| 1. |
- Thomas, HS, et al.
(författare)
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- 2019
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swepub:Mat__t
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| 2. |
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| 3. |
- Thoma, B, et al.
(författare)
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An international, interprofessional investigation of the self-reported podcast listening habits of emergency clinicians: A METRIQ Study
- 2020
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Ingår i: CJEM. - : Springer Science and Business Media LLC. - 1481-8043 .- 1481-8035. ; 22:1, s. 112-117
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesPodcasts are increasingly being used for medical education. A deeper understanding of usage patterns would inform both producers and researchers of medical podcasts. We aimed to determine how and why podcasts are used by emergency medicine and critical care clinicians.MethodsAn international interprofessional sample (medical students, residents, physicians, nurses, physician assistants, and paramedics) was recruited through direct contact and a multimodal social media (Twitter and Facebook) campaign. Each participant completed a survey outlining how and why they utilize medical podcasts. Recruitment materials included an infographic and study website.Results390 participants from 33 countries and 4 professions (medicine, nursing, paramedicine, physician assistant) completed the survey. Participants most frequently listened to medical podcasts to review new literature (75.8%), learn core material (75.1%), and refresh memory (71.8%). The majority (62.6%) were aware of the ability to listen at increased speeds, but most (76.9%) listened at 1.0 x (normal) speed. All but 25 (6.4%) participants concurrently performed other tasks while listening. Driving (72.3%), exercising (39.7%), and completing chores (39.2%) were the most common. A minority of participants used active learning techniques such as pausing, rewinding, and replaying segments of the podcast. Very few listened to podcasts multiple times.ConclusionsAn international cohort of emergency clinicians use medical podcasts predominantly for learning. Their listening habits (rarely employing active learning strategies and frequently performing concurrent tasks) may not support this goal. Further exploration of the impact of these activities on learning from podcasts is warranted.
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| 12. |
- Zeiser, R., et al.
(författare)
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Ruxolitinib in corticosteroid-refractory graft-versus-host disease after allogeneic stem cell transplantation: a multicenter survey
- 2015
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 29:10, s. 2062-2068
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Tidskriftsartikel (refereegranskat)abstract
- Despite major improvements in allogeneic hematopoietic cell transplantation over the past decades, corticosteroid-refractory (SR) acute (a) and chronic (c) graft-versus-host disease (GVHD) cause high mortality. Preclinical evidence indicates the potent anti-inflammatory properties of the JAK1/2 inhibitor ruxolitinib. In this retrospective survey, 19 stem cell transplant centers in Europe and the United States reported outcome data from 95 patients who had received ruxolitinib as salvage therapy for SR-GVHD. Patients were classified as having SR-aGVHD (n = 54, all grades III or IV) or SR-cGVHD (n = 41, all moderate or severe). The median number of previous GVHD-therapies was 3 for both SR-aGVHD (1-7) and SR-cGVHD (1-10). The overall response rate was 81.5% (44/54) in SR-aGVHD including 25 complete responses (46.3%), while for SR-cGVHD the ORR was 85.4% (35/41). Of those patients responding to ruxolitinib, the rate of GVHD-relapse was 6.8% (3/44) and 5.7% (2/35) for SR-aGVHD and SR-cGVHD, respectively. The 6-month-survival was 79% (67.3-90.7%, 95% confidence interval (CI)) and 97.4% (92.3-100%, 95% CI) for SR-aGVHD and SR-cGVHD, respectively. Cytopenia and cytomegalovirus-reactivation were observed during ruxolitinib treatment in both SR-aGVHD (30/54, 55.6% and 18/54, 33.3%) and SR-cGVHD (7/41, 17.1% and 6/41, 14.6%) patients. Ruxolitinib may constitute a promising new treatment option for SR-aGVHD and SR-cGVHD that should be validated in a prospective trial.
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| 13. |
- Mattsson, Niklas, et al.
(författare)
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Prevalence of the apolipoprotein E epsilon 4 allele in amyloid beta positive subjects across the spectrum of Alzheimers disease
- 2018
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Ingår i: Alzheimer's & Dementia. - : ELSEVIER SCIENCE INC. - 1552-5260 .- 1552-5279. ; 14:7, s. 913-924
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Apolipoprotein E (APOE) epsilon 4 is the major genetic risk factor for Alzheimers disease (AD), but its prevalence is unclear because earlier studies did not require biomarker evidence of amyloid beta(A beta) pathology. Methods: We included 3451 A beta+ subjects (853 AD-type dementia, 1810 mild cognitive impairment, and 788 cognitively normal). Generalized estimating equation models were used to assess APOE epsilon 4 prevalence in relation to age, sex, education, and geographical location. Results: The APOE epsilon 4 prevalence was 66% in AD-type dementia, 64% in mild cognitive impairment, and 51% in cognitively normal, and it decreased with advancing age in A beta+ cognitively normal and A beta+ mild cognitive impairment (P amp;lt;.05) but not in A beta+ AD dementia (P =.66). The prevalence was highest in Northern Europe but did not vary by sex or education. Discussion: The APOE E4 prevalence in AD was higher than that in previous studies, which did not require presence of A beta pathology. Furthermore, our results highlight disease heterogeneity related to age and geographical location. (C) 2018 the Alzheimers Association. Published by Elsevier Inc. All rights reserved.
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| 14. |
- Mattsson, Niklas, et al.
(författare)
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Prevalence of the apolipoprotein E ε4 allele in amyloid β positive subjects across the spectrum of Alzheimer's disease
- 2018
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Ingår i: Alzheimer's and Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 14:7, s. 913-924
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Apolipoprotein E (APOE) ε4 is the major genetic risk factor for Alzheimer's disease (AD), but its prevalence is unclear because earlier studies did not require biomarker evidence of amyloid β (Aβ) pathology. Methods: We included 3451 Aβ+ subjects (853 AD-type dementia, 1810 mild cognitive impairment, and 788 cognitively normal). Generalized estimating equation models were used to assess APOE ε4 prevalence in relation to age, sex, education, and geographical location. Results: The APOE ε4 prevalence was 66% in AD-type dementia, 64% in mild cognitive impairment, and 51% in cognitively normal, and it decreased with advancing age in Aβ+ cognitively normal and Aβ+ mild cognitive impairment (P <.05) but not in Aβ+ AD dementia (P =.66). The prevalence was highest in Northern Europe but did not vary by sex or education. Discussion: The APOE ε4 prevalence in AD was higher than that in previous studies, which did not require presence of Aβ pathology. Furthermore, our results highlight disease heterogeneity related to age and geographical location.
