Clinical and neuroimaging findings in 33 patients with MCAP syndrome: A survey to evaluate relevant endpoints for future clinical trials.

Megalencephaly-CApillary malformation-Polymicrogyria (MCAP) syndrome results from somatic mosaic gain-of-function variants in PIK3CA. Main features are macrocephaly, somatic overgrowth, cutaneous vascular malformations, connective tissue dysplasia, neurodevelopmental delay, and brain anomalies. The objectives of this study were to describe the clinical and radiological features of MCAP, to suggest relevant clinical endpoints applicable in future trials of targeted drug therapy. Based on a French collaboration, we collected clinical features of 33 patients (21 females, 12 males, median age of 9.9 years) with MCAP carrying mosaic PIK3CA pathogenic variants. MRI images were reviewed for 21 patients. The main clinical features reported were macrocephaly at birth (20/31), postnatal macrocephaly (31/32), body/facial asymmetry (21/33), cutaneous capillary malformations (naevus flammeus 28/33, cutis marmorata 17/33). Intellectual disability was present in 15 patients. Among the MRI images reviewed, the neuroimaging findings were megalencephaly (20/21), thickening of corpus callosum (16/21), Chiari malformation (12/21), ventriculomegaly/hydrocephaly (10/21), cerebral asymmetry (6/21) and polymicrogyria (2/21). This study confirms the main known clinical features that defines MCAP syndrome. Taking into account the phenotypic heterogeneity in MCAP patients, in the context of emerging clinical trials, we suggest that patients should be evaluated based on the main neurocognitive expression on each patient.

Neuropsychological study in 19 French patients with White-Sutton syndrome and POGZ mutations.

White-Sutton syndrome is a rare developmental disorder characterized by global developmental delay, intellectual disabilities (ID), and neurobehavioral abnormalities secondary to pathogenic pogo transposable element-derived protein with zinc finger domain (POGZ) variants. The purpose of our study was to describe the neurocognitive phenotype of an unbiased national cohort of patients with identified POGZ pathogenic variants. This study is based on a French collaboration through the AnDDI-Rares network, and includes 19 patients from 18 families with POGZ pathogenic variants. All clinical data and neuropsychological tests were collected from medical files. Among the 19 patients, 14 patients exhibited ID (six mild, five moderate and three severe). The five remaining patients had learning disabilities and shared a similar neurocognitive profile, including language difficulties, dysexecutive syndrome, attention disorders, slowness, and social difficulties. One patient evaluated for autism was found to have moderate autism spectrum disorder. This study reveals that the cognitive phenotype of patients with POGZ pathogenic variants can range from learning disabilities to severe ID. It highlights that pathogenic variations in the same genes can be reported in a large spectrum of neurocognitive profiles, and that children with learning disabilities could benefit from next generation sequencing techniques.

Parental Self-Efficacy for Reducing the Risk of Adolescent Depression and Anxiety: Scale Development and Validation.

Burgeoning research suggests that parents can reduce the risk of anxiety and depression in their adolescents and that parental self-efficacy (PSE) may be related to parental risk and protective factors for these disorders. As there are currently no measures available to assess PSE in relation to parenting behaviors that may reduce adolescent risk for depression and anxiety, we developed and validated a measure of PSE, the Parental Self-Efficacy Scale (PSES). Using a sample of 359 parents and 332 adolescents (aged 12-15), the PSES was found to have high reliability, confirmatory factor analysis supported its validity, and most of the hypothesized relationships between the PSES and other measures of parenting practices and adolescent depressive and anxiety symptoms were supported.

A Tailored Web-Based Intervention to Improve Parenting Risk and Protective Factors for Adolescent Depression and Anxiety Problems: Postintervention Findings From a Randomized Controlled Trial.

