Publications

@article{pmid39204272,

title = {BacSPaD: A Robust Bacterial Strains' Pathogenicity Resource Based on Integrated and Curated Genomic Metadata},

author = {Sara Ribeiro and Guillaume Chaumet and Karine Alves and Julien Nourikyan and Lei Shi and Jean-Pierre Lavergne and Ivan Mijakovic and Simon de Bernard and Laurent Buffat},

doi = {10.3390/pathogens13080672},

issn = {2076-0817},

year  = {2024},

date = {2024-08-01},

urldate = {2024-08-01},

journal = {Pathogens},

volume = {13},

number = {8},

abstract = {The vast array of omics data in microbiology presents significant opportunities for studying bacterial pathogenesis and creating computational tools for predicting pathogenic potential. However, the field lacks a comprehensive, curated resource that catalogs bacterial strains and their ability to cause human infections. Current methods for identifying pathogenicity determinants often introduce biases and miss critical aspects of bacterial pathogenesis. In response to this gap, we introduce BacSPaD (Bacterial Strains' Pathogenicity Database), a thoroughly curated database focusing on pathogenicity annotations for a wide range of high-quality, complete bacterial genomes. Our rule-based annotation workflow combines metadata from trusted sources with automated keyword matching, extensive manual curation, and detailed literature review. Our analysis classified 5502 genomes as pathogenic to humans (HP) and 490 as non-pathogenic to humans (NHP), encompassing 532 species, 193 genera, and 96 families. Statistical analysis demonstrated a significant but moderate correlation between virulence factors and HP classification, highlighting the complexity of bacterial pathogenicity and the need for ongoing research. This resource is poised to enhance our understanding of bacterial pathogenicity mechanisms and aid in the development of predictive models. To improve accessibility and provide key visualization statistics, we developed a user-friendly web interface.},

keywords = {medical data, omics},

pubstate = {published},

tppubtype = {article}

}

@article{pmid38510150,

title = {Exogenous IL-2 delays memory precursors generation and is essential for enhancing memory cells effector functions},

author = {Shaoying Wang and Margaux Prieux and Simon de Bernard and Maxence Dubois and Daphne Laubreton and Sophia Djebali and Manon Zala and Christophe Arpin and Laurent Genestier and Yann Leverrier and Olivier Gandrillon and Fabien Crauste and Wenzheng Jiang and Jacqueline Marvel},

doi = {10.1016/j.isci.2024.109411},

issn = {2589-0042},

year  = {2024},

date = {2024-04-01},

urldate = {2024-04-01},

journal = {iScience},

volume = {27},

number = {4},

pages = {109411},

abstract = {To investigate the impact of paracrine IL-2 signals on memory precursor (MP) cell differentiation, we activated CD8 T cell  in the presence or absence of exogenous IL-2 (ex-IL-2). We assessed memory differentiation by transferring these cells into virus-infected mice. Both conditions generated CD8 T cells that participate in the ongoing response and gave rise to similar memory cells. Nevertheless, when transferred into a naive host, T cells activated with ex-IL-2 generated a higher frequency of memory cells displaying increased functional memory traits. Single-cell RNA-seq analysis indicated that without ex-IL-2, cells rapidly acquire an MP signature, while in its presence they adopted an effector signature. This was confirmed at the protein level and in a functional assay. Overall, ex-IL-2 delays the transition into MP cells, allowing the acquisition of effector functions that become imprinted in their progeny. These findings may help to optimize the generation of therapeutic T cells.},

keywords = {omics},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {P-228 Les modèles mathématiques peuvent prédire l'activité des plaquettes humaines et les expressions protéiques en réponse à diverses stimulations},

author = {Fabrice Cognasse and Kim Anh Nguyen and Marco Heestermans and Charles-Antoine Arthaud and Marie-Ange Eyraud and Amélie Prier and Simon De Bernard and Julien Nourikyan and Anne-Claire Duchez and Stéphane Avril and Olivier Garraud and Hind Hamzeh-Cognasse},

doi = {10.1016/j.tracli.2023.09.272},

year  = {2023},

date = {2023-11-10},

urldate = {2023-11-10},

journal = {Transfusion Clinique et Biologique},

volume = {30},

issue = {S1},

pages = {S147},

keywords = {medical data},

pubstate = {published},

tppubtype = {article}

}

@article{pmid38015712,

title = {Chronological aging impacts abundance, function and microRNA content of extracellular vesicles produced by human epidermal keratinocytes},

author = {Taku Nedachi and Christelle Bonod and Julie Rorteau and Wafae Chinoune and Yuri Ishiuchi and Sandrine Hughes and Benjamin Gillet and Nicolas Bechetoille and Dominique Sigaudo-Roussel and Jérôme Lamartine},

doi = {10.18632/aging.205245},

issn = {1945-4589},

year  = {2023},

date = {2023-11-01},

urldate = {2023-11-01},

journal = {Aging (Albany NY)},

volume = {15},

number = {22},

pages = {12702--12722},

abstract = {The disturbance of intercellular communication is one of the hallmarks of aging. The goal of this study is to clarify the impact of chronological aging on extracellular vesicles (EVs), a key mode of communication in mammalian tissues. We focused on epidermal keratinocytes, the main cells of the outer protective layer of the skin which is strongly impaired in the skin of elderly. EVs were purified from conditioned medium of primary keratinocytes isolated from infant or aged adult skin. A significant increase of the relative number of EVs released from aged keratinocytes was observed whereas their size distribution was not modified. By small RNA sequencing, we described a specific microRNA (miRNA) signature of aged EVs with an increase abundance of miR-30a, a key regulator of barrier function in human epidermis. EVs from aged keratinocytes were found to be able to reduce the proliferation of young keratinocytes, to impact their organogenesis properties in a reconstructed epidermis model and to slow down the early steps of skin wound healing in mice, three features observed in aged epidermis. This work reveals that intercellular communication mediated by EVs is modulated during aging process in keratinocytes and might be involved in the functional defects observed in aged skin.},

keywords = {omics},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {P-CB-16 | Mathematical Models Can Predict Human Platelet Activity and Protein Expressions in Response to Various Stimulations},

author = {Fabrice Cognasse and Kim Anh Nguyen and Marco Heestermans and Simon De Bernard and Julien Nourikyan and Anne-Claire Duchez and Stéphane Avril and Olivier Garraud and Hind Hamzeh-Cognasse},

doi = {10.1111/trf.199_17554},

year  = {2023},

date = {2023-10-12},

urldate = {2023-10-12},

journal = {Transfusion},

volume = {63},

issue = {S5},

pages = {156A-156A},

keywords = {medical data},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37347665,

title = {The multi-level regulation of clownfish metamorphosis by thyroid hormones},

author = {Natacha Roux and Saori Miura and Mélanie Dussenne and Yuki Tara and Shu-Hua Lee and Simon de Bernard and Mathieu Reynaud and Pauline Salis and Agneesh Barua and Abdelhay Boulahtouf and Patrick Balaguer and Karine Gauthier and David Lecchini and Yann Gibert and Laurence Besseau and Vincent Laudet},

doi = {10.1016/j.celrep.2023.112661},

issn = {2211-1247},

year  = {2023},

date = {2023-06-01},

urldate = {2023-06-01},

journal = {Cell Rep},

volume = {42},

number = {7},

pages = {112661},

abstract = {Most marine organisms have a biphasic life cycle during which pelagic larvae transform into radically different juveniles. In vertebrates, the role of thyroid hormones (THs) in triggering this transition is well known, but how the morphological and physiological changes are integrated in a coherent way with the ecological transition remains poorly explored. To gain insight into this question, we performed an integrated analysis of metamorphosis of a marine teleost, the false clownfish (Amphiprion ocellaris). We show how THs coordinate a change in color vision as well as a major metabolic shift in energy production, highlighting how it orchestrates this transformation. By manipulating the activity of liver X regulator (LXR), a major regulator of metabolism, we also identify a tight link between metabolic changes and metamorphosis progression. Strikingly, we observed that these regulations are at play in the wild, explaining how hormones coordinate energy needs with available resources during the life cycle.},

keywords = {omics},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37275363,

title = {Ultrasound assessment of the respiratory system using diaphragm motion-volume indices},

author = {Alain Boussuges and Guillaume Chaumet and Martin Boussuges and Amelie Menard and Stephane Delliaux and Fabienne Brégeon},

doi = {10.3389/fmed.2023.1190891},

issn = {2296-858X},

year  = {2023},

date = {2023-05-19},

urldate = {2023-05-19},

journal = {Front Med (Lausanne)},

volume = {10},

pages = {1190891},

abstract = {BACKGROUND: Although previous studies have determined limit values of normality for diaphragm excursion and thickening, it would be beneficial to determine the normal diaphragm motion-to-inspired volume ratio that integrates the activity of the diaphragm and the quality of the respiratory system.



METHODS: To determine the normal values of selected ultrasound diaphragm motion-volume indices, subjects with normal pulmonary function testing were recruited. Ultrasound examination recorded diaphragm excursion on both sides during quiet breathing and deep inspiration. Diaphragm thickness was also measured. The inspired volumes of the corresponding cycles were systematically recorded using a spirometer. The indices were calculated using the ratio excursion, or percentage of thickening, divided by the corresponding breathing volume. From this corhort, normal values and limit values for normality were determined. These measurements were compared to those performed on the healthy side in patients with hemidiaphragm paralysis because an increase in hemidiaphragm activity has been previously demonstated in such circumstances.



RESULTS: A total of 122 subjects (51 women, 71 men) with normal pulmonary function were included in the study. Statistical analysis revealed that the ratio of excursion, or percentage of thickening, to inspired volume ratio significantly differed between males and females. When the above-mentioned indices using excursion were normalized by body weight, no gender differences were found. The indices differed between normal respiratory function subjects and patients with hemidiaphragm paralysis (27 women, 41 men). On the paralyzed side, the average ratio of the excursion divided by the inspired volume was zero. On the healthy side, the indices using the excursion and the percentage of thickening during quiet breathing or deep inspiration were significantly increased comparedto patients with normal lung function. According to the logistic regression analysis, the most relevant indice appeared to be the ratio of the excursion measured during quiet breathing to the inspired volume.



