| 1. |
- Pilotto, Andrea, et al.
(author)
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Plasma p-tau217 in Alzheimer's disease: Lumipulse and ALZpath SIMOA head-to-head comparison.
- 2024
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In: medRxiv : the preprint server for health sciences.
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Journal article (peer-reviewed)abstract
- Plasma phosphorylated-tau217 (p-tau217) has been shown to be one of the most accurate diagnostic markers for Alzheimer's disease (AD). No studies have compared the clinical performance of p-tau217 as assessed by the fully automated Lumipulse and SIMOA ALZpath p-tau217.To evaluate the diagnostic accuracy of Lumipulse and SIMOA plasma p-tau217 assays for AD.The study included 392 participants, 162 with AD, 70 with other neurodegenerative diseases (NDD) with CSF biomarkers and 160 healthy controls. Plasma p-tau217 levels were measured using the Lumipulse and ALZpath SIMOA assays. The ability of p-tau217 assessed by both techniques to discriminate AD from NDD and controls was investigated using ROC analyses.Both techniques showed high internal consistency of p-tau217 with similar correlation with CSF p-tau181 levels. In head-to-head comparison, Lumipulse and SIMOA showed similar diagnostic accuracy for differentiating AD from NDD (area under the curve [AUC] 0.952, 95%CI 0.927-0.978 vs 0.955, 95%CI 0.928-0.982, respectively) and HC (AUC 0.938, 95%CI 0.910-0.966 and 0.937, 95% CI0.907-0.967 for both assays).This study demonstrated the high precision and diagnostic accuracy of p-tau217 for the clinical diagnosis of Alzheimer's disease using either fully automated or semi-automated techniques.
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| 2. |
- Ashton, Nicholas J., et al.
(author)
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A multicentre validation study of the diagnostic value of plasma neurofilament light
- 2021
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12, s. 1-12
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Journal article (peer-reviewed)abstract
- Increased cerebrospinal fluid neurofilament light (NfL) is a recognized biomarker for neurodegeneration that can also be assessed in blood. Here, we investigate plasma NfL as a marker of neurodegeneration in 13 neurodegenerative disorders, Down syndrome, depression and cognitively unimpaired controls from two multicenter cohorts: King's College London (n = 805) and the Swedish BioFINDER study (n = 1,464). Plasma NfL was significantly increased in all cortical neurodegenerative disorders, amyotrophic lateral sclerosis and atypical parkinsonian disorders. We demonstrate that plasma NfL is clinically useful in identifying atypical parkinsonian disorders in patients with parkinsonism, dementia in individuals with Down syndrome, dementia among psychiatric disorders, and frontotemporal dementia in patients with cognitive impairment. Data-driven cut-offs highlighted the fundamental importance of age-related clinical cut-offs for disorders with a younger age of onset. Finally, plasma NfL performs best when applied to indicate no underlying neurodegeneration, with low false positives, in all age-related cut-offs.
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| 3. |
- Bauckneht, Matteo, et al.
(author)
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Associations among education, age, and the dementia with Lewy bodies (DLB) metabolic pattern: A European-DLB consortium project
- 2021
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In: Alzheimer's & Dementia. - : WILEY. - 1552-5260 .- 1552-5279. ; 17:8, s. 1277-1286
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Journal article (peer-reviewed)abstract
- Introduction We assessed the influence of education as a proxy of cognitive reserve and age on the dementia with Lewy bodies (DLB) metabolic pattern. Methods Brain 18F-fluorodeoxyglucose positron emission tomography and clinical/demographic information were available in 169 probable DLB patients included in the European DLB-consortium database. Principal component analysis identified brain regions relevant to local data variance. A linear regression model was applied to generate age- and education-sensitive maps corrected for Mini-Mental State Examination score, sex (and either education or age). Results Age negatively covaried with metabolism in bilateral middle and superior frontal cortex, anterior and posterior cingulate, reducing the expression of the DLB-typical cingulate island sign (CIS). Education negatively covaried with metabolism in the left inferior parietal cortex and precuneus (making the CIS more prominent). Discussion These findings point out the importance of tailoring interpretation of DLB biomarkers considering the concomitant effect of individual, non-disease-related variables such as age and cognitive reserve.
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| 4. |
- Etminani, Kobra, 1984-, et al.
