Psychological first aid in operation for military healthcare providers : a study on pre-deployment training.

INTRODUCTION: During operational missions, while the management of physical injuries in the field remains the priority, the identification of operational incapacity of psychological origin is necessary as it is equally crucial for the safety of the individual, the group and the mission. The French Military Health Service has developed a Psychological First Aid Training in Operation (PFATO) course based on relational simulations, for military service members. The aim is to identify the early signs of psychological distress in a comrade and to adopt an adapted and protective attitude. PFATO training is also offered to healthcare providers. METHODS: We conducted a descriptive cross-sectional study using a self-administered online questionnaire which was sent after deployment to all physicians or nurses trained in PFATO between July 2019 and July 2021 (n=80). The main objective of our work was to evaluate the relevance of this awareness training among physicians and nurses and to identify specific complementary expectations in operational psychiatry for this population. RESULTS: We obtained a response rate of 55%. Significantly, 21.62% of participants used PFATO during their last deployment and another 20% observed a team member using PFATO. The circumstances of use as reported by participants included acute stress related to combat, conflict with hierarchy or comrades, and suicidal crisis. Among those who used PFATO, the training helped 87.5% of them to identify signs of psychological distress and 100% of them to assist combatants . All respondents stressed the added value of practical simulations during PFATO education. Moreover, this study also makes it possible to identify adaptations needed to optimize this module for healthcare providers. CONCLUSION: The results suggest the value for healthcare provider of training in first-response psychological care using relational simulation based on the model of raising awareness about PFATO.

Enhanced train-the-trainer program for registered nurses and social workers to apply the founding principles of primary care in their practice: a pre-post study.

BACKGROUND: A train-the-trainer approach can effectively support the integration of new practice standards for health and social services professionals. This study describes the effects of an enhanced train-the-trainer program to support registered nurses and social workers working in primary care clinics in their understanding of the fundamental principles of primary care. METHODS: We implemented an enhanced train-the-trainer program for registered nurses and social workers in six primary care clinics. We conducted a pre-post study using quantitative and qualitative data to assess trainers' and trainees' intention, commitment, and confidence in applying acquired knowledge. RESULTS: We trained 11 trainers and 33 trainees. All the trainers and trainees were satisfied with the program. Trainers were less confident in their abilities as trainers following the training, especially regarding tailored coaching (p = 0.03). Trainees' commitment to becoming familiar with the functioning of their clinic (p = 0.05) and becoming part of the team increased significantly (p = 0.01); however, their intention to use their knowledge decreased (p = 0.02). Trainers and trainees identified organizational and professional barriers that may explain the observed decrease. CONCLUSION: An enhanced train-the-trainer program positively impacted registered nurses' and social workers' assimilation of the fundamental principles of primary care. Further research is needed to understand the long-term effects of train-the-trainer programs on primary care trainees and how these effects translate into patient care.

Case management in primary healthcare for people with complex needs to improve integrated care: a large-scale implementation study protocol.

INTRODUCTION: Case management (CM) is among the most studied effective models of integrated care for people with complex needs. The goal of this study is to scale up and assess CM in primary healthcare for people with complex needs. METHODS AND ANALYSIS: The research questions are: (1) which mechanisms contribute to the successful scale-up of CM for people with complex needs in primary healthcare?; (2) how do contextual factors within primary healthcare organisations contribute to these mechanisms? and (3) what are the relationships between the actors, contextual factors, mechanisms and outcomes when scaling-up CM for people with complex needs in primary healthcare? We will conduct a mixed methods Canadian interprovincial project in Quebec, New-Brunswick and Nova Scotia. It will include a scale-up phase and an evaluation phase. At inception, a scale-up committee will be formed in each province to oversee the scale-up phase. We will assess scale-up using a realist evaluation guided by the RAMESES checklist to develop an initial programme theory on CM scale-up. Then we will test and refine the programme theory using a mixed-methods multiple case study with 10 cases, each case being the scalable unit of the intervention in a region. Each primary care clinic within the case will recruit 30 adult patients with complex needs who frequently use healthcare services. Qualitative data will be used to identify contexts, mechanisms and certain outcomes for developing context-mechanism-outcome configurations. Quantitative data will be used to describe patient characteristics and measure scale-up outcomes. ETHICS AND DISSEMINATION: Ethics approval was obtained. Engaging researchers, decision-makers, clinicians and patient partners on the study Steering Committee will foster knowledge mobilisation and impact. The dissemination plan will be developed with the Steering Committee with messages and dissemination methods targeted for each audience.