CONCLUSION: The normal values of the diaphragm motion-volume indices could be useful to estimate the performance of the respiratory system. Proposed indices appear suitable in a context of hyperactivity.},

keywords = {medical data},

pubstate = {published},

tppubtype = {article}

}

@article{Sanlaville2023.02.15.528594,

title = {CD4 T cells and neutrophils contribute to epithelial-mesenchymal transition in breast cancer},

author = {Amélien Sanlaville and Aurélien Voissière and Dominique Poujol and Margaux Hubert and Suzanne André and Clémence Perret and Jean-Philippe Foy and Nadège Goutagny and Marine Malfroy and Isabelle Durand and Marie Châlons-Cottavoz and Jenny Valladeau-Guilemond and Pierre Saintigny and Alain Puisieux and Christophe Caux and Marie-Cécile Michallet and Isabelle Puisieux and Nathalie Bendriss-Vermare},

url = {https://www.biorxiv.org/content/early/2023/02/15/2023.02.15.528594},

doi = {10.1101/2023.02.15.528594},

year  = {2023},

date = {2023-02-15},

urldate = {2023-01-01},

journal = {bioRxiv},

publisher = {Cold Spring Harbor Laboratory},

abstract = {Epithelial-mesenchymal transition (EMT) is a central oncogenic mechanism, contributing both to transformation and metastatic dissemination. Inflammation and innate immune cells are known to favor EMT induction, but the role of adaptive immunity still remains unclear. Using an original murine mammary tumor model in immune cell subpopulation depletion experiments, we demonstrated that tumor cells maintain their epithelial phenotype in mice deficient for adaptive immune response, but undergo EMT in the presence of T-cells. This phenotypic conversion involves the major contribution of CD4 T cells, but not CD8 T cells nor B cells, undoubtedly demonstrating the pro-EMT role of CD4 T cells specifically among adaptive immune cells. Moreover, combined intra-tumor immune infiltrate and transcriptomic analyses of murine mammary tumors with various EMT phenotype revealed an inverse correlation between mesenchymal tumor cell and intratumoral neutrophil proportions, due to the reduced ability of mesenchymal cells to recruit neutrophils. Last, selective in vivo depletion of neutrophils and transcriptomic analysis of human breast tumor cohorts demonstrated the pro-EMT role of neutrophils and suggest a cooperation with CD4 T cells in EMT promotion. Collectively, our data highlight a novel mechanism of EMT regulation by both innate and adaptive immune compartments.Competing Interest StatementThe authors have declared no competing interest.},

keywords = {omics},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36832246,

title = {Performance of T-Track TB, a Novel Dual Marker RT-qPCR-Based Whole-Blood Test for Improved Detection of Active Tuberculosis},

author = {Johannes P Meier and Selina Möbus and Florian Heigl and Alexandra Asbach-Nitzsche and Hans Helmut Niller and Annelie Plentz and Korkut Avsar and Marion Heiß-Neumann and Bernhard Schaaf and Uwe Cassens and Bernd Seese and Daniel Teschner and Sabin Handzhiev and Uwe Graf and Christoph Lübbert and Monika Steinmaurer and Konstantina Kontogianni and Christoph Berg and Andreas Maieron and Stefan H Blaas and Ralf Wagner and Ludwig Deml and Sascha Barabas},

doi = {10.3390/diagnostics13040758},

issn = {2075-4418},

year  = {2023},

date = {2023-02-01},

urldate = {2023-02-01},

journal = {Diagnostics (Basel)},

volume = {13},

number = {4},

abstract = {Tuberculosis (TB) is one of the leading causes of death by an infectious disease. It remains a major health burden worldwide, in part due to misdiagnosis. Therefore, improved diagnostic tests allowing the faster and more reliable diagnosis of patients with active TB are urgently needed. This prospective study examined the performance of the new molecular whole-blood test T-Track TB, which relies on the combined evaluation of  and  mRNA levels, and compared it to that of the QuantiFERON-TB Gold Plus (QFT-Plus) enzyme-linked immunosorbent assay (ELISA). Diagnostic accuracy and agreement analyses were conducted on the whole blood of 181 active TB patients and 163 non-TB controls. T-Track TB presented sensitivity of 94.9% and specificity of 93.8% for the detection of active TB vs. non-TB controls. In comparison, the QFT-Plus ELISA showed sensitivity of 84.3%. The sensitivity of T-Track TB was significantly higher ( < 0.001) than that of QFT-Plus. The overall agreement of T-Track TB with QFT-Plus to diagnose active TB was 87.9%. Out of 21 samples with discordant results, 19 were correctly classified by T-Track TB while misclassified by QFT-Plus (T-Track TB-positive/QFT-Plus-negative), and two samples were misclassified by T-Track TB while correctly classified by QFT-Plus (T-Track TB-negative/QFT-Plus-positive). Our results demonstrate the excellent performance of the T-Track TB molecular assay and its suitability to accurately detect TB infection and discriminate active TB patients from non-infected controls.},

keywords = {omics},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36007550,

title = {MXD4/MAD4 Regulates Human Keratinocyte Precursor Fate},

author = {Julien Coutier and Frédéric Auvré and Gilles Lemaître and Jean-Jacques Lataillade and Jean-François Deleuze and Paul-Henri Roméo and Michèle T Martin and Nicolas O Fortunel},

doi = {10.1016/j.jid.2022.07.020},

issn = {1523-1747},

year  = {2023},

date = {2023-01-01},

urldate = {2023-01-01},

journal = {J Invest Dermatol},

volume = {143},

number = {1},

pages = {105--114.e12},

abstract = {Deciphering the pathways that regulate human epidermal precursor cell fate is necessary for future developments in skin repair and graft bioengineering. Among them, characterization of pathways regulating the keratinocyte (KC) precursor immaturity versus differentiation balance is required for improving the efficiency of KC precursor ex vivo expansion. In this study, we show that the transcription factor MXD4/MAD4 is expressed at a higher level in quiescent KC stem/progenitor cells located in the basal layer of human epidermis than in cycling progenitors. In holoclone KCs, stable short hairpin-RNA‒mediated decreased expression of MXD4/MAD4 increases MYC expression, whose modulation increases the proliferation of KC precursors and maintenance of their clonogenic potential and preserves the functionality of these precursors in three-dimensional epidermis organoid generation. Altogether, these results characterize MXD4/MAD4 as a major piece of the stemness puzzle in the human epidermis KC lineage and pinpoint an original avenue for ex vivo expansion of human KC precursors.},

keywords = {omics},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36482098,

title = {RNA-Seq comparative study reveals molecular effectors linked to the resistance of Pinna nobilis to Haplosporidium pinnae parasite},

author = {Pauline Salis and Claire Peyran and Titouan Morage and Simon de Bernard and Julien Nourikyan and Stéphane Coupé and Robert Bunet and Serge Planes},

doi = {10.1038/s41598-022-25555-x},

issn = {2045-2322},

year  = {2022},

date = {2022-12-01},

urldate = {2022-12-01},

journal = {Sci Rep},

volume = {12},

number = {1},

pages = {21229},

abstract = {With the intensification of maritime traffic, recently emerged infectious diseases have become major drivers in the decline and extinction of species. Since 2016, mass mortality events have decimated the endemic Mediterranean Sea bivalve Pinna nobilis, affecting ca. 100% of individuals. These events have largely been driven by Haplosporidium pinnae's infection, an invasive species which was likely introduced by shipping. While monitoring wild populations of P. nobilis, we observed individuals that survived such a mass mortality event during the summer of 2018 (France). We considered these individuals resistant, as they did not show any symptoms of the disease, while the rest of the population in the area was devastated. Furthermore, the parasite was not detected when we conducted a PCR amplification of a species-specific fragment of the small subunit ribosomal DNA. In parallel, the transcriptomic analysis showed evidence of some parasite RNA indicating that the resistant individuals had been exposed to the parasite without proliferating. To understand the underlying mechanisms of resistance in these individuals, we compared their gene expression with that of susceptible individuals. We performed de novo transcriptome assembly and annotated the expressed genes. A comparison of the transcriptomes in resistant and susceptible individuals highlighted a gene expression signature of the resistant phenotype. We found significant differential expressions of genes involved in immunity and cell architecture. This data provides the first insights into how individuals escape the pathogenicity associated with infection.},

keywords = {omics},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36410115,

title = {Comprehensive morphometric assessment of deltoid muscle development in children: A cross-sectional study},

author = {Teresinha Evangelista and Malick Kandji and Emmanuelle Lacene and Anaïs Chanut and Mai Thao Bui and Rudy Marty and Laurent Buffat and Kenneth Knoblauch and Brian B Rudkin and Norma Beatriz Romero},

doi = {10.1016/j.ebiom.2022.104367},

issn = {2352-3964},

year  = {2022},

date = {2022-12-01},

urldate = {2022-12-01},

journal = {EBioMedicine},

volume = {86},

pages = {104367},

abstract = {BACKGROUND: Normative values for different morphometric parameters of muscle fibres during paediatric development, i.e. from 0 to 18 years, are currently unavailable. They would be of major importance to accurately evaluate pathological changes and could be used as reference biomarkers for evaluating treatment response in clinical trials, or physiological adjustments in sports or ageing.



METHODS: Data were derived from 482 images with a total of 33 094 fibres from 10 μm cross-sections of snap-frozen muscle from 83 deltoid muscle biopsies from patients, 0-18 years, without neuromuscular pathology stained with ATPase 9.4. Data was acquired and analysed with patented image analysis algorithms from "CARPACCIO.cloud". Several parameters were extracted or calculated, including cross-sectional area (CSA), fibre type, circularity, as well as the Minimum diameter of Feret (MinFeret).



FINDINGS: This study illustrates changes in quantitative parameters for muscle morphology over the course of paediatric development and the pivotal changes occurring around puberty. Only fibre size parameters (MinFeret, CSA) are dependent on gender, and only after puberty. All other parameters vary in a similar manner for females and males. The proportion of type 1 fibres is essentially constant from birth to age 10, decreasing to ≈40% by age 18. Circularity decreases with age, to plateau after age 10 for both fibre types.



INTERPRETATION: Normative values and reference charts for muscle fibre types in this age range have been generated to allow comparison of data from patients in pathology laboratories working on neuromuscular diseases.



FUNDING: BPI FRANCE, PULSALYS, Association de l'Institut de Myologie, French National Research Agency (ANR), LABEX CORTEX of Université de Lyon.},

keywords = {medical data},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36065187,

title = {CD8 memory precursor cell generation is a continuous process},

author = {Helena Todorov and Margaux Prieux and Daphne Laubreton and Matteo Bouvier and Shaoying Wang and Simon de Bernard and Christophe Arpin and Robrecht Cannoodt and Wouter Saelens and Arnaud Bonnaffoux and Olivier Gandrillon and Fabien Crauste and Yvan Saeys and Jacqueline Marvel},

doi = {10.1016/j.isci.2022.104927},

issn = {2589-0042},

year  = {2022},

date = {2022-09-01},

urldate = {2022-09-01},

journal = {iScience},

volume = {25},

number = {9},

pages = {104927},

abstract = {In this work, we studied the generation of memory precursor cells following an acute infection by analyzing single-cell RNA-seq data that contained CD8 T cells collected during the postinfection expansion phase. We used different tools to reconstruct the developmental trajectory that CD8 T cells followed after activation. Cells that exhibited a memory precursor signature were identified and positioned on this trajectory. We found that these memory precursors are generated continuously with increasing numbers arising over time. Similarly, expression of genes associated with effector functions was also found to be raised in memory precursors at later time points. The ability of cells to enter quiescence and differentiate into memory cells was confirmed by BrdU pulse-chase experiment . Analysis of cell counts indicates that the vast majority of memory cells are generated at later time points from cells that have extensively divided.},

keywords = {omics},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35184302,

title = {Gene profiling reveals a contact allergy signature in most positive Amerchol L-101 patch test reactions},

author = {Linda Ljungberg Silic and Marine-Alexia Lefevre and Ola Bergendorff and Simon De Bernard and Julien Nourikyan and Laurent Buffat and Audrey Nosbaum and Magnus Bruze and Jean-François Nicolas and Cecilia Svedman and Marc Vocanson},

doi = {10.1111/cod.14077},

issn = {1600-0536},

year  = {2022},

date = {2022-07-01},

urldate = {2022-07-01},

journal = {Contact Dermatitis},

volume = {87},

number = {1},

pages = {40--52},

abstract = {BACKGROUND: Diagnosis of contact allergy (CA) to Amerchol L-101 (AL-101), a marker for lanolin allergy, is problematic. Positive patch test reactions are frequently doubtful or weakly positive and difficult to associate with clinical relevance.



OBJECTIVE: To gain further insight on the allergic or irritant nature of skin reactions induced by AL-101 patch test.



METHODS: We re-tested in a dose-response fashion, 10 subjects with AL-101 CA and performed comprehensive transcriptomic analysis (gene arrays, quantitative real-time polymerase chain reaction [qRT-PCR]) of samples of their skin reactions.



