Sorbonne University
  • Paris, France
Recent publications
Intervertebral disc degeneration is a major cause of neck and back pain, representing a significant global socioeconomic burden. The polysaccharide hyaluronan is key to maintaining disc physiology and mediating disc disease through its structural and biological roles in the nucleus pulposus, a component of the intervertebral disc highly susceptible to degeneration. In this study, we introduce a novel composite bioink designed for extrusion bioprinting of structures resembling the nucleus pulposus. Our bioink combines levels of hyaluronic acid and collagen that approach physiological concentrations and effectively mimics the disc's hydrated and mechanically resilient environment. We modulated the composite's mechanical properties through the tyramination of hyaluronic acid and subsequent photocrosslinking, influencing morphology and gene expression of embedded bovine nucleus pulposus cells. This allows us to replicate a range of properties from healthy to degenerated human nucleus pulposus, which would be challenging to achieve with traditional cell culture and in vivo models. Our results show that modulating hyaluronan physico-chemical properties influenced embedded cell phenotype. The outcomes of this study inform the future design of biomaterials for the modelling of disc disease and regeneration, and present a versatile platform that can be readily integrated with other biofabricated components to form engineered intervertebral disc-like structures.
We investigate the classical aspects of quantum theory and under which description quantum theory does appear classical. Although such descriptions or variables are known as “ontological” or “hidden,” they are not hidden at all but are dual classical states (in the sense of the general classical–quantum duality of nature). We analyze and interpret the dynamical scenario in an inherent quantum structure: (i) We show that the use of the known φ states in the circle [F. London, Z. Phys. 37, 915 (1926) and G. ’t Hooft, “The hidden ontological variable in quantum harmonic oscillators,” arXiv 2407.18153 (2024)] takes a true dimension only when the system is subjected to the minimal group representation action of the metaplectic group Mp(n). The Mp(n) Hermitian structure fully covers the symplectic Sp(n) group and, in certain cases, OSp(n). (ii) We compare the circle φ states and the cylinder ξ states in configuration space with the two sectors of the full Mp(2) Hilbert space corresponding to the even and odd n harmonic oscillators and their total sum. (iii) We compute the projections of the Mp(2) states on the circle φ and cylinder ξ states. The known London circle states are not normalizable. We compute here the general coset coherent states α,φ in the circle, with α being the coherent complex parameter. It allows full normalizability of the complete set of the circle states. (iv) The London states (ontological in ’t Hooft’s description) completely classicalize the inherent quantum structure only under the action of the Mp(n) minimal group representation. (v) For the coherent states in the cylinder (configuration space), all functions are analytic in the disk z=ωe−iφ<1. For the general coset coherent states α,φ in the circle, the complex variable is z′=ze−iα*/2: The analytic function is modified by the complex phase (φ − α*/2). (vi) The analyticity z′=ze−Imα/2<1 occurs when Im α ≠ 0 because of normalizability and Im α > 0 because of the identity condition. The circle topology induced by the α,φ coset coherent state also modifies the ratio of the disk due to the displacement by the coset. (vii) For the coset coherent cylinder states in configuration space, the classicalization is stronger due to screening exponential factors e−2n2, e−(2n+1/2), and e−(2n+1/2)2 for large n arising in the Mp(2) projections on them. The generalized Wigner function shows a bell-shaped distribution and stronger classicalization than the square norm functions. The application of the minimal group representation immediately classicalizes the system, with Mp(2) emerging as the group of the classical–quantum duality symmetry.