Co-development of a national, bilingual, post-licensure accredited educational program for registered nurses in primary care: A knowledge-to-action exemplar.

Registered nurses' practice in primary care varies and is sometimes sub-optimal. To fill the gap in primary care-specific knowledge, we co-constructed a national educational program to reinforce the nursing workforce. We based our project on the knowledge-to-action approach. Many lessons were learned during the development phase: (1) The experiential knowledge of patient partners and stakeholders allows an education program based on real needs; (2) The development of a national education program requires high-intensity investment from all involved persons; (3) An in-person meeting at the beginning of the project enables robust discussions and optimal co-creation; and (4) In a country where two official languages are spoken, it's essential to create a safe environment and a translation infrastructure that allows everyone to express themselves in the language of their choice. Finally, other initiatives in healthcare education or professional practice improvement could leverage our findings to realize national-scale projects using knowledge creation approaches.

Early automated classification of neonatal hypoxic-ischemic encephalopathy - An aid to the decision to use therapeutic hypothermia.

OBJECTIVE: The study aimed to address the challenge of early assessment of neonatal hypoxic-ischemic encephalopathy (HIE) severity to identify candidates for therapeutic hypothermia (TH). The objective was to develop an automated classification model for neonatal EEGs, enabling accurate HIE severity assessment 24/7. METHODS: EEGs recorded within 6 h of life after perinatal anoxia were visually graded into 3 severity groups (HIE French Classification) and quantified using 6 qEEG markers measuring amplitude, continuity and frequency content. Machine learning models were developed on a dataset of 90 EEGs and validated on an independent dataset of 60 EEGs. RESULTS: The selected model achieved an overall accuracy of 80.6% in the development phase and 80% in the validation phase. Notably, the model accurately identified 28 out of 30 children for whom TH was indicated after visual EEG analysis, with only 2 cases (moderate EEG abnormalities) not recommended for cooling. CONCLUSIONS: The combination of clinically relevant qEEG markers led to the development of an effective automated EEG classification model, particularly suited for the post-anoxic latency phase. This model successfully discriminated neonates requiring TH. SIGNIFICANCE: The proposed model has potential as a bedside clinical decision support tool for TH.

Resuscitation and Forensic Factors Influencing Outcome in Penetrating Cardiac Injury.

BACKGROUND: Cardiac injury caused by a sharp object is a medical and surgical therapeutic challenge. Mortality risk factors have been identified but there are major discrepancies in the literature. The aim of this study was to analyse the management of victims of penetrating cardiac injuries before and after admission to hospital and the anatomical characteristics of these injuries in order to facilitate diagnosis of the most critical patients. METHODS: To carry out this study, we conducted a retrospective analytical study with epidemiological data on victims of penetrating cardiac injuries. We included two types of patients, with those who underwent autopsy in our institution after death from sharp injury to the heart or great vessels and those who survived with treatment in the emergency department or intensive care unit between January 2015 and February 2022. RESULTS: We included 30 autopsied patients and 12 survivors aged between 18 and 73 years. Higher mortality was associated with prehospital or in-hospital cardiorespiratory arrest (OR = 4, CI [1.71-9.35]), preoperative mechanical ventilation (OR = 10, CI [1.53-65.41]), preoperative catecholamines (OR = 7, CI [1.12-6.29]), preoperative and perioperative adrenaline (OR = 13, CI [1.98-85.46] and [1.98-85.46]), penetrating cardiac injury (OR = 14, CI [2.10-93.22]), multiple cardiac injuries (OR = 1.5, CI [1.05-2.22]) and an Organ Injury Scaling of the American Association for the Surgery of Trauma (AAST-OIS) score of 5 (OR = 2.9, CI [1.04-8.54]; p = 0.0329) with an AUC-ROC curve value of 0.708 (CI [0.543-0.841]). CONCLUSIONS: This study identified risk mortality factors in penetrating cardiac injury patients. These findings can help improve the diagnosis and management of these patients. The AAST-OIS score may be a good tool to diagnose critical patients.

