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Topic-based search systems retrieve items by contextualizing the information seeking process on a topic of interest to the user. A key issue in topic-based search of text resources is how to automatically generate multiple queries that reflect the topic of interest in such a way that precision, recall, and diversity are achieved. The problem of generating topic-based queries can be effectively addressed by Multi-Objective Evolutionary Algorithms, which have shown promising results. However, two common problems with such an approach are loss of diversity and low global recall when combining results from multiple queries. This work proposes a family of Multi-Objective Genetic Programming strategies based on objective functions that attempt to maximize precision and recall while minimizing the similarity among the retrieved results. To this end, we define three novel objective functions based on result set similarity and on the information theoretic notion of entropy. Extensive experiments allow us to conclude that while the proposed strategies significantly improve precision after a few generations, only some of them are able to maintain or improve global recall. A comparative analysis against previous strategies based on Multi-Objective Evolutionary Algorithms, indicates that the proposed approach is superior in terms of precision and global recall. Furthermore, when compared to query-term-selection methods based on existing state-of-the-art term-weighting schemes, the presented Multi-Objective Genetic Programming strategies demonstrate significantly higher levels of precision, recall, and F1-score, while maintaining competitive global recall. Finally, we identify the strengths and limitations of the strategies and conclude that the choice of objectives to be maximized or minimized should be guided by the application at hand.

Mutations in the N-terminal WD40 domain of coatomer protein complex subunit α (COPA) cause a type I interferonopathy, typically characterized by alveolar hemorrhage, arthritis, and nephritis. We described 3 heterozygous mutations in the C-terminal domain (CTD) of COPA (p.C1013S, p.R1058C, and p.R1142X) in 6 children from 3 unrelated families with a similar syndrome of autoinflammation and autoimmunity. We showed that these CTD COPA mutations disrupt the integrity and the function of coat protein complex I (COPI). In COPAR1142X and COPAR1058C fibroblasts, we demonstrated that COPI dysfunction causes both an anterograde ER-to-Golgi and a retrograde Golgi-to-ER trafficking defect. The disturbed intracellular trafficking resulted in a cGAS/STING-dependent upregulation of the type I IFN signaling in patients and patient-derived cell lines, albeit through a distinct molecular mechanism in comparison with mutations in the WD40 domain of COPA. We showed that CTD COPA mutations induce an activation of ER stress and NF-κB signaling in patient-derived primary cell lines. These results demonstrate the importance of the integrity of the CTD of COPA for COPI function and homeostatic intracellular trafficking, essential to ER homeostasis. CTD COPA mutations result in disease by increased ER stress, disturbed intracellular transport, and increased proinflammatory signaling.

Background: Prostate cancer (PC) progression is strongly driven by dysregulated signaling pathways, with NF-κB playing a central role. Sesquiterpene lactones have been reported to modulate this pathway. This study evaluated and compared the cytotoxic effects of two structurally distinct sesquiterpene lactones: Tatridin A, a germacranolide, and desacetyl-β-cyclopyrethrosin, a eudesmanolide derivative. Their mechanisms of action were also examined, focusing on oxidative stress induction and NF-κB modulation. Methods: Chemical structures were confirmed by NMR and X-ray crystallography. Cytotoxicity was assessed in DU-145 and 22Rv1 PC cells using real-time cell analysis. Reactive oxygen species (ROS) and mitochondrial membrane potential (ΔΨm) were measured with fluorometric assays. NF-κB activity was determined in THP-1 reporter cells and by Western blot of IκBα phosphorylation. Results: Tatridin A markedly reduced viability, showing lower IC50 values (81.4 ± 2.7 µM in DU-145 and 50.7 ± 1.9 µM in 22Rv1 cells) than desacetyl-β-cyclopyrethrosin (166.9 ± 3.2 µM and 290.3 ± 8.3 µM, respectively). It also inhibited proliferation at markedly lower concentrations, with clonogenic IC50 values of 7.7 µM in DU-145 and 5.24 µM in 22Rv1cells. Both compounds increased ROS, but tatridin A induced earlier and stronger responses and ΔΨm loss. Furthermore, tatridin A more effectively inhibited NF-κB signaling than classical inhibitors. Conclusions: Tatridin A exerts cytotoxic effects through oxidative stress, mitochondrial impairment, and NF-κB inhibition, supporting the therapeutic potential of germacranolides for the treatment of advanced PC.

The new guidelines of the European Society of Cardiology on acute coronary syndromes (ACS) were published during the first day of the European Congress 2023.