BACKGROUND: Depression and anxiety disorders in young people are a global health concern. Parents have an important role in reducing the risk of these disorders, but cost-effective, evidence-based interventions for parents that can be widely disseminated are lacking. OBJECTIVE: This study aimed to examine the postintervention effects of the Partners in Parenting (PiP) program on parenting risk and protective factors for adolescent depression and anxiety, and on adolescent depression and anxiety symptoms. METHODS: A two-arm randomized controlled trial was conducted with 359 parent-adolescent dyads, recruited primarily through schools across Australia. Parents and adolescents were assessed at baseline and 3 months later (postintervention). Parents in the intervention condition received PiP, a tailored Web-based parenting intervention designed following Persuasive Systems Design (PSD) principles to target parenting factors associated with adolescents' risk for depression and anxiety problems. PiP comprises a tailored feedback report highlighting each parent's strengths and areas for improvement, followed by a set of interactive modules (up to nine) that is specifically recommended for the parent based on individually identified areas for improvement. Parents in the active-control condition received a standardized package of five Web-based factsheets about adolescent development and well-being. Parents in both conditions received a 5-min weekly call to encourage progress through their allocated program to completion. Both programs were delivered weekly via the trial website. The primary outcome measure at postintervention was parent-reported changes in parenting risk and protective factors, which were measured using the Parenting to Reduce Adolescent Depression and Anxiety Scale (PRADAS). Secondary outcome measures were the adolescent-report PRADAS, the parent- and child-report Short Mood and Feelings Questionnaire (depressive symptoms), and parent- and child-report Spence Children's Anxiety Scale (anxiety symptoms). RESULTS: Parents in the intervention condition completed a mean of 73.7% of their intended personalized PiP program. A total of 318 parents (88.6%, 318/359) and 308 adolescents (92.8%, 308/332) completed the postintervention assessment. Attrition was handled using mixed model of repeated measures analysis of variance. As hypothesized, we found a significant condition-by-time interaction on the PRADAS, with a medium effect size, Cohen d=0.57, 95% CI 0.34-0.79. No significant differences between conditions were found at postintervention on any of the secondary outcome measures, with adolescent depressive (parent-report only) and anxiety (both parent- and adolescent-report) symptoms decreasing significantly from baseline to postintervention in both conditions. CONCLUSIONS: The fully automated PiP intervention showed promising short-term effects on parenting behaviors that are associated with adolescents' risk for depression and anxiety. Long-term follow-up is required to ascertain whether these effects translate into reduced adolescent depression and anxiety problems. The intervention may be useful as a low-cost universal public health program to increase parenting practices believed to benefit adolescents' mental health. TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry: ACTRN12615000328572; https://www.anzctr.org.au/ Trial/Registration/TrialReview.aspx? id=368274 (Archived by WebCite at http://www.webcitation.org/6qgsZ3Aqj).

[Severe burned patient rehabilitation]. / Réhabilitation du brûlé grave.

Severe burned patient rehabilitation. The rehabilitation of the severe burn requires multidisciplinary care in a specialized rehabilitation center. We present in this article, the care offered in our service, detailing in particular the psychological aspects. Indeed, some patients with severe burns have a psychiatric history, while others will present a status with post-traumatic stress disease following the burn. The general principles of rehabilitation are the establishment of various ways of compression to fight against hypertrophy, as well as the achievement of postures to limit retractions. The organization of chain care minimizes the functional, aesthetic and psychological consequences of burns, and it accompanies the severe burned patients throughout scarring.

Réhabilitation du brûlé grave. La réhabilitation du brûlé grave nécessite une prise en charge pluridisciplinaire en centre de rééducation spécialisé. Nous présentons dans cet article les soins proposés dans notre service, en détaillant en particulier les aspects psychologiques. En effet, une partie des patients victimes de brûlures graves ont des antécédents psychiatriques, tandis que d'autres vont avoir un état de stress post-traumatique consécutif à la brûlure. Les principes généraux de la rééducation sont la mise en place de différents moyens de compression pour lutter contre l'hypertrophie, ainsi que la réalisation de postures pour limiter les rétractions. L'organisation des soins en filière permet de minimiser les conséquences fonctionnelles, esthétiques et psychologiques à la suite de la brûlure, en accompagnant le brûlé grave tout au long de la maturation cicatricielle.

BRAND: a platform for closed-loop experiments with deep network models.

