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BackgroundSAPHO syndrome (Synovitis, Acne, Palmoplantar Pustulosis, Hyperostosis and Osteitis) is a radio-clinical entity associating joint, bone and inflammatory skin disorders. The clinical presentation is very heterogeneous making the diagnosis difficult. The therapeutic strategy in SAPHO syndrome is poorly defined. The first-line treatment remains NSAIDs on demand, which are effective in treating painful flare-ups but rapidly become insufficient in 60% of cases during the course of the disease. TNF-αNF-O syndrome (S necrosis factor-alpha) are reserved for refractory forms and their efficacy is uncertain [1]. Bisphosphonates (BPs) seem to have potential interest [2].ObjectivesThe main objective of this study was to investigate the response to treatment with BPs and/or immunosuppressive drugs (DMARDs - Disease modifying anti-rheumatic drugs), conventional synthetic cs-DMARDs or biologic (b-DMARDs), according to the clinical form of rheumatological SAPHO (bony predominantly versus articular or mixed predominantly.MethodsAll patients aged 18 years or older with SAPHO syndrome meeting Benhamou’s criteria whose clinical, biological and radiological data were available in the files and who received at least one DMARD or BP treatment for their disease were included in Rouen (thanks to the health data warehouse), Caen, Le Havre/Lillebonne and Dieppe Centres. Each imaging examination was reviewed blinded to the treatments by a radiologist with expertise in osteoarticular disease. Patients were classified into 2 groups (bony versus joint/mixed) according to imaging data and clinical history. The response to treatment was considered positive if symptoms were improved by at least 50% (cut-off used in the literature). An χ2 patients aged 18 years or older with SAPHO syndrome meeting Benhamou’s criteria whose clinical, biological and a Mann-Whitney test for quantitative variables using SPSS software.ResultsThirty-four patients with SAPHO who had received DMARD or BP treatment were included and classified as follows: 13 in the bone group and 21 in the joint or mixed group. The 2 groups were comparable on demographics, duration of follow-up, previous chest involvement, existence of associated dermatological or inflammatory bowel disease, exposure to smoking, duration of exposure to a previous NSAID or antibiotic. Only the age of onset of symptoms differed between the two groups, with a younger onset of disease in the bone group (p=0.043). The prescribers’ therapeutic attitude differed significantly between the 2 groups (p=0.043) with a greater prescription of BPs as first line in the bone group (5/13 patients) and a DMARD in the joint/mixed group (19/21). Regarding treatment efficacy, 10/13 patients had effective treatment without escape during their follow-up in the bone group, which was not significantly different from the joint/mixed group (17/21). BPs achieved escape-free efficacy in significantly more cases in the bone group than DMARDs in the joint or mixed group (p= 0.002). The bone group used significantly fewer specific treatment lines (DMARDs or BP) than the joint/mixed group (1 specific line vs. at least 2) (p =0.046).ConclusionBPs appear to be more effective in SAPHO with predominantly bone involvement. This appears to be easier to treat compared to SAPHO with articular or mixed forms.References[1]Daoussis D, Konstantopoulou G, Kraniotis P, et al. Biologics in SAPHO syndrome: A systematic review. Seminars in Arthritis and Rheumatism 2019;48:618–25. doi:10.1016/j.semarthrit.2018.04.003[2]Wu N, Zhao Y, Tao W, et al. A single cohort, open-label study of the efficacy of pamidronate for palmoplantar pustulosis in synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome. Clin Exp Rheumatol 2020;38:1263–4.Disclosure of InterestsNone declared

