Retinal boundary segmentation in stargardt disease optical coherence tomography images using automated deep learning

Purpose: To use a deep learning model to develop a fully automated method (fully semantic network and graph search [FS-GS]) of retinal segmentation for optical coherence tomography (OCT) images from patients with Stargardt disease. Methods: Eighty-seven manually segmented (ground truth) OCT volume scan sets (5171 B-scans) from 22 patients with Stargardt disease were used for training, validation and testing of a novel retinal boundary detection approach (FS-GS) that combines a fully semantic deep learning segmentation method, which generates a per-pixel class prediction map with a graph-search method to extract retinal boundary positions. The performance was evaluated using the mean absolute boundary error and the differences in two clinical metrics (retinal thickness and volume) compared with the ground truth. The performance of a separate deep learning method and two publicly available software algorithms were also evaluated against the ground truth. Results: FS-GS showed an excellent agreement with the ground truth, with a boundary mean absolute error of 0.23 and 1.12 pixels for the internal limiting membrane and the base of retinal pigment epithelium or Bruch's membrane, respectively. The mean difference in thickness and volume across the central 6 mm zone were 2.10 µm and 0.059 mm3. The performance of the proposed method was more accurate and consistent than the publicly available OCTExplorer and AURA tools. Conclusions: The FS-GS method delivers good performance in segmentation of OCT images of pathologic retina in Stargardt disease. Translational Relevance: Deep learning models can provide a robust method for retinal segmentation and support a high-throughput analysis pipeline for measuring retinal thickness and volume in Stargardt disease

TELEX HEBDOMADAIRE NR 186 DU 12 OCTOBRE 1984 ADRESSE A L'ENSEMBLE DES DELEGATIONS EXTERIEURES ET BUREAUX DE PRESS ET D'INFORMATION INDEPENDANTS DANS LES PAYS TIERS = WEEKLY MEMO NO. 186 ON OCTOBER 12, 1984 TO FOREIGN DELEGATIONS AND PRESS BUREAUS OF THIRD COUNTRIES

Inhibitory activities against BoNT/A LC and holotoxin in proteolytic and cell-based assay for all tested compounds; fluorescence and UV–vis spectra for determination of 16 binding to HSA and AGP; ligand interaction diagrams, docking scores, and docking–in vitro inhibitory activity correlations; spectral and analytical data for all synthesized compounds; detailed procedures for the determination of the HPLC purity.Supporting information I for: Konstantinović, J. M., Kiris, E., Kota, K. P., Kugelman-Tonos, J., Videnović, M., Cazares, L. H., Terzić-Jovanović, N., Verbić, T., Anđelković, B. D., Duplantier, A. J., Bavari, S.,& Šolaja, B. (2018). New Steroidal 4-Aminoquinolines Antagonize Botulinum Neurotoxin Serotype A in Mouse Embryonic Stem Cell Derived Motor Neurons in Postintoxication Model. Journal of Medicinal Chemistry, American Chemical Society (ACS)., 61(4), 1595-1608. [https://doi.org/10.1021/acs.jmedchem.7b01710]The published version of the article: [https://cer.ihtm.bg.ac.rs/handle/123456789/2325]The peer-reviewed version of the article: [http://cer.ihtm.bg.ac.rs/handle/123456789/2935]Additional supporting information (NMR spectra and HPLC purity spectra of all tested compounds): [https://cer.ihtm.bg.ac.rs/handle/123456789/4516]Molecular formula strings and additional data: [https://cer.ihtm.bg.ac.rs/handle/123456789/4517

Supporting Information II for: "New Steroidal 4-Aminoquinolines Antagonize Botulinum Neurotoxin Serotype A in Mouse Embryonic Stem Cell Derived Motor Neurons in Postintoxication Model"

