| 1. |
- Tabiri, S, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 2. |
- Bravo, L, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 9. |
- Zaborowski, AM, et al.
(författare)
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Microsatellite instability in young patients with rectal cancer: molecular findings and treatment response
- 2022
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Ingår i: The British journal of surgery. - : Oxford University Press (OUP). - 1365-2168 .- 0007-1323. ; 109:3, s. 251-255
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Tidskriftsartikel (refereegranskat)abstract
- In this study of 400 patients with early-onset rectal cancer, 12.5 per cent demonstrated microsatellite instability (MSI). MSI was associated with a reduced likelihood of nodal positivity, an increased rate of pathological complete response, and improved disease-specific survival.
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| 10. |
- Carmona-Gutierrez, D, et al.
(författare)
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The flavonoid 4,4'-dimethoxychalcone promotes autophagy-dependent longevity across species
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 651-
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Tidskriftsartikel (refereegranskat)abstract
- Ageing constitutes the most important risk factor for all major chronic ailments, including malignant, cardiovascular and neurodegenerative diseases. However, behavioural and pharmacological interventions with feasible potential to promote health upon ageing remain rare. Here we report the identification of the flavonoid 4,4′-dimethoxychalcone (DMC) as a natural compound with anti-ageing properties. External DMC administration extends the lifespan of yeast, worms and flies, decelerates senescence of human cell cultures, and protects mice from prolonged myocardial ischaemia. Concomitantly, DMC induces autophagy, which is essential for its cytoprotective effects from yeast to mice. This pro-autophagic response induces a conserved systemic change in metabolism, operates independently of TORC1 signalling and depends on specific GATA transcription factors. Notably, we identify DMC in the plant Angelica keiskei koidzumi, to which longevity- and health-promoting effects are ascribed in Asian traditional medicine. In summary, we have identified and mechanistically characterised the conserved longevity-promoting effects of a natural anti-ageing drug.
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| 11. |
- Joseph, A, et al.
(författare)
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Metabolic and psychiatric effects of acyl coenzyme A binding protein (ACBP)/diazepam binding inhibitor (DBI)
- 2020
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Ingår i: Cell death & disease. - : Springer Science and Business Media LLC. - 2041-4889. ; 11:7, s. 502-
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Tidskriftsartikel (refereegranskat)abstract
- Acyl coenzyme A binding protein (ACBP), also known as diazepam binding inhibitor (DBI) is a multifunctional protein with an intracellular action (as ACBP), as well as with an extracellular role (as DBI). The plasma levels of soluble ACBP/DBI are elevated in human obesity and reduced in anorexia nervosa. Accumulating evidence indicates that genetic or antibody-mediated neutralization of ACBP/DBI has anorexigenic effects, thus inhibiting food intake and inducing lipo-catabolic reactions in mice. A number of anorexiants have been withdrawn from clinical development because of their side effects including an increase in depression and suicide. For this reason, we investigated the psychiatric impact of ACBP/DBI in mouse models and patient cohorts. Intravenously (i.v.) injected ACBP/DBI protein conserved its orexigenic function when the protein was mutated to abolish acyl coenzyme A binding, but lost its appetite-stimulatory effect in mice bearing a mutation in the γ2 subunit of the γ-aminobutyric acid (GABA) A receptor (GABAAR). ACBP/DBI neutralization by intraperitoneal (i.p.) injection of a specific mAb blunted excessive food intake in starved and leptin-deficient mice, but not in ghrelin-treated animals. Neither i.v. nor i.p. injected anti-ACBP/DBI antibody affected the behavior of mice in the dark–light box and open-field test. In contrast, ACBP/DBI increased immobility in the forced swim test, while anti-ACBP/DBI antibody counteracted this sign of depression. In patients diagnosed with therapy-resistant bipolar disorder or schizophrenia, ACBP/DBI similarly correlated with body mass index (BMI), not with the psychiatric diagnosis. Patients with high levels of ACBP/DBI were at risk of dyslipidemia and this effect was independent from BMI, as indicated by multivariate analysis. In summary, it appears that ACBP/DBI neutralization has no negative impact on mood and that human depression is not associated with alterations in ACBP/DBI concentrations.
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| 16. |
- Frontali, A., et al.
