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| 2. |
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| 3. |
- Wisse, L. E.M., et al.
(författare)
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Downstream effects of polypathology on neurodegeneration of medial temporal lobe subregions
- 2021
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Ingår i: Acta Neuropathologica Communications. - : Springer Science and Business Media LLC. - 2051-5960. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- The medial temporal lobe (MTL) is a nidus for neurodegenerative pathologies and therefore an important region in which to study polypathology. We investigated associations between neurodegenerative pathologies and the thickness of different MTL subregions measured using high-resolution post-mortem MRI. Tau, TAR DNA-binding protein 43 (TDP-43), amyloid-β and α-synuclein pathology were rated on a scale of 0 (absent)—3 (severe) in the hippocampus and entorhinal cortex (ERC) of 58 individuals with and without neurodegenerative diseases (median age 75.0 years, 60.3% male). Thickness measurements in ERC, Brodmann Area (BA) 35 and 36, parahippocampal cortex, subiculum, cornu ammonis (CA)1 and the stratum radiatum lacunosum moleculare (SRLM) were derived from 0.2 × 0.2 × 0.2 mm3 post-mortem MRI scans of excised MTL specimens from the contralateral hemisphere using a semi-automated approach. Spearman’s rank correlations were performed between neurodegenerative pathologies and thickness, correcting for age, sex and hemisphere, including all four proteinopathies in the model. We found significant associations of (1) TDP-43 with thickness in all subregions (r = − 0.27 to r = − 0.46), and (2) tau with BA35 (r = − 0.31) and SRLM thickness (r = − 0.33). In amyloid-β and TDP-43 negative cases, we found strong significant associations of tau with ERC (r = − 0.40), BA35 (r = − 0.55), subiculum (r = − 0.42) and CA1 thickness (r = − 0.47). This unique dataset shows widespread MTL atrophy in relation to TDP-43 pathology and atrophy in regions affected early in Braak stageing and tau pathology. Moreover, the strong association of tau with thickness in early Braak regions in the absence of amyloid-β suggests a role of Primary Age-Related Tauopathy in neurodegeneration.
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| 4. |
- Bölling, T, et al.
(författare)
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Development of Curative Therapies for Ewing Sarcomas by Interdisciplinary Cooperative Groups in Europe.
- 2015
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Ingår i: Klinische Pädiatrie. - : Georg Thieme Verlag KG. - 1439-3824 .- 0300-8630. ; 227:3, s. 108-115
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Forskningsöversikt (refereegranskat)abstract
- Curative therapies for Ewing sarcoma have been developed within cooperative groups. Consecutive clinical trials have systematically assessed the impact and timing of local therapy and the activity of cytotoxic drugs and their combinations. They have led to an increase of long-term disease-free survival to around 70% in patients with localized disease. Translational research in ES remains an area in which interdisciplinary and international cooperation is essential for future progress. This article reviews current state-of-the art therapy, with a focus on trials performed in Europe, and summarizes novel strategies to further advance both the cure rates and quality of survival.
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| 5. |
- Lawrie, E. A., et al.
(författare)
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Possible chirality in the doubly-odd Tl-198 nucleus: Residual interaction at play
- 2008
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 78:2
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Tidskriftsartikel (refereegranskat)abstract
- A candidate for chiral bands was found in Tl-198 for the first time in a mass region of oblate (or nonaxial with gamma >= 30 degrees) deformed nuclei. Two bands show very similar quasiparticle alignments, moments of inertia, and B(M1)/B(E2) ratios. They have a relative excitation energy of about 500 keV and different patterns of energy staggering. Calculations using the two-quasiparticle-plus-triaxial-rotor model with residual proton-neutron interaction included show that a triaxial deformation with gamma similar to 44 degrees agrees very well with all the experimental observations. Furthennore, considerable energy staggering for both partner bands was calculated for this pi h(9/2) circle times vi(13/2)(-1) configuration at gamma - 30 degrees, suggesting that chiral bands may have substantial energy staggering.
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| 6. |
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| 7. |
- Ruggeri, Kai, et al.
(författare)
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The general fault in our fault lines
- 2021
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Ingår i: Nature Human Behaviour. - : Springer Nature. - 2397-3374. ; 5:10, s. 1369-1380
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Tidskriftsartikel (refereegranskat)abstract
- Pervading global narratives suggest that political polarization is increasing, yet the accuracy of such group meta-perceptions has been drawn into question. A recent US study suggests that these beliefs are inaccurate and drive polarized beliefs about out-groups. However, it also found that informing people of inaccuracies reduces those negative beliefs. In this work, we explore whether these results generalize to other countries. To achieve this, we replicate two of the original experiments with 10,207 participants across 26 countries. We focus on local group divisions, which we refer to as fault lines. We find broad generalizability for both inaccurate meta-perceptions and reduced negative motive attribution through a simple disclosure intervention. We conclude that inaccurate and negative group meta-perceptions are exhibited in myriad contexts and that informing individuals of their misperceptions can yield positive benefits for intergroup relations. Such generalizability highlights a robust phenomenon with implications for political discourse worldwide.