Coordinated changes of cellular identity and plasticity are critical for pluripotent reprogramming (PR) and malignant transformation (MT). However, the molecular circuitries orchestrating these modifications, as well as their degree of analogy during reprogramming and transformation, remain unknown. To address this question, we generated “repro-transformable” mice models and dissected comparatively the early events underpinning PR - mediated by Oct4, Sox2, Klf4, c-Myc - and MT - triggered by oncogenic Ras and c-Myc. Transcriptomic analyses allowed the identification of a unique set of markers - the cell surface glycoprotein Thy1 and the transcription factor (TF) Bcl11b - that are commonly downregulated during PR and MT and delineate cellular intermediates (CI) highly amenable to generate pluripotent or malignant derivatives. Comprehensive transcriptomic, epigenomic and functional analyses of different CI, prone or refractory to PR/MT, unveiled that cellular plasticity acquisition precedes the broad extinction of cellular identity. It also demonstrated the existence of specific and shared molecular features of PR and MT while ensuring the identification of broad-range regulators of cellular plasticity. As a proof-of-concept, we revealed that the basic helix-loop-helix (bHLH) class A TF Atoh8 constrains rodent and human iPS cells generation as well as MT and direct neuron conversion. Mechanistically, this TF hampers the reactivation of the pluripotent network during PR and limits the acquisition of phenotypic plasticity during MT. Furthermore, an integrated analysis of Atoh8 genome-wide binding, alongside the other bHLH TFs c-Myc, Ascl1 and MyoD promoting reprogramming/transdifferentiation, unveiled how Atoh8 constrains cellular plasticity by occupying a specific subset of MEF enhancers and by finetuning WNT signalling activity. Collectively, by deconvoluting the early steps of the reprogramming and transformation roadmaps, this integrated study uncoupled changes of cellular plasticity and identity to shed light on novel insights into reprogramming and cancer biology.Graphical abstractOne-sentence summaryComparative roadmaps of cellular plasticity acquisition during pluripotent reprogramming and malignant transformation.

This paper describes the development of a novel method of producing nanocomposites consisting of gold nanoclusters anchored on graphene oxide nanosheets in a cost-effective and reproducible manner. The novelty of the technique hinges on the covalent functionalization of atomically precise subnanometer gold clusters protected by glutathione (Au15SG13 and Au25SG18) on to graphene oxide (GO) nanosheets according to the 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride crosslinking method, using the existing carboxylic groups present both at the surfaces of the nanoclusters and the GO nanosheets. The atomic precision of glutathione-protected gold nanoclusters was evidenced by electrospray ionization mass spectrometry. The formed hybrid nanocomposites were characterized by TEM measurements and exhibit nonlinear optical properties characteristic of GO, in particular a strong second harmonic scattering response as well as a multi-photon excited fluorescence spectrum characterized by a broad band in the visible range between 350 and 700 nm. Atomically precise nanoclusters covalently linked to GO nanosheets are therefore promising for new applications in the areas of optoelectronics and photovoltaics.

International audience; Long-range orientational correlations in liquids have received recent renewed interest, in particular for the neat water case. These long-range orientational correlations, exceeding several tens of nanometers, originate from the presence of the strong permanent water dipolar moment. However, the exact dependence with the dipolar moment and the role of other local forces like steric hindrance has never been addressed. In this work, we experimentally measure long-range correlations for a set of liquids differing by their molecular weight and dipolar moment, in order to reveal the origin of their long-range organization. Hence, we show that the dipolar moment of a solvent molecule is not the unique feature determining the orientational correlation. Steric hindrance significantly helps to structure the liquids as well. In order to quantify these long-range correlations, we also derive theoretically the polarization resolved second harmonic scattering intensity as a function of the rotational invariants describing the dipolar and octupolar interaction.

International audience; The two-photon excited fluorescence (TPEF) cross-section of Protoporphyrin IX (PpIX) in solution is determined at different excitation wavelengths. Maxima observed at 620 and 634 nm are associated with two different forms of PpIX already observed in one-photon excited fluorescence studies. In order to further provide insights into these two forms, first hyperpolarizabilities are also reported for these two forms with corresponding depolari-zation ratio further demonstrating the existence of specific symmetry differences. The static and the frequency dependent first hyperpolarizability were also calculated using Gaussian 09 and compared to the experimental data. This work shows that PpIX can exhibit two forms that might be targeted in applications like oncology clinical agents.

Aim: This retrospective, monocentric cohort study aimed at assessing clinical characteristics, lung function course and overall survival of patients with non-IPF PF-ILD in a real-world setting. Methods: All successive patients hospitalized in a French Rare Lung Disease Reference Centre between 2010 and 2017, aged ≥18 years, with at least 10% fibrosis extent at baseline high resolution computed tomography of chest (HRCT) were included. PF-ILD over a period of 2 years was defined as: relative decline in forced vital capacity (FVC) ≥ 10% with or without clinical deterioration (a); or a moderate relative decline between 5% and 10% associated with worsening respiratory symptoms or increased extent of fibrosis in HRCT (b); or increased extent of fibrosis on HRCT with worsening respiratory symptoms with or without FVC decline (c). Results: 165 patients (57% of women) were included with a mean age of 60 (±14 years). Most of patients (65%) were included with criterion (a), 24% with criterion (b) and 9% with criterion (c). Estimates of overall survival were 99%, 82%, and 66% at 1, 3 and 6 years, respectively. Mortality was significantly associated with FVC Conclusion: The natural history of non-IPF ILD in patients with PF phenotype follows a course characterized by worsening of respiratory symptoms, progressive lung function decline and early mortality despite appropriate management.