NMR spectra and HPLC purity spectra of all tested compoundsSupporting information II for: Konstantinović, J. M., Kiris, E., Kota, K. P., Kugelman-Tonos, J., Videnović, M., Cazares, L. H., Terzić-Jovanović, N., Verbić, T., Anđelković, B. D., Duplantier, A. J., Bavari, S.,& Šolaja, B. (2018). New Steroidal 4-Aminoquinolines Antagonize Botulinum Neurotoxin Serotype A in Mouse Embryonic Stem Cell Derived Motor Neurons in Postintoxication Model. Journal of Medicinal Chemistry, American Chemical Society (ACS)., 61(4), 1595-1608. [https://doi.org/10.1021/acs.jmedchem.7b01710]The published version of the article: [https://cer.ihtm.bg.ac.rs/handle/123456789/2325]The peer-reviewed version of the article: [http://cer.ihtm.bg.ac.rs/handle/123456789/2935]Additional supporting information: [https://cer.ihtm.bg.ac.rs/handle/123456789/4515]Molecular formula strings and additional data: [https://cer.ihtm.bg.ac.rs/handle/123456789/4517

Supplementary data for the article: Konstantinović, J.; Kiris, E.; Kota, K. P.; Kugelman-Tonos, J.; Videnović, M.; Cazares, L. H.; Terzić Jovanović, N.; Verbić, T. Ž.; Andjelković, B.; Duplantier, A. J.; et al. New Steroidal 4-Aminoquinolines Antagonize Botulinum Neurotoxin Serotype A in Mouse Embryonic Stem Cell Derived Motor Neurons in Postintoxication Model. Journal of Medicinal Chemistry 2018, 61 (4), 1595–1608. https://doi.org/10.1021/acs.jmedchem.7b01710

Supplementary material for: [https://doi.org/10.1021/acs.jmedchem.7b01710]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/2099

Contribution by Polymorphonucleate Granulocytes to Elevated Gamma-Glutamyltransferase in Cystic Fibrosis Sputum

Background: Cystic fibrosis (CF) is an autosomal recessive disorder characterized by a chronic neutrophilic airways inflammation, increasing levels of oxidative stress and reduced levels of antioxidants such as glutathione (GSH). Gammaglutamyltransferase (GGT), an enzyme induced by oxidative stress and involved in the catabolism of GSH and its derivatives, is increased in the airways of CF patients with inflammation, but the possible implications of its increase have not yet been investigated in detail. Principal Findings: The present study was aimed to evaluate the origin and the biochemical characteristics of the GGT detectable in CF sputum. We found GGT activity both in neutrophils and in the fluid, the latter significantly correlating with myeloperoxidase expression. In neutrophils, GGT was associated with intracellular granules. In the fluid, gel-filtration chromatography showed the presence of two distinct GGT fractions, the first corresponding to the human plasma b-GGT fraction, the other to the free enzyme. The same fractions were also observed in the supernatant of ionomycin and fMLPactivated neutrophils. Western blot analysis confirmed the presence of a single band of GGT immunoreactive peptide in the CF sputum samples and in isolated neutrophils. Conclusions: In conclusion, our data indicate that neutrophils are able to transport and release GGT, thus increasing GGT activity in CF sputum. The prompt release of GGT may have consequences on all GGT substrates, including major inflammatory mediators such as S-nitrosoglutathione and leukotrienes, and could participate in early modulation of inflammatory response

Phylodynamic assessment of intervention strategies for the West African Ebola virus outbreak

Genetic analyses have provided important insights into Ebola virus spread during the recent West African outbreak, but their implications for specific intervention scenarios remain unclear. Here, we address this issue using a collection of phylodynamic approaches. We show that long-distance dispersal events were not crucial for epidemic expansion and that preventing viral lineage movement to any given administrative area would, in most cases, have had little impact. However, major urban areas were critical in attracting and disseminating the virus: preventing viral lineage movement to all three capitals simultaneously would have contained epidemic size to one-third. We also show that announcements of border closures were followed by a significant but transient effect on international virus dispersal. By quantifying the hypothetical impact of different intervention strategies, as well as the impact of barriers on dispersal frequency, our study illustrates how phylodynamic analyses can help to address specific epidemiological and outbreak control questions.info:eu-repo/semantics/publishe

Nomenclature- and Database-Compatible Names for the Two Ebola Virus Variants that Emerged in Guinea and the Democratic Republic of the Congo in 2014