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| 9. |
- Dantonello, Tobias M, et al.
(författare)
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Challenges in the Local Treatment of Large Abdominal Embryonal Rhabdomyosarcoma
- 2014
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Ingår i: Annals of Surgical Oncology. - : Springer Science and Business Media LLC. - 1068-9265 .- 1534-4681. ; 21:11, s. 3579-3586
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Embryonal rhabdomyosarcoma is the most common pediatric soft tissue sarcoma. The best local treatment in large, nonmetastatic primary unresected nongenitourinary embryonal rhabdomyosarcoma of the abdomen (LARME) is however unclear.METHODS:We analyzed patients with LARME treated in four consecutive CWS trials. All diagnoses were confirmed by reference reviews. Treatment included multiagent chemotherapy and local treatment of the primary tumor with surgery and/or radiotherapy. The impact of primary debulking surgery (PDS) also was studied.RESULTS:One hundred patients <21 years with a median age of 4 years had LARME. Sixty-one of them had a tumor >10 cm in diameter at diagnosis. PDS was performed in 19 of 100 children. The outcomes of patients with PDS were similar to those of the other patients. In 36 children, the tumor was resected after induction chemotherapy; 60 RME were irradiated. The toxic effects of radiochemotherapy were not significantly increased compared with the nonirradiated patients. With a median follow-up of 10 years, the 5-year EFS and OS were 52 ± 10 and 65 ± 9 %, respectively. Significant risk factors in multivariate analysis were age >10 years; no achievement of complete remission; and inadequate secondary local treatment, defined as incomplete secondary resection or no radiation.CONCLUSIONS:Children with LARME have a fair prognosis, despite an often huge tumor size and unfavorable primary site, if the tumors can either be resected or irradiated following induction chemotherapy. PDS was only performed in a small subgroup. Radiation performed concomitantly with chemotherapy did not increase the acute toxicity significantly.
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| 11. |
- Dantonello, Tobias M., et al.
(författare)
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Initial patient characteristics can predict pattern and risk of relapse in localized rhabdomyosarcoma
- 2008
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Ingår i: Journal of Clinical Oncology. - 1527-7755. ; 26:3, s. 406-413
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Evaluation of primary tumor-, treatment-, and patient-related factors predicting relapse pattern, risk, and survival after relapse with the aim to design a risk-adapted, tumor- directed surveillance program for patients with localized rhabdomyosarcoma (RMS). Patients and Methods One thousand one hundred sixty-four patients with nonmetastatic RMS achieved complete remission at the end of multimodal therapy in the consecutive trials of the Cooperative Weichteilsarkom Studiengruppe (CWS)-81, CWS-86, CWS-91, and CWS-96 between 1980 and 2002 ( median follow-up, 5 years). Three hundred thirty-seven of these individuals developed either locoregional, metastatic, or combined relapses. Predictive factors for relapse, its pattern, and postrelapse survival were analyzed. Results Age, histology, tumor size, tumor site, postsurgical stage, and omission of radiotherapy were identified as factors associated with an increased relapse risk in multivariate analyses. Relapse rates did not differ among the CWS trials. Median time to relapse was 1.43 years from first diagnosis ( range, 0.13 to 13.5 years). There were 217 locoregional, 72 metastatic, and 48 combined recurrences. Only two patients developed metastases more than 4 years after diagnosis, and both had combined recurrences. Five-year postrelapse survival was 24%. Patient subsets with consistent relapse pattern, risk, and postrelapse survival rates were identified on the basis of histologic subtype and tumor size. Conclusion Initial patient and tumor characteristics predict pattern and risk of relapse and also correlate with postrelapse survival probabilities. In localized RMS, tumor- directed follow-up should focus on the primary site. Screening for metastatic relapse may not be necessary more than 4 years after diagnosis. The identification of subgroups with distinctive pattern and risk of relapse may be used to develop risk-adapted, tumor- directed guidance for detection of recurrent disease in localized RMS.
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| 12. |
- Dantonello, Tobias M, et al.