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| 15. |
- Jansen, Willemijn J, et al.
(författare)
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Association of Cerebral Amyloid-β Aggregation With Cognitive Functioning in Persons Without Dementia.
- 2018
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Ingår i: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 75:1, s. 84-95
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Tidskriftsartikel (refereegranskat)abstract
- Cerebral amyloid-β aggregation is an early event in Alzheimer disease (AD). Understanding the association between amyloid aggregation and cognitive manifestation in persons without dementia is important for a better understanding of the course of AD and for the design of prevention trials.To investigate whether amyloid-β aggregation is associated with cognitive functioning in persons without dementia.This cross-sectional study included 2908 participants with normal cognition and 4133 with mild cognitive impairment (MCI) from 53 studies in the multicenter Amyloid Biomarker Study. Normal cognition was defined as having no cognitive concerns for which medical help was sought and scores within the normal range on cognitive tests. Mild cognitive impairment was diagnosed according to published criteria. Study inclusion began in 2013 and is ongoing. Data analysis was performed in January 2017.Global cognitive performance as assessed by the Mini-Mental State Examination (MMSE) and episodic memory performance as assessed by a verbal word learning test. Amyloid aggregation was measured with positron emission tomography or cerebrospinal fluid biomarkers and dichotomized as negative (normal) or positive (abnormal) according to study-specific cutoffs. Generalized estimating equations were used to examine the association between amyloid aggregation and low cognitive scores (MMSE score ≤27 or memory z score≤-1.28) and to assess whether this association was moderated by age, sex, educational level, or apolipoprotein E genotype.Among 2908 persons with normal cognition (mean [SD] age, 67.4 [12.8] years), amyloid positivity was associated with low memory scores after age 70 years (mean difference in amyloid positive vs negative, 4% [95% CI, 0%-7%] at 72 years and 21% [95% CI, 10%-33%] at 90 years) but was not associated with low MMSE scores (mean difference, 3% [95% CI, -1% to 6%], P=.16). Among 4133 patients with MCI (mean [SD] age, 70.2 [8.5] years), amyloid positivity was associated with low memory (mean difference, 16% [95% CI, 12%-20%], P<.001) and low MMSE (mean difference, 14% [95% CI, 12%-17%], P<.001) scores, and this association decreased with age. Low cognitive scores had limited utility for screening of amyloid positivity in persons with normal cognition and those with MCI. In persons with normal cognition, the age-related increase in low memory score paralleled the age-related increase in amyloid positivity with an intervening period of 10 to 15 years.Although low memory scores are an early marker of amyloid positivity, their value as a screening measure for early AD among persons without dementia is limited.
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| 16. |
- Jansen, Willemijn J, et al.
(författare)
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Prevalence Estimates of Amyloid Abnormality Across the Alzheimer Disease Clinical Spectrum.
- 2022
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Ingår i: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 79:3, s. 228-243
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Tidskriftsartikel (refereegranskat)abstract
- One characteristic histopathological event in Alzheimer disease (AD) is cerebral amyloid aggregation, which can be detected by biomarkers in cerebrospinal fluid (CSF) and on positron emission tomography (PET) scans. Prevalence estimates of amyloid pathology are important for health care planning and clinical trial design.To estimate the prevalence of amyloid abnormality in persons with normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia and to examine the potential implications of cutoff methods, biomarker modality (CSF or PET), age, sex, APOE genotype, educational level, geographical region, and dementia severity for these estimates.This cross-sectional, individual-participant pooled study included participants from 85 Amyloid Biomarker Study cohorts. Data collection was performed from January 1, 2013, to December 31, 2020. Participants had normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia. Normal cognition and subjective cognitive decline were defined by normal scores on cognitive tests, with the presence of cognitive complaints defining subjective cognitive decline. Mild cognitive impairment and clinical AD dementia were diagnosed according to published criteria.Alzheimer disease biomarkers detected on PET or in CSF.Amyloid measurements were dichotomized as normal or abnormal using cohort-provided cutoffs for CSF or PET or by visual reading for PET. Adjusted data-driven cutoffs for abnormal amyloid were calculated using gaussian mixture modeling. Prevalence of amyloid abnormality was estimated according to age, sex, cognitive status, biomarker modality, APOE carrier status, educational level, geographical location, and dementia severity using generalized estimating equations.Among the 19097 participants (mean [SD] age, 69.1 [9.8] years; 10148 women [53.1%]) included, 10139 (53.1%) underwent an amyloid PET scan and 8958 (46.9%) had an amyloid CSF measurement. Using cohort-provided cutoffs, amyloid abnormality prevalences were similar to 2015 estimates for individuals without dementia and were similar across PET- and CSF-based estimates (24%; 95% CI, 21%-28%) in participants with normal cognition, 27% (95% CI, 21%-33%) in participants with subjective cognitive decline, and 51% (95% CI, 46%-56%) in participants with mild cognitive impairment, whereas for clinical AD dementia the estimates were higher for PET than CSF (87% vs 79%; mean difference, 8%; 95% CI, 0%-16%; P=.04). Gaussian mixture modeling-based cutoffs for amyloid measures on PET scans were similar to cohort-provided cutoffs and were not adjusted. Adjusted CSF cutoffs resulted in a 10% higher amyloid abnormality prevalence than PET-based estimates in persons with normal cognition (mean difference, 9%; 95% CI, 3%-15%; P=.004), subjective cognitive decline (9%; 95% CI, 3%-15%; P=.005), and mild cognitive impairment (10%; 95% CI, 3%-17%; P=.004), whereas the estimates were comparable in persons with clinical AD dementia (mean difference, 4%; 95% CI, -2% to 9%; P=.18).This study found that CSF-based estimates using adjusted data-driven cutoffs were up to 10% higher than PET-based estimates in people without dementia, whereas the results were similar among people with dementia. This finding suggests that preclinical and prodromal AD may be more prevalent than previously estimated, which has important implications for clinical trial recruitment strategies and health care planning policies.
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| 17. |
- Jansen, Willemijn J, et al.
