Chimeric antigen receptor (CAR) T cells have emerged as a promising treatment for patients with advanced B-cell cancers. However, widespread application of the therapy is currently limited by potentially life-threatening toxicities due to a lack of control of the highly potent transfused cells. Researchers have therefore developed several regulatory mechanisms in order to control CAR T cells in vivo. Clinical adoption of these control systems will depend on several factors, including the need for temporal and spatial control, the immunogenicity of the requisite components as well as whether the system allows reversible control or induces permanent elimination. Here we describe currently available and emerging control methods and review their function, advantages, and limitations.
As a living drug, CAR T cells bear the potential for rapid and massive activation and proliferation, which contributes to their therapeutic efficacy but simultaneously underlies the side effects associated with CAR T-cell therapy. The most well-known toxicity is called cytokine release syndrome (CRS) which is a systemic inflammatory response characterized by fever, hypotension and hypoxia (5–7). CRS is triggered by the activation of CAR T cells and their subsequent production of pro-inflammatory cytokines including IFNγ, IL-6 and IL-2. This is thought to result in additional activation of bystander immune and non-immune cells which further produce cytokines, including IL-10, IL-6, and IL-1. The severity of CRS is associated with tumor burden, and ranges from a mild fever to life-threatening organ failure (10, 11). Neurologic toxicity is another serious adverse event which can occur alongside CRS (12).
Irvine, Calif., Oct. 12 2021 — The extract of the plant Corydalis yanhusuo prevents morphine tolerance and dependence while also reversing opiate addiction, according to a recent study led by the University of California, Irvine. The findings were published in the October issue of the journal Pharmaceuticals.
Over the past two decades, dramatic increases in opioid overdose mortality have occurred in the United States and other nations. During the COVID-19 pandemic, the opioid epidemic has only worsened. The documented effects of YHS, the extract of the plant Corydalis yanhusuo, could have an immediate, positive impact to curb the opioid epidemic.
In the United States, animal health authorities are now on high alert. The US Department of Agriculture has pledged an emergency appropriation of $500 million to ramp up surveillance and keep the disease from crossing borders. African swine fever is so feared internationally that, if it were found in the US, pork exports—worth more than $7 billion a year—would immediately shut down.
“Long-distance transboundary spread of highly contagious and pathogenic diseases is a worse-case scenario,” Michael Ward, an epidemiologist and chair of veterinary public health at the University of Sydney, told WIRED by email. “In agriculture, it’s the analogue of Covid-19.”
As with the Covid pandemic at its start, there is no vaccine—but also as with Covid, there is the glimmer of hope for one, thanks to basic science that has been laying down findings for years without receiving much attention. Two weeks ago, a multinational team led by scientists at the USDA’s Agricultural Research Service announced that they had achieved a vaccine candidate, based on a weakened version of the virus with a key gene deleted, and demonstrated its effectiveness in a field trial, in pigs, in Vietnam.
To fully digitize the last mile of business, you need to distribute compute power where it’s needed most — right next to IoT devices that collect data from the real world.
SparkBeyond, a company that helps analysts use AI to generate new answers to business problems without requiring any code, today has released its product SparkBeyond Discovery.
The company aims to automate the job of a data scientist. Typically, a data scientist looking to solve a problem may be able to generate and test 10 or more hypotheses a day. With SparkBeyond’s machine, millions of hypotheses can be generated per minute from the data it leverages from the open web and a client’s internal data, the company says. Additionally, SparkBeyond explains its findings in natural language, so a no-code analyst can easily understand it.
The product is the culmination of work that started in 2013 when the company had the idea to build a machine to access the web and GitHub to find code and other building blocks to formulate new ideas for finding solutions to problems. To use SparkBeyond Discovery, all a client company needs to do is specify its domain and what exactly it wants to optimize.
Daily exposure to chemicals called phthalates, which are used in the manufacture of plastic food containers and many cosmetics, may lead to roughly 100,000 premature deaths among older Americans each year, a new study shows. The resulting annual economic burden is between $40 billion and $47 billion, a value more than quadruple that of previous estimates.
NYU Langone study shows deaths linked to endocrine-disrupting chemicals called phthalates may cost United States billions in lost productivity. Learn more.
Coastal artisanal fisheries, particularly those in developing countries, are facing a global crisis of overexploitation1. Artificial reefs (ARs), or human–made reefs2, have been widely advocated by governmental and non-governmental conservation and management organizations for addressing these issues. Industries, particularly oil and gas, seeking to avoid the costs of removal or conventional disposal of used materials are often major advocates for deploying ARs. Yet, major questions remain regarding the success of such efforts in the context of weak governance and poorly sustained international investment in AR development projects. There is frequently confusion over whether or not ARs should be fishing sites and the precise goals of constructing such ARs are often unclear, making difficult to evaluate their successfulness3. Over the last 40 years, both failures and success AR implementation programs have been reported4,5. The main point of the present work is to underline the importance of the governance issue and address social and management factors on AR “success”.
To improve fishery yields, it has been recommended that ARs must be no-take areas (e.g.,2). Yet, most ARs were historically delineated as sites for fishing4, and were rarely implemented at large scales in/for no-take zones, even in countries with centuries of experience in constructing ARs, such as Japan. In Japan, fishery authorities and local fishers use ARs to promote sustainable catches and to establish nursery grounds of target species6. However, fishery authorities and local fishery cooperatives in Japan have extensive management authority over ARs. For example, fishing around ARs is usually limited to hook and line techniques, with net fishing rarely being permitted in areas where risk of entanglement in ARs is high. Furthermore, during spawning, fishing gear and fishing season are often restricted around ARs in Japan. These practices are recognized for their effectiveness in maintaining good fishing performance and marine conservation in Japan and elsewhere where they have been implemented7.
Attempts to transpose ARs to developing countries have, however, frequently ended in failure8, particularly when project funding comes to an end9. Thus, it is important to provide recommendations to improve the sustainability of AR deployments and realize their biodiversity conservation and fisheries management goals. This is particularly important in developing countries, which are often characterized by poor governance. For fisheries scientists and marine ecologists, the effectiveness of ARs is primarily quantified by surveying fish populations on ARs. In particular, the question of whether ARs facilitate the “production” of new fish or whether they only attract the surrounding fish remains under debate10,11,12. Few studies have documented how ARs are managed, and the impacts of such management8,13, despite the key importance of protecting no-take ARs from illegal fishing being repeatedly highlighted2. Mathematical models, implemented to set the optimal AR volume to maximize catches, suggest that, although attraction and production effects can modulate the response, the effect of ARs on fisheries mostly depends on governance options and efficiency14. Existing models show that fishing exclusively on ARs has consistently negative impacts on the equilibrium of catches. In comparison, ARs can have negative or positive impacts on catches when fishing on areas surrounding them, as a function of the magnitude of the AR attraction effect14. Whether or not ARs are managed as no-take areas influences these phenomena. For instance, on unmanaged ARs, overexploitation risk increases, as fish become more accessible to fishing fleets. In comparison, when fishing is banned on ARs, the fish biomass concentrated near the AR rises, leading to a “spill-over” effect that enhances catch at equilibrium in adjacent fishing areas15.
