Radiomics-Based Assessment of OCT Angiography Images for Diabetic Retinopathy Diagnosis.

Purpose: To evaluate the diagnostic accuracy of machine learning (ML) techniques applied to radiomic features extracted from OCT and OCT angiography (OCTA) images for diabetes mellitus (DM), diabetic retinopathy (DR), and referable DR (R-DR) diagnosis. Design: Cross-sectional analysis of a retinal image dataset from a previous prospective OCTA study (ClinicalTrials.govNCT03422965). Participants: Patients with type 1 DM and controls included in the progenitor study. Methods: Radiomic features were extracted from fundus retinographies, OCT, and OCTA images in each study eye. Logistic regression, linear discriminant analysis, support vector classifier (SVC)-linear, SVC-radial basis function, and random forest models were created to evaluate their diagnostic accuracy for DM, DR, and R-DR diagnosis in all image types. Main Outcome Measures: Area under the receiver operating characteristic curve (AUC) mean and standard deviation for each ML model and each individual and combined image types. Results: A dataset of 726 eyes (439 individuals) were included. For DM diagnosis, the greatest AUC was observed for OCT (0.82, 0.03). For DR detection, the greatest AUC was observed for OCTA (0.77, 0.03), especially in the 3 × 3 mm superficial capillary plexus OCTA scan (0.76, 0.04). For R-DR diagnosis, the greatest AUC was observed for OCTA (0.87, 0.12) and the deep capillary plexus OCTA scan (0.86, 0.08). The addition of clinical variables (age, sex, etc.) improved most models AUC for DM, DR and R-DR diagnosis. The performance of the models was similar in unilateral and bilateral eyes image datasets. Conclusions: Radiomics extracted from OCT and OCTA images allow identification of patients with DM, DR, and R-DR using standard ML classifiers. OCT was the best test for DM diagnosis, OCTA for DR and R-DR diagnosis and the addition of clinical variables improved most models. This pioneer study demonstrates that radiomics-based ML techniques applied to OCT and OCTA images may be an option for DR screening in patients with type 1 DM. Financial Disclosures: Proprietary or commercial disclosure may be found after the references.

Taxonomic assessment of the inquiline fauna (Hymenoptera: Cynipidae: Synergini, Ceroptresini) reared from cynipid galls on oaks (Quercus spp.) from South Korea.

A complete taxonomic assessment of the inquiline fauna (Hymenoptera: Cynipidae: Synergini, Ceroptresini) reared from cynipid oak galls collected in South Korea is conducted for the first time. Previously, six species were known from this country (Ceroptres kovalevi Belizin, 1973; Synergus chinensis Melika, Ács Bechtold, 2004; Synergus japonicus Walker, 1874; Ufo koreanus Melika, Pujade-Villar Choi, 2007; and presumably, Saphonecrus chaodongzhui Melika, Ács Bechtold, 2004 and Ufo cerroneuroteri Tang Melika, 2012). The study of new material reared from cynipid galls collected from oaks (Quercus spp.) from various locations throughout South Korea has increased the total number of inquiline species known from this country to 14, of which seven are new country records (Saphonecrus shirakashii (Shinji, 1940); Sa. symbioticus Melika Schwéger, 2015; Synergus abei Melika Schwéger, 2015; S. belizinellus Schwéger Melika 2015; S. formosanus Schwéger Melika, 2015; S. ishikarii Melika Schwéger, 2015; and S. symbioticus Schwéger Melika, 2015), and one is a new species: Synergus minutus Lobato-Vila Pujade-Villar, sp. nov. The new species is formally described and illustrated. New biological and distribution data are provided for both the newly recorded species and the other reared species. The Korean fauna is compared with that from other countries within the Eastern Palearctic and the Oriental regions.

A new Diplolepis Geoffroy (Hymenoptera, Cynipidae, Diplolepidini) species from China: a rare example of a rose gall-inducer of economic significance.

A new species of the genus Diplolepis Geoffroy, Diplolepis abei Pujade-Villar & Wang sp. nov. is described on host plant Rosa sertata Rolfe × R. rugosa Thunb. from China with an integrative approach based on molecular and morphological data. Diagnosis, distribution and biology of the new species are included and illustrated. This species is the first known rose gall-inducer of economic importance. A review of Eastern Palearctic species of Diplolepis is given and a key to the Chinese fauna is presented.

Optimisation of a potency assay for the assessment of immunomodulative potential of clinical grade multipotent mesenchymal stromal cells.

Clinical use of multipotent Mesenchymal Stromal Cell (MSC)-based medicinal products requires their production in compliance with Good Manufacturing Practices, thus ensuring that the final drug product meets specifications consistently from batch to batch in terms of cell viability, identity, purity and potency. Potency relates to the efficacy of the medicine in its target clinical indication, so adequate release tests need to be defined and validated as quality controls. Herein we report the design and optimisation of parameters affecting the performance of an in vitro cell-based assay for assessing immunomodulatory potential of clinical grade MSC for human use, based on their capacity to inhibit proliferation of T lymphocytes under strong polyclonal stimuli. The resulting method was demonstrated to be reproducible and relatively simple to execute. Two case studies using clinical grade MSC are presented as examples to illustrate the applicability of the methodology described in this work.

Assessment of biodistribution using mesenchymal stromal cells: Algorithm for study design and challenges in detection methodologies.

BACKGROUND AIMS: Biodistribution of candidate cell-based therapeutics is a critical safety concern that must be addressed in the preclinical development program. We aimed to design a decision tree based on a series of studies included in actual dossiers approved by competent regulatory authorities, noting that the design, execution and interpretation of pharmacokinetics studies using this type of therapy is not straightforward and presents a challenge for both developers and regulators. METHODS: Eight studies were evaluated for the definition of a decision tree, in which mesenchymal stromal cells (MSCs) were administered to mouse, rat and sheep models using diverse routes (local or systemic), cell labeling (chemical or genetic) and detection methodologies (polymerase chain reaction [PCR], immunohistochemistry [IHC], fluorescence bioimaging, and magnetic resonance imaging [MRI]). Moreover, labeling and detection methodologies were compared in terms of cost, throughput, speed, sensitivity and specificity. RESULTS: A decision tree was defined based on the model chosen: (i) small immunodeficient animals receiving heterologous MSC products for assessing biodistribution and other safety aspects and (ii) large animals receiving homologous labeled products; this contributed to gathering data not only on biodistribution but also on pharmacodynamics. PCR emerged as the most convenient technique despite the loss of spatial information on cell distribution that can be further assessed by IHC. DISCUSSION: This work contributes to the standardization in the design of biodistribution studies by improving methods for accurate assessment of safety. The evaluation of different animal models and screening of target organs through a combination of techniques is a cost-effective and timely strategy.

Qualification of computerized monitoring systems in a cell therapy facility compliant with the good manufacturing practices.

AIM: Computerized systems (CS) are essential in the development and manufacture of cell-based medicines and must comply with good manufacturing practice, thus pushing academic developers to implement methods that are typically found within pharmaceutical industry environments. MATERIALS & METHODS: Qualitative and quantitative risk analyses were performed by Ishikawa and Failure Mode and Effects Analysis, respectively. RESULTS: A process for qualification of a CS that keeps track of environmental conditions was designed and executed. The simplicity of the Ishikawa analysis permitted to identify critical parameters that were subsequently quantified by Failure Mode Effects Analysis, resulting in a list of test included in the qualification protocols. CONCLUSION: The approach presented here contributes to simplify and streamline the qualification of CS in compliance with pharmaceutical quality standards.