| 1. |
- Murphy, Neil, et al.
(författare)
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Circulating Levels of Insulin-like Growth Factor 1 and Insulin-like Growth Factor Binding Protein 3 Associate With Risk of Colorectal Cancer Based on Serologic and Mendelian Randomization Analyses
- 2020
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Ingår i: Gastroenterology. - : Elsevier BV. - 0016-5085 .- 1528-0012. ; 158:5, s. 1300-1312.e20
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Human studies examining associations between circulating levels of insulin-like growth factor 1 (IGF1) and insulin-like growth factor binding protein 3 (IGFBP3) and colorectal cancer risk have reported inconsistent results. We conducted complementary serologic and Mendelian randomization (MR) analyses to determine whether alterations in circulating levels of IGF1 or IGFBP3 are associated with colorectal cancer development.Methods: Serum levels of IGF1 were measured in blood samples collected from 397,380 participants from the UK Biobank, from 2006 through 2010. Incident cancer cases and cancer cases recorded first in death certificates were identified through linkage to national cancer and death registries. Complete follow-up was available through March 31, 2016. For the MR analyses, we identified genetic variants associated with circulating levels of IGF1 and IGFBP3. The association of these genetic variants with colorectal cancer was examined with 2-sample MR methods using genome-wide association study consortia data (52,865 cases with colorectal cancer and 46,287 individuals without [controls])Results: After a median follow-up period of 7.1 years, 2665 cases of colorectal cancer were recorded. In a multivariable-adjusted model, circulating level of IGF1 associated with colorectal cancer risk (hazard ratio per 1 standard deviation increment of IGF1, 1.11; 95% confidence interval [CI] 1.05–1.17). Similar associations were found by sex, follow-up time, and tumor subsite. In the MR analyses, a 1 standard deviation increment in IGF1 level, predicted based on genetic factors, was associated with a higher risk of colorectal cancer risk (odds ratio 1.08; 95% CI 1.03–1.12; P = 3.3 × 10–4). Level of IGFBP3, predicted based on genetic factors, was associated with colorectal cancer risk (odds ratio per 1 standard deviation increment, 1.12; 95% CI 1.06–1.18; P = 4.2 × 10–5). Colorectal cancer risk was associated with only 1 variant in the IGFBP3 gene region (rs11977526), which also associated with anthropometric traits and circulating level of IGF2.Conclusions: In an analysis of blood samples from almost 400,000 participants in the UK Biobank, we found an association between circulating level of IGF1 and colorectal cancer. Using genetic data from 52,865 cases with colorectal cancer and 46,287 controls, a higher level of IGF1, determined by genetic factors, was associated with colorectal cancer. Further studies are needed to determine how this signaling pathway might contribute to colorectal carcinogenesis.
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| 2. |
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| 3. |
- Barchitta, Martina, et al.
(författare)
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The "Obiettivo Antibiotico" Campaign on Prudent Use of Antibiotics in Sicily, Italy : The Pilot Phase
- 2020
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Ingår i: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1661-7827 .- 1660-4601. ; 17:9, s. 3077-
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Tidskriftsartikel (refereegranskat)abstract
- The issue of antimicrobial resistance (AMR) is a focus of the World Health Organization, which proposes educational interventions targeting the public and healthcare professionals. Here, we present the first attempt at a regionwide multicomponent campaign in Sicily (Italy), called "Obiettivo Antibiotico", which aims to raise the awareness of prudent use of antibiotics in the public and in healthcare professionals. The campaign was designed by an interdisciplinary academic team, and an interactive website was populated with different materials, including key messages, letters, slogans, posters, factsheets, leaflets, and videos. The campaign was launched in November 2018 and, as of 21 December 2018, the website had a total of 1159 unique visitors, of which 190 became champions by pledging to take simple actions to support the fight against AMR. Data from social media showed that the audience was between 18 and 54 years of age, with a high proportion of female participants (64%). Interestingly, the LinkedIn page received more than 1200 followers, and Facebook 685 followers. The number of actions taken (pledges) by the audience was 458, evenly divided between experts (53%) and the general public (47%). Additional efforts are needed to reach more people, thus future efforts should focus on further promotion within the Sicilian region to sustain the engagement with the campaign.
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| 4. |
- Chigrinova, Ekaterina, et al.