(författare)
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Prevalence of cerebral amyloid pathology in persons without dementia: a meta-analysis.
- 2015
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Ingår i: JAMA. - : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 313:19, s. 1924-38
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Tidskriftsartikel (refereegranskat)abstract
- Cerebral amyloid-β aggregation is an early pathological event in Alzheimer disease (AD), starting decades before dementia onset. Estimates of the prevalence of amyloid pathology in persons without dementia are needed to understand the development of AD and to design prevention studies.
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| 18. |
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| 19. |
- Fransen, M. F., et al.
(författare)
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A Restricted Role for FcgammaR in the Regulation of Adaptive Immunity
- 2018
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Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 200:8, s. 2615-2626
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Tidskriftsartikel (refereegranskat)abstract
- By their interaction with IgG immune complexes, FcgammaR and complement link innate and adaptive immunity, showing functional redundancy. In complement-deficient mice, IgG downstream effector functions are often impaired, as well as adaptive immunity. Based on a variety of model systems using FcgammaR-knockout mice, it has been concluded that FcgammaRs are also key regulators of innate and adaptive immunity; however, several of the model systems underpinning these conclusions suffer from flawed experimental design. To address this issue, we generated a novel mouse model deficient for all FcgammaRs (FcgammaRI/II/III/IV(-/-) mice). These mice displayed normal development and lymphoid and myeloid ontogeny. Although IgG effector pathways were impaired, adaptive immune responses to a variety of challenges, including bacterial infection and IgG immune complexes, were not. Like FcgammaRIIb-deficient mice, FcgammaRI/II/III/IV(-/-) mice developed higher Ab titers but no autoantibodies. These observations indicate a redundant role for activating FcgammaRs in the modulation of the adaptive immune response in vivo. We conclude that FcgammaRs are downstream IgG effector molecules with a restricted role in the ontogeny and maintenance of the immune system, as well as the regulation of adaptive immunity.
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| 20. |
- Kruse, N., et al.
(författare)
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Validation of a quantitative cerebrospinal fluid alpha-synuclein assay in a European-wide interlaboratory study
- 2015
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580. ; 36:9, s. 2587-2596
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Tidskriftsartikel (refereegranskat)abstract
- Decreased levels of alpha-synuclein (aSyn) in cerebrospinal fluid (CSF) in Parkinson's disease and related synucleinopathies have been reported, however, not consistently in all cross-sectional studies. To test the performance of one recently released human-specific enzyme-linked immunosorbent assay (ELISA) for the quantification of aSyn in CSF, we carried out a round robin trial with 18 participating laboratories trained in CSF ELISA analyses within the BIOMARKAPD project in the EU Joint Program -Neurodegenerative Disease Research. CSF samples (homogeneous aliquots from pools) and ELISA kits (one lot) were provided centrally and data reported back to one laboratory for data analysis. Our study showed that although factors such as preanalytical sample handling and lot-to-lot variability were minimized by our study design, we identified high variation in absolute values of CSF aSyn even when the same samples and same lots of assays were applied. We further demonstrate that although absolute concentrations differ between laboratories the quantitative results are comparable. With further standardization this assay may become an attractive tool for comparing aSyn measurements in diverse settings. Recommendations for further validation experiments and improvement of the interlaboratory results obtained are given. (C) 2015 Elsevier Inc. All rights reserved.
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| 21. |
- van Doorn, Ljcv, et al.
(författare)
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Improved Cerebrospinal Fluid-Based Discrimination between Alzheimer's Disease Patients and Controls after Correction for Ventricular Volumes
- 2017
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Ingår i: Journal of Alzheimers Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 56:2, s. 543-555
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Tidskriftsartikel (refereegranskat)abstract
- Cerebrospinal fluid (CSF) biomarkers may support the diagnosis of Alzheimer's disease (AD). We studied if the diagnostic power of AD CSF biomarker concentrations, i.e., A beta(42), total tau (t-tau), and phosphorylated tau (p-tau), is affected by differences in lateral ventricular volume (VV), using CSF biomarker data and magnetic resonance imaging (MRI) scans of 730 subjects, from 13 European Memory Clinics. We developed a Matlab-algorithm for standardized automated segmentation analysis of T1 weighted MRI scans in SPM8 for determining VV, and computed its ratio with total intracranial volume (TIV) as proxy for total CSF volume. The diagnostic power of CSF biomarkers (and their combination), either corrected for VV/TIV ratio or not, was determined by ROC analysis. CSF A beta(42) levels inversely correlated to VV/TIV in the whole study population (A beta(42): r = -0.28; p < 0.0001). For CSF t-tau and p-tau, this association only reached statistical significance in the combined MCI and AD group (t-tau: r = -0.15; p-tau: r = -0.13; both p < 0.01). Correction for differences in VV/TIV improved the differentiation of AD versus controls based on CSF A beta(42) alone (AUC: 0.75 versus 0.81) or in combination with t-tau (AUC: 0.81 versus 0.91). In conclusion, differences in VV may be an important confounder in interpreting CSF A beta(42) levels.
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| 22. |
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| 23. |
- Mattsson, Niklas, 1979, et al.
(författare)
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CSF biomarker variability in the Alzheimer's Association quality control program
- 2013
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Ingår i: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 9:3, s. 251-261
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Tidskriftsartikel (refereegranskat)abstract
- Background The cerebrospinal fluid (CSF) biomarkers amyloid beta 1–42, total tau, and phosphorylated tau are used increasingly for Alzheimer's disease (AD) research and patient management. However, there are large variations in biomarker measurements among and within laboratories. Methods Data from the first nine rounds of the Alzheimer's Association quality control program was used to define the extent and sources of analytical variability. In each round, three CSF samples prepared at the Clinical Neurochemistry Laboratory (Mölndal, Sweden) were analyzed by single-analyte enzyme-linked immunosorbent assay (ELISA), a multiplexing xMAP assay, or an immunoassay with electrochemoluminescence detection. Results A total of 84 laboratories participated. Coefficients of variation (CVs) between laboratories were around 20% to 30%; within-run CVs, less than 5% to 10%; and longitudinal within-laboratory CVs, 5% to 19%. Interestingly, longitudinal within-laboratory CV differed between biomarkers at individual laboratories, suggesting that a component of it was assay dependent. Variability between kit lots and between laboratories both had a major influence on amyloid beta 1–42 measurements, but for total tau and phosphorylated tau, between-kit lot effects were much less than between-laboratory effects. Despite the measurement variability, the between-laboratory consistency in classification of samples (using prehoc-derived cutoffs for AD) was high (>90% in 15 of 18 samples for ELISA and in 12 of 18 samples for xMAP). Conclusions The overall variability remains too high to allow assignment of universal biomarker cutoff values for a specific intended use. Each laboratory must ensure longitudinal stability in its measurements and use internally qualified cutoff levels. Further standardization of laboratory procedures and improvement of kit performance will likely increase the usefulness of CSF AD biomarkers for researchers and clinicians.
