| 1. |
- Kranabetter, Lorenz, et al.
(författare)
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Considerable matrix shift in the electronic transitions of helium-solvated cesium dimer cation Cs2He+n
- 2019
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Ingår i: Physical Chemistry, Chemical Physics - PCCP. - : Royal Society of Chemistry (RSC). - 1463-9076 .- 1463-9084. ; 21:45, s. 25362-25368
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Tidskriftsartikel (refereegranskat)abstract
- We investigate the photodissociation of helium-solvated cesium dimer cations using action spectroscopy and quantum chemical calculations. The spectrum of Cs2He+ shows three distinct absorption bands into both bound and dissociative states. Upon solvation with further helium atoms, considerable shifts of the absorption bands are observed, exceeding 0.1 eV (850 cm(-1)) already for Cs2He10+, along with significant broadening. The shifts are highly sensitive to the character of the excited state. Our calculations show that helium atoms adsorb on the ends of Cs-2(+). The shifts are particularly pronounced if the excited state orbitals extend to the area occupied by the helium atoms. In this case, Pauli repulsion leads to a deformation of the excited state orbitals, resulting in the observed blue shift of the transition. Since the position of the weakly bound helium atoms is ill defined, Pauli repulsion also explains the broadening.
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| 2. |
- Liu, Si, et al.
(författare)
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Electrocatalytic Water Oxidation at Neutral pH–Deciphering the Rate Constraints for an Amorphous Cobalt‐Phosphate Catalyst System
- 2022
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Ingår i: Advanced Energy Materials. - : Wiley-VCH Verlagsgesellschaft. - 1614-6832 .- 1614-6840. ; 12:46
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Tidskriftsartikel (refereegranskat)abstract
- The oxygen evolution reaction (OER) is pivotal in sustainable fuel production. Neutral-pH OER reduces operational risks and enables direct coupling to electrochemical CO2 reduction, but typically is hampered by low current densities. Here, the rate limitations in neutral-pH OER are clarified. Using cobalt-based catalyst films and phosphate ions as essential electrolyte bases, current–potential curves are recorded and simulated. Operando X-ray spectroscopy shows the potential-dependent structural changes independent of the electrolyte phosphate concentration. Operando Raman spectroscopy uncovers electrolyte acidification at a micrometer distance from the catalyst surface, limiting the Tafel slope regime to low current densities. The electrolyte proton transport is facilitated by diffusion of either phosphate ions (base pathway) or H3O+ ions (water pathway). The water pathway is not associated with an absolute current limit but is energetically inefficient due to the Tafel-slope increase by 60 mV dec−1, shown by an uncomplicated mathematical model. The base pathway is a specific requirement in neutral-pH OER and can support high current densities, but only with accelerated buffer-base diffusion. Catalyst internal phosphate diffusion or other internal transport mechanisms do not limit the current densities. A proof-of-principle experiment shows that current densities exceeding 1 A cm−2 can also be achieved in neutral-pH OER.
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| 3. |
- Pasquini, Chiara, et al.
(författare)
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Operando tracking of oxidation-state changes by coupling electrochemistry with time-resolved X-ray absorption spectroscopy demonstrated for water oxidation by a cobalt-based catalyst film
- 2021
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Ingår i: Analytical and Bioanalytical Chemistry. - : Springer Nature. - 1618-2642 .- 1618-2650. ; 413:21, s. 5395-5408
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Tidskriftsartikel (refereegranskat)abstract
- Transition metal oxides are promising electrocatalysts for water oxidation, i.e., the oxygen evolution reaction (OER), which is critical in electrochemical production of non-fossil fuels. The involvement of oxidation state changes of the metal in OER electrocatalysis is increasingly recognized in the literature. Tracing these oxidation states under operation conditions could provide relevant information for performance optimization and development of durable catalysts, but further methodical developments are needed. Here, we propose a strategy to use single-energy X-ray absorption spectroscopy for monitoring metal oxidation-state changes during OER operation with millisecond time resolution. The procedure to obtain time-resolved oxidation state values, using two calibration curves, is explained in detail. We demonstrate the significance of this approach as well as possible sources of data misinterpretation. We conclude that the combination of X-ray absorption spectroscopy with electrochemical techniques allows us to investigate the kinetics of redox transitions and to distinguish the catalytic current from the redox current. Tracking of the oxidation state changes of Co ions in electrodeposited oxide films during cyclic voltammetry in neutral pH electrolyte serves as a proof of principle.
