Publications by authors named "Martin O"

712 Publications

Strongyloides in bronchoalveolar lavage fluid: Practical implications in the COVID-19 era.

J Travel Med 2021 Jul 22. Epub 2021 Jul 22.

National Referral Unit for Tropical Diseases, Infectious Diseases Department, Hospital Ramón y Cajal, IRYCIS, Madrid, Spain.

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http://dx.doi.org/10.1093/jtm/taab114DOI Listing
July 2021

Factors Associated with Clostridioides (Clostridium) Difficile Infection and Colonization: Ongoing Prospective Cohort Study in a French University Hospital.

Int J Environ Res Public Health 2021 Jul 15;18(14). Epub 2021 Jul 15.

Edouard Herriot Hospital, Hospices Civils de Lyon, 69437 Lyon, France.

Introduction: can be isolated from stool in 3% of healthy adults and in at least 10% of asymptomatic hospitalized patients. , the most common cause of hospital-acquired infectious diarrhea in the developed world, has re-emerged in recent years with increasing incidence and severity. In an effort to reduce the spread of the pathogen, published recommendations suggest isolation and contact precautions for patients suffering from infection (CDI). However, asymptomatic colonized patients are not targeted by infection control policies, and active surveillance for colonization is not routinely performed. Moreover, given the current changes in the epidemiology of CDI, particularly the emergence of new virulent strains either in the hospital or community settings, there is a need for identification of factors associated with colonization by and CDI. Methods and analysis: We are carrying out a prospective, observational, cohort study in Edouard Herriot Hospital, Hospices Civils de Lyon, a 900-bed university hospital in Lyon, France. All consecutive adult patients admitted on selected units are eligible to participate in the study. Stool samples or rectal swabs for testing are obtained on admission, every 3-5 days during hospitalization, at the onset of diarrhea (if applicable), and at discharge. Descriptive and logistic regression analyses will be completed to mainly estimate the proportion of asymptomatic colonization at admission, and to evaluate differences between factors associated with colonization and those related to CDI. Ethics: The study is conducted in accordance with the ethical principles of the Declaration of Helsinki, French law, and the Good Clinical Practice guidelines. The study protocol design was approved by the participating units, the ethics committee and the hospital institutional review board (Comité de protection des personnes et Comission Nationale de l'Informatique et des Libertés; N°: 00009118). Dissemination: The results of this study will be disseminated by presenting the findings locally at each participating ward, as well as national and international scientific meetings. Findings will be shared with interested national societies crafting guidelines in CDI.
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http://dx.doi.org/10.3390/ijerph18147528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307155PMC
July 2021

Microbeam Radiotherapy-A Novel Therapeutic Approach to Overcome Radioresistance and Enhance Anti-Tumour Response in Melanoma.

Int J Mol Sci 2021 Jul 20;22(14). Epub 2021 Jul 20.

Institute of Anatomy, University of Bern, 3012 Bern, Switzerland.

Melanoma is the deadliest type of skin cancer, due to its invasiveness and limited treatment efficacy. The main therapy for primary melanoma and solitary organ metastases is wide excision. Adjuvant therapy, such as chemotherapy and targeted therapies are mainly used for disseminated disease. Radiotherapy (RT) is a powerful treatment option used in more than 50% of cancer patients, however, conventional RT alone is unable to eradicate melanoma. Its general radioresistance is attributed to overexpression of repair genes in combination with cascades of biochemical repair mechanisms. A novel sophisticated technique based on synchrotron-generated, spatially fractionated RT, called Microbeam Radiation Therapy (MRT), has been shown to overcome these treatment limitations by allowing increased dose delivery. With MRT, a collimator subdivides the homogeneous radiation field into an array of co-planar, high-dose microbeams that are tens of micrometres wide and spaced a few hundred micrometres apart. Different preclinical models demonstrated that MRT has the potential to completely ablate tumours, or significantly improve tumour control while dramatically reducing normal tissue toxicity. Here, we discuss the role of conventional RT-induced immunity and the potential for MRT to enhance local and systemic anti-tumour immune responses. Comparative gene expression analysis from preclinical tumour models indicated a specific gene signature for an 'MRT-induced immune effect'. This focused review highlights the potential of MRT to overcome the inherent radioresistance of melanoma which could be further enhanced for future clinical use with combined treatment strategies, in particular, immunotherapy.
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http://dx.doi.org/10.3390/ijms22147755DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8303317PMC
July 2021

Accurately computing the electronic properties of a quantum ring.

Nature 2021 Jun 23;594(7864):508-512. Epub 2021 Jun 23.

Google Quantum AI, Mountain View, CA, USA.

