| 1. |
- Freischmidt, Axel, et al.
(författare)
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A serum microRNA sequence reveals fragile X protein pathology in amyotrophic lateral sclerosis
- 2021
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Ingår i: Brain. - : Oxford University Press. - 0006-8950 .- 1460-2156. ; 144:4, s. 1214-1229
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Tidskriftsartikel (refereegranskat)abstract
- Knowledge about converging disease mechanisms in the heterogeneous syndrome amyotrophic lateral sclerosis (ALS) is rare, but may lead to therapies effective in most ALS cases. Previously, we identified serum microRNAs downregulated in familial ALS, the majority of sporadic ALS patients, but also in presymptomatic mutation carriers. A 5-nucleotide sequence motif (GDCGG; D = G, A or U) was strongly enriched in these ALS-related microRNAs. We hypothesized that deregulation of protein(s) binding predominantly to this consensus motif was responsible for the ALS-linked microRNA fingerprint. Using microRNA pull-down assays combined with mass spectrometry followed by extensive biochemical validation, all members of the fragile X protein family, FMR1, FXR1 and FXR2, were identified to directly and predominantly interact with GDCGG microRNAs through their structurally disordered RGG/RG domains. Preferential association of this protein family with ALS-related microRNAs was confirmed by in vitro binding studies on a transcriptome-wide scale. Immunohistochemistry of lumbar spinal cord revealed aberrant expression level and aggregation of FXR1 and FXR2 in C9orf72- and FUS-linked familial ALS, but also patients with sporadic ALS. Further analysis of ALS autopsies and induced pluripotent stem cell-derived motor neurons with FUS mutations showed co-aggregation of FXR1 with FUS. Hence, our translational approach was able to take advantage of blood microRNAs to reveal CNS pathology, and suggests an involvement of the fragile X-related proteins in familial and sporadic ALS already at a presymptomatic stage. The findings may uncover disease mechanisms relevant to many patients with ALS. They furthermore underscore the systemic, extra-CNS aspect of ALS.
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| 2. |
- Witjes, J. Alfred, et al.
(författare)
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EAU-ESMO Consensus Statements on the Management of Advanced and Variant Bladder Cancer – An International Collaborative Multistakeholder Effort : Under the Auspices of the EAU-ESMO Guidelines Committees
- 2020
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Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 77:2, s. 223-250
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial.OBJECTIVE: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management.DESIGN: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts prior to voting during a consensus conference.SETTING: Online Delphi survey and consensus conference.PARTICIPANTS: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Statements were ranked by experts according to their level of agreement: 1-3 (disagree), 4-6 (equivocal), and 7-9 (agree). A priori (level 1) consensus was defined as ≥70% agreement and ≤15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus).RESULTS AND LIMITATIONS: Overall, 116 statements were included in the Delphi survey. Of these statements, 33 (28%) achieved level 1 consensus and 49 (42%) achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease, and the evolving role of checkpoint inhibitor therapy in metastatic disease.CONCLUSIONS: These consensus statements provide further guidance on controversial topics in advanced and variant bladder cancer management until a time when further evidence is available to guide our approach.PATIENT SUMMARY: This report summarises findings from an international, multistakeholder project organised by the EAU and ESMO. In this project, a steering committee identified areas of bladder cancer management where there is currently no good-quality evidence to guide treatment decisions. From this, they developed a series of proposed statements, 71 of which achieved consensus by a large group of experts in the field of bladder cancer. It is anticipated that these statements will provide further guidance to health care professionals and could help improve patient outcomes until a time when good-quality evidence is available.
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| 3. |
- Egan, Allyson C, et al.
(författare)
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The Sound of Interconnectivity; The European Vasculitis Society 2022 Report
- 2022
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Ingår i: Kidney International Reports. - : Elsevier BV. - 2468-0249. ; 7:8, s. 1745-1757
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Tidskriftsartikel (refereegranskat)abstract
- The first European Vasculitis Society (EUVAS) meeting report was published in 2017. Herein, we report on developments in the past 5 years which were greatly influenced by the pandemic. The adaptability to engage virtually, at this critical time in society, embodies the importance of networks and underscores the role of global collaborations. We outline state-of-the-art webinar topics, updates on developments in the last 5 years, and proposals for agendas going forward. A host of newly reported clinical trials is shaping practice on steroid minimization, maintenance strategies, and the role of newer therapies. To guide longer-term strategies, a longitudinal 10-year study investigating relapse, comorbidity, malignancy, and survival rates is at an advanced stage. Disease assessment studies are refining classification criteria to differentiate forms of vasculitis more fully. A large international validation study on the histologic classification of anti-neutrophil cytoplasmic antibody (ANCA) glomerulonephritis, recruiting new multicenter sites and comparing results with the Kidney Risk Score, has been conducted. Eosinophilic granulomatosis with polyangiitis (EGPA) genomics offers potential pathogenic subset and therapeutic insights. Among biomarkers, ANCA testing is favoring immunoassay as the preferred method for diagnostic evaluation. Consolidated development of European registries is progressing with an integrated framework to analyze large clinical data sets on an unprecedented scale.
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| 4. |
- Denault, Vincent, et al.
(författare)
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The Analysis of Nonverbal Communication: The Dangers of Pseudoscience in Security and Justice Contexts : Análisis de la comunicación no verbal: los peligros de la pseudociencia en entornos de seguridad y justicia
- 2020
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Ingår i: Anuario de Psicología Jurídica. - : Colegio Oficial de la Psicologia de Madrid. - 1133-0740 .- 2174-0542. ; 30:1, s. 1-12
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Forskningsöversikt (refereegranskat)abstract
- For security and justice professionals (e.g., police officers, lawyers, judges), the thousands of peer-reviewed articles on nonverbal communication represent important sources of knowledge. However, despite the scope of the scientific work carried out on this subject, professionals can turn to programs, methods, and approaches that fail to reflect the state of science. The objective of this article is to examine (i) concepts of nonverbal communication conveyed by these programs, methods, and approaches, but also (ii) the consequences of their use (e.g., on the life or liberty of individuals). To achieve this objective, we describe the scope of scientific research on nonverbal communication. A program (SPOT; Screening of Passengers by Observation Techniques), a method (the BAI; Behavior Analysis Interview) and an approach (synergology) that each run counter to the state of science are examined. Finally, we outline five hypotheses to explain why some organizations in the fields of security and justice are turning to pseudoscience and pseudoscientific techniques. We conclude the article by inviting these organizations to work with the international community of scholars who have scientific expertise in nonverbal communication and lie (and truth) detection to implement evidence-based practices.
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| 5. |
- Kaizer, Alexander M., et al.