In 2014, Ebola virus (EBOV) was identified as the etiological agent of a large and still expanding outbreak of Ebola virus disease (EVD) in West Africa and a much more confined EVD outbreak in Middle Africa. Epidemiological and evolutionary analyses confirmed that all cases of both outbreaks are connected to a single introduction each of EBOV into human populations and that both outbreaks are not directly connected. Coding-complete genomic sequence analyses of isolates revealed that the two outbreaks were caused by two novel EBOV variants, and initial clinical observations suggest that neither of them should be considered strains. Here we present consensus decisions on naming for both variants (West Africa: “Makona”, Middle Africa: “Lomela”) and provide database-compatible full, shortened, and abbreviated names that are in line with recently established filovirus sub-species nomenclatures

Two-Year Outcomes After Minimally Invasive Surfactant Therapy in Preterm Infants: Follow-Up of the OPTIMIST-A Randomized Clinical Trial

Importance: The long-term effects of surfactant administration via a thin catheter (minimally invasive surfactant therapy [MIST]) in preterm infants with respiratory distress syndrome remain to be definitively clarified. / Objective: To examine the effect of MIST on death or neurodevelopmental disability (NDD) at 2 years' corrected age. / Design, Setting, and Participants: Follow-up study of a randomized clinical trial with blinding of clinicians and outcome assessors conducted in 33 tertiary-level neonatal intensive care units in 11 countries. The trial included 486 infants with a gestational age of 25 to 28 weeks supported with continuous positive airway pressure (CPAP). Collection of follow-up data at 2 years' corrected age was completed on December 9, 2022. / Interventions: Infants assigned to MIST (n = 242) received exogenous surfactant (200 mg/kg poractant alfa) via a thin catheter; those assigned to the control group (n = 244) received sham treatment. / Main Outcomes and Measures: The key secondary outcome of death or moderate to severe NDD was assessed at 2 years' corrected age. Other secondary outcomes included components of this composite outcome, as well as hospitalizations for respiratory illness and parent-reported wheezing or breathing difficulty in the first 2 years. / Results: Among the 486 infants randomized, 453 had follow-up data available (median gestation, 27.3 weeks; 228 females [50.3%]); data on the key secondary outcome were available in 434 infants. Death or NDD occurred in 78 infants (36.3%) in the MIST group and 79 (36.1%) in the control group (risk difference, 0% [95% CI, -7.6% to 7.7%]; relative risk [RR], 1.0 [95% CI, 0.81-1.24]); components of this outcome did not differ significantly between groups. Secondary respiratory outcomes favored the MIST group. Hospitalization with respiratory illness occurred in 49 infants (25.1%) in the MIST group vs 78 (38.2%) in the control group (RR, 0.66 [95% CI, 0.54-0.81]) and parent-reported wheezing or breathing difficulty in 73 (40.6%) vs 104 (53.6%), respectively (RR, 0.76 [95% CI, 0.63-0.90]). / Conclusions and Relevance: In this follow-up study of a randomized clinical trial of preterm infants with respiratory distress syndrome supported with CPAP, MIST compared with sham treatment did not reduce the incidence of death or NDD by 2 years of age. However, infants who received MIST had lower rates of adverse respiratory outcomes during their first 2 years of life. / Trial Registration: anzctr.org.au Identifier: ACTRN12611000916943

Microbial Maintenance: A Critical Review on Its Quantification

Microbial maintenance is an important concept in microbiology. Its quantification, however, is a subject of continuous debate, which seems to be caused by (1) its definition, which includes nongrowth components other than maintenance; (2) the existence of partly overlapping concepts; (3) the evolution of variables as constants; and (4) the neglect of cell death in microbial dynamics. The two historically most important parameters describing maintenance, the specific maintenance rate and the maintenance coefficient, are based on partly different nongrowth components. There is thus no constant relation between these parameters and previous equations on this subject are wrong. In addition, the partial overlap between these parameters does not allow the use of a simple combination of these parameters. This also applies for combinations of a threshold concentration with one of the other estimates of maintenance. Maintenance estimates should ideally explicitly describe each nongrowth component. A conceptual model is introduced that describes their relative importance and reconciles the various concepts and definitions. The sensitivity of maintenance on underlying components was analyzed and indicated that overall maintenance depends nonlinearly on relative death rates, relative growth rates, growth yield, and endogenous metabolism. This quantitative sensitivity analysis explains the felt need to develop growth-dependent adaptations of existing maintenance parameters, and indicates the importance of distinguishing the various nongrowth components. Future experiments should verify the sensitivity of maintenance components under cellular and environmental conditions