A metaphorical history of DNA patents

The aim of this paper is to retrace the history of genetic patents, analyzing the metaphors used in the public debate, in patent offices, and in courtrooms. I have identified three frames with corresponding metaphor clusters: the first is the industrial frame, built around the idea that DNA is a chemical; the second is the informational frame, assembled around the concept of genetic information; last is the soul frame, based on the idea that DNA is or contains the essence of the individual

The SIB Swiss Institute of Bioinformatics' resources: focus on curated databases

The SIB Swiss Institute of Bioinformatics (www.isb-sib.ch) provides world-class bioinformatics databases, software tools, services and training to the international life science community in academia and industry. These solutions allow life scientists to turn the exponentially growing amount of data into knowledge. Here, we provide an overview of SIB's resources and competence areas, with a strong focus on curated databases and SIB's most popular and widely used resources. In particular, SIB's Bioinformatics resource portal ExPASy features over 150 resources, including UniProtKB/Swiss-Prot, ENZYME, PROSITE, neXtProt, STRING, UniCarbKB, SugarBindDB, SwissRegulon, EPD, arrayMap, Bgee, SWISS-MODEL Repository, OMA, OrthoDB and other databases, which are briefly described in this article

Adaptation and Optimization of an Intraneural Electrode to Interface with the Cervical Vagus Nerve

The modulation of the cervical vagus nerve (VN) using neural electrodes has shown great potential to treat cardiovascular, inflammatory, intestinal, or respiratory dysfunctions. Intraneural electrodes have shown great potentials for other neuroprosthetic applications. Therefore, their use for VN modulation could have great potential. Here we optimized an intraneural electrode originally developed for use in lower limb amputees. Based on histological data from the VN of 100 histological sections we adapted and optimized the dimensions of the Quick-to-implant peripheral neural electrode (Q-PINE). Parts of the Q- PINE were substituted to increase biocompatibility. The platinum-iridium (Pt/Ir) wires were substituted with a polyimide thin-film structure to optimize the electrodes' impedance. Mechanical and electrochemical characterization was performed to exclude negative alterations resulting from the design and material changes. The dimensional adaptation and material substitutions of the Q- PINE did not alter its mechanical or electrochemical properties. The tfQPINE shows promising results for the successful application with the VN

Bioelectronic medicine for the autonomic nervous system: clinical applications and perspectives

Bioelectronic medicine (BM) is an emerging new approach for developing novel neuromodulation therapies for pathologies that have been previously treated with pharmacological approaches. In this review, we will focus on the neuromodulation of autonomic nervous system (ANS) activity with implantable devices, a field of BM that has already demonstrated the ability to treat a variety of conditions, from inflammation to metabolic and cognitive disorders. Recent discoveries about immune responses to ANS stimulation are the laying foundation for a new field holding great potential for medical advancement and therapies and involving an increasing number of research groups around the world, with funding from international public agencies and private investors. Here, we summarize the current achievements and future perspectives for clinical applications of neural decoding and stimulation of the ANS. First, we present the main clinical results achieved so far by different BM approaches and discuss the challenges encountered in fully exploiting the potential of neuromodulatory strategies. Then, we present current preclinical studies aimed at overcoming the present limitations by looking for optimal anatomical targets, developing novel neural interface technology, and conceiving more efficient signal processing strategies. Finally, we explore the prospects for translating these advancements into clinical practice

A fast and accurate learning-based decoding algorithm for the classification of cardiovascular and respiratory challenges using intraneural electrodes in the pig vagus nerve

Bioelectronic medicine is a new approach for developing closed-loop neuromodulation protocols on the peripheral nervous system (PNS) to treat a wide range of disorders currently treated with pharmacological approaches. Algorithms need to have low computational cost in order to acquire, process and model data for the modulation of the PNS in real time. Here, we present a fast learning-based decoding algorithm for the classification of cardiovascular and respiratory functional alterations (i.e., challenges) by using neural signals recorded from intraneural electrodes implanted in the vagus nerve of 5 pigs. Our algorithm relies on 9 handcrafted features, extracted following signal temporal windowing, and a multi-layer perceptron (MLP) for feature classification. We achieved fast and accurate classification of the challenges, with a computational time for feature extraction and prediction lower than 1.5 ms. The MLP achieved a balanced accuracy higher than 80 % for all recordings. Our algorithm could represent a step towards the development of a closed-loop system based on a single intraneural interface with both the potential of real time classification and selective modulation of the PNS

