Differential impact of classical and non-canonical NF-κB pathway-related gene expression on the survival of breast cancer patients

Inflammation is a well-known driver of carcinogenesis and cancer progression, often attributed to the tumor microenvironment. However, tumor cells themselves are capable of secreting a variety of inflammatory molecules, leading to the activation of specific signaling pathways that promote tumor progression. The NF-κB signaling pathway is one of the most important connections between inflammation and tumorigenesis. NF-κB is a superfamily of transcription factors that plays an important role in several types of hematological and solid tumors, including breast cancer. However, the role of the NF-κB pathway in the survival of breast cancer patients is poorly studied. In this study, we analyzed and related the expression of both canonical and alternative NF-κB pathways and selected target genes with the relapse-free and overall survival of breast cancer patients. We used the public database Kaplan-Meier plotter (KMplot) which includes gene expression data and survival information of 3951 breast cancer patients. We found that the expression of IKKα was associated with poor relapse-free survival in patients with ER-positive tumors. Moreover, the expression of IL-8 and MMP-1 was associated with poor relapse-free and overall survival. In contrast, expression of IKKβ, p50, and p65 from the canonical pathway, and NIK and RELB from the alternative pathway correlated with better relapse-free survival also when the patients were classified by their hormonal and nodal status. Our study suggests that the expression of genes of the canonical and alternative NF-κB pathways is ultimately critical for tumor persistence. Understanding the communication between both pathways would help to find better therapeutic and prophylactic targets to prevent breast cancer progression and relapse

Aplastic Crisis as Primary Manifestation of Systemic Lupus Erythematosus

Aplastic crisis is an unusual feature of systemic lupus erythematosus (SLE). We report the case of a 54-year-old woman presenting with both (extravascular) Coombs-positive hemolytic anemia and laboratory findings of bone marrow hyporegeneration with concomitant severe neutropenia. A bone marrow biopsy confirmed aplastic crisis. Diagnostic work-up revealed soaring titers of autoantibodies (anti-nuclear, anti-double-stranded DNA, anti-cardiolipin-IgM, and anti-beta 2-glykoprotein-IgM antibodies), indicating a connective tissue disease as the most plausible reason for bone marrow insufficiency. As the criteria for SLE were fulfilled, we initiated an immunosuppressive therapy by steroids, which led to a rapid complete hematologic and clinical remission in our patient. In this case, we could report on one of the rare cases of SLE-induced aplastic crisis showing that this condition can be entirely reversed by immunosuppressive treatment and that SLE-induced aplastic crisis yields a good prognosis. In conclusion, in a case of aplastic crisis, physicians should be aware that SLE can be a rare cause that is accessible to specific treatment

Gravitational waves from single neutron stars: an advanced detector era survey

With the doors beginning to swing open on the new gravitational wave astronomy, this review provides an up-to-date survey of the most important physical mechanisms that could lead to emission of potentially detectable gravitational radiation from isolated and accreting neutron stars. In particular we discuss the gravitational wave-driven instability and asteroseismology formalism of the f- and r-modes, the different ways that a neutron star could form and sustain a non-axisymmetric quadrupolar "mountain" deformation, the excitation of oscillations during magnetar flares and the possible gravitational wave signature of pulsar glitches. We focus on progress made in the recent years in each topic, make a fresh assessment of the gravitational wave detectability of each mechanism and, finally, highlight key problems and desiderata for future work.Comment: 39 pages, 12 figures, 2 tables. Chapter of the book "Physics and Astrophysics of Neutron Stars", NewCompStar COST Action 1304. Minor corrections to match published versio

NGTS-11 b (TOI-1847 b): A Transiting Warm Saturn Recovered from a TESS Single-transit Event

We report the discovery of NGTS-11 b (=TOI-1847 b), a transiting Saturn in a 35.46-day orbit around a mid K-type star (Teff=5050 K). We initially identified the system from a single-transit event in a TESS full-frame image light-curve. Following seventy-nine nights of photometric monitoring with an NGTS telescope, we observed a second full transit of NGTS-11 b approximately one year after the TESS single-transit event. The NGTS transit confirmed the parameters of the transit signal and restricted the orbital period to a set of 13 discrete periods. We combined our transit detections with precise radial velocity measurements to determine the true orbital period and measure the mass of the planet. We find NGTS-11 b has a radius of 0.817+0.028-0.032 $R_J$, a mass of 0.344+0.092-0.073 $M_J$, and an equilibrium temperature of just 435+34-32 K, making it one of the coolest known transiting gas giants. NGTS-11 b is the first exoplanet to be discovered after being initially identified as a TESS single-transit event, and its discovery highlights the power of intense photometric monitoring in recovering longer-period transiting exoplanets from single-transit events

