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Article ; Online: Low-Cost UWB Based Real-Time Locating System: Development, Lab Test, Industrial Implementation and Economic Assessment.

Volpi, Andrea / Tebaldi, Letizia / Matrella, Guido / Montanari, Roberto / Bottani, Eleonora

2023 Volume 23, Issue 3

Abstract: This paper presents the technical development and subsequent testing of a Real-Time Locating System based on Ultra-Wideband signals, with the aim to appraise its potential implementation in a real industrial case. The system relies on a commercial Radio ... ...

Abstract	This paper presents the technical development and subsequent testing of a Real-Time Locating System based on Ultra-Wideband signals, with the aim to appraise its potential implementation in a real industrial case. The system relies on a commercial Radio Indoor Positioning System, called Qorvo MDEK1001, which makes use of UWB RF technology to determine the position of RF-tags placed on an item of interest, which in turn is located in an area covered by specific fixed antennas (anchors). Testing sessions were carried out both in an Italian laboratory and in a real industrial environment, to determine the best configurations according to some selected performance indicators. The results support the adoption of the proposed solution in industrial environments to track assets and work in progress. Moreover, most importantly, the solution developed is cheap in nature: indeed, normally tracking solutions involve a huge investment, quite often not affordable above all by small-, medium- and micro-sized enterprises. The proposed low-cost solution instead, as demonstrated by the economic assessment completing the work, justifies the feasibility of the investment. Hence, results of this paper ultimately constitute a guidance for those practitioners who intend to adopt a similar system in their business.
Language	English
Publishing date	2023-01-18
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2052857-7
ISSN	1424-8220 ; 1424-8220
ISSN (online)	1424-8220
ISSN	1424-8220
DOI	10.3390/s23031124
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Article ; Online: Evaluation of MRI-based machine learning approaches for computer-aided diagnosis of dementia in a clinical data warehouse.

Bottani, Simona / Burgos, Ninon / Maire, Aurélien / Saracino, Dario / Ströer, Sebastian / Dormont, Didier / Colliot, Olivier

Medical image analysis

2023 Volume 89, Page(s) 102903

Abstract: A variety of algorithms have been proposed for computer-aided diagnosis of dementia from anatomical brain MRI. These approaches achieve high accuracy when applied to research data sets but their performance on real-life clinical routine data has not been ...

Abstract	A variety of algorithms have been proposed for computer-aided diagnosis of dementia from anatomical brain MRI. These approaches achieve high accuracy when applied to research data sets but their performance on real-life clinical routine data has not been evaluated yet. The aim of this work was to study the performance of such approaches on clinical routine data, based on a hospital data warehouse, and to compare the results to those obtained on a research data set. The clinical data set was extracted from the hospital data warehouse of the Greater Paris area, which includes 39 different hospitals. The research set was composed of data from the Alzheimer's Disease Neuroimaging Initiative data set. In the clinical set, the population of interest was identified by exploiting the diagnostic codes from the 10th revision of the International Classification of Diseases that are assigned to each patient. We studied how the imbalance of the training sets, in terms of contrast agent injection and image quality, may bias the results. We demonstrated that computer-aided diagnosis performance was strongly biased upwards (over 17 percent points of balanced accuracy) by the confounders of image quality and contrast agent injection, a phenomenon known as the Clever Hans effect or shortcut learning. When these biases were removed, the performance was very poor. In any case, the performance was considerably lower than on the research data set. Our study highlights that there are still considerable challenges for translating dementia computer-aided diagnosis systems to clinical routine.
MeSH term(s)	Humans ; Contrast Media ; Data Warehousing ; Brain/diagnostic imaging ; Magnetic Resonance Imaging/methods ; Alzheimer Disease/diagnostic imaging ; Machine Learning ; Computers
Chemical Substances	Contrast Media
Language	English
Publishing date	2023-07-17
Publishing country	Netherlands
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	1356436-5
ISSN	1361-8423 ; 1361-8431 ; 1361-8415
ISSN (online)	1361-8423 ; 1361-8431
ISSN	1361-8415
DOI	10.1016/j.media.2023.102903
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Article ; Online: Automatic motion artefact detection in brain T1-weighted magnetic resonance images from a clinical data warehouse using synthetic data.