Background Cytokine induced memory-like natural killer (CIML NK) cells combined with an IL-15 super-agonist (N-803) are a novel modality to treat relapsed/refractory head and neck cancer. Methods We report data from a phase I trial of haploidentical CIML NK cells combined with N-803 with or without ipilimumab (IPI) in relapsed/refractory head and neck cancer patients after a median of 6 prior lines of therapy. The trial adhered to a 3 + 3 dose de-escalation design, with primary endpoint being safety. High-resolution immunophenotypic and transcriptional profiling characterized the NK cells and their interacting partners in vivo. Results The primary safety endpoint was established, with dose-limiting toxicity in 1/10 patients. A transient disease control rate correlated with donor NK cell expansion, the latter occurring irrespective of IPI. The combination of CIML NK cells with N-803 and IPI was associated with increased early NK cell proliferation, contraction of Treg: Tcon, rapid recovery of recipient CD8⁺ T cells, and subsequent accelerated rejection of donor NK cells. Conclusions CIML NK cells combined with N-803 and ipilimumab to treat head and neck cancer is safe, and associated with a more proliferative NK cell phenotype. However, the combination leads to reduced HLA mismatched NK cell persistence, resulting in an important limitation affecting NK cell combination therapies in clinical trials. These results inform evaluation of CIML NK therapy for advanced malignancies, with considerations for combination with IPI. Trial Registration NCT04290546.
Long‐term biodiversity monitoring is needed to track progress towards ambitious global targets to reduce species loss and restore ecosystems. The recent development of cheap and robust acoustic recording devices offers a cost‐effective means of gathering standardised long‐term datasets. Accounting for sources of bias in ecological monitoring and research is a fundamental part of the study design process. To highlight this issue in the context of long‐term terrestrial ecoacoustic monitoring, here we collate and discuss sources of bias arising from (i) hardware devices, (ii) firmware, software and analysis tools and (iii) the deployment environment. One important source of bias is unavoidable changes in recording hardware—to demonstrate how this potentially introduces bias, we present two case studies comparing the output from simultaneous recordings from different recorders. To mitigate biases, we recommend effective documentation of environmental and hardware‐related variables, as well as a long‐term data storage strategy that facilitates reanalysis. Additionally, the use of regular calibration tests to measure variation in the acoustic detection space will facilitate analytical approaches or post‐hoc AI solutions that remove unwanted biases. Synthesis and applications: The sources of bias and suggested mitigations described here will be of relevance to hardware manufacturers, ecological researchers and conservation practitioners. Researchers and conservation practitioners must be fully aware of relevant biases when designing long‐term ecoacoustic studies and should incorporate appropriate mitigations into their study design.
PURPOSE After radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC), prognosis is poor for high-risk patients. This study evaluated safety and efficacy of neoadjuvant chemotherapy (cisplatin or carboplatin + gemcitabine) in combination with durvalumab in these patients. PATIENTS AND METHODS This phase II trial (NCT04617756) included patients with non-metastatic, high-grade UTUC, based on the ureteroscopic biopsy or urine cytology, and/or infiltrative aspect of the renal pelvis/ureteral wall by CT imaging. Before RNU, patients received durvalumab plus gemcitabine/cisplatin (cohort 1) or durvalumab plus gemcitabine/carboplatin (cohort 2) every 3 weeks for a total of four cycles (cohort choice based on the glomerular filtration rate). The primary objective was the pathological complete response (ypT0) rate in each cohort. RESULTS Fifty patients were enrolled between 2021 and 2024 (31 in cohort 1; 19 in cohort 2). Median age was 68 years (range 38-79), 59% were men. Forty-five patients received 4 cycles of treatment, three patients 3 cycles, and one patient 2 cycles. Five patients switched to carboplatin during treatment. At surgery (n=45 patients), rates of pT0 were 13% (4/29) in cohort 1 and 5% (1/19) in cohort 2. Fifty percent (15/29) of patients were pTa /pT1 in cohort 1, and 42% (8/19) in cohort 2. No severe immunotherapy-mediated toxicity was observed. Four patients had chemotherapy-related grade 3 neutropenia, one grade 4; one patient had grade 3 thrombopenia, one grade 4; four patients had grade 3 anemia. CONCLUSION While our negative study did not meet its primary endpoint in either cohort, the combination of durvalumab and platin-based chemotherapy, especially cisplatin, showed promising results in terms of downstaging. The safety profile was good and the surgical risk was not increased.