A promising approach to study condensed-matter systems is to simulate them on an engineered quantum platform. However, the accuracy needed to outperform classical methods has not been achieved so far. Here, using 18 superconducting qubits, we provide an experimental blueprint for an accurate condensed-matter simulator and demonstrate how to investigate fundamental electronic properties. We benchmark the underlying method by reconstructing the single-particle band structure of a one-dimensional wire. We demonstrate nearly complete mitigation of decoherence and readout errors, and measure the energy eigenvalues of this wire with an error of approximately 0.01 rad, whereas typical energy scales are of the order of 1 rad. Insight into the fidelity of this algorithm is gained by highlighting the robust properties of a Fourier transform, including the ability to resolve eigenenergies with a statistical uncertainty of 10 rad. We also synthesize magnetic flux and disordered local potentials, which are two key tenets of a condensed-matter system. When sweeping the magnetic flux we observe avoided level crossings in the spectrum, providing a detailed fingerprint of the spatial distribution of local disorder. By combining these methods we reconstruct electronic properties of the eigenstates, observing persistent currents and a strong suppression of conductance with added disorder. Our work describes an accurate method for quantum simulation and paves the way to study new quantum materials with superconducting qubits.
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http://dx.doi.org/10.1038/s41586-021-03576-2DOI Listing
June 2021

Changes in the Gut Microbiota Following Bariatric Surgery Are Associated with Increased Alcohol Intake in a Female Rat Model.

Alcohol Alcohol 2021 Jun 21. Epub 2021 Jun 21.

Institute for Genome Sciences, University of Maryland School of Medicine, West Baltimore St. 21201, Baltimore, MD, USA.

Aims: We aimed to investigate if differences in gut microbiota diversity and composition are associated with post-operative alcohol intake following bariatric surgery in a rat model.

Methods: Twenty-four female rats were randomized to three treatment groups: sham surgery, vertical sleeve gastrectomy (VSG) or Roux-en-Y gastric bypass (RYGB). Stool was collected pre- and post-operatively and 16S rRNA gene amplification and sequencing was performed. Analysis focused on correlating microbial diversity, type of surgery and alcohol (EtOH) intake.

Results: Pre-operative stools samples on regular diet showed similar taxonomic composition and Shannon diversity among the three treatment groups. There was a significant decrease in Shannon diversity and a change in taxonomic composition of the gut microbiota after rats was fed high fat diet. Post-operatively, the RYGB group showed significantly lower taxonomic diversity than the VSG and sham groups, while the VSG and sham groups diversity were not significantly different. Taxonomic composition and function prediction based on PICRUSt analysis showed the RYGB group to be distinct from the VSG and sham groups. Shannon diversity was found to be negatively associated with EtOH intake.

Conclusions: Changes in the taxonomic profile of the gut microbiota following bariatric surgery, particularly RYGB, are associated with increased EtOH intake and may contribute to increased alcohol use disorder risk through the gut-brain-microbiome axis.
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http://dx.doi.org/10.1093/alcalc/agab041DOI Listing
June 2021

Scent of a killer: How could killer yeast boost its dispersal?

Ecol Evol 2021 Jun 1;11(11):5809-5814. Epub 2021 May 1.

Institute of Integrative Biology ETH Zürich Zürich Switzerland.

Vector-borne parasites often manipulate hosts to attract uninfected vectors. For example, parasites causing malaria alter host odor to attract mosquitoes. Here, we discuss the ecology and evolution of fruit-colonizing yeast in a tripartite symbiosis-the so-called "killer yeast" system. "Killer yeast" consists of yeast hosting two double-stranded RNA viruses (M satellite dsRNAs, L-A dsRNA helper virus). When both dsRNA viruses occur in a yeast cell, the yeast converts to lethal toxin‑producing "killer yeast" phenotype that kills uninfected yeasts. Yeasts on ephemeral fruits attract insect vectors to colonize new habitats. As the viruses have no extracellular stage, they depend on the same insect vectors as yeast for their dispersal. Viruses also benefit from yeast dispersal as this promotes yeast to reproduce sexually, which is how viruses can transmit to uninfected yeast strains. We tested whether insect vectors are more attracted to killer yeasts than to non‑killer yeasts. In our field experiment, we found that killer yeasts were more attractive to than non-killer yeasts. This suggests that vectors foraging on yeast are more likely to transmit yeast with a killer phenotype, allowing the viruses to colonize those uninfected yeast strains that engage in sexual reproduction with the killer yeast. Beyond insights into the basic ecology of the killer yeast system, our results suggest that viruses could increase transmission success by manipulating the insect vectors of their host.
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http://dx.doi.org/10.1002/ece3.7534DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8207343PMC
June 2021

Bacterial genotoxins induce T cell senescence.

