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Cluster globally, Reduce locally: Scalable efficient dictionary compression for magnetic resonance fingerprinting
No full textInternational audienceWith the rapid advancements in medical data acquisition and production, increasingly richer representations exist to characterize medical information. However, such large-scale data do not usually meet computing resource constraints or algorithmic complexity, and can only be processed after compression or reduction, at the potential loss of information. In this work, we consider specific Gaussian mixture models (HD-GMM), tailored to deal with high dimensional data and to limit information loss by providing component-specific lower dimensional representations. We also design anincremental algorithm to compute such representations for large data sets, overcoming hardware limitations of standard methods. Our procedure is illustrated in a magnetic resonance fingerprinting study, where it achieves a dictionary compression for faster and more accurate map reconstructions
Incidence and impact of other malignancies after immunochemotherapy by fludarabine, cyclophosphamide, and rituximab as frontline treatment for chronic lymphocytic leukemia: A single-center retrospective study.
No full textInternational audienceIndividuals with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) have a high risk of developing other malignancies (OMs). The development of OMs may be associated with the advanced age of CLL/SLL patients, presence of a tumor-promoting microenvironment, immune alterations inherent to CLL/SLL, or chemotherapy. Importantly, the occurrence of OMs following frontline fludarabine, cyclophosphamide and rituximab (FCR) treatment is associated with a reduction in the overall survival (OS). This retrospective study included 108 CLL/SLL patients treated with FCR immunochemotherapy, as a first line treatment. With a median follow-up of 94.9 (6-222) months, 31% developed an OM or more, within a median of 61.8 months post-FCR initiation. The most common OMs were non-melanoma skin cancers (7%), Richter's syndrome (RS) (7%), myelodysplastic syndromes (6%), prostate cancer (4%), and acute myeloid leukemia (3%). Patients with OMs had shorter survival compared to those without (104.0 versus 149.0 months, P=0.02), with RS having the worst OS at 4.8 months (P<0.0001), followed by therapy-related myeloid neoplasia (t-MN) at 14.5 months. Although the onset of OMs in patients with CLL/SLL was observed after considerable delays, its impact on survival is significant in the immunochemotherapy era, necessitating a better understanding of these patterns to improve CLL/SLL management and guide future treatment strategies
The HCF101 protein is an important component of the cytosolic iron–sulfur synthesis pathway in Toxoplasma gondii
No full textInternational audienceSeveral key cellular functions depend on proteins harboring an iron–sulfur (Fe-S) cofactor. As these Fe-S proteins localize to several subcellular compartments, they require a dedicated machinery for cofactor assembly. For instance, in plants and algae there are Fe-S cluster synthesis pathways localizing to the cytosol, but also present in the mitochondrion and in the chloroplast, 2 organelles of endosymbiotic origin. Toxoplasma gondii is a plastid-bearing parasitic protist responsible for a pathology affecting humans and other warm-blooded vertebrates. We have characterized the Toxoplasma homolog of HCF101, originally identified in plants as a protein transferring Fe-S clusters to photosystem I subunits in the chloroplast. Contrarily to plants, we have shown that HCF101 does not localize to the plastid in parasites, but instead is an important component of the cytosolic Fe-S assembly (CIA) pathway which is vital for Toxoplasma . While the CIA pathway is widely conserved in eukaryotes, it is the first time the involvement of HCF101 in this pan-eukaryotic machinery is established. Moreover, as this protein is essential for parasite viability and absent from its mammalian hosts, it constitutes a novel and promising potential drug target
Adult Internal Cerebrospinal Fluid Shunt Overall Survival: A Meta-Analysis of Restricted Mean Survival Times from Reconstructed Kaplan-Meier Data