(author)
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A 3D deep learning model to predict the diagnosis of dementia with Lewy bodies, Alzheimers disease, and mild cognitive impairment using brain 18F-FDG PET
- 2022
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In: European Journal of Nuclear Medicine and Molecular Imaging. - New York : Springer. - 1619-7070 .- 1619-7089. ; 49, s. 563-584
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Journal article (peer-reviewed)abstract
- Purpose The purpose of this study is to develop and validate a 3D deep learning model that predicts the final clinical diagnosis of Alzheimers disease (AD), dementia with Lewy bodies (DLB), mild cognitive impairment due to Alzheimers disease (MCI-AD), and cognitively normal (CN) using fluorine 18 fluorodeoxyglucose PET (18F-FDG PET) and compare models performance to that of multiple expert nuclear medicine physicians readers. Materials and methods Retrospective 18F-FDG PET scans for AD, MCI-AD, and CN were collected from Alzheimers disease neuroimaging initiative (556 patients from 2005 to 2020), and CN and DLB cases were from European DLB Consortium (201 patients from 2005 to 2018). The introduced 3D convolutional neural network was trained using 90% of the data and externally tested using 10% as well as comparison to human readers on the same independent test set. The models performance was analyzed with sensitivity, specificity, precision, F1 score, receiver operating characteristic (ROC). The regional metabolic changes driving classification were visualized using uniform manifold approximation and projection (UMAP) and network attention. Results The proposed model achieved area under the ROC curve of 96.2% (95% confidence interval: 90.6-100) on predicting the final diagnosis of DLB in the independent test set, 96.4% (92.7-100) in AD, 71.4% (51.6-91.2) in MCI-AD, and 94.7% (90-99.5) in CN, which in ROC space outperformed human readers performance. The network attention depicted the posterior cingulate cortex is important for each neurodegenerative disease, and the UMAP visualization of the extracted features by the proposed model demonstrates the reality of development of the given disorders. Conclusion Using only 18F-FDG PET of the brain, a 3D deep learning model could predict the final diagnosis of the most common neurodegenerative disorders which achieved a competitive performance compared to the human readers as well as their consensus.
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| 5. |
- Huber, Maria, et al.
(author)
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Metabolic correlates of dopaminergic loss in dementia with lewy bodies
- 2020
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In: Movement Disorders. - : WILEY. - 0885-3185 .- 1531-8257. ; 35, s. 595-605
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Journal article (peer-reviewed)abstract
- Background Striatal dopamine deficiency and metabolic changes are well-known phenomena in dementia with Lewy bodies and can be quantified in vivo by I-123-Ioflupane brain single-photon emission computed tomography of dopamine transporter and F-18-fluorodesoxyglucose PET. However, the linkage between both biomarkers is ill-understood. Objective We used the hitherto largest study cohort of combined imaging from the European consortium to elucidate the role of both biomarkers in the pathophysiological course of dementia with Lewy bodies. Methods We compared striatal dopamine deficiency and glucose metabolism of 84 dementia with Lewy body patients and comparable healthy controls. After normalization of data, we tested their correlation by region-of-interest-based and voxel-based methods, controlled for study center, age, sex, education, and current cognitive impairment. Metabolic connectivity was analyzed by inter-region coefficients stratified by dopamine deficiency and compared to healthy controls. Results There was an inverse relationship between striatal dopamine availability and relative glucose hypermetabolism, pronounced in the basal ganglia and in limbic regions. With increasing dopamine deficiency, metabolic connectivity showed strong deteriorations in distinct brain regions implicated in disease symptoms, with greatest disruptions in the basal ganglia and limbic system, coincident with the pattern of relative hypermetabolism. Conclusions Relative glucose hypermetabolism and disturbed metabolic connectivity of limbic and basal ganglia circuits are metabolic correlates of dopamine deficiency in dementia with Lewy bodies. Identification of specific metabolic network alterations in patients with early dopamine deficiency may serve as an additional supporting biomarker for timely diagnosis of dementia with Lewy bodies. (c) 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
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| 6. |
- Morbelli, Silvia, et al.
(author)
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Metabolic patterns across core features in dementia with lewy bodies
- 2019
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In: Annals of Neurology. - : John Wiley & Sons. - 0364-5134 .- 1531-8249. ; 85:5, s. 715-725
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Journal article (peer-reviewed)abstract
- ObjectiveTo identify brain regions whose metabolic impairment contributes to dementia with Lewy bodies (DLB) clinical core features expression and to assess the influence of severity of global cognitive impairment on the DLB hypometabolic pattern.MethodsBrain fluorodeoxyglucose positron emission tomography and information on core features were available in 171 patients belonging to the imaging repository of the European DLB Consortium. Principal component analysis was applied to identify brain regions relevant to the local data variance. A linear regression model was applied to generate core‐feature–specific patterns controlling for the main confounding variables (Mini‐Mental State Examination [MMSE], age, education, gender, and center). Regression analysis to the locally normalized intensities was performed to generate an MMSE‐sensitive map.ResultsParkinsonism negatively covaried with bilateral parietal, precuneus, and anterior cingulate metabolism; visual hallucinations (VH) with bilateral dorsolateral–frontal cortex, posterior cingulate, and parietal metabolism; and rapid eye movement sleep behavior disorder (RBD) with bilateral parieto‐occipital cortex, precuneus, and ventrolateral–frontal metabolism. VH and RBD shared a positive covariance with metabolism in the medial temporal lobe, cerebellum, brainstem, basal ganglia, thalami, and orbitofrontal and sensorimotor cortex. Cognitive fluctuations negatively covaried with occipital metabolism and positively with parietal lobe metabolism. MMSE positively covaried with metabolism in the left superior frontal gyrus, bilateral–parietal cortex, and left precuneus, and negatively with metabolism in the insula, medial frontal gyrus, hippocampus in the left hemisphere, and right cerebellum.InterpretationRegions of more preserved metabolism are relatively consistent across the variegate DLB spectrum. By contrast, core features were associated with more prominent hypometabolism in specific regions, thus suggesting a close clinical–imaging correlation, reflecting the interplay between topography of neurodegeneration and clinical presentation in DLB patients. Ann Neurol 2019;85:715–725
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| 7. |
- Soliman, Amira, 1980-, et al.