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| 24. |
- Wagner-Drouet, E, et al.
(författare)
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Standardized monitoring of cytomegalovirus-specific immunity can improve risk stratification of recurrent cytomegalovirus reactivation after hematopoietic stem cell transplantation
- 2021
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Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 1592-8721 .- 0390-6078. ; 106:2, s. 363-374
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Tidskriftsartikel (refereegranskat)abstract
- Recurrence of cytomegalovirus reactivation remains a major cause of morbidity and mortality following allogeneic hematopoietic stem cell transplantation. Monitoring cytomegalovirus-specific cellular immunity using a standardized assay might improve the risk stratification of patients. A prospective multicenter study was conducted in 175 intermediate- and high-risk allogeneic hematopoietic stem cell transplant recipients under preemptive antiviral therapy. Cytomegalovirus-specific cellular immunity was measured using a standardized IFN-γ ELISpot assay (T-Track® CMV). Primary aim was to evaluate the suitability of measuring cytomegalovirus-specific immunity after end of treatment for a first cytomegalovirus reactivation to predict recurrent reactivation. 40/101 (39.6%) patients with a first cytomegalovirus reactivation experienced recurrent reactivations, mainly in the high-risk group (cytomegalovirus-seronegative donor/cytomegalovirus-seropositive recipient). The positive predictive value of T-Track® CMV (patients with a negative test after the first reactivation experienced at least one recurrent reactivation) was 84.2% in high-risk patients. Kaplan-Meier analysis revealed a higher probability of recurrent cytomegalovirus reactivation in high-risk patients with a negative test after the first reactivation (hazard ratio 2.73; p=0.007). Interestingly, a post-hoc analysis considering T-Track® CMV measurements at day 100 post-transplantation, a time point highly relevant for outpatient care, showed a positive predictive value of 90.0% in high-risk patients. Our results indicate that standardized cytomegalovirus-specific cellular immunity monitoring may allow improved risk stratification and management of recurrent cytomegalovirus reactivation after hematopoietic stem cell transplantation. This study was registered at www.clinicaltrials.gov as #NCT02156479.
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| 28. |
- De Kort, A. M., et al.
(författare)
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Decreased Cerebrospinal Fluid Amyloid beta 38, 40, 42, and 43 Levels in Sporadic and Hereditary Cerebral Amyloid Angiopathy
- 2023
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Ingår i: Annals of neurology. - : Wiley. - 0364-5134 .- 1531-8249. ; 93:6, s. 1173-86
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Vascular amyloid beta (A beta) accumulation is the hallmark of cerebral amyloid angiopathy (CAA). The composition of cerebrospinal fluid (CSF) of CAA patients may serve as a diagnostic biomarker of CAA. We studied the diagnostic potential of the peptides A beta 38, A beta 40, A beta 42, and A beta 43 in patients with sporadic CAA (sCAA), hereditary Dutch-type CAA (D-CAA), and Alzheimer disease (AD).Methods: A beta peptides were quantified by immunoassays in a discovery group (26 patients with sCAA and 40 controls), a validation group (40 patients with sCAA, 40 patients with AD, and 37 controls), and a group of 22 patients with D-CAA and 54 controls. To determine the diagnostic accuracy, the area under the curve (AUC) was calculated using a receiver operating characteristic curve with 95% confidence interval (CI).Results: We found decreased levels of all A beta peptides in sCAA patients and D-CAA patients compared to controls. The difference was most prominent for A beta 42 (AUC of sCAA vs controls for discovery: 0.90, 95% CI = 0.82-0.99; for validation: 0.94, 95% CI = 0.89-0.99) and A beta 43 (AUC of sCAA vs controls for discovery: 0.95, 95% CI = 0.88-1.00; for validation: 0.91, 95% CI = 0.83-1.0). All A beta peptides except A beta 43 were also decreased in sCAA compared to AD (CSF A beta 38: AUC = 0.82, 95% CI = 0.71-0.93; CSF A beta 40: AUC = 0.88, 95% CI = 0.80-0.96; CSF A beta 42: AUC = 0.79, 95% CI = 0.66-0.92).Interpretation: A combined biomarker panel of CSF A beta 38, A beta 40, A beta 42, and A beta 43 has potential to differentiate sCAA from AD and controls, and D-CAA from controls. ANN NEUROL 2023
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| 29. |
- Mattsson, Niklas, 1979, et al.
(författare)
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Age and diagnostic performance of Alzheimer disease CSF biomarkers.
- 2012
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Ingår i: Neurology. - : American Academy of Neurology (AAN). - 1526-632X .- 0028-3878. ; 78:7, s. 468-76
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Tidskriftsartikel (refereegranskat)abstract
- Core CSF changes in Alzheimer disease (AD) are decreased amyloid β(1-42), increased total tau, and increased phospho-tau, probably indicating amyloid plaque accumulation, axonal degeneration, and tangle pathology, respectively. These biomarkers identify AD already at the predementia stage, but their diagnostic performance might be affected by age-dependent increase of AD-type brain pathology in cognitively unaffected elderly.
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| 30. |
- Roghanian, Ali, et al.
(författare)
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Antagonistic Human FcγRIIB (CD32B) Antibodies Have Anti-Tumor Activity and Overcome Resistance to Antibody Therapy In Vivo.