RESULTS: Eight of the 10 CA subjects reacted positively upon re-test, whereas two did not react. Most of AL-101 positive patch tests expressed an allergy signature with strong activation of gene modules associated with adaptive immunity and downregulation of cornification pathway genes. In addition, the breadth of gene modulation correlated with the magnitude of patch test reactions and the concentration of AL-101 applied. However, we observed that some of the positive patch test reactions to AL-101 expressed no/few allergy biomarkers, suggesting the induction of an irritant skin inflammation in these samples.



CONCLUSIONS: This study confirms that AL-101 is an allergen that can cause both contact allergy and contact irritation. Our results also highlight that molecular profiling might help to strengthen clinical diagnosis.},

keywords = {omics},

pubstate = {published},

tppubtype = {article}

}

@article{Roux2022.03.04.482938,

title = {The multi-level regulation of clownfish metamorphosis by thyroid hormones},

author = {Natacha Roux and Saori Miura and Mélanie Dussene and Yuki Tara and Fiona Lee and Simon Bernard and Mathieu Reynaud and Pauline Salis and Agneesh Barua and Abdelhay Boulahtouf and Patrick Balaguer and Karine Gauthier and David Lecchini and Yann Gibert and Laurence Besseau and Vincent Laudet},

url = {https://www.biorxiv.org/content/early/2022/03/04/2022.03.04.482938},

doi = {10.1101/2022.03.04.482938},

year  = {2022},

date = {2022-03-04},

urldate = {2022-01-01},

journal = {bioRxiv},

publisher = {Cold Spring Harbor Laboratory},

abstract = {Most marine organisms have a biphasic life cycle during which a pelagic larva is transformed into a radically different juvenile. In vertebrates the role of thyroid hormones (TH) in triggering this transition is well known, but how the morphological and physiological changes are integrated in a coherent way with the ecological transition remains poorly explored. To gain insight into this question, we performed an integrative analysis of metamorphosis of a marine teleost, the clownfish Amphiprion ocellaris. We reveal how TH coordinate a change in color vision as well as a major metabolic shift in energy production, hence highlighting its central integrative role in regulating this transformation. By manipulating the activity of LXR, a major regulator of metabolism, we also reveal a tight link between metabolic changes and metamorphosis progression. Strikingly, we observed that these regulations are at play in the wild revealing how hormones coordinate energy needs with available resources during life cycle.Competing Interest StatementThe authors have declared no competing interest.},

keywords = {omics},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34286840,

title = {Therapeutic siRNAs Targeting the JAK/STAT Signalling Pathway in Inflammatory Bowel Diseases},

author = {Flora Clément and Adrien Nougarède and Stéphanie Combe and Frédérique Kermarrec and Arindam K Dey and Patricia Obeid and Arnaud Millet and Fabrice P Navarro and Patrice N Marche and Eric Sulpice and Xavier Gidrol},

doi = {10.1093/ecco-jcc/jjab129},

issn = {1876-4479},

year  = {2022},

date = {2022-02-01},

urldate = {2022-02-01},

journal = {J Crohns Colitis},

volume = {16},

number = {2},

pages = {286--300},

abstract = {BACKGROUND AND AIMS: Inflammatory bowel diseases are highly debilitating conditions that require constant monitoring and life-long medication. Current treatments are focused on systemic administration of immunomodulatory drugs, but they have a broad range of undesirable side-effects. RNA interference is a highly specific endogenous mechanism that regulates the expression of the gene at the transcript level, which can be repurposed using exogenous short interfering RNA [siRNA] to repress expression of the target gene. While siRNA therapeutics can offer an alternative to existing therapies, with a high specificity critical for chronically administrated drugs, evidence of their potency compared to chemical kinase inhibitors used in clinics is still lacking in alleviating an adverse inflammatory response.



METHODS: We provide a framework to select highly specific siRNA, with a focus on two kinases strongly involved in pro-inflammatory diseases, namely JAK1 and JAK3. Using western-blot, real-time quantitative PCR and large-scale analysis, we assessed the specificity profile of these siRNA drugs and compared their efficacy to the most recent and promising kinase inhibitors for Janus kinases [Jakinibs], tofacitinib and filgotinib.



RESULTS: siRNA drugs can reach higher efficiency and selectivity at lower doses [5 pM vs 1 µM] than Jakinibs. Moreover, JAK silencing lasted up to 11 days, even with 6 h pulse transfection.



CONCLUSIONS: The siRNA-based drugs developed hold the potential to develop more potent therapeutics for chronic inflammatory diseases.},

keywords = {omics},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36387187,

title = {Mass cytometry analysis reveals attrition of naïve and anergized self-reactive non-malignant B cells in chronic lymphocytic leukemia patients},

author = {Thibault Andrieu and Paul Mondière and Pierre-Emmanuel Jouve and Sébastien Dussurgey and Victor Malassigné and Hugo Servanton and Lucille Baseggio and Frédéric Davi and Anne-Sophie Michallet and Thierry Defrance},

doi = {10.3389/fonc.2022.1020740},

issn = {2234-943X},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Front Oncol},

volume = {12},

pages = {1020740},

abstract = {Chronic Lymphocytic Leukemia (CLL) is characterized by the progressive accumulation of monoclonal mature B lymphocytes. Autoimmune complications are common in CLL occurring in up to a quarter of all patients during the course of the illness. Etiology of autoimmunity in CLL is unknown but it is widely admitted that the pathogenic auto-Abs do not originate from the tumoral clone but from the non-malignant B cell pool. This indicates that the developmental scheme of non-malignant B cells could also be perturbed in CLL patients. To address this question, we have designed a B cell-centered antibody panel and used time-of-flight mass cytometry to compare the residual non-malignant B cell pool of CLL patients with the peripheral B cell pool of age-matched healthy donors. We show that the non-malignant B cell compartment of the patients is characterized by profound attrition of naïve B cells and of a population of anergized autoreactive B cells, suggesting impaired B cell lymphopoeisis as well as perturbations of the B cell tolerance checkpoints.},

keywords = {cytometry},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36091672,

title = {Diaphragm dysfunction after severe COVID-19: An ultrasound study},

author = {Alain Boussuges and Paul Habert and Guillaume Chaumet and Rawah Rouibah and Lea Delorme and Amelie Menard and Matthieu Million and Axel Bartoli and Eric Guedj and Marion Gouitaa and Laurent Zieleskiewicz and Julie Finance and Benjamin Coiffard and Stephane Delliaux and Fabienne Brégeon},

doi = {10.3389/fmed.2022.949281},

issn = {2296-858X},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Front Med (Lausanne)},

volume = {9},

pages = {949281},

abstract = {BACKGROUND: SARS-CoV-2 infection can impair diaphragm function at the acute phase but the frequency of diaphragm dysfunction after recovery from COVID-19 remains unknown.



MATERIALS AND METHODS: This study was carried out on patients reporting persistent respiratory symptoms 3-4 months after severe COVID-19 pneumonia. The included patients were selected from a medical consultation designed to screen for recovery after acute infection. Respiratory function was assessed by a pulmonary function test, and diaphragm function was studied by ultrasonography.



RESULTS: In total, 132 patients (85M, 47W) were recruited from the medical consultation. During the acute phase of the infection, the severity of the clinical status led to ICU admission for 58 patients (44%). Diaphragm dysfunction (DD) was detected by ultrasonography in 13 patients, two of whom suffered from hemidiaphragm paralysis. Patients with DD had more frequently muscle pain complaints and had a higher frequency of prior cardiothoracic or upper abdominal surgery than patients with normal diaphragm function. Pulmonary function testing revealed a significant decrease in lung volumes and DLCO and the dyspnea scores (mMRC and Borg10 scores) were significantly increased in patients with DD. Improvement in respiratory function was recorded in seven out of nine patients assessed 6 months after the first ultrasound examination.



CONCLUSION: Assessment of diaphragm function by ultrasonography after severe COVID-19 pneumonia revealed signs of dysfunction in 10% of our population. In some cases, ultrasound examination probably discovered an un-recognized pre-existing DD. COVID-19 nonetheless contributed to impairment of diaphragm function. Prolonged respiratory physiotherapy led to improvement in respiratory function in most patients.



CLINICAL TRIAL REGISTRATION: [www.cnil.fr], identifier [#PADS20-207].},

keywords = {medical data},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35464449b,

title = {Dichotomy in Neutralizing Antibody Induction to Peptide-Conjugated Vaccine in Squalene Emulsion Contrast With Aluminum Hydroxide Formulation},

author = {Olivia Bonduelle and Chloé Chaudesaigues and Monica Tolazzi and Ehsan Suleiman and Simon de Bernard and Karine Alves and Julien Nourikyan and Mylene Bohec and Laura G Baudrin and Dietmar Katinger and Patrice Debré and Gabriella Scarlatti and Vincent Vieillard and Behazine Combadière},

doi = {10.3389/fimmu.2022.848571},

issn = {1664-3224},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Front Immunol},

volume = {13},

pages = {848571},

abstract = {W614A-3S peptide is a modified 3S motif of the HIV-gp41 (mutation W614A). We previously detected the presence of natural neutralizing antibodies directed against W614A-3S peptide (NAbs) in long-term non-progressor HIV patients. Here, we compared the efficacy of W614A-3S peptide formulated in either squalene emulsion (SQE) or in aluminum hydroxide (Alum) in inducing broadly-NAbs (bNAbs). Rabbit and mouse models were used to screen the induction of bNAbs following 4 immunizations. SQE was more efficient than Alum formulation in inducing W614A-3S-specific bNAbs with up to 67%-93% of HIV strains neutralized. We then analyzed the quality of peptide-specific murine B cells by single-cell gene expression by quantitative reverse transcription-PCR and single-cell V(D)J sequencing. We found more frequent germinal center B cells in SQE than in Alum, albeit with a different gene expression profile. The V(D)J sequencing of W614A-3S-specific BCR showed significant differences in BCR sequences and validates the dichotomy between adjuvant formulations. All sixteen BCR sequences which were cloned were specific of peptide. Adjuvant formulations of W614A-3S-peptide-conjugated immunogen impact the quantity and quality of B cell immune responses at both the gene expression level and BCR sequence.},

keywords = {omics},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34174113,

title = {Unique molecular signatures typify skin inflammation induced by chemical allergens and irritants},

author = {Marine-Alexia Lefevre and Audrey Nosbaum and Aurore Rozieres and Vanina Lenief and Amandine Mosnier and Angèle Cortial and Margaux Prieux and Simon De Bernard and Julien Nourikyan and Pierre-Emmanuel Jouve and Laurent Buffat and Florence Hacard and Marie-Christine Ferrier-Lebouedec and Pauline Pralong and Charles Dzviga and Anne Herman and Marie Baeck and Jean-François Nicolas and Marc Vocanson},

doi = {10.1111/all.14989},

issn = {1398-9995},

year  = {2021},

date = {2021-12-01},

urldate = {2021-12-01},

journal = {Allergy},

volume = {76},

number = {12},

pages = {3697--3712},

abstract = {BACKGROUND: Skin exposure to chemicals may induce an inflammatory disease known as contact dermatitis (CD). Distinguishing the allergic and irritant forms of CD often proves challenging in the clinic.



METHODS: To characterize the molecular signatures of chemical-induced skin inflammation, we conducted a comprehensive transcriptomic analysis on the skin lesions of 47 patients with positive patch tests to reference contact allergens and nonallergenic irritants.



RESULTS: A clear segregation was observed between allergen- and irritant-induced gene profiles. Distinct modules pertaining to the epidermal compartment, metabolism, and proliferation were induced by both contact allergens and irritants; whereas only contact allergens prompted strong activation of adaptive immunity, notably of cytotoxic T-cell responses. Our results also confirmed that: (a) unique pathways characterize allergen- and irritant-induced dermatitis; (b) the intensity of the clinical reaction correlates with the magnitude of immune activation. Finally, using a machine-learning approach, we identified and validated several minimal combinations of biomarkers to distinguish contact allergy from irritation.