Significant progress has been made in treating Coronavirus disease (COVID) – an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). An ominous turn in the pandemic is the evolving public health crisis emanating from persistent SARS-CoV-2 infection and its associated long-term impact. Long COVID or post–COVID syndrome describes protean symptoms that persist at least 3 months after the onset of acute illness and last for at least 2 months in individuals with a history of confirmed SARS-CoV-2 infection. Long COVID has become a public health concern. Millions of infected individuals are now facing chronic multi-organ failures, including neuropsychiatric, cardiovascular, pulmonary, and kidney complications. In general, the cause of long COVID syndrome is unclear but factors such as prolonged activation of immune responses, and viral persistence triggering transcription dysregulation of genes associated with normal thrombotic disease may play a role in cardiovascular complications. Although inflammatory biomarkers are reported in other disorders, it remains unclear whether similar biomarkers are associated with cardiovascular manifestations following COVID. Medications such as sulodexide directed at glycocalyx and coagulation have demonstrated benefits for long COVID in smaller studies. Here, we describe the outcomes of the symposium on the underlying cardiovascular mechanisms of the long COVID.
Background Mechanical ventilation, a crucial intervention for acute respiratory distress syndrome (ARDS), can lead to ventilator-induced lung injury (VILI). This study focuses on individualizing mechanical power (MP) in mechanically ventilated patients to minimize VILI and reduce ICU mortality. Methods A retrospective analysis was conducted using the Amsterdam University Medical Centers Database (AmsterdamUMCdb) data. The study included patients aged 18 and older who needed at least 48 hours of pressure-controlled mechanical ventilation. Patients who died or were extubated within 48 hours and those with inadequate data were excluded. Patients were categorized into hypoxemia groups based on their PaO2/FiO2 ratio. MP was calculated using a surrogate formula and normalized to ideal body weight (IBW). Statistical analyses and machine learning models, including logistic regression and random forest, were used to predict ICU mortality and establish safe upper limits for IBW-adjusted MP. Results Out of 23,106 admissions, 2,338 met the criteria. Nonsurvivors had a significantly higher time-weighted average MP (TWA-MP) than survivors. Safe upper limits for IBW-adjusted MP varied across hypoxemia groups. The XGBoost model showed the highest predictive accuracy for ICU mortality. An individualization method for mechanical ventilation settings, based on real-time physiological variables, demonstrated reduced predicted mortality in a subset of patients. Discussion Elevated TWA-MP is associated with increased ICU mortality, underscoring the need for personalized mechanical ventilation strategies. The study highlights the complexity of VILI and the multifactorial nature of ICU mortality. Further studies to define a safe upper limit for IBW-adjusted MP may help clinicians optimize mechanical ventilation settings and decrease the risk of VILI and mortality. Conclusions Despite the fact that the study’s retrospective design and reliance on a single-center database may limit the generalizability of findings, this study offers valuable insights into the relationship between mechanical power and ICU mortality, emphasizing the need for individualized mechanical ventilation strategies. The findings suggest a potential for more personalized, data-driven approach in managing mechanically ventilated patients, which could improve patient outcomes in critical care settings.
Aims Mortality risk after hospitalization for heart failure (HF) is high, especially in the first 90 days. This study aimed to construct a model automatically predicting 90 day post‐discharge mortality using electronic health record (EHR) data 48 h after admission and artificial intelligence. Methods All HF‐related admissions from 2015 to 2020 in a single hospital were included in the model training. Comprehensive EHR data were collected 48 h after admission. Natural language processing was applied to textual information. Deaths were identified from the French national database. After variable selection with least absolute shrinkage and selection operator, a logistic regression model was trained. Model performance [area under the receiver operating characteristic curve (AUC)] was tested in two independent cohorts of patients admitted to two hospitals between March and December 2021. Results The derivation cohort included 2257 admissions (248 deaths after hospitalization). The evaluation cohorts included 348 and 388 admissions (34 and 38 deaths, respectively). Forty‐two independent variables were selected. The model performed well in the derivation cohort [AUC: 0.817; 95% confidence interval (CI) (0.789–0.845)] and in both evaluation cohorts [AUC: 0.750; 95% CI (0.672–0.829) and AUC: 0.723; 95% CI (0.644–0.803]), with better performance than previous models in the literature. Calibration was good: ‘low‐risk’ (predicted mortality ≤8%), ‘intermediate‐risk’ (8–12.5%) and ‘high‐risk’ (>12.5%) patients had an observed 90 day mortality rate of 3.8%, 8.4% and 19.4%, respectively. Conclusions The study proposed a robust model for the automatic prediction of 90 day mortality risk 48 h after hospitalization for decompensated HF. This could be used to identify high‐risk patients for intensification of therapeutic management.