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| 4. |
- Bartocci, Ezio, et al.
(författare)
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TOOLympics 2019 : An overview of competitions in formal methods
- 2019
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Ingår i: Tools and Algorithms for the Construction and Analysis of Systems. - Cham : Springer. - 9783030175016 ; , s. 3-24
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Konferensbidrag (refereegranskat)abstract
- Evaluation of scientific contributions can be done in many different ways. For the various research communities working on the verification of systems (software, hardware, or the underlying involved mechanisms), it is important to bring together the community and to compare the state of the art, in order to identify progress of and new challenges in the research area. Competitions are a suitable way to do that.The first verification competition was created in 1992 (SAT competition), shortly followed by the CASC competition in 1996. Since the year 2000, the number of dedicated verification competitions is steadily increasing. Many of these events now happen regularly, gathering researchers that would like to understand how well their research prototypes work in practice. Scientific results have to be reproducible, and powerful computers are becoming cheaper and cheaper, thus, these competitions are becoming an important means for advancing research in verification technology.TOOLympics 2019 is an event to celebrate the achievements of the various competitions, and to understand their commonalities and differences. This volume is dedicated to the presentation of the 16 competitions that joined TOOLympics as part of the celebration of the 25?ℎ anniversary of the TACAS conference.
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| 5. |
- Belova, Valentina, et al.
(författare)
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Evidence for Anisotropic Electronic Coupling of Charge Transfer States in Weakly Interacting Organic Semiconductor Mixtures
- 2017
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 139:25, s. 8474-8486
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Tidskriftsartikel (refereegranskat)abstract
- We present a comprehensive investigation of the charge-transfer (CT) effect in weakly interacting organic semiconductor mixtures. The donor-acceptor pair diindenoperylene (DIP) and N,N′-bis(2-ethylhexyl)-1,7-dicyanoperylene-3,4/9,10-bis(dicarboxyimide) (PDIR-CN2) has been chosen as a model system. A wide range of experimental methods was used in order to characterize the structural, optical, electronic, and device properties of the intermolecular interactions. By detailed analysis, we demonstrate that the partial CT in this weakly interacting mixture does not have a strong effect on the ground state and does not generate a hybrid orbital. We also find a strong CT transition in light absorption as well as in photo- and electroluminescence. By using different layer sequences and compositions, we are able to distinguish electronic coupling in-plane vs out-of-plane and, thus, characterize the anisotropy of the CT state. Finally, we discuss the impact of CT exciton generation on charge-carrier transport and on the efficiency of photovoltaic devices.
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| 6. |
- Beyer, Paul, et al.