Objective.Artificial neural networks (ANNs) are state-of-the-art tools for modeling and decoding neural activity, but deploying them in closed-loop experiments with tight timing constraints is challenging due to their limited support in existing real-time frameworks. Researchers need a platform that fully supports high-level languages for running ANNs (e.g. Python and Julia) while maintaining support for languages that are critical for low-latency data acquisition and processing (e.g. C and C++).Approach.To address these needs, we introduce the Backend for Realtime Asynchronous Neural Decoding (BRAND). BRAND comprises Linux processes, termednodes, which communicate with each other in agraphvia streams of data. Its asynchronous design allows for acquisition, control, and analysis to be executed in parallel on streams of data that may operate at different timescales. BRAND uses Redis, an in-memory database, to send data between nodes, which enables fast inter-process communication and supports 54 different programming languages. Thus, developers can easily deploy existing ANN models in BRAND with minimal implementation changes.Main results.In our tests, BRAND achieved <600 microsecond latency between processes when sending large quantities of data (1024 channels of 30 kHz neural data in 1 ms chunks). BRAND runs a brain-computer interface with a recurrent neural network (RNN) decoder with less than 8 ms of latency from neural data input to decoder prediction. In a real-world demonstration of the system, participant T11 in the BrainGate2 clinical trial (ClinicalTrials.gov Identifier: NCT00912041) performed a standard cursor control task, in which 30 kHz signal processing, RNN decoding, task control, and graphics were all executed in BRAND. This system also supports real-time inference with complex latent variable models like Latent Factor Analysis via Dynamical Systems.Significance.By providing a framework that is fast, modular, and language-agnostic, BRAND lowers the barriers to integrating the latest tools in neuroscience and machine learning into closed-loop experiments.

Pseudo-linear Summation explains Neural Geometry of Multi-finger Movements in Human Premotor Cortex.

How does the motor cortex combine simple movements (such as single finger flexion/extension) into complex movements (such hand gestures or playing piano)? Motor cortical activity was recorded using intracortical multi-electrode arrays in two people with tetraplegia as they attempted single, pairwise and higher order finger movements. Neural activity for simultaneous movements was largely aligned with linear summation of corresponding single finger movement activities, with two violations. First, the neural activity was normalized, preventing a large magnitude with an increasing number of moving fingers. Second, the neural tuning direction of weakly represented fingers (e.g. middle) changed significantly as a result of the movement of other fingers. These deviations from linearity resulted in non-linear methods outperforming linear methods for neural decoding. Overall, simultaneous finger movements are thus represented by the combination of individual finger movements by pseudo-linear summation.

BRAND: A platform for closed-loop experiments with deep network models.

Artificial neural networks (ANNs) are state-of-the-art tools for modeling and decoding neural activity, but deploying them in closed-loop experiments with tight timing constraints is challenging due to their limited support in existing real-time frameworks. Researchers need a platform that fully supports high-level languages for running ANNs (e.g., Python and Julia) while maintaining support for languages that are critical for low-latency data acquisition and processing (e.g., C and C++). To address these needs, we introduce the Backend for Realtime Asynchronous Neural Decoding (BRAND). BRAND comprises Linux processes, termed nodes , which communicate with each other in a graph via streams of data. Its asynchronous design allows for acquisition, control, and analysis to be executed in parallel on streams of data that may operate at different timescales. BRAND uses Redis to send data between nodes, which enables fast inter-process communication and supports 54 different programming languages. Thus, developers can easily deploy existing ANN models in BRAND with minimal implementation changes. In our tests, BRAND achieved <600 microsecond latency between processes when sending large quantities of data (1024 channels of 30 kHz neural data in 1-millisecond chunks). BRAND runs a brain-computer interface with a recurrent neural network (RNN) decoder with less than 8 milliseconds of latency from neural data input to decoder prediction. In a real-world demonstration of the system, participant T11 in the BrainGate2 clinical trial performed a standard cursor control task, in which 30 kHz signal processing, RNN decoding, task control, and graphics were all executed in BRAND. This system also supports real-time inference with complex latent variable models like Latent Factor Analysis via Dynamical Systems. By providing a framework that is fast, modular, and language-agnostic, BRAND lowers the barriers to integrating the latest tools in neuroscience and machine learning into closed-loop experiments.

The knowledge transfer potential of online data pools on nature-based solutions.

Improving the adoption of Nature-based Solutions (NBS) requires learning from successes and failures. Knowledge derived from implemented cases helps to identify for instance drivers and barriers of NBS implementation, generates lessons learned, and supports their upscaling. Online data pools that catalogue information from NBS case studies may help scientists and practitioners to create this knowledge. The aim of this review is to assess the knowledge transfer potential of online data pools for implementing and upscaling NBS. For that, we compared 21 online data pools that report on NBS case studies in terms of topics, availability and quality of information on NBS. We found a high variability in quantity, type and quality of the information documented, hindering comparability and limiting knowledge transfer. Our results show that the most common knowledge provided was on actions undertaken on NBS, their outcomes, case study site descriptions, specific challenges and information on responsible entities and partners. Information on key attributes of NBS, such as on ecosystem processes and services as well as on governance and financing issues, was often omitted. The missing information however would be important for further comparative research to overcome implementation gaps for NBS. Based on the discussion of our findings we propose categories for a more efficient online data pool and give recommendations for further research on NBS.