Loizillon, Sophie / Bottani, Simona / Maire, Aurélien / Ströer, Sebastian / Dormont, Didier / Colliot, Olivier / Burgos, Ninon

Medical image analysis

2023 Volume 93, Page(s) 103073

Abstract: Containing the medical data of millions of patients, clinical data warehouses (CDWs) represent a great opportunity to develop computational tools. Magnetic resonance images (MRIs) are particularly sensitive to patient movements during image acquisition, ... ...

Abstract	Containing the medical data of millions of patients, clinical data warehouses (CDWs) represent a great opportunity to develop computational tools. Magnetic resonance images (MRIs) are particularly sensitive to patient movements during image acquisition, which will result in artefacts (blurring, ghosting and ringing) in the reconstructed image. As a result, a significant number of MRIs in CDWs are corrupted by these artefacts and may be unusable. Since their manual detection is impossible due to the large number of scans, it is necessary to develop tools to automatically exclude (or at least identify) images with motion in order to fully exploit CDWs. In this paper, we propose a novel transfer learning method from research to clinical data for the automatic detection of motion in 3D T1-weighted brain MRI. The method consists of two steps: a pre-training on research data using synthetic motion, followed by a fine-tuning step to generalise our pre-trained model to clinical data, relying on the labelling of 4045 images. The objectives were both (1) to be able to exclude images with severe motion, (2) to detect mild motion artefacts. Our approach achieved excellent accuracy for the first objective with a balanced accuracy nearly similar to that of the annotators (balanced accuracy>80 %). However, for the second objective, the performance was weaker and substantially lower than that of human raters. Overall, our framework will be useful to take advantage of CDWs in medical imaging and highlight the importance of a clinical validation of models trained on research data.
MeSH term(s)	Humans ; Artifacts ; Data Warehousing ; Motion ; Brain/diagnostic imaging ; Magnetic Resonance Imaging
Language	English
Publishing date	2023-12-23
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1356436-5
ISSN	1361-8423 ; 1361-8431 ; 1361-8415
ISSN (online)	1361-8423 ; 1361-8431
ISSN	1361-8415
DOI	10.1016/j.media.2023.103073
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Article ; Online: Contrast-enhanced to non-contrast-enhanced image translation to exploit a clinical data warehouse of T1-weighted brain MRI.

Bottani, Simona / Thibeau-Sutre, Elina / Maire, Aurélien / Ströer, Sebastian / Dormont, Didier / Colliot, Olivier / Burgos, Ninon

BMC medical imaging

2024 Volume 24, Issue 1, Page(s) 67

Abstract: Background: Clinical data warehouses provide access to massive amounts of medical images, but these images are often heterogeneous. They can for instance include images acquired both with or without the injection of a gadolinium-based contrast agent. ... ...

Abstract	Background: Clinical data warehouses provide access to massive amounts of medical images, but these images are often heterogeneous. They can for instance include images acquired both with or without the injection of a gadolinium-based contrast agent. Harmonizing such data sets is thus fundamental to guarantee unbiased results, for example when performing differential diagnosis. Furthermore, classical neuroimaging software tools for feature extraction are typically applied only to images without gadolinium. The objective of this work is to evaluate how image translation can be useful to exploit a highly heterogeneous data set containing both contrast-enhanced and non-contrast-enhanced images from a clinical data warehouse. Methods: We propose and compare different 3D U-Net and conditional GAN models to convert contrast-enhanced T1-weighted (T1ce) into non-contrast-enhanced (T1nce) brain MRI. These models were trained using 230 image pairs and tested on 77 image pairs from the clinical data warehouse of the Greater Paris area. Results: Validation using standard image similarity measures demonstrated that the similarity between real and synthetic T1nce images was higher than between real T1nce and T1ce images for all the models compared. The best performing models were further validated on a segmentation task. We showed that tissue volumes extracted from synthetic T1nce images were closer to those of real T1nce images than volumes extracted from T1ce images. Conclusion: We showed that deep learning models initially developed with research quality data could synthesize T1nce from T1ce images of clinical quality and that reliable features could be extracted from the synthetic images, thus demonstrating the ability of such methods to help exploit a data set coming from a clinical data warehouse.
MeSH term(s)	Humans ; Data Warehousing ; Gadolinium ; Brain/diagnostic imaging ; Magnetic Resonance Imaging/methods ; Neuroimaging/methods ; Image Processing, Computer-Assisted/methods
Chemical Substances	Gadolinium (AU0V1LM3JT)
Language	English
Publishing date	2024-03-20
Publishing country	England
Document type	Journal Article
ZDB-ID	2061975-3
ISSN	1471-2342 ; 1471-2342
ISSN (online)	1471-2342
ISSN	1471-2342
DOI	10.1186/s12880-024-01242-3
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Article ; Online: Myasthenia Gravis Treatment: From Old Drugs to Innovative Therapies with a Glimpse into the Future.