A lightweight learning-based decoding algorithm for intraneural vagus nerve activity classification in pigs

Objective.Bioelectronic medicine is an emerging field that aims at developing closed-loop neuromodulation protocols for the autonomic nervous system (ANS) to treat a wide range of disorders. When designing a closed-loop protocol for real time modulation of the ANS, the computational execution time and the memory and power demands of the decoding step are important factors to consider. In the context of cardiovascular and respiratory diseases, these requirements may partially explain why closed-loop clinical neuromodulation protocols that adapt stimulation parameters on patient's clinical characteristics are currently missing.Approach.Here, we developed a lightweight learning-based decoder for the classification of cardiovascular and respiratory functional challenges from neural signals acquired through intraneural electrodes implanted in the cervical vagus nerve (VN) of five anaesthetized pigs. Our algorithm is based on signal temporal windowing, nine handcrafted features, and random forest (RF) model for classification. Temporal windowing ranging from 50 ms to 1 s, compatible in duration with cardio-respiratory dynamics, was applied to the data in order to mimic a pseudo real-time scenario.Main results.We were able to achieve high balanced accuracy (BA) values over the whole range of temporal windowing duration. We identified 500 ms as the optimal temporal windowing duration for both BA values and computational execution time processing, achieving more than 86% for BA and a computational execution time of only ∼6.8 ms. Our algorithm outperformed in terms of BA and computational execution time a state of the art decoding algorithm tested on the same dataset (Valloneet al2021J. Neural Eng.180460a2). We found that RF outperformed other machine learning models such as support vector machines, K-nearest neighbors, and multi-layer perceptrons.Significance.Our approach could represent an important step towards the implementation of a closed-loop neuromodulation protocol relying on a single intraneural interface able to perform real-time decoding tasks and selective modulation of the VN

Surgical Anatomy of the Vertebrobasilar Territory and Posterior Circle of Willis

BACKGROUND: In the present era of microscopic and neuroendoscopic procedures, the surgical anatomy of the skull base vessels has gained increased significance. The pattern of the vertebrobasilar arterial complex and the posterior circle of Willis (COW) in Nigerians has not been previously reported despite various variants of these complexes existing in different populations.OBJECTIVE: To review and document the size, distribution and anomalies of the vertebrobasilar territory and posterior COW pattern in a Nigerian set of brains.Methods: The target population for this study was a group of Nigerian adults 18 years and above. Specimens from patients with an ante-mortem or post-mortem evidence of meningitis or atherosclerosis were excluded. The size, distribution and anomalies of the vertebrobasilar artery, its branches, and the posterior COW were defined in 50 brains.RESULTS: The male: female ratio was 1.9:1 and a mean age of 44 years. Statistical analysis showed significant differences between the sizes of posterior inferior cerebellar arteries and anterior inferior cerebellar arteries (Student’s t = –30.189; p-value = 0.000). Fifty-six percent of the brains had no anomalies. Thirty anomalies were noted in posterior COWcompared with six in the vertebrobasilar territory. There were no aneurysms in all the specimens studied. CONCLUSION: Anomalies in the region of the posterior COW are commoner than the vertebrobasilar territory and the region of the posterior communicating artery is the most common site of anomalies in the posterior COW territory. These variations should be taken into account during skull base and carotid surgeries, and cerebral angiography

Surgical access and stimulation of pudendal nerve in pigs to restore the micturition control