(författare)
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Segmental Colectomy for Ulcerative Colitis: Is There a Place in Selected Patients Without Active Colitis? An International Multicentric Retrospective Study in 72 Patients
- 2020
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Ingår i: Journal of Crohn's & Colitis. - : OXFORD UNIV PRESS. - 1873-9946 .- 1876-4479. ; 14:12, s. 1687-1692
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aims: The aim of this study was to report a multicentric experience of segmental colectomy [SC] in ulcerative colitis [UC] patients without active colitis, in order to assess if SC can or cannot represent an alternative to ileal pouch-anal anastomosis [IPAA]. Methods: All UC patients undergoing SC were included. Postoperative complications according to Clavien-Dindos classification, long-term results, and risk factors for postoperative colitis and reoperation for colitis on the remnant colon, were assessed. Results: A total of 72 UC patients underwent: sigmoidectomy [n = 28], right colectomy [n = 24], proctectomy [n = 11], or left colectomy [n = 9] for colonic cancer [n = 27], diverticulitis [n = 17], colonic stenosis [n = 5], dysplasia or polyps [n = 8], and miscellaneous [n = 15]. Three patients died postoperatively and 5/69 patients [7%] developed early flare of UC within 3 months after SC. After a median follow-up of 40 months, 24/ 69 patients [35%] were reoperated after a median delay after SC of 19 months [range, 2-158 months]: 22/24 [92%] underwent total colectomy and ileorectal anastomosis [n = 9] or total coloproctectomy [TCP] [n = 13] and 2/24 [8%] an additional SC. Reasons for reoperation were: colitis [n = 14; 20%], cancer [n = 3] or dysplasia [n = 3], colonic stenosis [n = 1], and unknown reasons [n = 3]. Endoscopic score of colitis before SC was Mayo 23 in 5/5 [100%] patients with early flare vs 15/42 without early flare [36%; p = 0.0101] and in 9/12 [75%] patients with reoperation for colitis vs 11/35 without reoperation [31%; p = 0.016]. Conclusions: After segmental colectomy in UC patients, postoperative early colitis is rare [7%]. Segmental colectomy could possibly represent an alternative to IPAA in selected UC patients without active colitis.
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| 22. |
- Zannad, F., et al.
(författare)
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Mineralocorticoid receptor antagonists for heart failure with reduced ejection fraction: integrating evidence into clinical practice
- 2012
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Ingår i: European heart journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 33:22, s. 2782-2795
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Tidskriftsartikel (refereegranskat)abstract
- Mineralocorticoid receptor antagonists (MRAs) improve survival and reduce morbidity in patients with heart failure, reduced ejection fraction (HF-REF), and mild-to-severe symptoms, and in patients with left ventricular systolic dysfunction and heart failure after acute myocardial infarction. These clinical benefits are observed in addition to those of angiotensin converting enzyme inhibitors or angiotensin receptor blockers and beta-blockers. The morbidity and mortality benefits of MRAs may be mediated by several proposed actions, including antifibrotic mechanisms that slow heart failure progression, prevent or reverse cardiac remodelling, or reduce arrhythmogenesis. Both eplerenone and spironolactone have demonstrated survival benefits in individual clinical trials. Pharmacologic differences exist between the drugs, which may be relevant for therapeutic decision making in individual patients. Although serious hyperkalaemia events were reported in the major MRA clinical trials, these risks can be mitigated through appropriate patient selection, dose selection, patient education, monitoring, and follow-up. When used appropriately, MRAs significantly improve outcomes across the spectrum of patients with HF-REF.
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| 23. |
- Bravo-San Pedro, JM, et al.
(författare)
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Pseudodiabetes-not a contraindication for metabolic interventions
- 2019
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Ingår i: Cell death & disease. - : Springer Science and Business Media LLC. - 2041-4889. ; 10:10, s. 765-
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Tidskriftsartikel (refereegranskat)abstract
- Type-2 diabetes is characterized by glycosuria, hyperglycemia, glucose intolerance, hyperinsulinemia, and insulin resistance. One or several among these alterations are also found after starvation, ketogenic diet, and pharmacological treatment with rapamycin or antibody-mediated neutralization of the obesogenic factor ACBP/DBI. Thus, a variety of metabolic interventions that improve metabolic health can induce a transient state of “pseudo-diabetes”.
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| 24. |
- Carleer, M. R., et al.
(författare)
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Validation of water vapour profiles from the Atmospheric Chemistry Experiment (ACE)
- 2008
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Ingår i: Atmospheric Chemistry and Physics Discussion: An Interactive Open Access Journal of the European Geosciences Union. ; 8:2, s. 4499-4559
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Tidskriftsartikel (refereegranskat)abstract
- The Atmospheric Chemistry Experiment (ACE) mission was launched in August 2003 to sound the atmosphere by solar occultation. Water vapour (H2O), one of the most important molecules for climate and atmospheric chemistry, is one of the key species provided by the two principal instruments, the infrared Fourier Transform Spectrometer (ACE-FTS) and the MAESTRO UV-Visible spectrometer (ACE-MAESTRO). The first instrument performs measurements on several lines in the 1362–2137 cm−1 range, from which vertically resolved H2O concentration profiles are retrieved, from 7 to 90 km altitude. ACE-MAESTRO measures profiles using the water absorption band in the near infrared part of the spectrum at 926.0–969.7 nm. This paper presents a comprehensive validation of the ACE-FTS profiles. We have compared the H2O volume mixing ratio profiles with space-borne (SAGE II, HALOE, POAM III, MIPAS, SMR) observations and measurements from balloon-borne frostpoint hygrometers and a ground based lidar. We show that the ACE-FTS measurements provide H2O profiles with small retrieval uncertainties in the stratosphere (better than 5% from 15 to 70 km, gradually increasing above). The situation is unclear in the upper troposphere, due mainly to the high variability of the water vapour volume mixing ratio in this region. A new water vapour data product from the ACE-MAESTRO (Measurement of Aerosol Extinction in the Stratosphere and Troposphere Retrieved by Occultation) is also presented and initial comparisons with ACE-FTS are discussed.