- 2015
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Ingår i: Cancer Cell. - : Elsevier BV. - 1878-3686 .- 1535-6108. ; 27:4, s. 473-488
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Tidskriftsartikel (refereegranskat)abstract
- Therapeutic antibodies have transformed cancer therapy, unlocking mechanisms of action by engaging the immune system. Unfortunately, cures rarely occur and patients display intrinsic or acquired resistance. Here, we demonstrate the therapeutic potential of targeting human (h) FcγRIIB (CD32B), a receptor implicated in immune cell desensitization and tumor cell resistance. FcγRIIB-blocking antibodies prevented internalization of the CD20-specific antibody rituximab, thereby maximizing cell surface accessibility and immune effector cell mediated antitumor activity. In hFcγRIIB-transgenic (Tg) mice, FcγRIIB-blocking antibodies effectively deleted target cells in combination with rituximab, and other therapeutic antibodies, from resistance-prone stromal compartments. Similar efficacy was seen in primary human tumor xenografts, including with cells from patients with relapsed/refractory disease. These data support the further development of hFcγRIIB antibodies for clinical assessment.
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| 31. |
- Verwey, N A, et al.
(författare)
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A worldwide multicentre comparison of assays for cerebrospinal fluid biomarkers in Alzheimer's disease.
- 2009
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Ingår i: Annals of clinical biochemistry. - : SAGE Publications. - 0004-5632 .- 1758-1001. ; 46:Pt 3, s. 235-40
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Different cerebrospinal fluid (CSF) amyloid-beta 1-42 (Abeta(1-42)), total Tau (Tau) and Tau phosphorylated at threonine 181 (P-Tau) levels are reported, but currently there is a lack of quality control programmes. The aim of this study was to compare the measurements of these CSF biomarkers, between and within centres. METHODS: Three CSF-pool samples were distributed to 13 laboratories in 2004 and the same samples were again distributed to 18 laboratories in 2008. In 2004 six laboratories measured Abeta(1-42), Tau and P-Tau and seven laboratories measured one or two of these marker(s) by enzyme-linked immunosorbent assays (ELISAs). In 2008, 12 laboratories measured all three markers, three laboratories measured one or two marker(s) by ELISAs and three laboratories measured the markers by Luminex. RESULTS: In 2004, the ELISA intercentre coefficients of variance (interCV) were 31%, 21% and 13% for Abeta(1-42), Tau and P-Tau, respectively. These were 37%, 16% and 15%, respectively, in 2008. When we restricted the analysis to the Innotest (N = 13) for Abeta(1-42), lower interCV were calculated (22%). The centres that participated in both years (N = 9) showed interCVs of 21%, 15% and 9% and intra-centre coefficients (intraCV) of variance of 25%,18% and 7% in 2008. CONCLUSIONS: The highest variability was found for Abeta(1-42). The variabilities for Tau and P-Tau were lower in both years. The centres that participated in both years showed a high intraCV comparable to their interCV, indicating that there is not only a high variation between but also within centres. Besides a uniform standardization of (pre)analytical procedures, the same assay should be used to decrease the inter/intracentre variation.
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| 32. |
- Wagner-Drouet, E, et al.
(författare)
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Comparison of Cytomegalovirus-Specific Immune Cell Response to Proteins versus Peptides Using an IFN-γ ELISpot Assay after Hematopoietic Stem Cell Transplantation
- 2021
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Ingår i: Diagnostics (Basel, Switzerland). - : MDPI AG. - 2075-4418. ; 11:2
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Tidskriftsartikel (refereegranskat)abstract
- Cytomegalovirus (CMV) infection is a major cause of morbidity and mortality following hematopoietic stem cell transplantation (HSCT). Measuring CMV-specific cellular immunity may improve the risk stratification and management of patients. IFN-γ ELISpot assays, based on the stimulation of peripheral blood mononuclear cells with CMV pp65 and IE-1 proteins or peptides, have been validated in clinical settings. However, it remains unclear to which extend the T-cell response to synthetic peptides reflect that mediated by full-length proteins processed by antigen-presenting cells. We compared the stimulating ability of pp65 and IE-1 proteins and corresponding overlapping peptides in 16 HSCT recipients using a standardized IFN-γ ELISpot assay. Paired qualitative test results showed an overall 74.4% concordance. Discordant results were mainly due to low-response tests, with one exception. One patient with early CMV reactivation and graft-versus-host disease, sustained CMV DNAemia and high CD8+ counts showed successive negative protein-based ELISpot results but a high and sustained response to IE-1 peptides. Our results suggest that the response to exogenous proteins, which involves their uptake and processing by antigen-presenting cells, more closely reflects the physiological response to CMV infection, while the response to exogenous peptides may lead to artificial in vitro T-cell responses, especially in strongly immunosuppressed patients.
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| 33. |
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| 34. |
- Huang, Miaozhen, et al.
(författare)
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Cross-disease analysis of depression, ataxia and dystonia highlights a role for synaptic plasticity and the cerebellum in the pathophysiology of these comorbid diseases
- 2021
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Ingår i: Biochimica et Biophysica Acta - Molecular Basis of Disease. - : Elsevier BV. - 0925-4439. ; 1867:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is growing evidence that the neuropsychiatric and neurological disorders depression, ataxia and dystonia share common biological pathways. We therefore aimed to increase our understanding of their shared pathophysiology by investigating their shared biological pathways and molecular networks. Methods: We constructed gene sets for depression, ataxia, and dystonia using the Human Phenotype Ontology database and genome-wide association studies, and identified shared genes between the three diseases. We then assessed shared genes in terms of functional enrichment, pathway analysis, molecular connectivity, expression profiles and brain-tissue-specific gene co-expression networks. Results: The 33 genes shared by depression, ataxia and dystonia are enriched in shared biological pathways and connected through molecular complexes in protein–protein interaction networks. Biological processes common/shared to all three diseases were identified across different brain tissues, highlighting roles for synaptic transmission, synaptic plasticity and nervous system development. The average expression of shared genes was significantly higher in the cerebellum compared to other brain regions, suggesting these genes have distinct cerebellar functions. Several shared genes also showed high expression in the cerebellum during prenatal stages, pointing to a functional role during development. Conclusions: The shared pathophysiology of depression, ataxia and dystonia seems to converge onto the cerebellum that maybe particularly vulnerable to changes in synaptic transmission, regulation of synaptic plasticity and nervous system development. Consequently, in addition to regulating motor coordination and motor function, the cerebellum may likely play a role in mood processing.
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| 35. |
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| 36. |
- Petzold, Axel, et al.
