Introduction Unlike paclitaxel-coated balloons, pre-clinical data comparing different paclitaxel-coated stents (PCSs) are weak. The study objective was to compare the features of the 2 main PCSs: Eluvia® (Boston Scientific, Marlborough, MA) versus ZilverPTX® (Cook Medical, Bloomington, IN). Method Analysis was carried out on 12 pigs divided into 2 groups: Eluvia® (n=6) and ZilverPTX® (n=6). The pigs received the PCS corresponding to their group in each external iliac artery and were paired one by one, to examine 6 different post-implantation timepoints: after 30 minutes, 6 hours, 24 hours, 3 days, 7 days, and 14 days. The paclitaxel concentration measurements and the histological analysis were carried out under blind testing on the plasma, arterial, lymph node, and muscle samples. A linear regression model and Wilcoxon Mann-Whitney test were used to study the variables. Results The plasma paclitaxel rate decrease over 24 hours after PCS implantation was significantly different between the two groups, expressed by the correlation coefficient 0.19 (0.14–0.23; p<0.001) with an undetectable concentration at the 10th hour for Eluvia® versus 3 days for ZilverPTX®. Significantly higher paclitaxel concentrations with ZilverPTX® PCS were observed in muscle samples at each timepoint: extensor digitorum brevis 3.2 (1.17–5.23; p=0.005), biceps femoris 4.27 (2.27–6.26; p<0.001), semi-tendinosus 3.79 (1.85–5.73; p=0.001), tibialis anterior 3.0 (1.37–4.64; p=0.001), and in the femoral nodes 2.27±1.74 ng/g versus 0.14±0.13 ng/g (p<0.001). Histological analysis revealed a trend for more marked intimal inflammation in the arteries stented with ZilverPTX® (p=0.063), especially after the 7th and 14th days. Conclusion Such a difference in the concentration of paclitaxel in the plasma, muscles, and lymph nodes between the two stents was higher than expected based on differences in device design. The clinical consequences of these results remain to be elucidated, particularly regarding the concerning presence of paclitaxel in muscles and adjacent lymph nodes. Clinical Impact This experimental study compares 2 paclitaxel-coated stents. It demonstrates that differences in stent designs and drug features (coatings and concentrations) translate into differences in terms of concentrations of paclitaxel in the plasma, muscles, and lymph nodes. Our results favor the Eluvia® stent over the ZilverPTX® stent, although more studies are required to confirm this conclusion.
Purpose There is a scarcity of summarizing data on the epidemiology of insomnia in older persons, especially when diagnosed with international criteria. This study aimed to estimate the prevalence and correlates of insomnia disorder in older persons, according to the Diagnostic and Statistical Manual of Mental Disorders (DSM). Methods Through PubMed/MEDLINE, EMBASE, and Web of Science (WoS), we searched for relevant articles published before June 28, 2023. The risk of bias was weighed using the Joanna Briggs Institute’s (JBI’s) critical appraisal checklist for studies reporting prevalence data. For our analyses, we used a random-effect model, with subgroup analyses, meta-regression, and sensitivity analyses to explore potential sources of heterogeneity. We followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement. Results We included 18,270 participants across 16 studies. The male/female ratio was 0.89 (12 studies), and the mean age varied from 65.9 to 83.1 years (8 studies). The pooled prevalence of insomnia was 19.6% (95% CI = [12.3%; 28.3%]), with substantial heterogeneity. This prevalence fluctuated according to the sample size, the minimal age for inclusion, and the study quality, considering that the risk of bias was moderate for most of studies. There was a publication bias, with a very low level of certainty. Insomnia disorder was associated with the female gender, depression, anxiety, and somatic illnesses notably cardiovascular, respiratory, and painful ones. Conclusion Nearly one in every five old individuals was considered to have insomnia disorder, which was associated with the gender and the existence of mental health and/or somatic conditions. https://rdcu.be/dmyEQ
The paper suggests a compound control that combines nonlinear flatness, active disturbance rejection control (ADRC), and sliding mode control (SMC). By employing the differential flatness methodology, the standard under-actuated wheeled mobile robot model is converted into a fully actuated one. Utilizing this model as a basis, a sliding feedback controller is suggested to address the issue of uncertainties associated with wheel slip and wind. However, as the uncertainties increase, a higher control input is required, resulting in an undesired chattering phenomenon. To reduce chattering in SMC, a boundary layer surrounding the switching surface is employed, and a continuous law is implemented within the boundary. The boundary layer width plays an important role in improving robustness and eliminating chatter. Indeed, increasing the thickness of the boundary layer significantly reduces chattering, but it may lead to a loss of robustness performance achieved by the discontinuous control provided by SMC. To resolve this problem, active disturbance rejection control is combined with boundary layer sliding mode control. When utilizing the ADRC method, the lumped uncertainties are estimated via an extended state observer and eliminated within the feedback loop. The newly obtained feedback control combines the advantages of boundary layer SMC and ADRC to achieve practical control and robust tracking performance. The stability properties exhibited by the closed-loop system are rigorously established through the application of Lyapunov theory. In conclusion, a series of simulations has been conducted to compare and evaluate the efficiency of the presented robust tracking controller against other existing control methods.
