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Preliminary trials in both humans and dogs demonstrate the potential efficacy of an mRNA-based vaccine for brain cancer

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A novel mRNA vaccine candidate for highly malignant brain cancer has exhibited encouraging results in a limited-scale clinical trial, albeit with a unique approach. In addition to conducting vaccine trials on a small number of human cancer patients, the researchers are also utilizing data from 10 pet dogs.

It is customary for drugs and treatments intended for human use to undergo animal trials initially. Frequently, this phase of the process occurs subsequent to laboratory experiments conducted on cells but prior to any involvement of human volunteers in the administration of the drug. Despite ongoing endeavors to diminish animal testing and substitute it with alternative methods, it remains a fundamental component of pharmaceutical research.

Typically, however, our intention is not to medically treat animals for a disease they acquired in a natural manner. Scientists create models in species with organ systems that closely resemble those of humans, utilizing drugs, surgery, or genetic modification to imitate human diseases.

In the context of this mRNA vaccine, that stage was accomplished in mice. However, there was an additional, atypical measure. Dogs are the exclusive nonhuman species that are susceptible to the occurrence of spontaneous brain tumors. This makes them a valuable resource for testing treatments in a more authentic environment.

Ten pet dog owners granted consent for their canines to participate. Glioma, a type of cancer, is universally lethal, making this trial their sole available treatment option. In contrast to the typical average survival time of 30–60 days following a diagnosis, the dogs experienced a median survival of 139 days after receiving the vaccine, allowing for a significant increase in opportunities for treats and belly rubs.

Following successful outcomes in both the mice and the dogs, the researchers proceeded to administer the vaccine to four human patients diagnosed with glioblastoma. This is the most malignant type of brain cancer, characterized by a low rate of survival.

At present, it is premature to have a comprehensive understanding of the clinical impacts of the vaccine. However, it is established that all patients experienced either a prolonged period without illness or a longer-than-anticipated survival rate. The results are so encouraging that a larger Phase I trial is now scheduled to encompass both pediatric and adult populations.

What is the mechanism of action of the vaccine?

As observed in previous advancements in this field, one significant benefit of mRNA-based vaccines for cancer is their ability to be customized for individual patients. The glioblastoma vaccine incorporates this feature alongside a pioneering delivery system.

“Rather than injecting individual particles, we are injecting clusters of particles that are coiling around each other, similar to onions in a bag,” explained Dr. Elias Sayour, senior author from the University of Florida, in a statement. “The rationale behind this approach in the context of cancer is that these clusters stimulate the immune system to a greater extent than individual particles.”

Due to the COVID-19 pandemic, we have gained a greater understanding of mRNA vaccines; however, the mechanisms behind their functioning differ slightly. The RNA is obtained from the tumor cells of each patient and then enclosed in a lipid nanoparticle “costume.”. Upon reintroduction into the bloodstream, the immune system perceives this substance as a virus, thereby preparing itself to react to any remaining cancerous cells.

The process of personalization customizes the vaccine to suit the individual patient, thereby optimizing its effectiveness. Additionally, the delivery system enhances the immune system’s ability to respond quickly.

“Within a span of less than 48 hours, we may witness a transformation of these tumors from an ‘immune cold’ state, characterized by a scarcity of immune cells and a suppressed immune response, to an ‘immune hot’ state, marked by a highly active immune response,” Sayour noted.

“The study’s discovery that producing an mRNA cancer vaccine in this manner elicits comparable and robust reactions in mice, pet dogs with naturally occurring cancer, and human patients with brain cancer is a highly significant finding. This is because it is often uncertain how well the results of preclinical studies in animals will translate into similar responses in patients,” stated Dr. Duane Mitchell, a co-author of the study.

Sayour stated that the vaccine has the potential to be integrated with other immunotherapies as part of a combined treatment. “I am optimistic that this could represent a novel paradigm for patient treatment, a cutting-edge platform technology for modulating the immune system,” he stated.

The research findings have been published in the scientific journal Cell.

As Editor here at GeekReply, I'm a big fan of all things Geeky. Most of my contributions to the site are technology related, but I'm also a big fan of video games. My genres of choice include RPGs, MMOs, Grand Strategy, and Simulation. If I'm not chasing after the latest gear on my MMO of choice, I'm here at GeekReply reporting on the latest in Geek culture.