(författare)
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Neurofilament ELISA validation
- 2010
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Ingår i: JOURNAL OF IMMUNOLOGICAL METHODS. - 0022-1759. ; 352:1-2, s. 23-31
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Tidskriftsartikel (refereegranskat)
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| 37. |
- Petzold, Axel, et al.
(författare)
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Neurofilament ELISA validation
- 2010
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Ingår i: JIM - Journal of Immunological Methods. - : Elsevier BV. - 0022-1759 .- 1872-7905. ; 352:1-2, s. 23-31
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Neurofilament proteins (Nf) are highly specific biomarkers for neuronal death and axonal degeneration. As these markers become more widely used, an inter-laboratory validation study is required to identify assay criteria for high quality performance. METHODS: The UmanDiagnostics NF-light (R)enzyme-linked immunoabsorbent assays (ELISA) for the neurofilament light chain (NfL, 68kDa) was used to test the intra-assay and inter-laboratory coefficient of variation (CV) between 35 laboratories worldwide on 15 cerebrospinal fluid (CSF) samples. Critical factors, such as sample transport and storage, analytical delays, reaction temperature and time, the laboratories' accuracy and preparation of standards were documented and used for the statistical analyses. RESULTS: The intra-laboratory CV averaged 3.3% and the inter-laboratory CV 59%. The results from the test laboratories correlated with those from the reference laboratory (R=0.60, p<0.0001). Correcting for critical factors improved the strength of the correlation. Differences in the accuracy of standard preparation were identified as the most critical factor. Correcting for the error introduced by variation in the protein standards improved the correlation to R=0.98, p<0.0001 with an averaged inter-laboratory CV of 14%. The corrected overall inter-rater agreement was subtantial (0.6) according to Fleiss' multi-rater kappa and Gwet's AC1 statistics. CONCLUSION: This multi-center validation study identified the lack of preparation of accurate and consistent protein standards as the main reason for a poor inter-laboratory CV. This issue is also relevant to other protein biomarkers based on this type of assay and will need to be solved in order to achieve an acceptable level of analytical accuracy. The raw data of this study is available online.
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| 38. |
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| 39. |
- Smeets, Cleo J. L. M., et al.
(författare)
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Altered secondary structure of Dynorphin A associates with loss of opioid signalling and NMDA-mediated excitotoxicity in SCA23
- 2016
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 25:13, s. 2728-2737
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Tidskriftsartikel (refereegranskat)abstract
- Spinocerebellar ataxia type 23 (SCA23) is caused by missense mutations in prodynorphin, encoding the precursor protein for the opioid neuropeptides alpha-neoendorphin, Dynorphin (Dyn) A and Dyn B, leading to neurotoxic elevated mutant Dyn A levels. Dyn A acts on opioid receptors to reduce pain in the spinal cord, but its cerebellar function remains largely unknown. Increased concentration of or prolonged exposure to Dyn A is neurotoxic and these deleterious effects are very likely caused by an N-methyl-D-aspartate-mediated non-opioidmechanism as Dyn A peptides were shown to bind NMDA receptors and potentiate their glutamate-evoked currents. In the present study, we investigated the cellular mechanisms underlying SCA23-mutant Dyn A neurotoxicity. We show that SCA23 mutations in the Dyn A-coding region disrupted peptide secondary structure leading to a loss of the N-terminal alpha-helix associated with decreased kappa-opioid receptor affinity. Additionally, the altered secondary structure led to increased peptide stability of R6W and R9C Dyn A, as these peptides showed marked degradation resistance, which coincided with decreased peptide solubility. Notably, L5S Dyn A displayed increased degradation and no aggregation. R6W and wt Dyn A peptides were most toxic to primary cerebellar neurons. For R6W Dyn A, this is likely because of a switch from opioid to NMDA-receptor signalling, while for wt Dyn A, this switch was not observed. We propose that the pathology of SCA23 results from converging mechanisms of loss of opioid-mediated neuroprotection and NMDA-mediated excitotoxicity.
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| 40. |
- van Noort, Suus A M, et al.
(författare)
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Early onset ataxia with comorbid myoclonus and epilepsy : A disease spectrum with shared molecular pathways and cortico-thalamo-cerebellar network involvement
- 2023
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Ingår i: European Journal of Paediatric Neurology. - 1090-3798. ; 45, s. 47-54
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Early onset ataxia (EOA) concerns a heterogeneous disease group, often presenting with other comorbid phenotypes such as myoclonus and epilepsy. Due to genetic and phenotypic heterogeneity, it can be difficult to identify the underlying gene defect from the clinical symptoms. The pathological mechanisms underlying comorbid EOA phenotypes remain largely unknown. The aim of this study is to investigate the key pathological mechanisms in EOA with myoclonus and/or epilepsy.METHODS: For 154 EOA-genes we investigated (1) the associated phenotype (2) reported anatomical neuroimaging abnormalities, and (3) functionally enriched biological pathways through in silico analysis. We assessed the validity of our in silico results by outcome comparison to a clinical EOA-cohort (80 patients, 31 genes).RESULTS: EOA associated gene mutations cause a spectrum of disorders, including myoclonic and epileptic phenotypes. Cerebellar imaging abnormalities were observed in 73-86% (cohort and in silico respectively) of EOA-genes independently of phenotypic comorbidity. EOA phenotypes with comorbid myoclonus and myoclonus/epilepsy were specifically associated with abnormalities in the cerebello-thalamo-cortical network. EOA, myoclonus and epilepsy genes shared enriched pathways involved in neurotransmission and neurodevelopment both in the in silico and clinical genes. EOA gene subgroups with myoclonus and epilepsy showed specific enrichment for lysosomal and lipid processes.CONCLUSIONS: The investigated EOA phenotypes revealed predominantly cerebellar abnormalities, with thalamo-cortical abnormalities in the mixed phenotypes, suggesting anatomical network involvement in EOA pathogenesis. The studied phenotypes exhibit a shared biomolecular pathogenesis, with some specific phenotype-dependent pathways. Mutations in EOA, epilepsy and myoclonus associated genes can all cause heterogeneous ataxia phenotypes, which supports exome sequencing with a movement disorder panel over conventional single gene panel testing in the clinical setting.
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| 41. |
- Van Wijk, Rob C., 1991-, et al.