Crisafulli, Salvatore / Boccanegra, Brigida / Carollo, Massimo / Bottani, Emanuela / Mantuano, Paola / Trifirò, Gianluca / De Luca, Annamaria

CNS drugs

2024 Volume 38, Issue 1, Page(s) 15–32

Abstract: Myasthenia gravis (MG) is a rare autoimmune disease that causes debilitating muscle weakness due to impaired neuromuscular transmission. Since most (about 80-90%) MG patients present autoantibodies against the acetylcholine receptor, standard medical ... ...

Abstract	Myasthenia gravis (MG) is a rare autoimmune disease that causes debilitating muscle weakness due to impaired neuromuscular transmission. Since most (about 80-90%) MG patients present autoantibodies against the acetylcholine receptor, standard medical therapy consists of symptomatic treatment with acetylcholinesterase inhibitors (e.g., pyridostigmine). In addition, considering the autoimmune basis of MG, standard therapy includes immunomodulating agents, such as corticosteroids, azathioprine, cyclosporine A, and cyclophosphamide. New strategies have been proposed for the treatment of MG and include complement blockade (i.e., eculizumab, ravulizumab, and zilucoplan) and neonatal Fc receptor antagonism (i.e., efgartigimod and rozanolixizumab). The aim of this review is to provide a detailed overview of the pre- and post-marketing evidence on the five pharmacological treatments most recently approved for the treatment of MG, by identifying both preclinical and clinical studies registered in clinicaltrials.gov. A description of the molecules currently under evaluation for the treatment of MG is also provided.
MeSH term(s)	Humans ; Infant, Newborn ; Acetylcholinesterase/therapeutic use ; Adrenal Cortex Hormones/therapeutic use ; Autoantibodies ; Myasthenia Gravis/drug therapy ; Receptors, Cholinergic/therapeutic use ; Therapies, Investigational
Chemical Substances	Acetylcholinesterase (EC 3.1.1.7) ; Adrenal Cortex Hormones ; Autoantibodies ; Receptors, Cholinergic
Language	English
Publishing date	2024-01-11
Publishing country	New Zealand
Document type	Journal Article ; Review
ZDB-ID	1203800-3
ISSN	1179-1934 ; 1172-7047
ISSN (online)	1179-1934
ISSN	1172-7047
DOI	10.1007/s40263-023-01059-8
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Article: Mitochondrial Dysfunction in Peripheral Blood Mononuclear Cells as Novel Diagnostic Tools for Non-Alcoholic Fatty Liver Disease: Visualizing Relationships with Known and Potential Disease Biomarkers.

Garrafa, Emirena / Segala, Agnese / Vezzoli, Marika / Bottani, Emanuela / Zanini, Barbara / Vetturi, Alice / Bracale, Renata / Ricci, Chiara / Valerio, Alessandra

Diagnostics (Basel, Switzerland)

2023 Volume 13, Issue 14

Abstract: Non-alcoholic fatty liver disease (NAFLD) is a health emergency worldwide due to its high prevalence and the lack of specific therapies. Noninvasive biomarkers supporting NAFLD diagnosis are urgently needed. Liver mitochondrial dysfunction is a central ... ...

