistochemistry using monoclonal antibodies against M30, Caspase 3, Caspase 8 and Caspase 9, as well as the terminal deoxynucleotidyl tranferase-mediated deoxyuridine triphosphate nick end labeling method. A higher prevalence of expression of apoptotic markers (94.4%) was observed in placentas associated with chorioamnionitis in comparison with those without inflammation. Our observations confirm that apoptosis is strikingly prevalent in placentas diagnosed with histologic chorioamnionitis, while the inflammation induces cell death

A Rapid and Highly Sensitive Method of Non Radioactive Colorimetric In Situ Hybridization for the Detection of mRNA on Tissue Sections

Background: Non Radioactive colorimetric In Situ Hybridization (NoRISH) with hapten labeled probes has been widely used for the study of gene expression in development, homeostasis and disease. However, improvement in the sensitivity of the method is still needed to allow for the analysis of genes expressed at low levels. Methodology/Principal Findings: A stable, non-toxic, zinc-based fixative was tested in NoRISH experiments on sections of mouse embryos using four probes (Lhx6, Lhx7, ncapg and ret) that have different spatial patterns and expression levels. We showed that Z7 can successfully replace paraformaldehyde used so far for tissue fixation in NoRISH; the morphology of the cryosections of Z7-fixed tissues was excellent, and the fixation time required for tissues sized 1 cm was 1 hr instead of 24 hr for paraformaldehyde. The hybridization signal on the sections of the Z7-treated embryos always appeared earlier than that of the PFA-fixed embryos. In addition, a 50–60 % shorter detection time was observed in specimen of Z7-treated embryos, reducing significantly the time required to complete the method. Finally and most importantly, the strength of the hybridization signal on the sections of the Z7-treated embryos always compared favorably to that of the sections of PFAfixed embryos; these data demonstrate a significant improvement of the sensitivity the method that allows for the analysis of mRNAs that are barely or not detected by the standard colorimetric NoRISH method. Conclusions/Significance: Our NoRISH method provides excellent preservation of tissue morphology, is rapid, highl

STUDY OF THE MATERNAL AND NEONATAL ACID-BASE STATUS AFTER PROPOFOL ADMINISTRATION FOR CAESAREAN SECTION IN RABBITS. (EXPERIMENTAL STUDY)