(författare)
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Anti‐tuberculosis effect of isoniazid scales accurately from zebrafish to humans
- 2020
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Ingår i: British Journal of Pharmacology. - : Wiley. - 0007-1188 .- 1476-5381. ; 177:24, s. 5518-5533
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Tidskriftsartikel (refereegranskat)abstract
- Background and purposeThere is a strong need for innovation in anti-tuberculosis drug development. The zebrafish larva is an attractive disease model in tuberculosis research. To translate pharmacological findings to higher vertebrates, including humans, the internal exposure of drugs needs to be quantified and linked to observed response.Experimental approachIn zebrafish studies, drugs are commonly dissolved in the external water, posing a challenge to quantify internal exposure. We developed experimental methods to quantify internal exposure, including nano-scale blood sampling, and to quantify the bacterial burden, using automated fluorescence imaging analysis, with isoniazid as paradigm compound. We used pharmacokinetic-pharmacodynamic modelling to quantify the exposure-response relationship responsible for the antibiotic response. To translate isoniazid response to humans, the quantitative exposure-response relationship in zebrafish was linked to simulated concentration-time profiles in humans, and two quantitative translational factors on sensitivity to isoniazid and stage of infection were included.Key resultsBlood concentration was only 20% of the external drug concentration. The bacterial burden increased exponentially and an isoniazid dose corresponding to 15 mg·L-1internal concentration (minimum inhibitory concentration) lead to bacteriostasis of the mycobacterial infection in the zebrafish. The concentration-effect relationship was quantified, and based on that relationship and the translational factors, the isoniazid response was translated to humans, which correlated well with observed data.Conclusions and implicationsThis proof-of-concept confirms the potential of the zebrafish larvae as tuberculosis disease model in translational pharmacology, and contributes to innovative anti-tuberculosis drug development which is strongly needed.
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| 42. |
- Wang, Lei, et al.
(författare)
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Experimental investigation of flow fields in a square channel roughened with various ribs on one wall
- 2006
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Ingår i: American Society of Mechanical Engineers, Fluids Engineering Division FED. - 0888-8116. - 0791837904 - 0791847705
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Konferensbidrag (refereegranskat)abstract
- The present work studies the separated flow in a square channel with ribs on one wall by using the PIV method. In this study, the spacing between ribs is kept constant and the heights of rib are varied in order to investigate the influence of the pitch-to-height ratio, P/e on the flow structures. Depending on the various pitch ratios, the enclosure between ribs can be regarded as closed or open cavity. Results are included for mean velocity, streamlines, skin-friction coefficient, anisotropy parameter, turbulent kinetic energy production and two-point correlation. It is found that the separated shear layer in the closed cavity has strong momentum exchange with the mainstream. By contrast, the fluid contained in the open cavity is self-sustained and the outside streamlines are almost parallel to the bottom wall. Moreover, for the open cavity, the velocity fluctuations become vigorous as the flow reattaches directly on the trailing edge. Copyright
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| 43. |
- Yasuma, R, et al.
(författare)
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Intravenous immune globulin suppresses angiogenesis in mice and humans
- 2016
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Ingår i: Signal transduction and targeted therapy. - : Springer Science and Business Media LLC. - 2095-9907 .- 2059-3635. ; 1
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Tidskriftsartikel (refereegranskat)abstract
- Human intravenous immune globulin (IVIg), a purified IgG fraction composed of ~60% IgG1 and obtained from the pooled plasma of thousands of donors, is clinically used for a wide range of diseases. The biological actions of IVIg are incompletely understood and have been attributed both to the polyclonal antibodies therein and also to their IgG (IgG) Fc regions. Recently, we demonstrated that multiple therapeutic human IgG1 antibodies suppress angiogenesis in a target-independent manner via FcγRI, a high-affinity receptor for IgG1. Here we show that IVIg possesses similar anti-angiogenic activity and inhibited blood vessel growth in five different mouse models of prevalent human diseases, namely, neovascular age-related macular degeneration, corneal neovascularization, colorectal cancer, fibrosarcoma and peripheral arterial ischemic disease. Angioinhibition was mediated by the Fc region of IVIg, required FcγRI and had similar potency in transgenic mice expressing human FcγRs. Finally, IVIg therapy administered to humans for the treatment of inflammatory or autoimmune diseases reduced kidney and muscle blood vessel densities. These data place IVIg, an agent approved by the US Food and Drug Administration, as a novel angioinhibitory drug in doses that are currently administered in the clinical setting. In addition, they raise the possibility of an unintended effect of IVIg on blood vessels.
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| 44. |
- Bakalkin, Georgy, et al.
(författare)
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Prodynorphin mutations cause the neurodegenerative disorder spinocerebellar ataxia type 23.
- 2010
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 87:5, s. 593-603
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Tidskriftsartikel (refereegranskat)abstract
- Spinocerebellar ataxias (SCAs) are dominantly inherited neurodegenerative disorders characterized by progressive cerebellar ataxia and dysarthria. We have identified missense mutations in prodynorphin (PDYN) that cause SCA23 in four Dutch families displaying progressive gait and limb ataxia. PDYN is the precursor protein for the opioid neuropeptides, α-neoendorphin, and dynorphins A and B (Dyn A and B). Dynorphins regulate pain processing and modulate the rewarding effects of addictive substances. Three mutations were located in Dyn A, a peptide with both opioid activities and nonopioid neurodegenerative actions. Two of these mutations resulted in excessive generation of Dyn A in a cellular model system. In addition, two of the mutant Dyn A peptides induced toxicity above that of wild-type Dyn A in cultured striatal neurons. The fourth mutation was located in the nonopioid PDYN domain and was associated with altered expression of components of the opioid and glutamate system, as evident from analysis of SCA23 autopsy tissue. Thus, alterations in Dyn A activities and/or impairment of secretory pathways by mutant PDYN may lead to glutamate neurotoxicity, which underlies Purkinje cell degeneration and ataxia. PDYN mutations are identified in a small subset of ataxia families, indicating that SCA23 is an infrequent SCA type (~0.5%) in the Netherlands and suggesting further genetic SCA heterogeneity.
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| 45. |
- Bridel, Claire, et al.