Mutations in the N-terminal WD40 domain of coatomer protein complex subunit a (CORA) cause a type I interferonopathy, typically characterized by alveolar hemorrhage, arthritis, and nephritis. We described 3 heterozygous mutations in the C-terminal domain (CTD) of CORA (p.C1O13S, p.R1058C, and p.R1142X) in 6 children from 3 unrelated families with a similar syndrome of autoinflammation and autoimmunity. We showed that these CTD CORA mutations disrupt the integrity and the function of coat protein complex I (CORI). In COPAR1142X and COPAR1O58C fibroblasts, we demonstrated that COPI dysfunction causes both an anterograde ER-to-Golgi and a retrograde Golgi-to-ER trafficking defect. The disturbed intracellular trafficking resulted in a cCAS/STINC-dependent upregulation of the type IIFN signaling in patients and patient-derived cell lines, albeit through a distinct molecular mechanism in comparison with mutations in the WD40 domain of COPA. We showed that CTD COPA mutations induce an activation of ER stress and NF-κB signaling in patient-derived primary cell lines. These results demonstrate the importance of the integrity of the CTD of COPA for COPI function and homeostatic intracellular trafficking, essential to ER homeostasis. CTD COPA mutations result in disease by increased ER stress, disturbed intracellular transport, and increased proinflammatory signaling.

This study evaluated the influence of thickness increment on degree of conversion (DC), Knoop microhardness (KHN), and polymerization-shrinkage stress (PSS) by photoelasticity of three dental composites. For DC and KHN, 45 samples were prepared and divided into nine groups (n=5), according to composite (microhybrid [Filtek Z250 - Z250], bulk-fill flowable [SureFil SDR Flow - SDR], and nanohybrid composite [N'Durance - NDU]) and increment thickness (1, 1.5, and 3 mm). PSS was measured by photoelastic analysis. Composites were placed into a photo-elastic model cavity and light-cured. DC and KHN data were subjected to two-way ANOVA and Bonferroni post hoc test. PSS results were qualitatively evaluated through Kruskal-Wallis test. SDR showed the highest DC values. At top and bottom surfaces, the highest KHN was obtained by Z250. Z250 showed higher PSS than SDR in 1.5 mm increments. NDU showed higher PSS than SDR in 3 mm increments. The bulk-fill composite demonstrated better DC and similar KHN and PSS in deeper layers compared to conventional composites. Bulk-fill composites may perform as well as conventional nanohybrid and microhybrid composites.

Background: Oncological patients have a higher risk of prolonged SARS-CoV-2 shedding, which, in turn, can lead to evolutionary mutations and emergence of novel viral variants. The aim of this study was to analyze biological samples of a cohort of oncological patients by deep sequencing to detect any significant viral mutations. Methods: High-throughput sequencing was performed on selected samples from a SARS-CoV-2-positive oncological patient cohort. Analysis of variants and minority variants was performed using a validated bioinformatics pipeline. Results: Among 54 oncological patients, we analyzed 12 samples of 6 patients, either serial nasopharyngeal swab samples or samples from the upper and lower respiratory tracts, by high-throughput sequencing. We identified amino acid changes D614G and P4715L as well as mutations at nucleotide positions 241 and 3037 in all samples. There were no other significant mutations, but we observed intra-host evolution in some minority variants, mainly in the ORF1ab gene. There was no significant mutation identified in the spike region and no minority variants common to several hosts. Conclusions: There was no major and rapid evolution of viral strains in this oncological patient cohort, but there was minority variant evolution, reflecting a dynamic pattern of quasi-species replication.

