| 1. |
- De Maria, Giovanni Luigi, et al.
(författare)
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Novel Indices of Coronary Physiology : Do We Need Alternatives to Fractional Flow Reserve?
- 2020
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Ingår i: Circulation. Cardiovascular Interventions. - 1941-7640 .- 1941-7632. ; 13:4
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Forskningsöversikt (refereegranskat)abstract
- Fractional flow reserve is the current invasive gold standard for assessing the ischemic potential of an angiographically intermediate coronary stenosis. Procedural cost and time, the need for coronary vessel instrumentation, and the need to administer adenosine to achieve maximal hyperemia remain integral components of invasive fractional flow reserve. The number of new alternatives to fractional flow reserve has proliferated over the last ten years using techniques ranging from alternative pressure wire metrics to anatomic simulation via angiography or intravascular imaging. This review article provides a critical description of the currently available or under-development alternatives to fractional flow reserve with a special focus on the available evidence, pros, and cons for each with a view towards their clinical application in the near future for the functional assessment of coronary artery disease.
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| 2. |
- Bonagas, Nadilly, et al.
(författare)
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Pharmacological targeting of MTHFD2 suppresses acute myeloid leukemia by inducing thymidine depletion and replication stress
- 2022
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Ingår i: NATURE CANCER. - : Springer Science and Business Media LLC. - 2662-1347. ; 3:2, s. 156-
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Tidskriftsartikel (refereegranskat)abstract
- The folate metabolism enzyme MTHFD2 (methylenetetrahydrofolate dehydrogenase/cyclohydrolase) is consistently overexpressed in cancer but its roles are not fully characterized, and current candidate inhibitors have limited potency for clinical development. In the present study, we demonstrate a role for MTHFD2 in DNA replication and genomic stability in cancer cells, and perform a drug screen to identify potent and selective nanomolar MTHFD2 inhibitors; protein cocrystal structures demonstrated binding to the active site of MTHFD2 and target engagement. MTHFD2 inhibitors reduced replication fork speed and induced replication stress followed by S-phase arrest and apoptosis of acute myeloid leukemia cells in vitro and in vivo, with a therapeutic window spanning four orders of magnitude compared with nontumorigenic cells. Mechanistically, MTHFD2 inhibitors prevented thymidine production leading to misincorporation of uracil into DNA and replication stress. Overall, these results demonstrate a functional link between MTHFD2-dependent cancer metabolism and replication stress that can be exploited therapeutically with this new class of inhibitors. Helleday and colleagues describe a nanomolar MTHFD2 inhibitor that causes replication stress and DNA damage accumulation in cancer cells via thymidine depletion, demonstrating a potential therapeutic strategy in AML tumors in vivo.
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| 3. |
- Casa, Marcello, et al.
(författare)
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Conductive adhesive based on mussel-inspired graphene decoration with silver nanoparticles
- 2018
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Ingår i: Journal of Nanoscience and Nanotechnology. - : American Scientific Publishers. - 1533-4880. ; 18:2, s. 1176-1185
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Tidskriftsartikel (refereegranskat)abstract
- Decoration with silver nanoparticles was obtained by coating graphene with a polydopamine layer, able to induce spontaneous metallic nanoparticles formation without any specific chemical interfacial modifier, neither using complex instrumentation. The choice of dopamine was inspired by the composition of adhesive proteins in mussels, related to their robust attach to solid surfaces. The synthesis procedure started from graphite and involved eco-friendly compounds, such as Vitamin C and glucose as reducing agent and water as reaction medium. Silver decorated graphene was inserted as secondary nanofiller in the formulation of a reference conductive adhesive based on epoxy resin and silver flakes. A wide characterization of the intermediate materials obtained along the step procedure for the adhesive preparation was carried out by several techniques. We have found that the presence of nanofiller yields, in addition to an improvement of the thermal conductivity (up to 7.6 W/m· K), a dramatic enhancement of the electrical conductivity of the adhesive. In particular, starting from 3 · 10 2 S/cm of the reference adhesive, we obtained a value of 4 · 10 4 S/cm at a nanofiller concentration of 11.5 wt%. The combined double filler conductivity was evaluated by Zallen’s model. The effect of the temperature on the resistivity of the adhesive has been also studied.