(author)
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Adopting transfer learning for neuroimaging : a comparative analysis with a custom 3D convolution neural network model
- 2022
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In: BMC Medical Informatics and Decision Making. - London : BioMed Central (BMC). - 1472-6947. ; 22, s. 1-15
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Journal article (peer-reviewed)abstract
- Background: In recent years, neuroimaging with deep learning (DL) algorithms have made remarkable advances in the diagnosis of neurodegenerative disorders. However, applying DL in different medical domains is usually challenged by lack of labeled data. To address this challenge, transfer learning (TL) has been applied to use state-of-the-art convolution neural networks pre-trained on natural images. Yet, there are differences in characteristics between medical and natural images, also image classification and targeted medical diagnosis tasks. The purpose of this study is to investigate the performance of specialized and TL in the classification of neurodegenerative disorders using 3D volumes of 18F-FDG-PET brain scans. Results: Results show that TL models are suboptimal for classification of neurodegenerative disorders, especially when the objective is to separate more than two disorders. Additionally, specialized CNN model provides better interpretations of predicted diagnosis. Conclusions: TL can indeed lead to superior performance on binary classification in timely and data efficient manner, yet for detecting more than a single disorder, TL models do not perform well. Additionally, custom 3D model performs comparably to TL models for binary classification, and interestingly perform better for diagnosis of multiple disorders. The results confirm the superiority of the custom 3D-CNN in providing better explainable model compared to TL adopted ones. © 2022, The Author(s).
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| 8. |
- Stockbauer, Anna, et al.
(author)
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Metabolic network alterations as a supportive biomarker in dementia with Lewy bodies with preserved dopamine transmission
- 2024
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In: European Journal of Nuclear Medicine and Molecular Imaging. - : SPRINGER. - 1619-7070 .- 1619-7089. ; 51:4, s. 1023-1034
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Journal article (peer-reviewed)abstract
- Purpose Metabolic network analysis of FDG-PET utilizes an index of inter-regional correlation of resting state glucose metabolism and has been proven to provide complementary information regarding the disease process in parkinsonian syndromes. The goals of this study were (i) to evaluate pattern similarities of glucose metabolism and network connectivity in dementia with Lewy bodies (DLB) subjects with subthreshold dopaminergic loss compared to advanced disease stages and to (ii) investigate metabolic network alterations of FDG-PET for discrimination of patients with early DLB from other neurodegenerative disorders (Alzheimer's disease, Parkinson's disease, multiple system atrophy) at individual patient level via principal component analysis (PCA).Methods FDG-PETs of subjects with probable or possible DLB (n = 22) without significant dopamine deficiency (z-score < 2 in putamen binding loss on DaT-SPECT compared to healthy controls (HC)) were scaled by global-mean, prior to volume-of-interest-based analyses of relative glucose metabolism. Single region metabolic changes and network connectivity changes were compared against HC (n = 23) and against DLB subjects with significant dopamine deficiency (n = 86). PCA was applied to test discrimination of patients with DLB from disease controls (n = 101) at individual patient level.Results Similar patterns of hypo- (parietal- and occipital cortex) and hypermetabolism (basal ganglia, limbic system, motor cortices) were observed in DLB patients with and without significant dopamine deficiency when compared to HC. Metabolic connectivity alterations correlated between DLB patients with and without significant dopamine deficiency (R2 = 0.597, p < 0.01). A PCA trained by DLB patients with dopamine deficiency and HC discriminated DLB patients without significant dopaminergic loss from other neurodegenerative parkinsonian disorders at individual patient level (area-under-the-curve (AUC): 0.912).Conclusion Disease-specific patterns of altered glucose metabolism and altered metabolic networks are present in DLB subjects without significant dopaminergic loss. Metabolic network alterations in FDG-PET can act as a supporting biomarker in the subgroup of DLB patients without significant dopaminergic loss at symptoms onset.
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| 9. |
- Abdelnour, Carla, et al.
