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Haugaard Luna opublikował 5 miesięcy, 2 tygodnie temu
Inflammatory breast cancer (IBC) is a rare and aggressive type of breast cancer whose molecular basis is poorly understood. We performed a comprehensive molecular analysis of 24 IBC biopsies naïve of treatment, using a high-resolution microarray platform and targeted next-generation sequencing (105 cancer-related genes). The genes more frequently affected by gains were MYC (75%) and MDM4 (71%), while frequent losses encompassed TP53 (71%) and RB1 (58%). Increased MYC and MDM4 protein expression levels were detected in 18 cases. These genes have been related to IBC aggressiveness, and MDM4 is a potential therapeutic target in IBC. Functional enrichment analysis revealed genes associated with inflammatory regulation and immune response. High homologous recombination (HR) deficiency scores were detected in triple-negative and metastatic IBC cases. A high telomeric allelic imbalance score was found in patients having worse overall survival (OS). The mutational profiling was compared with non-IBC (TCGA, n = 250) and IBC (n = 118) from four datasets, validating our findings. Higher frequency of TP53 and BRCA2 variants were detected compared to non-IBC, while PIKC3A showed similar frequency. Variants in mismatch repair and HR genes were associated with worse OS. Our study provided a framework for improved diagnosis and therapeutic alternatives for this aggressive tumor type.Maternal fish intake during pregnancy has been associated with reduced allergy development in the offspring and here, we hypothesized that components of fish stimulate fetal immune maturation. The aim of this study was to investigate how maternal fish intake during pregnancy and levels of n-3 long-chain polyunsaturated fatty acids (LCPUFAs) in the infant’s cord serum correlated with different subsets of B- and T-cells in cord blood and B-cell activating factor (BAFF) in cord plasma, and with doctor-diagnosed allergy at 3 and 8 years of age in the FARMFLORA birth-cohort consisting of 65 families. Principal component analysis showed that infant allergies at 3 or 8 years of age were negatively associated with the proportions of n-3 LCPUFAs (eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid) in infant cord serum, which, in turn correlated positively with maternal fish intake during pregnancy. Both maternal fish intake and cord serum n-3 LCPUFAs correlated negatively to CD5+ B cells and the FOXP3+CD25high of the CD4+ T cell subsets in cord blood, but not to BAFF in cord plasma. Our observational study suggests that fish might contain components that promote maturation of the infant’s immune system in a manner that protects against allergy development.The Internet of Things (IoT) is currently the most popular field in communication and information techniques. However, designing a secure and reliable authentication scheme for IoT-based architectures is still a challenge. In 2019, Zhou et al. showed that schemes pro-posed by Amin et al. and Maitra et al. are vulnerable to off-line guessing attacks, user tracking attacks, etc. On this basis, a lightweight authentication scheme based on IoT is proposed, and an authentication scheme based on IoT is proposed, which can resist various types of attacks and realize key security features such as user audit, mutual authentication, and session security. However, we found weaknesses in the scheme upon evaluation. Hence, we proposed an enhanced scheme based on their mechanism, thus achieving the security requirements and resisting well-known attacks.Siderophores produced in soil by plant growth-promoting rhizobacteria (PGPRs) play several roles, including nutrient mobilizers and can be useful as plants defense elicitors. We investigated the role of a synthetic mixed ligand bis-catechol-mono-hydroxamate siderophore (SID) that mimics the chemical structure of a natural siderophore, fimsbactin, produced by Acinetobacter spp. in the resistance against the phytopathogen Pseudomonas syringaepv tomato DC3000 (Pst DC3000), in Arabidopsis thaliana. We first tested the antibacterial activity of SID against Pst DC3000 in vitro. After confirming that SID had antibacterial activity against Pst DC3000, we tested whether the observed in vitro activity could translate into resistance of Arabidopsis to Pst DC3000, using bacterial loads as endpoints in a plant infection model. Furthermore, using quantitative polymerase chain reaction, we explored the molecular actors involved in the resistance of Arabidopsis induced by SID. Finally, to assure that SID would not interfere with PGPRs, we tested in vitro the influence of SID on the growth of a reference PGPR, Bacillus subtilis. We report here that SID is an antibacterial agent as well as an inducer of systemic priming of resistance in A. thaliana against Pst DC3000, and that SID can, at the same time, promote growth of a PGPR.Cancer survivors suffer from emotional distress, which varies depending on several factors. However, existing emotion management programs are insufficient and do not take into consideration all of the factors. Social media provides a platform for understanding the emotions of the public. The aim of this study was to explore the relationship between the public’s emotions about cancer and factors affecting emotions using social media data. We used 321,339 posts on cancer and emotions relating to cancer extracted from 22 social media channels between 1 January 2014, and 30 June 2017. The factors affecting emotions were analyzed using association rule mining and social network analysis. Hope/gratitude was the most frequently mentioned emotion group on social media followed by fear/anxiety/overwhelmed, sadness/depression/loneliness/guilt, and anger/denial. Acute survival stage, treatment method, and breast cancer were associated with hope/gratitude. Early stage, gastrointestinal problems, fatigue/pain/fever, and pancreatic cancer were associated with fear/anxiety/overwhelmed. Surgery, hair loss/skin problems, and fatigue/pain/fever were associated with sadness/depression/loneliness/guilt. Acute survival stage and hair loss/skin problems were associated with anger/denial. We found that emotions concerning cancer differed depending on the cancer type, cancer stage, survival stage, treatment, and symptoms. These findings could guide the development of tailored emotional management programs for cancer survivors that meet the public’s needs more effectively.