(författare)
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Effects of cohort, genotype, variant, and maternal β-blocker treatment on foetal heart rate predictors of inherited long QT syndrome
- 2023
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Ingår i: Europace. - : Oxford University Press. - 1099-5129 .- 1532-2092. ; 25:11
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: In long QT syndrome (LQTS), primary prevention improves outcome; thus, early identification is key. The most common LQTS phenotype is a foetal heart rate (FHR) < 3rd percentile for gestational age (GA) but the effects of cohort, genotype, variant, and maternal β-blocker therapy on FHR are unknown. We assessed the influence of these factors on FHR in pregnancies with familial LQTS and developed a FHR/GA threshold for LQTS.METHODS AND RESULTS: In an international cohort of pregnancies in which one parent had LQTS, LQTS genotype, familial variant, and maternal β-blocker effects on FHR were assessed. We developed a testing algorithm for LQTS using FHR and GA as continuous predictors. Data included 1966 FHRs at 7-42 weeks' GA from 267 pregnancies/164 LQTS families [220 LQTS type 1 (LQT1), 35 LQTS type 2 (LQT2), and 12 LQTS type 3 (LQT3)]. The FHRs were significantly lower in LQT1 and LQT2 but not LQT3 or LQTS negative. The LQT1 variants with non-nonsense and severe function loss (current density or β-adrenergic response) had lower FHR. Maternal β-blockers potentiated bradycardia in LQT1 and LQT2 but did not affect FHR in LQTS negative. A FHR/GA threshold predicted LQT1 and LQT2 with 74.9% accuracy, 71% sensitivity, and 81% specificity.CONCLUSION: Genotype, LQT1 variant, and maternal β-blocker therapy affect FHR. A predictive threshold of FHR/GA significantly improves the accuracy, sensitivity, and specificity for LQT1 and LQT2, above the infant's a priori 50% probability. We speculate this model may be useful in screening for LQTS in perinatal subjects without a known LQTS family history.
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| 6. |
- Karyotaki, Eirini, et al.
(författare)
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Internet-Based Cognitive Behavioral Therapy for Depression : A Systematic Review and Individual Patient Data Network Meta-analysis
- 2021
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Ingår i: JAMA psychiatry. - : American Medical Association. - 2168-6238 .- 2168-622X. ; 78:4, s. 361-371
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Forskningsöversikt (refereegranskat)abstract
- IMPORTANCE: Personalized treatment choices would increase the effectiveness of internet-based cognitive behavioral therapy (iCBT) for depression to the extent that patients differ in interventions that better suit them.OBJECTIVE: To provide personalized estimates of short-term and long-term relative efficacy of guided and unguided iCBT for depression using patient-level information.DATA SOURCES: We searched PubMed, Embase, PsycInfo, and Cochrane Library to identify randomized clinical trials (RCTs) published up to January 1, 2019.STUDY SELECTION: Eligible RCTs were those comparing guided or unguided iCBT against each other or against any control intervention in individuals with depression. Available individual patient data (IPD) was collected from all eligible studies. Depression symptom severity was assessed after treatment, 6 months, and 12 months after randomization.DATA EXTRACTION AND SYNTHESIS: We conducted a systematic review and IPD network meta-analysis and estimated relative treatment effect sizes across different patient characteristics through IPD network meta-regression.MAIN OUTCOMES AND MEASURES: Patient Health Questionnaire-9 (PHQ-9) scores.RESULTS: Of 42 eligible RCTs, 39 studies comprising 9751 participants with depression contributed IPD to the IPD network meta-analysis, of which 8107 IPD were synthesized. Overall, both guided and unguided iCBT were associated with more effectiveness as measured by PHQ-9 scores than control treatments over the short term and the long term. Guided iCBT was associated with more effectiveness than unguided iCBT (mean difference [MD] in posttreatment PHQ-9 scores, -0.8; 95% CI, -1.4 to -0.2), but we found no evidence of a difference at 6 or 12 months following randomization. Baseline depression was found to be the most important modifier of the relative association for efficacy of guided vs unguided iCBT. Differences between unguided and guided iCBT in people with baseline symptoms of subthreshold depression (PHQ-9 scores 5-9) were small, while guided iCBT was associated with overall better outcomes in patients with baseline PHQ-9 greater than 9.CONCLUSIONS AND RELEVANCE: In this network meta-analysis with IPD, guided iCBT was associated with more effectiveness than unguided iCBT for individuals with depression, benefits were more substantial in individuals with moderate to severe depression. Unguided iCBT was associated with similar effectiveness among individuals with symptoms of mild/subthreshold depression. Personalized treatment selection is entirely possible and necessary to ensure the best allocation of treatment resources for depression.
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| 7. |
- Koller, Volkmar, et al.
(författare)
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Critical Step in the HCl Oxidation Reaction over Single-Crystalline CeO2-x(111) : Peroxo-Induced Site Change of Strongly Adsorbed Surface Chlorine
- 2023
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Ingår i: ACS Catalysis. - 2155-5435. ; 13:19, s. 12994-13007
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Tidskriftsartikel (refereegranskat)abstract
- The catalytic oxidation of HCl by molecular oxygen (Deacon process) over ceria allows the recovery of molecular chlorine from the omnipresent HCl waste produced in various industrial processes. In previous density functional theory (DFT) model-calculations by Amrute et al. [ J. Catal. 2012, 286, 287−297.], it was proposed that the most critical reaction step in this process is the displacement of tightly bound chlorine at a vacant oxygen position on the CeO2(111) surface (Clvac) toward a less strongly bound cerium on-top (Cltop) position. This step is highly endothermic by more than 2 eV. On the basis of a dedicated model study, namely the reoxidation of a chlorinated single-crystalline Clvac-CeO2-x(111)-(Formula Presented × Formula Presented)R30° surface structure, we provide in situ synchrotron-based spectroscopic data (high resolution core level spectroscopy (HRCLS) and X-ray adsorption near edge structure (XANES)) for this oxygen-induced dechlorination process. Combined with theoretical evidence from DFT calculations, the Clvac → Cltop displacement reaction is predicted to be induced by an adsorbed peroxo species (O22-), making the displacement step concerted and exothermic by 0.6 eV with an activation barrier of only 1.04 eV. The peroxo species is shown to be important for the reoxidation of Clvac-CeO2-x(111) and is considered essential for understanding the function of ceria in oxidation catalysis.
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| 8. |
- Kronbichler, Andreas, et al.
(författare)
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The COVID-19 pandemic and ANCA-associated vasculitis - reports from the EUVAS meeting and EUVAS education forum
- 2021
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Ingår i: Autoimmunity Reviews. - : Elsevier. - 1568-9972 .- 1873-0183. ; 20:12
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Forskningsöversikt (refereegranskat)abstract
- The Coronavirus Disease 2019 (COVID-19) pandemic influenced the management of patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. A paucity of data exists on outcome of patients with vasculitis following COVID-19, but mortality is higher than in the general population and comparable to patients undergoing haemodialysis or kidney transplant recipients (reported mortality rates of 20-25%). Delays in diagnosis have been reported, which are associated with sequelae such as dialysis-dependency. Management of ANCA-associated vasculitis has not changed with the aim to suppress disease activity and reduce burden of disease. The use of rituximab, an important and widely used agent, is associated with a more severe hospital course of COVID-19 and absence of antibodies following severe acute respiratory syndrome (SARS)-CoV-2 infections, which prone patients to re-infection. Reports on vaccine antibody response are scarce at the moment, but preliminary findings point towards an impaired immune response, especially when patients receive rituximab as part of their treatment. Seropositivity was reported in less than 20% of patients when rituximab was administered within the prior six months, and the antibody response correlated with CD19+ B-cell repopulation. A delay in maintenance doses, if disease activity allows, has been suggested using a CD19+ B-cell guided strategy. Other immunosuppressive measures, which are used in ANCA-associated vasculitis, also impair humoral and cellular vaccine responses. Regular measurements of vaccine response or a healthcare-policy time-based strategy are indicated to provide additional doses ("booster") of COVID-19 vaccines. This review summarizes a recent educational forum and a recent virtual meeting of the European Vasculitis Society (EUVAS) focusing on COVID-19.