Population-based analysis of POT1 variants in a cutaneous melanoma case–control cohort

Pathogenic germline variants in the protection of telomeres 1 gene (POT1) have been associated with predisposition to a range of tumour types, including melanoma, glioma, leukaemia and cardiac angiosarcoma. We sequenced all coding exons of the POT1 gene in 2928 European-descent melanoma cases and 3298 controls, identifying 43 protein-changing genetic variants. We performed POT1-telomere binding assays for all missense and stop-gained variants, finding nine variants that impair or disrupt protein–telomere complex formation, and we further define the role of variants in the regulation of telomere length and complex formation through molecular dynamics simulations. We determine that POT1 coding variants are a minor contributor to melanoma burden in the general population, with only about 0.5% of melanoma cases carrying germline pathogenic variants in this gene, but should be screened in individuals with a strong family history of melanoma and/or multiple malignancies

Association of IL1B -511C/-31T haplotype and Helicobacter pylori vacA genotypes with gastric ulcer and chronic gastritis

<p>Abstract</p> <p>Background</p> <p>The association between proinflammatory cytokine gene polymorphisms and gastric diseases related to <it>Helicobacter pylori </it>varies by population and geographic area.</p> <p>Our objective was to determine if the <it>IL-1B </it>-<it>511 T>C </it>and -<it>31 C>T </it>polymorphisms and <it>H. pylori vacA </it>genotypes are associated with risk of chronic gastritis and gastric ulcer in a Mexican population.</p> <p>Methods</p> <p>We conducted endoscopic studies in 128 patients with symptoms of dyspepsia. We took two biopsies from the body, antrum, or ulcer edge from each patient, and classified our histopathological findings according to the Sydney System. <it>H. pylori </it>infection and <it>vacA </it>genotyping were accomplished via PCR from total DNA of the gastric biopsies. We confirmed the presence of anti-<it>H. pylori </it>serum IgG and IgM in 102 control subjects. In both case subjects and control subjects, the <it>IL-1B </it>-<it>511 T>C </it>polymorphism was genotyped by PCR-RFLPs and the <it>IL-1B -31 C>T </it>polymorphism was genotyped by pyrosequencing.</p> <p>Results</p> <p>Sixty-two point seven (62.7%) of the 102 control subjects were <it>H. pylori-</it>seropositive. Among the case subjects, 100 were diagnosed with chronic gastritis and 28 with gastric ulcer. We found that 77% of the patients with chronic gastritis and 85.7% of the patients with gastric ulcer were <it>H. pylori-</it>positive. The predominant <it>H. pylori </it>genotype was <it>vacA s1m1 </it>(58.4%) and the most frequent subtype was <it>vacA s1</it>. The -<it>511 TC</it>, (rs16944 -511 T>C) genotype and the -<it>511C </it>allele were associated with chronic gastritis (OR = 3.1, 95% CI = 1.4-6.8 and OR = 3.0, 95% CI = 1.4-6.0, respectively). The subjects carrying -<it>31T </it>(rs1143627 -31 C>T) were found to be at a higher risk of having chronic gastritis (OR = 2.8, 95% CI = 1.3-5.8). The <it>IL-1B </it>-<it>511C/-31T </it>haplotype was associated with chronic gastritis (OR = 2.1, 95% CI = 1.2-3.8) but not with gastric ulcer.</p> <p>Conclusions</p> <p>The <it>H. pylori vacA </it>genotypes identified herein were similar to those reported for other regions of Mexico. The <it>vacA s1m1 </it>genotype was not associated with gastric ulcer. In the southern Mexican population, the <it>IL-1B -511C </it>and -<it>31T </it>alleles and the -<it>511C/-31T </it>and -<it>511T/-31T </it>haplotypes are associated with increased risk of chronic gastritis and gastric ulcer.</p

Shared Decision Making Tools for People Facing Stroke Prevention Strategies in Atrial Fibrillation: A Systematic Review and Environmental Scan.