(författare)
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Fermi level pinned molecular donor/acceptor junctions : Reduction of induced carrier density by interfacial charge transfer complexes
- 2020
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Ingår i: Journal of Materials Chemistry C. - : Royal Society of Chemistry (RSC). - 2050-7534 .- 2050-7526. ; 8:43, s. 15199-15207
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Tidskriftsartikel (refereegranskat)abstract
- Increased hole density in an electron donor-type organic semiconductor can be achieved by deposition of a strong acceptor-type molecular layer on top, and has been shown to enable adjusting the carrier density in organic field effect transistors (OFETs). This interfacial charge transfer is due to simultaneous Fermi level (EF) pinning of the donor's highest occupied level and the acceptor's lowest unoccupied level. Here, we investigate the electrical properties of such an EF-pinned junction formed by diindenoperylene (DIP, as donor) and hexafluoro-tetracyano-naphthoquinodimethane (F6, as acceptor) in OFETs, as well as its electronic properties by photoelectron spectroscopy and electrostatic modelling. We find that, in addition to the EF-pinning induced integer charge transfer across the interface, DIP and F6 form charge transfer complexes (CPXs) at their junction. The molecularly thin CPX interlayer acts as insulator and significantly reduces the density of carriers induced on either side of the junction, compared to a scenario without such an interlayer. CPX formation is thus unfavourable for the effectiveness of controlling carrier density at molecular donor/acceptor junctions by EF-pinning. This journal is
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| 7. |
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| 8. |
- Boniolo, Manuel, et al.
(författare)
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Water Oxidation by Pentapyridyl Base Metal Complexes? : A Case Study
- 2022
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Ingår i: Inorganic Chemistry. - : American Chemical Society (ACS). - 0020-1669 .- 1520-510X. ; 61:24, s. 9104-9118
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Tidskriftsartikel (refereegranskat)abstract
- The design of molecular water oxidation catalysts (WOCs) requires a rational approach that considers the intermediate steps of the catalytic cycle, including water binding, deprotonation, storage of oxidizing equivalents, O–O bond formation, and O2 release. We investigated several of these properties for a series of base metal complexes (M = Mn, Fe, Co, Ni) bearing two variants of a pentapyridyl ligand framework, of which some were reported previously to be active WOCs. We found that only [Fe(Py5OMe)Cl]+ (Py5OMe = pyridine-2,6-diylbis[di-(pyridin-2-yl)methoxymethane]) showed an appreciable catalytic activity with a turnover number (TON) = 130 in light-driven experiments using the [Ru(bpy)3]2+/S2O82– system at pH 8.0, but that activity is demonstrated to arise from the rapid degradation in the buffered solution leading to the formation of catalytically active amorphous iron oxide/hydroxide (FeOOH), which subsequently lost the catalytic activity by forming more extensive and structured FeOOH species. The detailed analysis of the redox and water-binding properties employing electrochemistry, X-ray absorption spectroscopy (XAS), UV–vis spectroscopy, and density-functional theory (DFT) showed that all complexes were able to undergo the MIII/MII oxidation, but none was able to yield a detectable amount of a MIV state in our potential window (up to +2 V vs SHE). This inability was traced to (i) the preference for binding Cl– or acetonitrile instead of water-derived species in the apical position, which excludes redox leveling via proton coupled electron transfer, and (ii) the lack of sigma donor ligands that would stabilize oxidation states beyond MIII. On that basis, design features for next-generation molecular WOCs are suggested.
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| 9. |
- Brune, S., et al.
(författare)
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Serum neurofilament light chain concentration predicts disease worsening in multiple sclerosis
- 2022
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Ingår i: Multiple Sclerosis Journal. - : SAGE Publications. - 1352-4585 .- 1477-0970. ; 28:12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Serum neurofilament light (sNfL) chain is a promising biomarker reflecting neuro-axonal injury in multiple sclerosis (MS). However, the ability of sNfL to predict outcomes in real-world MS cohorts requires further validation. Objective: The aim of the study is to investigate the associations of sNfL concentration, magnetic resonance imaging (MRI) and retinal optical coherence tomography (OCT) markers with disease worsening in a longitudinal European multicentre MS cohort. Methods: MS patients (n = 309) were prospectively enrolled at four centres and re-examined after 2 years (n = 226). NfL concentration was measured by single molecule array assay in serum. The patients' phenotypes were thoroughly characterized with clinical examination, retinal OCT and MRI brain scans. The primary outcome was disease worsening at median 2-year follow-up. Results: Patients with high sNfL concentrations (> 8 pg/mL) at baseline had increased risk of disease worsening at median 2-year follow-up (odds ratio (95% confidence interval) = 2.8 (1.5-5.3), p = 0.001). We found no significant associations of MRI or OCT measures at baseline with risk of disease worsening. Conclusion: Serum NfL concentration was the only factor associated with disease worsening, indicating that sNfL is a useful biomarker in MS that might be relevant in a clinical setting.