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Medicine and Health

The largest-ever 3D-mapped segment of the human brain remains small enough to fit on a grain of rice

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This vibrant spectrum of cells depicts the most extensive and detailed three-dimensional map ever created of a specific region of the human brain. Although it is the largest, it is still only a cubic millimeter in size, which is approximately equivalent to half a grain of rice. Through this achievement, scientists are now able to observe the complex network of 57,000 cells, linked by 150 million synapses and numerous millimeters of blood vessels, which constitute this particular small area of the human cortex.

Over the past ten years, a partnership between scientists at Harvard University and Google has been dedicated to creating a comprehensive and detailed map of the mouse brain. This represents a significant and crucial advancement in our progress, as it unveils the previously unknown intricacy of a portion of brain matter at the level of synapses.

Senior author Jeff Lichtman stated that the term ‘fragment’ is ironic. His team generated electron microscopy images that serve as the foundation for the new map. “For the majority of individuals, a terabyte is considered to be enormous. However, even a small portion of the human brain, which is minuscule and tiny, still contains thousands of terabytes.”

Using AI algorithms created by Google Research, the imaging from Lichtman’s team at Harvard can be color-coded and reconstructed to unveil unparalleled levels of detail.

It is reasonable to assume that neurons, which are the fundamental nerve cells, would be the most prevalent in the primary organ of the central nervous system, as indicated by their name, correct? However, the team discovered that the number of these cells was actually twice as many as the supporting glial cells, which play a role in maintaining the optimal environment of the brain. The oligodendrocytes, which generate myelin, the crucial insulation surrounding nerve axons, were the most abundant cell type.

The tissue fragment displayed peculiarities such as robust neurons interconnected by 50 or more synapses each, enlarged axons containing what the research team referred to as “unusual material,” and a limited quantity of axons arranged in “extensive whorls.” Due to the fact that the tissue sample was obtained from a patient with epilepsy, it remains uncertain whether these characteristics are associated with the aforementioned condition or not.

Mapping down to this level of detail is crucial because it has the potential to offer future researchers valuable insights into the impact of small-scale connections within brain tissue. These connections may have significant effects on major functions and contribute to the development of diseases.

The scientific field that studies the connections within the brain is referred to as “connectomics.”. Recent advancements in the field include a large-scale global initiative to comprehensively map the intricate connections within the human brain, similar to how we have mapped the human genome. Additionally, the first comprehensive map of an insect brain has been published.

In addition to previous achievements such as last year’s unveiling of a brain cell atlas, scientists can now delve into our intricate network of “little gray cells” with unprecedented depth.

In order to advance this objective and increase the accessibility of these techniques to a wide range of scientists, the Harvard and Google teams have created a set of analytical tools that are openly accessible to the public. “Due to the substantial investment made in this project, it was crucial to present the findings in a manner that allows anyone else to easily access and derive advantages from them,” stated Viren Jain, a member of the Google Research team.

The ultimate objective of this project is to create a comprehensive map of the entire mouse brain. This map will yield approximately 1,000 times more data than what is currently being generated from this 1-cubic-millimeter fragment of the human brain. Therefore, there is still a considerable amount of progress to be made.

The authors acknowledge that approaches to understanding the meaning of neural circuit connectivity data are still in their early stages. However, they consider this petascale dataset as a starting point.

The research findings have been published in the scientific journal Science.

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A cutting-edge brain implant has been developed that can accurately translate imagined speech in real time, achieving the highest level of precision to date

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Caltech bioengineers’ new tool has proven to be exceptionally adept at deciphering brain signals related to internal speech. Although it has only been tested in two patients thus far, with further development, this technology has the potential to enable individuals who cannot speak to communicate solely through their thoughts.

BMIs are already achieving remarkable feats. These systems have been utilized to assist paralyzed patients in walking and, in the case of Neuralink’s first experimental subject, enable them to control a computer through a “telepathic” connection.

One of the primary applications of this technology involves facilitating communication. For people who are unable to speak, such as those with neurological conditions or brain injuries, BMIs can give them a voice.

There are some limitations to devices of this kind, like the one that the late Stephen Hawking famously used. One challenge is capturing the natural rhythm of speech, which scientists are actively researching, aided by Pink Floyd. Another limitation is that many speech BMIs rely on users attempting to vocalize words, which may not be feasible for everyone. An optimal solution would involve discovering a method to decipher internal speech, allowing individuals to simply imagine uttering a word. Progress in this field has been made, but it has been quite difficult, and the outcomes have been varied.

Now, the team at Caltech has created a system that can accurately decode internal speech with unprecedented precision.