Background Type 2 diabetes mellitus (T2DM) is a major global health issue and a significant risk factor for atherosclerosis. Atherosclerosis in T2DM patients has been associated with inflammation, insulin resistance, hyperglycemia, dyslipidemia, and oxidative stress. Identifying molecular features of atherosclerotic plaques in T2DM patients could provide valuable insights into the pathogenesis of the disease. Methods The MASCADI (Arachidonic Acid Metabolism in Carotid Stenosis Plaque in Diabetic Patients) study aimed to investigate the increase of 2-arachidonoyl-lysophatidylcholine (2-AA-LPC) in carotid plaques from T2DM and control patients and to explore its association with plaque vulnerability as well as with blood and intra-plaque biomarkers altered during diabetes. Results In a population of elderly, polymedicated patients with advanced stage of atherosclerosis, we found that T2DM patients had higher systemic inflammation markers, such as high-sensitivity C-reactive protein (hsCRP) and IL-1β, higher levels of oxysterols, increased triglyceride levels, and decreased HDL levels as compared to control patients. Furthermore, 2-AA-LPC was significantly enriched in plaques from diabetic patients, suggesting its potential role in diabetic atherosclerosis. Interestingly, 2-AA-LPC was not associated with systemic markers related to diabetes, such as hsCRP, triglycerides, or HDL cholesterol. However, it was significantly correlated with the levels of inflammatory markers within the plaques such as lysophospholipids and 25-hydroxycholesterol, strengthening the link between local inflammation, arachidonic acid metabolism and diabetes. Conclusion Our study is in line with a key role for inflammation in the pathogenesis of diabetic atherosclerosis and highlights the involvement of 2-AA-LPC. Further research is needed to better understand the local processes involved in the alteration of plaque composition in T2DM and to identify potential therapeutic targets. Trial registration The MASCADI was registered on ClinicalTrials.gov (clinical registration number: NCT03202823).
Grange syndrome (GRNG—MIM#135580) is a rare recessive disorder associating variable features including diffuse vascular stenosis, brachysyndactyly, osteopenia with increased bone fragility, cardiac malformations, and variable developmental delay. Since its first description in 1998, only 15 individuals from 10 families have been reported, carrying homozygous or compound heterozygous frameshift or nonsense variants in YY1AP1 . In a patient with cutaneous and bone syndactyly and a hemorrhagic stroke at the age of 16 months, consistent with a clinical diagnosis of GRNG, we performed exome sequencing after negative array‐CGH and congenital limb malformation panel results. Copy number variant analysis from exome data identified a homozygous intragenic out‐of‐frame deletion of 1.84 kb encompassing exons seven and eight of YY1AP1, confirming a molecular diagnosis of GRNG. Genetic counseling led to the identification of additional family members compatible with GRNG. Here, we provide new insights into the phenotypic variability associated with GRNG and highlight the utility of the detection of small copy number variants to identify the molecular causes of heterogeneous malformative genetic disorders.
Introduction: With the emergence of targeted therapies, there is a need to accurately identify more tumor biomarkers. The EXOMA trial was designed to offer tumor and germline exome sequencing (ES) to patients with solid malignant tumors and facing therapeutic failure. As hereditary cancer predispositions could be identified, with genetic counseling and health management implications, a genetic consultation was systematically established. This design needs to be discussed as genetic human resources are limited and indication of theranostic tests will increase. Methods: Genetic counseling was conducted within 15 days following inclusion in the study for patients recruited between December 2015 and July 2019. In silico analyses from theranostic ES were limited to 317 genes involved in oncogenesis, from both tumor and blood DNA. Results: Six hundred and sixty six patients had a genetic consultation before ES. In 65/666 patients, 66 germline pathogenic or likely pathogenic (P/LP) variants were identified in 16 actionable genes and seven non-actionable genes according to French guidelines. 24/65 patients had previously received genetic analysis for diagnostic purposes, and for 17 of them, a P/LP variant had already been identified. Among the 48/65 remaining cases for which the EXOMA protocol revealed a previously unknown P/LP variant, only 19 met the criteria for genetic testing for inherited cancer risk after familial survey. These criteria had not been identified by the oncologist in 10 cases. In 21/65 cases, the variant was considered incidental. Discussion: In 7.4% of patients, an undiagnosed hereditary genetic predisposition was identified, whether or not related to the clinical presentation, and germline analysis impacted oncological management for only 6.3% of the cohort. This low percentage should be weighed against the burden of systematic genetic consultation and urgent circuits. Information or training tools to form oncologists to the prescription of germline genetic analyses should be explored, as well as information supports and patient preferences.