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| 9. |
- Leinonen, Ville, et al.
(författare)
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Comparison of particle number size distribution trends in ground measurements and climate models
- 2022
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Ingår i: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 22:19, s. 12873-12905
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Tidskriftsartikel (refereegranskat)abstract
- Despite a large number of studies, out of all drivers of radiative forcing, the effect of aerosols has the largest uncertainty in global climate model radiative forcing estimates. There have been studies of aerosol optical properties in climate models, but the effects of particle number size distribution need a more thorough inspection. We investigated the trends and seasonality of particle number concentrations in nucleation, Aitken, and accumulation modes at 21 measurement sites in Europe and the Arctic. For 13 of those sites, with longer measurement time series, we compared the field observations with the results from five climate models, namely EC-Earth3, ECHAM-M7, ECHAM-SALSA, NorESM1.2, and UKESM1. This is the first extensive comparison of detailed aerosol size distribution trends between in situ observations from Europe and five earth system models (ESMs). We found that the trends of particle number concentrations were mostly consistent and decreasing in both measurements and models. However, for many sites, climate models showed weaker decreasing trends than the measurements. Seasonal variability in measured number concentrations, quantified by the ratio between maximum and minimum monthly number concentration, was typically stronger at northern measurement sites compared to other locations. Models had large differences in their seasonal representation, and they can be roughly divided into two categories: for EC-Earth and NorESM, the seasonal cycle was relatively similar for all sites, and for other models the pattern of seasonality varied between northern and southern sites. In addition, the variability in concentrations across sites varied between models, some having relatively similar concentrations for all sites, whereas others showed clear differences in concentrations between remote and urban sites. To conclude, although all of the model simulations had identical input data to describe anthropogenic mass emissions, trends in differently sized particles vary among the models due to assumptions in emission sizes and differences in how models treat size-dependent aerosol processes. The inter-model variability was largest in the accumulation mode, i.e. sizes which have implications for aerosol–cloud interactions. Our analysis also indicates that between models there is a large variation in efficiency of long-range transportation of aerosols to remote locations. The differences in model results are most likely due to the more complex effect of different processes instead of one specific feature (e.g. the representation of aerosol or emission size distributions). Hence, a more detailed characterization of microphysical processes and deposition processes affecting the long-range transport is needed to understand the model variability.
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| 10. |
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| 11. |
- Stepniewska, Kasia, et al.
(författare)
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Efficacy of single dose primaquine with artemisinin combination therapy on P. falciparum gametocytes and transmission : A WWARN individual patient meta-analysis.
- 2020
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 0022-1899 .- 1537-6613. ; 225:7, s. 1215-1226
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Since the World Health Organization recommended single low-dose (0.25mg/kg) primaquine (PQ) in combination with artemisinin-based combination therapies (ACTs) in areas of low transmission or artemisinin-resistant P. falciparum, several single-site studies have been conducted to assess its efficacy.METHODS: An individual patient meta-analysis to assess the gametocytocidal and transmission-blocking efficacy of PQ used in combination with different ACTs was conducted. Random effects logistic regression was used to quantify PQ effect on (i) gametocyte carriage in the first two weeks post-treatment; (ii) the probability of infecting at least one mosquito or of a mosquito becoming infected.RESULTS: In 2,574 participants from fourteen studies, PQ reduced PCR-determined gametocyte carriage on days 7 and 14, most apparently in patients presenting with gametocytaemia on day 0 (Odds Ratio (OR)=0.22; 95%CI 0.17-0.28 and OR=0.12; 95%CI 0.08-0.16, respectively). The rate of decline in gametocyte carriage was faster when PQ was combined with artemether-lumefantrine (AL) compared to dihydroartemisinin-piperaquine (DP) (p=0.010 for day 7). Addition of 0.25mg/kg PQ was associated with near complete prevention of transmission to mosquitoes.CONCLUSION: Primaquine's transmission-blocking effects are achieved with 0.25 mg/kg PQ. Gametocyte persistence and infectivity are lower when PQ is combined with AL compared to DP.
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| 12. |
- Stepniewska, Kasia, et al.
(författare)
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Safety of single-dose primaquine as a Plasmodium falciparum gametocytocide : a systematic review and meta-analysis of individual patient data
- 2022
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Ingår i: BMC Medicine. - : Springer Nature. - 1741-7015. ; 20:1
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Forskningsöversikt (refereegranskat)abstract
- BackgroundIn 2012, the World Health Organization (WHO) recommended single low-dose (SLD, 0.25 mg/kg) primaquine to be added as a Plasmodium (P.) falciparum gametocytocide to artemisinin-based combination therapy (ACT) without glucose-6-phosphate dehydrogenase (G6PD) testing, to accelerate malaria elimination efforts and avoid the spread of artemisinin resistance. Uptake of this recommendation has been relatively slow primarily due to safety concerns.MethodsA systematic review and individual patient data (IPD) meta-analysis of single-dose (SD) primaquine studies for P. falciparum malaria were performed. Absolute and fractional changes in haemoglobin concentration within a week and adverse effects within 28 days of treatment initiation were characterised and compared between primaquine and no primaquine arms using random intercept models.ResultsData comprised 20 studies that enrolled 6406 participants, of whom 5129 (80.1%) had received a single target dose of primaquine ranging between 0.0625 and 0.75 mg/kg. There was no effect of primaquine in G6PD-normal participants on haemoglobin concentrations. However, among 194 G6PD-deficient African participants, a 0.25 mg/kg primaquine target dose resulted in an additional 0.53 g/dL (95% CI 0.17-0.89) reduction in haemoglobin concentration by day 7, with a 0.27 (95% CI 0.19-0.34) g/dL haemoglobin drop estimated for every 0.1 mg/kg increase in primaquine dose. Baseline haemoglobin, young age, and hyperparasitaemia were the main determinants of becoming anaemic (Hb < 10 g/dL), with the nadir observed on ACT day 2 or 3, regardless of G6PD status and exposure to primaquine. Time to recovery from anaemia took longer in young children and those with baseline anaemia or hyperparasitaemia. Serious adverse haematological events after primaquine were few (9/3, 113, 0.3%) and transitory. One blood transfusion was reported in the primaquine arms, and there were no primaquine-related deaths. In controlled studies, the proportions with either haematological or any serious adverse event were similar between primaquine and no primaquine arms.ConclusionsOur results support the WHO recommendation to use 0.25 mg/kg of primaquine as a P. falciparum gametocytocide, including in G6PD-deficient individuals. Although primaquine is associated with a transient reduction in haemoglobin levels in G6PD-deficient individuals, haemoglobin levels at clinical presentation are the major determinants of anaemia in these patients.
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| 13. |
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| 14. |
- Burian, Alfred, et al.