Concordance Study of Diagnoses and Therapeutic Management for Military Personnel Evacuated for Medico-psychological Reasons: From the Theater of Operations to the Military Training Hospital.

INTRODUCTION: The evolving global landscape has led to increased involvement of the French armed forces, exposing military personnel to operational challenges that can affect their mental well-being. As a result, psychiatry has become the second most common reason for Medical Evacuation (MEDEVAC). In war zones where specialized medico-psychological consultations may not be readily available, medical officers play a vital role in providing initial care. Therefore, there is a growing emphasis on the precise evaluation of these practices. MATERIALS AND METHODS: In this retrospective observational study, we analyzed MEDEVAC request files from the Operational Health Headquarters (Patient Medical Request sheets), Aeromedical Evacuation Mission Order sheets, and hospital records from the entire military hospital complex in the Île-de-France region for French military personnel who underwent low-priority MEDEVAC (P3) for medico-psychological reasons from a non-metropolitan area to metropolitan France. The study spanned from January 1, 2013, to December 31, 2016. The primary objective is to evaluate the concordance of diagnoses between general practitioners and psychiatrists. The secondary objective is a detailed description of the introduction of psychotropic drugs, especially benzodiazepines, by the medical officer in the field. RESULTS: In total, our study included 610 patients. Significant differences were observed between diagnoses made by military general practitioners and military psychiatrists, except for "psychotic disorders" and "other diagnoses" categories. During hospitalization, benzodiazepines were prescribed to 26.5% of repatriated patients, antidepressants to 12.7%, hypnotics to 17.6%, neuroleptics to 24.23%, and hydroxyzine to 18.8%. Upon discharge, benzodiazepines were prescribed to 23.5% of patients, antidepressants to 17.8%, hypnotics to 9.9%, neuroleptics to 28.9%, and hydroxyzine to 19.7%. The chi-squared test revealed significant differences in prescription between military operations and hospitalization for all molecules except hydroxyzine. Among patients diagnosed with Psychological Disorder Related to a Traumatic Event (TPRET) (<1 and >1 month) by psychiatrists during hospitalization, 66.2% were prescribed benzodiazepines during operational theaters, 24.3% continued during hospitalization, and 16.8% received a prescription upon discharge.The duration of missions often hinders precise psychiatric diagnoses, leading medical officers to transmit clinical data for optimized specialized care at military training hospitals. Furthermore, significant differences in therapeutic administration between medical officers and psychiatrists, particularly in benzodiazepine prescriptions for patients with TPRET, highlight the importance of prioritizing psychotropic prescription modalities in the training of medical officers on mental disorders. Strengthening operational preparations in recent years could enable more practitioners to benefit from these measures. CONCLUSIONS: We suggest several measures to enhance the transmission of medical information between medical officers and military psychiatrists. First, optimizing the drafting of Patient Movement Requests could involve implementing pre-filled drop-down menus or providing an adapted bilingual lexicon, facilitating the optimal transmission of clinical information for repatriated patients. Second, strengthening the training of medical officers before deployment and sharing the "Emergency Psy Kit," a comprehensive support tool developed by French military psychiatrists, would further enhance the tool kit available to field practitioners for judiciously prescribing psychiatric drugs.