(author)
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Parsing heterogeneity within dementia with Lewy bodies using clustering of biological, clinical, and demographic data
- 2022
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In: Alzheimer's Research & Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 14:1
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Journal article (peer-reviewed)abstract
- Background: Dementia with Lewy bodies (DLB) includes various core clinical features that result in different phenotypes. In addition, Alzheimer's disease (AD) and cerebrovascular pathologies are common in DLB. All this increases the heterogeneity within DLB and hampers clinical diagnosis. We addressed this heterogeneity by investigating subgroups of patients with similar biological, clinical, and demographic features.Methods: We studied 107 extensively phenotyped DLB patients from the European DLB consortium. Factorial analysis of mixed data (FAMD) was used to identify dimensions in the data, based on sex, age, years of education, disease duration, Mini-Mental State Examination (MMSE), cerebrospinal fluid (CSF) levels of AD biomarkers, core features of DLB, and regional brain atrophy. Subsequently, hierarchical clustering analysis was used to subgroup individuals based on the FAMD dimensions.Results: We identified 3 dimensions using FAMD that explained 38% of the variance. Subsequent hierarchical clustering identified 4 clusters. Cluster 1 was characterized by amyloid-beta and cerebrovascular pathologies, medial temporal atrophy, and cognitive fluctuations. Cluster 2 had posterior atrophy and showed the lowest frequency of visual hallucinations and cognitive fluctuations and the worst cognitive performance. Cluster 3 had the highest frequency of tau pathology, showed posterior atrophy, and had a low frequency of parkinsonism. Cluster 4 had virtually normal AD biomarkers, the least regional brain atrophy and cerebrovascular pathology, and the highest MMSE scores.Conclusions: This study demonstrates that there are subgroups of DLB patients with different biological, clinical, and demographic characteristics. These findings may have implications in the diagnosis and prognosis of DLB, as well as in the treatment response in clinical trials.
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| 10. |
- Bentham, James, et al.
(author)
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A century of trends in adult human height
- 2016
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In: eLIFE. - 2050-084X. ; 5
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Journal article (peer-reviewed)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.522.7) and 16.5 cm (13.319.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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| 11. |
- Bentham, James, et al.
(author)
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A century of trends in adult human height
- 2016
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In: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 5
-
Journal article (peer-reviewed)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3– 19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8– 144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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| 12. |
- Bravo, Andrea G., et al.
(author)
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The interplay between total mercury, methylmercury and dissolved organic matter in fluvial systems : A latitudinal study across Europe
- 2018
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In: Water Research. - : Elsevier. - 0043-1354 .- 1879-2448. ; 144, s. 172-182
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Journal article (peer-reviewed)abstract
- Large-scale studies are needed to identify the drivers of total mercury (THg) and monomethyl-mercury (MeHg) concentrations in aquatic ecosystems. Studies attempting to link dissolved organic matter (DOM) to levels of THg or MeHg are few and geographically constrained. Additionally, stream and river systems have been understudied as compared to lakes. Hence, the aim of this study was to examine the influence of DOM concentration and composition, morphological descriptors, land uses and water chemistry on THg and MeHg concentrations and the percentage of THg as MeHg (%MeHg) in 29 streams across Europe spanning from 41°N to 64°N. THg concentrations (0.06–2.78 ng L−1) were highest in streams characterized by DOM with a high terrestrial soil signature and low nutrient content. MeHg concentrations (7.8–159 pg L−1) varied non-systematically across systems. Relationships between DOM bulk characteristics and THg and MeHg suggest that while soil derived DOM inputs control THg concentrations, autochthonous DOM (aquatically produced) and the availability of electron acceptors for Hg methylating microorganisms (e.g. sulfate) drive %MeHg and potentially MeHg concentration. Overall, these results highlight the large spatial variability in THg and MeHg concentrations at the European scale, and underscore the importance of DOM composition on mercury cycling in fluvial systems.
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| 13. |
- Bravo, Andrea G., et al.
(author)
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The interplay between total mercury, methylmercury and dissolved organic matter in fluvial systems : A latitudinal study across Europe
- 2018
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In: Water Research. - : Pergamon. - 0043-1354 .- 1879-2448. ; 144, s. 172-182
-
Journal article (peer-reviewed)abstract
- Large-scale studies are needed to identify the drivers of total mercury (THg) and monomethyl-mercury (MeHg) concentrations in aquatic ecosystems. Studies attempting to link dissolved organic matter (DOM) to levels of THg or MeHg are few and geographically constrained. Additionally, stream and river systems have been understudied as compared to lakes. Hence, the aim of this study was to examine the influence of DOM concentration and composition, morphological descriptors, land uses and water chemistry on THg and MeHg concentrations and the percentage of THg as MeHg (%MeHg) in 29 streams across Europe spanning from 41°N to 64 °N. THg concentrations (0.06–2.78 ng L−1) were highest in streams characterized by DOM with a high terrestrial soil signature and low nutrient content. MeHg concentrations (7.8–159 pg L−1) varied non-systematically across systems. Relationships between DOM bulk characteristics and THg and MeHg suggest that while soil derived DOM inputs control THg concentrations, autochthonous DOM (aquatically produced) and the availability of electron acceptors for Hg methylating microorganisms (e.g. sulfate) drive %MeHg and potentially MeHg concentration. Overall, these results highlight the large spatial variability in THg and MeHg concentrations at the European scale, and underscore the importance of DOM composition on mercury cycling in fluvial systems.
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| 14. |
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| 15. |
- Gonzalez, Maria C, et al.
(author)
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Association of Plasma p-tau181 and p-tau231 Concentrations With Cognitive Decline in Patients With Probable Dementia With Lewy Bodies.