Background: Millions of children have been born throughout the world thanks to ARTs, the harmlessness of which has not yet been fully demonstrated. For years, efforts to evaluate the specific effects of ART have focused on the embryo; however, it is the oocyte quality that mainly dictates first and foremost the developmental potential of the future embryo. Ovarian stimulation, cryopreservation, and IVM are sometimes necessary steps to obtain a mature oocyte, but they could alter the appropriate expression of the oocyte genome. Additionally, it is likely that female infertility, environmental factors, and lifestyle have a significant influence on oocyte transcriptomic quality, which may interfere with the outcome of an ART attempt. Objective and rationale: The objective of this review is to identify transcriptomic changes in the human oocyte caused by interventions specific to ART but also intrinsic factors such as age, reproductive health issues, and lifestyle. We also provide recommendations for future good practices to be conducted when attempting ART. Search methods: An in-depth literature search was performed on PubMed to identify studies assessing the human oocyte transcriptome following ART interventions, or in the context of maternal aging, suboptimal lifestyle, or reproductive health issues. Outcomes: ART success is susceptible to external factors, maternal aging, lifestyle factors (smoking, BMI), and infertility due to endometriosis or polycystic ovary syndrome. Indeed, all of these are likely to increase oxidative stress and alter mitochondrial processes in the foreground. Concerning ART techniques themselves, there is evidence that different ovarian stimulation regimens shape the oocyte transcriptome. The perturbation of processes related to the mitochondrion, oxidative phosphorylation, and metabolism is observed with IVM. Cryopreservation might dysregulate genes belonging to transcriptional regulation, ubiquitination, cell cycle, and oocyte growth pathways. For other ART laboratory factors such as temperature, oxygen tension, air pollution, and light, the evidence remains scarce. Focusing on genes involved in chromatin-based processes such as DNA methylation, heterochromatin modulation, histone modification, and chromatin remodeling complexes, but also genomic imprinting, we observed systematic dysregulation of such genes either after ART intervention or lifestyle exposure, as well as due to internal factors such as maternal aging and reproductive diseases. Alteration in the expression of such epigenetic regulators may be a common mechanism linked to adverse oocyte environments, explaining global transcriptomic modifications. Wider implications: Many IVF factors and additional external factors have the potential to impair oocyte transcriptomic integrity, which might not be innocuous for the developing embryo. Fortunately, it is likely that such dysregulations can be minimized by adapting ART protocols or reducing adverse exposure.
Three‐dimensional (3D) food printing is widely investigated in the food sectors, such as customised food designs, personalised nutrition and simplifying the supply chain. This study aimed to investigate the rheological properties and filament geometry of buttermilk‐mashed potatoes (BMP) to print 3D animal‐shaped foods through a syringe extrusion 3D printing technique using BMP as the printing material. The rheological studies showed that the BMP made with different weight ratios of mashed potato powder to milk‐water‐butter (BMP 1:4, 1:4.5, 1:5, 1:5.5 and 1:6) showed shear‐thinning properties that were suitable for 3D printing. The addition of liquid component is helpful in decreasing the viscosity of the BMP to flow through nozzles. Furthermore, water‐holding capacity decreased with an increased liquid ratio. The BMP 1:5 was optimal with high accuracy in all nozzles, and the optimal nozzle was 21G. It represented excellent shape fidelity and geometry. BMP1:5 with nozzle size 21G demonstrated 103.3% ± 1.3% active ingredient content, accurate ingredient content in various sizes of 3D‐printed objects and precision in weight. This study suggested that 3D printing based on BMP could produce complex‐shaped food patterns for further development and applications for active ingredient administration in children by a food base.