(författare)
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Food quantity-quality interactions and their impact on consumer behavior and trophic transfer
- 2020
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Ingår i: Ecological Monographs. - : Wiley. - 0012-9615 .- 1557-7015. ; 90:1
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Tidskriftsartikel (refereegranskat)abstract
- Food quantity-quality interactions determine growth rates and reproductive success of consumers and thereby regulate community dynamics and food web structure. Predator-prey models that shape our conceptual understanding of foraging ecology typically rely on the parametrization of fixed consumer responses to either food quantity or food quality. In nature, however, consumers optimize their fitness by responding simultaneously to changes in food quantity and quality. Therefore, we assessed consumer responses to changing food environments using a new fitness optimization model that accounted for food quality-quantity interactions to better capture the regulatory flexibility of consumers. Our simulations demonstrated that the impact of food quality on important consumer traits can be altered or even reversed by changes in food quality. Low food quality, for example, affected feeding rates negatively at low food concentrations but triggered surplus feeding at high food concentrations. The scope of surplus feeding was thereby mainly dependent on dynamics of nutrient digestion and in contrast to previous assumptions, energy costs of feeding played a minor role. Further, the regulation of digestive enzyme production, a crucial factor determining assimilation efficiencies, was strongly dependent on whether nonessential or essential nutrients were limiting growth. Consequently, not only the degree but also the type of nutrient limitation mediated the impact of the food environment on consumers' fitness. At the community level, food quality was key in shaping predator-prey biomass ratios. High food qualities resulted in top-heavy systems with larger consumer than prey biomass. Decreases of prey digestibility or the availability of essential nutrients, however, triggered a switch from inverted to classical pyramid shapes of bi-trophic systems. The impact of food quantity on trophic transfer and emerging structural ecosystem properties thus critically hinges on behavioral and physiological responses of consumers. The inclusion of the regulatory flexibility of consumers is therefore an essential next step to improve predator-prey models and our conceptual understanding of trophic interactions.
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| 15. |
- Burian, Alfred, et al.
(författare)
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The potential of fatty acid isotopes to trace trophic transfer in aquatic food-webs
- 2020
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Ingår i: Philosophical Transactions of the Royal Society of London. Biological Sciences. - : The Royal Society. - 0962-8436 .- 1471-2970. ; 375:1804
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Tidskriftsartikel (refereegranskat)abstract
- Compound-specific isotope analyses (CSIA) of fatty acids (FA) constitute a promising tool for tracing energy flows in food-webs. However, past applications of FA-specific carbon isotope analyses have been restricted to a relatively coarse food-source separation and mainly quantified dietary contributions from different habitats. Our aim was to evaluate the potential of FA-CSIA to provide high-resolution data on within-system energy flows using algae and zooplankton as model organisms. First, we investigated the power of FA-CSIA to distinguish among four different algae groups, namely cyanobacteria, chlorophytes, haptophytes and diatoms. We found substantial within-group variation but also demonstrated that delta C-13 of several FA (e.g. 18:3 omega 3 or 18:4 omega 3) differed among taxa, resulting in group-specific isotopic fingerprints. Second, we assessed changes in FA isotope ratios with trophic transfer. Isotope fractionation was highly variable in daphnids and rotifers exposed to different food sources. Only delta C-13 of nutritionally valuable poly-unsaturated FA remained relatively constant, highlighting their potential as dietary tracers. The variability in fractionation was partly driven by the identity of food sources. Such systematic effects likely reflect the impact of dietary quality on consumers' metabolism and suggest that FA isotopes could be useful nutritional indicators in the field. Overall, our results reveal that the variability of FA isotope ratios provides a substantial challenge, but that FA-CSIA nevertheless have several promising applications in food-web ecology. This article is part of the theme issue 'The next horizons for lipids as 'trophic biomarkers': evidence and significance of consumer modification of dietary fatty acids'.
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| 16. |
- Capobianco, Ivan, et al.
(författare)
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Development and internal validation of the Comprehensive ALPPS Preoperative Risk Assessment (CAPRA) score : is the patient suitable for Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS)?
- 2022
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Ingår i: Hepatobiliary surgery and nutrition. - Hong Kong : AME Publishing Company. - 2304-3881 .- 2304-389X. ; 11:1, s. 52-66
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Tidskriftsartikel (refereegranskat)abstract
- Background: Preoperative patient selection in associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is not always reliable with currently available scores, particularly in patients with primary liver tumor. This study aims to (I) to determine whether comorbidities and patients characteristics are a risk factor in ALPPS and (II) to create a score predicting 90-day mortality preoperatively. Methods: Thirteen high-volume centers participated in this retrospective multicentric study. A risk analysis based on patient characteristics, underlying disease and procedure type was performed to identify risk factors and model the CAPRA score. A nonparametric receiver operating characteristic analysis was performed to estimate the predictive ability of our score against the Charlson Comorbidity Index (CCI), the age-adjusted CCI (aCCI), the ALPPS risk score before Stage 1 (ALPPS-RS I) and Stage 2 (ALPPS-RS2). The model was internally validated applying bootstrapping. Results: A total of 451 patients were included. Mortality was 14.4%. The CAPRA score is calculated based on the following formula: (0.1*age) - (2*BSA) +1 (in the presence of primary liver tumor) +1 (in the presence of severe cardiovascular disease) +2 (in the presence of moderate or severe diabetes) +2 (in the presence of renal disease) +2 (if classic ALPPS is planned). The predictive ability was 0.837 for the CAPRA score, 0.443 for CCI, 0.519 for aCCI, 0.693 for ALPPS-RS I and 0.807 for ALPPS-RS2. After 1,000 cycles of bootstrapping the C statistic was 0.793. The accuracy plot revealed a cut-off for optimal prediction of postoperative mortality of 4.70. Conclusions: Comorbidities play an important role in ALPPS and should be carefully considered when planning the procedure. By assessing the patients preoperative condition in relation to ALPPS, the CAPRA score has a very good ability to predict postoperative mortality.
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| 17. |
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| 18. |
- Fougelberg, Julia, et al.
(författare)
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Dermoscopic Findings in Intraepidermal Carcinoma: an Interobserver Agreement Study
- 2023
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Ingår i: Dermatology Practical & Conceptual. - : Mattioli1885. - 2160-9381. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: A wide range of descriptive terms have been used for dermoscopic findings in intraepidermal carcinoma (IEC) and the clinical diagnostic accuracy of IEC can be challenging. Furthermore, dermoscopic findings in IEC have only rarely been evaluated in fair-skinned populations.Objectives: To measure the interobserver agreement between dermatologists for dermoscopic findings in IEC. Furthermore, to describe the frequency of these findings in a predominantly fair-skinned population. Methods: One hundred dermoscopic images of histopathologically verified IECs were collected. The 11 most common dermoscopic findings described in previous studies were re-defined in a new terminology in a pre-study consensus meeting. Images were assessed by eight experienced international dermoscopists. The frequency of findings and the interobserver agreement was analyzed.Results: Scales (83%), dotted/glomerular vessels (77%), pinkish-white areas (73%) and hemorrhage (46%) were the most commonly present dermoscopic findings. Pigmented structures were found in 32% and shiny white structures (follicular or stromal) in 54% of the IEC. Vascular structures (vessels and/or hemorrhage) could be seen in 89% of the lesions. Overall, the interobserver agreement for the respective dermoscopic findings was poor to moderate, with the highest kappa values noted for scales (0.55) and hemorrhage (0.54) and the lowest for pinkish-white areas (0.015).Conclusion: Our results confirm those of previous studies on dermoscopy in IEC, including the frequency of pigmented structures despite the fair-skinned population. The interobserver agreement was relatively low. The proposed new terminology and our findings can hopefully serve as a guideline for researchers, teachers and students on how to identify IEC.