- 2022
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In: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 79:1, s. 32-37
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Journal article (peer-reviewed)abstract
- Plasma phosphorylated tau (p-tau) has proven to be an accurate biomarker for Alzheimer disease (AD) pathologic characteristics, offering a less expensive and less invasive alternative to cerebrospinal fluid (CSF) and positron emission tomography biomarkers for amyloid-β and tau. Alzheimer disease comorbid pathologic characteristics are common and are associated with more rapid cognitive decline in patients with dementia with Lewy bodies (DLB); therefore, it is anticipated that plasma p-tau concentrations may have utility in assessing cognitive impairment in individuals with this disorder.To measure the concentrations of plasma p-tau (p-tau181 and p-tau231) and evaluate their associations with cognitive decline in individuals with probable DLB.This multicenter longitudinal cohort study included participants from the European-DLB (E-DLB) Consortium cohort enrolled at 10 centers with harmonized diagnostic procedures from January 1, 2002, to December 31, 2020, with up to 5 years of follow-up. A total of 1122 participants with plasma samples were available. Participants with acute delirium or terminal illness and patients with other previous major psychiatric or neurologic disorders were excluded, leaving a cohort of 987 clinically diagnosed participants with probable DLB (n=371), Parkinson disease (n=204), AD (n=207), as well as healthy controls (HCs) (n=205).The main outcome was plasma p-tau181 and p-tau231 levels measured with in-house single molecule array assays. The Mini-Mental State Examination (MMSE) was used to measure cognition.Among this cohort of 987 patients (512 men [51.9%]; mean [SD] age, 70.0 [8.8] years), patients with DLB did not differ significantly regarding age, sex, or years of education from those in the AD group, but the DLB group was older than the HC group and included more men than the AD and HC groups. Baseline concentrations of plasma p-tau181 and p-tau231 in patients with DLB were significantly higher than those in the HC group but lower than in the AD group and similar to the Parkinson disease group. Higher plasma concentrations of both p-tau markers were found in a subgroup of patients with DLB with abnormal CSF amyloid-β42 levels compared with those with normal levels (difference in the groups in p-tau181, -3.61 pg/mL; 95% CI, -5.43 to -1.79 pg/mL; P=.049; difference in the groups in p-tau231, -2.51 pg/mL; 95% CI, -3.63 to -1.39 pg/mL; P=.02). There was no difference between p-tau181 level and p-tau231 level across confirmed AD pathologic characteristcs based on reduced Aβ42 level in CSF in individuals with DLB. In DLB, a significant association was found between higher plasma p-tau181 and p-tau231 levels and lower MMSE scores at baseline (for p-tau181, -0.092 MMSE points; 95% CI, -0.12 to -0.06 MMSE points; P=.001; for p-tau231, -0.16 MMSE points; 95% CI, -0.21 to -0.12 MMSE points; P<.001), as well as more rapid MMSE decline over time. Plasma p-tau181 level was associated with a decrease of -0.094 MMSE points per year (95% CI, -0.144 to -0.052 MMSE points; P=.02), whereas plasma p-tau231 level was associated with an annual decrease of -0.130 MMSE points (95% CI, -0.201 to -0.071 MMSE points; P=.02), after adjusting for sex and age.This study suggests that plasma p-tau181 and p-tau231 levels may be used as cost-effective and accessible biomarkers to assess cognitive decline in individuals with DLB.
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| 16. |
- Gonzalez, Maria Camila, et al.
(author)
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Cognitive and motor decline in dementia with lewy bodies and Parkinson's disease dementia
- 2023
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In: Movement Disorders Clinical Practice. - : John Wiley & Sons. - 2330-1619. ; 10:6, s. 980-986
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Journal article (peer-reviewed)abstract
- Background: There is a need to better understand the rate of cognitive and motor decline of Dementia with Lewy bodies (DLB) and Parkinson's disease Dementia (PDD).Objectives: To compare the rate of cognitive and motor decline in patients with DLB and PDD from the E-DLB Consortium and the Parkinson's Incidence Cohorts Collaboration (PICC) Cohorts.Methods: The annual change in MMSE and MDS-UPDRS part III was estimated using linear mixed regression models in patients with at least one follow-up (DLB n = 837 and PDD n = 157).Results: When adjusting for confounders, we found no difference in the annual change in MMSE between DLB and PDD (−1.8 [95% CI −2.3, −1.3] vs. −1.9 [95% CI −2.6, −1.2] [P = 0.74]). MDS-UPDRS part III showed nearly identical annual changes (DLB 4.8 [95% CI 2.1, 7.5]) (PDD 4.8 [95% CI 2.7, 6.9], [P = 0.98]).Conclusions: DLB and PDD showed similar rates of cognitive and motor decline. This is relevant for future clinical trial designs.
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| 17. |
- Haase, Peter, et al.