The gut microbiota and dysbiosis have been implicated in various metabolic diseases and gastrointestinal disorders. Recently, there has been growing evidence suggesting the influence of gut microbiota on neurological disorders, including autism. Although the number of children diagnosed with autism is increasing, the exact cause of the disease remains unknown. Numerous factors, such as genetics, environment, and diet, appear to contribute to its onset. Nevertheless, a degree of general consensus exists regarding the notion that the disease’s progression likely demands the participation of multiple factors. Among the potential causes, the role of the microbiota is particularly intriguing. The gut and brain have extensive connections, with a significant number of neuronal cells in the gut, and autism is often associated with gastrointestinal issues. In this review, the most recent information available on autism and microbiota has been analyzed. Findings of this study indicate that: (1) the microbiota is clearly altered in individuals with autism spectrum disorder (ASD); (2) microbiota transplantation appears to be effective in reducing the severity of autism symptoms; (3) while the microbiota is not solely responsible for the onset of autism, it likely plays a significant role. Considering all the available information, it is suggested that modifying the gut microbiota may have a positive impact on individuals with autism. This opens up possibilities for the use of pre- or probiotics in the treatment of children with ASD, as well as the potential use of fecal microbiota transfer.
We study Toeplitz operators on the Bargmann space, with Toeplitz symbols given by exponentials of complex quadratic forms. We show that the boundedness of the corresponding Weyl symbols is necessary for the boundedness of the operators, thereby completing the proof of the Berger–Coburn conjecture in this case. We also show that the compactness of such Toeplitz operators is equivalent to the vanishing of their Weyl symbols at infinity.
Background: Parastomal incisional hernia (PH) is a frequent complication following the creation of an ileal conduit (IC), and it can be a significant detriment to quality of life. The aim of this study was to evaluate outcomes of PH repair following IC for urinary diversion. Method: A multicenter retrospective study was conducted of 6 academic hospitals in France. The study's population included patients who underwent surgical treatment for parastomal hernia following IC creation from 2013 to 2021. Results: Fifty-one patients were included in the study. Median follow up was 15.3 months. Eighteen patients presented with a recurrence (35%), with a median time to recurrence of 11.1 months. The vast majority of PH repair was performed through an open approach (88%). With regard to technique, Keyhole was the most reported technique (46%) followed by Sugarbaker (22%) and suture only (20%). The Keyhole technique was associated with a higher risk of recurrence compared to the Sugarbaker technique (52% vs 10%, p = 0.046). Overall, there was a 7.8% rate of major complications without a statistical difference between PH repair techniques for major complications. Conclusion: Surgical treatment of parastomal hernia following IC was associated with a high risk of recurrence. Novel surgical approaches to PH repair should be considered.
Background: Circulating endotoxins could result from bacterial digestive translocation during sepsis, thus contributing to uncontrolled systemic inflammation, leading in turn to organ dysfunction. We addressed this issue in the setting of severe pneumococcal pneumonia. Methods: Endotoxemia was measured in a clinically relevant rabbit model of ventilated pneumococcal pneumonia and in 110 patients with bacteraemic pneumonia, using a patented mass spectrometry (LC-MS/MS) method for detection of 3-OH fatty acids (C10, C12, C14, C16 and C18), which are molecules bound to the lipid A motif of LPS. Results: Whereas higher levels of systemic inflammation and organ dysfunctions were found, there was no significant difference in lipopolysaccharide concentrations when infected rabbits were compared to non-infected ones, or when patients were compared to healthy volunteers. Conclusions: Seemingly, endotoxins do not drive the overwhelming inflammation associated with severe forms of pneumococcal pneumonia.
Trace fossils offer a great potential to enhance our understanding of the rise of dinosaurs and their interactions with the environment. Here, we report a Rhaetian theropod footprint found in the Shazhenxi Formation of the Zigui Basin, representing the stratigraphically oldest dinosaur track recorded from the Middle Yangtze region and has great significance for understanding the Late Triassic theropods and their distribution across East Asia. The tridactyl track is assigned to cf. Eubrontes isp. and shows a similar morphology with some tracks from the Sichuan Basin, indicating that Eubrontes had a wider spatial distribution in the Upper Triassic than previously thought. This work highlights the great interest and importance of palaeoichnological prospecting in the Triassic deposits of the Zigui Basin.
One can observe that Coxeter groups and right‐angled Artin groups share the same solution to the word problem. On the other hand, in his study of reflection subgroups of Coxeter groups, Dyer introduces a family of groups, which we call Dyer groups, which contains both, Coxeter groups and right‐angled Artin groups. We show that all Dyer groups have this solution to the word problem, we show that a group which admits such a solution belongs to a little more general family of groups that we call quasi‐Dyer groups, and we show that this inclusion is strict. Then we show several results on parabolic subgroups in quasi‐Dyer groups and in Dyer groups. Notably, we prove that any intersection of parabolic subgroups in a Dyer group of finite type is a parabolic subgroup.
