1,721,103 research outputs found
Non-Invasive Molecular Status Differentiation of Pediatric Low-Grade Gliomas From Magnetic Resonance Images Using Machine Learning
Full text linkPediatric low-grade glioma (pLGG), the most prevalent central nervous system tumor in childhood, is often driven by one of two genetic alterations: BRAF Fusion or BRAF Mutation. Identification of genetic status is critical for optimal prognostication and treatment of pLGG. Genetic status is typically determined through biopsy, which has associated risks, and in some cases is not possible due to tumor location. A prior study showed that machine learning (ML) approaches could potentially detect pLGG genetic status non-invasively from MR images, reducing the need for surgery. Through three key studies, this thesis aimed to make progress towards a clinically deployable imaging-based pLGG genetic status prediction ML model.
When published, the study featured in Chapter 2 provided the most robust evidence available on the ability of ML to distinguish between patients with pLGG driven by BRAF Fusion and Mutation using radiomic features, such as shape or texture, extracted from manually segmented tumor regions of MR images. Strong performance was achieved using a larger cohort and more robust statistical methods than earlier works, verifying the potential of ML-based BRAF status prediction. Additionally, to help encourage clinical uptake, an uncertainty quantification framework and nomogram were developed and validated.
The study Chapter 3 was based on expanded beyond hand-crafted radiomics features to investigate an additional method of classifying medical images, deep learning (DL). This study focused on the more realistic task of grouping pLGGs into three categories: BRAF fusion, BRAF mutation, and non-BRAF altered, unlike most earlier studies which ignored cases in the latter class. A comprehensive ML framework combining DL and radiomics proved optimal, outperforming either approach on its own.
Chapter 4 introduced a segmentation-free approach, eliminating dependency on manual or automated tumor segmentations. Instead, whole-brain MR images were directly analyzed. A novel in-domain pretraining regimen was used to build tumor segmentation information into classification models. The segmentation-free framework achieved classification accuracy similar to a manual segmentation-based pipeline, without requiring tumor segmentations as an input.Collectively, the findings of this thesis demonstrate the potential of ML to enable non-invasive pLGG genetic profiling, which could help improve outcomes for patients with pLGG.Ph.D
Combined intracavitary and interstitial brachytherapy of cervical cancer using the novel hybrid applicator Venezia: Clinical feasibility and initial results
No full textTo report on first-in-human experience and the initial clinical results using the hybrid applicator Venezia (Elekta, Sweden) in the treatment of patients with locally advanced cervical cancer
TSPO PET imaging of natalizumab-associated progressive multifocal leukoencephalopathy
No full textAbstract Progressive multifocal leukoencephalopathy (PML) is a severe infection of the CNS caused by the polyomavirus JC that can occur in multiple sclerosis patients treated with natalizumab. Clinical management of patients with natalizumab-associated PML is challenging not least because current imaging tools for the early detection, longitudinal monitoring and differential diagnosis of PML lesions are limited. Here we evaluate whether translocator protein (TSPO) PET imaging can be applied to monitor the inflammatory activity of PML lesions over time and differentiate them from multiple sclerosis lesions. For this monocentre pilot study we followed eight patients with natalizumab-associated PML with PET imaging using the TSPO radioligand 18F-GE-180 combined with frequent 3 T MRI. In addition we compared TSPO PET signals in PML lesions with the signal pattern of multiple sclerosis lesions from 17 independent multiple sclerosis patients. We evaluated the standardized uptake value ratio as well as the morphometry of the TSPO uptake for putative PML and multiple sclerosis lesions areas compared to a radiologically unaffected pseudo-reference region in the cerebrum. Furthermore, TSPO expression in situ was immunohistochemically verified by determining the density and cellular identity of TSPO-expressing cells in brain sections from four patients with early natalizumab-associated PML as well as five patients with other forms of PML and six patients with inflammatory demyelinating CNS lesions (clinically isolated syndrome/multiple sclerosis). Histological analysis revealed a reticular accumulation of TSPO expressing phagocytes in PML lesions, while such phagocytes showed a more homogeneous distribution in putative multiple sclerosis lesions. TSPO PET imaging showed an enhanced tracer uptake in natalizumab-associated PML lesions that was present from the early to the chronic stages (up to 52 months after PML diagnosis). While gadolinium enhancement on MRI rapidly declined to baseline levels, TSPO tracer uptake followed a slow one phase decay curve. A TSPO-based 3D diagnostic matrix taking into account the uptake levels as well as the shape and texture of the TSPO signal differentiated >96% of PML and multiple sclerosis lesions. Indeed, treatment with rituximab after natalizumab-associated PML in three patients did not affect tracer uptake in the assigned PML lesions but reverted tracer uptake to baseline in the assigned active multiple sclerosis lesions. Taken together our study suggests that TSPO PET imaging can reveal CNS inflammation in natalizumab-associated PML. TSPO PET may facilitate longitudinal monitoring of disease activity and help to distinguish recurrent multiple sclerosis activity from PML progression.Abstract Progressive multifocal leukoencephalopathy (PML) is a severe infection of the CNS caused by the polyomavirus JC that can occur in multiple sclerosis patients treated with natalizumab. Clinical management of patients with natalizumab-associated PML is challenging not least because current imaging tools for the early detection, longitudinal monitoring and differential diagnosis of PML lesions are limited. Here we evaluate whether translocator protein (TSPO) PET imaging can be applied to monitor the inflammatory activity of PML lesions over