International audience; We report the chemical substitution-mediated doping of silver atoms into Au10SG10 (SG: glutathione) catenane nanoclusters (NCs) in a controllable manner. Two levels of doping were conducted leading to two silver-doped Au10–xAgxSG10 nanoclusters (with x = 0–2 and x = 1–4). Optical studies reveal that nanoclusters with a high level of doping (x = 1–4) show a blue shift in absorption and a significant red shift of ∼50 nm in the two-photon-excited emission spectrum with respect to pristine Au10SG10. The preservation of the catenane structure is confirmed by comparing the experimental and computational X-ray diffraction patterns and absorption spectra of Au10SG10 and its silver-doped analogs. In order to better address the structure–property relationship in such catenane clusters, further theoretical investigations were performed at the DFT level. A high-energy shift of the S1 state is evidenced in the calculated one-photon absorption spectra due to a larger s to d gap in silver caused by smaller relativistic effects in comparison to the gold atoms. Furthermore, the red shift in the two-photon excited emission band of the clusters is due to significantly larger calculated relaxation of the first excited state in nanoclusters with a high level of silver doping.

International audience; We report a polarization-resolved analysis of the second harmonic intensity collected in retro-reflection from a Lithium Niobate microcrystals powder. Depth intensity profiles exhibit first an increase due to the beam focus entering the powder then a decrease due to multiple scattering. With a polarization analysis performed at selected depths, we show that there is a competition between ballistic and multiply scattered photons. The contribution from the multiply scattered photons dominates at all depths whereas, at the maximum of the intensity depth profiles, the contribution of the ballistic photons is at its maximum and enhanced due to collection efficiency. This latter contribution from the ballistic photons is clearly observed through distortions in the polarization-resolved plots.

International audience; The fluorescence-free measurement of molecular second-order nonlinear optical properties (i.e. the first hyperpolarizability β) in solution for a set of fluorescent proteins and channel rhodopsins is reported. Because removing the fluorescence contribution is critical in providing accurate values for this nonlinear optical property, especially for the fluorescent proteins, we use and critically compare two different approaches to correct hyper Rayleigh scattering from the multiphoton fluorescence contribution. On the one hand, we use the frequency domain where the delayed fluorescence contribution is separated from the instantaneous hyper-Rayleigh scattering contribution through amplitude modulation and on the other hand we use the spectral domain where the broadband fluorescence spectrum is subtracted from the narrower hyper Rayleigh scattering line. The two methods, discussed in terms of their efficiency for routine measurements, yield similar first hyperpolarizability values, therefore establishing the robustness of the two approaches to correct for the fluorescence. From the data reported, the previously observed trend where more red-shifted fluorescent proteins have larger hyperpolarizability values because of their longer conjugated chromophore is unambiguously confirmed. For the channel rhodopsins, it is shown that despite their obligate dimeric and fairly symmetric nature, large first hyperpolarizabilities are measured, pointing to their potential use for second-harmonic imaging and membrane potential measurements in nonlinear optogenetics.

Joint manifestations of ANCA (antineutrophil cytoplasmic antibody) associated vasculitis (AAV) are extremely common in the progression of systemic damages. However, the joint involvement is rarely isolated. The diagnosis and the treatment are difficult in this particular situation and few data are available on the topic.We have observed two cases of joint manifestation revealing AAV we are going to describe here. The evolution toward a more severe disease raises the question of the treatment managing. The place of the ANCA research in relation to other immune tests is also discussed.Isolated joint manifestations of ANCA vasculitis are rare but can lead to a delay in diagnosis. ANCA vasculitis should be considered in seronegative symmetrical polyarthritis by looking for ANCA in a second line biological test. Methotrexate is the first treatment option to be considered. In case of insufficient response or failure, rituximab seems an interesting option in this context.

