Safely balancing a double-edged blade: identifying and mitigating emerging biosecurity risks in precision medicine.

Tools and methods of precision medicine are developing rapidly, through both iterative discoveries enabled by innovations in biomedical research (e.g., genome editing, synthetic biology, bioengineered devices). These are strengthened by advancements in information technology and the increasing body of data-as assimilated, analyzed, and made accessible-and affectable-through current and emerging cyber-and systems- technologies. Taken together, these approaches afford ever greater volume and availability of individual and collective human data. Machine learning and/or artificial intelligence approaches are broadening this dual use risk; and in the aftermath of COVID-19, there is growing incentive and impetus to gather more biological data from individuals and their environments on a routine basis. By engaging these data-and the interventions that are based upon them, precision medicine offer promise of highly individualized treatments for disease and injury, optimization of structure and function, and concomitantly, the potential for (mis) using data to incur harm. This double-edged blade of benefit and risk obligates the need to safeguard human data from purloinment, through systems, guidelines and policies of a novel discipline, cyberbiosecurity, which, as coupled to ethical precepts, aims to protect human privacy, agency, and safety in ways that remain apace with scientific and technological advances in biomedicine. Herein, current capabilities and trajectories precision medicine are described as relevant to their dual use potential, and approaches to biodata security (viz.- cyberbiosecurity) are proposed and discussed.

Proceedings of the Ninth Annual Deep Brain Stimulation Think Tank: Advances in Cutting Edge Technologies, Artificial Intelligence, Neuromodulation, Neuroethics, Pain, Interventional Psychiatry, Epilepsy, and Traumatic Brain Injury.

DBS Think Tank IX was held on August 25-27, 2021 in Orlando FL with US based participants largely in person and overseas participants joining by video conferencing technology. The DBS Think Tank was founded in 2012 and provides an open platform where clinicians, engineers and researchers (from industry and academia) can freely discuss current and emerging deep brain stimulation (DBS) technologies as well as the logistical and ethical issues facing the field. The consensus among the DBS Think Tank IX speakers was that DBS expanded in its scope and has been applied to multiple brain disorders in an effort to modulate neural circuitry. After collectively sharing our experiences, it was estimated that globally more than 230,000 DBS devices have been implanted for neurological and neuropsychiatric disorders. As such, this year's meeting was focused on advances in the following areas: neuromodulation in Europe, Asia and Australia; cutting-edge technologies, neuroethics, interventional psychiatry, adaptive DBS, neuromodulation for pain, network neuromodulation for epilepsy and neuromodulation for traumatic brain injury.

Hormesis and Ginkgo biloba (GB): Numerous biological effects of GB are mediated via hormesis.

Ginkgo biloba (GB) extracts have been shown to commonly induce biphasic dose responses in a range of cell types and endpoints (e.g., cochlea neural stem cells, cell viability, cell proliferation). The magnitude and width of the low dose stimulation of these biphasic dose responses are similar to those reported for hormetic dose responses. These hormetic dose responses occur within direct stimulatory responses as well as in preconditioning experimental protocols, displaying acquired resistance within an adaptive homeodynamic and temporal framework and repeated measurement protocols. The demonstrated GB dose responses further reflect the general occurrence of hormetic dose responses that consistently appear to be independent of the biological model, endpoint, inducing agent, and/or mechanism. These findings have important implications for consideration(s) of study designs involving dose selection, dose spacing, sample size, and statistical power. This illustrates and strengthens the need to characterize the low dose stimulatory response range and optimal dose in order to explore potential public health and clinical applications of plant-derived agents, such as GB.

Hormesis mediates dose-sensitive shifts in macrophage activation patterns.

The activation or polarization of macrophages to pro- or anti-inflammatory states evolved as an adaptation to protect against a spectrum of biological threats. Such an adaptation engages pro-oxidative mechanisms and enables macrophages to neutralize and kill threatening organisms (e.g., viruses, bacteria, mold), limit cancerous growths, and enhance recovery and repair processes. The present study demonstrates that (1) many diverse pharmacological, chemical and physical agents can mediate a dose/concentration-dependent shift between pro- and anti-inflammatory activation states, and (2) these shifts in activation states display biphasic dose-response relationships that are characteristic of hormesis. This study also reveals that preconditioning-another form of hormesis-similarly mediates tissue protection by the polarization of macrophages, but in this case, towards an anti-inflammatory phenotype. This assessment supports the generalizability and significance of hormesis in biology, medicine, and public health and further extends it to encompass the hormetic activation of macrophages.

Body -to-head transplant; a "caputal" crime? Examining the corpus of ethical and legal issues.

