Between 30% and 70% of patients with breast cancer have pre-existing chronic conditions, and more than half are on long-term non-cancer medication at the time of diagnosis. Preliminary ...epidemiological evidence suggests that some non-cancer medications may affect breast cancer risk, recurrence, and survival. In this nationwide cohort study, we assessed the association between medication use at breast cancer diagnosis and survival. We included 235,368 French women with newly diagnosed non-metastatic breast cancer. In analyzes of 288 medications, we identified eight medications positively associated with either overall survival or disease-free survival: rabeprazole, alverine, atenolol, simvastatin, rosuvastatin, estriol (vaginal or transmucosal), nomegestrol, and hypromellose; and eight medications negatively associated with overall survival or disease-free survival: ferrous fumarate, prednisolone, carbimazole, pristinamycin, oxazepam, alprazolam, hydroxyzine, and mianserin. Full results are available online from an interactive platform ( https://adrenaline.curie.fr ). This resource provides hypotheses for drugs that may naturally influence breast cancer evolution.
White spruce (Picea glauca) is a dominant conifer of the boreal forests of North America, and providing genomics resources for this commercially valuable tree will help improve forest management and ...conservation efforts. Sequencing and assembling the large and highly repetitive spruce genome though pushes the boundaries of the current technology. Here, we describe a whole-genome shotgun sequencing strategy using two Illumina sequencing platforms and an assembly approach using the ABySS software. We report a 20.8 giga base pairs draft genome in 4.9 million scaffolds, with a scaffold N50 of 20,356 bp. We demonstrate how recent improvements in the sequencing technology, especially increasing read lengths and paired end reads from longer fragments have a major impact on the assembly contiguity. We also note that scalable bioinformatics tools are instrumental in providing rapid draft assemblies.
The Picea glauca genome sequencing and assembly data are available through NCBI (Accession#: ALWZ0100000000 PID: PRJNA83435). http://www.ncbi.nlm.nih.gov/bioproject/83435.
Allergic asthma often coexists with different pathological conditions, called multimorbidities, that are mostly of allergic nature and share a common underlying inflammatory pathophysiological ...mechanism. Multimorbidities of allergic asthma may influence asthma control, its severity, and patients' response to treatment, and contribute to the overall socioeconomic burden of the disease. Immunoglobulin E (IgE) is known to play a central role in the pathogenesis of various allergic diseases, including asthma. Thus, IgE-mediated immunologic pathways present an attractive target for intervention in asthma and multimorbidities. In this review, we discuss the most frequently reported IgE-mediated multimorbidities in allergic asthma, including allergic rhinitis, rhinoconjunctivitis, atopic dermatitis, vernal keratoconjunctivitis, chronic rhinosinusitis with nasal polyps, food allergies, and allergic bronchopulmonary aspergillosis. Omalizumab is a recombinant humanized monoclonal antibody against IgE and has been in use to treat allergic asthma for more than a decade. We comprehensively review the clinical evidence for omalizumab in the treatment of the aforementioned multimorbidities in allergic asthma.
In this work, a hardware-in-the-loop (HIL) simulator is designed to diagnose the behavior of an autonomous sailboat as it navigates between waypoints. At its core, the HIL simulator includes the ...sailboat pilot on an embedded system. The sensor data input to the embedded system is fed by a navigation simulator that takes into account the different forces on the sailboat due to the wind, waves and current conditions. The HIL simulator is then tested for a navigation route from sea trials published in 2014, and the behavior of the automated pilot is compared to its behavior when the vessel is driven by a crew. As demonstrated, the automated system can outperform the man-operated vessel. The tool is also used to diagnose weaknesses in the sailboat autopilot algorithm that can be improved in the future.
Association studies are widely utilized to analyze complex traits but their ability to disclose genetic architectures is often limited by statistical constraints, and functional insights are usually ...minimal in nonmodel organisms like forest trees. We developed an approach to integrate association mapping results with co‐expression networks. We tested single nucleotide polymorphisms (SNPs) in 2652 candidate genes for statistical associations with wood density, stiffness, microfibril angle and ring width in a population of 1694 white spruce trees (Picea glauca). Associations mapping identified 229–292 genes per wood trait using a statistical significance level of P < 0.05 to maximize discovery. Over‐representation of genes associated for nearly all traits was found in a xylem preferential co‐expression group developed in independent experiments. A xylem co‐expression network was reconstructed with 180 wood associated genes and several known MYB and NAC regulators were identified as network hubs. The network revealed a link between the gene PgNAC8, wood stiffness and microfibril angle, as well as considerable within‐season variation for both genetic control of wood traits and gene expression. Trait associations were distributed throughout the network suggesting complex interactions and pleiotropic effects. Our findings indicate that integration of association mapping and co‐expression networks enhances our understanding of complex wood traits.