IN THIS INVESTIGATION WE STUDIED THE MATERNAL AND NEONATAL ACID-BASE STATUS OF THE RABBIT AFTER PROPOFOL ANAESTHESIA FOR CAESAREAN SECTION. WE USED 2 GROUPSOF 20 DOES EACH. THE ANAESTHESIA WAS INDUSED, IN BOTH GROUPS, WITH A SINGLE DOSE OF PROPOFOL, WHILE IT WAS MAINTAINED WITH BOLUS, IN THE FIRST GROUP, ANDCONTINUOUS, IN THE SECOND, INFUSIONS OF PROPOFOL. WE TOOK, EVERY 5 MINUTES DURING THE ANAESTHETIC PERIOD, AND ALSO AT THE FIRST 5 MINUTES OF RECOVERY, SAMPLES OF ARTERIAL BLOOD FROM THE PREGNANT DOES, WHERE PH, PCO2, PO2 AND HCO-3WERE CALCULATED IN ORDER TO EVALUATE THEIR ACID-BASE STATUS. SIMILAR SAMPLESWERE OBTAINED FROM, 60 PER GROUP, NEONATES IMMEDIATELY AFTER THEIR DELIVERY WITH CAESAREAN SECTION AND 24 HOURS LATER. BASED ON THE MATERNAL ARTERIAL BLOOD MEASUREMENTS, DURING THE ANAESTHETIC PERIOD, IN BOTH GROUPS, WE OBSERVED THE PRESENCE OF AN ACUTE RESPIRATORY ACIDOSIS. THIS ACID-BASE DISORDER WAS RESTORED DURING THE RECOVERY PERIOD. THE NEONATAL ACID-BASE STATUS IMMEDIATELY AFTER THEIR DELIVERY, IN BOTH GROUPS, WAS THAT OF A RESPIRATORY ACIDOSIS, WHICHWAS RESTORED 24 HOURS LATER. ALTHOUGH PROPOFOL CAUSES A MILD MATERNAL RESPIRATORY DEPRESSION OF THE PREGNANT DOE, IT DOESN'T SEEM TO ADVERSE EFFECT THE PHYSIOLOGICAL DEVELOPMENT OF THE NEONATAL ACID-BASE STATUS.ΣΤΗΝ ΕΡΕΥΝΑ ΑΥΤΗ ΜΕΛΕΤΗΣΑΜΕ ΤΗΝ ΟΞΕΟΒΑΣΙΚΗ ΚΑΤΑΣΤΑΣΗ ΤΟΥ ΜΗΤΡΙΚΟΥ ΚΑΙ ΝΕΟΓΝΙΚΟΥΟΡΓΑΝΙΣΜΟΥ ΚΟΥΝΕΛΙΟΥ ΜΕΤΑ ΑΠΟ ΧΟΡΗΓΗΣΗ ΠΡΟΠΟΦΟΛΗΣ ΓΙΑ ΤΗΝ ΑΝΑΙΣΘΗΣΙΑ ΚΑΙΣΑΡΙΚΗΣ ΤΟΜΗΣ. ΕΙΔΙΚΟΤΕΡΑ, ΧΡΗΣΙΜΟΠΟΙΗΣΑΜΕ 2 ΟΜΑΔΕΣ ΤΩΝ 20 ΚΟΥΝΕΛΙΩΝ. Η ΕΓΚΑΤΑΣΤΑΣΗ ΤΗΣ ΑΝΑΙΣΘΗΣΙΑΣ ΕΓΙΝΕ, ΣΤΗΝ ΠΡΩΤΗ ΟΜΑΔΑ, ΜΕ BOLUS ΚΑΙ ΣΤΗ ΔΕΥΤΕΡΗ ΜΕ ΣΤΑΓΔΗΝ ΧΟΡΗΓΗΣΗ ΠΡΟΠΟΦΟΛΗΣ. ΚΑΤΑ ΤΗ ΔΙΑΡΚΕΙΑ ΤΗΣ ΑΝΑΙΣΘΗΣΙΑΣ, ΑΝΑ 5 ΛΕΠΤΑ, ΚΑΘΩΣ ΚΑΙ ΣΤΑ ΠΡΩΤΑ 5 ΛΕΠΤΑ ΤΗΣ ΑΝΑΝΗΨΗΣ, ΛΑΜΒΑΝΑΜΕ ΔΕΙΓΜΑΤΑ ΑΡΤΗΡΙΑΚΟΥ ΑΙΜΑΤΟΣ ΑΠΟΤΙΣ ΕΓΚΥΕΣ ΚΟΥΝΕΛΕΣ, ΟΠΟΥ ΜΕΤΡΩΝΤΑΝ ΤΑ PH, PCO2, PO2 ΚΑΙ ΤΑ HCO-3 ΓΙΑ ΝΑ ΕΚΤΙΜΗΘΕΙ Η ΟΞΕΟΒΑΣΙΚΗ ΤΟΥΣ ΚΑΤΑΣΤΑΣΗ. ΠΑΡΟΜΟΙΑ ΔΕΙΓΜΑΤΑ ΠΗΡΑΜΕ ΑΠΟ, 60 ΑΝΑ ΟΜΑΔΑ, ΝΕΟΓΕΝΝΗΤΑ ΑΜΕΣΩΣ ΜΕΤΑ ΤΗ ΛΗΨΗ ΤΟΥΣ ΜΕ ΚΑΙΣΑΡΙΚΗ ΤΟΜΗ ΚΑΘΩΣ ΚΑΙ 24 ΩΡΕΣ ΑΡΓΟΤΕΡΑ. ΑΠΟ ΤΙΣ ΜΕΤΡΗΣΕΙΣ ΤΟΥ ΜΗΤΡΙΚΟΥ ΑΙΜΑΤΟΣ, ΚΑΤΑ ΤΗ ΔΙΑΡΚΕΙΑ ΤΗΣ ΑΝΑΙΣΘΗΣΙΑΣ, ΚΑΙ ΣΤΙΣ ΔΥΟ ΟΜΑΔΕΣ, ΔΙΑΠΙΣΤΩΣΑΜΕ ΤΗΝ ΠΑΡΟΥΣΙΑ ΟΞΕΙΑΣ ΑΝΑΠΝΕΥΣΤΙΚΗΣ ΟΞΕΩΣΗΣ. Η ΟΞΕΟΒΑΣΙΚΗ ΑΥΤΗ ΔΙΑΤΑΡΑΧΗ ΑΠΟΚΑΤΑΣΤΑΘΗΚΕ ΚΑΤΑ ΤΗΝ ΑΝΑΝΗΨΗ. Η ΟΞΕΟΒΑΣΙΚΗΚΑΤΑΣΤΑΣΗ ΤΩΝ ΝΕΟΓΕΝΝΗΤΩΝ ΑΜΕΣΩΣ ΜΕΤΑ ΤΗ ΛΗΨΗ ΤΟΥΣ, ΚΑΙ ΣΤΙΣ ΔΥΟ ΟΜΑΔΕΣ, ΠΑΡΟΥΣΙΑΖΕ ΕΙΚΟΝΑ ΑΝΑΠΝΕΥΣΤΙΚΗΣ ΟΞΕΩΣΗΣ, Η ΟΠΟΙΑ ΑΠΟΚΑΤΑΣΤΑΘΗΚΕ ΜΕΤΑ ΑΠΟ 24 ΩΡΕΣ. ΑΝ ΚΑΙ Η ΠΡΟΠΟΦΟΛΗ ΠΡΟΚΑΛΕΙ ΜΙΑ ΜΕΤΡΙΑ ΚΑΤΑΣΤΟΛΗ ΤΗΣ ΑΝΑΠΝΕΥΣΤΙΚΗΣ ΛΕΙΤΟΥΡΓΙΑΣ ΤΗΣ ΕΓΚΥΟΥ ΚΟΥΝΕΛΑΣ, ΔΕ ΦΑΙΝΕΤΑΙ ΝΑ ΕΠΗΡΕΑΖΕΙ ΤΗ ΦΥΣΙΟΛΟΓΙΚΗ ΕΞΕΛΙΞΗ ΤΗΣ ΟΞΕΟΒΑΣΙΚΗΣ ΚΑΤΑΣΤΑΣΗΣ ΤΟΥ ΝΕΟΓΕΝΝΗΤΟΥ