Cell Rep 2021 Jun;35(10):109220

LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, 2200 Copenhagen, Denmark. Electronic address:

Several types of pathogenic bacteria produce genotoxins that induce DNA damage in host cells. Accumulating evidence suggests that a central function of these genotoxins is to dysregulate the host's immune response, but the underlying mechanisms remain unclear. To address this issue, we investigated the effects of the most widely expressed bacterial genotoxin, the cytolethal distending toxin (CDT), on T cells-the key mediators of adaptive immunity. We show that CDT induces premature senescence in activated CD4 T cells in vitro and provide evidence suggesting that infection with genotoxin-producing bacteria promotes T cell senescence in vivo. Moreover, we demonstrate that genotoxin-induced senescent CD4 T cells assume a senescence-associated secretory phenotype (SASP) which, at least partly, is orchestrated by the ATM-p38 signaling axis. These findings provide insight into the immunomodulatory properties of bacterial genotoxins and uncover a putative link between bacterial infections and T cell senescence.
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http://dx.doi.org/10.1016/j.celrep.2021.109220DOI Listing
June 2021

Amebic abscess and sexual contact.

J Travel Med 2021 Jun 8. Epub 2021 Jun 8.

National Referral Unit for Tropical Diseases. Infectious Diseases Department. Ramón y Cajal University Hospital, IRYCIS, Madrid, Spain.

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http://dx.doi.org/10.1093/jtm/taab089DOI Listing
June 2021

Synchrotron X-Ray Radiation-Induced Bystander Effect: An Impact of the Scattered Radiation, Distance From the Irradiated Site and p53 Cell Status.

Front Oncol 2021 21;11:685598. Epub 2021 May 21.

Institute of Anatomy, University of Bern, Bern, Switzerland.

Synchrotron radiation, especially microbeam radiotherapy (MRT), has a great potential to improve cancer radiotherapy, but non-targeted effects of synchrotron radiation have not yet been sufficiently explored. We have previously demonstrated that scattered synchrotron radiation induces measurable -H2AX foci, a biomarker of DNA double-strand breaks, at biologically relevant distances from the irradiated field that could contribute to the apparent accumulation of bystander DNA damage detected in cells and tissues outside of the irradiated area. Here, we quantified an impact of scattered radiation to DNA damage response in "naïve" cells sharing the medium with the cells that were exposed to synchrotron radiation. To understand the effect of genetic alterations in naïve cells, we utilised p53-null and p53-wild-type human colon cancer cells HCT116. The cells were grown in two-well chamber slides, with only one of nine zones (of equal area) of one well irradiated with broad beam or MRT. -H2AX foci per cell values induced by scattered radiation in selected zones of the unirradiated well were compared to the commensurate values from selected zones in the irradiated well, with matching distances from the irradiated zone. Scattered radiation highly impacted the DNA damage response in both wells and a pronounced distance-independent bystander DNA damage was generated by broad-beam irradiations, while MRT-generated bystander response was negligible. For p53-null cells, a trend for a reduced response to scattered irradiation was observed, but not to bystander signalling. These results will be taken into account for the assessment of genotoxic effects in surrounding non-targeted tissues in preclinical experiments designed to optimise conditions for clinical MRT and for cancer treatment in patients.
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http://dx.doi.org/10.3389/fonc.2021.685598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175890PMC
May 2021

Clinical Relevance of Pharmacist Intervention: Development of a Named Entity Recognition Model on Unstructured Comments.

Stud Health Technol Inform 2021 May;281:492-493

Univ. Grenoble-Alpes / CNRS, TIMC UMR 5525, Grenoble, France.

We developed a clinical named entity recognition model to predict clinical relevance of pharmacist interventions (PIs) by identifying and labelling expressions from unstructured comments of PIs. Three labels, drug, kidney and dosage, had a great inter-annotator agreement (>60%) and could be used as reference labelization. These labels also showed a high precision (>70%) and a variable recall (50-90 %).
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http://dx.doi.org/10.3233/SHTI210210DOI Listing
May 2021

Love at First Click: Surgery Residency Websites in the Virtual Era.

J Surg Educ 2021 May 16. Epub 2021 May 16.

University of Maryland School of Medicine, Baltimore, Maryland. Electronic address:

Introduction: Frequently, a residency program's website is the first interaction students interested in surgery have with the program. In the setting of virtual interviews for residency in 2020, the online availability of program information is of heightened importance. We sought to assess how academic versus community-based general surgery residency programs compared with respect to certain details on their websites.

Methods: A total of n = 268 surgery residency programs were investigated. Our database of website characteristics included: direct link to residency website from the American Council on Graduate Medical Education (ACGME) program page, resident research requirement, listing of residents' publications, availability of residents' demographic information, program alumni information, board pass rates, attrition rate, detail of educational/academic activities, residents' evaluation methods, diversity, and mentorship. Inter-group analyses between academic and community-based programs were performed using Pearson's Chi-squared test.

Results: Academic and community-based general surgery residency program websites were compared based on twelve (12) different parameters. Statistically significant differences were observed for eight of these comparisons: direct website access from ACGME (p = 0.007), research highlighted (p < 0.001), resident research requirement (p = 0.002), resident demographic information available (p=0.004), alumni information (p = 0.005), resident evaluation methods (p = 0.016), diversity (p < 0.001), and mentorship (p = 0.012). Across these domains, academic programs had more information available on their websites than the community programs did. The program websites did not differ significantly based on the frequency of mentioning resident publications, board pass rate, attrition rate, or resident education.