The low-profile visualized intraluminal support junior (LVIS Jr.) is a new generation low-profile braided stent. Our aim was to evaluate the safety and efficacy of the LVIS Jr. in the stent-assisted coiling of unruptured middle cerebral artery (MCA) aneurysms. This was a multicenter retrospective study. Patient demographics, aneurysm characteristics, procedural details, complications, and the results of clinical and imaging follow-up were analyzed. Four centers participated in the study. A total of 162 consecutive patients with 162 unruptured MCA aneurysms were included for the analysis. The mean aneurysm size was 7.6 mm (range 2 to 37 mm) and 97.5% were wide-necked. Immediate postprocedural angiograms showed Raymond-Roy class 1 in 118 (72.8%), class 2 in 23 (14.2%), and class 3 in 21 patients (13%). Periprocedural complications occurred in 14 patients (8.6%). There were no procedure-related deaths. Follow-up imaging at 12-18 months post-procedure showed Raymond-Roy class 1 in 132 (81.5%), class 2 in 17 (10ural angiograms showed Raymond-Roy class 1 in 118 (72.8%), class 2 in 23 (14.2%), and class 3 in 21 patients (13%). Periprocedural complications occurred in 14 patients (8.6%). There were no procedure-related deaths. Follow-up imaging at 12-18 months post-procedure showed Raymond-Roy class 1 in 132 (81.5%), class 2 in 17 (10.5%), and class 3 in 13 patients (8%). There were 3 cases of in-stent stenosis (1.9%). All 162 patients had good clinical outcome (mRS score 0-2) at 90 days post-procedure. Stent-assisted coiling of unruptured MCA aneurysms with the LVIS Jr. stent is safe and effective, with high immediate and long-term total occlusion rates.Over 200 million people suffer from osteoporosis worldwide. Individuals with osteoporosis have increased rates of bone resorption while simultaneously having impaired osteogenesis. Most current treatments for osteoporosis focus on anti-resorptive methods to prevent further bone loss. However, it is important to identify safe and cost-efficient treatments that not only inhibit bone resorption, but also stimulate anabolic mechanisms to upregulate osteogenesis. Recent data suggest that macrophage polarization may contribute to osteoblast differentiation and increased osteogenesis as well as bone mineralization. Macrophages exist in two major polarization states, classically activated macrophages (M1) and alternatively activated macrophage (M2) macrophages. The polarization state of macrophages is dependent on molecules in the microenvironment including several cytokines and chemokines. Mechanistically, M2 macrophages secrete osteogenic factors that stimulate the differentiation and activation of pre-osteoblastic cells, such as mesenchymal stem cells (MSC’s), and subsequently increase bone mineralization. In this review, we cover the mechanisms by which M2 macrophages contribute to osteogenesis and postulate the hypothesis that regulating macrophage polarization states may be a potential treatment for the treatment of osteoporosis.Lipid biosynthesis produces glycerol, which is important in fueling turgor pressure necessary for germination and penetration of plant host by fungi. As the relationship between pathogenicity and the lipid biosynthetic pathway is not fully understood, we have elucidated the role of the fatty acid synthase beta subunit dehydratase (FAS1) gene in lipid biosynthesis. The FAS1 gene was silenced through homologous double crossover in Magnaporthe oryzae strain S6 to study the effect on lipid biosynthesis. The vegetative growth of Δfas1 mutants show the highest drop on oleic acid (between 10 and 50%), while the mycelial dry weight of mutants dropped significantly on all media. Conidiation of FAS1 mutants show a ~10- and ~5-fold reduction on oatmeal and Potato Dextrose Agar (PDA), respectively. Mutants formed mycelium that were mildly pigmented, indicating that the deletion of FAS1 may have affected melanin biosynthesis. Biochemical and gene expression studies concluded that the fatty acid degradation pathway might have been interrupted by FAS1 deletion. FAS1 mutants showed no enzyme activity on glucose or olive oil, suggesting that the mutants may lack functional peroxisomes and be defective in β-oxidation of fatty acids, hence explaining the reduced lipid deposits in the spores.Staphylococcus epidermidis is found naturally on the skin but is a common cause of persistent orthopaedic device-related infections (ODRIs). This study used a pan-genome and gene-by-gene approach to analyse the clonality of whole genome sequences (WGS) of 115 S. epidermidis isolates from 55 patients with persistent ODRIs. Analysis of the 522 gene core genome revealed that the isolates clustered into three clades, and MLST analysis showed that 83% of the isolates belonged to clonal complex 2 (CC2). Analysis also found 13 isolate pairs had different MLST types and less than 70% similarity within the genes; hence, these were defined as re-infection by a different S. epidermidis strain. Comparison of allelic diversity in the remaining 102 isolates (49 patients) revealed that 6 patients had microevolved infections (>7 allele differences), and only 37 patients (77 isolates) had a 'true’ persistent infection. Analysis of the core genomes of isolate pairs from 37 patients found 110/841 genes had variations; mainly in metabolism associated genes.