SpliceAI-visual: a free online tool to improve SpliceAI splicing variant interpretation.

SpliceAI is an open-source deep learning splicing prediction algorithm that has demonstrated in the past few years its high ability to predict splicing defects caused by DNA variations. However, its outputs present several drawbacks: (1) although the numerical values are very convenient for batch filtering, their precise interpretation can be difficult, (2) the outputs are delta scores which can sometimes mask a severe consequence, and (3) complex delins are most often not handled. We present here SpliceAI-visual, a free online tool based on the SpliceAI algorithm, and show how it complements the traditional SpliceAI analysis. First, SpliceAI-visual manipulates raw scores and not delta scores, as the latter can be misleading in certain circumstances. Second, the outcome of SpliceAI-visual is user-friendly thanks to the graphical presentation. Third, SpliceAI-visual is currently one of the only SpliceAI-derived implementations able to annotate complex variants (e.g., complex delins). We report here the benefits of using SpliceAI-visual and demonstrate its relevance in the assessment/modulation of the PVS1 classification criteria. We also show how SpliceAI-visual can elucidate several complex splicing defects taken from the literature but also from unpublished cases. SpliceAI-visual is available as a Google Colab notebook and has also been fully integrated in a free online variant interpretation tool, MobiDetails ( https://mobidetails.iurc.montp.inserm.fr/MD ).

Improving Pleasure and Motivation in Schizophrenia: A Randomized Controlled Clinical Trial.

BACKGROUND: Negative symptoms are frequent in patients with schizophrenia and are associated with marked impairments in social functioning. The efficacy of drug-based treatments and psychological interventions on primary negative symptoms remains limited. The Positive Emotions Programme for Schizophrenia (PEPS) is designed to improve pleasure and motivation in schizophrenia patients by targeting emotion regulation and cognitive skills relevant to apathy and anhedonia. The main hypothesis of this study is that patients who attend 8 one-hour sessions of PEPS and treatment as usual (TAU) will have lower total apathy-avolition and anhedonia-asociality composite scores on the Scale for the Assessment of Negative Symptoms (SANS) than patients who attend only TAU. METHODS: Eighty participants diagnosed with schizophrenia or schizoaffective disorder were randomized to receive either TAU or PEPS + TAU. The participants were assessed by independent evaluators before randomization (T0), in a post-test after 8 weeks of treatment (T1) and at a 6-month follow-up (T2). RESULTS: The post-test results and 6-month follow-up assessments according to an intention-to-treat analysis showed that the apathy and anhedonia composite scores on the SANS indicated statistically greater clinical improvements in PEPS participants than in non-PEPS participants. In the post-test, anhedonia but not apathy was significantly improved, thus favouring the PEPS condition. These results were sustained at the 6-month follow-up. CONCLUSIONS: PEPS is an effective intervention to reduce anhedonia in schizophrenia. PEPS is a short, easy-to-use, group-based, freely available intervention that is easy to implement in a variety of environments (ClinicalTrials.gov ID: NCT02593058).

An Evaluation of an Online Training Platform for Teaching Positive Emotions for People With Schizophrenia.

BACKGROUND: The dissemination of new interventions in clinical practice remains challenging. E-learning may provide wide access in various settings and allow tailored learning trajectories and an adapted training pace. This study evaluates an online platform to train professionals to lead the Positive Emotion Program for Schizophrenia (PEPS) for patients with anhedonia. This study aims to test the reception provided by clinicians to the platform and its perceived usefulness and investigate whether e-PEPS training improves knowledge about the facilitation of PEPS. MATERIALS AND METHODS: Participants were recruited through advertisements. All participants provided their informed consent on a registration form and completed two pre-test questionnaires, a knowledge test on negative symptoms in schizophrenia, learning strategies and the partnership relationship, and a test on the ability to savor pleasant moments. After the training, they completed the same questionnaire and an evaluation form of the training and its application in personal and professional life. RESULTS: Two-hundred and ten participants were registered to participate into the study, 185 received the access to the platform, and 101 participants completed the training and the post-test assessments. Satisfaction with training was high. The results showed that the participants significantly improved their knowledge about PEPS and increased the skills taught in their personal repertoire after the training. The training allows most clinicians to plan to lead a PEPS group in the year following training. DISCUSSION: As a result of this study, training has been improved and is now freely available to all interested clinicians.

Development of the Positive Emotions Program for Schizophrenia: An Intervention to Improve Pleasure and Motivation in Schizophrenia.

OBJECTIVES: The efficacy of drug-based treatments and psychological interventions on the primary negative symptoms of schizophrenia remains limited. Recent literature has distinguished negative symptoms associated with a diminished capacity to experience, from those associated with a limited capacity for expression. The positive emotions program for schizophrenia (PEPS) is a new method that specifically aims to reduce the syndrome of a diminished capacity to experience. METHODS: The intervention's vital ingredients were identified through a literature review of emotion in schizophrenia and positive psychology. The program has been beta-tested on various groups of health-care professionals. RESULTS: A detailed description of the final version of PEPS is presented here. The French version of the program is freely downloadable. CONCLUSION: PEPS is a specific, short, easy to use, group-based intervention to improve pleasure, and motivation in schizophrenia. It was built considering a recovery-oriented approach to schizophrenia.