Conclusion: Many general surgery programs are lacking detailed information on their websites. The amount of website information available on general surgery residency programs differs when comparing academic and community-based programs.
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http://dx.doi.org/10.1016/j.jsurg.2021.04.016DOI Listing
May 2021

Exploring the quality of protein structural models from a Bayesian perspective.

J Comput Chem 2021 Aug 14;42(21):1466-1474. Epub 2021 May 14.

Instituto de Matemática Aplicada San Luis, CONICET-UNSL, San Luis, Argentina.

We explore how ideas and practices common in Bayesian modeling can be applied to help assess the quality of 3D protein structural models. The basic premise of our approach is that the evaluation of a Bayesian statistical model's fit may reveal aspects of the quality of a structure when the fitted data is related to protein structural properties. Therefore, we fit a Bayesian hierarchical linear regression model to experimental and theoretical C chemical shifts. Then, we propose two complementary approaches for the evaluation of such fitting: (a) in terms of the expected differences between experimental and posterior predicted values; (b) in terms of the leave-one-out cross-validation point-wise predictive accuracy. Finally, we present visualizations that can help interpret these evaluations. The analyses presented in this article are aimed to aid in detecting problematic residues in protein structures. The code developed for this work is available on: https://github.com/BIOS-IMASL/Hierarchical-Bayes-NMR-Validation.
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http://dx.doi.org/10.1002/jcc.26556DOI Listing
August 2021

Role of electric currents in the Fano resonances of connected plasmonic structures.

Opt Express 2021 Apr;29(8):11635-11644

In this work, we use finite elements simulations to study the far field properties of two plasmonic structures, namely a dipole antenna and a cylinder dimer, connected to a pair of nanorods. We show that electrical, rather than near field, coupling between the modes of these structures results in a characteristic Fano lineshape in the far field spectra. This insight provides a way of tailoring the far field properties of such systems to fit specific applications, especially maintaining the optical properties of plasmonic antennas once they are connected to nanoelectrodes. This work extends the previous understanding of Fano resonances as generated by a simple near field coupling and provides a route to an efficient design of functional plasmonic electrodes.
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http://dx.doi.org/10.1364/OE.421951DOI Listing
April 2021

Clinical features and outcomes of COVID-19 patients hospitalized for psychiatric disorders: a French multi-centered prospective observational study.

Psychol Med 2021 Apr 27:1-9. Epub 2021 Apr 27.

Centre Psychothérapique de Nancy, LaxouF-54520, France.

Background: Patients with psychiatric disorders are exposed to high risk of COVID-19 and increased mortality. In this study, we set out to assess the clinical features and outcomes of patients with current psychiatric disorders exposed to COVID-19.

Methods: This multi-center prospective study was conducted in 22 psychiatric wards dedicated to COVID-19 inpatients between 28 February and 30 May 2020. The main outcomes were the number of patients transferred to somatic care units, the number of deaths, and the number of patients developing a confusional state. The risk factors of confusional state and transfer to somatic care units were assessed by a multivariate logistic model. The risk of death was analyzed by a univariate analysis.

Results: In total, 350 patients were included in the study. Overall, 24 (7%) were transferred to medicine units, 7 (2%) died, and 51 (15%) patients presented a confusional state. Severe respiratory symptoms predicted the transfer to a medicine unit [odds ratio (OR) 17.1; confidence interval (CI) 4.9-59.3]. Older age, an organic mental disorder, a confusional state, and severe respiratory symptoms predicted mortality in univariate analysis. Age >55 (OR 4.9; CI 2.1-11.4), an affective disorder (OR 4.1; CI 1.6-10.9), and severe respiratory symptoms (OR 4.6; CI 2.2-9.7) predicted a higher risk, whereas smoking (OR 0.3; CI 0.1-0.9) predicted a lower risk of a confusional state.

Conclusion: COVID-19 patients with severe psychiatric disorders have multiple somatic comorbidities and have a risk of developing a confusional state. These data underline the need for extreme caution given the risks of COVID-19 in patients hospitalized for psychiatric disorders.
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http://dx.doi.org/10.1017/S0033291721001537DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144831PMC
April 2021

Influence of the microenvironment on modulation of the host response by typhoid toxin.