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| 10. |
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| 11. |
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| 12. |
- Fischer, Stefanie, et al.
(författare)
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Outcome of men with relapse after adjuvant carboplatin for clinical stage i seminoma
- 2017
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Ingår i: Journal of Clinical Oncology. - 0732-183X. ; 35:2, s. 194-
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Adjuvant carboplatin is one of three management strategies that may follow inguinal orchiectomy in clinical stage I seminoma. However, little is known about the outcome of patients who experience a relapse after such treatment. Patients and Methods Data from 185 patients who relapsed after adjuvant carboplatin between January 1987 and August 2013 at 31 centers/groups from 20 countries were collected and retrospectively analyzed. Primary outcomes were disease-free survival and overall survival. Secondary outcomes were time to, stage at, and treatment of relapse as well as rate of subsequent relapses. Results With a median follow-up of 53 months (95% CI, 48 to 60 months) the 5-year disease-free survival was 82% (95% CI, 77% to 89%), and the 5-year overall survival was 98% (95% CI, 95% to 100%). The median time from orchiectomy to relapse was 19 months (95% CI, 17 to 23 months); 15% (95% CI, 10% to 21%) of relapses occurred > 3 years after treatment. The majority of relapses were detected by computed tomography scan during routine follow-up, 98% in the International Germ Cell Cancer Collaborative Group good prognosis group. Chemotherapy was administered to 92% of patients, mostly as standard first-line treatment corresponding to stage; 8% of patients had additional local treatments. Only 28 patients experienced a second relapse. At last follow-up, 174 (94%) of 185 patients were alive without disease, and four patients with disease. Seven patients died, three of whom due to progressive disease. Conclusion Within the limitations of a retrospective analysis, the results suggest that the majority of patients who experience a relapse after adjuvant carboplatin for clinical stage I seminoma can be successfully treated with a cisplatin-based chemotherapy regimen adequate for stage. Because 15% of the relapses occurred > 3 years after adjuvant treatment, a minimum of 5 years follow-up is recommended.
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| 13. |
- Gandaglia, Giorgio, et al.
(författare)
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Clinical Characterization of Patients Diagnosed with Prostate Cancer and Undergoing Conservative Management : A PIONEER Analysis Based on Big Data
- 2023
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Ingår i: European Urology. - 0302-2838.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Conservative management is an option for prostate cancer (PCa) patients either with the objective of delaying or even avoiding curative therapy, or to wait until palliative treatment is needed. PIONEER, funded by the European Commission Innovative Medicines Initiative, aims at improving PCa care across Europe through the application of big data analytics. Objective: To describe the clinical characteristics and long-term outcomes of PCa patients on conservative management by using an international large network of real-world data. Design, setting, and participants: From an initial cohort of >100 000 000 adult individuals included in eight databases evaluated during a virtual study-a-thon hosted by PIONEER, we identified newly diagnosed PCa cases (n = 527 311). Among those, we selected patients who did not receive curative or palliative treatment within 6 mo from diagnosis (n = 123 146). Outcome measurements and statistical analysis: Patient and disease characteristics were reported. The number of patients who experienced the main study outcomes was quantified for each stratum and the overall cohort. Kaplan-Meier analyses were used to estimate the distribution of time to event data. Results and limitations: The most common comorbidities were hypertension (35–73%), obesity (9.2–54%), and type 2 diabetes (11–28%). The rate of PCa-related symptomatic progression ranged between 2.6% and 6.2%. Hospitalization (12–25%) and emergency department visits (10–14%) were common events during the 1st year of follow-up. The probability of being free from both palliative and curative treatments decreased during follow-up. Limitations include a lack of information on patients and disease characteristics and on treatment intent. Conclusions: Our results allow us to better understand the current landscape of patients with PCa managed with conservative treatment. PIONEER offers a unique opportunity to characterize the baseline features and outcomes of PCa patients managed conservatively using real-world data. Patient summary: Up to 25% of men with prostate cancer (PCa) managed conservatively experienced hospitalization and emergency department visits within the 1st year after diagnosis; 6% experienced PCa-related symptoms. The probability of receiving therapies for PCa decreased according to time elapsed after the diagnosis.