CONCLUSION: These results highlight the value of molecular profiling of chemical-induced skin inflammation for improving the diagnosis of allergic versus irritant contact dermatitis.},

keywords = {omics},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33973663,

title = {Low-Level Light Therapy Downregulates Scalp Inflammatory Biomarkers in Men With Androgenetic Alopecia and Boosts Minoxidil 2% to Bring a Sustainable Hair Regrowth Activity},

author = {Yann F Mahe and Ahsène Cheniti and Charlotte Tacheau and Rosaria Antonelli and Lien Planard-Luong and Simon de Bernard and Laurent Buffat and Philippe Barbarat and Leila Kanoun-Copy},

doi = {10.1002/lsm.23398},

issn = {1096-9101},

year  = {2021},

date = {2021-11-01},

urldate = {2021-11-01},

journal = {Lasers Surg Med},

volume = {53},

number = {9},

pages = {1208--1219},

abstract = {BACKGROUND AND OBJECTIVES: Low-level light therapies using visible to infrared light are known to activate several cellular functions, such as adenosine triphosphate and nitric oxide synthesis. However, few clinical observations report its biological consequences for skin and scalp homeostasis. Since scalp inflammation was recognized as a potential physiological obstacle to the efficacy of the reference hair regrowth drug Minoxidil in vivo and since perifollicular inflammation is the hallmark of about 50%-70% follicular units in androgenetic alopecia, we decided to investigate whether the anti-inflammatory activity of LLLT/GentleWaves® device were assigned to L'Oréal by Light BioScience L.L.C., Virginia Beach, VA (US) could enhance hair regrowth activity of Minoxidil.



STUDY DESIGN/MATERIALS AND METHODS: We conducted a first experimental clinical study on 64 men with androgenetic alopecia using LLLT/GentleWaves®, 590-nm predominant wavelength 70 seconds, specifically pulsed once per day, for 3 days, and we performed a whole-genome analysis of treated scalp biopsies. In a second clinical study, including 135 alopecic volunteers, we evaluated the hair regrowth activity in response to the upgraded LLLT/GentleWaves® device and Minoxidil.



RESULTS: In the first clinical study, whole-genome analysis of treated scalp biopsies showed downregulation of scalp inflammatory biomarkers, such as AP1/FOSB messenger RNA (mRNA) and mir21, together with the disappearance of CD69 mRNA, specific to scalp-infiltrating T cells of about 50% of the studied volunteers prior to the LLLT/GentleWaves® treatment. In the second clinical study, we observed that LLLT/GentleWaves® was able to boost the hair regrowth activity of a Minoxidil 2% lotion to the extent of the highest concentration (5%) in terms of efficacy, number of responders, and perceived performance.



CONCLUSIONS: Altogether, these observations suggest the potential benefit of LLLT/GentleWaves® as a noninvasive adjunctive technology for skin and scalp conditions, where a mild perifollicular inflammation is involved. Lasers Surg. Med. 2021. Copyright © 2021 Wiley Periodicals LLC.},

keywords = {omics},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33626291,

title = {Humoral and cellular immunogenicity and safety following a booster dose of a tetravalent dengue vaccine 5+ years after completion of the primary series in Singapore: 2-year follow-up of a randomized phase II, placebo-controlled trial},

author = {Juliana Park and Sophia Archuleta and May-Lin Helen Oh and Lynette Pei-Chi Shek and Hao Wang and Matthew Bonaparte and Carina Frago and Alain Bouckenooghe and Frederique Jantet-Blaudez and Sarah Begue and Sophie Gimenez-Fourage and Anke Pagnon},

doi = {10.1080/21645515.2020.1861875},

issn = {2164-554X},

year  = {2021},

date = {2021-07-01},

urldate = {2021-07-01},

journal = {Hum Vaccin Immunother},

volume = {17},

number = {7},

pages = {2107--2116},

abstract = {The tetravalent dengue vaccine (CYD-TDV) is approved for use as a 3-dose series for the prevention of dengue in seropositive individuals ≥9 years. A randomized, placebo-controlled, phase II study of a booster dose of CYD-TDV in individuals who completed the 3-dose schedule >5 years previously (NCT02824198), demonstrated that a booster restored neutralizing antibody titers to post-dose 3 levels. We present additional immunogenicity assessments up to 24 months post-booster, and B- and T-cell responses in a participant subset. Participants aged 9-45 years that had received all three doses of CYD-TDV were randomized 3:1 to receive a booster dose of CYD-TDV (n = 89) or placebo (n = 29). Neutralizing antibody levels at Months 1, 6, 12, and 24 post-booster were assessed by plaque reduction neutralization test. In a subset, B-cell responses were assessed by a fluorescent immunospot assay, and T-cells analyzed by flow cytometry at Days 0, 7, 12, Months 1 and 12. We observed an increase of antibody titers Month 1 post-booster, then a gradual decline to Month 24. In the CYD-TDV booster group, an increase in plasmablasts was seen at Day 7 declining by Day 14, an increase in memory B-cells was observed at Day 28 with no persistence at Month 12. CYD-TDV booster recalled a CD8+ T-cell response, dominated by IFN-γ secretion, which decreased 12 months post-booster. This study showed a short-term increase in antibody titers and then gradual decrease following CYD-TDV booster injection >5 years after primary immunization, and the presence of memory B-cells activated following the booster, but with low persistence.},

keywords = {cytometry},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33497037,

title = {Integrative Analysis Reveals a Molecular Stratification of Systemic Autoimmune Diseases},

author = {Guillermo Barturen and Sepideh Babaei and Francesc Català-Moll and Manuel Martínez-Bueno and Zuzanna Makowska and Jordi Martorell-Marugán and Pedro Carmona-Sáez and Daniel Toro-Domínguez and Elena Carnero-Montoro and María Teruel and Martin Kerick and Marialbert Acosta-Herrera and Lucas Le Lann and Christophe Jamin and Javier Rodríguez-Ubreva and Antonio García-Gómez and Jorge Kageyama and Anne Buttgereit and Sikander Hayat and Joerg Mueller and Ralf Lesche and Maria Hernandez-Fuentes and Maria Juarez and Tania Rowley and Ian White and Concepción Marañón and Tania Gomes Anjos and Nieves Varela and Rocío Aguilar-Quesada and Francisco Javier Garrancho and Antonio López-Berrio and Manuel Rodriguez Maresca and Héctor Navarro-Linares and Isabel Almeida and Nancy Azevedo and Mariana Brandão and Ana Campar and Raquel Faria and Fátima Farinha and António Marinho and Esmeralda Neves and Ana Tavares and Carlos Vasconcelos and Elena Trombetta and Gaia Montanelli and Barbara Vigone and Damiana Alvarez-Errico and Tianlu Li and Divya Thiagaran and Ricardo Blanco Alonso and Alfonso Corrales Martínez and Fernanda Genre and Raquel López Mejías and Miguel A Gonzalez-Gay and Sara Remuzgo and Begoña Ubilla Garcia and Ricard Cervera and Gerard Espinosa and Ignasi Rodríguez-Pintó and Ellen De Langhe and Jonathan Cremer and Rik Lories and Doreen Belz and Nicolas Hunzelmann and Niklas Baerlecken and Katja Kniesch and Torsten Witte and Michaela Lehner and Georg Stummvoll and Michael Zauner and Maria Angeles Aguirre-Zamorano and Nuria Barbarroja and Maria Carmen Castro-Villegas and Eduardo Collantes-Estevez and Enrique de Ramon and Isabel Díaz Quintero and Alejandro Escudero-Contreras and María Concepción Fernández Roldán and Yolanda Jiménez Gómez and Inmaculada Jiménez Moleón and Rosario Lopez-Pedrera and Rafaela Ortega-Castro and Norberto Ortego and Enrique Raya and Carolina Artusi and Maria Gerosa and Pier Luigi Meroni and Tommaso Schioppo and Aurélie De Groof and Julie Ducreux and Bernard Lauwerys and Anne-Lise Maudoux and Divi Cornec and Valérie Devauchelle-Pensec and Sandrine Jousse-Joulin and Pierre-Emmanuel Jouve and Bénédicte Rouvière and Alain Saraux and Quentin Simon and Montserrat Alvarez and Carlo Chizzolini and Aleksandra Dufour and Donatienne Wynar and Attila Balog and Márta Bocskai and Magdolna Deák and Sonja Dulic and Gabriella Kádár and László Kovács and Qingyu Cheng and Velia Gerl and Falk Hiepe and Laleh Khodadadi and Silvia Thiel and Emanuele de Rinaldis and Sambasiva Rao and Robert J Benschop and Chris Chamberlain and Ernst R Dow and Yiannis Ioannou and Laurence Laigle and Jacqueline Marovac and Jerome Wojcik and Yves Renaudineau and Maria Orietta Borghi and Johan Frostegård and Javier Martín and Lorenzo Beretta and Esteban Ballestar and Fiona McDonald and Jacques-Olivier Pers and Marta E Alarcón-Riquelme},

doi = {10.1002/art.41610},

issn = {2326-5205},

year  = {2021},

date = {2021-06-01},

urldate = {2021-06-01},

journal = {Arthritis Rheumatol},

volume = {73},

number = {6},

pages = {1073--1085},

abstract = {OBJECTIVE: Clinical heterogeneity, a hallmark of systemic autoimmune diseases, impedes early diagnosis and effective treatment, issues that may be addressed if patients could be classified into groups defined by molecular pattern. This study was undertaken to identify molecular clusters for reclassifying systemic autoimmune diseases independently of clinical diagnosis.



METHODS: Unsupervised clustering of integrated whole blood transcriptome and methylome cross-sectional data on 955 patients with 7 systemic autoimmune diseases and 267 healthy controls was undertaken. In addition, an inception cohort was prospectively followed up for 6 or 14 months to validate the results and analyze whether or not cluster assignment changed over time.



RESULTS: Four clusters were identified and validated. Three were pathologic, representing "inflammatory," "lymphoid," and "interferon" patterns. Each included all diagnoses and was defined by genetic, clinical, serologic, and cellular features. A fourth cluster with no specific molecular pattern was associated with low disease activity and included healthy controls. A longitudinal and independent inception cohort showed a relapse-remission pattern, where patients remained in their pathologic cluster, moving only to the healthy one, thus showing that the molecular clusters remained stable over time and that single pathogenic molecular signatures characterized each individual patient.