We retrospectively analyzed the impact of conditioning intensity on transplant outcomes according to their cytogenetic/molecular risk in a cohort of 1823 patients with acute myeloid leukemia (AML) and intermediate- or adverse-risk cytogenetics in first complete remission (CR1). These patients received their first hematopoietic stem cell transplantation (HSCT) using post-transplant cyclophosphamide (PTCy). The intermediate-risk cytogenetic group included 1386 (76%) patients, and 608 (34%) had mutated FLT3-ITD. Myeloablative conditioning was used in 930 patients (51%), while 1130 (62%) received an intensified conditioning (score ≥2.5) based on the transplant conditioning intensity (TCI) score. Conditioning intensity using the myeloablative/reduced intensity stratification did not impact transplant outcomes across the entire cohort. However, a higher TCI score was associated with a lower risk of relapse, with no effect on survival. In specific cytogenetic risk groups, a higher TCI score did not influence outcomes in the adverse-risk group. In the intermediate-risk group, the impact varied with FLT3-ITD status. Patients with FLT3-ITD mutation who received a higher TCI showed a beneficial effect on relapse, leukemia-free survival (LFS), and overall survival. Conversely, in FLT3-ITD wild-type patients, more intense conditioning had a detrimental effect on graft-versus-host disease-free, and relapse-free survival with no effect on other outcomes. In conclusion, for AML patients in CR1 undergoing HSCT with PTCy, it is crucial to consider cytogenetic risk and molecular status when selecting the conditioning regimen. Intensive conditioning should be considered for patients with intermediate-risk cytogenetics and mutated FLT3-ITD but should probably be avoided for those with wild-type FLT3-ITD.
Updated checklist of bees of mainland France (Hymenoptera: Apocrita: Apoidea). - The checklist of bees from metropolitan France is presented here, with an update of the previous checklist published in 1995 which included 865 species. A total of 150 species have been added to this previous checklist, 114 thanks to new distributional records and 36 due to an update of their taxonomic status. In addition, 32 have been removed from the previous list, along with 12 species recently reported in French territory whose presence has either been refuted, deemed doubtful, or requires confirmation. This work results in a list of the 983 confirmed bee species for metropolitan France. This high species richness is related to the high variety of climatic and biogeographic contexts throughout the country. The amount of changes between the previous and the current checklists, most of them related to changes that happened in the past few years, illustrates the importance of keeping our efforts on improving the knowledge of the French bee fauna even today and in the years to come. This update represents an initial step toward supporting these efforts, including the forthcoming red list of French wild bees.