(författare)
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Two main genetic pathways lead to the transformation of chronic lymphocytic leukemia to Richter syndrome
- 2013
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 122:15, s. 2673-2682
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Tidskriftsartikel (refereegranskat)abstract
- Richter syndrome (RS) occurs in up to 15% of patients with chronic lymphocytic leukemia (CLL). Although RS, usually represented by the histologic transformation to a diffuse large B-cell lymphoma (DLBCL), is associated with a very poor outcome, especially when clonally related to the preexisting CLL, the mechanisms leading to RS have not been clarified. To better understand the pathogenesis of RS, we analyzed a series of cases including 59 RS, 28 CLL phase of RS, 315 CLL, and 127 de novo DLBCL. RS demonstrated a genomic complexity intermediate between CLL and DLBCL. Cell-cycle deregulation via inactivation of TP53 and of CDKN2A was a main mechanism in the histologic transformation from CLL phase, being present in approximately one half of the cases, and affected the outcome of the RS patients. A second major subgroup was characterized by the presence of trisomy 12 and comprised one third of the cases. Although RS shared some of the lesions seen in de novo DLBCL, its genomic profile was clearly separate. The CLL phase preceding RS had not a generalized increase in genomic complexity compared with untransformed CLL, but it presented clear differences in the frequency of specific genetic lesions.
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| 5. |
- Di Cori, Andrea, et al.
(författare)
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Clinical impact of antithrombotic therapy in transvenous lead extraction complications : a sub-analysis from the ESC-EORP EHRA ELECTRa (European Lead Extraction ConTRolled) Registry
- 2019
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Ingår i: Europace. - : Oxford University Press. - 1099-5129 .- 1532-2092. ; 21:7, s. 1096-1105
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: A sub-analysis of the ESC-EHRA European Lead Extraction ConTRolled (ELECTRa) Registry to evaluate the clinical impact of antithrombotic (AT) on transvenous lead extraction (TLE) safety and efficacy.METHODS AND RESULTS: ELECTRa outcomes were compared between patients without AT therapy (No AT Group) and with different pre-operative AT regimens, including antiplatelets (AP), anticoagulants (AC), or both (AP + AC). Out of 3510 pts, 2398 (68%) were under AT pre-operatively. AT patients were older with more comorbidities (P < 0.0001). AT subgroups, defined as AP, AC, or AP + AC, were 1096 (31.2%), 985 (28%), and 317 (9%), respectively. Regarding AP patients, 1413 (40%) were under AP, 1292 (91%) with a single AP, interrupted in 26% about 3.8 ± 3.7 days before TLE. In total, 1302 (37%) patients were under AC, 881 vitamin K antagonist (68%), 221 (17%) direct oral anticoagulants, 155 (12%) low weight molecular heparin, and 45 (3.5%) unfractionated heparin. AC was 'interrupted without bridging' in 696 (54%) and 'interrupted with bridging' in 504 (39%) about 3.3 ± 2.3 days before TLE, and 'continued' in 87 (7%). TLE success rate was high in all subgroups. Only overall in-hospital death (1.4%), but not the procedure-related one, was higher in the AT subgroups (P = 0.0500). Age >65 years and New York Heart Association Class III/IV, but not AT regimens, were independent predictors of death for any cause. Haematomas were more frequent in AT subgroups, especially in AC 'continued' (P = 0.025), whereas pulmonary embolism in the No-AT (P < 0.01).CONCLUSIONS: AT minimization is safe in patients undergoing TLE. AT does not seem to predict death but identifies a subset of fragile patients with a worse in-hospital TLE outcome.
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| 6. |
- Fehmi, Janev, et al.
