Molecular characterization of diffuse large B-cell lymphomas associated with hepatitis C virus infection.

Hepatitis C virus (HCV)-associated diffuse large B-cell lymphoma (DLBCL) displays peculiar clinicopathological characteristics, but its molecular landscape is not fully elucidated. In this study, we investigated the clinicopathological and molecular features of 54 patients with HCV-associated DLBCL. The median age was 71 years. An underlying marginal zone lymphoma component was detected in 14.8% of cases. FISH analysis showed rearrangements involving BCL6 in 50.9% of cases, MYC in 11.3% and BCL2 in 3.7%. Lymph2Cx-based assay was successful in 38 cases, recognizing 16 cases (42.1%) as ABC and 16 cases as GCB subtypes, while six resulted unclassified. ABC cases exhibited a higher lymphoma-related mortality (LRM). Next-generation sequencing analysis showed mutations in 158/184 evaluated genes. The most frequently mutated genes were KMT2D (42.6%), SETD1B (33.3%), RERE (29.4%), FAS and PIM1 (27.8%) and TBL1XR1 (25.9%). A mutation in the NOTCH pathway was detected in 25.9% of cases and was associated with worst LRM. Cluster analysis by LymphGen classified 29/54 cases within definite groups, including BN2 in 14 (48.2%), ST2 in seven (24.2%) and MCD and EZB in four each (13.8%). Overall, these results indicate a preferential marginal zone origin for a consistent subgroup of HCV-associated DLBCL cases and suggest potential implications for molecularly targeted therapies.

Monitoring Flexions and Torsions of the Trunk via Gyroscope-Calibrated Capacitive Elastomeric Wearable Sensors.

Reliable, easy-to-use, and cost-effective wearable sensors are desirable for continuous measurements of flexions and torsions of the trunk, in order to assess risks and prevent injuries related to body movements in various contexts. Piezo-capacitive stretch sensors, made of dielectric elastomer membranes coated with compliant electrodes, have recently been described as a wearable, lightweight and low-cost technology to monitor body kinematics. An increase of their capacitance upon stretching can be used to sense angular movements. Here, we report on a wearable wireless system that, using two sensing stripes arranged on shoulder straps, can detect flexions and torsions of the trunk, following a simple and fast calibration with a conventional tri-axial gyroscope on board. The piezo-capacitive sensors avoid the errors that would be introduced by continuous sensing with a gyroscope, due to its typical drift. Relative to stereophotogrammetry (non-wearable standard system for motion capture), pure flexions and pure torsions could be detected by the piezo-capacitive sensors with a root mean square error of ~8° and ~12°, respectively, whilst for flexion and torsion components in compound movements, the error was ~13° and ~15°, respectively.

Wearable Detection of Trunk Flexions: Capacitive Elastomeric Sensors Compared to Inertial Sensors.

Continuous monitoring of flexions of the trunk via wearable sensors could help various types of workers to reduce risks associated with incorrect postures and movements. Stretchable piezo-capacitive elastomeric sensors based on dielectric elastomers have recently been described as a wearable, lightweight and cost-effective technology to monitor human kinematics. Their stretching causes an increase of capacitance, which can be related to angular movements. Here, we describe a wearable wireless system to detect flexions of the trunk, based on such sensors. In particular, we present: (i) a comparison of different calibration strategies for the capacitive sensors, using either an accelerometer or a gyroscope as an inclinometer; (ii) a comparison of the capacitive sensors' performance with those of the accelerometer and gyroscope; to that aim, the three types of sensors were evaluated relative to stereophotogrammetry. Compared to the gyroscope, the capacitive sensors showed a higher accuracy. Compared to the accelerometer, their performance was lower when used as quasi-static inclinometers but also higher in case of highly dynamic accelerations. This makes the capacitive sensors attractive as a complementary, rather than alternative, technology to inertial sensors.

Electrically tunable directional light scattering from soft thin membranes.