Dystonia is a rare-disease trait for which large-scale genomic investigations are still underrepresented. Genetic heterogeneity among patients with unexplained dystonia warrants interrogation of entire genome sequences, but this has not yet been systematically evaluated. To significantly enhance our understanding of the genetic contribution to dystonia, we (re)analyzed 2,874 whole-exome sequencing (WES), 564 whole-genome sequencing (WGS), as well as 80 fibroblast-derived proteomics datasets, representing the output of high-throughput analyses in 1,990 patients and 973 unaffected relatives from 1,877 families. Recruitment and precision-phenotyping procedures were driven by long-term collaborations of international experts with access to overlooked populations. By exploring WES data, we found that continuous scaling of sample sizes resulted in steady gains in the number of associated disease genes without plateauing. On average, every second diagnosis involved a gene not previously implicated in our cohort. Second-line WGS focused on a subcohort of undiagnosed individuals with high likelihood of having monogenic forms of dystonia, comprising large proportions of patients with early onset (81.3%), generalized symptom distribution (50.8%) and/or coexisting features (68.9%). We undertook extensive searches for variants in nuclear and mitochondrial genomes to uncover 38 (ultra)rare diagnostic-grade findings in 37 of 305 index patients (12.1%), many of which had remained undetected due to methodological inferiority of WES or pipeline limitations. WGS-identified elusive variations included alterations in exons poorly covered by WES, RNA-gene variants, mitochondrial-DNA mutations, small copy-number variants, complex rearranged genome structure, and short tandem repeats. For improved variant interpretation in WGS-inconclusive cases, we employed systematic integration of quantitative proteomics. This aided in verifying diagnoses related to technically challenging variants and in upgrading a variant of uncertain significance (3 of 70 WGS-inconclusive index patients, 4.3%). Further, unsupervised proteomic outlier-analysis supplemented with transcriptome sequencing revealed pathological gene underexpression induced by transcript disruptions in three more index patients with underlying (deep) intronic variants (3/70, 4.3%), highlighting the potential for targeted antisense-oligonucleotide therapy development. Finally, trio-WGS prioritized a de-novo missense change in the candidate PRMT1, encoding a histone-methyltransferase. Data-sharing strategies supported the discovery of three distinct PRMT1 de-novo variants in four phenotypically similar patients, associated with loss-of-function effects in in-vitro assays. This work underscores the importance of continually expanding sequencing cohorts to characterize the extensive spectrum of gene aberrations in dystonia. We show that a pool of unresolved cases is amenable to WGS and complementary multi-omic studies, directing advanced etiopathological concepts and future diagnostic-practice workflows for dystonia.
Introduction In an effort to address the limitations of current lasers, pulsed-waved Thulium: YAG laser devices were released. The purpose of this systematic review is to present all existing data, arising exclusively from human studies and clinical practice, regarding the endourological applications of the new pulsed-waved Thulium: YAG laser technology in stone disease management. Patients and methods Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement, three databases (PubMed, Scopus and Cochrane) were thoroughly investigated from inception to 30 December 2024. The following search string was utilized: (pulsed OR hybrid) AND (thulium: YAG OR Tm: YAG). Results In total eight studies satisfied all inclusion criteria and were finally included in the qualitative analysis. Six studies reported the use of the pulsed-waved Thulium: YAG laser during ureteroscopic lithotripsy (URSL) or retrograde intrarenal surgery (RIRS) and two studies reported its use during percutaneous nephrolithotomy (PCNL). In included studies, the lasing time ranged from 6.7 (2.7–13.9) to 36 (11–52) minutes. Stone-free rates (SFRs) ranged from 82 to 95%, while the Grade I-II and III-IV complications, based on the Clavien-Dindo Classification System, ranged from 3.3 to 30% and from 0 to 2%, respectively. Conclusion The purely pulsed Thulio® and hybrid RevoLix® Thulium: YAG lasers demonstrate promising safety and efficacy for RIRS and PCNL, with high peak power enabling efficient stone disintegration and effective dusting. However, the evidence is limited by small sample sizes, heterogeneity, and a lack of high-quality comparative trials. Further robust studies are needed to confirm these findings and draw reliable conclusions.
Introduction To accelerate transformation toward value‐based, equitable care, health systems need a viable approach for engaging and aligning multiple stakeholders to promote innovation. Building and sustaining learning communities offers one possible solution. Methods We describe how one learning community has leveraged the collective strengths, assets, and expertise of multiple stakeholders to improve care value for subpopulations who experience low‐quality, high‐cost, and/or inequitable health outcomes. Results By providing critical infrastructure and support, UPMC's Learning Community was able to (1) accelerate adoption of risk‐based payment models that promote shared accountability among providers, payers, and families/caregivers for the total costs of care of children and adolescents with medically complex conditions, (2) drive widespread practice change for improving physical and mental wellness for individuals with serious mental illness, and (3) increase access to evidence‐based treatment and improve outcomes for individuals with opioid and substance use disorders. Conclusions Learning communities can serve as important catalyzers for the payment, practice, and service delivery innovation necessary to achieve a high‐value, equitable health system.