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| 19. |
- Guenter, Alexander, et al.
(författare)
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Mural Serum Response Factor (SRF) Deficiency Provides Insights into Retinal Vascular Functionality and Development
- 2023
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Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 24:16
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Tidskriftsartikel (refereegranskat)abstract
- Serum response factor (SRF) controls the expression of muscle contraction and motility genes in mural cells (MCs) of the vasculature. In the retina, MC-SRF is important for correct angiogenesis during development and the continuing maintenance of the vascular tone. The purpose of this study was to provide further insights into the effects of MC SRF deficiency on the vasculature and function of the mature retina in SrfiMCKO mice that carry a MC-specific deletion of Srf. Retinal morphology and vascular integrity were analyzed in vivo via scanning laser ophthalmoscopy (SLO), angiography, and optical coherence tomography (OCT). Retinal function was evaluated with full-field electroretinography (ERG). We found that retinal blood vessels of these mutants exhibited different degrees of morphological and functional alterations. With increasing severity, we found vascular bulging, the formation of arteriovenous (AV) anastomoses, and ultimately, a retinal detachment (RD). The associated irregular retinal blood pressure and flow distribution eventually induced hypoxia, indicated by a negative ERG waveform shape. Further, the high frequency of interocular differences in the phenotype of individual SrfiMCKO mice points to a secondary nature of these developments far downstream of the genetic defect and rather dependent on the local retinal context.
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| 20. |
- Hebelka, Hanna, 1977, et al.
(författare)
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Coexistence of Vertebral and Intervertebral Disc Changes in Low Back Pain Patients—In Depth Characterization with Same Day MRI and CT Discography
- 2023
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Ingår i: Diagnostics. - 2075-4418. ; 13:23
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate to what extent annular fissures, vertebral and endplate changes, and Modic changes (MCs), coexist in low back pain (LBP) patients by using multiple imaging modalities. Sixty-two LBP patients (mean age 45 years, range 24–63, 53% men) were examined with same-day CT-discography and MRI. Intervertebral discs punctured for discography (n = 204) were evaluated on MRI [Pfirrmann grade, High-Intensity Zone (HIZ)] and on CT-discograms [Modified Dallas Discogram Score (DDS)]. DDS≥ 1, i.e., disc fissures involving the outer annulus were further digitomized into delimitable fissuring (<50% of annulus affected) or non-delimitable annular fissuring. Using both MRI and CT, adjacent vertebrae and endplates were assessed for MC, vertebral sclerosis, and a modified endplate defect score (EPS). In 194 discs the contrast agent was adequately injected during discography, of which 160 (83%) displayed outer annular fissures, with 91 (47%) of the latter being delimitable fissures. Most discs with delimitable fissures were moderately degenerated; 68% Pfirrmann grade ≤3, 71% EPS ≤ 2, and 12% displayed MC. The majority (76%) of MCs were associated with advanced adjacent disc degeneration; 84% Pfirrmann grade ≥4, 76% with non-delimitable annular fissuring, 59% EPS≥ 4, and 34% EPS of 3. A total 95 HIZ (47%) were found, of which 54 had delimitable fissuring, while the remainder displayed non-delimitable fissuring. Vertebral sclerosis was commonly observed (26%), both with MCs (73%) and without MCs (27%), and not specifically linked to MC type 3. A total of 97% of segments with vertebral sclerosis displayed outer annular fissures. These findings were significant (0.046 > p > 0.0001), except between HIZ and adjacent sclerosis (p = 0.303). To conclude, the present study confirmed a close interplay between the disc and adjacent vertebra and endplates. The fact that a majority of discs with delimitable annular fissures did not coexist with pronounced endplate changes and/or MCs, however, supports the theory that disc fissuring is an early event in the degenerative cascade. This was further supported by the fact that MCs were strongly linked to extensive disc fissuring and to advanced endplate damage. Further, vertebral sclerosis was common also in vertebra without MCs and strongly associated to annular fissuring, indicating that sclerosis is a previously underestimated feature of a general degenerative process.
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| 21. |
- Hebelka, Hanna, 1977, et al.
(författare)
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Loading of the Spine in Low Back Pain Patients Does Not Induce MRI Changes in Modic Lesions: A Prospective Clinical Study
- 2022
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Ingår i: Diagnostics (Basel). - : MDPI AG. - 2075-4418. ; 12:8
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Tidskriftsartikel (refereegranskat)abstract
- Modic changes (MCs) are gaining increased interest as potential generators of low back pain (LBP). The current aim was to investigate possible spinal loading effects on the MRI signal in MCs in patients with LBP. Supine lumbar MRIs were performed and immediately repeated with axial loading in 100 LBP patients. A total of 43 patients (23 male, mean age 45.7 years) had MCs. Each Modic was outlined on all sagittal T2-weighted images (>25% affected vertebrae). For reference, regions of interest were placed in both vertebrae without Modic and in Modic-free tissue in vertebrae with Modic. The Modic signal intensity, normalized to cerebrospinal fluid, and Modic volume were compared between MRIs with and without spinal loading. Of the 94 MCs, 36.2% (n = 34) were type I, 58.5% (n = 55) were type II, and 5.3% (n = 5) were type III. No differences in Modic volume (mean 0.046 cm3; p = 0.25) between the MRIs with and without spinal loading were found. In addition, no significant changes in Modic signal were induced by loading (mean 1.5% difference; p = 0.308). Loading increased the signal in the reference regions of interest in vertebrae both with Modic (mean 5.5%; p = 0.002) and without (mean 3.5%; SD 0.09; p = 0.02). To conclude, MRIs performed with and without spinal loading showed no change in either volume or signal of MCs, suggesting that most MCs are not instantaneously influenced by biomechanical load.
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| 22. |
- Hellmich, Bernhard, et al.
(författare)
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2018 Update of the EULAR recommendations for the management of large vessel vasculitis
- 2020
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 79:1, s. 19-30
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Tidskriftsartikel (refereegranskat)abstract
- Background: Since the publication of the European League Against Rheumatism (EULAR) recommendations for the management of large vessel vasculitis (LVV) in 2009, several relevant randomised clinical trials and cohort analyses have been published, which have the potential to change clinical care and therefore supporting the need to update the original recommendations. Methods: Using EULAR standardised operating procedures for EULAR-endorsed recommendations, the EULAR task force undertook a systematic literature review and sought opinion from 20 experts from 13 countries. We modified existing recommendations and created new recommendations. Results: Three overarching principles and 10 recommendations were formulated. We recommend that a suspected diagnosis of LVV should be confirmed by imaging or histology. High dose glucocorticoid therapy (40-60 mg/day prednisone-equivalent) should be initiated immediately for induction of remission in active giant cell arteritis (GCA) or Takayasu arteritis (TAK). We recommend adjunctive therapy in selected patients with GCA (refractory or relapsing disease, presence of an increased risk for glucocorticoid-related adverse events or complications) using tocilizumab. Methotrexate may be used as an alternative. Non-biological glucocorticoid-sparing agents should be given in combination with glucocorticoids in all patients with TAK and biological agents may be used in refractory or relapsing patients. We no longer recommend the routine use of antiplatelet or anticoagulant therapy for treatment of LVV unless it is indicated for other reasons. Conclusions: We have updated the recommendations for the management of LVV to facilitate the translation of current scientific evidence and expert opinion into better management and improved outcome of patients in clinical practice.