Abstract	Non-alcoholic fatty liver disease (NAFLD) is a health emergency worldwide due to its high prevalence and the lack of specific therapies. Noninvasive biomarkers supporting NAFLD diagnosis are urgently needed. Liver mitochondrial dysfunction is a central NAFLD pathomechanism that changes throughout disease progression. Blood-cell bioenergetics reflecting mitochondrial organ dysfunction is emerging for its potential applications in diagnostics. We measured real-time mitochondrial respirometry in peripheral blood mononuclear cells (PBMCs), anthropometric parameters, routine blood analytes, and circulating cytokines from a cohort of NAFLD patients (N = 19) and non-NAFLD control subjects (N = 18). PBMC basal respiration, ATP-linked respiration, maximal respiration, and spare respiratory capacity were significantly reduced in NAFLD compared to non-NAFLD cases. Correlation plots were applied to visualize relationships between known or potential NAFLD-related biomarkers, while non-parametric methods were applied to identify which biomarkers are NAFLD predictors. Basal and ATP-linked mitochondrial respiration were negatively correlated with triglycerides and fasting insulin levels and HOMA index. Maximal and spare respiratory capacity were negatively correlated with IL-6 levels. All the mitochondrial respiratory parameters were positively correlated with HDL-cholesterol level and negatively correlated with fatty liver index. We propose including blood cell respirometry in panels of NAFLD diagnostic biomarkers to monitor disease progression and the response to current and novel therapies, including mitochondrial-targeted ones.
Language	English
Publishing date	2023-07-13
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662336-5
ISSN	2075-4418
ISSN	2075-4418
DOI	10.3390/diagnostics13142363
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Article: Gene Therapy for Mitochondrial Diseases: Current Status and Future Perspective.

Di Donfrancesco, Alessia / Massaro, Giulia / Di Meo, Ivano / Tiranti, Valeria / Bottani, Emanuela / Brunetti, Dario

Pharmaceutics

2022 Volume 14, Issue 6

Abstract: Mitochondrial diseases (MDs) are a group of severe genetic disorders caused by mutations in the nuclear or mitochondrial genome encoding proteins involved in the oxidative phosphorylation (OXPHOS) system. MDs have a wide range of symptoms, ranging from ... ...

Abstract	Mitochondrial diseases (MDs) are a group of severe genetic disorders caused by mutations in the nuclear or mitochondrial genome encoding proteins involved in the oxidative phosphorylation (OXPHOS) system. MDs have a wide range of symptoms, ranging from organ-specific to multisystemic dysfunctions, with different clinical outcomes. The lack of natural history information, the limits of currently available preclinical models, and the wide range of phenotypic presentations seen in MD patients have all hampered the development of effective therapies. The growing number of pre-clinical and clinical trials over the last decade has shown that gene therapy is a viable precision medicine option for treating MD. However, several obstacles must be overcome, including vector design, targeted tissue tropism and efficient delivery, transgene expression, and immunotoxicity. This manuscript offers a comprehensive overview of the state of the art of gene therapy in MD, addressing the main challenges, the most feasible solutions, and the future perspectives of the field.
Language	English
Publishing date	2022-06-17
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527217-2
ISSN	1999-4923
ISSN	1999-4923
DOI	10.3390/pharmaceutics14061287
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Article ; Online: Macular dystrophy in Kabuki syndrome due to de novo KMT2D variants: refining the phenotype with multimodal imaging and follow-up over 10 years: insight into pathophysiology.

Vaclavik, Veronika / Navarro, Aurelie / Jacot-Guillarmod, Alain / Bottani, Armand / Sun, Young Joo / Franco, Joel A / Mahajan, Vinit B / Smirnov, Vasily / Bouvet-Drumare, Isabelle

Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie

2024

Abstract: Background: Kabuki Syndrome is a rare and genetically heterogenous condition with both ophthalmic and systemic complications and typical facial features. We detail the macular phenotype in two unrelated patients with Kabuki syndrome due to de novo ... ...

Abstract	Background: Kabuki Syndrome is a rare and genetically heterogenous condition with both ophthalmic and systemic complications and typical facial features. We detail the macular phenotype in two unrelated patients with Kabuki syndrome due to de novo nonsense variants in KMT2D, one novel. A follow-up of 10 years is reported. Pathogenicity of both de novo nonsense variants is analyzed. Methods: Four eyes of two young patients were studied by full clinical examination, kinetic perimetry, short wavelength autofluorescence, full field (ff) ERGs, and spectral-domain optical coherence tomography (SD-OCT). One patient had adaptive optic (AO) imaging. Whole exome sequencing was performed in both patients. Results: Both patients had de novo nonsense variants in KMTD2. One patient had c.14843C>G; p. (Ser4948ter) novel variant and the second c.11119C>T; p. (Arg3707ter). Both had a stable Snellen visual acuity of 0.2-0.3. The retinal multimodal imaging demonstrated abnormalities at the fovea in both eyes: hyperreflectivity to blue light and a well-delimited gap-disruption of ellipsoid and interdigitation layer on OCT. The dark area on AO imaging is presumed to be absent for, or with structural change to photoreceptors. The ff ERGs and kinetic visual fields were normal. The foveal findings remained stable over several years. Conclusion: Kabuki syndrome-related maculopathy is a distinct loss of photoreceptors at the fovea as shown by multimodal imaging including, for the first time, AO imaging. This report adds to the literature of only one case with maculopathy with two additional macular dystrophies in patients with Kabuki syndrome. Although underestimated, these cases further raise awareness of the potential impact of retinal manifestations of Kabuki syndrome not only among ophthalmologists but also other healthcare professionals involved in the care of patients with this multisystem disorder.
Language	English
Publishing date	2024-01-11
Publishing country	Germany
Document type	Journal Article
ZDB-ID	8435-9
ISSN	1435-702X ; 0721-832X
ISSN (online)	1435-702X
ISSN	0721-832X
DOI	10.1007/s00417-023-06345-1
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Article ; Online: Hill function-based models of transcriptional switches: impact of specific, nonspecific, functional and nonfunctional binding.