(author)
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Moderate warming over the past 25 years has already reorganized stream invertebrate communities
- 2019
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In: Science of the Total Environment. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 658, s. 1531-1538
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Journal article (peer-reviewed)abstract
- Climate warming often results in species range shifts, biodiversity loss and accumulated climatic debts of biota (i.e. slower changes in biota than in temperature). Here, we analyzed the changes in community composition and temperature signature of stream invertebrate communities over 25 years (1990-€“2014), based on a large set of samples (n = 3782) over large elevation, latitudinal and longitudinal gradients in central Europe. Although warming was moderate (average 0.5°C), we found a strong reorganization of stream invertebrate communities. Total abundance (+35.9%) and richness (+39.2%) significantly increased. The share of abundance (TA) and taxonomic richness (TR) of warm-dwelling taxa (TA: +73.2%; TR: +60.2%) and medium-temperature-dwelling taxa (TA: +0.4%; TR: +5.8%) increased too, while cold-dwelling taxa declined (TA: -61.5%; TR: -ˆ’47.3%). The community temperature index, representing the temperature signature of stream invertebrate communities, increased at a similar pace to physical temperature, indicating a thermophilization of the communities and, for the first time, no climatic debt. The strongest changes occurred along the altitudinal gradient, suggesting that stream invertebrates use the spatial configuration of river networks to track their temperature niche uphill. Yet, this may soon come to an end due to the summit trap effect. Our results indicate an ongoing process of replacement of cold-adapted species by thermophilic species at only 0.5 °C warming, which is particularly alarming in the light of the more drastic climate warming projected for coming decades.
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| 18. |
- Imarisio, Alberto, et al.
(author)
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Plasma Cystatin C correlates with plasma NfL levels and predicts disease progression in Parkinson's disease.
- 2021
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In: Neuro-degenerative diseases. - : S. Karger AG. - 1660-2862 .- 1660-2854. ; 21, s. 109-116
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Journal article (peer-reviewed)abstract
- Previous studies reported increased plasma levels of Cystatin C (Cys-C) in Parkinson's disease (PD) and claimed for a possible association with disease severity and progression. The aim of this study was to evaluate plasma Cys-C in PD and healthy controls (HC) and test its association with markers of peripheral inflammation, neurodegeneration and clinical progression in a longitudinal study.Plasma Cys-C, high-sensitive C-reactive protein (hsCRP), interleukin 6 (IL-6) and Neurofilament Light Chain (NfL) were assessed at the baseline in 71 consecutive non-demented PD and 69 HC. PD patients underwent an extensive motor and cognitive assessment at baseline and after 2 years of follow-up. The association of Cys-C with disease severity was evaluated in a multilinear model adjusted for the effect of age, sex, disease duration and peripheral inflammation.Cys-C levels appeared to be higher in PD compared to controls and correlated with the plasma neuronal marker NfL (r = 0.204, p = 0.046). In longitudinal analyses, PD patients with higher Cys-C levels exhibited faster motor progression at two years of follow-up independently from the peripheral inflammatory profile.Cys-C was associated with higher NfL levels and a remarkably faster motor progression in PD independently from peripheral inflammation. Further studies are needed in order to understand the mechanisms underpinning the association of Cys-C with higher neuronal damage markers in neurodegenerative diseases.
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| 19. |
- Jourdan, Jonas, et al.
(author)
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Effects of changing climate on European stream invertebrate communities : A long-term data analysis
- 2018
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In: Science of the Total Environment. - : Elsevier. - 0048-9697 .- 1879-1026. ; 621, s. 588-599
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Journal article (peer-reviewed)abstract
- Long-term observations on riverine benthic invertebrate communities enable assessments of the potential impacts of global change on stream ecosystems. Besides increasing average temperatures, many studies predict greater temperature extremes and intense precipitation events as a consequence of climate change. In this study we examined long-term observation data (10–32years) of 26 streams and rivers from four ecoregions in the European Long-Term Ecological Research (LTER) network, to investigate invertebrate community responses to changing climatic conditions. We used functional trait and multi-taxonomic analyses and combined examinations of general long-term changes in communities with detailed analyses of the impact of different climatic drivers (i.e., various temperature and precipitation variables) by focusing on the response of communities to climatic conditions of the previous year. Taxa and ecoregions differed substantially in their response to climate change conditions. We did not observe any trend of changes in total taxonomic richness or overall abundance over time or with increasing temperatures, which reflects a compensatory turnover in the composition of communities; sensitive Plecoptera decreased in response to warmer years and Ephemeroptera increased in northern regions. Invasive species increased with an increasing number of extreme days which also caused an apparent upstream community movement. The observed changes in functional feeding group diversity indicate that climate change may be associated with changes in trophic interactions within aquatic food webs. These findings highlight the vulnerability of riverine ecosystems to climate change and emphasize the need to further explore the interactive effects of climate change variables with other local stressors to develop appropriate conservation measures.
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| 20. |
- Lerche, Stefanie, et al.
(author)
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Cognitive impairment in Glucocerebrosidase (GBA)-associated PD: Not primarily associated with cerebrospinal fluid Abeta and Tau profiles.