The possibility of electrically tuning the scattering of light from surfaces by dynamically varying their properties is desirable for controllable transparency devices and diffusion filters. As a difference from state-of-the-art approaches where scattering is changed isotropically, this paper presents the first smart-material-based technology enabling electrical modulations in a single or multiple directions, which can be selected dynamically. The effect is achieved from thin soft membranes with transparent PEDOT:PSS coatings, which are electrically deformed along a single or multiple axes, using dielectric elastomer actuation. Anisotropic scattering is induced by electrically tuning the formation of directional surface wrinkles. As a proof of concept, a bi-directional device is obtained by overlapping two 90°-shifted mono-directional layers that can be controlled independently. According to the activation of the layers, light can be scattered along either direction, as well as both of them. Prototypes made of an acrylic elastomer were demonstrated with mono- and bi-directional operations. Devices with a window-to-total area ratio of 1:4 also showed a maximum electrical reduction of optical transmittance from 75% to 4%. This functionality and possible extensions to more than two controllable directions suggest applicability as electrically controllable anisotropic light diffusers for dynamic light shaping, as well as tunable transparency surfaces.

How to Easily Make Self-Sensing Pneumatic Inverse Artificial Muscles.

Wearable mechatronics for powered orthoses, exoskeletons and prostheses require improved soft actuation systems acting as 'artificial muscles' that are capable of large strains, high stresses, fast response and self-sensing and that show electrically safe operation, low specific weight and large compliance. Among the diversity of soft actuation technologies under investigation, pneumatic devices have been the focus, during the last couple of decades, of renewed interest as an intrinsically soft artificial muscle technology, due to technological advances stimulated by applications in soft robotics. As of today, quite a few solutions are available to endow a pneumatic soft device with linear actuation and self-sensing ability, while also easily achieving these features with off-the-shelf materials and low-cost fabrication processes. Here, we describe a simple process to make self-sensing pneumatic actuators, which may be used as 'inverse artificial muscles', as, upon pressurisation, they elongate instead of contracting. They are made of an elastomeric tube surrounded by a plastic coil, which constrains radial expansions. As a novelty relative to the state of the art, the self-sensing ability was obtained with a piezoresistive stretch sensor shaped as a conductive elastomeric body along the tube's central axis. Moreover, we detail, also by means of video clips, a step-by-step manufacturing process, which uses off-the-shelf materials and simple procedures, so as to facilitate reproducibility.

Gold-Hydrogel Nanocomposites for High-Resolution Laser-Based 3D Printing of Scaffolds with SERS-Sensing Properties.

Although visible light-based stereolithography (SLA) represents an affordable technology for the rapid prototyping of 3D scaffolds for in vitro support of cells, its potential could be limited by the lack of functional photocurable biomaterials that can be SLA-structured at micrometric resolution. Even if innovative photocomposites showing biomimetic, bioactive, or biosensing properties have been engineered by loading inorganic particles into photopolymer matrices, main examples rely on UV-assisted extrusion-based low-resolution processes. Here, SLA-printable composites were obtained by mixing a polyethylene glycol diacrylate (PEGDA) hydrogel with multibranched gold nanoparticles (NPs). NPs were engineered to copolymerize with the PEGDA matrix by implementing a functionalization protocol involving covalent grafting of allylamine molecules that have C═C pendant moieties. The formulations of gold nanocomposites were tailored to achieve high-resolution fast prototyping of composite scaffolds via visible light-based SLA. Furthermore, it was demonstrated that, after mixing with a polymer and after laser structuring, gold NPs still retained their unique plasmonic properties and could be exploited for optical detection of analytes through surface-enhanced Raman spectroscopy (SERS). As a proof of concept, SERS-sensing performances of 3D printed plasmonic scaffolds were successfully demonstrated with a Raman probe molecule (e.g., 4-mercaptobenzoic acid) from the perspective of future extensions to real-time sensing of cell-specific markers released within cultures. Finally, biocompatibility tests preliminarily demonstrated that embedded NPs also played a key role by inducing physiological cell-cytoskeleton rearrangements, further confirming the potentialities of such hybrid nanocomposites as groundbreaking materials in laser-based bioprinting.

Soft robotic patterning of liquids.