(författare)
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Malignant ectomesenchymoma in children and adolescents : Report from the Cooperative Weichteilsarkom Studiengruppe (CWS)
- 2013
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Ingår i: Pediatric Blood & Cancer. - : Wiley. - 1545-5009 .- 1545-5017. ; 60:2, s. 224-229
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Malignant ectomesenchymoma (MEM) is a soft tissue tumor with heterologous rhabdomyoblastic components believed to arise from pluripotent migratory neural crest cells. To date merely 50 cases have been published and the knowledge about the course of disease and optimal treatment is limited.METHODS: Six patients with MEM were registered 1996-2009. The diagnosis was confirmed according to current criteria. Their treatment and outcome was analyzed.RESULTS:The median age of the three females and three males was 0.6 years (range, 0.2-13.5). The mesenchymal component in all tumors was rhabdomyosarcoma (RMS), the neural component ganglioneuroblastoma/neuroblastoma (n = 5) and peripheral primitive neuroectodermal tumor in one case. Five patients presented with localized, one with metastatic disease. All but one patient received multiagent chemotherapy during their initial treatment. The tumors of 4/5 patients with localized MEM were at least grossly resected at best surgery; the patient without gross resection was additionally irradiated. Three of four evaluable tumors responded well to induction chemotherapy. All patients achieved a first complete remission (CR), but three recurrences (two local, one systemic) occurred. The individual with metastatic MEM did not survive, but all five patients with localized MEM are currently alive in CR with a median follow-up of 5 years (range: 2.1-13.7).CONCLUSIONS: Risk-factors and outcome of MEM appear to be comparable with other highly malignant pediatric soft tissue sarcoma when a multimodal treatment strategy including chemotherapy and adequate local treatment is pursued. We propose that treatment of patients with MEM be done according to pediatric protocols similar to other rhabdomyosarcoma-like soft tissue sarcoma.
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| 13. |
- Dantonello, Tobias M., et al.
(författare)
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Survival following disease recurrence of primary localized alveolar rhabdomyosarcoma
- 2013
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Ingår i: Pediatric Blood & Cancer. - : Wiley. - 1545-5009 .- 1545-5017. ; 60:8, s. 1267-1273
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Tidskriftsartikel (refereegranskat)abstract
- Background Recurrences in primary localized alveolar rhabdomyosarcoma (RMA) are common. Post-relapse survival is poor. We evaluated prognostic factors including relapse treatment in patients with recurrent RMA. Methods Relapses occurred in 115/235 patients with nonmetastatic RMA treated in four consecutive CWS-trials after achievement of a complete remission. Sufficient information about post-relapse treatment and outcome could be obtained in 99 patients and was retrospectively analyzed. Results Nine of 99 patients received no salvage therapy and died after a median of 2 months. The remaining 90 patients received multimodal relapse treatment including mandatory chemotherapy. Recurrences were grossly resected in 39 patients; 57 patients received radiation. At a median follow-up from relapse of 8 years, 20 patients were alive and disease-free (5-year post-relapse survival [PROS] 21.3 +/- 8). All surviving patients apart from a single individual had an isolated, circumscribed recurrence. Sixteen of 20 survivors were treated with adequate local relapse therapy (ALRT, i.e., either complete resection or gross resection+radiation). Survival in the subgroup of 27 individuals with circumscribed recurrences and ALRT was significantly better (PROS 53.7 +/- 19) compared with disseminated recurrences and/or tumors treated without ALRT. Absence of primary lymph node involvement, circumscribed relapses, ALRT, and achievement of a second CR were identified as independent favorable risk factors. Conclusion Post-relapse survival for primary localized RMA is generally poor. However, certain patient groups differed significantly in their likelihood of survival and 50% of patients with circumscribed relapses treated with ALRT survived. These findings may form the basis for an evidence-based risk-stratification for recurrent disease including relapse treatment.
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| 15. |
- Delion, D. S., et al.
(författare)
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Shell model plus cluster description of negative parity states in Po-212
- 2012
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Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 85:6, s. 064306-
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Tidskriftsartikel (refereegranskat)abstract
- The intraband electromagnetic transitions in Po-210 and Pb-210 are well described within the shell model approach. In contrast, similar transitions in Po-212 are one order ofmagnitude smaller than the experimental values, suggesting the existence of an alpha-cluster component in the structure of this nucleus. To probe this assumption we introduced Gaussian-like components in the single-particle orbitals. We thus obtained an enhancement of intraband transitions, as well as a proper description of the absolute alpha-decay width in Po-212. We analyzed the recently measured unnatural parity states I- in Po-212 in terms of the collective octupole excitation in Pb-208 coupled to positive parity states in Pb-210. They are connected by relatively large dipole transitions to yrast positive natural parity states. We described E1 transitions by using the same alpha-cluster component and an effective neutron dipole charge e(nu) = -eZ/A. B(E2) values and absolute alpha-decay width in Po-212 are simultaneously described within the shell model plus a cluster component depending upon one free strength parameter.