Impact of age on safety of Busulfan-Melphalan followed by autologous hematopoietic stem-cell transplantation versus standard chemotherapy in the patients of the EURO-E.W.I.N.G. 99 and Ewing 2008 clinical trials.

INTRODUCTION: Ewing sarcoma (ES), is a rare cancer affecting children, adolescents and adults. After VIDE (vincristine-ifosfamide-doxorobucin-etoposide) induction chemotherapy, Busulfan-Melphalan (BuMel) high-dose chemotherapy followed by autologous hematopoietic stem cells transplantation improved outcomes in unfavourable localized ES, but with more toxicities than conventional chemotherapy (VAI: Vincristine-dactinomycin-Ifosfamide). We evaluated whether the risk of acute toxicity associated with BuMel compared to VAI varied according to age in patients recruited in the R2Loc and R2Pulm randomised trials of the Euro-E.W.I.N.G.99 and Ewing-2008 trials. METHODS: We included patients with a localized high-risk disease, or pulmonary or pleural metastasis. We analysed the risk of severe toxicity according to randomised treatment group (VAI versus BuMel) and age group (<12 years, 12-17 years, 18-24 years, ≥25 years). We evaluated the heterogeneity of treatment effects by age group using interaction terms in logistic multivariable models. RESULTS: The analysis included 243 patients treated with VAI and 205 with BuMel. Overall, BuMel was associated with a higher risk of severe acute toxicity than VAI particularly haematological, gastrointestinal, liver, sinusoidal occlusive syndrome, and infections. Severe haematological toxicity and lower general condition were significantly more frequent in younger patients, whatever treatment. We did not observe any significant heterogeneity in terms of the excess risk of severe toxicities associated with BuMel compared to VAI according to age group. CONCLUSION: The excess of acute toxicity associated with BuMel compared to VAI does not vary significantly with age, suggesting the feasibility of BuMel across all age groups.

Biological Sample Collection to Advance Research and Treatment: A Fight Osteosarcoma Through European Research and Euro Ewing Consortium Statement.

Osteosarcoma and Ewing sarcoma are bone tumors mostly diagnosed in children, adolescents, and young adults. Despite multimodal therapy, morbidity is high and survival rates remain low, especially in the metastatic disease setting. Trials investigating targeted therapies and immunotherapies have not been groundbreaking. Better understanding of biological subgroups, the role of the tumor immune microenvironment, factors that promote metastasis, and clinical biomarkers of prognosis and drug response are required to make progress. A prerequisite to achieve desired success is a thorough, systematic, and clinically linked biological analysis of patient samples, but disease rarity and tissue processing challenges such as logistics and infrastructure have contributed to a lack of relevant samples for clinical care and research. There is a need for a Europe-wide framework to be implemented for the adequate and minimal sampling, processing, storage, and analysis of patient samples. Two international panels of scientists, clinicians, and patient and parent advocates have formed the Fight Osteosarcoma Through European Research consortium and the Euro Ewing Consortium. The consortia shared their expertise and institutional practices to formulate new guidelines. We report new reference standards for adequate and minimally required sampling (time points, diagnostic samples, and liquid biopsy tubes), handling, and biobanking to enable advanced biological studies in bone sarcoma. We describe standards for analysis and annotation to drive collaboration and data harmonization with practical, legal, and ethical considerations. This position paper provides comprehensive guidelines that should become the new standards of care that will accelerate scientific progress, promote collaboration, and improve outcomes.

Traumatic axonal injury: Clinic, forensic and biomechanics perspectives.