- 2017
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In: Movement disorders : official journal of the Movement Disorder Society. - : Wiley. - 1531-8257. ; 32:12, s. 1780-1783
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Journal article (peer-reviewed)abstract
- A proportion of idiopathic Parkinson's disease patients (PDidiopathic ) with dementia show altered CSF profiles of amyloid β (Aβ) and Tau. PD patients with Glucocerebrosidase (GBA) mutations (PDGBA ) present with even more cognitive decline than seen in PDidiopathic .The objective of this study was to evaluate whether CSF profiles of Aβ and tau are associated with the prominent cognitive impairment in PDGBA .CSF levels of Aβ1-42 , t-Tau, p-Tau, and total alpha-synuclein were assessed in 479 participants (50 PDGBA , 308 PDidiopathic , 121 healthy controls).Older age was associated with cognitive impairment in PDGBA and PDidiopathic . Despite prominent cognitive impairment, PDGBA showed similar CSF levels of Aβ1-42 , t-Tau, and p-Tau as seen in healthy controls. In contrast, lower levels of Aβ1-42 and higher levels of t-Tau and p-Tau were associated with worse cognitive performance in PDidiopathic .The prominent cognitive impairment in PDGBA seems not primarily associated with Aβ and Tau profiles in CSF. © 2017 International Parkinson and Movement Disorder Society.
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| 21. |
- Lucchini, Roberto G., et al.
(author)
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Metal Exposure and SNCA rs356219 Polymorphism Associated With Parkinson Disease and Parkinsonism
- 2020
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In: Frontiers in Neurology. - : Frontiers Media SA. - 1664-2295. ; 11
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Journal article (peer-reviewed)abstract
- Objective: In the province of Brescia, Italy, historical neurotoxic metal exposure has occurred for several decades. This study aimed to explore the role of metal exposure and genetics on Parkinson's Disease (PD) and Parkinsonism. Methods: Cases were enrolled from four local clinics for movement disorders. Randomly selected controls non-affected by neurological or psychiatric conditions were enrolled from the same health centers keeping a similar gender ratio and age distribution as for cases. Data on sociodemographic variables, clinical onset and life habits were collected besides accurate occupational and residential history. Blood samples were collected from all participants for genotyping of target polymorphisms in genes linked to PD and/or metal transport. Results: A total number of 432 cases and 444 controls were enrolled in the study, with average age of 71 years (72.2 for cases and 70 for controls). The average age at diagnosis was 65.9 years (SD 9.9). Among the potential risk factors, family history of PD or Parkinsonism showed the strongest association with the diseases (OR = 4.2, 95% CI 2.3, 7.6 on PD; OR = 4.3, 95% CI 1.9, 9.5 for Parkinsonism), followed by polymorphism rs356219 in the alpha-synuclein (SNCA) gene (OR = 2.03, 95% CI 1.3, 3.3 for CC vs. TT on PD; OR = 2.5, 95% CI 1.1, 5.3 for CC vs. TT on Parkinsonism), exposure to metals (OR = 2.4;, 95% CI 1.3, 4.2 on PD), being born in a farm (OR = 1.8; 95% CI 1.1, 2.8 on PD; OR = 2.6; 95% CI 1.4, 4.9 on Parkinsonism) and being born in the province of Brescia (OR = 1.7; 95% CI 1.0, 2.9 on PD). Conditional OR of having PD depending by SNCA polymorphism and metal exposure highlights higher risk of PD among CC SNCA carriers and being exposed to metals. However, the interaction term was not statistically significant. Conclusions: Lifetime exposure to metals and genetic variation in SNCA gene are relevant determinants of PD and Parkinsonism in the highly industrialized area of Brescia, Italy. The lack of evidence of statistical interaction between environmental and genetic factors may be due to the low frequencies of subjects representing the exposure categories and the polymorphism variants and does not rule out the biological interaction.
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| 22. |
- Mastrantuono, Luciana, et al.
(author)
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Response of littoral macroinvertebrates to morphological disturbances in Mediterranean lakes : the case of Lake Piediluco (central Italy)
- 2015
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In: Fundamental and Applied Limnology. - : Publishing Technology. - 1863-9135. ; 186:4, s. 297-310
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Journal article (peer-reviewed)abstract
- The assessment of the impacts of human morphological alterations on lake ecological condition based on littoral benthic fauna is still in its infancy, especially in the Mediterranean area of Europe. Lake Piediluco is a riverine lake, sited in Central Italy, whose water level is strictly regulated for hydroelectric reasons and hence can be classified as a Heavily Modified Water Body (HMWB) according to the E.U. Water Framework Directive (WDF). Here, we aim at comparing the invertebrate assemblages among sites with a different degree of morphological alterations by identifying potential indicator species and metrics sensitive to morphological alterations, and by comparing the fauna composition collected using two sampling procedures (composite vs habitat-specific samples) with different processing times. Our results show that the invertebrate assemblages of Lake Piediluco differed according to the three types of shoreline alteration (natural, soft- and hard-altered sites) and this was more evident when we analyzed the habitat-specific samples. Several taxa, diversity and metrics based on the number of Ephemeroptera, Trichoptera, Odonata and Mollusca taxa (ETO and ETOM) are found to be sensitive to shoreline alterations and are candidates for inclusion in assessment metrics for WDF compliant monitoring of the ecological status of this lake. While habitat-specific sampling provided a more detailed picture of the assemblages, composite samples provided consistent results and could be used when processing cost is an issue.