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| 4. |
- Casa, Marcello, et al.
(författare)
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Silver decorated graphene-polyvinyl alcohol hybrid hydrogel as catalyst for benzonitrile conversion
- 2017
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Ingår i: Advanced Science Letters. - : American Scientific Publishers. - 1936-7317 .- 1936-6612. ; 23:6, s. 5980-5983
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Tidskriftsartikel (refereegranskat)abstract
- In this work, we have synthetized a reduced graphene oxide functionalized with silver nanoparticles (G/Ag) by a method developed in our previous study and incorporated it in a hydrogel based on polyvinyl alcohol (PVA) as gelator through a freezing/thawing method. The hydrogel has been tested to catalyze the reduction at room temperature of nitrile group of benzonitrile in water by using glucose as a natural and mild reducing agent.
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| 5. |
- Degerlund, Maria, et al.
(författare)
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Functional diversity in cryptic species of Chaetoceros socialis Lauder (Bacillariophyceae)
- 2012
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Ingår i: Journal of Plankton Research. - : Oxford University Press. - 0142-7873 .- 1464-3774. ; 34:5, s. 416-431
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Tidskriftsartikel (refereegranskat)abstract
- The cosmopolitan distribution of the marine planktonic diatom Chaetoceros socialis Lauder is generally interpreted as a case of wide ecological plasticity. However, cryptic diversity has recently been observed within this taxon and this genetic diversity could extend to phenotypic differences between allopatric populations. Monoclonal strains of C. socialis isolated from NE Atlantic/Arctic and Tyrrhenian Sea waters were cultivated at 2.5, 8 and 13°C, and analysed for morphological, phylogenetic (LSU rRNA gene) and physiological (growth rate, photosynthetic yield) traits. The molecular analysis indicated an unequivocal divergence between the southern and the northern strains. Clear differences in spore morphology between the two groups were also observed, despite their morphological similarity in vegetative form. The physiological data demonstrated a functional partition between the northern and southern strains. The northern strains showed significantly higher growth rates than the southern ones at the lower temperatures, and vice versa at 13°C. Differences between the groups were also observed in the photosynthetic yields. These results reveal the expression of allopatric speciation in several phenotypic characters, providing a functional dimension to the cryptic, or rather pseudo-cryptic, diversity observed within C. socialis. We believe that such an integrated approach is useful for robust taxonomic and functional delimitations of presumed cosmopolitan microorganisms.
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| 6. |
- Manzi, Maria Virginia, et al.
(författare)
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SEX-RELATED DIFFERENCES IN THROMBUS BURDEN IN ST-ELEVATION MYOCARDIAL INFARCTION PATIENTS UNDERGOING PRIMARY PERCUTANEOUS CORONARY INTERVENTION
- 2022
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Ingår i: European Heart Journal, Supplement. - : Oxford University Press. - 1520-765X .- 1554-2815. ; 24:Suppl. K, s. K124-K125
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Women have a worse prognosis after ST-segment elevation myocardial infarction (STEMI) than men. The prognostic role of thrombus burden (TB) in influencing the sex-related differences in clinical outcomes after STEMI has not been clearly investigated.Objectives: The aim of this study was to assess the sex-related differences in TB and its clinical implication in patients with STEMI.Methods: We analyzed individual patient data from the 3 major randomized clinical trials of manual thrombus aspiration, encompassing a total of 19,047 patients with STEMI, of whom 13,885 (76.1%) were men and 4,371 (23.9%) were women. The primary outcome of interest was 1-year cardiovascular (CV) death. The secondary outcomes of interest were recurrent myocardial infarction, heart failure, all-cause mortality, stroke, stent thrombosis (ST), and target vessel revascularization at 1 year.Results: Patients with high TB (HTB) had worse 1-year outcomes compared with those presenting with low TB (adjusted HR for CV death; 1.52; 95% CI: 1.10-2.12; P=0.01). In unadjusted analyses, female sex was associated with an increased risk for 1-year CV death regardless of TB. After adjustment, this risk for 1-year CV death was higher only in women with HTB (HR 1.23, 95% CI: 1.18-1.28; P<0.001) who also had an increased risk for all-cause death and ST than men.Conclusion: In patients with STEMI, angiographic evidence of HTB negatively affected prognosis. Among patients with HTB, women had an excess risk for stent thrombosis, CV and all-cause mortality than men. Further investigations are warranted to better understand the pathophysiological mechanisms leading to excess mortality in women with STEMI and HTB.