No full textInternational audienceObjective: To assess the overall survival (OS) of internal cerebrospinal fluid shunt (ICSFS) in the adult population.Methods: MEDLINE database was searched from 2000 to 2023 to identify studies reporting on ICSFS OS. Only articles reporting on adult ICSFS OS by a Kaplan-Meier (KM) OS curve were included. Numerical data were extracted from KM curves and were then reconstructed to estimate 3, 6, 9, 12, 18, 24, 36, 48, and 60 months restricted mean survival times (RMSTs). RMSTs of ICSFS and its SE at each time of interest were used as summary measure and primary outcome across studies. To account for the effect of between-study heterogeneity, RMSTs were pooled using a random effects model.Results: Out of 421 screened studies, only 6 were included in the meta-analysis. Calculated ICSFS OS at 3, 6, 9, 12, 18, 24, 36, 48, and 60 months were 92.4% (95% CI, 89.6-95.2), 89.5% (95% CI, 86.3-92.8), 87.5% (95% CI, 83.9-91.1), 85.2% (95% CI, 80.4-90.0), 83.4% (95% CI, 79.0-87.9), 81.6% (95% CI, 76.7-86.5), 78.8% (95% CI, 72.9-84.6), 76.7% (95% CI, 70.3-83.1), and 74.5% (95% CI, 67.8-81.1), respectively. There was a significant heterogeneity as indicated by a high I2 value of 82.5% (95% CI, 63.1-91.7). Heterogeneity test of Q = 28.63 was also significant (P < 0.001).Conclusions: On contrary to what one might think, there are few available studies assessing adult ICSFS OS. We used a novel technique to meta-analyze adult ICSFS OS. ICSFS failure rate is maximal within the 3 to 6 postoperative months. Afterward, the risk slowly decreases over time. At 5 years, less than three quarters of the patients still have a naïve functional ICSFS never revised
Integration of clinical, pathological, radiological, and transcriptomic data improves prediction for first-line immunotherapy outcome in metastatic non-small cell lung cancer
No full textInternational audienceAbstract Immunotherapy is improving the survival of patients with metastatic non-small cell lung cancer (NSCLC), yet reliable biomarkers are needed to identify responders prospectively and optimize patient care. In this study, we explore the benefits of multimodal approaches to predict immunotherapy outcome using multiple machine learning algorithms and integration strategies. We analyze baseline multimodal data from a cohort of 317 metastatic NSCLC patients treated with first-line immunotherapy, including positron emission tomography images, digitized pathological slides, bulk transcriptomic profiles, and clinical information. Testing multiple integration strategies, most of them yield multimodal models surpassing both the best unimodal models and established univariate biomarkers, such as PD-L1 expression. Additionally, several multimodal combinations demonstrate improved patient risk stratification compared to models built with routine clinical features only. Our study thus provides evidence of the superiority of multimodal over unimodal approaches, advocating for the collection of large multimodal NSCLC datasets to develop and validate robust and powerful immunotherapy biomarkers
Efficacy of anti‐PD1 therapy in extranodal NK/T cell lymphoma: A matched cohort analysis from the LYSA
No full textInternational audienceNo abstract availabl
Mitigating analytical variability in fMRI results with style transfer
No full textAccepté à MIDL 2025.International audienceWe propose a novel approach to improve the reproducibility of neuroimaging results by converting statistic maps across different functional MRI pipelines. We make the assumption that pipelines used to compute fMRI statistic maps can be considered as a style component and we propose to use different generative models, among which, Generative Adversarial Networks (GAN) and Diffusion Models (DM) to convert statistic maps across different pipelines. We explore the performance of multiple GAN frameworks, and design a new DM framework for unsupervised multi-domain styletransfer. We constrain the generation of 3D fMRI statistic maps using the latent space of an auxiliary classifier that distinguishes statistic maps from different pipelines and extend traditional sampling techniques used in DM to improve the transition performance. Our experiments demonstrate that our proposed methods aresuccessful: pipelines can indeed be transferred as a style component, providing animportant source of data augmentation for future medical studies
Microsporidiosis in patients with autoimmune diseases undergoing monoclonal antibody associated therapy