Cell Rep 2021 Apr;35(1):108931

Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden; Department of Molecular Biology, Umeå University, Umeå, Sweden; Umeå Centre for Microbial Research (UCMR), Umeå University, Umeå, Sweden. Electronic address:

Bacterial genotoxins cause DNA damage in eukaryotic cells, resulting in activation of the DNA damage response (DDR) in vitro. These toxins are produced by Gram-negative bacteria, enriched in the microbiota of inflammatory bowel disease (IBD) and colorectal cancer (CRC) patients. However, their role in infection remains poorly characterized. We address the role of typhoid toxin in modulation of the host-microbial interaction in health and disease. Infection with a genotoxigenic Salmonella protects mice from intestinal inflammation. We show that the presence of an active genotoxin promotes DNA fragmentation and senescence in vivo, which is uncoupled from an inflammatory response and unexpectedly associated with induction of an anti-inflammatory environment. The anti-inflammatory response is lost when infection occurs in mice with acute colitis. These data highlight a complex context-dependent crosstalk between bacterial-genotoxin-induced DDR and the host immune response, underlining an unexpected role for bacterial genotoxins.
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http://dx.doi.org/10.1016/j.celrep.2021.108931DOI Listing
April 2021

Siland a R package for estimating the spatial influence of landscape.

Sci Rep 2021 Apr 5;11(1):7488. Epub 2021 Apr 5.

INRAE, BioSP, 84914, Avignon, France.

The spatial distributions of populations are both influenced by local variables and by characteristics of surrounding landscapes. Understanding how landscape features spatially structure the frequency of a trait in a population, the abundance of a species or the species' richness remains difficult specially because the spatial scale effects of the landscape variables are unknown. Various methods have been proposed but their results are not easily comparable. Here, we introduce "siland", a general method for analyzing the effect of landscape features. Based on a sequential procedure of maximum likelihood estimation, it simultaneously estimates the spatial scales and intensities of landscape variable effects. It does not require any information about the scale of effect. It integrates two landscape effects models: one is based on focal sample site (Bsiland, b for buffer) and one is distance weighted using Spatial Influence Function (Fsiland, f for function). We implemented "siland" in the adaptable and user-friendly R eponym package. It performs landscape analysis on georeferenced point observations (described in a Geographic Information System shapefile format) and allows for effects tests, effects maps and models comparison. We illustrated its use on a real dataset by the study of a crop pest (codling moth densities).
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http://dx.doi.org/10.1038/s41598-021-86900-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021544PMC
April 2021

Adjuvant Sirolimus Does Not Improve Outcome in Pet Dogs Receiving Standard-of-Care Therapy for Appendicular Osteosarcoma: A Prospective, Randomized Trial of 324 Dogs.

Clin Cancer Res 2021 Jun 22;27(11):3005-3016. Epub 2021 Mar 22.

Department of Clinical Sciences, Cummings School of Veterinary Medicine at Tufts University, North Grafton, Massachusetts.

Purpose: The mTOR pathway has been identified as a key nutrient signaling hub that participates in metastatic progression of high-grade osteosarcoma. Inhibition of mTOR signaling is biologically achievable with sirolimus, and might slow the outgrowth of distant metastases. In this study, pet dogs with appendicular osteosarcoma were leveraged as high-value biologic models for pediatric osteosarcoma, to assess mTOR inhibition as a therapeutic strategy for attenuating metastatic disease progression.

Patients And Methods: A total of 324 pet dogs diagnosed with treatment-naïve appendicular osteosarcoma were randomized into a two-arm, multicenter, parallel superiority trial whereby dogs received amputation of the affected limb, followed by adjuvant carboplatin chemotherapy ± oral sirolimus therapy. The primary outcome measure was disease-free interval (DFI), as assessed by serial physical and radiologic detection of emergent macroscopic metastases; secondary outcomes included overall 1- and 2-year survival rates, and sirolimus pharmacokinetic variables and their correlative relationship to adverse events and clinical outcomes.

Results: There was no significant difference in the median DFI or overall survival between the two arms of this trial; the median DFI and survival for standard-of-care (SOC; defined as amputation and carboplatin therapy) dogs was 180 days [95% confidence interval (CI), 144-237] and 282 days (95% CI, 224-383) and for SOC + sirolimus dogs, it was 204 days (95% CI, 157-217) and 280 days (95% CI, 252-332), respectively.

Conclusions: In a population of pet dogs nongenomically segmented for predicted mTOR inhibition response, sequentially administered adjuvant sirolimus, although well tolerated when added to a backbone of therapy, did not extend DFI or survival in dogs with appendicular osteosarcoma.
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http://dx.doi.org/10.1158/1078-0432.CCR-21-0315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172450PMC
June 2021

Enhancing backcross programs through increased recombination.

Genet Sel Evol 2021 Mar 9;53(1):25. Epub 2021 Mar 9.

Université Paris-Saclay, INRAE, CNRS, AgroParisTech, GQE - Le Moulon, 91190, Gif-sur-Yvette, France.

Background: Introgression of a quantitative trait locus (QTL) by successive backcrosses is used to improve elite lines (recurrent parent) by introducing alleles from exotic material (donor parent). In the absence of selection, the proportion of the donor genome decreases by half at each generation. However, since selection is for the donor allele at the QTL, elimination of the donor genome around that QTL will be much slower than in the rest of the genome (i.e. linkage drag). Using markers to monitor the genome around the QTL and in the genetic background can accelerate the return to the recurrent parent genome. Successful introgression of a locus depends partly on the occurrence of crossovers at favorable positions. However, the number of crossovers per generation is limited and their distribution along the genome is heterogeneous. Recently, techniques have been developed to modify these two recombination parameters.