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| 14. |
- Gumberidze, Alexandre, et al.
(författare)
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Angular Distribution of Characteristic Radiation Following the Excitation of He-Like Uranium in Relativistic Collisions
- 2021
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Ingår i: Atoms. - : MDPI AG. - 2218-2004. ; 9:2
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Tidskriftsartikel (refereegranskat)abstract
- In this paper, we present an experimental and theoretical study of excitation processes for the heaviest stable helium-like ion, that is, He-like uranium occurring in relativistic collisions with hydrogen and argon targets. In particular, we concentrate on angular distributions of the characteristic K alpha radiation following the K -> L excitation of He-like uranium. We pay special attention to the magnetic sub-level population of the excited 1s2l(j) states, which is directly related to the angular distribution of the characteristic K alpha radiation. We show that the experimental data can be well described by calculations taking into account the excitation by the target nucleus as well as by the target electrons. Moreover, we demonstrate for the first time an important influence of the electron-impact excitation process on the angular distributions of the K alpha radiation produced by excitation of He-like uranium in collisions with different targets.
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| 15. |
- Huber, Maria, et al.
(författare)
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Metabolic correlates of dopaminergic loss in dementia with lewy bodies
- 2020
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Ingår i: Movement Disorders. - : WILEY. - 0885-3185 .- 1531-8257. ; 35, s. 595-605
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Tidskriftsartikel (refereegranskat)abstract
- Background Striatal dopamine deficiency and metabolic changes are well-known phenomena in dementia with Lewy bodies and can be quantified in vivo by I-123-Ioflupane brain single-photon emission computed tomography of dopamine transporter and F-18-fluorodesoxyglucose PET. However, the linkage between both biomarkers is ill-understood. Objective We used the hitherto largest study cohort of combined imaging from the European consortium to elucidate the role of both biomarkers in the pathophysiological course of dementia with Lewy bodies. Methods We compared striatal dopamine deficiency and glucose metabolism of 84 dementia with Lewy body patients and comparable healthy controls. After normalization of data, we tested their correlation by region-of-interest-based and voxel-based methods, controlled for study center, age, sex, education, and current cognitive impairment. Metabolic connectivity was analyzed by inter-region coefficients stratified by dopamine deficiency and compared to healthy controls. Results There was an inverse relationship between striatal dopamine availability and relative glucose hypermetabolism, pronounced in the basal ganglia and in limbic regions. With increasing dopamine deficiency, metabolic connectivity showed strong deteriorations in distinct brain regions implicated in disease symptoms, with greatest disruptions in the basal ganglia and limbic system, coincident with the pattern of relative hypermetabolism. Conclusions Relative glucose hypermetabolism and disturbed metabolic connectivity of limbic and basal ganglia circuits are metabolic correlates of dopamine deficiency in dementia with Lewy bodies. Identification of specific metabolic network alterations in patients with early dopamine deficiency may serve as an additional supporting biomarker for timely diagnosis of dementia with Lewy bodies. (c) 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
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| 16. |
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| 17. |
- Kaufmann, Tobias, et al.