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| 23. |
- Pilotto, Andrea, et al.
(author)
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Differences Between Plasma and Cerebrospinal Fluid p-tau181 and p-tau231 in Early Alzheimer's Disease.
- 2022
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In: Journal of Alzheimer's disease : JAD. - 1875-8908. ; 87:3, s. 991-997
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Journal article (peer-reviewed)abstract
- Plasma phosphorylated tau species have been recently proposed as peripheral markers of Alzheimer's disease (AD) pathology. In this cross-sectional study including 91 subjects, plasma and cerebrospinal fluid (CSF) p-tau181 and p-tau231 levels were elevated in the early symptomatic stages of AD. Plasma p-tau231 and p-tau181 were strongly related to CSF phosphorylated tau, total tau and amyloid and exhibited a high accuracy-close to CSF p-tau231 and p-tau181-to identify AD already in the early stage of the disease. The findings might support the use as diagnostic and prognostic peripheral AD biomarkers in both research and clinical settings.
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| 24. |
- Pilotto, Andrea, et al.
(author)
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SARS-CoV-2 encephalitis is a cytokine release syndrome: evidences from cerebrospinal fluid analyses.
- 2021
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In: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. - : Oxford University Press (OUP). - 1537-6591. ; 73:9
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Journal article (peer-reviewed)abstract
- Recent findings indicated that SARS-CoV-2 related neurological manifestations involve cytokine release syndrome along with endothelial activation, blood brain barrier dysfunction, and immune-mediated mechanisms. Very few studies have fully investigated the CSF correlates of SARS-CoV-2 encephalitis.Patients with PCR-confirmed SARS-CoV-2 infection and encephalitis (COV-Enc), encephalitis without SARS-CoV-2 infection (ENC) and healthy controls (HC) underwent an extended panel of CSF neuronal (NfL, T-tau), glial (GFAP, TREM2, YKL-40) and inflammatory biomarkers (IL-1β, IL-6, Il-8, TNF- α, CXCL-13 and β2-microglobulin).Thirteen COV-Enc, 21 ENC and 18 HC entered the study. In COV-Enc cases, CSF was negative for SARS-CoV-2 real-time PCR but exhibited increased IL-8 levels independently from presence of pleocytosis/hyperproteinorracchia. COV-Enc patients showed increased IL-6, TNF- α, and β2-microglobulin and glial markers (GFAP, sTREM-2, YKL-40) levels similar to ENC but normal CXCL13 levels. Neuronal markers NfL and T-Tau were abnormal only in severe cases.SARS-CoV-2-related encephalitis were associated with prominent glial activation and neuroinflammatory markers, whereas neuronal markers were increased in severe cases only. The pattern of CSF alterations suggested a cytokine-release syndrome as the main inflammatory mechanism of SARS-CoV-2 related encephalitis.
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| 25. |
- Pilotto, Francesca, et al.
(author)
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Decline in niche specialization and trait β-diversity in benthic invertebrate communities of Central European low-mountain streams over 25 years
- 2022
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In: Science of the Total Environment. - : Elsevier. - 0048-9697 .- 1879-1026. ; 810
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Journal article (peer-reviewed)abstract
- Biotic homogenization is one of the key aspects of the current biodiversity crisis. Here we analyzed the trends of three facets of niche homogenization, i.e. niche specialization, trait α-diversity and spatial β-diversity, over a period of 25 years (1990–2014) using a large dataset of 3782 stream benthic invertebrate samples collected from central European low-mountain streams. We studied a set of traits describing the ecological niche of species and their functions: body size, feeding groups, substrate preferences, flow preferences, stream zonation preferences and saprobity. Trait composition changed significantly during the study period, and we identified an overall increase in niche homogenization. Specifically, community niche specialization significantly decreased by 20.3% over the 25-year period, with declines ranging from −16.0 to −40.9% for zonation-, flow-, substrate-preferences, body size and feeding traits. Trait diversity did not change significantly, although we recorded significant decreases by −14.2% and −10.2% for flow- and substrate-preference and increases by 5.8% and 22.6% for feeding traits and zonation preference over the study period. Trait spatial β-diversity significantly decreased by −53.0%, with substrate-preference, feeding groups and flow-preference traits declining from −61.9% to −75.3% over the study period. This increased niche homogenization is likely driven by the increase of down-stream typical taxa, which are favored by warming temperatures. Further, it is in apparent contradiction with the recorded increase in abundance (+35.9%) and taxonomic richness (+39.2%) over the same period. Even such increases do not safeguard communities from undergoing niche homogenization, indicating that recovery processes may differ with regard to community taxonomic composition and traits. Our results emphasize the complexity of community responses to global change and warrant caution when founding conclusions based solely on single community metrics.
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