This article proposes to connect the history of European integration with that of protest movements. Drawing on a transnational approach, it highlights a double link between the protest movements of spring 1968 in France and autumn 1969 in West Germany and the rise of the European Economic Community. Firstly, the completion of the common market on 1 July 1968 increased competition between European economies, fostering social demands on the eve of the protest. Secondly, the economic consequences of May 1968, both in France and in West Germany, underlined the new interdependencies of French and German societies within the common market. The need for convergence towards a ‘community of stability’ paved the way for negotiations on an economic and monetary union after the relaunch at the Congress of The Hague in December 1969.
Ecological Momentary Assessment (EMA) enables the real-time capture of health-related behaviours, their situational contexts, and associated subjective experiences. This study aimed to evaluate the feasibility of an EMA targeting physical and eating behaviours, optimise its protocol, and provide recommendations for future large-scale EMA data collections. The study involved 52 participants (age 31±9 years, 56% females) from Czechia, France, Germany, and Ireland completing a 9-day free-living EMA protocol using the HealthReact platform connected to a Fitbit tracker. The EMA protocol included time-based (7/day), event-based (up to 10/day), and self-initiated surveys, each containing 8 to 17 items assessing physical and eating behaviours and related contextual factors such as affective states, location, and company. Qualitative insights were gathered from post-EMA feedback interviews. Compliance was low (median 49%), particularly for event-based surveys (median 34%), and declined over time. Many participants were unable or unwilling to complete surveys in certain contexts (e.g., when with family), faced interference with their daily schedules, and encountered occasional technical issues, suggesting the need for thorough initial training, an individualised protocol, and systematic compliance monitoring. The number of event-based surveys was less than desired for the study, with a median of 2.4/day for sedentary events, when 4 were targeted, and 0.9/day for walking events, when 3 were targeted. Conducting simulations using participants’ Fitbit data allowed for optimising the triggering rules, achieving the desired median number of sedentary and walking surveys (3.9/day for both) in similar populations. Self-initiated reports of meals and drinks yielded more reports than those prompted in time-based and event-based EMA surveys, suggesting that self-initiated surveys might better reflect actual eating behaviours. This study highlights the importance of assessing feasibility and optimising EMA protocols to enhance subsequent compliance and data quality. Conducting pre-tests to refine protocols and procedures, including simulations using participants’ activity data for optimal event-based triggering rules, is crucial for successful large-scale data collection in EMA studies of physical and eating behaviours.
Parkinson disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy are synucleinopathies, characterized by neuronal loss, gliosis and the abnormal deposition of α-synuclein in vulnerable areas of the nervous system. Neurodegeneration begins however several years before clinical onset of motor, cognitive or autonomic symptoms. The isolated form of REM sleep behavior disorder (RBD), a parasomnia with dream enactment behaviors and excessive muscle activity during REM sleep, is an early stage synucleinopathy. The neurophysiological hallmark of RBD is REM sleep without atonia (RWSA), i.e. the loss of physiological muscle atonia during REM sleep. RBD pathophysiology is not fully clarified yet, but clinical and basic science suggest that ɑ-syn pathology begins in the lower brainstem where REM atonia circuits are located, including the sublaterodorsal tegmental/subcoeruleus nucleus and the ventral medulla, then propagates rostrally to brain regions such as the substantia nigra, limbic system, cortex. Genetically, there is only a partial overlap between RBD, PD and DLB, and individuals with iRBD may represent a specific subpopulation. A genome-wide association study identified five loci, which all seem to revolve around the GBA1 pathway. iRBD patients often show subtle motor, cognitive, autonomic and/or sensory signs, neuroimaging alterations as well as biofluid and tissue markers of neurodegeneration (in particular pathologic α-synuclein aggregates), which can be useful for risk stratification. Patients with iRBD represent thus the ideal population for neuroprotective/neuromodulating trials. This review provides insights into these aspects, highlighting and substantiating the central role of iRBD in treatment development strategies for synucleinopathies.
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13,029 members
Ali Abou Hassan
  • Laboratoire PHysico-Chimie des Electrolytes et Nanosystèmes InterfaciauX (PHENIX)
Rodrigue Lescouezec
  • Institut Parisien de Chimie Moléculaire (IPCM)
Mounir Mesbah
  • Laboratoire de statistique théorique et appliquée (LSTA)
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