(författare)
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Common brain disorders are associated with heritable patterns of apparent aging of the brain
- 2019
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Ingår i: Nature Neuroscience. - : Nature Publishing Group. - 1097-6256 .- 1546-1726. ; 22:10, s. 1617-
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Tidskriftsartikel (refereegranskat)abstract
- Common risk factors for psychiatric and other brain disorders are likely to converge on biological pathways influencing the development and maintenance of brain structure and function across life. Using structural MRI data from 45,615 individuals aged 3-96 years, we demonstrate distinct patterns of apparent brain aging in several brain disorders and reveal genetic pleiotropy between apparent brain aging in healthy individuals and common brain disorders.
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| 18. |
- Kowal-Bielecka, Otylia, et al.
(författare)
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Update of EULAR recommendations for the treatment of systemic sclerosis
- 2017
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 76, s. 1327-1339
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Tidskriftsartikel (refereegranskat)abstract
- The aim was to update the 2009 European League against Rheumatism (EULAR) recommendations for the treatment of systemic sclerosis (SSc), with attention to new therapeutic questions. Update of the previous treatment recommendations was performed according to EULAR standard operating procedures. The task force consisted of 32 SSc clinical experts from Europe and the USA, 2 patients nominated by the pan-European patient association for SSc (Federation of European Scleroderma Associations (FESCA)), a clinical epidemiologist and 2 research fellows. All centres from the EULAR Scleroderma Trials and Research group were invited to submit and select clinical questions concerning SSc treatment using a Delphi approach. Accordingly, 46 clinical questions addressing 26 different interventions were selected for systematic literature review. The new recommendations were based on the available evidence and developed in a consensus meeting with clinical experts and patients. The procedure resulted in 16 recommendations being developed (instead of 14 in 2009) that address treatment of several SSc-related organ complications: Raynaud's phenomenon (RP), digital ulcers (DUs), pulmonary arterial hypertension (PAH), skin and lung disease, scleroderma renal crisis and gastrointestinal involvement. Compared with the 2009 recommendations, the 2016 recommendations include phosphodiesterase type 5 (PDE-5) inhibitors for the treatment of SSc-related RP and DUs, riociguat, new aspects for endothelin receptor antagonists, prostacyclin analogues and PDE-5 inhibitors for SSc-related PAH. New recommendations regarding the use of fluoxetine for SSc-related RP and haematopoietic stem cell transplantation for selected patients with rapidly progressive SSc were also added. In addition, several comments regarding other treatments addressed in clinical questions and suggestions for the SSc research agenda were formulated. These updated data-derived and consensus-derived recommendations will help rheumatologists to manage patients with SSc in an evidence-based way. These recommendations also give directions for future clinical research in SSc.
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| 19. |
- Lawlor, Ailbhe, et al.
(författare)
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Predictive Models for Assessing Patients’ Response to Treatment in Metastatic Prostate Cancer : A Systematic Review
- 2024
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Ingår i: European Urology Open Science. - 2666-1691. ; 63, s. 126-135
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Forskningsöversikt (refereegranskat)abstract
- Background and objective: The treatment landscape of metastatic prostate cancer (mPCa) has evolved significantly over the past two decades. Despite this, the optimal therapy for patients with mPCa has not been determined. This systematic review identifies available predictive models that assess mPCa patients’ response to treatment. Methods: We critically reviewed MEDLINE and CENTRAL in December 2022 according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. Only quantitative studies in English were included with no time restrictions. The quality of the included studies was assessed using the PROBAST tool. Data were extracted following the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews criteria. Key findings and limitations: The search identified 616 citations, of which 15 studies were included in our review. Nine of the included studies were validated internally or externally. Only one study had a low risk of bias and a low risk concerning applicability. Many studies failed to detail model performance adequately, resulting in a high risk of bias. Where reported, the models indicated good or excellent performance. Conclusions and clinical implications: Most of the identified predictive models require additional evaluation and validation in properly designed studies before these can be implemented in clinical practice to assist with treatment decision-making for men with mPCa. Patient summary: In this review, we evaluate studies that predict which treatments will work best for which metastatic prostate cancer patients. We found that existing studies need further improvement before these can be used by health care professionals.