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| 23. |
- Iyadurai, Lalitha, et al.
(författare)
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Reducing intrusive memories after trauma via an imagery-competing task intervention in COVID-19 intensive care staff : a randomised controlled trial
- 2023
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Ingår i: Translational Psychiatry. - : Springer Nature. - 2158-3188. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Intrusive memories (IMs) after traumatic events can be distressing and disrupt mental health and functioning. We evaluated the impact of a brief remotely-delivered digital imagery-competing task intervention on the number of IMs for intensive care unit (ICU) staff who faced repeated trauma exposure during the COVID-19 pandemic using a two-arm, parallel-group, single-blind randomised controlled trial, with the comparator arm receiving delayed access to active treatment (crossover). Eligible participants worked clinically in a UK NHS ICU during the pandemic and had at least 3 IMs of work-related traumatic events in the week before recruitment. Participants were randomly assigned (1:1) to immediate (weeks 1-4) or delayed (weeks 5-8) intervention access. Sequential Bayesian analyses to optimise the intervention and increase trial efficiency are reported elsewhere [1]. The primary endpoint for the pre-specified frequentist analysis of the final study population compared the number of IMs experienced in week 4 between the immediate and delayed access arms. Secondary outcomes included clinical symptoms, work functioning and wellbeing. Safety was assessed throughout the trial by scheduled questions and free report. All analyses were undertaken on an intention-to-treat basis (86 randomised participants). There were significantly fewer intrusive memories during week 4 in the immediate (median = 1, IQR = 0-3, n = 43), compared to the comparator delayed arm (median = 10, IQR = 6-17, n = 43), IRR 0.31, 95% CI: 0.20-0.48, p < 0.001. After crossover, the delayed arm also showed a significant reduction in IMs at week 8 compared to week 4. There were convergent findings for symptoms of PTSD, insomnia and anxiety, work engagement and burnout, general functioning and quality of life. The intervention was found safe and acceptable to participants. All adverse events were unrelated to the study. Our study provides the first evidence of a benefit on reducing IMs, improving other clinical symptoms, work functioning and wellbeing, as well as safety of a brief remotely-delivered digital imagery-competing task intervention. An efficacy trial with an active control and longer follow-up is warranted. The trial is registered at ClinicalTrials.gov (NCT04992390).
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| 24. |
- Jones, Alfred J. H., et al.
(författare)
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Visualizing band structure hybridization and superlattice effects in twisted MoS2/WS2 heterobilayers
- 2022
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Ingår i: Current Opinion in Chemical Engineering. - : IOP Publishing Ltd. - 2211-3398. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- A mismatch of atomic registries between single-layer transition metal dichalcogenides (TMDs) in a two-dimensional (2D) van der Waals heterostructure produces a moire superlattice with a periodic potential, which can be fine-tuned by introducing a twist angle between the materials. This approach is promising both for controlling the interactions between the TMDs and for engineering their electronic band structures, yet direct observation of the changes to the electronic structure introduced with varying twist angle has so far been missing. Here, we probe heterobilayers comprised of single-layer MoS2 and WS2 with twist angles ranging from 2 degrees to 20 degrees and determine the twist angle-dependent evolution of the electronic band structure using micro-focused angle-resolved photoemission spectroscopy. We find strong interlayer hybridization between MoS2 and WS2 electronic states at the (Gamma) over bar -point of the Brillouin zone, leading to a shift of the valence band maximum in the heterostructure. Replicas of the hybridized states are observed at the center of twist angle-dependent moire mini Brillouin zones. We confirm that these replica features arise from the inherent moire potential by comparing our experimental observations with density functional theory calculations of the superlattice dispersion. Our direct visualization of these features underscores the potential of using twisted heterobilayer semiconductors to engineer hybrid electronic states and superlattices that alter the electronic and optical properties of 2D heterostructures for a wide range of twist angles.
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| 25. |
- Kirkeby, Carsten, et al.
(författare)
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Advances in automatic identification of flying insects using optical sensors and machine learning
- 2021
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Worldwide, farmers use insecticides to prevent crop damage caused by insect pests, while they also rely on insect pollinators to enhance crop yield and other insect as natural enemies of pests. In order to target pesticides to pests only, farmers must know exactly where and when pests and beneficial insects are present in the field. A promising solution to this problem could be optical sensors combined with machine learning. We obtained around 10,000 records of flying insects found in oilseed rape (Brassica napus) crops, using an optical remote sensor and evaluated three different classification methods for the obtained signals, reaching over 80% accuracy. We demonstrate that it is possible to classify insects in flight, making it possible to optimize the application of insecticides in space and time. This will enable a technological leap in precision agriculture, where focus on prudent and environmentally-sensitive use of pesticides is a top priority.
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| 26. |
- Liu, Ilon, et al.
(författare)
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The landscape of tumor cell states and spatial organization in H3-K27M mutant diffuse midline glioma across age and location
- 2022
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 54:12, s. 1881-1894
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Tidskriftsartikel (refereegranskat)abstract
- Histone 3 lysine27-to-methionine (H3-K27M) mutations most frequently occur in diffuse midline gliomas (DMGs) of the childhood pons but are also increasingly recognized in adults. Their potential heterogeneity at different ages and midline locations is vastly understudied. Here, through dissecting the single-cell transcriptomic, epigenomic and spatial architectures of a comprehensive cohort of patient H3-K27M DMGs, we delineate how age and anatomical location shape glioma cell-intrinsic and -extrinsic features in light of the shared driver mutation. We show that stem-like oligodendroglial precursor-like cells, present across all clinico-anatomical groups, display varying levels of maturation dependent on location. We reveal a previously underappreciated relationship between mesenchymal cancer cell states and age, linked to age-dependent differences in the immune microenvironment. Further, we resolve the spatial organization of H3-K27M DMG cell populations and identify a mitotic oligodendroglial-lineage niche. Collectively, our study provides a powerful framework for rational modeling and therapeutic interventions.
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| 27. |
- Miller, Timothy, et al.
