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A groundbreaking human trial is being conducted to explore the possibility of transforming lymph nodes into functioning livers

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After more than ten years of work, the first clinical study for a treatment for end-stage liver disease (ESLD) that aims to turn lymph nodes into working livers has begun.

Dr. Michael Hufford, co-founder and CEO of LyGenesis, said that we have successfully administered the first dose of a clinical trial to a patient using their own lymph nodes as living bioreactors to regenerate an ectopic organ. This is a groundbreaking achievement in the field of medicine.

The treatment involves extracting hepatocytes, the primary functional cells of a donated liver, and administering them via injection into the lymph nodes. These lymph nodes, which act as filters for foreign particles, such as infection-causing viruses, play a crucial role in supporting the immune system.

After entering the lymph nodes, the liver cells will undergo growth and division, establishing connections with the circulatory system through the development of blood vessels. “Over time, the lymph node will gradually vanish, leaving behind a small-scale organ,” explained Hufford to New Scientist.

This method has previously demonstrated success with certain animals. Scientists conducted an experiment on pigs by surgically modifying their livers to replicate human liver disease. They then introduced healthy liver cells into the lymph nodes by injection. Each of the six pigs had surgery and successfully grew miniature livers. As a result, they exhibited indications of recuperation from liver failure.

The human trial aims to assess the safety, tolerability, and efficacy of this regenerative cell therapy in a maximum of 12 individuals with end-stage liver disease (ESLD), a condition characterized by irreparable liver damage.

Under these conditions, a transplantation procedure is frequently necessary, but several variables can impede its progress. Certain patients may be deemed medically unfit for surgery due to their severe illness, for instance.

Nevertheless, a significant issue lies in the extensive duration of the transplant waiting list. Currently, there is a population of approximately 10,000 individuals in the United States who are awaiting a liver transplant from a donor. However, the unfortunate reality is that these individuals may have to endure a wait of up to five years until a suitable liver becomes available. Approximately 12 percent of individuals on the list will perish annually.

It is anticipated that this novel therapy will address the issue. “If our study proves successful and we receive FDA approval, our allogeneic cell therapy has the potential to treat numerous ESLD patients with just one donated liver. This could help to address the current imbalance between the supply and demand of organs, benefiting the patients,” stated Hufford.

The initial findings of the experiment will take some time to be revealed. However, researchers will closely monitor the patients enrolled for a year to determine the ideal dosage and safety of the treatment, as well as its effectiveness in addressing the indications and symptoms of end-stage liver disease (ESLD).

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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Bionics

A new syndrome linked to COVID that could be fatal has appeared

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There is a new outbreak of a rare but deadly autoimmune disorder in the north of England. New research suggests that the outbreak may be linked to COVID-19. Anti-MDA5-positive dermatomyositis is the name of the disease. It was mostly found in Asian people before the pandemic, but now it’s becoming more common among white people in Yorkshire.

Antibodies that target the MDA5 (melanoma differentiation-associated protein 5) enzyme are what cause the illness. It is linked to progressive interstitial lung disease, which scars lung tissue. Between 2020 and 2022, doctors in Yorkshire reported 60 cases of MDA5 autoimmunity, which was the highest number ever. Eight people died as a result.

What the researchers found when they looked at this sudden rise in cases is that it happened at the same time as the main waves of COVID-19 infections during the pandemic’s peak years. This caught their attention right away because MDA5 is an RNA receptor that is very important for finding the SARS-CoV-2 virus.

The study authors write, “This is to report a rise in the rate of anti-MDA5 positivity testing in our region (Yorkshire) in the second year of the COVID-19 pandemic. This was noteworthy because this entity is not commonly found in the UK.” They say this is likely a sign of “a distinct form of MDA5+ disease in the COVID-19 era.” They have named it “MDA5-autoimmunity and Interstitial Pneumonitis Contemporaneous with COVID-19” (MIP-C).

The researchers used tools that look for shared traits among people in the same medical cohort to figure out how this newly discovered symptom works. In this way, they found that people who had MDA5 autoimmunity also tended to have high levels of interleukin-15 (IL-15), a cytokine that causes inflammation.

The author of the study, Pradipta Ghosh, said in a statement that IL-15 “can push cells to the brink of exhaustion and create an immunologic phenotype that is very, very often seen as a hallmark of progressive interstitial lung disease, or fibrosis of the lung.”

Overall, only eight of the 60 patients had tested positive for COVID-19 before. This means that a lot of them may have had infections that didn’t cause any symptoms that they weren’t aware of. This means that even mild infections with no early symptoms might be enough to cause MDA5 autoimmunity.

The researchers say, “Given that the highest number of positive MDA5 tests happened after the highest number of COVID-19 cases in 2021 and at the same time as the highest number of vaccinations, these results suggest an immune reaction or autoimmunity against MDA5 after exposure to SARS-CoV-2 and/or vaccines.”

Ghosh says that the event probably isn’t just happening in Yorkshire. Reports on MIP-C are now coming in from all over the world.

The study was written up in the eBioMedicine journal.

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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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Medicine and Health

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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