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| 20. |
- Muraro, Antonella, et al.
(författare)
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Managing food allergy: GA2LEN guideline 2022.
- 2022
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Ingår i: The World Allergy Organization journal. - : Elsevier BV. - 1939-4551. ; 15:9
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Tidskriftsartikel (refereegranskat)abstract
- Food allergy affects approximately 2-4% of children and adults. This guideline provides recommendations for managing food allergy from the Global Allergy and Asthma European Network (GA2LEN). A multidisciplinary international Task Force developed the guideline using the Appraisal of Guidelines for Research and Evaluation (AGREE) II framework and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. We reviewed the latest available evidence as of April 2021 (161 studies) and created recommendations by balancing benefits, harms, feasibility, and patient and clinician experiences. We suggest that people diagnosed with food allergy avoid triggering allergens (low certainty evidence). We suggest that infants with cow's milk allergy who need a breastmilk alternative use either hypoallergenic extensively hydrolyzed cow's milk formula or an amino acid-based formula (moderate certainty). For selected children with peanut allergy, we recommend oral immunotherapy (high certainty), though epicutaneous immunotherapy might be considered depending on individual preferences and availability (moderate certainty). We suggest considering oral immunotherapy for children with persistent severe hen's egg or cow's milk allergy (moderate certainty). There are significant gaps in evidence about safety and effectiveness of the various strategies. Research is needed to determine the best approaches to education, how to predict the risk of severe reactions, whether immunotherapy is cost-effective and whether biological therapies are effective alone or combined with allergen immunotherapy.
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| 21. |
- Rise, H. H., et al.
(författare)
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Brain disconnectome mapping derived from white matter lesions and serum neurofilament light levels in multiple sclerosis: A longitudinal multicenter study
- 2022
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Ingår i: Neuroimage-Clinical. - : Elsevier BV. - 2213-1582. ; 35
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objectives: Connectivity-based approaches incorporating the distribution and magnitude of the extended brain network aberrations caused by lesions may offer higher sensitivity for axonal damage in patients with multiple sclerosis (MS) than conventional lesion characteristics. Using individual brain disconnectome mapping, we tested the longitudinal associations between putative imaging-based brain network aberrations and levels of serum neurofilament light chain (NfL) as a neuroaxonal injury biomarker. Methods: MS patients (n = 312, mean age 42.9 years, 71 % female) and healthy controls (HC) (n = 59, mean age 39.9 years, 78 % female) were prospectively enrolled at four European MS centres, and reassessed after two years (MS, n = 242; HC, n = 30). Post-processing of 3 Tesla (3 T) MRI data was performed at one centre using a harmonized pipeline, and disconnectome maps were calculated using BCBtoolkit based on individual lesion maps. Global disconnectivity (GD) was defined as the average disconnectome probability in each patient's white matter. Serum NfL concentrations were measured by single molecule array (Simoa). Robust linear mixed models (rLMM) with GD or T2-lesion volume (T2LV) as dependent variables, patient as a random factor, serum NfL, age, sex, timepoint for visit, diagnosis, treatment, and center as fixed factors were run. Results: rLMM revealed significant associations between GD and serum NfL (t = 2.94, p = 0.003), age (t = 4.21, p = 2.5 x 10(-5)), and longitudinal changes in NfL (t =-2.29, p = 0.02), but not for sex (t = 0.63, p = 0.53) or treatments (t = 0.80-0.83, p = 0.41-0.42). Voxel-wise analyses revealed significant associations between dysconnectivity in cerebellar and brainstem regions and serum NfL (t = 7.03, p < 0.001). Discussion: In our prospective multi-site MS cohort, rLMMs demonstrated that the extent of global and regional brain disconnectivity is sensitive to a systemic biomarker of axonal damage, serum NfL, in patients with MS. These findings provide a neuroaxonal correlate of advanced disconnectome mapping and provide a platform for further investigations of the functional and potential clinical relevance of brain disconnectome mapping in patients with brain disorders.