(författare)
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Contactin-1 links autoimmune neuropathy and membranous glomerulonephritis
- 2023
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 18:3 March
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Tidskriftsartikel (refereegranskat)abstract
- Membranous glomerulonephritis (MGN) is a common cause of nephrotic syndrome in adults, mediated by glomerular antibody deposition to an increasing number of newly recognised antigens. Previous case reports have suggested an association between patients with anti-contactin-1 (CNTN1)-mediated neuropathies and MGN. In an observational study we investigated the pathobiology and extent of this potential cause of MGN by examining the association of antibodies against CNTN1 with the clinical features of a cohort of 468 patients with suspected immune-mediated neuropathies, 295 with idiopathic MGN, and 256 controls. Neuronal and glomerular binding of patient IgG, serum CNTN1 antibody and protein levels, as well as immune-complex deposition were determined. We identified 15 patients with immune-mediated neuropathy and concurrent nephrotic syndrome (biopsy proven MGN in 12/12), and 4 patients with isolated MGN from an idiopathic MGN cohort, all seropositive for IgG4 CNTN1 antibodies. CNTN1-containing immune complexes were found in the renal glomeruli of patients with CNTN1 antibodies, but not in control kidneys. CNTN1 peptides were identified in glomeruli by mass spectroscopy. CNTN1 seropositive patients were largely resistant to first-line neuropathy treatments but achieved a good outcome with escalation therapies. Neurological and renal function improved in parallel with suppressed antibody titres. The reason for isolated MGN without clinical neuropathy is unclear. We show that CNTN1, found in peripheral nerves and kidney glomeruli, is a common target for autoantibody-mediated pathology and may account for between 1 and 2% of idiopathic MGN cases. Greater awareness of this cross-system syndrome should facilitate earlier diagnosis and more timely use of effective treatment.
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| 7. |
- Giuffrida, Giovanni, et al.
(författare)
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Analyzing Communication Broadcasting in the Digital Space : 7th International Conference, LOD 2021, Grasmere, UK, October 4–8, 2021, Revised Selected Papers, Part II
- 2022
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Ingår i: Machine Learning, Optimization, and Data Science (LOD 2021), PT II. - Cham : Springer Nature. ; , s. 518-530
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Konferensbidrag (refereegranskat)abstract
- This paper aims to understand complex social events that arise when communicating general concepts in the digital space. Today, we get informed through many different channels, at different times of the day, in different contexts, and on many different devices. In addition to that, more complexity is added by the bidirectional nature of the communication itself. People today react very quickly to specific topics through various means such as rating, sharing, commenting, tagging, icons, tweeting, etc. Such activities generate additional metadata to the information itself which become part of the original message. When planning proper communication we should consider all this. In such a complicated environment, the likelihood of a message's real meaning being received in a distorted or confused way is very high. However, as we have seen recently during the Covid-19 pandemic, at times, there is the need to communicate something, somewhat complicated in nature, while we need to make sure citizens fully understand the actual terms and meaning of the communication. This was the case faced by many governments worldwide when informing their population on the rules of conduct during the various lockdown periods. We analyzed trends and structure of social network data generated as a reaction to those official communications in Italy. Our goal is to derive a model to estimate whether the communication intended by the government was properly understood by the large population. We discovered some regularities in social media generated data related to "poorly" communicated issues. We believe it is possible to derive a model to measure how well the recipients grasp a specific topic. And this can be used to trigger real-time alerts when the need for clarification arises.
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| 8. |
- Gobom, Johan, et al.
(författare)
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Validation of the LUMIPULSE automated immunoassay for the measurement of core AD biomarkers in cerebrospinal fluid.
- 2022
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Ingår i: Clinical chemistry and laboratory medicine. - : Walter de Gruyter GmbH. - 1437-4331 .- 1434-6621. ; 60:2, s. 207-219
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Tidskriftsartikel (refereegranskat)abstract
- The core cerebrospinal fluid (CSF) biomarkers; total tau (tTau), phospho-tau (pTau), amyloid β1-42(Aβ 1-42), and the Aβ 1-42/Aβ 1-40 ratio have transformed Alzheimer's disease (AD) research and are today increasingly used in clinical routine laboratories as diagnostic tools. Fully automated immunoassay instruments with ready-to-use assay kits and calibrators has simplified their analysis and improved reproducibility of measurements. We evaluated the analytical performance of the fully automated immunoassay instrument LUMIPULSE G (Fujirebio) for measurement of the four core AD CSF biomarkers and determined cutpoints for AD diagnosis.Comparison of the LUMIPULSE G assays was performed with the established INNOTEST ELISAs (Fujirebio) for hTau Ag, pTau 181, β-amyloid 1-42, and with V-PLEX Plus Aβ Peptide Panel 1 (6E10) (Meso Scale Discovery) for Aβ 1-42/Aβ 1-40, as well as with a LC-MS reference method for Aβ 1-42. Intra- and inter-laboratory reproducibility was evaluated for all assays. Clinical cutpoints for Aβ 1-42, tTau, and pTau was determined by analysis of three cohorts of clinically diagnosed patients, comprising 651 CSF samples. For the Aβ 1-42/Aβ 1-40 ratio, the cutpoint was determined by mixture model analysis of 2,782 CSF samples.The LUMIPULSE G assays showed strong correlation to all other immunoassays (r>0.93 for all assays). The repeatability (intra-laboratory) CVs ranged between 2.0 and 5.6%, with the highest variation observed for β-amyloid 1-40. The reproducibility (inter-laboratory) CVs ranged between 2.1 and 6.5%, with the highest variation observed for β-amyloid 1-42. The clinical cutpoints for AD were determined to be 409ng/L for total tau, 50.2ng/L for pTau 181, 526ng/L for β-amyloid 1-42, and 0.072 for the Aβ 1-42/Aβ 1-40 ratio.Our results suggest that the LUMIPULSE G assays for the CSF AD biomarkers are fit for purpose in clinical laboratory practice. Further, they corroborate earlier presented reference limits for the biomarkers.