CONCLUSION: Patients with systemic autoimmune diseases can be jointly stratified into 3 stable disease clusters with specific molecular patterns differentiating different molecular disease mechanisms. These results have important implications for future clinical trials and the study of nonresponse to therapy, marking a paradigm shift in our view of systemic autoimmune diseases.},

keywords = {cytometry},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33334933,

title = {Identifying early pulmonary arterial hypertension biomarkers in systemic sclerosis: machine learning on proteomics from the DETECT cohort},

author = {Yasmina Bauer and Simon de Bernard and Peter Hickey and Karri Ballard and Jeremy Cruz and Peter Cornelisse and Harbajan Chadha-Boreham and Oliver Distler and Daniel Rosenberg and Martin Doelberg and Sebastien Roux and Oliver Nayler and Allan Lawrie},

doi = {10.1183/13993003.02591-2020},

issn = {1399-3003},

year  = {2021},

date = {2021-06-01},

urldate = {2021-06-01},

journal = {Eur Respir J},

volume = {57},

number = {6},

abstract = {Pulmonary arterial hypertension (PAH) is a devastating complication of systemic sclerosis (SSc). Screening for PAH in SSc has increased detection, allowed early treatment for PAH and improved patient outcomes. Blood-based biomarkers that reliably identify SSc patients at risk of PAH, or with early disease, would significantly improve screening, potentially leading to improved survival, and provide novel mechanistic insights into early disease. The main objective of this study was to identify a proteomic biomarker signature that could discriminate SSc patients with and without PAH using a machine learning approach and to validate the findings in an external cohort.Serum samples from patients with SSc and PAH (n=77) and SSc without pulmonary hypertension (non-PH) (n=80) were randomly selected from the clinical DETECT study and underwent proteomic screening using the Myriad RBM Discovery platform consisting of 313 proteins. Samples from an independent validation SSc cohort (PAH n=22 and non-PH n=22) were obtained from the University of Sheffield (Sheffield, UK).Random forest analysis identified a novel panel of eight proteins, comprising collagen IV, endostatin, insulin-like growth factor binding protein (IGFBP)-2, IGFBP-7, matrix metallopeptidase-2, neuropilin-1, N-terminal pro-brain natriuretic peptide and RAGE (receptor for advanced glycation end products), that discriminated PAH from non-PH in SSc patients in the DETECT Discovery Cohort (average area under the receiver operating characteristic curve 0.741, 65.1% sensitivity/69.0% specificity), which was reproduced in the Sheffield Confirmatory Cohort (81.1% accuracy, 77.3% sensitivity/86.5% specificity).This novel eight-protein biomarker panel has the potential to improve early detection of PAH in SSc patients and may provide novel insights into the pathogenesis of PAH in the context of SSc.},

keywords = {omics},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34112769,

title = {A new molecular classification to drive precision treatment strategies in primary Sjögren's syndrome},

author = {Perrine Soret and Christelle Le Dantec and Emiko Desvaux and Nathan Foulquier and Bastien Chassagnol and Sandra Hubert and Christophe Jamin and Guillermo Barturen and Guillaume Desachy and Valérie Devauchelle-Pensec and Cheïma Boudjeniba and Divi Cornec and Alain Saraux and Sandrine Jousse-Joulin and Nuria Barbarroja and Ignasi Rodríguez-Pintó and Ellen De Langhe and Lorenzo Beretta and Carlo Chizzolini and László Kovács and Torsten Witte and Eléonore Bettacchioli and Anne Buttgereit and Zuzanna Makowska and Ralf Lesche and Maria Orietta Borghi and Javier Martin and Sophie Courtade-Gaiani and Laura Xuereb and Mickaël Guedj and Philippe Moingeon and Marta E Alarcón-Riquelme and Laurence Laigle and Jacques-Olivier Pers},

doi = {10.1038/s41467-021-23472-7},

issn = {2041-1723},

year  = {2021},

date = {2021-06-01},

urldate = {2021-06-01},

journal = {Nat Commun},

volume = {12},

number = {1},

pages = {3523},

abstract = {There is currently no approved treatment for primary Sjögren's syndrome, a disease that primarily affects adult women. The difficulty in developing effective therapies is -in part- because of the heterogeneity in the clinical manifestation and pathophysiology of the disease. Finding common molecular signatures among patient subgroups could improve our understanding of disease etiology, and facilitate the development of targeted therapeutics. Here, we report, in a cross-sectional cohort, a molecular classification scheme for Sjögren's syndrome patients based on the multi-omic profiling of whole blood samples from a European cohort of over 300 patients, and a similar number of age and gender-matched healthy volunteers. Using transcriptomic, genomic, epigenetic, cytokine expression and flow cytometry data, combined with clinical parameters, we identify four groups of patients with distinct patterns of immune dysregulation. The biomarkers we identify can be used by machine learning classifiers to sort future patients into subgroups, allowing the re-evaluation of response to treatments in clinical trials.},

keywords = {cytometry},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34916955b,

title = {Changes in Diaphragmatic Function Induced by an Increased Inspiratory Load Experienced by Military Divers: An Ultrasound Study},

author = {Sarah Rives and Bruno Schmid and Guillaume Chaumet and Fabienne Brégeon and Alain Boussuges},

doi = {10.3389/fphys.2021.756533},

issn = {1664-042X},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {Front Physiol},

volume = {12},

pages = {756533},

abstract = { Inspiratory loading is experienced by military divers when they use rebreather device. Our objective was to assess the changes in diaphragm function induced by an increase in inspiratory load at values similar to those experienced by divers in real life. : We recorded the excursion and the thickness of the right hemidiaphragm in 22 healthy male volunteers under inspiratory load conditions, using ultrasound in B- and M-mode. The measurements were performed at tidal volume and during breathing at 50% of inspiratory capacity. The breathing rate was regulated and similar in the various sessions with and without load.  The rebreather device used by French military divers leads to an increase in inspiratory load of close to 30 cmHO. Consequently, the session under load was performed using a device set to this threshold. Significant increases in the excursion and the thickening fraction of the diaphragm were observed between the sessions at tidal volume and at high volume. With addition of the inspiratory load, the excursion of the right hemidiaphragm increased significantly from 2.3 to 3.4cm at tidal volume and from 3.9 to 4.7cm at high volume. The thickening fraction increased significantly from 30.4 to 76.6% at tidal volume and from 70 to 123% at high volume. The statistical analysis demonstrated that assessment of the changes of the thickening fraction during breathing at tidal volume was the most relevant marker to assess the impact of the inspiratory load on the diaphragm.  Diaphragm ultrasound can be used to assess the changes in the diaphragm contraction pattern secondary to an increase in the respiratory load that can be generated by use a diving apparatus. The recording of the changes of the motion, and more importantly of the thickness of the diaphragm, during the breathing cycle is able to provide relevant information regarding the inspiratory load.},

keywords = {medical data},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33778044,

title = {Diaphragmatic motion recorded by M-mode ultrasonography: limits of normality},

author = {Alain Boussuges and Julie Finance and Guillaume Chaumet and Fabienne Brégeon},

doi = {10.1183/23120541.00714-2020},

issn = {2312-0541},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {ERJ Open Res},

volume = {7},

number = {1},

abstract = {Chest ultrasonography has proven to be useful in the diagnosis of diaphragm dysfunction. The aim of the present study was to determine the normal values of the motion of both hemidiaphragms recorded by M-mode ultrasonography. Healthy volunteers were studied while in a seated position. Diaphragmatic excursions and diaphragm profiles were measured during quiet breathing, voluntary sniffing and deep breathing. Diaphragmatic excursions were assessed by M-mode ultrasonography, using an approach perpendicular to the posterior part of the diaphragm. Anatomical M-mode was used for the recording of the complete excursion during deep breathing. The study included 270 men and 140 women. The diaphragmatic motions during quiet breathing and voluntary sniffing were successfully recorded in all of the participants. The use of anatomical M-mode was particularly suitable for measurement of the entire diaphragmatic excursion during deep breathing. The statistical analysis showed that the diaphragmatic excursions were larger in men compared to women, supporting the determination of normal values based on sex. The lower and upper limits of normal excursion were determined for men and women for both hemidiaphragms during the three manoeuvres that were investigated. The lower limits of normal diaphragmatic excursions during deep breathing should be used to detect diaphragmatic hypokinesia,  3.3 and 3.2 cm in women and 4.1 and 4.2 cm in men for the right and the left sides, respectively. The normal values of the diaphragmatic motion and the lower and upper limits of normal excursion can be used by clinicians to detect diaphragmatic dysfunction.},

keywords = {medical data},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34778304b,

title = {Ultrasound Assessment of Diaphragm Thickness and Thickening: Reference Values and Limits of Normality When in a Seated Position},

author = {Alain Boussuges and Sarah Rives and Julie Finance and Guillaume Chaumet and Nicolas Vallée and Jean-Jacques Risso and Fabienne Brégeon},

doi = {10.3389/fmed.2021.742703},

issn = {2296-858X},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {Front Med (Lausanne)},

volume = {8},

pages = {742703},

abstract = { Diagnosing diaphragm dysfunction in the absence of complete paralysis remains difficult. The aim of the present study was to assess the normal values of the thickness and the inspiratory thickening of both hemidiaphragms as measured by ultrasonography in healthy volunteers while in a seated position.  Healthy volunteers with a normal pulmonary function test were recruited. The diaphragmatic thickness was measured on both sides at the zone of apposition of the diaphragm to the rib cage during quiet breathing at end-expiration, end-inspiration, and after maximal inspiration. The thickening ratio, the thickening fraction, and the thickness at end-inspiration divided by the thickness at deep breathing were determined. The mean values and the lower and upper limits of normal were determined for men and women.  200 healthy volunteers (100 men and 100 women) were included in the study. The statistical analysis revealed that women had a thinner hemidiaphragm than men on both sides and at the various breathing times studied. The lower limit of normality of the diaphragm thickness measured at end-expiration was estimated to be 1.3 mm in men and 1.1 mm in women, on both sides. The thickening fraction did not differ significantly between men and women. In men, it ranged from 60 to 260% on the left side and from 57 to 200% on the right side. In women, it ranged from 58 to 264% on the left side and from 60 to 229% on the right side. The lower limits of normality of the thickening fraction were determined to be 40 and 39% in men and 39 and 48% in women for the right and left hemidiaphragms, respectively. The upper limit for normal of the mean of both sides of the ratio thickness at end-inspiration divided by the thickness at deep breathing was determined to be 0.78 in women and 0.79 in men.  The normal values of thickness and the indexes of diaphragmatic function should help clinicians with detecting diaphragm atrophy and dysfunction.},

keywords = {medical data},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33004331,

title = {Genomic Risk Score impact on susceptibility to systemic sclerosis},

author = {Lara Bossini-Castillo and Gonzalo Villanueva-Martin and Martin Kerick and Marialbert Acosta-Herrera and Elena López-Isac and Carmen P Simeón and Norberto Ortego-Centeno and Shervin Assassi and Nicolas Hunzelmann and Armando Gabrielli and J K de Vries-Bouwstra and Yannick Allanore and Carmen Fonseca and Christopher P Denton and Timothy Rdj Radstake and Marta Eugenia Alarcón-Riquelme and Lorenzo Beretta and Maureen D Mayes and Javier Martin},

doi = {10.1136/annrheumdis-2020-218558},

issn = {1468-2060},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {Ann Rheum Dis},

volume = {80},

number = {1},

pages = {118--127},

abstract = {OBJECTIVES: Genomic Risk Scores (GRS) successfully demonstrated the ability of genetics to identify those individuals at high risk for complex traits including immune-mediated inflammatory diseases (IMIDs). We aimed to test the performance of GRS in the prediction of risk for systemic sclerosis (SSc) for the first time.



METHODS: Allelic effects were obtained from the largest SSc Genome-Wide Association Study (GWAS) to date (9 095 SSc and 17 584 healthy controls with European ancestry). The best-fitting GRS was identified under the additive model in an independent cohort that comprised 400 patients with SSc and 571 controls. Additionally, GRS for clinical subtypes (limited cutaneous SSc and diffuse cutaneous SSc) and serological subtypes (anti-topoisomerase positive (ATA+) and anti-centromere positive (ACA+)) were generated. We combined the estimated GRS with demographic and immunological parameters in a multivariate generalised linear model.



RESULTS: The best-fitting SSc GRS included 33 single nucleotide polymorphisms (SNPs) and discriminated between patients with SSc and controls (area under the receiver operating characteristic (ROC) curve (AUC)=0.673). Moreover, the GRS differentiated between SSc and other IMIDs, such as rheumatoid arthritis and Sjögren's syndrome. Finally, the combination of GRS with age and immune cell counts significantly increased the performance of the model (AUC=0.787). While the SSc GRS was not able to discriminate between ATA+ and ACA+ patients (AUC<0.5), the serological subtype GRS, which was based on the allelic effects observed for the comparison between ACA+ and ATA+ patients, reached an AUC=0.693.