Bottani, Samuel / Veitia, Reiner A

Biological reviews of the Cambridge Philosophical Society

2017 Volume 92, Issue 2, Page(s) 953–963

Abstract: We explore minimalist models of transcription in which we take into account that a cis-regulatory sequence is embedded in, and interacts with, a complex genome. The classical Hill equation is the simplest way to represent a transcriptional response. ... ...

Abstract	We explore minimalist models of transcription in which we take into account that a cis-regulatory sequence is embedded in, and interacts with, a complex genome. The classical Hill equation is the simplest way to represent a transcriptional response. However, it may overlook the fact that a transcription factor (TF) establishes specific and nonspecific nonfunctional interactions with chromatin. Classical papers have shown that nonfunctional binding (not leading to transcription) may influence gene expression. We examine how the presence of additional binding sites for a TF, besides those on the gene(s) of interest, affect the shape and parameters of the transcriptional response. We consider two conditions: at equilibrium and at steady-state. In many cases the TF level is determined by the position of the cell within a spatial or temporal gradient. We show that such gradients can be adjusted by evolutionary selection to compensate for the alteration of the gene transcription response by the presence of nonfunctional binding sites. Finally, we analyse how the transcriptional response is affected by a decrease in TF concentration, as in cases of haploinsufficiency. We show that the nonlinearity of the transcriptional response as a function of [TF] exacerbates the effect of a decrease in the latter, at least for weakly expressed TFs. Although decades of work on TFs have led to the impression that almost everything is known about the control of gene expression, we show that even the simplest models of transcription control have not delivered all their secrets yet.
Language	English
Publishing date	2017-05
Publishing country	England
Document type	Journal Article
ZDB-ID	1423558-4
ISSN	1469-185X ; 0006-3231 ; 1464-7931
ISSN (online)	1469-185X
ISSN	0006-3231 ; 1464-7931
DOI	10.1111/brv.12262
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Article ; Online: Generation of mouse hippocampal brain organoids from primary embryonic neural stem cells.

Ciarpella, Francesca / Zamfir, Raluca Georgiana / Campanelli, Alessandra / Pedrotti, Giulia / Di Chio, Marzia / Bottani, Emanuela / Decimo, Ilaria

STAR protocols

2023 Volume 4, Issue 3, Page(s) 102413

Abstract: Here we present a protocol to generate standardized cerebral organoids with hippocampal regional specification using morphogen WNT3a. We describe steps for isolating mouse embryonic (E14.5) neural stem cells from the brain subgranular zone, preparing ... ...

Abstract	Here we present a protocol to generate standardized cerebral organoids with hippocampal regional specification using morphogen WNT3a. We describe steps for isolating mouse embryonic (E14.5) neural stem cells from the brain subgranular zone, preparing organoids samples for immunofluorescence, calcium imaging, and metabolic profiling. This protocol can be used to generate mouse brain organoids for developmental studies, modeling disease, and drug screening. Organoids can be obtained in one month, thus providing a rapid tool for high-throughput data validation. For complete details on the use and execution of this protocol, please refer to Ciarpella et al. "Murine cerebral organoids develop network of functional neurons and hippocampal brain region identity".
MeSH term(s)	Animals ; Mice ; Neural Stem Cells ; Neurons ; Hippocampus ; Brain ; Organoids
Language	English
Publishing date	2023-07-15
Publishing country	United States
Document type	Journal Article
ISSN	2666-1667
ISSN (online)	2666-1667
DOI	10.1016/j.xpro.2023.102413
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