No full textInternational audienceWe present Enterocytozoon bieneusi infection in four patients with autoimmune diseases undergoing prolonged monoclonal antibody therapies. Two patients suffered from inflammatory bowel disease and received anti-TNF therapies, whereas two other patients suffered from systemic lupus erythematosus with renal involvement and received anti-CD20 or anti-BLyS protein therapies. Three out of four patients consulted for diarrhea with abdominal pain without intestinal inflammation or bleeding at the time of sampling. The fourth patient did not declare intestinal troubles. Microsporidia genotype detected in this study were S9, C, Wildboard3 with one patient harboring 2 genotypes S6 and EBCMAP-038Management of microsporidia infection included albendazole and reduction of immunosuppression treatment, but no specific treatment was implemented in two other patients. In conclusion, microsporidia infection occurs in patients with autoimmune diseases undergoing prolonged monoclonal antibody therapies. Diagnosis should be carefully assessed in this population and a thorough benefit-risk analysis is essential prior to initiating therapeutic interventions
Prenatal Hemoglobin Concentration and Long-Term Child Neurocognitive Development
No full textInternational audienceAnemia in pregnancy, defined by a hemoglobin level (Hb) of less than 110 g/L, contributes to infant mortality and morbidity in sub-Saharan Africa. Maternal Hb changes physiologically and pathologically during pregnancy. However, the impact of these changes on long-term child neurocognitive function is unknown. This study therefore investigates the association between Hb at specific antenatal care visits and prenatal Hb trajectories during pregnancy and long-term child neurocognitive function. We analyzed data from a prospective cohort study that included 6-year-old singleton children born to women enrolled before 29 weeks of gestation into an antimalarial drug clinical trial. Hemoglobin level was analyzed from venous blood collected at least twice during pregnancy and at delivery. We used group-based trajectory modeling to identify distinct prenatal Hb trajectories. In total, 478 children (75.1% of eligible children) had assessment of cognitive and motor functions at 6 years of age. Three distinct Hb trajectories were identified: persistently anemic (Hb &amp;lt;110 g/L throughout the second and third trimesters), anemic to nonanemic (Hb &amp;lt;110 g/L at second trimester with increasing Hb toward the third trimester to Hb ≥110 g/L), and persistently nonanemic (Hb ≥110 g/L throughout the second and third trimesters). Children of women in the persistently anemic and anemic-to-nonanemic groups had significantly lower neurocognitive scores than children of women in the persistently nonanemic group (β = −6.8, 95% CI: −11.7 to −1.8; and β = −6.3, 95% CI: −10.4 to −2.2, respectively). The study shows that maintaining an elevation of Hb at or above 110 g/L from the second to third trimester of pregnancy may be associated with optimal long-term child neurocognitive function
L’anhédonie : de la clinique aux biomarqueurs
No full textInternational audienceAnhedonia, a complex symptom, is characterized by a decrease in experience of pleasure, reduced motivation, and/or impaired reward learning. Although these aspects are often linked to dopaminergic pathways, recent research shows that immuno-inflammatory alterations present in psychiatric disorders may also play a role, affecting dopaminergic, glutamatergic, and opioid pathways, as well as cellular immune responses (such as the mTOR pathway). These perturbations, through inflammation in the central nervous system, affect reward and motor circuits, contributing to the anhedonia and the psychomotor slowing that are often-associated. Animal models show that chronic inflammation can reduce motivation, providing a preclinical model for anhedonia. This dysfunction is not specific to a single pathology but is common to a variety ofpsychiatric disorders, including psychotic, mood, and neurodevelopmental disorders. These common dimensions of anhedonia across different pathologies open up perspects for targeted treatments, including dopaminergic treatments, glutamatergic treatments (such as ketamine), anti-inflammatory therapies, and the development of new molecules.L'anhédonie, symptôme complexe, se caractérise par une diminution de l'expérience de plaisir, une baisse de motivation, et/ou une altération de l'apprentissage de la récompense. Bien que ces aspects soient souvent liés aux voies dopaminergiques, des recherches récentes montrent que des altérations immuno-inflammatoires peuvent également jouer un rôle en affectant les voies dopaminergiques, glutamatergiques, opioïdes, et les réponses immunitaires cellulaires (comme la voie mTOR). Ces modifications influencent les circuits de récompense et les circuits moteurs, contribuant à l'anhédonie et au ralentissement psychomoteur souvent associé. Ces dimensions communes de l'anhédonie dans différentes maladies ouvrent des perspectives pour des traitements ciblés, incluant des traitements dopaminergiques, glutamatergiques (comme la kétamine), et des anti-inflammatoires, ainsi que le développement de nouvelles molécules