OBJECTIVE: Shared decision making (SDM) tools can help implement guideline recommendations for patients with atrial fibrillation (AF) considering stroke prevention strategies. We sought to characterize all available SDM tools for this purpose and examine their quality and clinical impact. METHODS: We searched through multiple bibliographic databases, social media, and an SDM tool repository from inception to May 2020 and contacted authors of identified SDM tools. Eligible tools had to offer information about warfarin and ≥1 direct oral anticoagulant. We extracted tool characteristics, assessed their adherence to the International Patient Decision Aids Standards, and obtained information about their efficacy in promoting SDM. RESULTS: We found 14 SDM tools. Most tools provided up-to-date information about the options, but very few included practical considerations (e.g., out-of-pocket cost). Five of these SDM tools, all used by patients prior to the encounter, were tested in trials at high risk of bias and were found to produce small improvements in patient knowledge and reductions in decisional conflict. CONCLUSION: Several SDM tools for stroke prevention in AF are available, but whether they promote high-quality SDM is yet to be known. The implementation of guidelines for SDM in this context requires user-centered development and evaluation of SDM tools that can effectively promote high-quality SDM and improve stroke prevention in patients with AF

Cell Free Expression of hif1α and p21 in Maternal Peripheral Blood as a Marker for Preeclampsia and Fetal Growth Restriction

Preeclampsia, a severe unpredictable complication of pregnancy, occurs in 6% of pregnancies, usually in the second or third trimester. The specific etiology of preeclampsia remains unclear, although the pathophysiological hallmark of this condition appears to be an inadequate blood supply to the placenta. As a result of the impaired placental blood flow, intrauterine growth restriction (IUGR) and consequential fetal oxidative stress may occur. Consistent with this view, pregnancies complicated by preeclampsia and IUGR are characterized by up-regulation of key transcriptional regulators of the hypoxic response including, hif1α and as well as p53 and its target genes. Recently, the presence of circulating cell-free fetal RNA has been documented in maternal plasma. We speculated that pregnancies complicated by preeclampsia and IUGR, will be associated with an abnormal expression of p53 and/or hif1α related genes in the maternal plasma. Maternal plasma from 113 singleton pregnancies (72 normal and 41 complicated pregnancies) and 19 twins (9 normal and 10 complicated pregnancies) were collected and cell free RNA was extracted. The expression of 18 genes was measured by one step real-time RT-PCR and was analyzed for prevalence of positive/negative expression levels. Results indicate that, among the genes examined, cell free plasma expressions of p21 and hif1α were more prevalent in pregnancies complicated by hypoxia and/or IUGR (p<0.001). To conclude, we present in this manuscript data to support the association between two possible surrogate markers of hypoxia and common complications of pregnancy. More work is needed in order to implement these findings in clinical practice

Identification of carbon dioxide in an exoplanet atmosphere

Carbon dioxide (CO2) is a key chemical species that is found in a wide range of planetary atmospheres. In the context of exoplanets, CO2 is an indicator of the metal enrichment (that is, elements heavier than helium, also called ‘metallicity’)1–3, and thus the formation processes of the primary atmospheres of hot gas giants4–6. It is also one of the most promising species to detect in the secondary atmospheres of terrestrial exoplanets7–9. Previous photometric measurements of transiting planets with the Spitzer Space Telescope have given hints of the presence of CO2, but have not yielded definitive detections owing to the lack of unambiguous spectroscopic identification10–12. Here we present the detection of CO2 in the atmosphere of the gas giant exoplanet WASP-39b from transmission spectroscopy observations obtained with JWST as part of the Early Release Science programme13,14. The data used in this study span 3.0–5.5 micrometres in wavelength and show a prominent CO2 absorption feature at 4.3 micrometres (26-sigma significance). The overall spectrum is well matched by one-dimensional, ten-times solar metallicity models that assume radiative–convective–thermochemical equilibrium and have moderate cloud opacity. These models predict that the atmosphere should have water, carbon monoxide and hydrogen sulfide in addition to CO2, but little methane. Furthermore, we also tentatively detect a small absorption feature near 4.0 micrometres that is not reproduced by these models