Neurosurgeon Sergio Canavero proposed the HEAVEN procedure - i.e. head anastomosis venture - several years ago, and has recently received approval from the relevant regulatory bodies to perform this body-head transplant (BHT) in China. The BHT procedure involves attaching the donor body (D) to the head of the recipient (R), and discarding the body of R and head of D. Canavero's proposed procedure will be incredibly difficult from a medical standpoint. Aside from medical doubt, the BHT has been met with great resistance from many, if not most bio- and neuroethicists.Given both the known challenges and unknown outcomes of HEAVEN, several important neuroethical and legal questions have emerged should Canavero be successful, including: (1) What are the implications for transplantology in the U.S., inclusive of issues of expense, distributive justice, organizational procedures, and the cost(s) of novel insight(s)? (2) How do bioethical and neuroethical principles, and legal regulations of human subject research apply? (3) What are the legal consequences for Canavero (or any other surgeon) performing a BHT? (4) What are the tentative implications for the metaphysical and legal identity of R should they survive post-BHT? These questions are analyzed, issues are identified, and several solutions are proposed in an attempt to re-configure HEAVEN into a safe, clinically effective, and thus (more) realistically viable procedure.Notably, the permissibility of conducting the BHT in China fosters additional, important questions, focal to (1) whether Western ethics and professional norms be used to guide the BHT - or any neuroscientific research and its use - in non-Western countries, such as China; (2) if the models of responsible conduct of research are identical, similar, or applicable to the intent and conduct of research in China; and (3) what economic and political implications (for China and other countries) are fostered if/when such avant garde techniques are successful.These questions are discussed as a further impetus to develop a globally applicable neuroethical framework that would enable both local articulation and cosmopolitan inquiry and oversight of those methods and approaches deemed problematic, if and when rendered in more international settings.

Evolving Applications, Technological Challenges and Future Opportunities in Neuromodulation: Proceedings of the Fifth Annual Deep Brain Stimulation Think Tank.

The annual Deep Brain Stimulation (DBS) Think Tank provides a focal opportunity for a multidisciplinary ensemble of experts in the field of neuromodulation to discuss advancements and forthcoming opportunities and challenges in the field. The proceedings of the fifth Think Tank summarize progress in neuromodulation neurotechnology and techniques for the treatment of a range of neuropsychiatric conditions including Parkinson's disease, dystonia, essential tremor, Tourette syndrome, obsessive compulsive disorder, epilepsy and cognitive, and motor disorders. Each section of this overview of the meeting provides insight to the critical elements of discussion, current challenges, and identified future directions of scientific and technological development and application. The report addresses key issues in developing, and emphasizes major innovations that have occurred during the past year. Specifically, this year's meeting focused on technical developments in DBS, design considerations for DBS electrodes, improved sensors, neuronal signal processing, advancements in development and uses of responsive DBS (closed-loop systems), updates on National Institutes of Health and DARPA DBS programs of the BRAIN initiative, and neuroethical and policy issues arising in and from DBS research and applications in practice.

Proceedings of the Fourth Annual Deep Brain Stimulation Think Tank: A Review of Emerging Issues and Technologies.

This paper provides an overview of current progress in the technological advances and the use of deep brain stimulation (DBS) to treat neurological and neuropsychiatric disorders, as presented by participants of the Fourth Annual DBS Think Tank, which was convened in March 2016 in conjunction with the Center for Movement Disorders and Neurorestoration at the University of Florida, Gainesveille FL, USA. The Think Tank discussions first focused on policy and advocacy in DBS research and clinical practice, formation of registries, and issues involving the use of DBS in the treatment of Tourette Syndrome. Next, advances in the use of neuroimaging and electrochemical markers to enhance DBS specificity were addressed. Updates on ongoing use and developments of DBS for the treatment of Parkinson's disease, essential tremor, Alzheimer's disease, depression, post-traumatic stress disorder, obesity, addiction were presented, and progress toward innovation(s) in closed-loop applications were discussed. Each section of these proceedings provides updates and highlights of new information as presented at this year's international Think Tank, with a view toward current and near future advancement of the field.

Proceedings of the Third Annual Deep Brain Stimulation Think Tank: A Review of Emerging Issues and Technologies.

The proceedings of the 3rd Annual Deep Brain Stimulation Think Tank summarize the most contemporary clinical, electrophysiological, imaging, and computational work on DBS for the treatment of neurological and neuropsychiatric disease. Significant innovations of the past year are emphasized. The Think Tank's contributors represent a unique multidisciplinary ensemble of expert neurologists, neurosurgeons, neuropsychologists, psychiatrists, scientists, engineers, and members of industry. Presentations and discussions covered a broad range of topics, including policy and advocacy considerations for the future of DBS, connectomic approaches to DBS targeting, developments in electrophysiology and related strides toward responsive DBS systems, and recent developments in sensor and device technologies.