Endometriosis affects women in reproductive age and can involve bowel in 6–12 % of the patients. In case of bowel occlusion or deep pain, radical laparoscopic endometriosic surgery associated with bowel resection is recommended. The purpose of this study was to analyze the conception rate, the obstetric complications, and the pregnancy outcome. This is a retrospective study; we investigated 51 patients with deep endometriosis who underwent surgical treatment with bowel resection during the period between 2000 and 2007. Among the 30 patients who gave birth to at least one live child after surgery, we considered only the first pregnancy following bowel resection and we investigated the incidence of pregnancy disorders, the gestational age at delivery, the baby birth weight, and the complications related to the different ways of delivery. We compared the results with a control group of 93 patients with no previous abdominal surgery. The whole group of 51 patients tried to conceive after surgery, and 30 women had at least one pregnancy with the birth of an alive baby. Considering only the first pregnancies after surgery, 6 (20 %) experienced gestational hypertensive disorders, 3 (10 %) had placenta previa, 6 (20 %) had preterm birth (<37 weeks), and 1 patient (3.3 %) gestational diabetes. In this group, the average newborn weight was 3000 ± 545 g. Compared with the control group, women with previous bowel resection for deep endometriosis had a higher risk of hypertensive disorders ( p  < 0.05), placenta previa ( p  < 0.05), and lower newborn weight ( p  < 0.05), while the association with preterm birth and gestational diabetes was not statistically significant. These patients experience 12 vaginal deliveries (40 %) and 18 caesarean sections (60 %). Comparing with the caesarean rate in the control group (29.03 %), the incidence of caesarean section in the study population was substantially higher ( p  < 0.01) with 33.3 % of the sections performed because of previous bowel surgery. No differences in severe complication rates were observed between vaginal and caesarean deliveries (ns). Complete removal of endometriosis with bowel segmental resection seems to improve the pregnancy rate, but in this group, there is an increased incidence of hypertensive disorders, placenta previa, and lower newborn weight. Despite the small number of patients, we do not observe more complications in the vaginal group than in the caesarean group, so we hypothesize the previous radical surgery should not influence the way of delivery.

Background There are inconsistencies in the literature on reproductive and genital health determinants of human papillomavirus (HPV) infection, the primary cause of cervical cancer. We examined these factors in the Ludwig-McGill Cohort Study, a longitudinal, repeated-measurements investigation on the natural history of HPV infection. Methods We analyzed a cohort subset of 1867 women with one complete year of follow-up. We calculated odds ratios (OR) and 95 % confidence intervals (CI) for reproductive and genital health characteristics from questionnaire and laboratory data in relation to 1-year period prevalence of HPV infection. Two outcomes were measured; the first based on phylogenetic grouping of HPV types based on tissue tropism and oncogenicity (Alphapapillomavirus Subgenus 1: species 1, 8, 10 and 13; Subgenus 2: species 5, 6, 7, 9, 11; Subgenus 3: species 3, 4 and 14) and the second based on transient or persistent HPV infections. Results Lifetime (Subgenus 3 OR = 2.00, CI: 1.23–3.24) and current (Subgenus 3 OR = 2.00, CI: 1.15–3.47) condom use and use of contraceptive injections (Subgenus 1 OR = 1.96, CI: 1.22–3.16, Subgenus 2 OR = 1.34, CI: 1.00–1.79) were associated with increased risk of HPV infection. Intrauterine device use was protective (Subgenus 1 OR = 0.48, CI: 0.30–0.75, Subgenus 2 OR = 0.78, CI: 0.62–0.98). These factors were not associated with persistence of HPV infection. Tampon use, previous gynecologic infections and cervical inflammation were associated with an overall increased risk of HPV infection. Conclusions Cervical HPV infection was associated with reproductive and genital health factors. Further studies are necessary to confirm the low to moderate associations observed.

Objectives In many settings, human papillomavirus (HPV) DNA testing already plays an important role in cervical cancer screening. It is unclear whether hormonal fluctuations associated with menstrual phase or oral contraceptive (OC) use have any effect on HPV detection. We evaluated the effects of OC use and timing of cervical sampling in relation to women's last menstrual period (LMP) on HPV detection, and viral load in the Brazilian Ludwig–McGill cohort study. Methods Women in the cohort were followed every 4–6 months, and at each clinic visit they were asked to complete a questionnaire and to provide a cervical sample for HPV testing. Specimens from 6093 patient visits (n=2209 women) were categorised according to date of LMP into four distinct phases: follicular (days 5–9), midcycle (days 10–15), luteal (days 16–22), or late luteal (days 23–31). Results Compared with follicular phase (referent group), HPV detection did not differ according to reported LMP for midcycle (OR=1.14, 95% CI 0.95 to 1.37), luteal (OR=1.03, 95% CI 0.85 to 1.25), or late luteal menstrual phase (OR=1.01, 95% CI 0.83 to 1.24), and was also not influenced by OC use. Analyses restricted to high-risk HPV types (grouped) and HPVs 16 and 18 (separately), produced similar non-significant associations. For HPV-positive samples, we found that the menstrual phase did not influence the total viral load. Conclusions These results indicate HPV detection is not associated with menstrual phase. Our findings suggest that standardising the timing of specimen collection for HPV testing is not necessary.