Microelectrode arrays were surgically inserted into the brains of two male patients who were experiencing tetraplegia, one aged 33 and the other aged 39. The team focused on the primary somatosensory cortex and the supramarginal gyrus (SMG), a brain region that has not been investigated in previous studies on speech BMI.

The interface was trained on a combination of real and made-up words to determine their impact on the system’s effectiveness. The participants were presented with each word either visually or audibly and were subsequently instructed to mentally simulate saying the word for a duration of 1.5 seconds. They were then requested to vocalize the word.

According to first author Sarah Wandelt, this technology would be especially beneficial for individuals who have lost their ability to move. For example, let’s consider a condition such as locked-in syndrome.

Using the BMI, the researchers were able to analyze the real-time activity in the SMG while the participants were contemplating each word. One participant achieved an accuracy of 79 percent, which is comparable to the accuracy of decoding vocalized speech, according to Wandelt and co-author David Bjånes. The other participant, however, only achieved an accuracy of 23 percent.

The technology will require additional refinement and testing on a larger sample size with a broader range of words. However, the study does indicate that the SMG shows promise as a brain region to focus on.

“Although the second participant did not replicate these results, this study holds significance as it is, to my knowledge, the first successful implementation of a real-time speech brain-computer interface using single unit recordings in the SMG,” remarked Blaise Yvert of The Grenoble Institute of Neuroscience, who was not part of the study.

Additionally, the team is interested in exploring whether the BMI can effectively differentiate between different letters of the alphabet. Wandelt and Bjånes propose that decoding individual sound units of speech, known as phonemes, may offer a potential avenue for investigation.

According to Giacomo Ariani, the Associate Editor of the paper, this proof-of-concept study on high-performance decoding of internal speech will undoubtedly capture the attention of researchers who are dedicated to advancing the capabilities of BMIs and other therapeutic devices for individuals who have lost their ability to speak.

The study has been published in the prestigious journal Nature Human Behavior.

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Medicine and Health

AstraZeneca took its COVID-19 vaccine off the market. Why did they do this? What You Need To Know

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The Oxford-AstraZeneca COVID-19 vaccine is poised to be globally discontinued, almost 3.5 years after its initial authorization. The vaccine’s discontinuation has attracted attention due to its notorious reputation. However, what is the underlying reason for this decision? It is not as sensational as some may imply.

As per a statement observed by the BBC, the decision was made for commercial reasons due to an excess of updated vaccines that has resulted in a decrease in demand.

Viruses have the ability to undergo mutations and evolutionary changes, and this holds true for SARS-CoV-2, the virus responsible for causing COVID-19. Consequently, a wide array of distinct variations has emerged, prompting certain vaccine manufacturers to develop revised vaccines specifically designed to combat these variations.

Nevertheless, AstraZeneca has not taken the same action. Professor Adam Finn from the University of Bristol stated to the Science Media Centre (SMC) that this implies that the vaccine, currently known as Vaxzevria, is likely significantly less efficacious than its initial effectiveness.

Therefore, it is highly unlikely that there is any economic justification for the ongoing production and distribution of the vaccine. This is likely the primary factor influencing the company’s decision to cease manufacturing and selling it.

The company has emphasized the effects of Vaxzevria since its implementation. The statement indicated that independent estimates showed that more than 6.5 million lives were preserved solely in the initial year of implementation. “Governments worldwide have acknowledged our endeavors and consider them to be a crucial element in bringing an end to the global pandemic.”

However, the vaccine did encounter some issues. In 2021, multiple countries halted the use of Vaxzevria as a precautionary measure due to reports of individuals experiencing a rare condition called thrombosis with thrombocytopenia syndrome (TTS) after receiving the vaccine.

The incidence of vaccine-induced TTS, however, has been determined to be significantly low. According to data from the UK, the likelihood of developing it after receiving the vaccination is estimated to be approximately 4 cases per 1 million individuals.

A comprehensive study of more than 29 million individuals revealed that contracting COVID-19 carries a significantly higher likelihood of developing blood clots compared to receiving the AstraZeneca vaccine.

“When considering our actions, we must always weigh the potential harm against the potential benefits. During the height of the pandemic, the AZ vaccine provided greater benefits than harm. However, now there are more effective and safer options available,” stated Professor Jonathan Ball, Deputy Director of the Liverpool School of Tropical Medicine, in an interview with the SMC.

“Maybe its relevance has diminished,” commented Dr. Michael Head, a global health researcher. The Oxford AstraZeneca vaccine has been instrumental in the global pandemic response for the majority of countries.

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