Impacts histo-morphologiques et biochimiques de la mutation laurina sur les graines et les plantules de Coffea arabica L.

Coffea arabica var Laurina (Bourbon pointu, BP), is a natural mutant of C. arabica ‘Bourbon’ (B). The laurina mutation is recessive, monolocus and Mendelian, with pleiotropic effects. This work highlighted new effects of this mutation, with histological, morphological and biochemical approaches on seeds development and on seedlings. Simultaneous fitting of growth curves of B and BP and their standardization allow comparisons of these varieties and fine study of polysaccharide cell wall (PCW) composition over time. Thus, anatomic specificities, development stages (st) and fruit age were linked (growth: st 1-2 to 4; maturation: st 5 to 7). When taking in account the CWP evolution in time-course, three phases occurred: φ 1 (st 1-2, 3), φ 2 (st 3, 4 and the beginning of 5), and φ 3 (the end of 5, st 6, 7). The two first were affected by the mutation probably through maternal effect (perisperm). In seedlings, the hypocotyls semi-dwarfism in light growth condition is an effect of the mutation and was due to a lower cell number than in B. The phytohormones content was also affected (ABA, auxine, cytokinins). But, neither CWP composition nor chlorogenics acids (CQA) content were affected by the mutation, or growth condition (expected for CQA content in roots). The composition in CWP and CQA was different depending on organs. Finally, caffeine (CAF) content was affected by the mutation in light or darkness conditions. These results represent an important step in 1/ the characterization of the pleiotropic effects of the laurina mutation, 2/ the understanding of the CWP evolution in seed time course, and 3/ new knowledge on seedlings (hormone, CAF, CQA and CWP composition).Coffea arabica var. Laurina (Bourbon pointu, BP) est un mutant naturel de C. arabica ‘Bourbon’ (B). La mutation laurina est récessive, monolocus, Mendélienne et ses effets pléiotropiques. Ces effets ont été étudiés sur le développement des graines et chez les plantules en histologie, morphologie et biochimie. La standardisation de la croissance en taille des graines était primordiale, notamment pour l'étude fine de la composition en polysaccharides pariétaux (PP). Les stades (st) de développement ont été reliés à l'âge des fruits et leur aspect histo-morphologique (st 1-2, 3, 4 : croissance ; st 5 à 7 : maturation). L'étude de la composition en PP a mis en évidence trois phases : φ 1 (st 1-2, 3), φ 2 (st 3, 4, première partie du 5), et φ 3 (deuxième partie du 5, st 6 et 7). La mutation affecte les φ 1 et 2, probablement par le biais du périsperme. Chez la plantule, la mutation affecte la longueur des hypocotyles exposés à la lumière en provoquant le semi-nanisme de BP par rapport à B par un nombre moindre de cellules. Les teneurs en ABA, auxine et cytokinines sont aussi touchées. La composition en PP et en acides chlorogéniques (CQA) n'est affectée ni par la mutation, ni par la lumière pendant la croissance des plantules (sauf pour les CQA ses racines). Un effet-organe est mis en évidence. La mutation réduit la teneur en caféine (CAF) et la différence variétale est présente à la lumière et à l'obscurité. Ces résultats permettent de mieux caractériser les effets pléiotropiques de la mutation laurina. Ils permettent une meilleure 1/ compréhension de l'évolution des PP de la graine au cours de son développement et 2/ connaissance des hormones, CAF, CQA et PP des plantules

IDEAL approach to the evaluation of machine learning technology in epilepsy surgery: protocol for the MAST trial

Epilepsy and epilepsy surgery lend themselves well to the application of machine learning (ML) and artificial intelligence (AI) technologies. This is evidenced by the plethora of tools developed for applications such as seizure detection and analysis of imaging and electrophysiological data. However, few of these tools have been directly used to guide patient management. In recent years, the Idea, Development, Exploration, Assessment, Long-Term Follow-Up (IDEAL) collaboration has formalised stages for the evaluation of surgical innovation and medical devices, and, in many ways, this pragmatic framework is also applicable to ML/AI technology, balancing innovation and safety. In this protocol paper, we outline the preclinical (IDEAL stage 0) evaluation and the protocol for a prospective (IDEAL stage 1/2a) study to evaluate the utility of an ML lesion detection algorithm designed to detect focal cortical dysplasia from structural MRI, as an adjunct in the planning of stereoelectroencephalography trajectories in children undergoing intracranial evaluation for drug-resistant epilepsy

Relationship-centred care in health: A 20-year scoping review

Relationship-centred care (RCC) is a framework for conceptualizing health care which recognizes that the nature and quality of relationships in health care influence the process and outcomes of health care. Our goal was to undertake a scoping review of the peer-reviewed and grey literature on RCC in health. Using Arksey and O’Malley’s scoping review methodology we identified literature about RCC in teaching, learning and clinical practice. Electronic databases were searched, and targeted searches were also conducted for grey literature to capture unpublished material. Subsequently, data abstraction tools were used with eligible studies for analysis. Sixty-nine publications originated mainly from the United States and the United Kingdom by authors from various academic disciplines, of which medicine and nursing were dominant. Thematic analysis revealed that the most commonly cited definition of RCC emerged from the Pew-Fetzer report and focused on the central role of relationships between practitioners and their patients, the community and other practitioners in providing quality care and improving outcomes. The concept of RCC was found to be influenced by theories of sociology, social psychology and psychiatry. The practice of RCC was demonstrated through organizational environments that model RCC, practice settings that focus on the patient or family in care planning, and health professional education that is based on RCC principles. RCC is important to: humanize health care and improve patient care. Our review identified three sub-categories that could add to the relational dimension of the practitioner-organization: practitioner–education, practitioner–profession, and practitioner–practice. Recommendations for future research include: outcome and process studies of health professions education and health care that focuses on RCC. The RCC approach provides a paradigm to move beyond the patient-centred care model by focusing on the central role of all relationships in the delivery and outcomes of care