Phosphatidylinositol 4,5-bisphosphate-induced conformational change of ezrin and formation of ezrin oligomers.

The plasma membrane-cytoskeleton interface is a dynamic structure involved in a variety of cellular events. Ezrin, a protein from the ERM family, provides a direct linkage between the cytoskeleton and the membrane via its interaction with phosphatidylinositol 4,5-bisphosphate (PIP2). In this paper, we investigate the interaction between PIP2 and ezrin in vitro using PIP2 dispersed in a unimolecular way in buffer. We compared the results obtained with full-length ezrin to those obtained with an ezrin mutant, which was previously found not to be localized at the cell membrane, and with the N-terminal membrane binding domain (FERM domain) of ezrin. We show that PIP2 induced a conformational change in full-length ezrin. PIP2 was also found to induce, in vitro, the formation of oligomers of wild-type ezrin, but not of mutant ezrin. These oligomers had previously been observed in vivo, but their role is yet to be clarified. Our finding hints at a possible role for PIP2 in the formation of ezrin oligomers.

Upstanding Youngsters: Ivorian Scouting and the Manufacture of a Subordinate Citizenship (1937-1979).

This research focuses on Ivoirian scouting from its colonial implementation in the late 1930s up to the late 1970s, under Félix Houphouet-Boigny's regime. Using a novel perspective, it highlights the gender lines of scouting youth training in West Africa. Furthermore, this paper argues that understanding this history of Ivoirian youth through the lens of the scouting movement allows us to articulate youth governance between the colonial and postcolonial era, notably in order to understand the political and moral subordination of Ivoirian youth during the twentieth century. This research is based on archives collected in France, Côte d'Ivoire and Switzerland as well as biographical interviews conducted in 2016.

Fluorescent labeling in semi-solid medium for selection of mammalian cells secreting high-levels of recombinant proteins.

BACKGROUND: Despite the powerful impact in recent years of gene expression markers like the green fluorescent protein (GFP) to link the expression of recombinant protein for selection of high producers, there is a strong incentive to develop rapid and efficient methods for isolating mammalian cell clones secreting high levels of marker-free recombinant proteins. Recently, a method combining cell colony growth in methylcellulose-based medium with detection by a fluorescently labeled secondary antibody or antigen has shown promise for the selection of Chinese Hamster Ovary (CHO) cell lines secreting recombinant antibodies. Here we report an extension of this method referred to as fluorescent labeling in semi-solid medium (FLSSM) to detect recombinant proteins significantly smaller than antibodies, such as IGF-E5, a 25 kDa insulin-like growth factor derivative. RESULTS: CHO cell clones, expressing 300 microg/ml IGF-E5 in batch culture, were isolated more easily and quickly compared to the classic limiting dilution method. The intensity of the detected fluorescent signal was found to be proportional to the amount of IGF-E5 secreted, thus allowing the highest producers in the population to be identified and picked. CHO clones producing up to 9.5 microg/ml of Tissue-Plasminogen Activator (tPA, 67 kDa) were also generated using FLSSM. In addition, IGF-E5 high-producers were isolated from 293SF transfectants, showing that cell selection in semi-solid medium is not limited to CHO and lymphoid cells. The best positive clones were collected with a micromanipulator as well as with an automated colony picker, thus demonstrating the method's high throughput potential. CONCLUSION: FLSSM allows rapid visualization of the high secretors from transfected pools prior to picking, thus eliminating the tedious task of screening a high number of cell isolates. Because of its rapidity and its simplicity, FLSSM is a versatile method for the screening of high producers for research and industry.

Layer-by-layer films as a biomimetic reservoir for rhBMP-2 delivery: controlled differentiation of myoblasts to osteoblasts.

