Machine-learning-aided prediction of brain metastases development in non-small-cell lung cancers

Purpose Non–small-cell lung cancer (NSCLC) shows a high incidence of brain metastases (BM). Early detection is crucial to improve clinical prospects. We trained and validated classifier models to identify patients with a high risk of developing BM, as they could potentially benefit from surveillance brain MRI. Methods Consecutive patients with an initial diagnosis of NSCLC from January 2011 to April 2019 and an in-house chest-CT scan (staging) were retrospectively recruited at a German lung cancer center. Brain imaging was performed at initial diagnosis and in case of neurological symptoms (follow-up). Subjects lost to follow-up or still alive without BM at the data cut-off point (12/2020) were excluded. Covariates included clinical and/or 3D-radiomics-features of the primary tumor from staging chest-CT. Four machine learning models for prediction (80/20 training) were compared. Gini Importance and SHAP were used as measures of importance; sensitivity, specificity, area under the precision-recall curve, and Matthew's Correlation Coefficient as evaluation metrics. Results Three hundred and ninety-five patients compromised the clinical cohort. Predictive models based on clinical features offered the best performance (tuned to maximize recall: sensitivity∼70%, specificity∼60%). Radiomics features failed to provide sufficient information, likely due to the heterogeneity of imaging data. Adenocarcinoma histology, lymph node invasion, and histological tumor grade were positively correlated with the prediction of BM, age, and squamous cell carcinoma histology were negatively correlated. A subgroup discovery analysis identified 2 candidate patient subpopulations appearing to present a higher risk of BM (female patients + adenocarcinoma histology, adenocarcinoma patients + no other distant metastases). Conclusion Analysis of the importance of input features suggests that the models are learning the relevant relationships between clinical features/development of BM. A higher number of samples is to be prioritized to improve performance. Employed prospectively at initial diagnosis, such models can help select high-risk subgroups for surveillance brain MRI

Cancellous bone and theropod dinosaur locomotion. Part I—an examination of cancellous bone architecture in the hindlimb bones of theropods

This paper is the first of a three-part series that investigates the architecture of cancellous (‘spongy’) bone in the main hindlimb bones of theropod dinosaurs, and uses cancellous bone architectural patterns to infer locomotor biomechanics in extinct non-avian species. Cancellous bone is widely known to be highly sensitive to its mechanical environment, and has previously been used to infer locomotor biomechanics in extinct tetrapod vertebrates, especially primates. Despite great promise, cancellous bone architecture has remained little utilized for investigating locomotion in many other extinct vertebrate groups, such as dinosaurs. Documentation and quantification of architectural patterns across a whole bone, and across multiple bones, can provide much information on cancellous bone architectural patterns and variation across species. Additionally, this also lends itself to analysis of the musculoskeletal biomechanical factors involved in a direct, mechanistic fashion. On this premise, computed tomographic and image analysis techniques were used to describe and analyse the three-dimensional architecture of cancellous bone in the main hindlimb bones of theropod dinosaurs for the first time. A comprehensive survey across many extant and extinct species is produced, identifying several patterns of similarity and contrast between groups. For instance, more stemward non-avian theropods (e.g. ceratosaurs and tyrannosaurids) exhibit cancellous bone architectures more comparable to that present in humans, whereas species more closely related to birds (e.g. paravians) exhibit architectural patterns bearing greater similarity to those of extant birds. Many of the observed patterns may be linked to particular aspects of locomotor biomechanics, such as the degree of hip or knee flexion during stance and gait. A further important observation is the abundance of markedly oblique trabeculae in the diaphyses of the femur and tibia of birds, which in large species produces spiralling patterns along the endosteal surface. Not only do these observations provide new insight into theropod anatomy and behaviour, they also provide the foundation for mechanistic testing of locomotor hypotheses via musculoskeletal biomechanical modelling

Growth, assembly and collective integration of ZnO nanowires : application to biosensing

Les réseaux bidimensionnels de nanofils (NFs) d’oxyde de zinc (ZnO) aléatoirement orientés, ou nanonets (pour « nanowire networks »), constituent des nanostructures innovantes et prometteuses pour de nombreuses applications. L’objectif de cette thèse est de développer des nanonets de ZnO en vue d’applications à la détection de molécules biologiques ou gazeuses, en particulier de l’ADN, ceci selon une procédure bas coût et industrialisable. Dans ce but, il est essentiel de bien maitriser les différentes étapes d’élaboration qui sont : (i) le dépôt de couches minces de germination de ZnO sur des substrats de silicium par voie sol-gel, (ii) la croissance de NFs de ZnO sur ces couches de germination par synthèse hydrothermale, et (iii) l’assemblage par filtration sous vide de ces NFs en nanonets de ZnO. Des études approfondies de chacun de ces procédés ont donc été menées. Ces travaux ont permis d’élaborer des couches minces, des NFs et des nanonets de ZnO reproductibles et homogènes dont les propriétés morphologiques sont précisément contrôlées sur une large gamme. Deux protocoles de biofonctionnalisation des nanonets avec de l’ADN ont ensuite été développés et ont abouti à des résultats encourageants mais restant à optimiser. Les nanonets ont également été intégrés au sein de dispositifs fonctionnels et les premières caractérisations électriques ont fourni des résultats prometteurs. A terme, ce travail ouvre la voie à l’intégration collective de NFs de ZnO qui permettrait la réalisation d’une nouvelle génération de capteurs (de biomolécules, de gaz…) à la fois portables, rapides et très sensibles.Two-dimensional randomly oriented zinc oxide (ZnO) nanowire (NW) networks, or nanonets, represent innovative and promising nanostructures for numerous applications. The objective of this thesis is to develop ZnO nanonets for the detection of biological or gaseous molecules, in particular DNA, by using a low cost and scalable procedure. To this end, it is essential to control the different elaboration steps which are: (i) the deposition of ZnO seed layer films on silicon substrates by sol-gel approach, (ii) the growth of ZnO NWs on these seed layer films by hydrothermal synthesis, and (iii) the assembly of these NWs into ZnO nanonets by vacuum filtration. In-depth studies of each of these processes were thus carried out. This work enabled to elaborate reproducible and homogenous ZnO thin films, NWs and nanonets whose morphological properties are precisely controlled over a wide range. Two DNA biofunctionnalization protocols were then developed for the nanonets and led to encouraging results which need however to be further optimized. The nanonets were also integrated into functional devices and the first electrical characterizations provided promising results. In the longer term, this work opens the way to the collective integration of ZnO NWs which would enable the development of a new generation of portable, fast and ultra-sensitive (bio- or gas-) sensors