(författare)
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Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology : A Systematic Review and Meta-analysis
- 2019
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Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 76:9, s. 1035-1048
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Forskningsöversikt (refereegranskat)abstract
- Importance Neurofilament light protein (NfL) is elevated in cerebrospinal fluid (CSF) of a number of neurological conditions compared with healthy controls (HC) and is a candidate biomarker for neuroaxonal damage. The influence of age and sex is largely unknown, and levels across neurological disorders have not been compared systematically to date.Objectives To assess the associations of age, sex, and diagnosis with NfL in CSF (cNfL) and to evaluate its potential in discriminating clinically similar conditions.Data Sources PubMed was searched for studies published between January 1, 2006, and January 1, 2016, reporting cNfL levels (using the search terms neurofilament light and cerebrospinal fluid) in neurological or psychiatric conditions and/or in HC.Study Selection Studies reporting NfL levels measured in lumbar CSF using a commercially available immunoassay, as well as age and sex.Data Extraction and Synthesis Individual-level data were requested from study authors. Generalized linear mixed-effects models were used to estimate the fixed effects of age, sex, and diagnosis on log-transformed NfL levels, with cohort of origin modeled as a random intercept.Main Outcome and Measure The cNfL levels adjusted for age and sex across diagnoses.Results Data were collected for 10 059 individuals (mean [SD] age, 59.7 [18.8] years; 54.1% female). Thirty-five diagnoses were identified, including inflammatory diseases of the central nervous system (n = 2795), dementias and predementia stages (n = 4284), parkinsonian disorders (n = 984), and HC (n = 1332). The cNfL was elevated compared with HC in a majority of neurological conditions studied. Highest levels were observed in cognitively impaired HIV-positive individuals (iHIV), amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and Huntington disease. In 33.3% of diagnoses, including HC, multiple sclerosis, Alzheimer disease (AD), and Parkinson disease (PD), cNfL was higher in men than women. The cNfL increased with age in HC and a majority of neurological conditions, although the association was strongest in HC. The cNfL overlapped in most clinically similar diagnoses except for FTD and iHIV, which segregated from other dementias, and PD, which segregated from atypical parkinsonian syndromes.Conclusions and Relevance These data support the use of cNfL as a biomarker of neuroaxonal damage and indicate that age-specific and sex-specific (and in some cases disease-specific) reference values may be needed. The cNfL has potential to assist the differentiation of FTD from AD and PD from atypical parkinsonian syndromes.
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| 46. |
- Del Duca, V., et al.
(författare)
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All-Order Amplitudes at any Multiplicity in the Multi-Regge Limit
- 2020
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 124:16
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Tidskriftsartikel (refereegranskat)abstract
- We propose an all-loop expression for scattering amplitudes in planar N = 4 super Yang-Mills theory in multi-Regge kinematics valid for all multiplicities, all helicity configurations, and arbitrary logarithmic accuracy. Our expression is arrived at from comparing explicit perturbative results with general expectations from the integrable structure of a closely related collinear limit. A crucial ingredient of the analysis is an all-order extension for the central emission vertex that we recently computed at next-to-leading logarithmic accuracy. As an application, we use our all-order formula to prove that all amplitudes in this theory in multi-Regge kinematics are single-valued multiple polylogarithms of uniform transcendental weight.
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| 47. |
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| 48. |
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| 49. |
- Koraeus, Mats
(författare)
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Stressing Knowledge : Organisational closed-ness and knowledge acquisition under pressure
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Organisations have been analytically conceptualised as being somewhat analogous to individuals for a long time. They have culture; they can learn; and they can behave in various odd ways. But how far can the simile be stretched? What other types of organisational cognition can we imagine? And what benefits can we gain by introducing new perspectives of this kind? This study shows that organisations can exhibit familiar symptoms of stress, such as closing themselves to the outside world and becoming unreceptive to external stimuli and input. They retreat to what is familiar and safe and put on blinders to hide anything that does not already fit with how they feel things should be, often in situations where they would be best served by being as open to and perceptive of these external stimuli as possible. Using a model of organisational behaviour that connects external pressure to an internal mode of operation and to specific knowledge-seeking behaviours, the study examines two case pairs—two success stories and two catastrophic failures—to examine patterns of organisational cognition. By comparing and contrasting the failure of the FBI during the 1993 Waco siege with its subsequent success during the 1996 Montana Freemen standoff, and doing the same with the Swedish Foreign Ministry’s handling of the 2004 Southeast Asian tsunami and the 2006 evacuation from the war in Lebanon, a pattern emerges where certain types of knowledge proved to be the key to staying as open-minded, responsive, and dynamic as these crises demanded. This knowledge can be used both during a crisis to resolve some of the confusion and time pressure that is endemic to such situations, as well as before a crisis to mitigate or even stave off the approaching chaos.
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| 50. |
- Le, Phu Tran Phong, et al.
(författare)
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Tailoring Vanadium Dioxide Film Orientation Using Nanosheets : a Combined Microscopy, Diffraction, Transport, and Soft X-Ray in Transmission Study
- 2020
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Ingår i: Advanced Functional Materials. - : WILEY-V C H VERLAG GMBH. - 1616-301X .- 1616-3028. ; 30:1
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Tidskriftsartikel (refereegranskat)abstract
- Vanadium dioxide (VO2) is a much-discussed material for oxide electronics and neuromorphic computing applications. Here, heteroepitaxy of VO2 is realized on top of oxide nanosheets that cover either the amorphous silicon dioxide surfaces of Si substrates or X-ray transparent silicon nitride membranes. The out-of-plane orientation of the VO2 thin films is controlled at will between (011)(M1)/(110)(R) and (-402)(M1)/(002)(R) by coating the bulk substrates with Ti0.87O2 and NbWO6 nanosheets, respectively, prior to VO2 growth. Temperature-dependent X-ray diffraction and automated crystal orientation mapping in microprobe transmission electron microscope mode (ACOM-TEM) characterize the high phase purity, the crystallographic and orientational properties of the VO2 films. Transport measurements and soft X-ray absorption in transmission are used to probe the VO2 metal-insulator transition, showing results of a quality equal to those from epitaxial films on bulk single-crystal substrates. Successful local manipulation of two different VO2 orientations on a single substrate is demonstrated using VO2 grown on lithographically patterned lines of Ti0.87O2 and NbWO6 nanosheets investigated by electron backscatter diffraction. Finally, the excellent suitability of these nanosheet-templated VO2 films for advanced lensless imaging of the metal-insulator transition using coherent soft X-rays is discussed.
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