International audience; Gold nanoparticles are widely used in different fields. They are currently under extensive investigation with regard to their linear and nonlinear optical properties. So far, nanoparticles with centrosymmetrical shapes, such as nanospheres or nanorods, have received the main attention. In this work, the properties of gold nanoprisms exhibiting a highly noncentrosymmetrical threefold symmetry are investigated with hyper-Rayleigh scattering (HRS). Aqueous solutions of gold nanospheres and nanoprisms with different sizes were synthesized. The first hyperpolarizability magnitudes of both the nanospheres and nanoprisms were determined separately with the assumption of a surface origin of the nonlinearity. Using polarization-resolved HRS, retardation is shown to be largely underdeveloped for the nanoprisms as opposed to the nanospheres. The nanoprism shape noncentrosymmetry has therefore a leading role in the HRS response although it is also shown that surface defects induce deviations from the ideal threefold symmetry.

International audience; Nonlinear photon conversion is a fundamental physical process that lies on the basis of many modern disciplines, from bioimaging and theranostics in nanomedicine to material characterization in materials science and nanotechnology. It also holds great promise in laser physics with applications in information technology for optical signal processing and in the development of novel coherent light sources. The capability to efficiently generate harmonics at the nanoscale will have an enormous impact on all these fields, since it would allow one to realize much more compact devices and to interrogate matter in extremely confined volumes. Here, we present a perspective on the most recent advances in the generation of nonlinear optical processes at the nanoscale and their applications, proposing a palette of future perspectives that range from material characterization and the development of novel compact platforms for efficient photon conversion to bioimaging and sensing.

INTRODUCTION: Histologic subtypes of malignant pleural mesothelioma are a major prognostic indicator and decision denominator for all therapeutic strategies. In an ambiguous case, a rare transitional mesothelioma (TM) pattern may be diagnosed by pathologists either as epithelioid mesothelioma (EM), biphasic mesothelioma (BM), or sarcomatoid mesothelioma (SM). This study aimed to better characterize the TM subtype from a histological, immunohistochemical, and molecular standpoint. Deep learning of pathologic slides was applied to this cohort. METHODS: A random selection of 49 representative digitalized sections from surgical biopsies of TM was reviewed by 16 panelists. We evaluated BAP1 expression and CDKN2A (p16) homozygous deletion. We conducted a comprehensive, integrated, transcriptomic analysis. An unsupervised deep learning algorithm was trained to classify tumors. RESULTS: The 16 panelists recorded 784 diagnoses on the 49 cases. Even though a Kappa value of 0.42 is moderate, the presence of a TM component was diagnosed in 51%. In 49% of the histological evaluation, the reviewers classified the lesion as EM in 53%, SM in 33%, or BM in 14%. Median survival was 6.7 months. Loss of BAP1 observed in 44% was less frequent in TM than in EM and BM. p16 homozygous deletion was higher in TM (73%), followed by BM (63%) and SM (46%). RNA sequencing unsupervised clustering analysis revealed that TM grouped together and were closer to SM than to EM. Deep learning analysis achieved 94% accuracy for TM identification. CONCLUSION: These results revealed that the TM pattern should be classified as non-EM or at minimum as a subgroup of the SM type. ispartof: JOURNAL OF THORACIC ONCOLOGY vol:15 issue:6 pages:1037-1053 ispartof: location:United States status: published

BACKGROUND: Mesenchymal epithelial transition receptor (MET) alterations, including MET exon 14 skipping mutation, are oncogenic in non-small cell lung cancer (NSCLC) and may confer sensitivity to targeted therapy. Given the rarity and the diversity of exon 14 skipping mutations, diagnosis may be challenging on small-biopsy specimens. METHODS: Between March 2014 and May 2018, tissue samples from patients with metastatic NSCLC were analysed for MET exon 14 skipping mutation as part of routine practice in the Pathology Department of the Hospices Civils de Lyon, France. Over the study period, Sanger sequencing and/or two different DNA-based next generation sequencing (NGS) assays were used. RESULTS: Genomic alterations of MET exon 14 were detected in 2.6% (62/2,369) samples of NSCLC analysed for MET exon 14 mutations. Patients were mainly women (38/62, 61%) without smoking history (22/39, 56%) and the median age was 75 years. MET exon 14 skipping mutations were diagnosed by NGS in 50 cases and by classical Sanger sequencing in 12 cases. The frequency of MET mutations was 15.4% when Sanger sequencing was performed at the request of the clinician and 4.1% when the DNA-based NGS assay coverage included the 3' and 5' parts of the MET exon 14 and performed systematically. CONCLUSIONS: The frequency of genomic alterations is highly dependent on patient selection and the technical approach.