time and differentiate them from multiple sclerosis lesions. For this monocentre pilot study we followed eight patients with natalizumab-associated PML with PET imaging using the TSPO radioligand 18F-GE-180 combined with frequent 3 T MRI. In addition we compared TSPO PET signals in PML lesions with the signal pattern of multiple sclerosis lesions from 17 independent multiple sclerosis patients. We evaluated the standardized uptake value ratio as well as the morphometry of the TSPO uptake for putative PML and multiple sclerosis lesions areas compared to a radiologically unaffected pseudo-reference region in the cerebrum. Furthermore, TSPO expression in situ was immunohistochemically verified by determining the density and cellular identity of TSPO-expressing cells in brain sections from four patients with early natalizumab-associated PML as well as five patients with other forms of PML and six patients with inflammatory demyelinating CNS lesions (clinically isolated syndrome/multiple sclerosis). Histological analysis revealed a reticular accumulation of TSPO expressing phagocytes in PML lesions, while such phagocytes showed a more homogeneous distribution in putative multiple sclerosis lesions. TSPO PET imaging showed an enhanced tracer uptake in natalizumab-associated PML lesions that was present from the early to the chronic stages (up to 52 months after PML diagnosis). While gadolinium enhancement on MRI rapidly declined to baseline levels, TSPO tracer uptake followed a slow one phase decay curve. A TSPO-based 3D diagnostic matrix taking into account the uptake levels as well as the shape and texture of the TSPO signal differentiated >96% of PML and multiple sclerosis lesions. Indeed, treatment with rituximab after natalizumab-associated PML in three patients did not affect tracer uptake in the assigned PML lesions but reverted tracer uptake to baseline in the assigned active multiple sclerosis lesions. Taken together our study suggests that TSPO PET imaging can reveal CNS inflammation in natalizumab-associated PML. TSPO PET may facilitate longitudinal monitoring of disease activity and help to distinguish recurrent multiple sclerosis activity from PML progression
Cognitive and functional deficits are associated with white matter abnormalities in two independent cohorts of patients with schizophrenia
No full textAbstract Background Significant evidence links white matter (WM) microstructural abnormalities to cognitive impairment in schizophrenia (SZ), but the relationship of these abnormalities with functional outcome remains unclear. Methods In two independent cohorts (C1, C2), patients with SZ were divided into two subgroups: patients with higher cognitive performance (SZ-HCP-C1, n = 25; SZ-HCP-C2, n = 24) and patients with lower cognitive performance (SZ-LCP-C1, n = 25; SZ-LCP-C2, n = 24). Healthy controls (HC) were included in both cohorts (HC-C1, n = 52; HC-C2, n = 27). We compared fractional anisotropy (FA) of the whole-brain WM skeleton between the three groups (SZ-LCP, SZ-HCP, HC) by a whole-brain exploratory approach and an atlas-defined WM regions-of-interest approach via tract-based spatial statistics. In addition, we explored whether FA values were associated with Global Assessment of Functioning (GAF) scores in the SZ groups. Results In both cohorts, mean FA values of whole-brain WM skeleton were significantly lower in the SCZ-LCP group than in the SCZ-HCP group. Whereas in C1 the FA of the frontal part of the left inferior fronto-occipital fasciculus (IFOF) was positively correlated with GAF score, in C2 the FA of the temporal part of the left IFOF was positively correlated with GAF score. Conclusions We provide robust evidence for WM microstructural abnormalities in SZ. These abnormalities are more prominent in patients with low cognitive performance and are associated with the level of functioning.Abstract Background Significant evidence links white matter (WM) microstructural abnormalities to cognitive impairment in schizophrenia (SZ), but the relationship of these abnormalities with functional outcome remains unclear. Methods In two independent cohorts (C1, C2), patients with SZ were divided into two subgroups: patients with higher cognitive performance (SZ-HCP-C1, n = 25; SZ-HCP-C2, n = 24) and patients with lower cognitive performance (SZ-LCP-C1, n = 25; SZ-LCP-C2, n = 24). Healthy controls (HC) were included in both cohorts (HC-C1, n = 52; HC-C2, n = 27). We compared fractional anisotropy (FA) of the whole-brain WM skeleton between the three groups (SZ-LCP, SZ-HCP, HC) by a whole-brain exploratory approach and an atlas-defined WM regions-of-interest approach via tract-based spatial statistics. In addition, we explored whether FA values were associated with Global Assessment of Functioning (GAF) scores in the SZ groups. Results In both cohorts, mean FA values of whole-brain WM skeleton were significantly lower in the SCZ-LCP group than in the SCZ-HCP group. Whereas in C1 the FA of the frontal part of the left inferior fronto-occipital fasciculus (IFOF) was positively correlated with GAF score, in C2 the FA of the temporal part of the left IFOF was positively correlated with GAF score. Conclusions We provide robust evidence for WM microstructural abnormalities in SZ. These abnormalities are more prominent in patients with low cognitive performance and are associated with the level of functioning
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
CTLA4 as Immunological Checkpoint in the Development of Multiple Sclerosis
No full textWe investigated a patient who developed multiple sclerosis (MS) during treatment with the CTLA4-blocking antibody ipilimumab for metastatic melanoma. Initially he showed subclinical magnetic resonance imaging (MRI) changes (radiologically isolated syndrome). Two courses of ipilimumab were each followed by a clinical episode of MS, 1 of which was accompanied by a massive increase of MRI activity. Brain biopsy confirmed active, T-cell type MS. Quantitative next generation sequencing of T-cell receptor genes revealed distinct oligoclonal CD4(+) and CD8(+) T-cell repertoires in the primary melanoma and cerebrospinal fluid. Our results pinpoint the coinhibitory molecule CTLA4 as an immunological checkpoint and therapeutic target in MS
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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