Identification of Traumatic axonal injury (TAI) is critical in clinical practice, particularly in terms of long-term prognosis, but also for medico-legal issues, to verify whether the death or the after-effects were attributable to trauma. Multidisciplinary approaches are an undeniable asset when it comes to solving these problems. The aim of this work is therefore to list the different techniques needed to identify axonal lesions and to understand the lesion mechanisms involved in their formation. Imaging can be used to assess the consequences of trauma, to identify indirect signs of TAI, to explain the patient's initial symptoms and even to assess the patient's prognosis. Three-dimensional reconstructions of the skull can highlight fractures suggestive of trauma. Microscopic and immunohistochemical techniques are currently considered as the most reliable tools for the early identification of TAI following trauma. Finite element models use mechanical equations to predict biomechanical parameters, such as tissue stresses and strains in the brain, when subjected to external forces, such as violent impacts to the head. These parameters, which are difficult to measure experimentally, are then used to predict the risk of injury. The integration of imaging data with finite element models allows researchers to create realistic and personalized computational models by incorporating actual geometry and properties obtained from imaging techniques. The personalization of these models makes their forensic approach particularly interesting.

Impaired photoacclimation in a kleptoplastidic dinoflagellate reveals physiological limits of early stages of endosymbiosis.

Dinophysis dinoflagellates are predators of Mesodinium ciliates, from which they retain only the plastids of cryptophyte origin. The absence of nuclear photosynthetic cryptophyte genes in Dinophysis raises intriguing physiological and evolutionary questions regarding the functional dynamics of these temporary kleptoplastids within a foreign cellular environment. In an experimental setup including two light conditions, the comparative analysis with Mesodinium rubrum and the cryptophyte Teleaulax amphioxeia revealed that Dinophysis acuminata possessed a smaller and less dynamic functional photosynthetic antenna for green light, a function performed by phycoerythrin. We showed that the lack of the cryptophyte nucleus prevented the synthesis of the phycoerythrin α subunit, thereby hindering the formation of a complete phycoerythrin in Dinophysis. In particular, biochemical analyses showed that Dinophysis acuminata synthesized a poorly stable, incomplete phycoerythrin composed of chromophorylated ß subunits, with impaired performance. We show that, consequently, a continuous supply of new plastids is crucial for growth and effective photoacclimation in this organism. Transcriptome analyses revealed that all examined strains of Dinophysis spp. have acquired the cryptophyte pebA and pebB genes through horizontal gene transfer, suggesting a potential ability to synthesize the phycobilin pigments bound to the cryptophyte phycoerythrin. By emphasizing that a potential long-term acquisition of the cryptophyte plastid relies on establishing genetic independence for essential functions such as light harvesting, this study highlights the intricate molecular challenges inherent in the enslavement of organelles and the processes involved in the diversification of photosynthetic organisms through endosymbiosis.

Pratiquer la responsabilité sociale en santé : de la théorie à la pratique. Une étude Delphi internationale.

INTRODUCTION: Health professionals’ social responsibility in health resists translation into skills that can be taught and implemented concretely in professional practice. PURPOSE OF THE RESEARCH: This study, conducted by the Réseau International Francophone pour la Responsabilité Sociale en Santé (RIFRESS), aims to develop a consensus on the components of doctors’ social responsibility in health from the perspective of experts in medical education. Its findings are intended to inform the creation of a skills profile. A three-round Delphi consensus method was used, with an open first round and closed second and third rounds. Mesydel software was used to organize the process and to do the qualitative analysis of the first round. SPSS was used for consensus analysis for rounds 2 and 3. RESULTS: Thirty-four experts responded to the study. During the first round, 62 codes emerged, grouped into 13 themes. From the initial analysis, 40 items were submitted for the Delphi round 2. Of these 40 items, 23 came out consensual after the second round, as did 13 of the 18 resubmitted items after the third. Examples of items that emerged as consensual are eco-responsibility, advocacy, defense of the common good, critical analysis of practice, and collaborative leadership. CONCLUSIONS: The present study represents a much-needed effort to concretely define the components of doctors’ social responsibility in health. Local context must be taken into account when using these findings. They can help to train tomorrow’s doctors to better meet the priority health needs of society in a profoundly changing world.

Validation of HPLC and TLC analytical methods to determine radiochemical purity of 99mTc-cAbVCAM1-5, a new experimental radiotracer.