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| 22. |
- Stockbauer, Anna, et al.
(författare)
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Metabolic network alterations as a supportive biomarker in dementia with Lewy bodies with preserved dopamine transmission
- 2024
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Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : SPRINGER. - 1619-7070 .- 1619-7089. ; 51:4, s. 1023-1034
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Metabolic network analysis of FDG-PET utilizes an index of inter-regional correlation of resting state glucose metabolism and has been proven to provide complementary information regarding the disease process in parkinsonian syndromes. The goals of this study were (i) to evaluate pattern similarities of glucose metabolism and network connectivity in dementia with Lewy bodies (DLB) subjects with subthreshold dopaminergic loss compared to advanced disease stages and to (ii) investigate metabolic network alterations of FDG-PET for discrimination of patients with early DLB from other neurodegenerative disorders (Alzheimer's disease, Parkinson's disease, multiple system atrophy) at individual patient level via principal component analysis (PCA).Methods FDG-PETs of subjects with probable or possible DLB (n = 22) without significant dopamine deficiency (z-score < 2 in putamen binding loss on DaT-SPECT compared to healthy controls (HC)) were scaled by global-mean, prior to volume-of-interest-based analyses of relative glucose metabolism. Single region metabolic changes and network connectivity changes were compared against HC (n = 23) and against DLB subjects with significant dopamine deficiency (n = 86). PCA was applied to test discrimination of patients with DLB from disease controls (n = 101) at individual patient level.Results Similar patterns of hypo- (parietal- and occipital cortex) and hypermetabolism (basal ganglia, limbic system, motor cortices) were observed in DLB patients with and without significant dopamine deficiency when compared to HC. Metabolic connectivity alterations correlated between DLB patients with and without significant dopamine deficiency (R2 = 0.597, p < 0.01). A PCA trained by DLB patients with dopamine deficiency and HC discriminated DLB patients without significant dopaminergic loss from other neurodegenerative parkinsonian disorders at individual patient level (area-under-the-curve (AUC): 0.912).Conclusion Disease-specific patterns of altered glucose metabolism and altered metabolic networks are present in DLB subjects without significant dopaminergic loss. Metabolic network alterations in FDG-PET can act as a supporting biomarker in the subgroup of DLB patients without significant dopaminergic loss at symptoms onset.
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| 23. |
- Winbanks, Catherine E., et al.
(författare)
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The bone morphogenetic protein axis is a positive regulator of skeletal muscle mass
- 2013
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Ingår i: Journal of Cell Biology. - : Rockefeller University Press. - 0021-9525 .- 1540-8140. ; 203:2, s. 345-357
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Tidskriftsartikel (refereegranskat)abstract
- Although the canonical transforming growth factor. signaling pathway represses skeletal muscle growth and promotes muscle wasting, a role in muscle for the parallel bone morphogenetic protein (BMP) signaling pathway has not been defined. We report, for the first time, that the BMP pathway is a positive regulator of muscle mass. Increasing the expression of BMP7 or the activity of BMP receptors in muscles induced hypertrophy that was dependent on Smad1/5-mediated activation of mTOR signaling. In agreement, we observed that BMP signaling is augmented in models of muscle growth. Importantly, stimulation of BMP signaling is essential for conservation of muscle mass after disruption of the neuromuscular junction. Inhibiting the phosphorylation of Smad1/5 exacerbated denervation-induced muscle atrophy via an HDAC4-myogenin-dependent process, whereas increased BMP-Smad1/5 activity protected muscles from denervation- induced wasting. Our studies highlight a novel role for the BMP signaling pathway in promoting muscle growth and inhibiting muscle wasting, which may have significant implications for the development of therapeutics for neuromuscular disorders.
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| 24. |
- Bravo, L, et al.
(författare)
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- 2021
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swepub:Mat__t
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