Patterning of two or more liquids, either homogeneous in each phase or mixed with particles (including biological matter, such as cells and proteins), by controlling their flow dynamics, is relevant to several applications. Examples include dynamic spatial confinement of liquids in microfluidic systems (such as lab-on-a-chip and organ-on-a-chip devices) or structuring of polymers to modulate various properties (such as strength, conductivity, transparency and surface finishing). State-of-the-art strategies use various technologies, including positioners, shakers and acoustic actuators, which often combine limited versatility of mixing with significant inefficiency, energy consumption, and noise, as well as tendency to increase the temperature of the liquids. Here, we describe a new kind of robotic mixers of liquids, based on electro-responsive smart materials (dielectric elastomer actuators). We show for the first time how an efficient soft robotic device can be used to produce, via combinations of rotations and translations, various spatial patterns in liquids and maintain them stable for a few minutes. Moreover, we show that, as compared to a conventional orbital shaker, the new type of robotic device can mix liquids with a higher efficacy (~ 94% relative to ~ 80%, after 8 min of mixing) and with a significantly lower increase of the liquids' temperature (+ 1 °C relative to + 5 °C, after 6 h of mixing). This is especially beneficial when mixing should occur according to controllable spatial features and should involve temperature-sensitive matter (such as biological cells, proteins, pre-polymers and other thermolabile molecules).

Electrically Tunable Lenses: A Review.

Optical lenses with electrically controllable focal length are of growing interest, in order to reduce the complexity, size, weight, response time and power consumption of conventional focusing/zooming systems, based on glass lenses displaced by motors. They might become especially relevant for diverse robotic and machine vision-based devices, including cameras not only for portable consumer electronics (e.g. smart phones) and advanced optical instrumentation (e.g. microscopes, endoscopes, etc.), but also for emerging applications like small/micro-payload drones and wearable virtual/augmented-reality systems. This paper reviews the most widely studied strategies to obtain such varifocal "smart lenses", which can electrically be tuned, either directly or via electro-mechanical or electro-thermal coupling. Only technologies that ensure controllable focusing of multi-chromatic light, with spatial continuity (i.e. continuous tunability) in wavefronts and focal lengths, as required for visible-range imaging, are considered. Both encapsulated fluid-based lenses and fully elastomeric lenses are reviewed, ranging from proof-of-concept prototypes to commercially available products. They are classified according to the focus-changing principles of operation, and they are described and compared in terms of advantages and drawbacks. This systematic overview should help to stimulate further developments in the field.

LEAP Motion Technology and Psychology: A Mini-Review on Hand Movements Sensing for Neurodevelopmental and Neurocognitive Disorders.

Technological advancement is constantly evolving, and it is also developing in the mental health field. Various applications, often based on virtual reality, have been implemented to carry out psychological assessments and interventions, using innovative human-machine interaction systems. In this context, the LEAP Motion sensing technology has raised interest, since it allows for more natural interactions with digital contents, via an optical tracking of hand and finger movements. Recent research has considered LEAP Motion features in virtual-reality-based systems, to meet specific needs of different clinical populations, varying in age and type of disorder. The present paper carried out a systematic mini-review of the available literature using Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. The inclusion criteria were (i) publication date between 2013 and 2020, (ii) being an empirical study or project report, (iii) written in English or Italian languages, (iv) published in a scholarly peer-reviewed journal and/or conference proceedings, and (v) assessing LEAP Motion intervention for four specific psychological domains (i.e., autism spectrum disorder, attention-deficit/hyperactivity disorder, dementia, and mild cognitive impairment), objectively. Nineteen eligible empirical studies were included. Overall, results show that protocols for attention-deficit hyperactivity disorder and autism spectrum disorder can promote psychomotor and psychosocial rehabilitation in contexts that stimulate learning. Moreover, virtual reality and LEAP Motion seem promising for the assessment and screening of functional abilities in dementia and mild cognitive impairment. As evidence is, however, still limited, deeper investigations are needed to assess the full potential of the LEAP Motion technology, possibly extending its applications. This is relevant, considering the role that virtual reality could have in overcoming barriers to access assessment, therapies, and smart monitoring.