Efficient delivery of growth or survival factors to cells is one of the most important long-term challenges of current cell-based tissue engineering strategies. The extracellular matrix acts as a reservoir for a number of growth factors through interactions with its components. In the matrix, growth factors are protected against circulating proteases and locally concentrated. Thus, the localized and long-lasting delivery of a matrix-bound recombinant human bone morphogenetic protein 2 (rhBMP-2) from a biomaterial surface would mimic in vivo conditions and increase BMP-2 efficiency by limiting its degradation. Herein, it is shown that crosslinked poly(L-lysine)/hyaluronan (HA) layer-by-layer films can serve as a reservoir for rhBMP-2 delivery to myoblasts and induce their differentiation into osteoblasts in a dose-dependent manner. The amount of rhBMP-2 loaded in the films is controlled by varying the deposition conditions and the film thickness. Its local concentration in the film is increased up to approximately 500-fold when compared to its initial solution concentration. Its adsorption on the films, as well as its diffusion within the films, is evidenced by microfluorimetry and confocal microscopy observations. A direct interaction of rhBMP-2 with HA is demonstrated by size-exclusion chromatography, which could be at the origin of the rhBMP-2 "trapping" in the film and of its low release from the films. The bioactivity of rhBMP-2-loaded films is due neither to film degradation nor to rhBMP-2 release. The rhBMP-2-containing films are extremely resistant and could sustain three successive culture sequences while remaining bioactive, thus confirming the important and protective effect of rhBMP-2 immobilization. These films may find applications in the local delivery of immobilized growth factors for tissue-engineered constructs and for metallic biomaterial surfaces, as they can be deposited on a wide range of substrates with different shapes, sizes, and composition.

Alkylamino hydrazide derivatives of hyaluronic acid: synthesis, characterization in semidilute aqueous solutions, and assembly into thin multilayer films.

A series of biodegradable alkylamino hydrazide hyaluronic acid (HA) derivatives were prepared and used to design new biocompatible films able to release hydrophobic drugs in a controlled manner. The first step of this work thus consisted in optimizing the synthetic conditions of hydrazide HA derivatives bearing pendant hexyl, octyl, decyl, and citronellyl chains with a degree of substitution of 0.05 or 0.10. The behavior in aqueous solution of these water-soluble modified HA samples was then examined in the semidilute regime. The decylamino hydrazide derivatives of HA exhibited remarkable associating properties, giving rise to transparent gels. These gels were found to be more resistant to degradation by hyaluronidase compared to solutions of nonmodified HA at the same concentration. The other derivatives of which the lengths of grafted alkyl chains range from 6 to 8 carbon atoms lead to more or less viscous solutions. Different viscometric features for these derivatives could be observed as a function of the molecular weight of HA. As derivatives prepared from a HA sample of 600,000 g/mol (HA-600) exhibited a much higher tendency to self-aggregate than their counterparts prepared from a HA sample of 200,000 g/mol (HA-200), the latter derivatives were selected for the build up of multilayer films. The topography and z-section of (PLL/HA derivatives) films assembled layer-by-layer were observed by atomic force microscopy (AFM) in liquid and confocal laser scanning microscopy (CLSM) using PLL(FITC) as ending layer. Moreover, the ability of the films made of the different HA derivatives to incorporate the hydrophobic dye nile red (NR) was investigated. Films containing decylamino hydrazide HA derivatives were the most efficient for incorporating and retaining nile red, which confirms the formation of stable hydrophobic nanodomains in the films.

Sarcoidosis and Wound Healing After Cellulitis of the Lower Limb: Is Methotrexate Responsible for Skin Graft Failure?

The authors report the case of a 53-year-old man with diffuse cutaneous and mediastinal pulmonary sarcoidosis and well-controlled steroid-induced diabetes. He was hospitalized for cellulitis of his left leg. His standard treatment for sarcoidosis consisted of prednisone and methotrexate. Prednisone was stopped at his admission. He received antibiotics for 4 weeks to treat the cellulitis. In parallel, the leg wound was treated with daily silver sulfadiazine applications until necrosis removal, then by skin autografting. Four successive procedures were performed, but all failed despite lack of surgical problem or local infection. Methotrexate was stopped after the fourth grafting procedure failed; the fifth, and final, autografting procedure was successfully performed.

Two new risk factors for heterotopic ossification development after severe burns.