International audience; The air–ionic liquid interface for a series of ionic liquids involving imidazolium cations [Cnmim] with different alkyl chain lengths (n = 2, 4, 6, 8, 10, and 12) and the same [NTf2] imide anion has been studied by polarization-resolved second harmonic generation (SHG). An increase as a function of the alkyl chain length of the orientational parameter reveals the increasing ordering of the air–pure ionic liquid interfaces although it is not possible to disentangle the change in mean tilt angle from a change in the tilt angle probability distribution width. Besides, the study of the air–mixed ([C12mim])x([C2mim])1–x[NTf2] ionic liquid interface clearly demonstrates the interfacial nonideality of the mixed ionic liquids. The long alkyl chain cation perturbs the interface as seen from the orientational parameter and displaces the short alkyl chain one for bulk mixture contents as low as 10%. At higher long alkyl chain cation bulk mixture contents, the interface behaves close to a pure long alkyl chain ionic liquid.

BackgroundCopy Number Variants (CNVs) associated with autism and schizophrenia have large effects on brain anatomy. Yet, neuroimaging studies have been conducted one mutation at a time. We hypothesize that neuropsychiatric CNVs may exert general effects on brain morphometry because they confer risk for overlapping psychiatric conditions.MethodsWe analyzed T1-weighted MRIs and characterized shared patterns on brain anatomy across 8 neuropsychiatric CNVs. Clinically ascertained samples included 1q21.1 (n=48), 16p11.2 (n=156), or 22q11.2 (n=96) and 331 non-carriers. Non-clinically ascertained samples from the UK Biobank included 1q21.1 (n=19), 16p11.2 (n=8), 22q11.2 (n=9), 15q11.2 (n=148) and 965 non-carriers. Canonical correlation analysis (CCA) and univariate models were used to interrogate brain morphometry changes across 8 CNVs.ResultsEight CNVs affect regional brain volumes along two main gene-morphometry dimensions identified by CCA. While fronto-temporal regions contributed to dimension 1, dimension 2 was driven by subcortical, parietal and occipital regions. Consistently, voxel-wise whole-brain analyses identified the same regions involved in patterns of alteration present across the 4 deletions and duplications. These neuroanatomical patterns are similar to those observed in cross-psychiatric disorder meta-analyses. Deletions and duplications at all 4 loci show mirror effects at either the global and/or the regional level.ConclusionNeuropsychiatric CNVs share neuroanatomical signatures characterized by a parsimonious set of brain dimensions. The latter may underlie the risk conferred by CNVs for a similar spectrum of neuropsychiatric conditions.

Software Product Lines Engineering (SPLE) proposes techniques to model, create and improve groups of related software systems in a systematic way, with different alternatives formally expressed, e.g., as Feature Models. Selecting the 'best' software system(s) turns into a problem of improving the quality of selected subsets of software features (components) from feature models, or as it is widely known, Feature Configuration. When there are different independent dimensions to assess how good a software product is, the problem becomes even more challenging- it is then a multi-objective optimisation problem. Another big issue for software systems is evolution where software components change. This is common in the industry but, as far as we know, there is no algorithm designed to the particular case of multi-objective optimisation of evolving software product lines. In this paper we present MILPIBEA, a novel hybrid algorithm which combines the scalability of a genetic algorithm (IBEA) with the accuracy of a mixed-integer linear programming solver (IBM ILOG CPLEX). We also study the behaviour of our solution (MILPIBEA) in contrast with SATIBEA, a state-of-the-art algorithm in static software product lines. We demonstrate that MILPIBEA outperforms SATIBEA on average, especially for the most challenging problem instances, and that MILPIBEA is the one that continues to improve the quality of the solutions when SATIBEA stagnates (in the evolving context). Science Foundation Ireland

International audience; In this communication, we report the second harmonic scattering from mass characterized 2D graphene oxide sheets dispersed in an aqueous suspension, in the femtosecond regime at 800 nm laser excitation. Charge-detection mass-spectrometry, performing at the single sheet level, allows for an exhaustive molar mass distribution and thus concentration for these 2D nanomaterials samples. The orientation-averaged hyperpolarizability value is (1.36 ± 0.15) × 10−25 esu as determined by the concentration-dependent harmonic scattering signal. In addition, the multi-photon excited fluorescence spectrum is characterized by a broad band in the visible range between 350 and 700 nm centered at about 500 nm.