Tactile display of softness on fingertip.

Multi-sensory human-machine interfaces are currently challenged by the lack of effective, comfortable and affordable actuation technologies for wearable tactile displays of softness in virtual- or augmented-reality environments. They should provide fingertips with tactile feedback mimicking the tactual feeling perceived while touching soft objects, for applications like virtual reality-based training, tele-rehabilitation, tele-manipulation, tele-presence, etc. Displaying a virtual softness on a fingertip requires the application of quasi-static (non-vibratory) forces via a deformable surface, to control both the contact area and the indentation depth of the skin. The state of the art does not offer wearable devices that can combine simple structure, low weight, low size and electrically safe operation. As a result, wearable softness displays are still missing for real-life uses. Here, we present a technology based on fingertip-mounted small deformable chambers, which weight about 3 g and are pneumatically driven by a compact and cost-effective unit. Weighting less than 400 g, the driving unit is easily portable and can be digitally controlled to stimulate up to three fingertips independently. Psychophysical tests proved ability to generate useful perceptions, with a Just Noticeable Difference characterised by a Weber constant of 0.15. The system was made of off-the-shelf materials and components, without any special manufacturing process, and is fully disclosed, providing schematics and lists of components. This was aimed at making it easily and freely usable, so as to turn tactile displays of softness on fingertips into a technology 'at fingertips'.

Bioreactor With Electrically Deformable Curved Membranes for Mechanical Stimulation of Cell Cultures.

Physiologically relevant in vitro models of stretchable biological tissues, such as muscle, lung, cardiac and gastro-intestinal tissues, should mimic the mechanical cues which cells are exposed to in their dynamic microenvironment in vivo. In particular, in order to mimic the mechanical stimulation of tissues in a physiologically relevant manner, cell stretching is often desirable on surfaces with dynamically controllable curvature. Here, we present a device that can deform cell culture membranes without the current need for external pneumatic/fluidic or electrical motors, which typically make the systems bulky and difficult to operate. We describe a modular device that uses elastomeric membranes, which can intrinsically be deformed by electrical means, producing a dynamically tuneable curvature. This approach leads to compact, self-contained, lightweight and versatile bioreactors, not requiring any additional mechanical equipment. This was obtained via a special type of dielectric elastomer actuator. The structure, operation and performance of early prototypes are described, showing preliminary evidence on their ability to induce changes on the spatial arrangement of the cytoskeleton of fibroblasts dynamically stretched for 8 h.

Electrically tuning soft membranes to both a higher and a lower transparency.

The possibility to electrically tune the optical transparency of thin membranes is of significant interest for a number of possible applications, such as controllable light diffusers and smart windows, both for residential and mobile use. As a difference from state-of-the-art approaches, where with an applied voltage the transparency can only increase or decrease, this paper presents the first concept to make it electrically tuneable to both higher and lower values, within the same device. The concept is applicable to any soft insulating membrane, by coating both of its surfaces with a circular transparent stretchable conductor, surrounded by a stretchable annular conductor. The two conductors are used as independently addressable electrodes to generate a dielectric elastomer-based actuation of the membrane, so as to electrically control its surface topography. We show that the optical transmittance can electrically be modulated within a broad range, between 25% and 83%. This approach could be especially advantageous for systems that require such a broad tuning range within structures that have to be thin, lightweight and acoustically silent in operation.

Smart Lenses with Electrically Tuneable Astigmatism.

The holy grail of reconfigurable optics for microscopy, machine vision and other imaging technologies is a compact, in-line, low cost, refractive device that could dynamically tune optical aberrations within a range of about 2-5 wavelengths. This paper presents the first electrically reconfigurable, fully elastomeric, tuneable optical lenses with motor-less electrical controllability of astigmatism in the visible range. By applying different voltage combinations to thin dielectric elastomer actuator segments surrounding a soft silicone lens, we show that the latter can be electrically deformed either radially or along selectable directions, so as to tune defocus or astigmatism, up to about 3 wavelengths. By mounting the new lenses on a commercial camera, we demonstrate their functionality, showing how electrically reconfiguring their shape can be used to dynamically control directional blurring while taking images of different targets, so as to emphasize directional features having orthogonal spatial orientations. Results suggest that the possibility of electrically controlling aberrations inherent to these smart lenses holds promise to develop highly versatile new components for adaptive optics.