(författare)
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Phase 1-2 Trial of Antisense Oligonucleotide Tofersen for SOD1 ALS
- 2020
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Ingår i: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 383:2, s. 109-119
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Tidskriftsartikel (refereegranskat)abstract
- Background: Tofersen is an antisense oligonucleotide that mediates the degradation of superoxide dismutase 1 (SOD1) messenger RNA to reduce SOD1 protein synthesis. Intrathecal administration of tofersen is being studied for the treatment of amyotrophic lateral sclerosis (ALS) due to SOD1 mutations.Methods: We conducted a phase 1-2 ascending-dose trial evaluating tofersen in adults with ALS due to SOD1 mutations. In each dose cohort (20, 40, 60, or 100 mg), participants were randomly assigned in a 3:1 ratio to receive five doses of tofersen or placebo, administered intrathecally for 12 weeks. The primary outcomes were safety and pharmacokinetics. The secondary outcome was the change from baseline in the cerebrospinal fluid (CSF) SOD1 concentration at day 85. Clinical function and vital capacity were measured.Results: A total of 50 participants underwent randomization and were included in the analyses; 48 participants received all five planned doses. Lumbar puncture-related adverse events were observed in most participants. Elevations in CSF white-cell count and protein were reported as adverse events in 4 and 5 participants, respectively, who received tofersen. Among participants who received tofersen, one died from pulmonary embolus on day 137, and one from respiratory failure on day 152; one participant in the placebo group died from respiratory failure on day 52. The difference at day 85 in the change from baseline in the CSF SOD1 concentration between the tofersen groups and the placebo group was 2 percentage points (95% confidence interval [CI], -18 to 27) for the 20-mg dose, -25 percentage points (95% CI, -40 to -5) for the 40-mg dose, -19 percentage points (95% CI, -35 to 2) for the 60-mg dose, and -33 percentage points (95% CI, -47 to -16) for the 100-mg dose.Conclusions: In adults with ALS due to SOD1 mutations, CSF SOD1 concentrations decreased at the highest concentration of tofersen administered intrathecally over a period of 12 weeks. CSF pleocytosis occurred in some participants receiving tofersen. Lumbar puncture-related adverse events were observed in most participants. (Funded by Biogen; ClinicalTrials.gov number, NCT02623699; EudraCT number, 2015-004098-33.)In a phase 1-2 dose-escalation trial involving adults with ALS due to SOD1 mutations who received intrathecal tofersen (an antisense oligonucleotide) or placebo, the levels of mutant SOD1 in the CSF were 33 percentage points lower in the highest-dose tofersen group than in the placebo group.
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| 28. |
- Nielsen, Wils, et al.
(författare)
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OMERACT 2023 Systemic Lupus Erythematosus Special Interest Group : Winnowing and Binning Preliminary Candidate Domains for the Core Outcome Set
- 2024
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Ingår i: Seminars in Arthritis & Rheumatism. - : Elsevier. - 0049-0172 .- 1532-866X. ; 65
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The Outcome Measures in Rheumatology (OMERACT) Systemic Lupus Erythematosus (SLE) Working Group held a Special Interest Group (SIG) at the OMERACT 2023 conference in Colorado Springs where SLE collaborators reviewed domain sub-themes generated through qualitative research and literature review.OBJECTIVE: The objective of the SIG and the subsequent meetings of the SLE Working Group was to begin the winnowing and binning of candidate domain sub-themes into a preliminary list of candidate domains that will proceed to the consensus Delphi exercise for the SLE COS.METHODS: Four breakout groups at the SLE SIG in Colorado Springs winnowed and binned 132 domain sub-themes into candidate domains, which was continued with a series of virtual meetings by an advisory group of SLE patient research partners (PRPs), members of the OMERACT SLE Working Group Steering Committee, and other collaborators.RESULTS: The 132 domain sub-themes were reduced to a preliminary list of 20 candidate domains based on their clinical and research relevance for clinical trials and research studies.CONCLUSION: A meaningful and substantial winnowing and binning of candidate domains for the SLE COS was achieved resulting in a preliminary list of 20 candidate domains.
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| 29. |
- Orlich, Michael M., et al.
(författare)
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Mural Cell SRF Controls Pericyte Migration, Vessel Patterning and Blood Flow
- 2022
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Ingår i: Circulation Research. - : LIPPINCOTT WILLIAMS & WILKINS. - 0009-7330 .- 1524-4571. ; 131:4, s. 308-327
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Tidskriftsartikel (refereegranskat)abstract
- Background: Pericytes and vascular smooth muscle cells, collectively known as mural cells, are recruited through PDGFB (platelet-derived growth factor B)-PDGFRB (platelet-derived growth factor receptor beta) signaling. MCs are essential for vascular integrity, and their loss has been associated with numerous diseases. Most of this knowledge is based on studies in which MCs are insufficiently recruited or fully absent upon inducible ablation. In contrast, little is known about the physiological consequences that result from impairment of specific MC functions. Here, we characterize the role of the transcription factor SRF (serum response factor) in MCs and study its function in developmental and pathological contexts.Methods: We generated a mouse model of MC-specific inducible Srf gene deletion and studied its consequences during retinal angiogenesis using RNA-sequencing, immunohistology, in vivo live imaging, and in vitro techniques.Results: By postnatal day 6, pericytes lacking SRF were morphologically abnormal and failed to properly comigrate with angiogenic sprouts. As a consequence, pericyte-deficient vessels at the retinal sprouting front became dilated and leaky. By postnatal day 12, also the vascular smooth muscle cells had lost SRF, which coincided with the formation of pathological arteriovenous shunts. Mechanistically, we show that PDGFB-dependent SRF activation is mediated via MRTF (myocardin-related transcription factor) cofactors. We further show that MRTF-SRF signaling promotes pathological pericyte activation during ischemic retinopathy. RNA-sequencing, immunohistology, in vivo live imaging, and in vitro experiments demonstrated that SRF regulates expression of contractile SMC proteins essential to maintain the vascular tone.Conclusions: SRF is crucial for distinct functions in pericytes and vascular smooth muscle cells. SRF directs pericyte migration downstream of PDGFRB signaling and mediates pathological pericyte activation during ischemic retinopathy. In vascular smooth muscle cells, SRF is essential for expression of the contractile machinery, and its deletion triggers formation of arteriovenous shunts. These essential roles in physiological and pathological contexts provide a rationale for novel therapeutic approaches through targeting SRF activity in MCs.
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| 30. |
- Pfaff, Sebastian, et al.
(författare)
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Operando Reflectance Microscopy on Polycrystalline Surfaces in Thermal Catalysis, Electrocatalysis, and Corrosion
- 2021
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Ingår i: ACS applied materials & interfaces. - : American Chemical Society (ACS). - 1944-8244 .- 1944-8252. ; 13:16, s. 19530-19540
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Tidskriftsartikel (refereegranskat)abstract
- We have developed a microscope with a spatial resolution of 5 μm, which can be used to image the two-dimensional surface optical reflectance (2D-SOR) of polycrystalline samples in operando conditions. Within the field of surface science, operando tools that give information about the surface structure or chemistry of a sample under realistic experimental conditions have proven to be very valuable to understand the intrinsic reaction mechanisms in thermal catalysis, electrocatalysis, and corrosion science. To study heterogeneous surfaces in situ, the experimental technique must both have spatial resolution and be able to probe through gas or electrolyte. Traditional electron-based surface science techniques are difficult to use under high gas pressure conditions or in an electrolyte due to the short mean free path of electrons. Since it uses visible light, SOR can easily be used under high gas pressure conditions and in the presence of an electrolyte. In this work, we use SOR in combination with a light microscope to gain information about the surface under realistic experimental conditions. We demonstrate this by studying the different grains of three polycrystalline samples: Pd during CO oxidation, Au in electrocatalysis, and duplex stainless steel in corrosion. Optical light-based techniques such as SOR could prove to be a good alternative or addition to more complicated techniques in improving our understanding of complex polycrystalline surfaces with operando measurements.