Highlights • Rapid determination of PD-L1 expression has become a necessity in lung cancer. • The decalcification process is a critical point for bone metastasis specimens. • EDTA or formic acid decalcification may be used for PD-L1 IHC in routine practice., As for molecular alterations of lung adenocarcinoma, it is critical that pathologists are able to give PD-L1 expression status before first-line of treatment. The present study compared PD-L1 expression (clone 22-C3) in decalcified using EDTA or formic acid and non-decalcified lung cancer metastases bone samples. Amongst the 84 bone samples analysed for PD-L1 expression, and independently of decalcification, TPS ≥ 1% was 25.0% and ≥ 50% was 11.4%. There was no significant difference between decalcified samples (n = 45) and non-decalcified samples (n = 39) for both TPS ≥ 1% (p = 0.32) and TPS ≥ 50% (p = 1). To conclude, we confirm decalcified bone metastasis specimens may be used for PD-L1 IHC in routine practice. These results also highlight potentially interesting specificities of the bone microenvironment that should be further studied

Large effect-size mutations such as copy number variants (CNVs) have the potential to provide key insights into the underlying biological mechanisms linking deleterious genetic variants to brain architecture and neuropsychiatric disorders. To date, the effect of CNVs on functional brain connectivity remains mostly unstudied, and findings are derived from analyses conducted one mutation at a time. The lack of systematic cross-CNV comparisons hinders our understanding of any potential general mechanisms linking CNVs to effects on brain organization. We performed connectome-wide analyses using resting-state functional MRI data from 436 carriers of neuropsychiatric CNVs at the 1q21.1, 15q11.2, 16p11.2, 22q11.2 loci, and 4 neutral-effect CNVs, 66 carriers of scarcer neuropsychiatric CNVs, 756 individuals with idiopathic autism spectrum disorder (ASD), schizophrenia, attention deficit hyperactivity disorder, and 5,377 controls. Neuropsychiatric CNVs showed global shifts of mean connectivity. The effect size of CNVs on relative connectivity (adjusted for the mean) was correlated with the known level of neuropsychiatric risk conferred by CNVs. We reported architecture similarities between individuals with idiopathic psychiatric conditions and high-risk neuropsychiatric-CNVs, predominantly in the thalamus, the posterior cingulate cortex, and the anterior insula. We identified a linear relationship between connectivity and intolerance to haploinsufficiency measured for all genes encompassed by CNVs across 18 loci. This profile involved the thalamus, the basal ganglia, somatomotor and frontoparietal networks and was correlated with lower general intelligence and higher autism severity scores. An exploratory factor analysis confirmed the contribution of these regions to three latent components shared across CNVs and neuropsychiatric disorders. We posit that deleting genes intolerant to haploinsufficiency reorganize connectivity along general dimensions irrespective of where deletions occur in the genome. This haploinsufficiency brain signature opens new avenues to understand polygenicity in psychiatric conditions and the pleiotropic effect of CNVs on cognition and risk for neuropsychiatric disorders.

Introduction: Histopathological definition of bone and joint infection (BJI) is based on Mirra's criterion (≥ 5 polymorphonuclears (PMNs) per field in 5 high power fields (HPFs)). However, this definition does not seem appropriate for chronic BJIs caused by slow-growing germs such as Cutibacterium acnes (C. acnes). The aim of this study was to confirm that Mirra's criterion is not adequate for diagnosis of BJIs due to C. acnes. The second objective was to determine if plasma cell infiltration could be useful for the diagnosis of chronic BJIs due to C. acnes. Methods: We retrospectively selected 25 consecutive patients from 2009 to 2013 with chronic BJIs due to C. acnes. Histological analysis was performed on the 21 cases with at least two C. acnes positive cultures. In addition of Mirra's criterion, the number of plasma cells (≥5 plasma cells/5 HPFs, defined as “CRIOAc Lyon's criterion”) was implemented in the histopathological analysis. Patients were defined as infected, if at least one of the two criteria were present. Results: According to Mirra's and CRIOAc Lyon's criteria, positive histopathology was observed in 12 (57.1%) and 15 (71.4%) cases respectively. Considering the 9 cases with negative Mirra's criterion, high plasma cell infiltration (≥5 plasma cells per field/5 HPFs) was observed in 5 cases (55.6%), and low plasma cells infiltration (2-5 plasma cells per field/5 HPFs) was observed in 4 other cases (44.4%). Conclusions: Adding CRIOAc Lyon's criterion to Mirra's criterion might restore some histopathological diagnosis of chronic BJIs due to C. acnes when a chronic BJI is clinically suspected.