Purpose: Survivors after acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19) are at high risk of developing respiratory sequelae and functional impairment. The healthcare crisis caused by the pandemic hit socially disadvantaged populations. We aimed to evaluate the influence of socio-economic status on respiratory sequelae after COVID-19 ARDS. Methods: We carried out a prospective multicenter study in 30 French intensive care units (ICUs), where ARDS survivors were pre-enrolled if they fulfilled the Berlin ARDS criteria. For patients receiving high flow oxygen therapy, a flow ≥ 50 l/min and an FiO2 ≥ 50% were required for enrollment. Socio-economic deprivation was defined by an EPICES (Evaluation de la Précarité et des Inégalités de santé dans les Centres d'Examens de Santé - Evaluation of Deprivation and Inequalities in Health Examination Centres) score ≥ 30.17 and patients were included if they performed the 6-month evaluation. The primary outcome was respiratory sequelae 6 months after ICU discharge, defined by at least one of the following criteria: forced vital capacity < 80% of theoretical value, diffusing capacity of the lung for carbon monoxide < 80% of theoretical value, oxygen desaturation during a 6-min walk test and fibrotic-like findings on chest computed tomography. Results: Among 401 analyzable patients, 160 (40%) were socio-economically deprived and 241 (60%) non-deprived; 319 (80%) patients had respiratory sequelae 6 months after ICU discharge (81% vs 78%, deprived vs non-deprived, respectively). No significant effect of socio-economic status was identified on lung sequelae (odds ratio (OR), 1.19 [95% confidence interval (CI), 0.72-1.97]), even after adjustment for age, sex, most invasive respiratory support, obesity, most severe P/F ratio (adjusted OR, 1.02 [95% CI 0.57-1.83]). Conclusions: In COVID-19 ARDS survivors, socio-economic status had no significant influence on respiratory sequelae 6 months after ICU discharge.
Although there is a wide range of shape descriptors available in the literature, most of them are restricted to a specific class of shapes and no one can achieve satisfactory shape retrieval results when used with different classes of shapes. Introducing new descriptors, improving, or merging existing descriptors are potential strategies for enhancing shape retrieval algorithms. In this paper, we propose a Query Perturbation-based (QPert) method for shape retrieval. QPert perturbs the query shape to create copies or clones that are closer than the query itself to the database shapes. Clones are created by adding a small noise to the coordinates of a randomly selected subset of mesh vertices or applying genetic operators between existing clones. A Genetic Algorithm (GA) gradually develops a population of clones so that the fittest clones get closer and closer to their most similar shapes in the database. The GA is implemented as a multiagent system (MAS) that enables any number of shape descriptors, classical or modern, to cooperate without the need for synchronization or direct communication between agents. Experimental results and comparisons demonstrate the advantages of this approach, regardless of the shape descriptors used.
The microsporidian genus Nosema is primarily known to infect insects of economic importance stimulating high research interest, while other hosts remain understudied. Nosema granulosis is one of the formally described Nosema species infecting amphipod crustaceans, being known to infect only two host species. Our first aim was to characterize Nosema spp. infections in different amphipod species from various European localities using the small subunit ribosomal DNA (SSU) marker. Second, we aimed to assess the phylogenetic diversity, host specificity and to explore the evolutionary history that may explain the diversity of gammarid-infecting Nosema lineages by performing a phylogenetic reconstruction based on RNA polymerase II subunit B1 (RPB1) gene sequences. For the host species Gammarus balcanicus, we also analyzed sex ratios of progenies to test for sex ratio distortion in relation with Nosema infection. We identified Nosema spp. in 316 individuals from nine amphipod species being widespread in Europe. The RPB1-based phylogenetic reconstruction using newly reported sequences and available data from other invertebrates identified 39 haplogroups being associated with amphipods. These haplogroups clustered into five clades (A-E) that did not form a single amphipod-infecting monophyletic group. Closely related sister clades C and D correspond to Nosema granulosis. Clades A, B and E might represent unknown Nosema species infecting amphipods. Host specificity seemed to be variable with some clades being restricted to single hosts, and some that could be found in several host species. We show that Nosema parasite richness in gammarid hosts is much higher than expected, illustrating the advantage of the use of RPB1 marker over SSU. Finally, we found no hint of sex ratio distortion in Nosema clade A infecting G. balcanicus. This study shows that Nosema spp. are abundant, widespread and diverse in European gammarids. Thus, Nosema is as diverse in aquatic as in terrestrial hosts.
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