Cardiovascular diseases, including fatal myocardial infarctions from atheromatous plaques, are the primary global mortality cause. Detecting stenotic atheromatous plaques is possible through coronary angiography, but vulnerable plaques with eccentric remodeling are undetectable with current diagnostic methods. Addressing this challenge, our group developed a radiopharmaceutical drug targeting vascular cell adhesion molecule 1 (VCAM-1), radiolabeled with technetium-99m. Given the absence of a monograph in the European Pharmacopoeia, and in order to draft the investigational medicinal product documentation, analytical methods had to be validated by high performance liquid chromatography (HPLC) and thin layer chromatography (TLC) to determine the radiochemical purity (RCP) of 99mTc-cAbVCAM1-5. This study therefore presents the results of the validation of analytical methods obtained in this context. The method validation followed the European Association of Nuclear Medicine (EANM) recommendations adapted from ICH Q2(R1), ensuring conformity with specificity, accuracy, repeatability and intermediate precision, linearity, robustness, quantification limit (LoQ), and range criteria. Regarding the results of specificity, both HPLC and TLC methods demonstrated excellent separation of 99mTc-cAbVCAM1-5 from impurities 99mTcO4-. Accuracy results indicated recovery percentages within the range of 99.52-101.40% for the HPLC and 99.51-101.97% for TLC, ensuring reliable measurements for each concentration of 99mTcO4-. Precision of the methods was validated by assessing repeatability and intermediate precision. Linearity was determined over the usual concentrations range and the correlation coefficient was greater than 0.99 for both methods. The limit of quantification was measured by diluting the 99mTcO4- to obtain a signal-to-noise ratio of around 10:1. Under these conditions, we obtained an LOQ of 2.10 MBq/mL for HPLC and 2Mbq/mL for TLC. In conclusion, the analytical methods developed in this study comply with EANM recommendations. This therefore allows us to correctly assess the radiochemical purity of 99mTc-cAbVCAM1-5, a new radiotracer targeting inflammation in vulnerable plaques.

Modulation of plasmacytoid dendritic cells response in inflammation and autoimmunity.

The discovery of toll-like receptors (TLRs) and the subsequent recognition that endogenous nucleic acids (NAs) could serve as TLR ligands have led to essential insights into mechanisms of healthy immune responses as well as pathogenic mechanisms relevant to systemic autoimmune and inflammatory diseases. In systemic lupus erythematosus, systemic sclerosis, and rheumatoid arthritis, NA-containing immune complexes serve as TLR ligands, with distinct implications depending on the additional immune stimuli available. Plasmacytoid dendritic cells (pDCs), the robust producers of type I interferon (IFN-I), are providing critical insights relevant to TLR-mediated healthy immune responses and tissue repair, as well as generation of inflammation, autoimmunity and fibrosis, processes central to the pathogenesis of many autoimmune diseases. In this review, we describe recent data characterizing the role of platelets and NA-binding chemokines in modulation of TLR signaling in pDCs, as well as implications for how the IFN-I products of pDCs contribute to the generation of inflammation and wound healing responses by monocyte/macrophages. Chemokine modulators of TLR-mediated B cell tolerance mechanisms and interactions between TLR signaling and metabolic pathways are also considered. The modulators of TLR signaling and their contribution to the pathogenesis of systemic autoimmune diseases suggest new opportunities for identification of novel therapeutic targets.

Resilient anatomy and local plasticity of naive and stress haematopoiesis.