CONCLUSIONS: GRS was successfully implemented in SSc. The model discriminated between patients with SSc and controls or other IMIDs, confirming the potential of GRS to support early and differential diagnosis for SSc.},

keywords = {cytometry},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32573786,

title = {Dysregulation of microRNA expression in the skin during cutaneous adverse drug reactions},

author = {Eric Pedruzzi and François Chasset and Isabelle Duroux-Richard and David Bocarra and Florence Apparailly and Julien Nourikyan and Mathilde Lumy and Simon de Bernard and Olivia Bonduelle and Laurent Buffat and Behazine Combadière and Angèle Soria},

doi = {10.1111/all.14464},

issn = {1398-9995},

year  = {2020},

date = {2020-12-01},

urldate = {2020-12-01},

journal = {Allergy},

volume = {75},

number = {12},

pages = {3279--3283},

keywords = {omics},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32052923,

title = {AVAPS-AE versus ST mode: A randomized controlled trial in patients with obesity hypoventilation syndrome},

author = {Maxime Patout and Frédéric Gagnadoux and Claudio Rabec and Wojciech Trzepizur and Marjolaine Georges and Christophe Perrin and Renaud Tamisier and Jean-Louis Pépin and Claudia Llontop and Valerie Attali and Frederic Goutorbe and Sandrine Pontier-Marchandise and Pierre Cervantes and Vanessa Bironneau and Adriana Portmann and Jacqueline Delrieu and Antoine Cuvelier and Jean-François Muir},

doi = {10.1111/resp.13784},

issn = {1440-1843},

year  = {2020},

date = {2020-10-01},

urldate = {2020-10-01},

journal = {Respirology},

volume = {25},

number = {10},

pages = {1073--1081},

abstract = {BACKGROUND AND OBJECTIVE: Average volume-assured pressure support-automated expiratory positive airway pressure (AVAPS-AE) combines an automated positive expiratory pressure to maintain upper airway patency to an automated pressure support with a targeted tidal volume. The aim of this study was to compare the effects of 2-month AVAPS-AE ventilation versus pressure support (ST) ventilation on objective sleep quality in stable patients with OHS. Secondary outcomes included arterial blood gases, health-related quality of life, daytime sleepiness, subjective sleep quality and compliance to NIV.



METHODS: This is a prospective multicentric randomized controlled trial. Consecutive OHS patients included had daytime P CO  > 6 kPa, BMI ≥ 30 kg/m , clinical stability for more than 2 weeks and were naive from home NIV. PSG were analysed centrally by two independent experts. Primary endpoint was sleep quality improvement at 2 months.



RESULTS: Among 69 trial patients, 60 patients had successful NIV setup. Baseline and follow-up PSG were available for 26 patients randomized in the ST group and 30 in the AVAPS-AE group. At baseline, P CO was 6.94 ± 0.71 kPa in the ST group and 6.61 ± 0.71 in the AVAPS-AE group (P = 0.032). No significant between-group difference was observed for objective sleep quality indices. Improvement in P CO was similar between groups with a mean reduction of -0.87 kPa (95% CI: -1.12 to -0.46) in the ST group versus -0.87 kPa (95% CI: -1.14 to -0.50) in the AVAPS-AE group (P = 0.984). Mean NIV use was 6.2 h per night in both groups (P = 0.93). NIV setup duration was shorter in the AVAPS-AE group (P = 0.012).



CONCLUSION: AVAPS-AE and ST ventilation for 2 months had similar impact on sleep quality and gas exchange.},

keywords = {medical data},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32998444,

title = {When the Search for Stemness Genes Meets the Skin Substitute Bioengineering Field: KLF4 Transcription Factor under the Light},

author = {Nicolas O Fortunel and Michèle T Martin},

doi = {10.3390/cells9102188},

issn = {2073-4409},

year  = {2020},

date = {2020-09-01},

urldate = {2020-09-01},

journal = {Cells},

volume = {9},

number = {10},

abstract = {The transcription factor "Kruppel-like factor 4" (KLF4) is a central player in the field of pluripotent stem cell biology. In particular, it was put under the spotlight as one of the four factors of the cocktail originally described for reprogramming into induced pluripotent stem cells (iPSCs). In contrast, its possible functions in native tissue stem cells remain largely unexplored. We recently published that KLF4 is a regulator of "stemness" in human keratinocytes. We show that reducing the level of expression of this transcription factor by RNA interference or pharmacological repression promotes the ex vivo amplification and regenerative capacity of two types of cells of interest for cutaneous cell therapy: native keratinocyte stem and progenitor cells from adult epidermis, which have been used for more than three decades in skin graft bioengineering, and keratinocytes generated by the lineage-oriented differentiation of embryonic stem cells (ESCs), which have potential for the development of skin bio-bandages. At the mechanistic level, KLF4 repression alters the expression of a large set of genes involved in TGF-β1 and WNT signaling pathways. Major regulators of TGF-β bioavailability and different TGF-β receptors were targeted, notably modulating the ALK1/Smad1/5/9 axis. At a functional level, KLF4 repression produced an antagonist effect on TGFβ1-induced keratinocyte differentiation.},

keywords = {omics},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32561607,

title = {Genome-wide whole blood transcriptome profiling in a large European cohort of systemic sclerosis patients},

author = {Lorenzo Beretta and Guillermo Barturen and Barbara Vigone and Chiara Bellocchi and Nicolas Hunzelmann and Ellen De Langhe and Ricard Cervera and Maria Gerosa and László Kovács and Rafaela Ortega Castro and Isabel Almeida and Divi Cornec and Carlo Chizzolini and Jacques-Olivier Pers and Zuzanna Makowska and Ralf Lesche and Martin Kerick and Marta Eugenia Alarcón-Riquelme and Javier Martin },

doi = {10.1136/annrheumdis-2020-217116},

issn = {1468-2060},

year  = {2020},

date = {2020-09-01},

urldate = {2020-09-01},

journal = {Ann Rheum Dis},

volume = {79},

number = {9},

pages = {1218--1226},

abstract = {OBJECTIVES: The analysis of annotated transcripts from genome-wide expression studies may help to understand the pathogenesis of complex diseases, such as systemic sclerosis (SSc). We performed a whole blood (WB) transcriptome analysis on RNA collected in the context of the European PRECISESADS project, aiming at characterising the pathways that differentiate SSc from controls and that are reproducible in geographically diverse populations.



METHODS: Samples from 162 patients and 252 controls were collected in RNA stabilisers. Cases and controls were divided into a discovery (n=79+163; Southern Europe) and validation cohort (n=83+89; Central-Western Europe). RNA sequencing was performed by an Illumina assay. Functional annotations of Reactome pathways were performed with the Functional Analysis of Individual Microarray Expression (FAIME) algorithm. In parallel, immunophenotyping of 28 circulating cell populations was performed. We tested the presence of differentially expressed genes/pathways and the correlation between absolute cell counts and RNA transcripts/FAIME scores in regression models. Results significant in both populations were considered as replicated.



RESULTS: Overall, 15 224 genes and 1277 functional pathways were available; of these, 99 and 225 were significant in both sets. Among replicated pathways, we found a deregulation in type-I interferon, Toll-like receptor cascade, tumour suppressor p53 protein function, platelet degranulation and activation. RNA transcripts or FAIME scores were jointly correlated with cell subtypes with strong geographical differences; neutrophils were the major determinant of gene expression in SSc-WB samples.



CONCLUSIONS: We discovered a set of differentially expressed genes/pathways validated in two independent sets of patients with SSc, highlighting a number of deregulated processes that have relevance for the pathogenesis of autoimmunity and SSc.},

keywords = {cytometry},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32665668,

title = {Standardization procedure for flow cytometry data harmonization in prospective multicenter studies},

author = {Lucas Le Lann and Pierre-Emmanuel Jouve and Marta Alarcón-Riquelme and Christophe Jamin and Jacques-Olivier Pers},

doi = {10.1038/s41598-020-68468-3},

issn = {2045-2322},

year  = {2020},

date = {2020-07-01},

urldate = {2020-07-01},

journal = {Sci Rep},

volume = {10},

number = {1},

pages = {11567},

abstract = {One of the most challenging objective for clinical cytometry in prospective multicenter immunomonitoring trials is to compare frequencies, absolute numbers of leukocyte populations and further the mean fluorescence intensities of cell markers, especially when the data are generated from different instruments. Here, we describe an innovative standardization workflow to compare all data to carry out any large-scale, prospective multicentric flow cytometry analysis whatever the duration, the number or type of instruments required for the realization of such projects.},

keywords = {cytometry},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32264937,

title = {Delayed persistence of elevated monocytic MDSC associates with deleterious outcomes in septic shock: a retrospective cohort study},

author = {Louis Waeckel and Fabienne Venet and Morgane Gossez and Céline Monard and Thomas Rimmelé and Guillaume Monneret},

doi = {10.1186/s13054-020-02857-y},

issn = {1466-609X},

year  = {2020},

date = {2020-04-01},

urldate = {2020-04-01},

journal = {Crit Care},

volume = {24},

number = {1},

pages = {132},

keywords = {cytometry},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32231305,

title = {Netrin-1 promotes naive pluripotency through Neo1 and Unc5b co-regulation of Wnt and MAPK signalling},

author = {Aurélia Huyghe and Giacomo Furlan and Duygu Ozmadenci and Christina Galonska and Jocelyn Charlton and Xavier Gaume and Noémie Combémorel and Christina Riemenschneider and Nicolas Allègre and Jenny Zhang and Pauline Wajda and Nicolas Rama and Pauline Vieugué and Isabelle Durand and Marie Brevet and Nicolas Gadot and Thomas Imhof and Bradley J Merrill and Manuel Koch and Patrick Mehlen and Claire Chazaud and Alexander Meissner and Fabrice Lavial},

doi = {10.1038/s41556-020-0483-2},

issn = {1476-4679},

year  = {2020},

date = {2020-04-01},

urldate = {2020-04-01},

journal = {Nat Cell Biol},

volume = {22},

number = {4},

pages = {389--400},

abstract = {In mouse embryonic stem cells (mESCs), chemical blockade of Gsk3α/β and Mek1/2 (2i) instructs a self-renewing ground state whose endogenous inducers are unknown. Here we show that the axon guidance cue Netrin-1 promotes naive pluripotency by triggering profound signalling, transcriptomic and epigenetic changes in mESCs. Furthermore, we demonstrate that Netrin-1 can substitute for blockade of Gsk3α/β and Mek1/2 to sustain self-renewal of mESCs in combination with leukaemia inhibitory factor and regulates the formation of the mouse pluripotent blastocyst. Mechanistically, we reveal how Netrin-1 and the balance of its receptors Neo1 and Unc5B co-regulate Wnt and MAPK pathways in both mouse and human ESCs. Netrin-1 induces Fak kinase to inactivate Gsk3α/β and stabilize β-catenin while increasing the phosphatase activity of a Ppp2r2c-containing Pp2a complex to reduce Erk1/2 activity. Collectively, this work identifies Netrin-1 as a regulator of pluripotency and reveals that it mediates different effects in mESCs depending on its receptor dosage, opening perspectives for balancing self-renewal and lineage commitment.},

keywords = {omics},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33244316,

title = {Immune Profiles Identification by Vaccinomics After MVA Immunization in Randomized Clinical Study},

author = {Jorge Sanchez and Elena Gonçalves and Anuska Llano and Pedro Gonzáles and María Fernández-Maldonado and Annika Vogt and Angele Soria and Susana Perez and Samandhy Cedeño and Marco Antonio Fernández and Julien Nourikyan and Simon de Bernard and Carmela Ganoza and Eric Pedruzzi and Olivia Bonduelle and Beatriz Mothe and Carmen E Gòmez and Mariano Esteban and Felipe Garcia and Javier R Lama and Christian Brander and Behazine Combadiere},

doi = {10.3389/fimmu.2020.586124},

issn = {1664-3224},

year  = {2020},

date = {2020-01-01},

urldate = {2020-01-01},

journal = {Front Immunol},

volume = {11},

pages = {586124},

abstract = {BACKGROUND: Our previous work has demonstrated the benefits of transcutaneous immunization in targeting Langerhans cells and preferentially inducing CD8 T-cell responses.