Robust and Generalisable Segmentation of Subtle Epilepsy-causing Lesions: a Graph Convolutional Approach

Focal cortical dysplasia (FCD) is a leading cause of drug-resistant focal epilepsy, which can be cured by surgery. These lesions are extremely subtle and often missed even by expert neuroradiologists. "Ground truth" manual lesion masks are therefore expensive, limited and have large inter-rater variability. Existing FCD detection methods are limited by high numbers of false positive predictions, primarily due to vertex- or patch-based approaches that lack whole-brain context. Here, we propose to approach the problem as semantic segmentation using graph convolutional networks (GCN), which allows our model to learn spatial relationships between brain regions. To address the specific challenges of FCD identification, our proposed model includes an auxiliary loss to predict distance from the lesion to reduce false positives and a weak supervision classification loss to facilitate learning from uncertain lesion masks. On a multi-centre dataset of 1015 participants with surface-based features and manual lesion masks from structural MRI data, the proposed GCN achieved an AUC of 0.74, a significant improvement against a previously used vertex-wise multi-layer perceptron (MLP) classifier (AUC 0.64). With sensitivity thresholded at 67%, the GCN had a specificity of 71% in comparison to 49% when using the MLP. This improvement in specificity is vital for clinical integration of lesion-detection tools into the radiological workflow, through increasing clinical confidence in the use of AI radiological adjuncts and reducing the number of areas requiring expert review.Comment: accepted at MICCAI 202

In vitro and in vivo effects of Pelargonium sidoides DC. root extract EPs® 7630 and selected constituents against SARS-CoV-2 B.1, Delta AY.4/AY.117 and Omicron BA.2

The occurrence of immune-evasive SARS-CoV-2 strains emphasizes the importance to search for broad-acting antiviral compounds. Our previous in vitro study showed that Pelargonium sidoides DC. root extract EPs® 7630 has combined antiviral and immunomodulatory properties in SARS-CoV-2-infected human lung cells. Here we assessed in vivo effects of EPs® 7630 in SARS-CoV-2-infected hamsters, and investigated properties of EPs® 7630 and its functionally relevant constituents in context of phenotypically distinct SARS-CoV-2 variants. We show that EPs® 7630 reduced viral load early in the course of infection and displayed significant immunomodulatory properties positively modulating disease progression in hamsters. In addition, we find that EPs® 7630 differentially inhibits SARS-CoV-2 variants in nasal and bronchial human airway epithelial cells. Antiviral effects were more pronounced against Omicron BA.2 compared to B.1 and Delta, the latter two preferring TMPRSS2-mediated fusion with the plasma membrane for cell entry instead of receptor-mediated low pH-dependent endocytosis. By using SARS-CoV-2 Spike VSV-based pseudo particles (VSVpp), we confirm higher EPs® 7630 activity against Omicron Spike-VSVpp, which seems independent of the serine protease TMPRSS2, suggesting that EPs® 7630 targets endosomal entry. We identify at least two molecular constituents of EPs® 7630, i.e., (−)-epigallocatechin and taxifolin with antiviral effects on SARS-CoV-2 replication and cell entry. In summary, our study shows that EPs® 7630 ameliorates disease outcome in SARS-CoV-2-infected hamsters and has enhanced activity against Omicron, apparently by limiting late endosomal SARS-CoV-2 entry

Pediatric epilepsy surgery from 2000 to 2018: Changes in referral and surgical volumes, patient characteristics, genetic testing, and postsurgical outcomes

OBJECTIVE: Neurosurgery is a safe and effective form of treatment for select children with drug-resistant epilepsy. Still, there is concern that it remains underutilized, and that seizure freedom rates have not improved over time. We investigated referral and surgical practices, patient characteristics, and postoperative outcomes over the past two decades. METHODS: We performed a retrospective cohort study of children referred for epilepsy surgery at a tertiary center between 2000 and 2018. We extracted information from medical records and analyzed temporal trends using regression analyses. RESULTS: A total of 1443 children were evaluated for surgery. Of these, 859 (402 females) underwent surgical resection or disconnection at a median age of 8.5 years (interquartile range [IQR] = 4.6-13.4). Excluding palliative procedures, 67% of patients were seizure-free and 15% were on no antiseizure medication (ASM) at 1-year follow-up. There was an annual increase in the number of referrals (7%, 95% confidence interval [CI] = 5.3-8.6; p < .001) and surgeries (4% [95% CI = 2.9-5.6], p < .001) over time. Duration of epilepsy and total number of different ASMs trialed from epilepsy onset to surgery were, however, unchanged, and continued to exceed guidelines. Seizure freedom rates were also unchanged overall but showed improvement (odds ratio [OR] 1.09, 95% CI = 1.01-1.18; p = .027) after adjustment for an observed increase in complex cases. Children who underwent surgery more recently were more likely to be off ASMs postoperatively (OR 1.04, 95% CI = 1.01-1.08; p = .013). There was a 17% annual increase (95% CI = 8.4-28.4, p < .001) in children identified to have a genetic cause of epilepsy, which was associated with poor outcome. SIGNIFICANCE: Children with drug-resistant epilepsy continue to be put forward for surgery late, despite national and international guidelines urging prompt referral. Seizure freedom rates have improved over the past decades, but only after adjustment for a concurrent increase in complex cases. Finally, genetic testing in epilepsy surgery patients has expanded considerably over time and shows promise in identifying patients in whom surgery is less likely to be successful