Following the administration of immune checkpoint inhibitors, an unexpected pattern of response designated as hyperprogression may be observed in certain patients. This paradoxical response corresponds to an acceleration in tumor growth and a dramatic decrease of patient survival. The reported incidence rates of hyperprogressive disease are highly variable, ranging between 4 and 29%. In this review, we have performed a literature search on hyperprogressive disease, including both retrospective studies and case reports, and discuss potential predictive biomarkers as well as potential mechanisms associated with immune-checkpoint inhibitor associated hyperprogression.

Carriers of large recurrent copy number variants (CNVs) have a higher risk of developing neurodevelopmental disorders. The 16p11.2 distal CNV predisposes carriers to e.g., autism spectrum disorder and schizophrenia. We compared subcortical brain volumes of 12 16p11.2 distal deletion and 12 duplication carriers to 6882 non-carriers from the large-scale brain Magnetic Resonance Imaging collaboration, ENIGMA-CNV. After stringent CNV calling procedures, and standardized FreeSurfer image analysis, we found negative dose-response associations with copy number on intracranial volume and on regional caudate, pallidum and putamen volumes (β = -0.71 to -1.37; P

Carriers of large recurrent copy number variants (CNVs) have a higher risk of developing neurodevelopmental disorders. The 16p11.2 distal CNV predisposes carriers to e.g., autism spectrum disorder and schizophrenia. We compared subcortical brain volumes of 12 16p11.2 distal deletion and 12 duplication carriers to 6882 non-carriers from the large-scale brain Magnetic Resonance Imaging collaboration, ENIGMA-CNV. After stringent CNV calling procedures, and standardized FreeSurfer image analysis, we found negative dose-response associations with copy number on intracranial volume and on regional caudate, pallidum and putamen volumes (β = -0.71 to -1.37; P 0.0005). In an independent sample, consistent results were obtained, with significant effects in the pallidum (β = -0.95, P = 0.0042). The two data sets combined showed significant negative dose-response for the accumbens, caudate, pallidum, putamen and ICV (P = 0.0032, 8.9 × 10

Prior to and following the publication of this article the authors noted that the complete list of authors was not included in the main article and was only present in Supplementary Table 1. The author list in the original article has now been updated to include all authors, and Supplementary Table 1 has been removed. All other supplementary files have now been updated accordingly. Furthermore, in Table 1 of this Article, the replication cohort for the row Close relative in data set, n (%) was incorrect. All values have now been corrected to 0(0%). The publishers would like to apologise for this error and the inconvenience it may have caused.

International audience; Gliomas are diffuse brain tumors still hardly curable due to the difficulties to identify margins. 5-ALA induced PpIX fluorescence measurements enable to gain in sensitivity but are still limited to discriminate margin from healthy tissue. In this fluorescence spectroscopic study, we compare an expert-based model assuming that two states of PpIX contribute to total fluorescence and machine learning-based models. We show that machine learning retrieves the main features identified by the expert approach. We also show that machine learning approach slightly overpasses expert-based model for the identification of healthy tissues. These results might help to improve fluorescence-guided resection of gliomas by discriminating healthy tissues from tumor margins.

International audience; Hyper Rayleigh Scattering (HRS) is a method allowing the retrieval of metallic nanoparticles morphology. It is usually conducted in a right angle geometry preventing the full determination of all the sample information. To alleviate this problem, we report experiments in this manuscript where we have employed a multi-angle geometry in order to further complement the study. This method is applied to a standard push-pull molecular compound, a well-defined symmetry model system, and then is extended to gold metallic nanoparticles with a diameter of 5 nm. In this way, it is possible to observe how shape deformation, or in other words symmetry, is obtained as compared to the one solely retrieved from the right-angle geometry.