Results: In this paper, we assess, by simulations in the context of Brassicaceae, the effect of increased recombination on the efficiency of introgression programs by studying the decrease in linkage drag and the recovery of the recurrent genome. The simulated selection schemes begin by two generations of foreground selection and continue with one or more generations of background selection. Our results show that, when the QTL is in a region that initially lacked crossovers, an increase in recombination rate can decrease linkage drag by nearly ten-fold after the foreground selection and improves the return to the recurrent parent. However, if the QTL is in a region that is already rich in crossovers, an increase in recombination rate is detrimental.

Conclusions: Depending on the recombination rate in the region targeted for introgression, increasing it can be beneficial or detrimental. Thus, the simulations analysed in this paper help us understand how an increase in recombination rate can be beneficial. They also highlight the best methods that can be used to increase recombination rate, depending on the situation.
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http://dx.doi.org/10.1186/s12711-021-00619-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7941899PMC
March 2021

Two-year follow-up of 196 interstitial lung disease patients after ICU stay.

Int J Tuberc Lung Dis 2021 03;25(3):199-205

Service de Réanimation Médico-Chirurgicale, Hôpital Avicenne, Assistance Publique-Hôpitaux de Paris, Bobigny, Université Paris XIII, Sorbonne Paris Cité, Paris, Unité 942, F-75010, INSERM, Paris, France.

Interstitial lung diseases (ILDs) are associated with poor prognosis in the intensive care unit (ICU). We aimed to assess factors associated with hospital mortality in ILD patients admitted to the ICU and to investigate long-term outcome. This was a retrospective study in a teaching hospital specialised in ILD management. Patients with ILD who were hospitalised in the ICU between 2000 and 2014 were included. Independent predictors of hospital mortality were identified using logistic regression. A total of 196 ILD patients were admitted to the ICU during the study period. Overall hospital mortality was 55%. Two years after ICU admission, 70 (36%) patients were still alive. Of the 196 patients, 108 (55%) required invasive mechanical ventilation, of whom 21 (20%) were discharged alive from hospital. Acute exacerbation of ILD and multi-organ failure were highly associated with hospital mortality (OR 5.4, 95% CI 1.9-15.5 and OR 12.6, 95% CI 4.9-32.5, respectively). Hospital mortality among ILD patients hospitalised in the ICU was high, but even where invasive mechanical ventilation was required, a substantial number of patients were discharged alive from hospital. Multi-organ failure could lead to major ethical concerns.
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http://dx.doi.org/10.5588/ijtld.20.0706DOI Listing
March 2021

High flow nasal oxygen therapy to avoid invasive mechanical ventilation in SARS-CoV-2 pneumonia: a retrospective study.

Ann Intensive Care 2021 Feb 27;11(1):37. Epub 2021 Feb 27.

Intensive Care Unit, CHU Avicenne, Groupe Hospitalier Paris Seine Saint-Denis, AP-HP, 125 rue de Stalingrad, 93000, Bobigny, France.

Background: The efficacy of high flow nasal canula oxygen therapy (HFNO) to prevent invasive mechanical ventilation (IMV) is not well established in severe coronavirus disease 2019 (COVID-19). The aim of this study was to compare the risk of IMV between two strategies of oxygenation (conventional oxygenation and HFNO) in critically ill COVID 19 patients.

Methods: This was a bicenter retrospective study which took place in two intensive care units (ICU) of tertiary hospitals in the Paris region from March 11, to May 3, 2020. We enrolled consecutive patients hospitalized for COVID-19 and acute respiratory failure (ARF) who did not receive IMV at ICU admission. The primary outcome was the rate of IMV after ICU admission. Secondary outcomes were death at day 28 and day 60, length of ICU stay and ventilator-free days at day 28. Data from the HFNO group were compared with those from the standard oxygen therapy (SOT) group using weighted propensity score.

Results: Among 138 patients who met the inclusion criteria, 62 (45%) were treated with SOT alone, and 76 (55%) with HFNO. In HFNO group, 39/76 (51%) patients received IMV and 46/62 (74%) in SOT group (OR 0.37 [95% CI, 0.18-0.76] p = 0.007). After weighted propensity score, HFNO was still associated with a lower rate of IMV (OR 0.31 [95% CI, 0.14-0.66] p = 0.002). Length of ICU stay and mortality at day 28 and day 60 did not significantly differ between HFNO and SOT groups after weighted propensity score. Ventilator-free days at days 28 was higher in HNFO group (21 days vs 10 days, p = 0.005). In the HFNO group, predictive factors associated with IMV were SAPS2 score (OR 1.13 [95%CI, 1.06-1.20] p = 0.0002) and ROX index > 4.88 (OR 0.23 [95%CI, 0.008-0.64] p = 0.006).