OBJECTIVES: Life after severe burns is conditioned by the remaining sequelae. The pathophysiology and risk factors of Heterotopic Ossification (HO) after burns are still poorly understood. The aim of this study was to determine: 1) the incidence of HO after burns and 2) the risk factors associated with HO development, in a large retrospective study. METHODS: A case-control study of patients admitted to the burns intensive care unit of Percy Hospital, Paris, from the 1st January 2009 to the 31st December 2013 and then admitted to one of three centres specialised in the rehabilitation of patients with burns. Multivariate analysis was carried out to analyse the relationship between HO development and demographic and clinical data. RESULTS: 805 patients were included. 32 patients (4.0%) developed a total of 74 heterotopic ossifications, that is a little higher incidence than the incidence found in the literature. The epidemiological characteristics of the population studied was similar to the literature. HOs were mainly localized around the elbows, followed by the hips, shoulders and knees. Each case-patient was paired with 3 control-patients. There were significant associations between HO development and the length of stay in the burns intensive care unit, the extent and depth of the burns, the occurrence of pulmonary or cutaneous infections, use of curare and use of an air-fluidized bed. CONCLUSION: In addition to recognized risk factors (duration of stay in the intensive care burns unit, extent and depth of burns, pulmonary and cutaneous infections), the use of curare and the use of a fluidized bed (with the duration of use) were significantly associated with HO formation.

Enzymatic assays for probing mitochondrial apoptosis.

Isolated mitochondria are an invaluable analytical tool to probe mitochondrial function and evaluate apoptosis induction via the so-called mitochondrial pathway. Irrespective of their tissue origin (e.g., heart, liver, muscle, brain), these organelles participate actively to cell and life decision by producing energy for cell metabolism, but also by undergoing a lethal and irreversible mitochondrial membrane permeabilization (MMP) in stress and pathological conditions. MMP consequences consist, at least in part, in loss of mitochondrial transmembrane potential (ΔΨm), matrix swelling, arrest of respiration and ATP production, and cytochrome c release from the intermembrane space to the cytosol. These parameters can be evaluated in vitro via several miniaturized assays, which have tremendous applications in the field of pharmacology, toxicology, diagnosis, as well as drug discovery.

[The care of the burn patient in the rehabilitation center]. / La prise en charge des patients brûlés en centre de rééducation.

The rehabilitation of a patient with serious burns involves several disciplines. The initial objective is to reduce the appearance or evolution of functional sequelae. The patient's future will depend on the quality of this rehabilitation.

Polyelectrolyte multilayer nanofilms used as thin materials for cell mechano-sensitivity studies.

Three types of multilayer films made from poly(L-lysine)/hyaluronan, chitosan/hyaluronan, and poly(allylamine hydrochloride)/poly(L-glutamic acid), were used to investigate the interplay between film mechano-chemical properties and cell adhesion. We showed that C2C12 myoblast adhesion and proliferation depended on the extent of film cross-linking for all films whatever their internal chemistry. Cell spreading areas were found to correlate with the film's stiffness and to be distributed over a unique curve. Immuno-staining of the cytoskeletal components revealed the formation of F-actin stress fibers and vinculin plaques only on stiff films. Finally, we compared our results with previous studies performed on polyacrylamide and PDMS gels, two recognized materials for mechano-sensitivity studies. We found that the effect of substrate stiffness on cell spreading is material-dependent.

Nano-scale control of cellular environment to drive embryonic stem cells selfrenewal and fate.

Embryonic stem cells (ESC) are pluripotent cells capable to give rise to any embryonic cell lineage. In culture, these cells form colonies creating their own niche. Depending upon the molecular and physico-chemical environment, the pluripotent cells oscillate between two metastable states of pluripotency either reminiscent of the inner cell mass of the embryo or the epiblast, a stage of development which give rise to the three embryonic layers, ectoderm, endoderm and mesoderm. Herein, we used PLL/HA nanofilms cross-linked to various degrees to modulate the nanoenvironment of ESCs. Adhesion of ESC on nanofilms increased from native films to highly cross-linked films. The adhesion process was associated with cell proliferation. Expression of genes markers of the ICM decreased with adhesion of cells to cross-linked films. In parallel, genes more reminiscent of the epiblast, were turned on. ESC differentiation within embryoid bodies further revealed that cell pluripotency was better retained when cells did not adhere on native films. We further report that both the stiffness and the chemistry of nanofilms play a key role in modulating the niche of ESC and in turn govern their selfrenewal and fate.