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| 16. |
- Gueorguieva, E., et al.
(författare)
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High-spin states in Au-191 : Evidence for triaxial shape?
- 2003
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Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 68:5, s. 543081-5430814
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Tidskriftsartikel (refereegranskat)abstract
- The level scheme of Au-191 was considerably extended to high spin using gamma spectroscopy with the Eurogam-II array and internal conversion measurements with the Orsay electron spectrometer. Several bands that appear as strongly coupled were associated with low- Omega configurations in Au-191 . Using total routhian surface and cranked shell model calculations it was shown that these bands have a rotation-aligned nature and are most likely generated by the nonaxiallity of the nucleus induced by the odd proton. The predictions for the presence of such bands in Au-191 and in the oblate nuclei in the Pt-Au-Hg region found excellent agreement with the experimental data, as well as the predictions for their alignments and band-crossing frequencies in Au-191 .
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| 17. |
- Gueorguieva, E., et al.
(författare)
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Sets of rotation-aligned bands indicating nonaxiality in Au-190
- 2004
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Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 69:4, s. 044320-
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Tidskriftsartikel (refereegranskat)abstract
- The level scheme of Au-190 was extended up to high spin using gamma spectroscopy with the Eurogam-II array and internal conversion measurements with the electron- gamma spectrometer of Orsay. Several sets of rotation-aligned bands were found and associated with high- j, low- K configurations. According to the total Routhian surface and cranked shell model calculations these bands are caused by the nonaxiality of the nuclear deformation (gammaless than or equal to-70degrees). Furthermore, very good agreement was obtained between the experimental data and the theoretical predictions for the properties of these bands, such as alignments, band-crossing frequencies, and signature inversion, thus supporting the suggested nonaxial shapes.
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| 19. |
- Nguyen Ngoc, Hung, et al.
(författare)
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Chemical composition and morphology of individual aerosol particles from a CARIBIC flight at 10 km altitude between 50 degrees N and 30 degrees S
- 2008
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Ingår i: Journal of Geophysical Research. - 2156-2202. ; 113:D23
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Tidskriftsartikel (refereegranskat)abstract
- Analysis of individual particles by analytical electron microscopy as well as quantitative analysis using particle-induced X-ray emission (PIXE) and particle elastic scattering analysis (PESA) were carried out on samples collected from a flight at 10 km altitude between 50 degrees N and 30 degrees S as part of the Civil Aircraft for Regular Investigation of the atmosphere Based on an Instrument Container (CARIBIC) project (http://www.caribic-atmospheric.com). Particle morphology showed large variability with sampling latitude. Complicated branched structures dominated the large particles of the extratropical northern and southern hemisphere and the northern tropics. Particles in the tropics of the southern hemisphere were small in size and large in number concentration, whereas particles in or close to the intertropical convergence zone were few and small in size. Particles in the lowermost stratosphere were found to have similar structures but more branched than the ones found in the upper troposphere of the extratropics. Quantitative analysis revealed that the sulfur concentration varied by a factor of 50 in the nine samples analyzed in this study. The carbon-to-sulfur mass concentration ratio was lowest in the lowermost stratosphere (0.5) and highest in the tropics of the southern hemisphere (3.5). The elemental distribution of carbon and sulfur in individual particles was mapped by energy-filtered transmission electron microscopy (EFTEM). Almost all particles analyzed contained a mixture of carbonaceous and sulfurous matter. Particles with satellites were found by EFTEM to contain both carbon and sulfur in the central particle, whereas in the satellite particles only carbonaceous material was detected.
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| 20. |
- Pokorna, E, et al.