Wearable Kinematic Monitoring System Based on Piezocapacitive Sensors.

Measuring the kinematics of human body movements is important for several biomedical and non-biomedical uses, such as rehabilitation, sports medicine, control of virtual reality systems, etc. This is typically performed employing accelerometers, electrogoniometers, electromagnetic sensors or cameras, which however are usually bulky, or can cause discomfort to the user, or are insufficiently accurate, or require expensive instrumentation. As an alternative to those state-of-the-art systems, stretchable piezocapacitive sensors based on dielectric elastomers (DE) represent a recently described competitive technology, which might enable wearable, lightweight and cost-effective devices. DE sensors consist of stretchable capacitors whose mechanical deformation causes a change of capacitance, which can be measured and related to linear or angular motions, depending on the sensors' arrangement. Here, we present a wearable wireless system able to monitor the flexion and torsion of the lumbar region of the back. The system consists of two DE sensors arranged on shoulder straps, and a custom-made wireless electronics designed to measure the capacitance of the sensors and calibrate them when the user wears them for the first time. We describe preliminary results related to the characterisation of the sensors and the electronics.

Magnetic robotic manoeuvring of gastrointestinal video capsules: preliminary phantom tests.

Ingestible video capsules enable today non-invasive and comfortable gastrointestinal explorations. As such, capsule endoscopy is progressively emerging as an attractively simple wireless technology for optical investigations of the digestive tube and, in particular, as a useful complementary diagnostic tool with respect to traditional probe endoscopy. In spite of this, capsule endoscopes still show at present a major technical lack, capable of seriously limiting their clinical efficacy: their motion cannot be controlled by an external operator. In fact, the lack of a navigation control system makes their movements and orientations totally random, being exclusively driven by visceral peristalsis and gravity. In order to provide motion control properties, a technique based on the application of external magnetic fields, capable of manoeuvring a capsule previously equipped with a magnetic component, was recently proposed. This paper presents preliminary results of the first experimental implementation of this concept with a magnetic robotic system recently introduced in the clinical practice, although for different applications in the field of cardiology. The potentialities offered by this robotic system for magnetic controls of gastrointestinal capsules were preliminarily assessed in this work with manoeuvring tests of a video capsule inside a plastic replica of a human bust. Results showed the possibility of magnetically guiding the navigation of an endoscopic capsule within the considered experimental set-up, by advantageously using the reliable robotic navigation system already employed for clinical applications. Such an outcome encourages further investigations within more challenging experimental conditions.

Enabling portable multiple-line refreshable Braille displays with electroactive elastomers.

Full-page (multiple-lines), electrically refreshable, portable and affordable Braille displays do not currently exist. There is a need for such an assistive technology, which could be used as the Braille-coded tactile analogue for blind people of the digital tablets used by sighted people. Turning those highly desirable systems into reality requires a radically new technology for Braille dot actuation. Here, we describe standard-sized refreshable Braille dots based on an innovative actuation technology that uses electro-responsive smart materials known as dielectric elastomers. Owing to a significantly reduced lateral size with respect to conventional Braille dot drives, the proposed solution is suitable to array multiple dots in multiple lines, so as to form full-page Braille displays. Furthermore, a significant reduction also of the vertical size makes the design suitable for the development of thin and lightweight displays, thus enabling portability. We present the first prototype samples of these new refreshable Braille dots, showing that the achievable active displacements are adequately close to the standard Braille requirements, although the force has to be further improved. The paper discusses the remaining challenges and describes promising strategies to address them.

Controlled navigation of endoscopic capsules: concept and preliminary experimental investigations.