Conclusions: High flow nasal canula oxygen for ARF due to COVID-19 is associated with a lower rate of invasive mechanical ventilation.
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http://dx.doi.org/10.1186/s13613-021-00825-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910764PMC
February 2021

Hot carrier-mediated avalanche multiphoton photoluminescence from coupled Au-Al nanoantennas.

J Chem Phys 2021 Feb;154(7):074701

Institute of Physical and Theoretical Chemistry, Eberhard Karls University of Tübingen, Auf der Morgenstelle 15, 72076 Tübingen, Germany.

Avalanche multiphoton photoluminescence (AMPL) is observed from coupled Au-Al nanoantennas under intense laser pumping, which shows more than one order of magnitude emission intensity enhancement and distinct spectral features compared with ordinary metallic photoluminescence. The experiments are conducted by altering the incident laser intensity and polarization using a home-built scanning confocal optical microscope. The results show that AMPL originates from the recombination of avalanche hot carriers that are seeded by multiphoton ionization. Notably, at the excitation stage, multiphoton ionization is shown to be assisted by the local electromagnetic field enhancement produced by coupled plasmonic modes. At the emission step, the giant AMPL intensity can be evaluated as a function of the local field environment and the thermal factor for hot carriers, in accordance with a linear relationship between the power law exponent coefficient and the emitted photon energy. The dramatic change in the spectral profile is explained by spectral linewidth broadening mechanisms. This study offers nanospectroscopic evidence of both the potential optical damages for plasmonic nanostructures and the underlying physical nature of light-matter interactions under a strong laser field; it illustrates the significance of the emerging topics of plasmonic-enhanced spectroscopy and laser-induced breakdown spectroscopy.
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http://dx.doi.org/10.1063/5.0032611DOI Listing
February 2021

Lactation curve model with explicit representation of perturbations as a phenotyping tool for dairy livestock precision farming.

Animal 2021 Jan 10;15(1):100074. Epub 2020 Dec 10.

Université Paris-Saclay, INRAE, AgroParisTech, UMR Modélisation Systémique Appliquée aux Ruminants, 75005 Paris, France.

In the context of dairy farming, ruminant females often face challenges inducing perturbations that affect their performance and welfare. A key issue is how to assess the effect of perturbations and provide metrics to quantify how animals cope with their environment. Milk production dynamics are good candidates to address this issue: i) they are easily accessible, ii) overall dynamics throughout lactation process are well described and iii) perturbations are visible through milk losses. In this study, a perturbed lactation model (PLM) with explicit representation of perturbations was developed. The model combines two components: i) the unperturbed lactation model that describes a theoretical lactation curve, assumed to reflect female production potential and ii) the perturbation model that describes all the deviations from the unperturbed lactation model with four parameters: starting date, intensity and shape (collapse and recovery). To illustrate the use of the PLM as a phenotyping tool, it was fitted on a data set of 319 complete lactations from 181 individual dairy goats. A total of 2 354 perturbations were detected, with an average of 7.40 perturbations per lactation. Loss of milk production for the whole lactation due to perturbations varied between 2 and 19% of the milk production predicted by the unperturbed lactation model. The number of perturbations was not the major factor explaining the loss of milk production, suggesting that there are different types of animal response to challenges. By incorporating explicit representation of perturbations in a lactation model, it was possible to determine for each female the potential milk production, characteristics of each perturbation and milk losses induced by perturbations. Further, it was possible to compare animals and analyze individual variability. The indicators produced by the PLM are likely to be useful to move from raw data to decision support tools in dairy production.
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http://dx.doi.org/10.1016/j.animal.2020.100074DOI Listing
January 2021

Plant roots sense soil compaction through restricted ethylene diffusion.

Science 2021 01;371(6526):276-280

School of Biosciences, University of Nottingham, Sutton Bonington LE12 5RD, UK.

Soil compaction represents a major challenge for modern agriculture. Compaction is intuitively thought to reduce root growth by limiting the ability of roots to penetrate harder soils. We report that root growth in compacted soil is instead actively suppressed by the volatile hormone ethylene. We found that mutant and rice roots that were insensitive to ethylene penetrated compacted soil more effectively than did wild-type roots. Our results indicate that soil compaction lowers gas diffusion through a reduction in air-filled pores, thereby causing ethylene to accumulate in root tissues and trigger hormone responses that restrict growth. We propose that ethylene acts as an early warning signal for roots to avoid compacted soils, which would be relevant to research into the breeding of crops resilient to soil compaction.
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http://dx.doi.org/10.1126/science.abf3013DOI Listing
January 2021

Volatile anaesthesia and peri-operative outcomes related to cancer: a feasibility and pilot study for a large randomised control trial.

Anaesthesia 2021 Jan 13. Epub 2021 Jan 13.

Department of Anaesthesia, Peri-operative and Pain Medicine, Peter MacCallum Cancer Centre, Melbourne, Australia.