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| 9. |
- Jones, Geraint H., et al.
(författare)
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The Comet Interceptor Mission
- 2024
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Ingår i: Space Science Reviews. - : Springer Nature. - 0038-6308 .- 1572-9672. ; 220:1
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Tidskriftsartikel (refereegranskat)abstract
- Here we describe the novel, multi-point Comet Interceptor mission. It is dedicated to the exploration of a little-processed long-period comet, possibly entering the inner Solar System for the first time, or to encounter an interstellar object originating at another star. The objectives of the mission are to address the following questions: What are the surface composition, shape, morphology, and structure of the target object? What is the composition of the gas and dust in the coma, its connection to the nucleus, and the nature of its interaction with the solar wind? The mission was proposed to the European Space Agency in 2018, and formally adopted by the agency in June 2022, for launch in 2029 together with the Ariel mission. Comet Interceptor will take advantage of the opportunity presented by ESA’s F-Class call for fast, flexible, low-cost missions to which it was proposed. The call required a launch to a halo orbit around the Sun-Earth L2 point. The mission can take advantage of this placement to wait for the discovery of a suitable comet reachable with its minimum Δ V capability of 600 ms − 1 . Comet Interceptor will be unique in encountering and studying, at a nominal closest approach distance of 1000 km, a comet that represents a near-pristine sample of material from the formation of the Solar System. It will also add a capability that no previous cometary mission has had, which is to deploy two sub-probes – B1, provided by the Japanese space agency, JAXA, and B2 – that will follow different trajectories through the coma. While the main probe passes at a nominal 1000 km distance, probes B1 and B2 will follow different chords through the coma at distances of 850 km and 400 km, respectively. The result will be unique, simultaneous, spatially resolved information of the 3-dimensional properties of the target comet and its interaction with the space environment. We present the mission’s science background leading to these objectives, as well as an overview of the scientific instruments, mission design, and schedule.
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| 10. |
- Loizides, Michael, et al.
(författare)
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Has taxonomic vandalism gone too far? A case study, the rise of the pay-to-publish model and the pitfalls of Morchella systematics
- 2022
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Ingår i: Mycological progress. - : Springer Science and Business Media LLC. - 1617-416X .- 1861-8952. ; 21:1, s. 7-38
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Tidskriftsartikel (refereegranskat)abstract
- The genus Morchella has gone through turbulent taxonomic treatments. Although significant progress in Morchella systematics has been achieved in the past decade, several problems remain unresolved and taxonomy in the genus is still in flux. In late 2019, a paper published in the open-access journal Scientific Reports raised serious concerns about the taxonomic stability of the genus, but also about the future of academic publishing. The paper, entitled “High diversity of Morchella and a novel lineage of the esculenta clade from the north Qinling Mountains revealed by GCPSR-based study” by Phanpadith and colleagues, suffered from gross methodological errors, included false results and artifactual phylogenies, had misapplied citations throughout, and proposed a new species name invalidly. Although the paper was eventually retracted by Scientific Reports in 2021, the fact that such an overtly flawed and scientifically unsound paper was published in a high-ranked Q1 journal raises alarming questions about quality controls and safekeeping procedures in scholarly publishing. Using this paper as a case study, we provide a critical review on the pitfalls of Morchella systematics followed by a series of recommendations for the delimitation of species, description of taxa, and ultimately for a sustainable taxonomy in Morchella. Problems and loopholes in the academic publishing system are also identified and discussed, and additional quality controls in the pre- and post-publication stages are proposed.
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