METHODS: In this randomized phase Ib clinical trial including 20 HIV uninfected volunteers, we compared the safety and immunogenicity of the MVA recombinant vaccine expressing HIV-B antigen (MVA-B) by transcutaneous and intramuscular routes. We hypothesized that the quality of innate and adaptive immunity differs according to the route of immunization and explored the quality of the vector vaccine-induced immune responses. We also investigated the early blood transcriptome and serum cytokine levels to identify innate events correlated with the strength and quality of adaptive immunity.



RESULTS: We demonstrate that MVA-B vaccine is safe by both routes, but that the quality and intensity of both innate and adaptive immunity differ significantly. Transcutaneous vaccination promoted CD8 responses in the absence of antibodies and slightly affected gene expression, involving mainly genes associated with metabolic pathways. Intramuscular vaccination, on the other hand, drove robust changes in the expression of genes involved in IL-6 and interferon signalling pathways, mainly those associated with humoral responses, and also some levels of CD8 response.



CONCLUSION: Thus, vaccine delivery route perturbs early innate responses that shape the quality of adaptive immunity.



CLINICAL TRIAL REGISTRATION: http://ClinicalTrials.gov, identifier PER-073-13.},

keywords = {omics},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32116800,

title = {Hyperoxia During Exercise: Impact on Adenosine Plasma Levels and Hemodynamic Data},

author = {Alain Boussuges and Sarah Rives and Marion Marlinge and Guillaume Chaumet and Nicolas Vallée and Régis Guieu and Olivier Gavarry},

doi = {10.3389/fphys.2020.00097},

issn = {1664-042X},

year  = {2020},

date = {2020-01-01},

urldate = {2020-01-01},

journal = {Front Physiol},

volume = {11},

pages = {97},

abstract = {INTRODUCTION: Adenosine is an ATP derivative that is strongly implicated in the cardiovascular adaptive response to exercise. In this study, we hypothesized that during exercise the hyperemia, commonly observed during exercise in air, was counteracted by the downregulation of the adenosinergic pathway during hyperoxic exposure.



METHODS: Ten healthy volunteers performed two randomized sessions including gas exposure (Medical air or Oxygen) at rest and during exercise performed at 40% of maximal intensity, according to the individual fitness of the volunteers. Investigations included the measurement of adenosine plasma level (APL) and the recording of hemodynamic data [i.e., cardiac output (CO) and systemic vascular resistances (SVR) using pulsed Doppler and echocardiography].



RESULTS: Hyperoxia significantly decreased APL (from 0.58 ± 0.06 to 0.21 ± 0.05 μmol L,  < 0.001) heart rate and CO and increased SVR in healthy volunteers at rest. During exercise, an increase in APL was recorded in the two sessions when compared with measurements at rest (+0.4 ± 0.4 vs. +0.3 ± 0.2 μmol L for medical air and oxygen exposures, respectively). APL was lower during the exercise performed under hyperoxia when compared with medical air exposure (0.5 ± 0.06 vs. 1.03 ± 0.2 μmol L, respectively  < 0.001). This result could contribute to the hemodynamic differences between the two conditions, such as the increase in SVR and the decrease in both heart rate and CO when exercises were performed during oxygen exposure as compared to medical air.



CONCLUSION: Hyperoxia decreased APLs in healthy volunteers at rest but did not eliminate the increase in APL and the decrease in SVR during low intensity exercise.},

keywords = {medical data},

pubstate = {published},

tppubtype = {article}

}

@article{pmid31636412,

title = {KLF4 inhibition promotes the expansion of keratinocyte precursors from adult human skin and of embryonic-stem-cell-derived keratinocytes},

author = {Nicolas O Fortunel and Loubna Chadli and Julien Coutier and Gilles Lemaître and Frédéric Auvré and Sophie Domingues and Emmanuelle Bouissou-Cadio and Pierre Vaigot and Sophie Cavallero and Jean-François Deleuze and Paul-Henri Roméo and Michèle T Martin},

doi = {10.1038/s41551-019-0464-6},

issn = {2157-846X},

year  = {2019},

date = {2019-12-01},

urldate = {2019-12-01},

journal = {Nat Biomed Eng},

volume = {3},

number = {12},

pages = {985--997},

abstract = {Expanded autologous skin keratinocytes are currently used in cutaneous cell therapy, and embryonic-stem-cell-derived keratinocytes could become a complementary alternative. Regardless of keratinocyte provenance, for efficient therapy it is necessary to preserve immature keratinocyte precursors during cell expansion and graft processing. Here, we show that stable and transient downregulation of the transcription factor Krüppel-like factor 4 (KLF4) in keratinocyte precursors from adult skin, using anti-KLF4 RNA interference or kenpaullone, promotes keratinocyte immaturity and keratinocyte self-renewal in vitro, and enhances the capacity for epidermal regeneration in mice. Both stable and transient KLF4 downregulation had no impact on the genomic integrity of adult keratinocytes. Moreover, transient KLF4 downregulation in human-embryonic-stem-cell-derived keratinocytes increased the efficiency of skin-orientated differentiation and of keratinocyte immaturity, and was associated with improved generation of epidermis. As a regulator of the cell fate of keratinocyte precursors, KLF4 could be used for promoting the ex vivo expansion and maintenance of functional immature keratinocyte precursors.},

keywords = {omics},

pubstate = {published},

tppubtype = {article}

}

@article{pmid31092846,

title = {Reconstructed Skin Models Revealed Unexpected Differences in Epidermal African and Caucasian Skin},

author = {Sarah Girardeau-Hubert and Céline Deneuville and Hervé Pageon and Kahina Abed and Charlotte Tacheau and Nükhet Cavusoglu and Mark Donovan and Dominique Bernard and Daniel Asselineau},

doi = {10.1038/s41598-019-43128-3},

issn = {2045-2322},

year  = {2019},

date = {2019-05-01},

urldate = {2019-05-01},

journal = {Sci Rep},

volume = {9},

number = {1},

pages = {7456},

abstract = {Clinical observations of both normal and pathological skin have shown that there is a heterogeneity based on the skin origin type. Beside external factors, intrinsic differences in skin cells could be a central element to determine skin types. This study aimed to understand the in vitro behaviour of epidermal cells of African and Caucasian skin types in the context of 3D reconstructed skin. Full-thickness skin models were constructed with site matched human keratinocytes and papillary fibroblasts to investigate potential skin type related differences. We report that reconstructed skin epidermis exhibited remarkable differences regarding stratification and differentiation according to skin types, as demonstrated by histological appearance, gene expression analysed by DNA microarray and quantitative proteomic analysis. Signalling pathways and processes related to terminal differentiation and lipid/ceramide metabolism were up-regulated in epidermis constructed with keratinocytes from Caucasian skin type when compared to that of keratinocytes from African skin type. Specifically, the expression of proteins involved in the processing of filaggrins was found different between skin models. Overall, we show unexpected differences in epidermal morphogenesis and differentiation between keratinocytes of Caucasian and African skin types in in vitro reconstructed skin containing papillary fibroblasts that could explain the differences in ethnic related skin behaviour.},

keywords = {omics},

pubstate = {published},

tppubtype = {article}

}

@article{pmid31156454,

title = {Mental Workload Alters Heart Rate Variability, Lowering Non-linear Dynamics},

author = {Stéphane Delliaux and Alexis Delaforge and Jean-Claude Deharo and Guillaume Chaumet},

doi = {10.3389/fphys.2019.00565},

issn = {1664-042X},

year  = {2019},

date = {2019-01-01},

urldate = {2019-01-01},

journal = {Front Physiol},

volume = {10},

pages = {565},

abstract = {Mental workload is known to alter cardiovascular function leading to increased cardiovascular risk. Nevertheless, there is no clear autonomic nervous system unbalance to be quantified during mental stress. We aimed to characterize the mental workload impact on the cardiovascular function with a focus on heart rate variability (HRV) non-linear indexes. A 1-h computerized switching task (letter recognition) was performed by 24 subjects while monitoring their performance (accuracy, response time), electrocardiogram and blood pressure waveform (finger volume clamp method). The HRV was evaluated from the beat-to-beat RR intervals (RRI) in time-, frequency-, and informational- domains, before (Control) and during the task. The task induced a significant mental workload (visual analog scale of fatigue from 27 ± 26 to 50 ± 31 mm,  < 0.001, and NASA-TLX score of 56 ± 17). The heart rate, blood pressure and baroreflex function were unchanged, whereas most of the HRV parameters markedly decreased. The maximum decrease occurred during the first 15 min of the task (P1), before starting to return to the baseline values reached at the end of the task (P4). The RRI dimension correlation (D2) decrease was the most significant (P1 vs. Control: 1.42 ± 0.85 vs. 2.21 ± 0.8,  < 0.001) and only D2 lasted until the task ended (P4 vs. Control: 1.96 ± 0.9 vs. 2.21 ± 0.9,  < 0.05). D2 was identified as the most robust cardiovascular variable impacted by the mental workload as determined by posterior predictive simulations ( = 0.9). The Spearman correlation matrix highlighted that D2 could be a marker of the generated frustration ( = -0.61,  < 0.01) induced by a mental task, as well as the myocardial oxygen consumption changes assessed by the double product ( = -0.53,  < 0.05). In conclusion, we showed that mental workload sharply lowered the non-linear RRI dynamics, particularly the RRI correlation dimension.},

keywords = {medical data},

pubstate = {published},

tppubtype = {article}

}

@article{pmid31281261b,

title = {High Bubble Grade After Diving: The Role of the Blood Pressure Regimen},

author = {Alain Boussuges and Guillaume Chaumet and Nicolas Vallée and Jean Jacques Risso and Jean Michel Pontier},

doi = {10.3389/fphys.2019.00749},

issn = {1664-042X},

year  = {2019},

date = {2019-01-01},

urldate = {2019-01-01},

journal = {Front Physiol},

volume = {10},

pages = {749},

abstract = { Previous studies have suggested that the circulatory system was involved in the production of circulatory bubbles after diving. This study was designed to research the cardio-vascular function characteristics related to the production of high bubble grades after diving.  Thirty trained divers were investigated both at baseline and after a 30-msw SCUBA dive. At baseline, the investigations included blood pressure measurement, echocardiography, and assessment of aerobic fitness using VO peak measurement. Blood samples were taken at rest, to measure the plasma concentration of NOx and endothelin-1. After diving, circulating bubbles were detected in the pulmonary artery by pulsed Doppler at 20-min intervals during the 90 min after surfacing. The global bubble quantity production was estimated by the KISS index.  Divers with a high bubble grade (KISS > 7.5) had systolic blood pressure, pulse pressure, weight, and height significantly higher than divers with a low bubble grade. By contrast, total arterial compliance, plasma NOx level, and percentage of predicted value of peak oxygen uptake were significantly lower in divers with a high bubble grade. Cardiac dimensions, left ventricular function, and plasma endothelin-1 concentration were not significantly different between groups. The multivariate analysis identified blood pressure as the main contributor of the quantity of bubble production. The model including pulse pressure, plasma NOx level, and percentage of predicted value of peak oxygen uptake has an explanatory power of 49.22%.  The viscoelastic properties of the arterial tree appeared to be an important contributor to the circulating bubble production after a dive.},