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| 25. |
- Castoldi, F, et al.
(författare)
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Autophagy-mediated metabolic effects of aspirin
- 2020
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Ingår i: Cell death discovery. - : Springer Science and Business Media LLC. - 2058-7716. ; 6:1, s. 129-
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Tidskriftsartikel (refereegranskat)abstract
- Salicylate, the active derivative of aspirin (acetylsalicylate), recapitulates the mode of action of caloric restriction inasmuch as it stimulates autophagy through the inhibition of the acetyltransferase activity of EP300. Here, we directly compared the metabolic effects of aspirin medication with those elicited by 48 h fasting in mice, revealing convergent alterations in the plasma and the heart metabolome. Aspirin caused a transient reduction of general protein acetylation in blood leukocytes, accompanied by the induction of autophagy. However, these effects on global protein acetylation could not be attributed to the mere inhibition of EP300, as determined by epistatic experiments and exploration of the acetyl-proteome from salicylate-treated EP300-deficient cells. Aspirin reduced high-fat diet-induced obesity, diabetes, and hepatosteatosis. These aspirin effects were observed in autophagy-competent mice but not in two different models of genetic (Atg4b−/− or Bcln1+/−) autophagy-deficiency. Aspirin also improved tumor control by immunogenic chemotherapeutics, and this effect was lost in T cell-deficient mice, as well as upon knockdown of an essential autophagy gene (Atg5) in cancer cells. Hence, the health-improving effects of aspirin depend on autophagy.
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| 29. |
- Rodrigues, Arthur, et al.
(författare)
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Enhancing Context Specifications for Dependable Adaptive Systems: A Data Mining Approach
- 2019
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Ingår i: Information and Software Technology. - : Elsevier BV. - 0950-5849. ; 112, s. 115-131
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Tidskriftsartikel (refereegranskat)abstract
- Context: Adaptive systems are expected to cater for various operational contexts by having multiple strategies in achieving their objectives and the logic for matching strategies to an actual context. The prediction of relevant contexts at design time is paramount for dependability. With the current trend on using data mining to support the requirements engineering process, this task of understanding context for adaptive system at design time can benefit from such techniques as well. Objective: The objective is to provide a method to refine the specification of contextual variables and their relation to strategies for dependability. This refinement shall detect dependencies between such variables, priorities in monitoring them, and decide on their relevance in choosing the right strategy in a decision tree. Method: Our requirements-driven approach adopts the contextual goal modelling structure in addition to the operationalization values of sensed information to map contexts to the system’s behaviour. We propose a design time analysis process using a subset of data mining algorithms to extract a list of relevant contexts and their related variables, tasks, and/or goals. Results: We experimentally evaluated our proposal on a Body Sensor Network system (BSN), simulating 12 resources that could lead to a variability space of 4096 possible context conditions. Our approach was able to elicit subtle contexts that would significantly affect the service provided to assisted patients and relations between contexts, assisting the decision on their need, and priority in monitoring. Conclusion: The use of some data mining techniques can mitigate the lack of precise definition of contexts and their relation to system strategies for dependability. Our method is practical and supportive to traditional requirements specification methods, which typically require intense human intervention.
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| 30. |
- Rodrigues, Gabriel S., et al.
(författare)
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GoalD: A Goal-Driven Deployment Framework for Dynamic and Heterogeneous Computing Environments
- 2019
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Ingår i: Information and Software Technology. - : Elsevier BV. - 0950-5849. ; 111, s. 159-176
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Tidskriftsartikel (refereegranskat)abstract
- Context Emerging paradigms like Internet of Things and Smart Cities utilize advanced sensing and communication infrastructures, where heterogeneity is an inherited feature. Applications targeting such environments require adaptability and context-sensitivity to uncertain availability and failures in resources and their ad-hoc networks. Such heterogeneity is often hard to predict, making the deployment process a challenging task. Objective This paper proposes GoalD as a goal-driven framework to support autonomous deployment of heterogeneous computational resources to fulfill requirements, seen as goals, and their correlated components on one hand, and the variability space of the hosting computing and sensing environment on the other hand. Method GoalD comprises an offline and an online stage to fulfill autonomous deployment by leveraging the use of goals. Deployment configuration strategies arise from the variability structure of the Contextual Goal Model as an underlying structure to guide autonomous planning by selecting available as well as suitable resources at runtime. Results We evaluate GoalD on an existing exemplar from the self-adaptive systems community – the Tele Assistance Service provided by Weyns and Calinescu [1]. Furthermore, we evaluate the scalability of GoalD on a repository consisting of 430,500 artifacts. The evaluation results demonstrate the usefulness and scalability of GoalD in planning the deployment of a system with thousands of components in a few milliseconds. Conclusion GoalD is a framework to systematically tackle autonomous deployment in highly heterogeneous computing environments, partially unknown at design-time following a goal-oriented approach to achieve the user goals in a target environment. GoalD has demonstrated itself able to scale for deployment planning dealing with thousands of components in a few milliseconds.
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