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| 31. |
- Puglisi, A., et al.
(författare)
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KURVS: the outer rotation curve shapes and dark matter fractions of z ∼1.5 star-forming galaxies
- 2023
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Ingår i: Monthly Notices of the Royal Astronomical Society. - 0035-8711 .- 1365-2966. ; 524:2, s. 2814-2835
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Tidskriftsartikel (refereegranskat)abstract
- We present first results from the KMOS Ultra-deep Rotation Velocity Survey (KURVS), aimed at studying the outer rotation curves shape and dark matter content of 22 star-forming galaxies at z ∼1.5. These galaxies represent 'typical' star-forming discs at z ∼1.5, being located within the star-forming main sequence and stellar mass-size relation with stellar masses 9.5 ≤ log(M*/M⊙) ≤ 11.5. We use the spatially resolved H α emission to extract individual rotation curves out to 4 times the effective radius, on average, or ∼10-15 kpc. Most rotation curves are flat or rising between three and six disc scale radii. Only three objects with dispersion-dominated dynamics (vrot/σ0 ∼0.2) have declining outer rotation curves at more than 5σ significance. After accounting for seeing and pressure support, the nine rotation-dominated discs with vrot/σ0 ≥ 1.5 have average dark matter fractions of at the effective radius, similar to local discs. Together with previous observations of star-forming galaxies at cosmic noon, our measurements suggest a trend of declining dark matter fraction with increasing stellar mass and stellar mass surface density at the effective radius. Measurements of simulated EAGLE galaxies are in quantitative agreement with observations up to log, and overpredict the dark matter fraction of galaxies with higher mass surface densities by a factor of ∼3. We conclude that the dynamics of typical rotationally-supported discs at z ∼1.5 is dominated by dark matter from effective radius scales, in broad agreement with cosmological models. The tension with observations at high stellar mass surface density suggests that the prescriptions for baryonic processes occurring in the most massive galaxies (such as bulge growth and quenching) need to be reassessed.
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| 32. |
- Silva, José P.B., et al.
(författare)
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Roadmap on ferroelectric hafnia- and zirconia-based materials and devices
- 2023
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Ingår i: APL Materials. - 2166-532X. ; 11:8
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Tidskriftsartikel (refereegranskat)abstract
- Ferroelectric hafnium and zirconium oxides have undergone rapid scientific development over the last decade, pushing them to the forefront of ultralow-power electronic systems. Maximizing the potential application in memory devices or supercapacitors of these materials requires a combined effort by the scientific community to address technical limitations, which still hinder their application. Besides their favorable intrinsic material properties, HfO2-ZrO2 materials face challenges regarding their endurance, retention, wake-up effect, and high switching voltages. In this Roadmap, we intend to combine the expertise of chemistry, physics, material, and device engineers from leading experts in the ferroelectrics research community to set the direction of travel for these binary ferroelectric oxides. Here, we present a comprehensive overview of the current state of the art and offer readers an informed perspective of where this field is heading, what challenges need to be addressed, and possible applications and prospects for further development.
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| 33. |
- Stockwell, Jason D., et al.
(författare)
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Storm impacts on phytoplankton community dynamics in lakes
- 2020
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Ingår i: Global Change Biology. - : WILEY. - 1354-1013 .- 1365-2486. ; 26:5, s. 2756-2784
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Forskningsöversikt (refereegranskat)abstract
- In many regions across the globe, extreme weather events such as storms have increased in frequency, intensity, and duration due to climate change. Ecological theory predicts that such extreme events should have large impacts on ecosystem structure and function. High winds and precipitation associated with storms can affect lakes via short-term runoff events from watersheds and physical mixing of the water column. In addition, lakes connected to rivers and streams will also experience flushing due to high flow rates. Although we have a well-developed understanding of how wind and precipitation events can alter lake physical processes and some aspects of biogeochemical cycling, our mechanistic understanding of the emergent responses of phytoplankton communities is poor. Here we provide a comprehensive synthesis that identifies how storms interact with lake and watershed attributes and their antecedent conditions to generate changes in lake physical and chemical environments. Such changes can restructure phytoplankton communities and their dynamics, as well as result in altered ecological function (e.g., carbon, nutrient and energy cycling) in the short- and long-term. We summarize the current understanding of storm-induced phytoplankton dynamics, identify knowledge gaps with a systematic review of the literature, and suggest future research directions across a gradient of lake types and environmental conditions.
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| 34. |
- Yáñez-Vilches, Aurora, et al.
(författare)
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Physical interactions between specifically regulated subpopulations of the MCM and RNR complexes prevent genetic instability
- 2024
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Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 20:5
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Tidskriftsartikel (refereegranskat)abstract
- The helicase MCM and the ribonucleotide reductase RNR are the complexes that provide the substrates (ssDNA templates and dNTPs, respectively) for DNA replication. Here, we demonstrate that MCM interacts physically with RNR and some of its regulators, including the kinase Dun1. These physical interactions encompass small subpopulations of MCM and RNR, are independent of the major subcellular locations of these two complexes, augment in response to DNA damage and, in the case of the Rnr2 and Rnr4 subunits of RNR, depend on Dun1. Partial disruption of the MCM/RNR interactions impairs the release of Rad52 -but not RPA-from the DNA repair centers despite the lesions are repaired, a phenotype that is associated with hypermutagenesis but not with alterations in the levels of dNTPs. These results suggest that a specifically regulated pool of MCM and RNR complexes plays non-canonical roles in genetic stability preventing persistent Rad52 centers and hypermutagenesis.
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| 35. |
- Zimmermann, Alfred, et al.
(författare)
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Conceptualizing Artificial Intelligence-Based Service Ecosystems
- 2021
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Ingår i: Advances in the Human Side of Service Engineering - Proceedings of the AHFE 2021 Virtual Conference on The Human Side of Service Engineering, July 25-29, 2021, USA. - Cham : Springer. - 9783030808396 - 9783030808402 ; , s. 377-384
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Konferensbidrag (refereegranskat)abstract
- Platforms and their surrounding ecosystems are becoming increasingly important components of many companies' strategies. Artificial Intelligence, in particular, has created new opportunities to create and develop ecosystems around the platform. However, there is not yet a methodology to systematically develop these new opportunities for enterprise development strategy. Therefore, this paper aims to lay a foundation for the conceptualization of Artificial Intelligence-based service ecosystems exploiting a Service-Dominant Logic. The basis for conceptualization is the study of value creation and particularly effective network effects. This research investigates the fundamental idea of extending specific digital concepts considering the influence of Artificial Intelligence on the design of intelligent services, along with their architecture of digital platforms and ecosystems, to enable a smooth evolutionary path and adaptability for human-centric collaborative systems and services. The paper explores an extended digital enterprise conceptual model through a combined, iterative, and permanent task of co-creating value between humans and intelligent systems as part of a new idea of cognitively adapted intelligent services.
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