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| 7. |
- Manzi, Maria Virginia, et al.
(författare)
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Sex-Related Differences in Thrombus Burden in STEMI Patients Undergoing Primary Percutaneous Coronary Intervention
- 2022
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Ingår i: JACC. - : Elsevier. - 1936-8798 .- 1876-7605. ; 15:20, s. 2066-2076
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Women have a worse prognosis after ST-segment elevation myocardial infarction (STEMI) than men. The prognostic role of thrombus burden (TB) in influencing the sex-related differences in clinical outcomes after STEMI has not been clearly investigated.OBJECTIVES: The aim of this study was to assess the sex-related differences in TB and its clinical implications in patients with STEMI.METHODS: Individual patient data from the 3 major randomized clinical trials of manual thrombus aspiration were analyzed, encompassing a total of 19,047 patients with STEMI, of whom 13,885 (76.1%) were men and 4,371 (23.9%) were women. The primary outcome of interest was 1-year cardiovascular (CV) death. The secondary outcomes of interest were recurrent myocardial infarction, heart failure, all-cause mortality, stroke, stent thrombosis (ST), and target vessel revascularization at 1 year.RESULTS: Patients with high TB (HTB) had worse 1-year outcomes compared with those presenting with low TB (adjusted HR for CV death: 1.52; 95% CI: 1.10-2.12; P = 0.01). In unadjusted analyses, female sex was associated with an increased risk for 1-year CV death regardless of TB. After adjustment, the risk for 1-year CV death was higher only in women with HTB (HR: 1.23; 95% CI: 1.18-1.28; P < 0.001), who also had an increased risk for all-cause death and ST than men.CONCLUSIONS: In patients with STEMI, angiographic evidence of HTB negatively affected prognosis. Among patients with HTB, women had an excess risk for ST, CV, and all-cause mortality than men. Further investigations are warranted to better understand the pathophysiological mechanisms leading to excess mortality in women with STEMI and HTB.
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| 8. |
- Sarno, Debora, et al.
(författare)
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A processual view on sustainability transitions in service ecosystems
- 2024
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Ingår i: Journal of Service Management. - : Emerald Group Publishing Limited. - 1757-5818 .- 1757-5826.
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Sustainability transitions (STs) refer to large-scale step changes in complex systems required to face sustainability issues. We aim to delineate how they can unfold in service ecosystems, especially when inspired by regenerative thinking. Design/methodology/approach: We develop a conceptual framework based on a processual view of STs and provide a propositional inventory based on literature leveraging deductive reasoning. Moreover, we contextualize our conceptualizations by showing illustrative examples of cities coping with STs. Findings: We connect the perception of unsustainability with the shift toward service-dominant (S-D) logic and identify them as triggers of an ST; we focus on the role of nested service ecosystems and the adoption of regenerative thinking in STs; finally, we highlight the domino effect that can drive continuous change towards sustainability in service ecosystems. Future research could be focused on (loss of) sensemaking for driving STs, practical approaches to deal with institutional tensions in nested service ecosystems and the possible fractality of ST processes in service ecosystems. Originality/value: This study supports the understanding of STs in cities and other systems such as industries, markets and organizations. It contributes to ST literature by suggesting the adoption of S-D logic and system lenses to identify, drive and cope with system changes toward sustainability, showing implications for policymakers and practitioners. Furthermore, it contributes to S-D logic by unfolding the self-adjustment of service ecosystems and the focus of sustainability initiatives on nested service ecosystems to sustain the broader systems. Finally, it contributes to transformative service research by identifying how the procedural and inspirational principles characterizing regenerative thinking can support design for STs. © 2024, Emerald Publishing Limited.
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