The bone marrow adjusts blood cell production to meet physiological demands in response to insults. The spatial organization of normal and stress responses are unknown owing to the lack of methods to visualize most steps of blood production. Here we develop strategies to image multipotent haematopoiesis, erythropoiesis and lymphopoiesis in mice. We combine these with imaging of myelopoiesis1 to define the anatomy of normal and stress haematopoiesis. In the steady state, across the skeleton, single stem cells and multipotent progenitors distribute through the marrow enriched near megakaryocytes. Lineage-committed progenitors are recruited to blood vessels, where they contribute to lineage-specific microanatomical structures composed of progenitors and immature cells, which function as the production sites for each major blood lineage. This overall anatomy is resilient to insults, as it was maintained after haemorrhage, systemic bacterial infection and granulocyte colony-stimulating factor (G-CSF) treatment, and during ageing. Production sites enable haematopoietic plasticity as they differentially and selectively modulate their numbers and output in response to insults. We found that stress responses are variable across the skeleton: the tibia and the sternum respond in opposite ways to G-CSF, and the skull does not increase erythropoiesis after haemorrhage. Our studies enable in situ analyses of haematopoiesis, define the anatomy of normal and stress responses, identify discrete microanatomical production sites that confer plasticity to haematopoiesis, and uncover unprecedented heterogeneity of stress responses across the skeleton.

Head injury: Importance of the deep brain nuclei in force transmission to the brain.

Finite element modeling provides a digital representation of the human body. It is currently the most pertinent method to study the mechanisms of head injury, and is becoming a scientific reference in forensic expert reports. Improved biofidelity is a recurrent aim of research studies in biomechanics in order to improve earlier models whose mechanical properties conformed to simplified elastic behavior and mechanic laws. We aimed to study force transmission to the brain following impacts to the head, using a finite element head model with increased biofidelity. To the model developed by the Laboratory of Applied Biomechanics of Marseille, we added new brain structures (thalamus, central gray nuclei and ventricular systems) as well as three tracts involved in the symptoms of head injury: the corpus callosum, uncinate tracts and corticospinal tracts. Three head impact scenarios were simulated: an uppercut with the prior model and an uppercut with the improved model in order to compare the two models, and a lateral impact with an impact velocity of 6.5 m/s in the improved model. In these conditions, in uppercuts the maximum stress values did not exceed the injury risk threshold. On the other hand, the deep gray matter (thalamus and central gray nuclei) was the region at highest risk of injury during lateral impacts. Even if injury to the deep gray matter is not immediately life-threatening, it could explain the chronic disabling symptoms of even low-intensity head injury.

Cirscan: a shiny application to identify differentially active sponge mechanisms and visualize circRNA-miRNA-mRNA networks.

BACKGROUND: Non-coding RNAs represent a large part of the human transcriptome and have been shown to play an important role in disease such as cancer. However, their biological functions are still incompletely understood. Among non-coding RNAs, circular RNAs (circRNAs) have recently been identified for their microRNA (miRNA) sponge function which allows them to modulate the expression of miRNA target genes by taking on the role of competitive endogenous RNAs (ce-circRNAs). Today, most computational tools are not adapted to the search for ce-circRNAs or have not been developed for the search for ce-circRNAs from user's transcriptomic data. RESULTS: In this study, we present Cirscan (CIRcular RNA Sponge CANdidates), an interactive Shiny application that automatically infers circRNA-miRNA-mRNA networks from human multi-level transcript expression data from two biological conditions (e.g. tumor versus normal conditions in the case of cancer study) in order to identify on a large scale, potential sponge mechanisms active in a specific condition. Cirscan ranks each circRNA-miRNA-mRNA subnetwork according to a sponge score that integrates multiple criteria based on interaction reliability and expression level. Finally, the top ranked sponge mechanisms can be visualized as networks and an enrichment analysis is performed to help its biological interpretation. We showed on two real case studies that Cirscan is capable of retrieving sponge mechanisms previously described, as well as identifying potential novel circRNA sponge candidates. CONCLUSIONS: Cirscan can be considered as a companion tool for biologists, facilitating their ability to prioritize sponge mechanisms for experimental validations and identifying potential therapeutic targets. Cirscan is implemented in R, released under the license GPL-3 and accessible on GitLab ( https://gitlab.com/geobioinfo/cirscan_Rshiny ). The scripts used in this paper are also provided on Gitlab ( https://gitlab.com/geobioinfo/cirscan_paper ).