Published data suggest that the type of general anaesthesia used during surgical resection for cancer may impact on patient long-term outcome. However, robust prospective clinical evidence is essential to guide a change in clinical practice. We explored the feasibility of conducting a randomised controlled trial to investigate the impact of total intravenous anaesthesia with propofol vs. inhalational volatile anaesthesia on postoperative outcomes of patients undergoing major cancer surgery. We undertook a randomised, double-blind feasibility and pilot study of propofol total intravenous anaesthesia or volatile-based maintenance anaesthesia during cancer resection surgery at three tertiary hospitals in Australia and the USA. Patients were randomly allocated to receive propofol total intravenous anaesthesia or volatile-based maintenance anaesthesia. Primary outcomes for this study were successful recruitment to the study and successful delivery of the assigned anaesthetic treatment as per randomisation arm. Of the 217 eligible patients approached, 146 were recruited, a recruitment rate of 67.3% (95%CI 60.6-73.5%). One hundred and forty-five patients adhered to the randomised treatment arm, 99.3% (95%CI 96.2-100%). Intra-operative patient characteristics and postoperative complications were comparable between the two intervention groups. This feasibility and pilot study supports the viability of the protocol for a large, randomised controlled trial to investigate the effect of anaesthesia technique on postoperative cancer outcomes. The volatile anaesthesia and peri-operative outcomes related to cancer (VAPOR-C) study that is planned to follow this feasibility study is an international, multicentre trial with the aim of providing evidence-based guidelines for the anaesthetic management of patients undergoing major cancer surgery.
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http://dx.doi.org/10.1111/anae.15354DOI Listing
January 2021

Hydrozirconation/bromination, followed by a Michaelis-Arbuzov reaction, as a convenient approach towards polyfunctional glycosylphosphonates.

Carbohydr Res 2021 Jan 31;499:108228. Epub 2020 Dec 31.

Normandie Univ, INSA Rouen, UNIROUEN, CNRS, COBRA UMR 6014, 76000, Rouen, France. Electronic address:

In this note, an hydrozirconation/bromination/Michaelis-Arbuzov sequence was developped to introduce a trimethylene phosphonate unit on ketopyranosides. Performed on polyfunctional substrates bearing orthogonal protecting groups, this new approach provided a straightforward entry towards a large diversity of glycophosphomimetics having a quaternary anomeric position.
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http://dx.doi.org/10.1016/j.carres.2020.108228DOI Listing
January 2021

Expression of immunoreactive inducible nitric oxide synthase in pancreatic islet cells from newly diagnosed and long-term type 1 diabetic donors is heterogeneous and not disease-associated.

Cell Tissue Res 2021 Jun 11;384(3):655-674. Epub 2021 Jan 11.

Faculty of Dentistry, University of Oslo, Oslo, Norway.

Exposure of isolated human islets to proinflammatory cytokines leads to up-regulation of inducible nitric oxide synthase (iNOS), raised NO, and beta cell toxicity. These findings have led to increasing interest in the clinical utility of iNOS blockade to mitigate beta cell destruction in human type 1 diabetes (T1D). However, recent studies show that iNOS-derived NO may also confer beta cell protection. To investigate this dichotomy, we compared islet cell distributions and intensity of iNOS immunostaining in pancreatic sections, co-stained for insulin and glucagon, from new-onset T1D donors (group 1), with non-diabetic autoantibody-negative (group 2), non-diabetic autoantibody-positive (group 3) and long-term diabetic donors (group 4). The cellular origins of iNOS, its frequency and graded intensities in islets and number in peri-islet, intra-islet and exocrine regions were determined. All donors showed iNOS positivity, irrespective of disease and presence of beta cells, had variable labelling intensities, without significant differences in the frequency of iNOS-positive islets among study groups. iNOS was co-localised in selective beta, alpha and other endocrine cells, and in beta cell-negative islets of diabetic donors. The number of peri- and intra-islet iNOS cells was low, being significantly higher in the peri-islet area. Exocrine iNOS cells also remained low, but were much lower in group 1. We demonstrate that iNOS expression in islet cells is variable, heterogeneous and independent of co-existing beta cells. Its distribution and staining intensities in islets and extra-islet areas do not correlate with T1D or its duration. Interventions to inactivate the enzyme to alleviate disease are currently not justified.
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http://dx.doi.org/10.1007/s00441-020-03340-4DOI Listing
June 2021

[Promoting autonomy by redesigning support in psychiatry].

Soins 2020 Dec;65(851):39-42

Groupement hospitalier universitaire Paris psychiatrie et neurosciences, 1 rue Cabanis, 75014 Paris, France.

Therapeutic patient education in psychiatry is a unique form of support in which the relational aspect is used as a means of developing the patient's capabilities and awareness of the disorder. This time helps to support users' autonomy and favours health professionals' participative approach.
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http://dx.doi.org/10.1016/S0038-0814(20)30306-6DOI Listing
December 2020
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