Anti-IgE therapy with omalizumab reduces serum levels of free IgE and downregulates expression of IgE receptors (FcεRI) on mast cells and basophils. In the airways of patients with mild allergic ...asthma, omalizumab reduces FcεRI
+ and IgE
+ cells and causes a profound reduction in tissue eosinophilia, together with reductions in submucosal T-cell and B-cell numbers. In patients with seasonal allergic rhinitis, omalizumab inhibits the allergen-induced seasonal increases in circulating and tissue eosinophils. Omalizumab decreases FcεRI expression on circulating dendritic cells, which might lead to a reduction in allergen presentation, T
H2 cell activation, and proliferation. As a systemic anti-IgE agent, omalizumab has demonstrated clinical efficacy in patients with moderate and severe allergic asthma and in those with seasonal and perennial allergic rhinitis, as well as in patients with concomitant allergic asthma and allergic rhinitis. The anti-inflammatory effects of omalizumab at different sites of allergic inflammation and the clinical benefits of anti-IgE therapy in patients with allergic asthma and allergic rhinitis emphasize the fundamental importance of IgE in allergic inflammation.
Whether long-term exposure air to pollution has effects on allergic sensitization is controversial.
Our aim was to investigate associations of air pollution exposure at birth and at the time of later ...biosampling with IgE sensitization against common food and inhalant allergens, or specific allergen molecules, in children aged up to 16 years.
A total of 6163 children from 4 European birth cohorts participating in the Mechanisms of the Development of ALLergy MeDALL consortium were included in this meta-analysis of the following studies: Children, Allergy, Milieu, Stockholm, Epidemiology (BAMSE) (Sweden), Influences of Lifestyle-Related Factors on the Human Immune System and Development of Allergies in Childhood (LISA)/German Infant Study on the Influence of Nutrition Intervention PLUS Environmental and Genetic Influences on Allergy Development (GINIplus) (Germany), and Prevention and Incidence of Asthma and Mite Allergy (PIAMA) (The Netherlands). The following indicators were modeled by land use regression: individual residential outdoor levels of particulate matter with aerodynamic diameters less than 2.5 μm, less than 10 μm, and between 2.5 and 10 μm; PM2.5 absorbance (a measurement of the blackness of PM2.5 filters); and nitrogen oxides levels. Blood samples drawn at ages 4 to 6 (n = 5989), 8 to 10 (n = 6603), and 15 to 16 (n = 5825) years were analyzed for IgE sensitization to allergen extracts by ImmunoCAP. Additionally, IgE against 132 allergen molecules was measured by using the MedALL microarray chip (n = 1021).
Air pollution was not consistently associated with IgE sensitization to any common allergen extract up to age 16 years. However, allergen-specific analyses suggested increased risks of sensitization to birch (odds ratio OR = 1.12 95% CI = 1.01-1.25 per 10-μg/m3 increase in NO2 exposure). In a subpopulation with microarray data, IgE to the major timothy grass allergen Phleum pratense 1 (Phl p 1) and the cat allergen Felis domesticus 1 (Fel d 1) greater than 3.5 Immuno Solid-phase Allergen Chip standardized units for detection of IgE antibodies were related to PM2.5 exposure at birth (OR = 3.33 95% CI = 1.40-7.94 and OR = 4.98 95% CI = 1.59-15.60, respectively, per 5-μg/m3 increase in exposure).
Air pollution exposure does not seem to increase the overall risk of allergic sensitization; however, sensitization to birch as well as grass pollen Phl p 1 and cat Fel d 1 allergen molecules may be related to specific pollutants.
Systemic/oral corticosteroids (OCS) have been used for decades in the management of acute asthma exacerbations and chronically in patients with uncontrolled severe asthma. However, while OCS are ...effective at treating acute exacerbations, there is only empirical evidence regarding the efficacy of OCS at reducing the rate of exacerbations. Evidence, although scarce, is suggestive of high exacerbation rates in severe asthma patients even when receiving maintenance treatment with OCS. In addition, use of OCS is associated with undesirable effects. Despite all this, physicians have continued to use OCS for managing severe asthma and acute exacerbation due to the lack of availability of effective alternatives. Fortunately, in the last decade several biologics have been proven safe and effective for patients with uncontrolled severe asthma. This has led to the Global Initiative for Asthma (GINA) recommending the use of biologics, instead of maintenance OCS, in patients with severe asthma (GINA Step 5). These include one biologic targeting immunoglobulin E (IgE) (omalizumab), and different biologics targeting interleukin-5 (IL-5), the IL-5 receptor (IL-5R) or IL-4 receptor α-unit (IL-4R α), including mepolizumab (subcutaneous), reslizumab (intravenous), benralizumab (subcutaneous) and dupilumab (subcutaneous).
Omalizumab for the treatment of severe allergic asthma reduces exacerbations, irrespective of blood eosinophil levels. Anti-IL-5/IL-5R biologics are indicated in patients with severe eosinophilic asthma and repetitive exacerbations, irrespective of the presence or absence of allergy. Recently, an anti-IL4Rα biologic has been approved by the FDA for eosinophilic phenotype or oral corticosteroid-dependent asthma. Finally, physicians should consider using biologics as an alternative to chronic OCS therapy.
•Oral corticosteroids (OCS) are associated with several adverse effects.•OCS should be prescribed to patients after careful assessments of potential risks compared to benefits.•Omalizumab has 15 years of clinical experience with more than 800,000 patient-years of exposure which make it the first choice of add-on therapy in patients with severe allergic asthma.•Biologics such as omalizumab (anti-immunoglobulin-E) or anti-interleukin (IL), IL-5 and IL-4/IL13, targeting biologics should be considered as alternatives to OCS in patients with uncontrolled severe asthma.•Physicians should either prescribe the appropriate biologic therapy or refer patients with corticosteroid-dependent severe asthma to a specialist.
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