Pelvic floor disorders (PFDs) are a series of conditions related to weakening and or tears of pelvic muscles and endopelvic fascia, that are generally poorly tolerated, negatively affecting women's quality of life. Among all PFDs, bladder‐related symptoms tend to be the most reported; however, urinary symptoms do not necessarily correlate with an underlying pathology and instrumental findings. Urodynamics is the milestone for the assessment of lower urinary tract dysfunctions but, despite its usefulness, its role has been recently questioned and several attempts have been made to develop models to predict urodynamics findings based on clinical data. Unfortunately so far, predictive models resulted in unsatisfactory performances. Our study aims to evaluate, in a large cohort of patients, the agreement between lower urinary tract symptoms and corresponding urodynamic diagnosis and build predictive models

Sensitivity to temporal parameters of intraneural tactile sensory feedback

Background Recent studies have shown that neural stimulation can be used to provide artificial sensory feedback to amputees eliciting sensations referred on the amputated hand. The temporal properties of the neural stimulation modulate aspects of evoked sensations that can be exploited in a bidirectional hand prosthesis. Methods We previously collected evidence that the derivative of the amplitude of the stimulation (intra-digit temporal dynamics) allows subjects to recognize object compliance and that the time delay among stimuli injected through electrodes implanted in different nerves (inter-digit temporal distance) allows to recognize object shapes. Nevertheless, a detailed characterization of the subjects' sensitivity to variations of intra-digit temporal dynamic and inter-digit temporal distance of the intraneural tactile feedback has not been executed. An exhaustive understanding of the overall potentials and limits of intraneural stimulation to deliver sensory feedback is of paramount importance to bring this approach closer and closer to the natural situation. To this aim, here we asked two trans-radial amputees to identify stimuli with different temporal characteristics delivered to the same active site (intra-digit temporal Dynamic Recognition (DR)) or between two active sites (inter-digit Temporal distance Recognition (TR)). Finally, we compared the results achieved for (simulated) TR with conceptually similar experiments with real objects with one subject. Results We found that the subjects were able to identify stimuli with temporal differences (perceptual thresholds) larger than 0.25 s for DR and larger than 0.125 s for TR, respectively. Moreover, we also found no statistically significant differences when the subjects were asked to identify three objects during simulated 'open-loop' TR experiments or real 'closed-loop' tests while controlling robotic hand. Conclusions This study is a new step towards a more detailed analysis of the overall potentials and limits of intraneural sensory feedback. A full characterization is necessary to develop more advanced prostheses capable of restoring all lost functions and of being perceived more as a natural limb by users

Sensitivity to temporal parameters of intraneural tactile sensory feedback

Background Recent studies have shown that neural stimulation can be used to provide artificial sensory feedback to amputees eliciting sensations referred on the amputated hand. The temporal properties of the neural stimulation modulate aspects of evoked sensations that can be exploited in a bidirectional hand prosthesis. Methods We previously collected evidence that the derivative of the amplitude of the stimulation (intra-digit temporal dynamics) allows subjects to recognize object compliance and that the time delay among stimuli injected through electrodes implanted in different nerves (inter-digit temporal distance) allows to recognize object shapes. Nevertheless, a detailed characterization of the subjects’ sensitivity to variations of intra-digit temporal dynamic and inter-digit temporal distance of the intraneural tactile feedback has not been executed. An exhaustive understanding of the overall potentials and limits of intraneural stimulation to deliver sensory feedback is of paramount importance to bring this approach closer and closer to the natural situation. To this aim, here we asked two trans-radial amputees to identify stimuli with different temporal characteristics delivered to the same active site (intra-digit temporal Dynamic Recognition (DR)) or between two active sites (inter-digit Temporal distance Recognition (TR)). Finally, we compared the results achieved for (simulated) TR with conceptually similar experiments with real objects with one subject. Results We found that the subjects were able to identify stimuli with temporal differences (perceptual thresholds) larger than 0.25 s for DR and larger than 0.125 s for TR, respectively. Moreover, we also found no statistically significant differences when the subjects were asked to identify three objects during simulated ‘open-loop’ TR experiments or real ‘closed-loop’ tests while controlling robotic hand. Conclusions This study is a new step towards a more detailed analysis of the overall potentials and limits of intraneural sensory feedback. A full characterization is necessary to develop more advanced prostheses capable of restoring all lost functions and of being perceived more as a natural limb by users.ISSN:1743-000