keywords = {medical data},

pubstate = {published},

tppubtype = {article}

}

@article{pmid30031067,

title = {Gene profile of zebrafish fin regeneration offers clues to kinetics, organization and biomechanics of basement membrane},

author = {Pauline Nauroy and Alexandre Guiraud and Julien Chlasta and Marilyne Malbouyres and Benjamin Gillet and Sandrine Hughes and Elise Lambert and Florence Ruggiero},

doi = {10.1016/j.matbio.2018.07.005},

issn = {1569-1802},

year  = {2019},

date = {2019-01-01},

urldate = {2019-01-01},

journal = {Matrix Biol},

volume = {75-76},

pages = {82--101},

abstract = {How some animals regenerate missing body parts is not well understood. Taking advantage of the zebrafish caudal fin model, we performed a global unbiased time-course transcriptomic analysis of fin regeneration. Biostatistics analyses identified extracellular matrix (ECM) as the most enriched gene sets. Basement membranes (BMs) are specialized ECM structures that provide tissues with structural cohesion and serve as a major extracellular signaling platform. While the embryonic formation of BM has been extensively investigated, its regeneration in adults remains poorly studied. We therefore focused on BM gene expression kinetics and showed that it recapitulates many aspects of development. As such, the re-expression of the embryonic col14a1a gene indicated that col14a1a is part of the regeneration-specific program. We showed that laminins and col14a1a genes display similar kinetics and that the corresponding proteins are spatially and temporally controlled during regeneration. Analysis of our CRISPR/Cas9-mediated col14a1a knockout fish showed that collagen XIV-A contributes to timely deposition of laminins. As changes in ECM organization can affect tissue mechanical properties, we analyzed the biomechanics of col14a1a regenerative BM using atomic force microscopy (AFM). Our data revealed a thinner BM accompanied by a substantial increase of the stiffness when compared to controls. Further AFM 3D-reconstructions showed that BM is organized as a checkerboard made of alternation of soft and rigid regions that is compromised in mutants leading to a more compact structure. We conclude that collagen XIV-A transiently acts as a molecular spacer responsible for BM structure and biomechanics possibly by helping laminins integration within regenerative BM.},

keywords = {omics},

pubstate = {published},

tppubtype = {article}

}

@article{pmid29721761,

title = {A Cross-Sectional Study Assessing the Contributions of Body Fat Mass and Fat-Free Mass to Body Mass Index Scores in Male Youth Rugby Players},

author = {Olivier Gavarry and Gregory Lentin and Patrick Pezery and Anne Delextrat and Guillaume Chaumet and Alain Boussuges and Julien Piscione},

doi = {10.1186/s40798-018-0130-7},

issn = {2199-1170},

year  = {2018},

date = {2018-05-01},

urldate = {2018-05-01},

journal = {Sports Med Open},

volume = {4},

number = {1},

pages = {17},

abstract = {BACKGROUND: In some sports such as rugby, a large body size is an advantage, and the desire to gain weight can bring young players to become overweight or obese. The aim of this study was to evaluate the prevalence of overweight and obesity and the contribution of body fat mass index (BFMI) and fat-free mass index (FFMI) to body mass index (BMI) changes among young male rugby players (15-a-side rugby).



METHODS: The criteria of the International Obesity Task Force were used to define overweight and obesity from BMI. The method of skinfold thickness was used to assess percentage of body fat (%BF), BFMI, and FFMI. Excess body fat was defined by using BFMI and %BF above the 75th percentile. Data were grouped according to the age categories of the French Rugby Federation (U11, under 11 years; U13, under 13 years; U15, under 15 years) and to BMI status (NW normal-weight versus OW/OB overweight/obese).



RESULTS: Overall, 32.8% of the young players were overweight, and 13.8% were obese. However, 53% of young players classified as obese and overweight by BMI had an excess body fat by using BFMI above the 75th percentile. FFMI increased significantly between U11 and U13 in both groups, without significant change in BMI and BFMI. Both groups had similar significant gains in BMI and FFMI between U13 and U15, while BFMI only increased significantly in OW/OB (+ 18.5%). The strong correlations between BMI and %BF were systematically lower than those between BMI and BFMI. FFMI was strongly or moderately associated with BFMI.



CONCLUSIONS: Chart analysis of BFMI and FFMI could be used to distinguish changes in body composition across age categories in young male rugby players classified as normal-weight, overweight, and obese by BMI.},

keywords = {medical data},

pubstate = {published},

tppubtype = {article}

}

@article{pmid29632146,

title = {Antigen-Induced but Not Innate Memory CD8 T Cells Express NKG2D and Are Recruited to the Lung Parenchyma upon Viral Infection},

author = {Morgan Grau and Séverine Valsesia and Julien Mafille and Sophia Djebali and Martine Tomkowiak and Anne-Laure Mathieu and Daphné Laubreton and Simon de Bernard and Pierre-Emmanuel Jouve and Erwan Ventre and Laurent Buffat and Thierry Walzer and Yann Leverrier and Jacqueline Marvel},

doi = {10.4049/jimmunol.1701698},

issn = {1550-6606},

year  = {2018},

date = {2018-05-01},

urldate = {2018-05-01},

journal = {J Immunol},

volume = {200},

number = {10},

pages = {3635--3646},

abstract = {The pool of memory-phenotype CD8 T cells is composed of Ag-induced (AI) and cytokine-induced innate (IN) cells. IN cells have been described as having properties similar to those of AI memory cells. However, we found that pathogen-induced AI memory cells can be distinguished in mice from naturally generated IN memory cells by surface expression of NKG2D. Using this marker, we described the increased functionalities of AI and IN memory CD8 T cells compared with naive cells, as shown by comprehensive analysis of cytokine secretion and gene expression. However, AI differed from IN memory CD8 T cells by their capacity to migrate to the lung parenchyma upon inflammation or infection, a process dependent on their expression of ITGA1/CD49a and ITGA4/CD49d integrins.},

keywords = {cytometry},

pubstate = {published},

tppubtype = {article}

}

@article{pmid28975560,

title = {Observational study of potential risk factors of immersion pulmonary edema in healthy divers: exercise intensity is the main contributor},

author = {A Boussuges and K Ayme and G Chaumet and E Albier and M Borgnetta and O Gavarry},

doi = {10.1186/s40798-017-0104-1},

issn = {2199-1170},

year  = {2017},

date = {2017-10-01},

urldate = {2017-10-01},

journal = {Sports Med Open},

volume = {3},

number = {1},

pages = {35},

abstract = {BACKGROUND: The risk factors of pulmonary edema induced by diving in healthy subjects are not well known. The aim of the present study was to assess the parameters contributing to the increase in extravascular lung water after diving.



METHODS: This study was carried out in a professional diving institute. All divers participating in the teaching program from June 2012 to June 2014 were included in the study. Extravascular lung water was assessed using the detection of ultrasound lung comets (ULC) by chest ultrasonography. Clinical parameters and dive profiles were recorded using a questionnaire and a dive computer.



RESULTS: One-hundred six divers were investigated after 263 dives. They used an open-circuit umbilical supplying compressed gas diving apparatus in 202 cases and a self-contained underwater breathing apparatus in 61 cases. A generalized linear mixed model analysis was performed which demonstrated that the dive induced a significant increase in ULC score (incidence rate ratio: 3.16). It also identified that the predictive variable of increased extravascular lung water after the dive was the exercise intensity at depth (z = 3.99, p < 0.0001). The other parameters studied such as the water temperature, dive profile, hyperoxic exposure, or anthropometric data were not associated with the increase in extravascular lung water after the dive.



CONCLUSIONS: In this study, the exercise intensity was the main contributor to the increase in extravascular lung water in healthy divers. To improve the prevention of immersion pulmonary edema, the exercise intensity experienced during the dive should thus be adapted to the aerobic fitness level of the divers.},

keywords = {medical data},

pubstate = {published},

tppubtype = {article}

}

@article{pmid28435843,

title = {MMP-7 is a predictive biomarker of disease progression in patients with idiopathic pulmonary fibrosis},

author = {Yasmina Bauer and Eric S White and Simon de Bernard and Peter Cornelisse and Isabelle Leconte and Adele Morganti and Sebastien Roux and Oliver Nayler},

doi = {10.1183/23120541.00074-2016},

issn = {2312-0541},

year  = {2017},

date = {2017-01-01},

urldate = {2017-01-01},

journal = {ERJ Open Res},

volume = {3},

number = {1},

abstract = {Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with poor prognosis, which is characterised by destruction of normal lung architecture and excessive deposition of lung extracellular matrix. The heterogeneity of disease progression in patients with IPF poses significant obstacles to patient care and prevents efficient development of novel therapeutic interventions. Blood biomarkers, reflecting pathobiological processes in the lung, could provide objective evidence of the underlying disease. Longitudinally collected serum samples from the Bosentan Use in Interstitial Lung Disease (BUILD)-3 trial were used to measure four biomarkers (metalloproteinase-7 (MMP-7), Fas death receptor ligand, osteopontin and procollagen type I C-peptide), to assess their potential prognostic capabilities and to follow changes during disease progression in patients with IPF. In baseline BUILD-3 samples, only MMP-7 showed clearly elevated protein levels compared with samples from healthy controls, and further investigations demonstrated that MMP-7 levels also increased over time. Baseline levels of MMP-7 were able to predict patients who had higher risk of worsening and, notably, baseline levels of MMP-7 could predict changes in FVC as early as month 4. MMP-7 shows potential to be a reliable predictor of lung function decline and disease progression.},

keywords = {omics},

pubstate = {published},

tppubtype = {article}

}

@article{pmid27924814,

title = {Mature IgM-expressing plasma cells sense antigen and develop competence for cytokine production upon antigenic challenge},

author = {Pascal Blanc and Ludovic Moro-Sibilot and Lucas Barthly and Ferdinand Jagot and Sébastien This and Simon de Bernard and Laurent Buffat and Sébastien Dussurgey and Renaud Colisson and Elias Hobeika and Thierry Fest and Morgan Taillardet and Olivier Thaunat and Antoine Sicard and Paul Mondière and Laurent Genestier and Stephen L Nutt and Thierry Defrance},

doi = {10.1038/ncomms13600},

issn = {2041-1723},

year  = {2016},

date = {2016-12-01},

urldate = {2016-12-01},

journal = {Nat Commun},

volume = {7},

pages = {13600},

abstract = {Dogma holds that plasma cells, as opposed to B cells, cannot bind antigen because they have switched from expression of membrane-bound immunoglobulins (Ig) that constitute the B-cell receptor (BCR) to production of the secreted form of immunoglobulins. Here we compare the phenotypical and functional attributes of plasma cells generated by the T-cell-dependent and T-cell-independent forms of the hapten NP. We show that the nature of the secreted Ig isotype, rather than the chemical structure of the immunizing antigen, defines two functionally distinct populations of plasma cells. Fully mature IgM-expressing plasma cells resident in the bone marrow retain expression of a functional BCR, whereas their IgG counterparts do not. Antigen boost modifies the gene expression profile of IgM plasma cells and initiates a cytokine production program, characterized by upregulation of CCL5 and IL-10. Our results demonstrate that IgM-expressing plasma cells can sense antigen and acquire competence for cytokine production upon antigenic challenge.},

keywords = {omics},

pubstate = {published},

tppubtype = {article}

}