Croissance, assemblage et intégration collective de nanofils de ZnO : application à la biodétection

Two-dimensional randomly oriented zinc oxide (ZnO) nanowire (NW) networks, or nanonets, represent innovative and promising nanostructures for numerous applications. The objective of this thesis is to develop ZnO nanonets for the detection of biological or gaseous molecules, in particular DNA, by using a low cost and scalable procedure. To this end, it is essential to control the different elaboration steps which are: (i) the deposition of ZnO seed layer films on silicon substrates by sol-gel approach, (ii) the growth of ZnO NWs on these seed layer films by hydrothermal synthesis, and (iii) the assembly of these NWs into ZnO nanonets by vacuum filtration. In-depth studies of each of these processes were thus carried out. This work enabled to elaborate reproducible and homogenous ZnO thin films, NWs and nanonets whose morphological properties are precisely controlled over a wide range. Two DNA biofunctionnalization protocols were then developed for the nanonets and led to encouraging results which need however to be further optimized. The nanonets were also integrated into functional devices and the first electrical characterizations provided promising results. In the longer term, this work opens the way to the collective integration of ZnO NWs which would enable the development of a new generation of portable, fast and ultra-sensitive (bio- or gas-) sensors.Les réseaux bidimensionnels de nanofils (NFs) d’oxyde de zinc (ZnO) aléatoirement orientés, ou nanonets (pour « nanowire networks »), constituent des nanostructures innovantes et prometteuses pour de nombreuses applications. L’objectif de cette thèse est de développer des nanonets de ZnO en vue d’applications à la détection de molécules biologiques ou gazeuses, en particulier de l’ADN, ceci selon une procédure bas coût et industrialisable. Dans ce but, il est essentiel de bien maitriser les différentes étapes d’élaboration qui sont : (i) le dépôt de couches minces de germination de ZnO sur des substrats de silicium par voie sol-gel, (ii) la croissance de NFs de ZnO sur ces couches de germination par synthèse hydrothermale, et (iii) l’assemblage par filtration sous vide de ces NFs en nanonets de ZnO. Des études approfondies de chacun de ces procédés ont donc été menées. Ces travaux ont permis d’élaborer des couches minces, des NFs et des nanonets de ZnO reproductibles et homogènes dont les propriétés morphologiques sont précisément contrôlées sur une large gamme. Deux protocoles de biofonctionnalisation des nanonets avec de l’ADN ont ensuite été développés et ont abouti à des résultats encourageants mais restant à optimiser. Les nanonets ont également été intégrés au sein de dispositifs fonctionnels et les premières caractérisations électriques ont fourni des résultats prometteurs. A terme, ce travail ouvre la voie à l’intégration collective de NFs de ZnO qui permettrait la réalisation d’une nouvelle génération de capteurs (de biomolécules, de gaz…) à la fois portables, rapides et très sensibles

Study of sol-gel ZnO thin films – A 1st step toward ZnO nanowire growth and their integration into DNA biosensors

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ZnO nanowire networks: Fabrication and application to label-free electrical DNA biosensors

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Comprehensive study of ZnO nanowires grown by hydrothermal synthesis

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Comprehensive study of hydrothermally grown ZnO nanowires

International audienceA hydrothermal procedure has been implemented to grow single-crystal ZnO nanowires (NWs) on sol–gel deposited seed layers. The main characteristics (diameter, length, and aspect ratio) of derived NWs have been studied by scanning electron microscopy in relation to morphological and structural properties of the ZnO films (mean grain size, surface coverage rate, and texture coefficient) and growth process parameters (growth duration and multi-growth procedure). It is shown how suitable combinations arising from the influence of the seed layer properties, growths of various durations, and implementation of a multi-growth process enable to finely tune the NW characteristics in a large range of values, i.e., a diameter, length, and aspect ratio varying in the 30–225 nm, 1.0–9.0 µm, and 30–50 ranges, respectively. On the basis of investigated experimental conditions, a simple model is developed that suitably describes the NW crystal growth as a function of the seed layer properties and growth duration. According to this model, lateral and longitudinal growth rates of around 0.01 nm/min and 25–30 nm/min, respectively, are extracted from experimental data and a minimal NW diameter of around 20 nm is predicted

Etude de la croissance de n anofils de ZnO par synthèse hydrothermale : une 1ère étape vers la réalisation de biocapteurs d’ADN électriques sans marqueurs à base de réseaux de nanofils de ZnO

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ZnO nanonets: functional nanomateials designed for electrical detection

Session sensing (Highlight)International audienc