(författare)
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Estimated and measured donor creatinine clearance are poor predictors of long-term renal graft function and survival
- 2002
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Ingår i: American Journal of Transplantation. - : Elsevier BV. - 1600-6135. ; 2:4, s. 373-380
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to evaluate estimated and measured donor renal function in predicting graft function long-term and to identify donor criteria associated with nonacceptable graft prognosis. In 200 consecutive cadaver donors creatinine clearance was measured at explantation and estimated using the Cockcroft formula on admission serum creatinine. Graft function was evaluated in recipients (n = 387) by 24-h creatinine clearance regularly during 3years after transplantation. Measured creatinine clearance correlated to some extent with long-term graft function, while Cockcroft estimation was slightly superior and similar to using donor age only. Kidneys from donors with intra-operative creatinine clearance less than or equal to555mL/min (median 50mL/min) produced acceptable recipient graft function of 48mL/min at 3years and 76% 3-year graft survival. Donor age greater than or equal to60years resulted in clearance at 3years of 29mL/min and 78% 3-year graft survival; adding the criteria of admission Cockcroft less than or equal to60mL/min, graft function at 3years (28mL/min) and 3-year graft survival (76%) were similar. In conclusion, creatinine-based estimates of the functional capacity of the donor kidney, calculated or intra-operatively measured, do little to improve the ability of donor age alone to predict long-term allograft function after renal transplantation, and nonacceptable donors are not discriminated.
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| 21. |
- Roh, Hyung S., et al.
(författare)
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Integrating Color Deconvolution Thresholding and Weakly Supervised Learning for Automated Segmentation of Neurofibrillary Tangle and Neuropil Threads
- 2023
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Ingår i: Medical Imaging 2023 : Digital and Computational Pathology - Digital and Computational Pathology. - 1605-7422. - 9781510660472 ; 12471
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Konferensbidrag (refereegranskat)abstract
- Abnormally phosphorylated tau proteins are known to be a major indicator of Alzheimer's Disease (AD) with strong association with memory loss and cognitive decline. Automated generation of pixel-wise accurate neurofibrillary tangles (NFTs) and neuropil threads (NTs) segmentation is a challenging task, due to lack of ground truth segmentation data of these abnormal tau pathology. This problem is most prominent in the case of segmenting NTs, where the small threadlike morphology makes pixel-wise labeling a laborious task and unrealistic for large-scale studies. Lack of ground truth data poses a significant limitation for many learning-based methods to generate accurate segmentations of NFTs and NTs. This work presents an automated pipeline for pixel level segmentation of NFTs and NTs that does not rely on ground truth segmentation data. The pipeline is composed of four main steps: (1) color deconvolution is used to separate histopathology images into staining channels (DAB, Hematoxylin, and Eosin), (2) Otsu's thresholding is used on the DAB stain channel to generate pixel level segmentation of abnormal tau proteins staining, (3) a weakly-supervised learning paradigm (WildCat), using only global descriptors of images, is used to generate density maps of potential regions of NFTs and NTs, and (4) density maps and segmentations are then integrated using connected component analysis to localize NFTs and NTs in the detected tau segmentations. Our results show high global classification accuracy for NFTs (Acc:0.96) and NTs (Acc:0.91), and statistically significant distinctions when evaluating the percent area occupied of the detected NTs relative to expert ratings of NTs severity. Qualitative assessment of the NFTs and NTs results showed accurate pixel-level segmentations of the NFTs, while modest performance for NTs.
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| 22. |
- Sadaghiani, Shokufeh, et al.
(författare)
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Associations of phosphorylated tau pathology with whole-hemisphere ex vivo morphometry in 7 tesla MRI
- 2023
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Ingår i: Alzheimer's and Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 19:6, s. 2355-2364
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Neurodegenerative disorders are associated with different pathologies that often co-occur but cannot be measured specifically with in vivo methods. Methods: Thirty-three brain hemispheres from donors with an Alzheimer's disease (AD) spectrum diagnosis underwent T2-weighted magnetic resonance imaging (MRI). Gray matter thickness was paired with histopathology from the closest anatomic region in the contralateral hemisphere. Results: Partial Spearman correlation of phosphorylated tau and cortical thickness with TAR DNA-binding protein 43 (TDP-43) and α-synuclein scores, age, sex, and postmortem interval as covariates showed significant relationships in entorhinal and primary visual cortices, temporal pole, and insular and posterior cingulate gyri. Linear models including Braak stages, TDP-43 and α-synuclein scores, age, sex, and postmortem interval showed significant correlation between Braak stage and thickness in the parahippocampal gyrus, entorhinal cortex, and Broadman area 35. Conclusion: We demonstrated an association of measures of AD pathology with tissue loss in several AD regions despite a limited range of pathology in these cases. Highlights: Neurodegenerative disorders are associated with co-occurring pathologies that cannot be measured specifically with in vivo methods. Identification of the topographic patterns of these pathologies in structural magnetic resonance imaging (MRI) may provide probabilistic biomarkers. We demonstrated the correlation of the specific patterns of tissue loss from ex vivo brain MRI with underlying pathologies detected in postmortem brain hemispheres in patients with Alzheimer's disease (AD) spectrum disorders. The results provide insight into the interpretation of in vivo structural MRI studies in patients with AD spectrum disorders.
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