Μεθοδολογία Αποκριτικών Επιφανειών-Σχεδιασμοί Υποσυνόλου

60 σ.Η μεθοδολογία των αποκριρικών επιφανειών περιλαμβάνει τεχνικές των μαθηματικών και της στατιστικής, χρήσιμες για την μοντελοποίηση και την ανάλυση προβλημάτων, στα οποία η απόκριση επηρεάζεται απο ορισμένες μεταβλητές.The methodology of response surface uses mathematical and statistical instruments in order to descrise the response.Πέτρος-Παύλος Δ. Υψηλάντη

Immune and Inflammatory Responses of the Intestinal Mucosa following Extended Liver Radiofrequency Ablation

Background and Aim. Extended liver radiofrequency ablation (RFA) has been shown to disrupt gut barrier integrity with subsequent bacterial translocation. The aim of the present project was to study the immune and inflammatory responses of the intestinal mucosa after extended RFA of the liver. Methods. Twelve Wistar rats were either subjected to RFA of the left lateral hepatic lobe (approximately 30% of the liver mass) after midline laparotomy (group RFA, n=6) or sham operation (group Sham, n=6). Forty-eight hours later, ileal tissue specimens were excised for immunohistochemical assessment of CD68+ macrophages, CD4+ T-lymphocytes, CD8+ T-lymphocytes, mucosal addressin cell adhesion molecule-1 (MAdCAM-1), tumor necrosis factor-α (TNFα), interleukin-6 (IL-6), and nuclear factor-κB (NFκB) expression. Results. Immune response biomarkers were upregulated in the RFA group. Expression of CD4+ and CD8+ T-lymphocytes was moderate, while that of CD68+ macrophages and MAdCAM-1 was high. Inflammatory response biomarkers were also upregulated in the RFA group. TNFα, IL-6, and NFκB expression was low, moderate, and high, respectively. Conclusions. Extended liver RFA evokes both immune and inflammatory responses of the gut mucosa