This paper describes a technique to control the navigation of traditional wireless endoscopic capsules and reports preliminary proof-of-concept investigations. These capsules are used for noninvasive explorations of the digestive tube. At present, their motion cannot be controlled and they proceed by means of the visceral peristalsis. In order to enable motion controls, the technique proposed here adopts magnetic shells which are to be applied to available capsules, immediately before their use. The shells are used to control the capsule movement by means of external magnetic fields. This solution is readily applicable to any endoscopic capsule, avoiding internal modifications. Prototype elastic shells made of silicone elastomers mixed with magnetic particles were fabricated. They were tested with the most diffused capsule (model M2A, Given Imaging Ltd., Yoqneam, Israel), by studying the performance of the capsule/shell complex in simplified experimental conditions. Bench tests permitted to demonstrate controlled translations, rotations, and rototranslations of the capsule/shell complex within tubular structures coated with pieces of bovine tissues. The use of a new instrumentation, recently developed for cardiovascular treatments, is proposed as a potential means enabling the application of controlled magnetic fields for intrabody navigations.

Magnetic shells for gastrointestinal endoscopic capsules as a means to control their motion.

Wireless endoscopic video capsules are becoming largely used today for non-invasive explorations of the digestive tube. Traditional types of such capsules present a major drawback: their motion can not be controlled, since they proceed by means of the visceral peristalsis only. In order to enable a wireless control of their motion, this paper describes a new concept based on the use of external magnetic fields. The proposed technique exploits magnetic shells to be applied to traditional capsules prior to their use. The shells are capable of interacting with an imposed external magnetic field, providing a means to control the capsule movement and orientation. This solution is readily and cheaply applicable to any commercial endoscopic capsule, avoiding internal modifications. The paper reports results of preliminary bench tests. Prototype elastic shells made of a silicone elastomer mixed with magnetic particles were fabricated and tested with the Given Imaging M2A capsule in simplified experimental conditions. These tests permitted to demonstrate translations, rotations and roto-translations of the capsule/shell complex onto pieces of bovine tissues.

Electrically tunable soft solid lens inspired by reptile and bird accommodation.

Electrically tunable lenses are conceived as deformable adaptive optical components able to change focus without motor-controlled translations of stiff lenses. In order to achieve large tuning ranges, large deformations are needed. This requires new technologies for the actuation of highly stretchable lenses. This paper presents a configuration to obtain compact tunable lenses entirely made of soft solid matter (elastomers). This was achieved by combining the advantages of dielectric elastomer actuation (DEA) with a design inspired by the accommodation of reptiles and birds. An annular DEA was used to radially deform a central solid-body lens. Using an acrylic elastomer membrane, a silicone lens and a simple fabrication method, we assembled a tunable lens capable of focal length variations up to 55%, driven by an actuator four times larger than the lens. As compared to DEA-based liquid lenses, the novel architecture halves the required driving voltages, simplifies the fabrication process and allows for a higher versatility in design. These new lenses might find application in systems requiring large variations of focus with low power consumption, silent operation, low weight, shock tolerance, minimized axial encumbrance and minimized changes of performance against vibrations and variations in temperature.

A bioreactor with an electro-responsive elastomeric membrane for mimicking intestinal peristalsis.

This study describes an actuated bioreactor which mimics the pulsatile contractile motion of the intestinal barrier using electro-responsive elastomers as smart materials that undergo deformation upon electrical stimulation. The device consists of an annular dielectric elastomer actuator working as a radial artificial muscle able to rhythmically contract and relax a central cell culture well. The bioreactor maintained up to 4 h of actuation at a frequency of 0.15 Hz and a strain of 8%-10%, to those of the cyclic contraction and relaxation of the small intestine. In vitro tests demonstrated that the device was biocompatible and cell-adhesive for Caco-2 cells, which formed a confluent monolayer following 21 days of culture in the central well. In addition, cellular adhesion and cohesion were maintained after 4 h of continuous cyclic strain. These preliminary results encourage further investigations on the use of dielectric elastomer actuation as a versatile technology that might overcome the limitations of commercially available pneumatic driving systems to obtain bioreactors that can cyclically deform cell cultures in a biomimetic fashion.